Cardiovascular autonomic neuropathy in patients with diabetes mellitus

Lozano, T.; Ena, J.

doi:10.1016/j.rceng.2016.07.003

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SBR: sensibilidad barorrefleja;VFC: variabilidad de la frecuencia cardiaca." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "T. Lozano, J. Ena" "autores" => array:2 [ 0 => array:2 [ "nombre" => "T." "apellidos" => "Lozano" ] 1 => array:2 [ "nombre" => "J." 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Abbreviations: Fe, iron; Hb, hemoglobin; HF, heart failure; TSAT, transferrin saturation index." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "N. Manito, J.M. Cerqueiro, J. Comín-Colet, J.M. García-Pinilla, A. González-Franco, J. Grau-Amorós, J.R. Peraira, L. Manzano" "autores" => array:8 [ 0 => array:2 [ "nombre" => "N." "apellidos" => "Manito" ] 1 => array:2 [ "nombre" => "J.M." "apellidos" => "Cerqueiro" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Comín-Colet" ] 3 => array:2 [ "nombre" => "J.M." "apellidos" => "García-Pinilla" ] 4 => array:2 [ "nombre" => "A." "apellidos" => "González-Franco" ] 5 => array:2 [ "nombre" => "J." "apellidos" => "Grau-Amorós" ] 6 => array:2 [ "nombre" => "J.R." "apellidos" => "Peraira" ] 7 => array:2 [ "nombre" => "L." "apellidos" => "Manzano" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0014256516301278" "doi" => "10.1016/j.rce.2016.08.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256516301278?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887416300716?idApp=WRCEE" "url" => "/22548874/0000021700000001/v1_201701170152/S2254887416300716/v1_201701170152/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Cardiovascular autonomic neuropathy in patients with diabetes mellitus" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "46" "paginaFinal" => "54" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "T. Lozano, J. Ena" "autores" => array:2 [ 0 => array:4 [ "nombre" => "T." "apellidos" => "Lozano" "email" => array:1 [ 0 => "tereloz@yahoo.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J." "apellidos" => "Ena" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Cardiología, Hospital General Universitario de Alicante, Alicante, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Medicina Interna, Hospital Marina Baixa, Villajoyosa, Alicante, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Neuropatía autonómica cardiovascular en pacientes con diabetes mellitus" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1344 "Ancho" => 2497 "Tamanyo" => 148407 ] ] "descripcion" => array:1 [ "en" => "Progression of cardiovascular autonomic neuropathy in diabetes mellitus." ] ] ] "textoCompleto" => "Case reportA 70-year-old man was assessed for episodes of syncope during the postoperative period of knee arthroplasty. Twenty-four hours after the surgery, the patient had experienced 3 syncopes when standing, with brief prodrome and pallor, following by complete recovery in less than a minute, with no abnormal movements or relaxation of the sphincters. The patient reported no chest pain or palpitations. The patient's medical history indicated at least 5 episodes of syncope in the last 3 years and a diagnosis of vasovagal syncope. He had also been evaluated by the cardiology and neurology department last year and had undergone an electrocardiogram (ECG), echocardiogram, Holter-ECG and Doppler of the supra-aortic trunk, which showed no abnormalities. The patient's history included the presence of type 2 diabetes mellitus (DM) for the last 20 years and a cumulative tobacco consumption of 45 packs/year, having stopped smoking 4 months ago. The patient reported no paresthesia, cramps, gastrointestinal disorders or erectile dysfunction. The periodic ophthalmologic exams showed no diabetic retinopathy. The patient presented no known cardiovascular disease. His standard medication included metformin, insulin glargine and simvastatin.The physical examination revealed a blood pressure (BP) of 130/70mmHg, heart rate (HR) of 60 beats per minute (bpm), normal color of the skin and mucous membranes and normal respiration. The patient's recorded weight and height were 76.2kg and 1.60m, respectively, with a body mass index of 29.7. The results of the cardiovascular examination at the time were normal. An ECG was requested and showed a sinus rhythm of 60bpm, with no conduction or repolarization abnormalities. The emergency laboratory tests that included a hemogram, electrolyte and creatinine levels and a basic coagulation study showed no relevant abnormalities. Laboratory tests performed last month revealed fasting glycemia of 162mg/dL, an HbA1c of 8%, a low-density lipoprotein cholesterol level of 135mg/dL, a creatinine level of 1.13mg/dL, an estimated glomerular filtration rate (CKD-EPI formula) of 65.24mL/min/1.73m2 and an albumin/creatinine ratio <3mg/g.In terms of the suspected cardiovascular autonomic neuropathy (CVAN), what diagnostic strategy should be performed? What treatment should be established?The clinical problemCVAN is a frequent complication of DM and has prognostic implications. It is estimated that approximately 7% of patients with a recent diagnosis of DM experience CVAN.<a class="elsevierStyleCrossRef" href="#bib0245">1</a> Patients with DM can present somatic or autonomic nerve fiber involvement. CVAN occurs when there is a lesion in the autonomic fibers that regulate heart rate, cardiac contractility and cardiac electrophysiology, as well as the phenomena of vasoconstriction and vasodilation.The etiopathogenesis of diabetic neuropathy is multifaceted and has been attributed to metabolic disorders, neurovascular insufficiency, autoimmune damage and nerve growth factor deficiency. The result of this multifactorial process is cell necrosis and activation of the genes involved in neuronal damage.<a class="elsevierStyleCrossRef" href="#bib0250">2</a>The earliest finding with CVAN is reduced heart rate variability (HRV).<a class="elsevierStyleCrossRef" href="#bib0255">3</a> The clinical manifestations of CVAN are highly varied and appear after several years of DM progression. The initial symptomatology most characteristic of CVAN is resting tachycardia, exercise intolerance and postprandial hypotension. Orthostatic hypotension occurs in cases of severe and advanced disease (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>In terms of the prognostic implications of CVAN, this condition is clearly associated with silent myocardial ischemia. Additionally, CVAN is a risk factor for the onset of heart failure and malignant arrhythmias.Diagnostic assessmentThe methods for assessing CVAN in DM in clinical practice include evaluating the clinical manifestations, performing an ECG and testing cardiovascular autonomic reflexes.<a class="elsevierStyleCrossRefs" href="#bib0260">4–7</a> Outpatient HR monitoring aimed at the study of the circadian variations mediated by the autonomic nervous system is also recommended.<a class="elsevierStyleCrossRef" href="#bib0280">8</a>Clinical manifestations (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>)Heart rate variability disorderHRV is the physiological variation of the interval between heart beats, governed by the interaction between the sympathetic and parasympathetic nervous system.<a class="elsevierStyleCrossRef" href="#bib0285">9</a> A wide variability reflects the heart's ability to adapt to the body's metabolic needs.<a class="elsevierStyleCrossRefs" href="#bib0285">9,10</a> HRV reduction in CVAN occurs in the subclinical phase and can be detected by simple diagnostic tests that are described later in this article (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Resting tachycardiaA resting heart rate of 90–100bpm is often identified in patients with CVAN and parasympathetic denervation. As the disease progresses and affects the sympathetic nervous system, the HR tends to return to within normal limits, although it remains higher in healthy individuals. A fixed HR that does not respond to exercise, stress or sleep suggests total cardiac denervation, which indicates severe CVAN.Exercise toleranceExercise intolerance in CVAN is due to the inability to increase the HR, BP and cardiac output during exercise. Hypotension or hypertension can also occur after performing intense exercise, especially when starting a physical activity program. Caution is therefore advised in these circumstances. A progressive increase in the level of effort is recommended to help the autonomic nervous system adapt.Intraoperative cardiovascular instabilityThe normal autonomic response of vasoconstriction and increased HR is inadequate to compensate for the negative vasodilator and chronotropic effects of anesthesia. For this reason, patients with diabetes and CVAN are exposed to a greater risk of hypotension, bradycardia and shock, especially during anesthesia induction.<a class="elsevierStyleCrossRef" href="#bib0295">11</a>Blood pressure circadian rhythm disorderNormal HR behavior during outpatient monitoring shows circadian variations, decreasing during sleep and increasing during activity. The loss of parasympathetic tone during sleep in CVAN causes impairment of this circadian rhythm, resulting in a BP reduction of less than 10% in this period. This non-dipper pattern can sometimes include a riser pattern (night-time BP increase) and lead to difficult-to-control supine hypertension, especially when associated with orthostatic hypotension.<a class="elsevierStyleCrossRef" href="#bib0280">8</a>Some patients can experience deep hypotension 1–2h after meals (postprandial hypotension).<a class="elsevierStyleCrossRef" href="#bib0300">12</a>Orthostatic hypotensionOrthostatic hypotension is defined as a reduction in systolic BP >20mmHg or a reduction in diastolic BP >10mmHg after 2min of standing, after a previous period of 5min in decubitus. In CVAN, this condition develops as a consequence of denervation of the sympathetic vasomotor nerves and represents a late manifestation that entails irreversibility of the autonomic damage.<a class="elsevierStyleCrossRef" href="#bib0305">13</a> Orthostatic hypotension is responsible for the onset of symptoms such as instability, blurred vision, presyncope and syncope when standing. A number of drugs can promote orthostatic hypotension, including vasodilators, diuretics, phenothiazines, insulin (through an endothelium-dependent vasodilator mechanism) and particularly tricyclic antidepressants (employed for neuropathic pain relief) and drugs that affect the central nervous system.<a class="elsevierStyleCrossRef" href="#bib0310">14</a>Orthostatic tachycardiaOccasionally, an orthostatic intolerance mediated by excessive tachycardization is detected in the absence of significant BP reduction, due to autonomic regulation abnormalities. The diagnosis requires the demonstration of an HR increase >30bpm compared with baseline when standing up or the presence of a standing HR >120bpm.Silent myocardial ischemiaCoronary artery disease is considered a major complication of DM and is also more extensive than in the nondiabetic population. Silent myocardial ischemia is defined as the objective documentation of myocardial ischemia in the absence of angina and can present as diaphoresis, dyspnea, fatigability, instability, confusion, palpitations, dyspepsia, nausea and vomiting. CVAN can promote silent ischemia by pain transmission impairment caused by dysfunction of the afferent fibers of the autonomic nervous system.<a class="elsevierStyleCrossRefs" href="#bib0315">15–17</a>QT interval prolongationThe ECG QT interval is the elapsed time between the start of the depolarization (QRS complex) and the end of the T wave. This interval should be corrected by the HR (QTc), and its measure is inversely proportional to the HR. The QTc interval is considered prolonged if >450ms in men and >460ms in women. The origin of QTc prolongation is multifactorial and includes cardiac sympathetic innervation imbalance, hyperinsulinemia, hyperglycemia and acute hypoglycemia.<a class="elsevierStyleCrossRef" href="#bib0250">2</a> In patients with DM, QTc prolongation frequently occurs during nighttime hypoglycemic episodes and is associated with malignant ventricular arrhythmia and a reactive increase in sympathetic activity. This association could explain the harmful effects of intensive glycemic control observed in a number of studies, compared with less rigorous control.<a class="elsevierStyleCrossRef" href="#bib0290">10</a>Sudden deathSevere asymptomatic ischemia that induces fatal arrhythmias has been postulated as the main potential cause of sudden death in CVAN. Other mechanisms include QTc interval prolongation, increased sympathetic activity and oxidative stress.<a class="elsevierStyleCrossRefs" href="#bib0330">18–22</a>Diabetic cardiomyopathyDiabetic cardiomyopathy is defined as myocardial structural and functional impairment, in the absence of coronary artery disease, hypertension or valvular heart disease.<a class="elsevierStyleCrossRef" href="#bib0325">17</a> This condition is especially characterized by diastolic dysfunction. The mechanisms responsible are left ventricular hypertrophy, myocardial lipotoxicity, increased oxidative stress, interstitial and perivascular fibrosis, reduced contractile reserve, mitochondrial dysfunction and changes in the myocardium's metabolic substrate.<a class="elsevierStyleCrossRef" href="#bib0355">23</a>Renal and cerebrovascular eventsA number of studies have showed an independent association between CVAN and adverse renal (microalbuminuria and renal failure progression) and cerebrovascular events in both type 1 and type 2 DM.<a class="elsevierStyleCrossRefs" href="#bib0365">25–27</a>ScreeningAccording to the 2011 recommendations of the expert panel of Toronto<a class="elsevierStyleCrossRef" href="#bib0270">6</a> and the 2016 recommendations of the American Diabetes Association,<a class="elsevierStyleCrossRef" href="#bib0360">24</a> CVAN screening should be performed for the following circumstances:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.Type 2 DM at the time of diagnosis.</li><li class="elsevierStyleListItem" id="lsti0010">2.Type 1 DM in the first 5 years of the diagnosis.</li><li class="elsevierStyleListItem" id="lsti0015">3.In the presence of compatible symptoms or microvascular complications.</li><li class="elsevierStyleListItem" id="lsti0020">4.As part of the preoperative assessment.</li><li class="elsevierStyleListItem" id="lsti0025">5.Before starting an intensive physical activity program.</li><li class="elsevierStyleListItem" id="lsti0030">6.The annual reassessment of symptoms and the use of diagnostic tests for detection in the subclinical phase are also recommended.</li></ul>CVAN screening helps not only in diagnosing the condition but also in early detection and risk stratification and serves as a guide for optimizing treatment, both in terms of glycemic control and cardiovascular risk factors.Diagnostic methodsHeart rate variability disorder and blood pressureThe most commonly employed methods for diagnosing CVAN are based on assessing HRV and on the physiological changes in BP when certain stimuli are applied. These tests are simple, noninvasive and objective and have high sensitivity and specificity. During the 1970s, Ewing et al. described five tests that are still being used today as the basis for diagnosing CVAN:<a class="elsevierStyleCrossRef" href="#bib0365">25</a><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0035">1.HR response to respiration.</li><li class="elsevierStyleListItem" id="lsti0040">2.HR response to standing.</li><li class="elsevierStyleListItem" id="lsti0045">3.HR and BP behavior during the Valsalva maneuver.</li><li class="elsevierStyleListItem" id="lsti0050">4.BP changes during orthostatism.</li><li class="elsevierStyleListItem" id="lsti0055">5.BP changes during isometric exercise.</li></ul><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows these tests and their methodology, as well as the normal and pathological values. To implement these tests, the following conditions are required:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0060">1.Clinically stable patient.</li><li class="elsevierStyleListItem" id="lsti0065">2.No tobacco, caffeine or insulin consumption in the previous 2h.</li><li class="elsevierStyleListItem" id="lsti0070">3.No intense exercise in the previous 24h.</li><li class="elsevierStyleListItem" id="lsti0075">4.Withdraw drugs that could interfere with the results, such as antidepressants, antihistamines, vasodilators and diuretics.</li></ul><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>These tests constitute the gold standard for diagnosing CVAN. After the 8th International Symposium on Diabetic Neuropathy in 2010, the criteria for the diagnosis and staging of CVAN were defined.<a class="elsevierStyleCrossRef" href="#bib0270">6</a><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0080">1.One abnormal test result: possible CVAN.</li><li class="elsevierStyleListItem" id="lsti0085">2.At least 2 abnormal test results: confirmed CVAN.</li><li class="elsevierStyleListItem" id="lsti0090">3.Presence of orthostatic hypotension+1 test result of abnormal HR: severe advanced CVAN.</li></ul>Other methods that are particularly employed in research require more sophisticated techniques than the simple tests mentioned above: HRV analysis using the domains of time and frequency, scintigraphy assessment of cardiac sympathetic innervation and the study of baroreflex sensitivity, which assesses the reflex ability to increase parasympathetic activity in response to a sudden increase in BP.<a class="elsevierStyleCrossRefs" href="#bib0280">8,26</a> However, their implementation in clinical practice is limited.TreatmentEarly detection of CVAN is essential for the success of therapeutic strategies because cardiovascular denervation can be reversible in the initial stages. The proposed therapeutic strategies are as follows:Optimization of glycemic control and cardiovascular risk factorsProper glycemic control is one of the essential pillars of CVAN treatment,<a class="elsevierStyleCrossRefs" href="#bib0375">27–31</a> especially in type 1 DM. In the Diabetes Control and Complications Trial, intensive insulin therapy in patients with type 1 DM lowered the incidence rate of CVAN by 7%, when compared with conventional therapy, after 5 years of follow-up (control group, 14%; intervention group 7%).<a class="elsevierStyleCrossRef" href="#bib0400">32</a> The benefit of intensive glycemic control in the prevention and progression of CVAN is less apparent in type 2 DM. In the Steno-2 study performed on patients with type 2 DM and microalbuminuria, intensive multifactorial therapy (control of glycemia, hypertension and dyslipidemia and lifestyle changes) lowered the incidence rate of CVAN by approximately 60%.<a class="elsevierStyleCrossRefs" href="#bib0405">33,34</a> There is evidence of the favorable effect of physical exercise on the functioning of the autonomic nervous system.<a class="elsevierStyleCrossRefs" href="#bib0415">35–37</a> Nevertheless, exercise should be performed progressively to allow the patients’ cardiovascular system to adapt, attenuating the physiological response to exercise.Treatment of orthostatic hypotensionIn general, the treatment is aimed at symptom relief, especially with nondrug measures. BP readings are not, strictly speaking, an objective of this treatment (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). Data from randomized studies that assessed the efficacy of nondrug measures are scarce. However, clinical experience suggests clear benefits, which helps avoid the adverse effects of drugs.<a class="elsevierStyleCrossRef" href="#bib0430">38</a><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Nondrug-related measuresThe nondrug treatments include the following:<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0095">•Avoid standing abruptly, especially first thing in the morning.</li><li class="elsevierStyleListItem" id="lsti0100">•Perform dorsiflexion exercises of the feet before sitting up.</li><li class="elsevierStyleListItem" id="lsti0105">•Raise the head of the bed by 10–20°.</li><li class="elsevierStyleListItem" id="lsti0110">•Avoid certain drugs, such as vasodilators, diuretics, phenothiazines and tricyclic antidepressants, which promote hypotension.</li><li class="elsevierStyleListItem" id="lsti0115">•Increase fluid intake to 2–3l a day, with abundant hydration before performing exercise, during meals and before getting up in the morning. Increased salt in the diet is another effective recommendation,<a class="elsevierStyleCrossRef" href="#bib0435">39</a> although it is not appropriate for patients with arterial hypertension.</li><li class="elsevierStyleListItem" id="lsti0120">•Avoid standing up in hot environments.</li><li class="elsevierStyleListItem" id="lsti0125">•Avoid maneuvers that increase intrathoracic and intraabdominal pressure, given that these can reduce venous reflux.</li><li class="elsevierStyleListItem" id="lsti0130">•A number of preventive physical maneuvers, such as crossing the legs, tensing the buttocks, and squatting, can attenuate the BP reduction when standing.</li></ul>Compression stockings to the waist are recommended to compensate for splanchnic and leg blood stasis. The stockings’ main limitation is poor tolerance by some patients, particularly those with neuropathic pain, and discomfort during hot weather. The stockings should be used with caution in conditions of ischemia due to peripheral vascular disease or in the presence of skin lesions.Drug treatmentNondrug measures are often insufficient to control the symptoms of orthostatism, making drug treatments necessary. Numerous agents from various therapeutic groups have been employed, but evidence is limited with all of them.<a class="elsevierStyleCrossRef" href="#bib0460">44</a> It is important to improve symptoms and minimize the adverse effects. Progressive treatment starting with fludrocortisone is typically employed.The main objective of drug treatment is to increase plasma volume using a mineralocorticoid agent (fludrocortisone at a starting dosage of 0.1mg/day in the morning, with weekly increases to a maximum of 0.3mg/day depending on the response). The treatment can promote hypertension and peripheral edema. Potassium levels should be monitored a week after each dosage adjustment.Midodrine, a selective alpha-1 agonist, is a second-choice drug in the event of intolerance or lack of response to fludrocortisone. The drug may be used as an alternative or added to the treatment. The results of randomized studies are favorable,<a class="elsevierStyleCrossRefs" href="#bib0445">41,42</a> although the drug's efficacy is low.<a class="elsevierStyleCrossRef" href="#bib0455">43</a> The dosage should be titrated from 2.5 to 10mg three times a day. The adverse effects include piloerection, pruritus, supine hypertension, gastrointestinal discomfort and urinary retention. This drug is contraindicated for patients with advanced heart failure, uncontrolled hypertension or urinary retention.Other treatments have been studied with varying results and can be used as second-line treatment for patients with persistent symptoms. These treatments include pyridostigmine, nonsteroidal anti-inflammatory drugs, caffeine and erythropoietin for patients with concomitant anemia.<a class="elsevierStyleCrossRef" href="#bib0480">48</a> Other agents undergoing research include fluoxetine,<a class="elsevierStyleCrossRef" href="#bib0465">45</a> oral or intranasal desmopressin, subcutaneous octreotide, yohimbine, somatostatin and dihydroergotamine.Treatment of postprandial hypotensionPostprandial hypotension that occurs in some individuals 1–2h after eating can be minimized by employing the following recommendations: eating very light meals with very little carbohydrates; increasing hydration during meals; reducing alcohol intake, lying down in a semiseated position after eating and avoiding standing activities immediately after eating.<a class="elsevierStyleCrossRef" href="#bib0430">38</a>Supine hypertension treatmentSupine hypertension, usually nighttime, is characteristic of autonomic neuropathy and reflects the imbalance between the parasympathetic and sympathetic nervous system. Some patients experience severe supine hypertension combined with orthostatic hypotension. Their management is challenging because of the lack of effective treatments.<a class="elsevierStyleCrossRefs" href="#bib0435">39,40</a> One strategy that could be of use in controlling supine hypertension and minimizing hypotension when standing after waking consists of administering antihypertensive agents with short half-lives, such as captopril, diltiazem and verapamil, shortly before going to bed for the night. Nighttime nitroglycerin patches are also recommended; these patches are withdrawn before standing up in the morning. Wearing compression stockings before getting up in the morning can help attenuate the orthostatism.Treatment of orthostatic tachycardiaThere is uncertainty regarding the most appropriate treatment for this condition. Triggers should be avoided, and physical activity and hydration should be encouraged. Increased salt intake in the absence of hypertension is recommended. There are no quality studies that have evaluated the efficacy of drug therapy in orthostatic tachycardia.<a class="elsevierStyleCrossRef" href="#bib0470">46</a> Drugs such as fludrocortisone and midodrine and, in more severe cases, beta-blockers and ivabradine may be used,<a class="elsevierStyleCrossRef" href="#bib0475">47</a> although none of them have been specifically studied in the diabetic population.Areas of uncertaintyIn 1996, a consensus document was created by the European Society of Cardiology and the American Society of Electrophysiology that emphasized the use of computing techniques, called “spectral analysis”, in the interpretation of diagnostic tests.<a class="elsevierStyleCrossRef" href="#bib0480">48</a> These techniques have been criticized because they are not based on biological tests but rather on indirectly obtained signs. Subsequently, the Italian consensus and the Toronto consensus indicated the need for multiple diagnostic tests based on cardiovascular reflexes of the autonomic nervous system to confirm the diagnosis.<a class="elsevierStyleCrossRef" href="#bib0270">6</a> The Italian consensus indicated that the use of tests that assess both the sympathetic and the parasympathetic system reduce the risk of false positives.<a class="elsevierStyleCrossRef" href="#bib0285">9</a> The Toronto consensus proposed spectral analysis (3 tests) as a diagnostic method, along with the 4 traditional tests.<a class="elsevierStyleCrossRef" href="#bib0270">6</a>ConclusionsAlthough common and severe, CVAN is a little-known complication of DM and is underdiagnosed and undertreated. The condition is related to intraoperative and perioperative cardiovascular instability, an abnormal BP profile, orthostatic hypotension, silent myocardial ischemia, arrhythmias, diabetic cardiomyopathy and an increase in cardiovascular morbidity and mortality. Patients can remain in the subclinical phase for several years. Due to the fact that the progression of cardiovascular denervation is partially reversible or can slow down in the initial phases, the current recommendations support routine screening for CVAN in patients with diabetes. The assessment of CVAN is possible using various methods, especially the clinical data and cardiovascular autonomic reflex tests that study the variations in heart rate and BP when certain stimuli are applied. The main pillars of treatment are early detection, blood glucose control optimization, management of cardiovascular risk factors and lifestyle changes. Orthostatic hypotension is associated with the advanced and irreversible phases of CVAN. Its treatment is essentially symptomatic and is based on nondrug measures.Final recommendationsIn practice, the recommendations we consider most relevant regarding CVAN can be summarize into 3 features:<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0135">(1)CVAN screening in DM: to whom?<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0140">-Type 2 DM: at the time of diagnosis.</li><li class="elsevierStyleListItem" id="lsti0145">-Type 1 DM: in the first 5 years of the diagnosis.</li><li class="elsevierStyleListItem" id="lsti0150">-Annually for inadequate blood glucose control, high cardiovascular risk or microangiopathy.</li><li class="elsevierStyleListItem" id="lsti0155">-In the presence of compatible symptoms.</li></ul></li><li class="elsevierStyleListItem" id="lsti0160">(2)Performing the diagnosis<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0165">-Early detection of HRV reduction (subclinical phase) using the hyperventilation or standing test.</li><li class="elsevierStyleListItem" id="lsti0170">-In the advanced phase: orthostatism test (orthostatic hypotension).</li></ul></li><li class="elsevierStyleListItem" id="lsti0175">(3)What is the approach when the diagnosis is CVAN?<ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0180">-Control of blood glucose levels and cardiovascular risk factors, as well as lifestyle changes.</li><li class="elsevierStyleListItem" id="lsti0185">-Symptomatic treatment of the orthostatic and postprandial hypotension, supine hypertension and orthostatic tachycardia.</li></ul></li></ul>Case resolutionAfter a detailed case history review, the presence of orthostatic hypotension was suspected as the cause of recurrent syncope. An orthostatism test was performed, with a systolic BP drop of 40mmHg and associated symptoms consisting of blurred vision and overall weakness, which were resolved by lying prone. The patient was indicated abundant hydration, a diet with salt, raising the head of the bed and sitting up progressively while tensing the leg muscles. The next day, the patient could stand up without presenting symptoms and was discharged from the hospital. After the hospital discharge, tests were performed to assess HRV with inspiration and standing. The first test showed a difference of 5bpm between inspiration and expiration. In the second test, the R–R ratio between beat 30 and beat 15 of the ECG performed after standing had a value of 1.Based on the results of the 2 tests and the presence of orthostatic hypotension, the patient was diagnosed with advanced and probably irreversible CVAN.The patient was reminded of the nondrug measures for controlling the orthostatic symptoms, and the antidiabetic and lipid-lowering therapy was reinforced. Regular aerobic exercise adapted to the patient's physical capabilities and compression stockings were also recommended. At the 3-month follow-up, the patient presented no new syncopes.Conflicts of interestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:19 [ 0 => array:3 [ "identificador" => "xres790048" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec788320" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres790047" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec788321" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Case report" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "The clinical problem" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Diagnostic assessment" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Clinical manifestations (Table 1)" "secciones" => array:11 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Heart rate variability disorder" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Resting tachycardia" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Exercise tolerance" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Intraoperative cardiovascular instability" ] 4 => array:2 [ "identificador" => "sec0045" "titulo" => "Blood pressure circadian rhythm disorder" ] 5 => array:2 [ "identificador" => "sec0050" "titulo" => "Orthostatic hypotension" ] 6 => array:2 [ "identificador" => "sec0055" "titulo" => "Orthostatic tachycardia" ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "Silent myocardial ischemia" ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "QT interval prolongation" ] 9 => array:2 [ "identificador" => "sec0070" "titulo" => "Sudden death" ] 10 => array:2 [ "identificador" => "sec0075" "titulo" => "Diabetic cardiomyopathy" ] ] ] 8 => array:2 [ "identificador" => "sec0080" "titulo" => "Renal and cerebrovascular events" ] 9 => array:2 [ "identificador" => "sec0085" "titulo" => "Screening" ] 10 => array:3 [ "identificador" => "sec0090" "titulo" => "Diagnostic methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0095" "titulo" => "Heart rate variability disorder and blood pressure" ] ] ] 11 => array:3 [ "identificador" => "sec0100" "titulo" => "Treatment" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0105" "titulo" => "Optimization of glycemic control and cardiovascular risk factors" ] 1 => array:2 [ "identificador" => "sec0110" "titulo" => "Treatment of orthostatic hypotension" ] 2 => array:2 [ "identificador" => "sec0115" "titulo" => "Nondrug-related measures" ] 3 => array:2 [ "identificador" => "sec0120" "titulo" => "Drug treatment" ] 4 => array:2 [ "identificador" => "sec0125" "titulo" => "Treatment of postprandial hypotension" ] 5 => array:2 [ "identificador" => "sec0130" "titulo" => "Supine hypertension treatment" ] 6 => array:2 [ "identificador" => "sec0135" "titulo" => "Treatment of orthostatic tachycardia" ] ] ] 12 => array:2 [ "identificador" => "sec0140" "titulo" => "Areas of uncertainty" ] 13 => array:2 [ "identificador" => "sec0145" "titulo" => "Conclusions" ] 14 => array:2 [ "identificador" => "sec0150" "titulo" => "Final recommendations" ] 15 => array:2 [ "identificador" => "sec0155" "titulo" => "Case resolution" ] 16 => array:2 [ "identificador" => "sec0160" "titulo" => "Conflicts of interest" ] 17 => array:2 [ "identificador" => "xack264452" "titulo" => "Acknowledgements" ] 18 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-03-17" "fechaAceptado" => "2016-07-18" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec788320" "palabras" => array:4 [ 0 => "Diabetes mellitus" 1 => "Cardiovascular autonomic neuropathy" 2 => "Heart rate variability" 3 => "Cardiovascular reflexes" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec788321" "palabras" => array:4 [ 0 => "Diabetes mellitus" 1 => "Neuropatía autonómica cardiovascular" 2 => "Variabilidad de la frecuencia cardiaca" 3 => "Reflejos cardiovasculares" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Cardiovascular autonomic neuropathy associated with diabetes mellitus is caused by an impairment of the autonomic system. The prevalence of this condition ranges from 20% to 65%, depending on the duration of the diabetes mellitus. Clinically, the autonomic function disorder is associated with resting tachycardia, exercise intolerance, orthostatic hypotension, intraoperative cardiovascular instability, silent myocardial ischemia and increased mortality. For the diagnosis, the integrity of the parasympathetic and sympathetic nervous system is assessed. Parasympathetic activity is examined by measuring heart rate variability in response to deep breathing, standing and the Valsalva manoeuvre. Sympathetic integrity is examined by measuring blood pressure in response to standing and isometric exercise. The treatment includes the metabolic control of diabetes mellitus and of the cardiovascular risk factors. Treating symptoms such as orthostatic hypotension requires special attention." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La neuropatía autonómica cardiovascular asociada a la diabetes mellitus está causada por una alteración del sistema autonómico. Su prevalencia varía entre el 20 y 65% dependiendo de la duración de la diabetes mellitus. Clínicamente, el trastorno de la función autonómica se asocia con taquicardia en reposo, intolerancia al ejercicio, hipotensión ortostática, inestabilidad cardiovascular intraoperatoria, isquemia miocárdica silente y aumento de la mortalidad. Para el diagnóstico se evalúa la integridad del sistema nervioso parasimpático y simpático. La actividad parasimpática se explora midiendo la variabilidad de la frecuencia cardiaca en respuesta a la respiración profunda, bipedestación o maniobra de Valsalva. La integridad simpática se explora midiendo la presión arterial en respuesta a la bipedestación y al esfuerzo isométrico. El tratamiento incluye el control metabólico de la diabetes mellitus y de los factores de riesgo cardiovascular. Especial atención requiere el tratamiento de los síntomas tales como la hipotensión ortostática." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Lozano T, Ena J. Neuropatía autonómica cardiovascular en pacientes con diabetes mellitus. Rev Clin Esp. 2017;217:46–54." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1344 "Ancho" => 2497 "Tamanyo" => 148407 ] ] "descripcion" => array:1 [ "en" => "Progression of cardiovascular autonomic neuropathy in diabetes mellitus." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations: bpm, beats per minute; BP, blood pressure." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Resting tachycardia >100bpm \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Orthostatic tachycardia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Exercise intolerance \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Orthostatic hypotension \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Supine hypertension \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Postprandial hypotension \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BP circadian rhythm disorder \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anesthesia complications (hemodynamic lability) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">QT interval prolongation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Malignant arrhythmias \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Silent myocardial ischemia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Heart failure by diabetic cardiomyopathy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sudden death \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1319704.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical manifestations of the cardiovascular autonomic neuropathy of diabetes mellitus." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations: BP, blood pressure; DBP, diastolic blood pressure; ECG, electrocardiogram; HR, heart rate; bpm, beats/breaths per minute; SN, sympathetic nervous; SBP, systolic blood pressure; CVAN, cardiovascular autonomic neuropathy." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Test \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Technique \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Normal response and values \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HR variability beat to beat \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Supine patient. The HR is monitored with the ECG while the patient breathes deeply at a rate of 6bpm. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal: Increased HR during inspiration and decreased HR during expiration. The difference in inspiration/expiration HR should be >15bpm \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">– Evaluates the parasympathetic NS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Abnormal: difference <10bpm \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The R–R interval ratio in expiration/inspiration decreases with age: 20–24 years: ≥1.17; 25–29:≥1.15; 30–34:≥1.13; 35–39:≥1.12; 40–44:≥1.10; 45–49:≥1.08; 50–54:≥1.07; 55–59:≥1.06; 60–64:≥1.04; 65–69:≥1.03; 70–75:≥1.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HR response to standing \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Patient goes from the sitting position to standing while monitored. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Physiological response to standing: tachycardia followed by HR reduction. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">– Evaluates the parasympathetic NS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The R–R interval is measured in milliseconds in beat no. 15 and no. 30 in standing \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal value: R–R ratio 30:15≥1.03 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HR response to the Valsalva maneuver \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The patient blows with a pressure gauge to 40mmHg for 15s while monitored \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Physiological response: tachycardia and vasoconstriction during the pressure phase and bradycardia in the relaxation phase. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">– Evaluates the parasympathetic and sympathetic NS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The shortest R–R interval in the pressure phase and longest in the relaxation phase are measured. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal value: greater R–R/lesser R–R interval ≥1.12 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SBP response to standing \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Patient supine for 5min. The BP is measured. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Physiological response: reduction in SBP ≤10mmHg when standing. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">– Evaluates the sympathetic NS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The patient stands for 3 min, and the blood pressure is once again measured. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive test if the SBP reduction ≥30mmHg \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DBP response to isometric effort \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The patient squeezes a dynamometer as hard as possible. The patient then maintains a force of 30% of the maximum force exerted for 5min. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal response: increase in DBP ≥16mmHg in the contralateral arm. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">– Evaluates the sympathetic NS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The DBP is measured before and after the exercise. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive test: increase in DBP ≤10mmHg in the contralateral arm. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Diagnostic criteria of CVAN: 1 abnormal test result→possible CVAN; at least 2 abnormal test results→confirmed CVAN; presence of orthostatic hypotension+1 test result of abnormal HR→severe or advanced CVAN</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Other recommended tests that should warn of the presence of CVAN:</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">– HR reading at rest</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">– ECG at rest with QTc calculation</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">– Outpatient HR monitoring for studying the circadian variations.</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">All patients with diabetes and abnormal results in these tests should undergo autonomic function tests.</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1319702.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Assessment tests of autonomic reflexes." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Progressively adopt the standing position. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Perform dorsiflexion exercises of the feet before sitting up. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Raise the head of the bed by 10–20°. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Restrict the prescription of drugs that promote orthostatic hypotension. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Increase the fluid intake. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Increase the salt intake (for patients who do not have high blood pressure). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Avoid standing up in hot environments. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Avoid maneuvers that increase intrathoracic and intraabdominal pressure. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Physical maneuvers (see text). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Compression stockings. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1319703.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Nondrug treatment of orthostatic hypotension." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:48 [ 0 => array:3 [ "identificador" => "bib0245" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The epidemiology of diabetic neuropathy. DiaCAN Multicenter Study Group" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D. Ziegler" 1 => "F.A. Gries" 2 => "M. Spüler" 3 => "F. Lessmann" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Diabet Med" "fecha" => "1993" "volumen" => "10" "numero" => "Suppl. 2" "paginaInicial" => "82S" "paginaFinal" => "86S" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8334851" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0250" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiac autonomic neuropathy in patients with diabetes mellitus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Dimitropoulos" 1 => "A.A. Tahrani" 2 => "M.J. Stevens" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4239/wjd.v5.i1.17" "Revista" => array:7 [ "tituloSerie" => "World J Diabetes" "fecha" => "2014" "volumen" => "5" "paginaInicial" => "17" "paginaFinal" => "39" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24567799" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S009167491401481X" "estado" => "S300" "issn" => "00916749" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0255" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The natural history of diabetic autonomic neuropathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D.J. Ewing" 1 => "I.W. Campbell" 2 => "B.F. Clarke" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Q J Med" "fecha" => "1980" "volumen" => "49" "paginaInicial" => "95" "paginaFinal" => "108" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7433630" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0260" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Metodología para el diagnóstico y seguimiento de la neuropatía autonómica cardiovascular en pacientes con diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. Cabezas-Cerrato" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Av Diabetol" "fecha" => "2005" "volumen" => "21" "paginaInicial" => "266" "paginaFinal" => "272" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0265" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recommendations for the use of cardiovascular tests in diagnosing diabetic autonomic neuropathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Spallone" 1 => "F. Bellavere" 2 => "L. Scionti" 3 => "S. Maule" 4 => "R. Quadri" 5 => "G. Bax" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.numecd.2010.07.005" "Revista" => array:6 [ "tituloSerie" => "Nutr Metab Cardiovasc Dis" "fecha" => "2011" "volumen" => "21" "paginaInicial" => "69" "paginaFinal" => "78" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21247746" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0270" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Spallone" 1 => "D. Ziegler" 2 => "R. Freeman" 3 => "L. Bernardi" 4 => "S. Frontoni" 5 => "R. Pop-Busui" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/dmrr.1239" "Revista" => array:6 [ "tituloSerie" => "Diabetes Metab Res Rev" "fecha" => "2011" "volumen" => "27" "paginaInicial" => "639" "paginaFinal" => "653" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21695768" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0275" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiac autonomic neuropathy in diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R. Pop-Busui" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc09-1294" "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2010" "volumen" => "33" "paginaInicial" => "434" "paginaFinal" => "441" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20103559" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0280" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiac autonomic neuropathy, estimated cardiovascular risk, and circadian blood pressure pattern in diabetes mellitus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. Cabezas-Cerrato" 1 => "R.C. Hermida" 2 => "J.M. Cabezas-Agricola" 3 => "D.E. Ayala" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/07420520903044448" "Revista" => array:6 [ "tituloSerie" => "Chronobiol Int" "fecha" => "2009" "volumen" => "26" "paginaInicial" => "942" "paginaFinal" => "957" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19637052" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0285" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A combined abnormality in heart rate variation and QT corrected interval is a strong predictor of cardiovascular death in type 1 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.A. Lykke" 1 => "L. Tarnow" 2 => "H.H. Parving" 3 => "J. Hilsted" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/00365510802018330" "Revista" => array:6 [ "tituloSerie" => "Scand J Clin Lab Invest" "fecha" => "2008" "volumen" => "68" "paginaInicial" => "654" "paginaFinal" => "659" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19378439" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0290" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Heart rate variability: a diagnostic and prognostic tool in anesthesia and intensive care" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.T. Mazzeo" 1 => "E. La Monaca" 2 => "R. di Leo" 3 => "G. Vita" 4 => "L.B. Santamaria" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Acta Anesth Scand" "fecha" => "2011" "volumen" => "55" "paginaInicial" => "797" "paginaFinal" => "811" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0295" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diabetic cardiac autonomic neuropathy and anesthetic management: review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "I. Oakley" 1 => "L. Emond" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "AANA J" "fecha" => "2011" "volumen" => "79" "paginaInicial" => "473" "paginaFinal" => "479" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22400413" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0300" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Postprandial hypotension: epidemiology, pathophysiology, and clinical management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.W. Jansen" 1 => "L.A. Lipsitz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Ann Intern Med" "fecha" => "1995" "volumen" => "122" "paginaInicial" => "286" "paginaFinal" => "295" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7825766" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0091674909027341" "estado" => "S300" "issn" => "00916749" ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0305" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reappraisal of the diagnostic role of orthostatic hypotension in diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "V. Spallone" 1 => "R. Morganti" 2 => "T. Fedele" 3 => "C. D’Amato" 4 => "M.R. Maiello" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10286-009-0517-0" "Revista" => array:6 [ "tituloSerie" => "Clin Auton Res" "fecha" => "2009" "volumen" => "19" "paginaInicial" => "58" "paginaFinal" => "64" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19199088" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0310" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Managed care approach to the treatment of neurogenic orthostatic hypotension" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S.H. Isaacson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Manag Care" "fecha" => "2015" "volumen" => "21" "paginaInicial" => "S258" "paginaFinal" => "S268" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26790110" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0315" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G.V. Heller" 1 => "A.E. Iskandrian" 2 => "S.D. Wittlin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.2009.476" "Revista" => array:7 [ "tituloSerie" => "JAMA" "fecha" => "2009" "volumen" => "301" "paginaInicial" => "1547" "paginaFinal" => "1555" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19366774" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673600027999" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0320" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Silent myocardial ischemia: role of subclinical neuropathy in patients with and without diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "B. Marchant" 1 => "V. Umachandran" 2 => "R. Stevenson" 3 => "P.G. Kopelman" 4 => "A.D. Timmis" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "1993" "volumen" => "22" "paginaInicial" => "1433" "paginaFinal" => "1437" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8227802" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S009167491001273X" "estado" => "S300" "issn" => "00916749" ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0325" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.J. Wackers" 1 => "L.H. Young" 2 => "S.E. Inzucchi" 3 => "D.A. Chyun" 4 => "J.A. Davey" 5 => "E.J. Barrett" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2004" "volumen" => "27" "paginaInicial" => "1954" "paginaFinal" => "1961" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15277423" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0330" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mortality in diabetic autonomic neuropathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D.J. Ewing" 1 => "I.W. Campbell" 2 => "B.F. Clarke" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1976" "volumen" => "1" "paginaInicial" => "601" "paginaFinal" => "603" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2564122" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0335" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "QT interval prolongation and sudden cardiac death in diabetic autonomic neuropathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.K. Kahn" 1 => "J.C. Sisson" 2 => "A.I. Vinik" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jcem-64-4-751" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "1987" "volumen" => "64" "paginaInicial" => "751" "paginaFinal" => "754" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3818902" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0340" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.E. Maser" 1 => "B.D. Mitchell" 2 => "A.I.F.R. Vinik" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2003" "volumen" => "26" "paginaInicial" => "1895" "paginaFinal" => "1901" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12766130" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0345" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prediction of mortality using measures of cardiac autonomic dysfunction in the diabetic and nondiabetic population: the MONICA/KORA Augsburg Cohort Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Ziegler" 1 => "C.P. Zentai" 2 => "S. Perz" 3 => "W. Rathmann" 4 => "B. Haastert" 5 => "A. Döring" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc07-1615" "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2008" "volumen" => "31" "paginaInicial" => "556" "paginaFinal" => "561" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18086873" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0350" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Pop-Busui" 1 => "G.W. Evans" 2 => "H.C. Gerstein" 3 => "V. Fonseca" 4 => "J.L. Fleg" 5 => "B.J. Hoogwerf" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc10-0125" "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2010" "volumen" => "33" "paginaInicial" => "1578" "paginaFinal" => "1584" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20215456" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0355" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diabetic cardiomyopathy: understanding the molecular and cellular basis to progress in diagnosis and treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "I. Falcao Pires" 1 => "A. Leite-Moreira" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10741-011-9257-z" "Revista" => array:6 [ "tituloSerie" => "Heart Fail Rev" "fecha" => "2012" "volumen" => "17" "paginaInicial" => "325" "paginaFinal" => "344" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21626163" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0360" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The value of cardiovascular autonomic function test: 10 years experience in diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D.J. Ewing" 1 => "C.N. Martyn" 2 => "R.J. Young" 3 => "B.F. Clarke" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Diabetes Care" "fecha" => "1985" "volumen" => "8" "paginaInicial" => "491" "paginaFinal" => "498" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4053936" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0091674914003352" "estado" => "S300" "issn" => "00916749" ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0365" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diabetic cardiovascular autonomic neuropathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A.Z.D. Vinik" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.106.634949" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2007" "volumen" => "115" "paginaInicial" => "387" "paginaFinal" => "397" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17242296" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0370" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of glycemic and blood pressure variability on surrogate measures of cardiovascular outcomes in type 2 diabetic patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Di Flaviani" 1 => "F. Picconi" 2 => "P. di Stefano" 3 => "I. Giordani" 4 => "I. Malandrucco" 5 => "P. Maggio" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc11-0034" "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2011" "volumen" => "34" "paginaInicial" => "1605" "paginaFinal" => "1609" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21610126" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0375" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Microvascular complications and foot care. Standards of Medical Care in Diabetes 2016" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "American Diabetes Association" "etal" => false "autores" => array:1 [ 0 => "F. Care" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc16-S012" "Revista" => array:7 [ "tituloSerie" => "Diabetes Care" "fecha" => "2016" "volumen" => "39" "paginaInicial" => "S72" "paginaFinal" => "S80" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26696685" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0091674913008300" "estado" => "S300" "issn" => "00916749" ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0380" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of glucose variability on the risk of microvascular complications in type 1 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E.S. Kilpatrick" 1 => "A.S. Rigby" 2 => "S.L. Atkin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc06-0293" "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2006" "volumen" => "29" "paginaInicial" => "1486" "paginaFinal" => "1490" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16801566" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0385" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of glucose variability on the long-term risk of microvascular complications in type 1 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E.S. Kilpatrick" 1 => "A.S. Rigby" 2 => "S.L. Atkin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc09-0109" "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2009" "volumen" => "32" "paginaInicial" => "1901" "paginaFinal" => "1903" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19549736" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0390" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L. Nalysnyk" 1 => "M. Hernandez-Medina" 2 => "G. Krishnarajah" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1463-1326.2009.01160.x" "Revista" => array:6 [ "tituloSerie" => "Diabetes Obes Metab" "fecha" => "2010" "volumen" => "12" "paginaInicial" => "288" "paginaFinal" => "298" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20380649" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0395" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The association between glycemic variability and diabetic cardiovascular autonomic neuropathy in patients with type 2 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.E. Jun" 1 => "S. Jin" 2 => "J. Baek" 3 => "S. Oh" 4 => "K.Y. Hur" 5 => "M. Lee" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12933-015-0233-0" "Revista" => array:5 [ "tituloSerie" => "Cardiovasc Diabetol" "fecha" => "2015" "volumen" => "14" "paginaInicial" => "70" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26041130" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0400" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of intensive diabetes therapy on measures of autonomic nervous system function in the Diabetes Control and Complications Trial (DCCT)" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "The DCCT Research Group" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Diabetologia" "fecha" => "1998" "volumen" => "41" "paginaInicial" => "416" "paginaFinal" => "423" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9562345" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0405" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "P. Gaede" 1 => "P. Vedel" 2 => "N. Larsen" 3 => "G.V. Jensen" 4 => "H.H. Parving" 5 => "O. Pedersen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "N Eng J Med" "fecha" => "2003" "volumen" => "348" "paginaInicial" => "283" "paginaFinal" => "293" ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0410" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "P. Gaede" 1 => "P. Vedel" 2 => "H.H. Parving" 3 => "O. Pedersen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(98)07368-1" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1999" "volumen" => "353" "paginaInicial" => "617" "paginaFinal" => "622" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10030326" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0415" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recovery pattern of baroreflex sensitivity after exercise" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "T.H. Niemelä" 1 => "A.M. Kiviniemi" 2 => "A.J. Hautala" 3 => "J.A. Salmi" 4 => "V. Linnamo" 5 => "M.P. Tulppo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Sci Sport Exerc" "fecha" => "2008" "volumen" => "40" "paginaInicial" => "864" "paginaFinal" => "870" ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0420" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.R. Colberg" 1 => "R.J. Sigal" 2 => "B. Fernhall" 3 => "J.G. Regensteiner" 4 => "B.J. Blissmer" 5 => "R.R. Rubin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc10-9990" "Revista" => array:7 [ "tituloSerie" => "Diabetes Care" "fecha" => "2010" "volumen" => "33" "paginaInicial" => "e147" "paginaFinal" => "e167" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21115758" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022202X15370652" "estado" => "S300" "issn" => "0022202X" ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0425" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Exercise improves cardiac autonomic function in obesity and diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C. Voulgari" 1 => "S. Pagoni" 2 => "A. Vinik" 3 => "P. Poirier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.metabol.2012.09.005" "Revista" => array:6 [ "tituloSerie" => "Metab Clin Exp" "fecha" => "2013" "volumen" => "62" "paginaInicial" => "609" "paginaFinal" => "621" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23084034" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0430" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nonpharmacologic management of orthostatic hypotension: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "P.B. Mills" 1 => "C.K. Fung" 2 => "A. Travlos" 3 => "A. Krassioukov" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.apmr.2014.09.028" "Revista" => array:6 [ "tituloSerie" => "Arch Phys Med Rehabil" "fecha" => "2015" "volumen" => "96" "paginaInicial" => "366" "paginaFinal" => "375" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25449193" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0435" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ASH position paper: evaluation and treatment of orthostatic hypotension" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C. Shibao" 1 => "L.A. Lipsitz" 2 => "I. Biaggioni" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Clin Hypertens (Greenwich)" "fecha" => "2013" "volumen" => "15" "paginaInicial" => "147" "paginaFinal" => "153" ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0440" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of treatments for orthostatic hypotension: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "I.C. Logan" 1 => "M.D. Witham" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ageing/afs061" "Revista" => array:6 [ "tituloSerie" => "Age Ageing" "fecha" => "2012" "volumen" => "41" "paginaInicial" => "587" "paginaFinal" => "594" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22591985" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0445" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alpha sympathomimetic treatment of autonomic insufficiency with orthostatic hypotension" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "F.M. Fouad-Tarazi" 1 => "M. Okabe" 2 => "H. 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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Case report</span><p id="par0005" class="elsevierStylePara elsevierViewall">A 70-year-old man was assessed for episodes of syncope during the postoperative period of knee arthroplasty&#46; Twenty-four hours after the surgery&#44; the patient had experienced 3 syncopes when standing&#44; with brief prodrome and pallor&#44; following by complete recovery in less than a minute&#44; with no abnormal movements or relaxation of the sphincters&#46; The patient reported no chest pain or palpitations&#46; The patient&#39;s medical history indicated at least 5 episodes of syncope in the last 3 years and a diagnosis of vasovagal syncope&#46; He had also been evaluated by the cardiology and neurology department last year and had undergone an electrocardiogram &#40;ECG&#41;&#44; echocardiogram&#44; Holter-ECG and Doppler of the supra-aortic trunk&#44; which showed no abnormalities&#46; The patient&#39;s history included the presence of type 2 diabetes mellitus &#40;DM&#41; for the last 20 years and a cumulative tobacco consumption of 45 packs&#47;year&#44; having stopped smoking 4 months ago&#46; The patient reported no paresthesia&#44; cramps&#44; gastrointestinal disorders or erectile dysfunction&#46; The periodic ophthalmologic exams showed no diabetic retinopathy&#46; The patient presented no known cardiovascular disease&#46; His standard medication included metformin&#44; insulin glargine and simvastatin&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The physical examination revealed a blood pressure &#40;BP&#41; of 130&#47;70<span class="elsevierStyleHsp" style=""></span>mmHg&#44; heart rate &#40;HR&#41; of 60 beats per minute &#40;bpm&#41;&#44; normal color of the skin and mucous membranes and normal respiration&#46; The patient&#39;s recorded weight and height were 76&#46;2<span class="elsevierStyleHsp" style=""></span>kg and 1&#46;60<span class="elsevierStyleHsp" style=""></span>m&#44; respectively&#44; with a body mass index of 29&#46;7&#46; The results of the cardiovascular examination at the time were normal&#46; An ECG was requested and showed a sinus rhythm of 60<span class="elsevierStyleHsp" style=""></span>bpm&#44; with no conduction or repolarization abnormalities&#46; The emergency laboratory tests that included a hemogram&#44; electrolyte and creatinine levels and a basic coagulation study showed no relevant abnormalities&#46; Laboratory tests performed last month revealed fasting glycemia of 162<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; an HbA1c of 8&#37;&#44; a low-density lipoprotein cholesterol level of 135<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; a creatinine level of 1&#46;13<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; an estimated glomerular filtration rate &#40;CKD-EPI formula&#41; of 65&#46;24<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and an albumin&#47;creatinine ratio &#60;3<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In terms of the suspected cardiovascular autonomic neuropathy &#40;CVAN&#41;&#44; what diagnostic strategy should be performed&#63; What treatment should be established&#63;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">The clinical problem</span><p id="par0020" class="elsevierStylePara elsevierViewall">CVAN is a frequent complication of DM and has prognostic implications&#46; It is estimated that approximately 7&#37; of patients with a recent diagnosis of DM experience CVAN&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">1</span></a> Patients with DM can present somatic or autonomic nerve fiber involvement&#46; CVAN occurs when there is a lesion in the autonomic fibers that regulate heart rate&#44; cardiac contractility and cardiac electrophysiology&#44; as well as the phenomena of vasoconstriction and vasodilation&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The etiopathogenesis of diabetic neuropathy is multifaceted and has been attributed to metabolic disorders&#44; neurovascular insufficiency&#44; autoimmune damage and nerve growth factor deficiency&#46; The result of this multifactorial process is cell necrosis and activation of the genes involved in neuronal damage&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The earliest finding with CVAN is reduced heart rate variability &#40;HRV&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">3</span></a> The clinical manifestations of CVAN are highly varied and appear after several years of DM progression&#46; The initial symptomatology most characteristic of CVAN is resting tachycardia&#44; exercise intolerance and postprandial hypotension&#46; Orthostatic hypotension occurs in cases of severe and advanced disease &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">In terms of the prognostic implications of CVAN&#44; this condition is clearly associated with silent myocardial ischemia&#46; Additionally&#44; CVAN is a risk factor for the onset of heart failure and malignant arrhythmias&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Diagnostic assessment</span><p id="par0040" class="elsevierStylePara elsevierViewall">The methods for assessing CVAN in DM in clinical practice include evaluating the clinical manifestations&#44; performing an ECG and testing cardiovascular autonomic reflexes&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">4&#8211;7</span></a> Outpatient HR monitoring aimed at the study of the circadian variations mediated by the autonomic nervous system is also recommended&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Clinical manifestations &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Heart rate variability disorder</span><p id="par0045" class="elsevierStylePara elsevierViewall">HRV is the physiological variation of the interval between heart beats&#44; governed by the interaction between the sympathetic and parasympathetic nervous system&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">9</span></a> A wide variability reflects the heart&#39;s ability to adapt to the body&#39;s metabolic needs&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">9&#44;10</span></a> HRV reduction in CVAN occurs in the subclinical phase and can be detected by simple diagnostic tests that are described later in this article &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resting tachycardia</span><p id="par0050" class="elsevierStylePara elsevierViewall">A resting heart rate of 90&#8211;100<span class="elsevierStyleHsp" style=""></span>bpm is often identified in patients with CVAN and parasympathetic denervation&#46; As the disease progresses and affects the sympathetic nervous system&#44; the HR tends to return to within normal limits&#44; although it remains higher in healthy individuals&#46; A fixed HR that does not respond to exercise&#44; stress or sleep suggests total cardiac denervation&#44; which indicates severe CVAN&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Exercise tolerance</span><p id="par0055" class="elsevierStylePara elsevierViewall">Exercise intolerance in CVAN is due to the inability to increase the HR&#44; BP and cardiac output during exercise&#46; Hypotension or hypertension can also occur after performing intense exercise&#44; especially when starting a physical activity program&#46; Caution is therefore advised in these circumstances&#46; A progressive increase in the level of effort is recommended to help the autonomic nervous system adapt&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Intraoperative cardiovascular instability</span><p id="par0060" class="elsevierStylePara elsevierViewall">The normal autonomic response of vasoconstriction and increased HR is inadequate to compensate for the negative vasodilator and chronotropic effects of anesthesia&#46; For this reason&#44; patients with diabetes and CVAN are exposed to a greater risk of hypotension&#44; bradycardia and shock&#44; especially during anesthesia induction&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Blood pressure circadian rhythm disorder</span><p id="par0065" class="elsevierStylePara elsevierViewall">Normal HR behavior during outpatient monitoring shows circadian variations&#44; decreasing during sleep and increasing during activity&#46; The loss of parasympathetic tone during sleep in CVAN causes impairment of this circadian rhythm&#44; resulting in a BP reduction of less than 10&#37; in this period&#46; This non-dipper pattern can sometimes include a riser pattern &#40;night-time BP increase&#41; and lead to difficult-to-control supine hypertension&#44; especially when associated with orthostatic hypotension&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">8</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Some patients can experience deep hypotension 1&#8211;2<span class="elsevierStyleHsp" style=""></span>h after meals &#40;postprandial hypotension&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Orthostatic hypotension</span><p id="par0075" class="elsevierStylePara elsevierViewall">Orthostatic hypotension is defined as a reduction in systolic BP &#62;20<span class="elsevierStyleHsp" style=""></span>mmHg or a reduction in diastolic BP &#62;10<span class="elsevierStyleHsp" style=""></span>mmHg after 2<span class="elsevierStyleHsp" style=""></span>min of standing&#44; after a previous period of 5<span class="elsevierStyleHsp" style=""></span>min in decubitus&#46; In CVAN&#44; this condition develops as a consequence of denervation of the sympathetic vasomotor nerves and represents a late manifestation that entails irreversibility of the autonomic damage&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">13</span></a> Orthostatic hypotension is responsible for the onset of symptoms such as instability&#44; blurred vision&#44; presyncope and syncope when standing&#46; A number of drugs can promote orthostatic hypotension&#44; including vasodilators&#44; diuretics&#44; phenothiazines&#44; insulin &#40;through an endothelium-dependent vasodilator mechanism&#41; and particularly tricyclic antidepressants &#40;employed for neuropathic pain relief&#41; and drugs that affect the central nervous system&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Orthostatic tachycardia</span><p id="par0080" class="elsevierStylePara elsevierViewall">Occasionally&#44; an orthostatic intolerance mediated by excessive tachycardization is detected in the absence of significant BP reduction&#44; due to autonomic regulation abnormalities&#46; The diagnosis requires the demonstration of an HR increase &#62;30<span class="elsevierStyleHsp" style=""></span>bpm compared with baseline when standing up or the presence of a standing HR &#62;120<span class="elsevierStyleHsp" style=""></span>bpm&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Silent myocardial ischemia</span><p id="par0085" class="elsevierStylePara elsevierViewall">Coronary artery disease is considered a major complication of DM and is also more extensive than in the nondiabetic population&#46; Silent myocardial ischemia is defined as the objective documentation of myocardial ischemia in the absence of angina and can present as diaphoresis&#44; dyspnea&#44; fatigability&#44; instability&#44; confusion&#44; palpitations&#44; dyspepsia&#44; nausea and vomiting&#46; CVAN can promote silent ischemia by pain transmission impairment caused by dysfunction of the afferent fibers of the autonomic nervous system&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">15&#8211;17</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">QT interval prolongation</span><p id="par0090" class="elsevierStylePara elsevierViewall">The ECG QT interval is the elapsed time between the start of the depolarization &#40;QRS complex&#41; and the end of the T wave&#46; This interval should be corrected by the HR &#40;QTc&#41;&#44; and its measure is inversely proportional to the HR&#46; The QTc interval is considered prolonged if &#62;450<span class="elsevierStyleHsp" style=""></span>ms in men and &#62;460<span class="elsevierStyleHsp" style=""></span>ms in women&#46; The origin of QTc prolongation is multifactorial and includes cardiac sympathetic innervation imbalance&#44; hyperinsulinemia&#44; hyperglycemia and acute hypoglycemia&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">2</span></a> In patients with DM&#44; QTc prolongation frequently occurs during nighttime hypoglycemic episodes and is associated with malignant ventricular arrhythmia and a reactive increase in sympathetic activity&#46; This association could explain the harmful effects of intensive glycemic control observed in a number of studies&#44; compared with less rigorous control&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Sudden death</span><p id="par0095" class="elsevierStylePara elsevierViewall">Severe asymptomatic ischemia that induces fatal arrhythmias has been postulated as the main potential cause of sudden death in CVAN&#46; Other mechanisms include QTc interval prolongation&#44; increased sympathetic activity and oxidative stress&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">18&#8211;22</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Diabetic cardiomyopathy</span><p id="par0100" class="elsevierStylePara elsevierViewall">Diabetic cardiomyopathy is defined as myocardial structural and functional impairment&#44; in the absence of coronary artery disease&#44; hypertension or valvular heart disease&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">17</span></a> This condition is especially characterized by diastolic dysfunction&#46; The mechanisms responsible are left ventricular hypertrophy&#44; myocardial lipotoxicity&#44; increased oxidative stress&#44; interstitial and perivascular fibrosis&#44; reduced contractile reserve&#44; mitochondrial dysfunction and changes in the myocardium&#39;s metabolic substrate&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">23</span></a></p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Renal and cerebrovascular events</span><p id="par0105" class="elsevierStylePara elsevierViewall">A number of studies have showed an independent association between CVAN and adverse renal &#40;microalbuminuria and renal failure progression&#41; and cerebrovascular events in both type 1 and type 2 DM&#46;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">25&#8211;27</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Screening</span><p id="par0110" class="elsevierStylePara elsevierViewall">According to the 2011 recommendations of the expert panel of Toronto<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">6</span></a> and the 2016 recommendations of the American Diabetes Association&#44;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">24</span></a> CVAN screening should be performed for the following circumstances&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0115" class="elsevierStylePara elsevierViewall">Type 2 DM at the time of diagnosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0120" class="elsevierStylePara elsevierViewall">Type 1 DM in the first 5 years of the diagnosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0125" class="elsevierStylePara elsevierViewall">In the presence of compatible symptoms or microvascular complications&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0130" class="elsevierStylePara elsevierViewall">As part of the preoperative assessment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5&#46;</span><p id="par0135" class="elsevierStylePara elsevierViewall">Before starting an intensive physical activity program&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">6&#46;</span><p id="par0140" class="elsevierStylePara elsevierViewall">The annual reassessment of symptoms and the use of diagnostic tests for detection in the subclinical phase are also recommended&#46;</p></li></ul></p><p id="par0145" class="elsevierStylePara elsevierViewall">CVAN screening helps not only in diagnosing the condition but also in early detection and risk stratification and serves as a guide for optimizing treatment&#44; both in terms of glycemic control and cardiovascular risk factors&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Diagnostic methods</span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Heart rate variability disorder and blood pressure</span><p id="par0150" class="elsevierStylePara elsevierViewall">The most commonly employed methods for diagnosing CVAN are based on assessing HRV and on the physiological changes in BP when certain stimuli are applied&#46; These tests are simple&#44; noninvasive and objective and have high sensitivity and specificity&#46; During the 1970s&#44; Ewing et al&#46; described five tests that are still being used today as the basis for diagnosing CVAN&#58;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">25</span></a><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">1&#46;</span><p id="par0155" class="elsevierStylePara elsevierViewall">HR response to respiration&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">2&#46;</span><p id="par0160" class="elsevierStylePara elsevierViewall">HR response to standing&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">3&#46;</span><p id="par0165" class="elsevierStylePara elsevierViewall">HR and BP behavior during the Valsalva maneuver&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">4&#46;</span><p id="par0170" class="elsevierStylePara elsevierViewall">BP changes during orthostatism&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">5&#46;</span><p id="par0175" class="elsevierStylePara elsevierViewall">BP changes during isometric exercise&#46;</p></li></ul></p><p id="par0180" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows these tests and their methodology&#44; as well as the normal and pathological values&#46; To implement these tests&#44; the following conditions are required&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">1&#46;</span><p id="par0185" class="elsevierStylePara elsevierViewall">Clinically stable patient&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">2&#46;</span><p id="par0190" class="elsevierStylePara elsevierViewall">No tobacco&#44; caffeine or insulin consumption in the previous 2<span class="elsevierStyleHsp" style=""></span>h&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">3&#46;</span><p id="par0195" class="elsevierStylePara elsevierViewall">No intense exercise in the previous 24<span class="elsevierStyleHsp" style=""></span>h&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">4&#46;</span><p id="par0200" class="elsevierStylePara elsevierViewall">Withdraw drugs that could interfere with the results&#44; such as antidepressants&#44; antihistamines&#44; vasodilators and diuretics&#46;</p></li></ul></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0205" class="elsevierStylePara elsevierViewall">These tests constitute the gold standard for diagnosing CVAN&#46; After the 8th International Symposium on Diabetic Neuropathy in 2010&#44; the criteria for the diagnosis and staging of CVAN were defined&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">6</span></a><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">1&#46;</span><p id="par0210" class="elsevierStylePara elsevierViewall">One abnormal test result&#58; possible CVAN&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">2&#46;</span><p id="par0215" class="elsevierStylePara elsevierViewall">At least 2 abnormal test results&#58; confirmed CVAN&#46;</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">3&#46;</span><p id="par0220" class="elsevierStylePara elsevierViewall">Presence of orthostatic hypotension<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1 test result of abnormal HR&#58; severe advanced CVAN&#46;</p></li></ul></p><p id="par0225" class="elsevierStylePara elsevierViewall">Other methods that are particularly employed in research require more sophisticated techniques than the simple tests mentioned above&#58; HRV analysis using the domains of time and frequency&#44; scintigraphy assessment of cardiac sympathetic innervation and the study of baroreflex sensitivity&#44; which assesses the reflex ability to increase parasympathetic activity in response to a sudden increase in BP&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">8&#44;26</span></a> However&#44; their implementation in clinical practice is limited&#46;</p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Treatment</span><p id="par0230" class="elsevierStylePara elsevierViewall">Early detection of CVAN is essential for the success of therapeutic strategies because cardiovascular denervation can be reversible in the initial stages&#46; The proposed therapeutic strategies are as follows&#58;</p><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Optimization of glycemic control and cardiovascular risk factors</span><p id="par0235" class="elsevierStylePara elsevierViewall">Proper glycemic control is one of the essential pillars of CVAN treatment&#44;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">27&#8211;31</span></a> especially in type 1 DM&#46; In the Diabetes Control and Complications Trial&#44; intensive insulin therapy in patients with type 1 DM lowered the incidence rate of CVAN by 7&#37;&#44; when compared with conventional therapy&#44; after 5 years of follow-up &#40;control group&#44; 14&#37;&#59; intervention group 7&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">32</span></a> The benefit of intensive glycemic control in the prevention and progression of CVAN is less apparent in type 2 DM&#46; In the Steno-2 study performed on patients with type 2 DM and microalbuminuria&#44; intensive multifactorial therapy &#40;control of glycemia&#44; hypertension and dyslipidemia and lifestyle changes&#41; lowered the incidence rate of CVAN by approximately 60&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">33&#44;34</span></a> There is evidence of the favorable effect of physical exercise on the functioning of the autonomic nervous system&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">35&#8211;37</span></a> Nevertheless&#44; exercise should be performed progressively to allow the patients&#8217; cardiovascular system to adapt&#44; attenuating the physiological response to exercise&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Treatment of orthostatic hypotension</span><p id="par0240" class="elsevierStylePara elsevierViewall">In general&#44; the treatment is aimed at symptom relief&#44; especially with nondrug measures&#46; BP readings are not&#44; strictly speaking&#44; an objective of this treatment &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Data from randomized studies that assessed the efficacy of nondrug measures are scarce&#46; However&#44; clinical experience suggests clear benefits&#44; which helps avoid the adverse effects of drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">38</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Nondrug-related measures</span><p id="par0245" class="elsevierStylePara elsevierViewall">The nondrug treatments include the following&#58;<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">&#8226;</span><p id="par0250" class="elsevierStylePara elsevierViewall">Avoid standing abruptly&#44; especially first thing in the morning&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">&#8226;</span><p id="par0255" class="elsevierStylePara elsevierViewall">Perform dorsiflexion exercises of the feet before sitting up&#46;</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">&#8226;</span><p id="par0260" class="elsevierStylePara elsevierViewall">Raise the head of the bed by 10&#8211;20&#176;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">&#8226;</span><p id="par0265" class="elsevierStylePara elsevierViewall">Avoid certain drugs&#44; such as vasodilators&#44; diuretics&#44; phenothiazines and tricyclic antidepressants&#44; which promote hypotension&#46;</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">&#8226;</span><p id="par0270" class="elsevierStylePara elsevierViewall">Increase fluid intake to 2&#8211;3<span class="elsevierStyleHsp" style=""></span>l a day&#44; with abundant hydration before performing exercise&#44; during meals and before getting up in the morning&#46; Increased salt in the diet is another effective recommendation&#44;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">39</span></a> although it is not appropriate for patients with arterial hypertension&#46;</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">&#8226;</span><p id="par0275" class="elsevierStylePara elsevierViewall">Avoid standing up in hot environments&#46;</p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">&#8226;</span><p id="par0280" class="elsevierStylePara elsevierViewall">Avoid maneuvers that increase intrathoracic and intraabdominal pressure&#44; given that these can reduce venous reflux&#46;</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">&#8226;</span><p id="par0285" class="elsevierStylePara elsevierViewall">A number of preventive physical maneuvers&#44; such as crossing the legs&#44; tensing the buttocks&#44; and squatting&#44; can attenuate the BP reduction when standing&#46;</p></li></ul></p><p id="par0290" class="elsevierStylePara elsevierViewall">Compression stockings to the waist are recommended to compensate for splanchnic and leg blood stasis&#46; The stockings&#8217; main limitation is poor tolerance by some patients&#44; particularly those with neuropathic pain&#44; and discomfort during hot weather&#46; The stockings should be used with caution in conditions of ischemia due to peripheral vascular disease or in the presence of skin lesions&#46;</p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Drug treatment</span><p id="par0295" class="elsevierStylePara elsevierViewall">Nondrug measures are often insufficient to control the symptoms of orthostatism&#44; making drug treatments necessary&#46; Numerous agents from various therapeutic groups have been employed&#44; but evidence is limited with all of them&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">44</span></a> It is important to improve symptoms and minimize the adverse effects&#46; Progressive treatment starting with fludrocortisone is typically employed&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">The main objective of drug treatment is to increase plasma volume using a mineralocorticoid agent &#40;fludrocortisone at a starting dosage of 0&#46;1<span class="elsevierStyleHsp" style=""></span>mg&#47;day in the morning&#44; with weekly increases to a maximum of 0&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;day depending on the response&#41;&#46; The treatment can promote hypertension and peripheral edema&#46; Potassium levels should be monitored a week after each dosage adjustment&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">Midodrine&#44; a selective alpha-1 agonist&#44; is a second-choice drug in the event of intolerance or lack of response to fludrocortisone&#46; The drug may be used as an alternative or added to the treatment&#46; The results of randomized studies are favorable&#44;<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">41&#44;42</span></a> although the drug&#39;s efficacy is low&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">43</span></a> The dosage should be titrated from 2&#46;5 to 10<span class="elsevierStyleHsp" style=""></span>mg three times a day&#46; The adverse effects include piloerection&#44; pruritus&#44; supine hypertension&#44; gastrointestinal discomfort and urinary retention&#46; This drug is contraindicated for patients with advanced heart failure&#44; uncontrolled hypertension or urinary retention&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">Other treatments have been studied with varying results and can be used as second-line treatment for patients with persistent symptoms&#46; These treatments include pyridostigmine&#44; nonsteroidal anti-inflammatory drugs&#44; caffeine and erythropoietin for patients with concomitant anemia&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">48</span></a> Other agents undergoing research include fluoxetine&#44;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">45</span></a> oral or intranasal desmopressin&#44; subcutaneous octreotide&#44; yohimbine&#44; somatostatin and dihydroergotamine&#46;</p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Treatment of postprandial hypotension</span><p id="par0315" class="elsevierStylePara elsevierViewall">Postprandial hypotension that occurs in some individuals 1&#8211;2<span class="elsevierStyleHsp" style=""></span>h after eating can be minimized by employing the following recommendations&#58; eating very light meals with very little carbohydrates&#59; increasing hydration during meals&#59; reducing alcohol intake&#44; lying down in a semiseated position after eating and avoiding standing activities immediately after eating&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">38</span></a></p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Supine hypertension treatment</span><p id="par0320" class="elsevierStylePara elsevierViewall">Supine hypertension&#44; usually nighttime&#44; is characteristic of autonomic neuropathy and reflects the imbalance between the parasympathetic and sympathetic nervous system&#46; Some patients experience severe supine hypertension combined with orthostatic hypotension&#46; Their management is challenging because of the lack of effective treatments&#46;<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">39&#44;40</span></a> One strategy that could be of use in controlling supine hypertension and minimizing hypotension when standing after waking consists of administering antihypertensive agents with short half-lives&#44; such as captopril&#44; diltiazem and verapamil&#44; shortly before going to bed for the night&#46; Nighttime nitroglycerin patches are also recommended&#59; these patches are withdrawn before standing up in the morning&#46; Wearing compression stockings before getting up in the morning can help attenuate the orthostatism&#46;</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Treatment of orthostatic tachycardia</span><p id="par0325" class="elsevierStylePara elsevierViewall">There is uncertainty regarding the most appropriate treatment for this condition&#46; Triggers should be avoided&#44; and physical activity and hydration should be encouraged&#46; Increased salt intake in the absence of hypertension is recommended&#46; There are no quality studies that have evaluated the efficacy of drug therapy in orthostatic tachycardia&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">46</span></a> Drugs such as fludrocortisone and midodrine and&#44; in more severe cases&#44; beta-blockers and ivabradine may be used&#44;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">47</span></a> although none of them have been specifically studied in the diabetic population&#46;</p></span></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Areas of uncertainty</span><p id="par0330" class="elsevierStylePara elsevierViewall">In 1996&#44; a consensus document was created by the European Society of Cardiology and the American Society of Electrophysiology that emphasized the use of computing techniques&#44; called &#8220;spectral analysis&#8221;&#44; in the interpretation of diagnostic tests&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">48</span></a> These techniques have been criticized because they are not based on biological tests but rather on indirectly obtained signs&#46; Subsequently&#44; the Italian consensus and the Toronto consensus indicated the need for multiple diagnostic tests based on cardiovascular reflexes of the autonomic nervous system to confirm the diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">6</span></a> The Italian consensus indicated that the use of tests that assess both the sympathetic and the parasympathetic system reduce the risk of false positives&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">9</span></a> The Toronto consensus proposed spectral analysis &#40;3 tests&#41; as a diagnostic method&#44; along with the 4 traditional tests&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Conclusions</span><p id="par0335" class="elsevierStylePara elsevierViewall">Although common and severe&#44; CVAN is a little-known complication of DM and is underdiagnosed and undertreated&#46; The condition is related to intraoperative and perioperative cardiovascular instability&#44; an abnormal BP profile&#44; orthostatic hypotension&#44; silent myocardial ischemia&#44; arrhythmias&#44; diabetic cardiomyopathy and an increase in cardiovascular morbidity and mortality&#46; Patients can remain in the subclinical phase for several years&#46; Due to the fact that the progression of cardiovascular denervation is partially reversible or can slow down in the initial phases&#44; the current recommendations support routine screening for CVAN in patients with diabetes&#46; The assessment of CVAN is possible using various methods&#44; especially the clinical data and cardiovascular autonomic reflex tests that study the variations in heart rate and BP when certain stimuli are applied&#46; The main pillars of treatment are early detection&#44; blood glucose control optimization&#44; management of cardiovascular risk factors and lifestyle changes&#46; Orthostatic hypotension is associated with the advanced and irreversible phases of CVAN&#46; Its treatment is essentially symptomatic and is based on nondrug measures&#46;</p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Final recommendations</span><p id="par0340" class="elsevierStylePara elsevierViewall">In practice&#44; the recommendations we consider most relevant regarding CVAN can be summarize into 3 features&#58;<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">&#40;1&#41;</span><p id="par0345" class="elsevierStylePara elsevierViewall">CVAN screening in DM&#58; to whom&#63;<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">-</span><p id="par0350" class="elsevierStylePara elsevierViewall">Type 2 DM&#58; at the time of diagnosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">-</span><p id="par0355" class="elsevierStylePara elsevierViewall">Type 1 DM&#58; in the first 5 years of the diagnosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0150"><span class="elsevierStyleLabel">-</span><p id="par0360" class="elsevierStylePara elsevierViewall">Annually for inadequate blood glucose control&#44; high cardiovascular risk or microangiopathy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0155"><span class="elsevierStyleLabel">-</span><p id="par0365" class="elsevierStylePara elsevierViewall">In the presence of compatible symptoms&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0160"><span class="elsevierStyleLabel">&#40;2&#41;</span><p id="par0370" class="elsevierStylePara elsevierViewall">Performing the diagnosis<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0165"><span class="elsevierStyleLabel">-</span><p id="par0375" class="elsevierStylePara elsevierViewall">Early detection of HRV reduction &#40;subclinical phase&#41; using the hyperventilation or standing test&#46;</p></li><li class="elsevierStyleListItem" id="lsti0170"><span class="elsevierStyleLabel">-</span><p id="par0380" class="elsevierStylePara elsevierViewall">In the advanced phase&#58; orthostatism test &#40;orthostatic hypotension&#41;&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0175"><span class="elsevierStyleLabel">&#40;3&#41;</span><p id="par0385" class="elsevierStylePara elsevierViewall">What is the approach when the diagnosis is CVAN&#63;<ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0180"><span class="elsevierStyleLabel">-</span><p id="par0390" class="elsevierStylePara elsevierViewall">Control of blood glucose levels and cardiovascular risk factors&#44; as well as lifestyle changes&#46;</p></li><li class="elsevierStyleListItem" id="lsti0185"><span class="elsevierStyleLabel">-</span><p id="par0395" class="elsevierStylePara elsevierViewall">Symptomatic treatment of the orthostatic and postprandial hypotension&#44; supine hypertension and orthostatic tachycardia&#46;</p></li></ul></p></li></ul></p></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Case resolution</span><p id="par0400" class="elsevierStylePara elsevierViewall">After a detailed case history review&#44; the presence of orthostatic hypotension was suspected as the cause of recurrent syncope&#46; An orthostatism test was performed&#44; with a systolic BP drop of 40<span class="elsevierStyleHsp" style=""></span>mmHg and associated symptoms consisting of blurred vision and overall weakness&#44; which were resolved by lying prone&#46; The patient was indicated abundant hydration&#44; a diet with salt&#44; raising the head of the bed and sitting up progressively while tensing the leg muscles&#46; The next day&#44; the patient could stand up without presenting symptoms and was discharged from the hospital&#46; After the hospital discharge&#44; tests were performed to assess HRV with inspiration and standing&#46; The first test showed a difference of 5<span class="elsevierStyleHsp" style=""></span>bpm between inspiration and expiration&#46; In the second test&#44; the R&#8211;R ratio between beat 30 and beat 15 of the ECG performed after standing had a value of 1&#46;</p><p id="par0405" class="elsevierStylePara elsevierViewall">Based on the results of the 2 tests and the presence of orthostatic hypotension&#44; the patient was diagnosed with advanced and probably irreversible CVAN&#46;</p><p id="par0410" class="elsevierStylePara elsevierViewall">The patient was reminded of the nondrug measures for controlling the orthostatic symptoms&#44; and the antidiabetic and lipid-lowering therapy was reinforced&#46; Regular aerobic exercise adapted to the patient&#39;s physical capabilities and compression stockings were also recommended&#46; At the 3-month follow-up&#44; the patient presented no new syncopes&#46;</p></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Conflicts of interest</span><p id="par0415" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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            1 => "Cardiovascular autonomic neuropathy"
            2 => "Heart rate variability"
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            0 => "Diabetes mellitus"
            1 => "Neuropat&#237;a auton&#243;mica cardiovascular"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cardiovascular autonomic neuropathy associated with diabetes mellitus is caused by an impairment of the autonomic system&#46; The prevalence of this condition ranges from 20&#37; to 65&#37;&#44; depending on the duration of the diabetes mellitus&#46; Clinically&#44; the autonomic function disorder is associated with resting tachycardia&#44; exercise intolerance&#44; orthostatic hypotension&#44; intraoperative cardiovascular instability&#44; silent myocardial ischemia and increased mortality&#46; For the diagnosis&#44; the integrity of the parasympathetic and sympathetic nervous system is assessed&#46; Parasympathetic activity is examined by measuring heart rate variability in response to deep breathing&#44; standing and the Valsalva manoeuvre&#46; Sympathetic integrity is examined by measuring blood pressure in response to standing and isometric exercise&#46; The treatment includes the metabolic control of diabetes mellitus and of the cardiovascular risk factors&#46; Treating symptoms such as orthostatic hypotension requires special attention&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La neuropat&#237;a auton&#243;mica cardiovascular asociada a la diabetes mellitus est&#225; causada por una alteraci&#243;n del sistema auton&#243;mico&#46; Su prevalencia var&#237;a entre el 20 y 65&#37; dependiendo de la duraci&#243;n de la diabetes mellitus&#46; Cl&#237;nicamente&#44; el trastorno de la funci&#243;n auton&#243;mica se asocia con taquicardia en reposo&#44; intolerancia al ejercicio&#44; hipotensi&#243;n ortost&#225;tica&#44; inestabilidad cardiovascular intraoperatoria&#44; isquemia mioc&#225;rdica silente y aumento de la mortalidad&#46; Para el diagn&#243;stico se eval&#250;a la integridad del sistema nervioso parasimp&#225;tico y simp&#225;tico&#46; La actividad parasimp&#225;tica se explora midiendo la variabilidad de la frecuencia cardiaca en respuesta a la respiraci&#243;n profunda&#44; bipedestaci&#243;n o maniobra de Valsalva&#46; La integridad simp&#225;tica se explora midiendo la presi&#243;n arterial en respuesta a la bipedestaci&#243;n y al esfuerzo isom&#233;trico&#46; El tratamiento incluye el control metab&#243;lico de la diabetes mellitus y de los factores de riesgo cardiovascular&#46; Especial atenci&#243;n requiere el tratamiento de los s&#237;ntomas tales como la&#160;hipotensi&#243;n ortost&#225;tica&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Lozano T&#44; Ena J&#46; Neuropat&#237;a auton&#243;mica cardiovascular en pacientes con diabetes mellitus&#46; Rev Clin Esp&#46; 2017&#59;217&#58;46&#8211;54&#46;</p>"
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          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; bpm&#44; beats per minute&#59; BP&#44; blood pressure&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Resting tachycardia &#62;100<span class="elsevierStyleHsp" style=""></span>bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Orthostatic tachycardia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Exercise intolerance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Orthostatic hypotension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Supine hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Postprandial hypotension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BP circadian rhythm disorder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anesthesia complications &#40;hemodynamic lability&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">QT interval prolongation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Malignant arrhythmias&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Silent myocardial ischemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Heart failure by diabetic cardiomyopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sudden death&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Clinical manifestations of the cardiovascular autonomic neuropathy of diabetes mellitus&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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        "mostrarDisplay" => false
        "detalles" => array:1 [
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            "identificador" => "at2"
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; BP&#44; blood pressure&#59; DBP&#44; diastolic blood pressure&#59; ECG&#44; electrocardiogram&#59; HR&#44; heart rate&#59; bpm&#44; beats&#47;breaths per minute&#59; SN&#44; sympathetic nervous&#59; SBP&#44; systolic blood pressure&#59; CVAN&#44; cardiovascular autonomic neuropathy&#46;</p>"
          "tablatextoimagen" => array:1 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Test&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Technique&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Normal response and values&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">HR variability beat to beat</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Supine patient&#46; The HR is monitored with the ECG while the patient breathes deeply at a rate of 6<span class="elsevierStyleHsp" style=""></span>bpm&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&#58; Increased HR during inspiration and decreased HR during expiration&#46; The difference in inspiration&#47;expiration HR should be &#62;15<span class="elsevierStyleHsp" style=""></span>bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8211; Evaluates the parasympathetic NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Abnormal&#58; difference &#60;10<span class="elsevierStyleHsp" style=""></span>bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The R&#8211;R interval ratio in expiration&#47;inspiration decreases with age&#58; 20&#8211;24 years&#58; &#8805;1&#46;17&#59; 25&#8211;29&#58;&#8805;1&#46;15&#59; 30&#8211;34&#58;&#8805;1&#46;13&#59; 35&#8211;39&#58;&#8805;1&#46;12&#59; 40&#8211;44&#58;&#8805;1&#46;10&#59; 45&#8211;49&#58;&#8805;1&#46;08&#59; 50&#8211;54&#58;&#8805;1&#46;07&#59; 55&#8211;59&#58;&#8805;1&#46;06&#59; 60&#8211;64&#58;&#8805;1&#46;04&#59; 65&#8211;69&#58;&#8805;1&#46;03&#59; 70&#8211;75&#58;&#8805;1&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">HR response to standing</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Patient goes from the sitting position to standing while monitored&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Physiological response to standing&#58; tachycardia followed by HR reduction&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8211; Evaluates the parasympathetic NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The R&#8211;R interval is measured in milliseconds in beat no&#46; 15 and no&#46; 30 in standing&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal value&#58; R&#8211;R ratio 30&#58;15<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>1&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">HR response to the Valsalva maneuver</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The patient blows with a pressure gauge to 40<span class="elsevierStyleHsp" style=""></span>mmHg for 15<span class="elsevierStyleHsp" style=""></span>s while monitored&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Physiological response&#58; tachycardia and vasoconstriction during the pressure phase and bradycardia in the relaxation phase&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8211; Evaluates the parasympathetic and sympathetic NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The shortest R&#8211;R interval in the pressure phase and longest in the relaxation phase are measured&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal value&#58; greater R&#8211;R&#47;lesser R&#8211;R interval &#8805;1&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">SBP response to standing</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Patient supine for 5<span class="elsevierStyleHsp" style=""></span>min&#46; The BP is measured&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Physiological response&#58; reduction in SBP &#8804;10<span class="elsevierStyleHsp" style=""></span>mmHg when standing&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8211; Evaluates the sympathetic NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The patient stands for 3 min&#44; and the blood pressure is once again measured&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive test if the SBP reduction &#8805;30<span class="elsevierStyleHsp" style=""></span>mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">DBP response to isometric effort</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The patient squeezes a dynamometer as hard as possible&#46; The patient then maintains a force of 30&#37; of the maximum force exerted for 5<span class="elsevierStyleHsp" style=""></span>min&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal response&#58; increase in DBP &#8805;16<span class="elsevierStyleHsp" style=""></span>mmHg in the contralateral arm&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8211; Evaluates the sympathetic NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The DBP is measured before and after the exercise&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive test&#58; increase in DBP &#8804;10<span class="elsevierStyleHsp" style=""></span>mmHg in the contralateral arm&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Diagnostic criteria of CVAN</span>&#58; 1 abnormal test result<span class="elsevierStyleHsp" style=""></span>&#8594;<span class="elsevierStyleHsp" style=""></span>possible CVAN&#59; at least 2 abnormal test results<span class="elsevierStyleHsp" style=""></span>&#8594;<span class="elsevierStyleHsp" style=""></span>confirmed CVAN&#59; presence of orthostatic hypotension<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1 test result of abnormal HR<span class="elsevierStyleHsp" style=""></span>&#8594;<span class="elsevierStyleHsp" style=""></span>severe or advanced CVAN</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Other recommended tests that should warn of the presence of CVAN</span>&#58;</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8211; HR reading at rest</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8211; ECG at rest with QTc calculation</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8211; Outpatient HR monitoring for studying the circadian variations&#46;</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">All patients with diabetes and abnormal results in these tests should undergo autonomic function tests&#46;</span></td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Assessment tests of autonomic reflexes&#46;</p>"
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        "etiqueta" => "Table 3"
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            "identificador" => "at3"
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        "tabla" => array:1 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Progressively adopt the standing position&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Perform dorsiflexion exercises of the feet before sitting up&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Raise the head of the bed by 10&#8211;20&#176;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Restrict the prescription of drugs that promote orthostatic hypotension&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Increase the fluid intake&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Increase the salt intake &#40;for patients who do not have high blood pressure&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Avoid standing up in hot environments&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Avoid maneuvers that increase intrathoracic and intraabdominal pressure&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Physical maneuvers &#40;see text&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Compression stockings&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nondrug treatment of orthostatic hypotension&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:48 [
            0 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The epidemiology of diabetic neuropathy&#46; DiaCAN Multicenter Study Group"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46; Ziegler"
                            1 => "F&#46;A&#46; Gries"
                            2 => "M&#46; Sp&#252;ler"
                            3 => "F&#46; Lessmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Diabet Med"
                        "fecha" => "1993"
                        "volumen" => "10"
                        "numero" => "Suppl&#46; 2"
                        "paginaInicial" => "82S"
                        "paginaFinal" => "86S"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8334851"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiac autonomic neuropathy in patients with diabetes mellitus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "G&#46; Dimitropoulos"
                            1 => "A&#46;A&#46; Tahrani"
                            2 => "M&#46;J&#46; Stevens"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4239/wjd.v5.i1.17"
                      "Revista" => array:7 [
                        "tituloSerie" => "World J Diabetes"
                        "fecha" => "2014"
                        "volumen" => "5"
                        "paginaInicial" => "17"
                        "paginaFinal" => "39"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24567799"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S009167491401481X"
                          "estado" => "S300"
                          "issn" => "00916749"
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                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The natural history of diabetic autonomic neuropathy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "D&#46;J&#46; Ewing"
                            1 => "I&#46;W&#46; Campbell"
                            2 => "B&#46;F&#46; Clarke"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Q J Med"
                        "fecha" => "1980"
                        "volumen" => "49"
                        "paginaInicial" => "95"
                        "paginaFinal" => "108"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7433630"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metodolog&#237;a para el diagn&#243;stico y seguimiento de la neuropat&#237;a auton&#243;mica cardiovascular en pacientes con diabetes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46; Cabezas-Cerrato"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Av Diabetol"
                        "fecha" => "2005"
                        "volumen" => "21"
                        "paginaInicial" => "266"
                        "paginaFinal" => "272"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
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                      "titulo" => "Recommendations for the use of cardiovascular tests in diagnosing diabetic autonomic neuropathy"
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                          "autores" => array:6 [
                            0 => "V&#46; Spallone"
                            1 => "F&#46; Bellavere"
                            2 => "L&#46; Scionti"
                            3 => "S&#46; Maule"
                            4 => "R&#46; Quadri"
                            5 => "G&#46; Bax"
                          ]
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                    0 => array:2 [
                      "doi" => "10.1016/j.numecd.2010.07.005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nutr Metab Cardiovasc Dis"
                        "fecha" => "2011"
                        "volumen" => "21"
                        "paginaInicial" => "69"
                        "paginaFinal" => "78"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21247746"
                            "web" => "Medline"
                          ]
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                      "titulo" => "Cardiovascular autonomic neuropathy in diabetes&#58; clinical impact&#44; assessment&#44; diagnosis&#44; and management"
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                          "etal" => true
                          "autores" => array:6 [
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                            2 => "R&#46; Freeman"
                            3 => "L&#46; Bernardi"
                            4 => "S&#46; Frontoni"
                            5 => "R&#46; Pop-Busui"
                          ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/dmrr.1239"
                      "Revista" => array:6 [
                        "tituloSerie" => "Diabetes Metab Res Rev"
                        "fecha" => "2011"
                        "volumen" => "27"
                        "paginaInicial" => "639"
                        "paginaFinal" => "653"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21695768"
                            "web" => "Medline"
                          ]
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                      "titulo" => "Cardiac autonomic neuropathy in diabetes"
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                            0 => "R&#46; Pop-Busui"
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                    0 => array:2 [
                      "doi" => "10.2337/dc09-1294"
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                        "tituloSerie" => "Diabetes Care"
                        "fecha" => "2010"
                        "volumen" => "33"
                        "paginaInicial" => "434"
                        "paginaFinal" => "441"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20103559"
                            "web" => "Medline"
                          ]
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                    0 => array:2 [
                      "titulo" => "Cardiac autonomic neuropathy&#44; estimated cardiovascular risk&#44; and circadian blood pressure pattern in diabetes mellitus"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46; Cabezas-Cerrato"
                            1 => "R&#46;C&#46; Hermida"
                            2 => "J&#46;M&#46; Cabezas-Agricola"
                            3 => "D&#46;E&#46; Ayala"
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                    0 => array:2 [
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                      "Revista" => array:6 [
                        "tituloSerie" => "Chronobiol Int"
                        "fecha" => "2009"
                        "volumen" => "26"
                        "paginaInicial" => "942"
                        "paginaFinal" => "957"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19637052"
                            "web" => "Medline"
                          ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "A combined abnormality in heart rate variation and QT corrected interval is a strong predictor of cardiovascular death in type 1 diabetes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;A&#46; Lykke"
                            1 => "L&#46; Tarnow"
                            2 => "H&#46;H&#46; Parving"
                            3 => "J&#46; Hilsted"
                          ]
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/00365510802018330"
                      "Revista" => array:6 [
                        "tituloSerie" => "Scand J Clin Lab Invest"
                        "fecha" => "2008"
                        "volumen" => "68"
                        "paginaInicial" => "654"
                        "paginaFinal" => "659"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19378439"
                            "web" => "Medline"
                          ]
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              ]
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              "identificador" => "bib0290"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Heart rate variability&#58; a diagnostic and prognostic tool in anesthesia and intensive care"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46;T&#46; Mazzeo"
                            1 => "E&#46; La Monaca"
                            2 => "R&#46; di Leo"
                            3 => "G&#46; Vita"
                            4 => "L&#46;B&#46; Santamaria"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Acta Anesth Scand"
                        "fecha" => "2011"
                        "volumen" => "55"
                        "paginaInicial" => "797"
                        "paginaFinal" => "811"
                      ]
                    ]
                  ]
                ]
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                    0 => array:2 [
                      "titulo" => "Diabetic cardiac autonomic neuropathy and anesthetic management&#58; review of the literature"
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                          "etal" => false
                          "autores" => array:2 [
                            0 => "I&#46; Oakley"
                            1 => "L&#46; Emond"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "AANA J"
                        "fecha" => "2011"
                        "volumen" => "79"
                        "paginaInicial" => "473"
                        "paginaFinal" => "479"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22400413"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Postprandial hypotension&#58; epidemiology&#44; pathophysiology&#44; and clinical management"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46;W&#46; Jansen"
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "1995"
                        "volumen" => "122"
                        "paginaInicial" => "286"
                        "paginaFinal" => "295"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7825766"
                            "web" => "Medline"
                          ]
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                          "issn" => "00916749"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Reappraisal of the diagnostic role of orthostatic hypotension in diabetes"
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                          "etal" => false
                          "autores" => array:5 [
                            0 => "V&#46; Spallone"
                            1 => "R&#46; Morganti"
                            2 => "T&#46; Fedele"
                            3 => "C&#46; D&#8217;Amato"
                            4 => "M&#46;R&#46; Maiello"
                          ]
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                      ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10286-009-0517-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Auton Res"
                        "fecha" => "2009"
                        "volumen" => "19"
                        "paginaInicial" => "58"
                        "paginaFinal" => "64"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19199088"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0310"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Managed care approach to the treatment of neurogenic orthostatic hypotension"
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                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46;H&#46; Isaacson"
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Manag Care"
                        "fecha" => "2015"
                        "volumen" => "21"
                        "paginaInicial" => "S258"
                        "paginaFinal" => "S268"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26790110"
                            "web" => "Medline"
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                    0 => array:2 [
                      "titulo" => "Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes"
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                          "autores" => array:3 [
                            0 => "G&#46;V&#46; Heller"
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                    0 => array:2 [
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                        "tituloSerie" => "JAMA"
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                        "volumen" => "301"
                        "paginaInicial" => "1547"
                        "paginaFinal" => "1555"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19366774"
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                          "pii" => "S0140673600027999"
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                          "issn" => "01406736"
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              "identificador" => "bib0320"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Silent myocardial ischemia&#58; role of subclinical neuropathy in patients with and without diabetes"
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                          "etal" => false
                          "autores" => array:5 [
                            0 => "B&#46; Marchant"
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                            2 => "R&#46; Stevenson"
                            3 => "P&#46;G&#46; Kopelman"
                            4 => "A&#46;D&#46; Timmis"
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "1993"
                        "volumen" => "22"
                        "paginaInicial" => "1433"
                        "paginaFinal" => "1437"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8227802"
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              "identificador" => "bib0325"
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                    0 => array:2 [
                      "titulo" => "Detection of silent myocardial ischemia in asymptomatic diabetic subjects&#58; the DIAD study"
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                          "autores" => array:6 [
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                            3 => "D&#46;A&#46; Chyun"
                            4 => "J&#46;A&#46; Davey"
                            5 => "E&#46;J&#46; Barrett"
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                    0 => array:1 [
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                        "tituloSerie" => "Diabetes Care"
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                        "volumen" => "27"
                        "paginaInicial" => "1954"
                        "paginaFinal" => "1961"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15277423"
                            "web" => "Medline"
                          ]
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                ]
              ]
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              "identificador" => "bib0330"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mortality in diabetic autonomic neuropathy"
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                        0 => array:2 [
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                            0 => "D&#46;J&#46; Ewing"
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                            2 => "B&#46;F&#46; Clarke"
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                  "host" => array:1 [
                    0 => array:1 [
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                        "tituloSerie" => "Lancet"
                        "fecha" => "1976"
                        "volumen" => "1"
                        "paginaInicial" => "601"
                        "paginaFinal" => "603"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2564122"
                            "web" => "Medline"
                          ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "QT interval prolongation and sudden cardiac death in diabetic autonomic neuropathy"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46;K&#46; Kahn"
                            1 => "J&#46;C&#46; Sisson"
                            2 => "A&#46;I&#46; Vinik"
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                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jcem-64-4-751"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "1987"
                        "volumen" => "64"
                        "paginaInicial" => "751"
                        "paginaFinal" => "754"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3818902"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0340"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes&#58; a meta-analysis"
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                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Diabetes Care"
                        "fecha" => "2003"
                        "volumen" => "26"
                        "paginaInicial" => "1895"
                        "paginaFinal" => "1901"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12766130"
                            "web" => "Medline"
                          ]
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                      ]
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                  ]
                ]
              ]
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              "identificador" => "bib0345"
              "etiqueta" => "21"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Prediction of mortality using measures of cardiac autonomic dysfunction in the diabetic and nondiabetic population&#58; the MONICA&#47;KORA Augsburg Cohort Study"
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                        0 => array:2 [
                          "etal" => true
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                            1 => "C&#46;P&#46; Zentai"
                            2 => "S&#46; Perz"
                            3 => "W&#46; Rathmann"
                            4 => "B&#46; Haastert"
                            5 => "A&#46; D&#246;ring"
                          ]
                        ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2337/dc07-1615"
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                        "tituloSerie" => "Diabetes Care"
                        "fecha" => "2008"
                        "volumen" => "31"
                        "paginaInicial" => "556"
                        "paginaFinal" => "561"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18086873"
                            "web" => "Medline"
                          ]
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                ]
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            21 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes &#40;ACCORD&#41; trial"
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                          "etal" => true
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                            1 => "G&#46;W&#46; Evans"
                            2 => "H&#46;C&#46; Gerstein"
                            3 => "V&#46; Fonseca"
                            4 => "J&#46;L&#46; Fleg"
                            5 => "B&#46;J&#46; Hoogwerf"
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                      ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2337/dc10-0125"
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                        "tituloSerie" => "Diabetes Care"
                        "fecha" => "2010"
                        "volumen" => "33"
                        "paginaInicial" => "1578"
                        "paginaFinal" => "1584"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20215456"
                            "web" => "Medline"
                          ]
                        ]
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                    ]
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                ]
              ]
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              "identificador" => "bib0355"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Diabetic cardiomyopathy&#58; understanding the molecular and cellular basis to progress in diagnosis and treatment"
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                          "etal" => false
                          "autores" => array:2 [
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                        "tituloSerie" => "Heart Fail Rev"
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                        "paginaFinal" => "344"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21626163"
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                      "titulo" => "The value of cardiovascular autonomic function test&#58; 10 years experience in diabetes"
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                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46;J&#46; Ewing"
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                            2 => "R&#46;J&#46; Young"
                            3 => "B&#46;F&#46; Clarke"
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                        "tituloSerie" => "Diabetes Care"
                        "fecha" => "1985"
                        "volumen" => "8"
                        "paginaInicial" => "491"
                        "paginaFinal" => "498"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4053936"
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                          ]
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                    0 => array:2 [
                      "titulo" => "Diabetic cardiovascular autonomic neuropathy"
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                          "etal" => false
                          "autores" => array:1 [
                            0 => "A&#46;Z&#46;D&#46; Vinik"
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                    0 => array:2 [
                      "doi" => "10.1161/CIRCULATIONAHA.106.634949"
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                        "tituloSerie" => "Circulation"
                        "fecha" => "2007"
                        "volumen" => "115"
                        "paginaInicial" => "387"
                        "paginaFinal" => "397"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17242296"
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                          ]
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                    0 => array:2 [
                      "titulo" => "Impact of glycemic and blood pressure variability on surrogate measures of cardiovascular outcomes in type 2 diabetic patients"
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                          "etal" => true
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                            2 => "P&#46; di Stefano"
                            3 => "I&#46; Giordani"
                            4 => "I&#46; Malandrucco"
                            5 => "P&#46; Maggio"
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                    0 => array:2 [
                      "doi" => "10.2337/dc11-0034"
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                        "tituloSerie" => "Diabetes Care"
                        "fecha" => "2011"
                        "volumen" => "34"
                        "paginaInicial" => "1605"
                        "paginaFinal" => "1609"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21610126"
                            "web" => "Medline"
                          ]
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                    0 => array:2 [
                      "titulo" => "Microvascular complications and foot care&#46; Standards of Medical Care in Diabetes 2016"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "American Diabetes Association"
                          "etal" => false
                          "autores" => array:1 [
                            0 => "F&#46; Care"
                          ]
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                    0 => array:2 [
                      "doi" => "10.2337/dc16-S012"
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                        "tituloSerie" => "Diabetes Care"
                        "fecha" => "2016"
                        "volumen" => "39"
                        "paginaInicial" => "S72"
                        "paginaFinal" => "S80"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26696685"
                            "web" => "Medline"
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              "identificador" => "bib0380"
              "etiqueta" => "28"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effect of glucose variability on the risk of microvascular complications in type 1 diabetes"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "E&#46;S&#46; Kilpatrick"
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                            2 => "S&#46;L&#46; Atkin"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2337/dc06-0293"
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                        "tituloSerie" => "Diabetes Care"
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                        "paginaInicial" => "1486"
                        "paginaFinal" => "1490"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16801566"
                            "web" => "Medline"
                          ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Effect of glucose variability on the long-term risk of microvascular complications in type 1 diabetes"
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                          "etal" => false
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                    0 => array:2 [
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                        "tituloSerie" => "Diabetes Care"
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                        "volumen" => "32"
                        "paginaInicial" => "1901"
                        "paginaFinal" => "1903"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19549736"
                            "web" => "Medline"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Glycaemic variability and complications in patients with diabetes mellitus&#58; evidence from a systematic review of the literature"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "L&#46; Nalysnyk"
                            1 => "M&#46; Hernandez-Medina"
                            2 => "G&#46; Krishnarajah"
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                    ]
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                    0 => array:2 [
                      "doi" => "10.1111/j.1463-1326.2009.01160.x"
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                        "tituloSerie" => "Diabetes Obes Metab"
                        "fecha" => "2010"
                        "volumen" => "12"
                        "paginaInicial" => "288"
                        "paginaFinal" => "298"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20380649"
                            "web" => "Medline"
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                    0 => array:2 [
                      "titulo" => "The association between glycemic variability and diabetic cardiovascular autonomic neuropathy in patients with type 2 diabetes"
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;E&#46; Jun"
                            1 => "S&#46; Jin"
                            2 => "J&#46; Baek"
                            3 => "S&#46; Oh"
                            4 => "K&#46;Y&#46; Hur"
                            5 => "M&#46; Lee"
                          ]
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                    ]
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                    0 => array:2 [
                      "doi" => "10.1186/s12933-015-0233-0"
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                        "tituloSerie" => "Cardiovasc Diabetol"
                        "fecha" => "2015"
                        "volumen" => "14"
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                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26041130"
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                          ]
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                ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "The effect of intensive diabetes therapy on measures of autonomic nervous system function in the Diabetes Control and Complications Trial &#40;DCCT&#41;"
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                          "colaboracion" => "The DCCT Research Group"
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                        "tituloSerie" => "Diabetologia"
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                        "paginaInicial" => "416"
                        "paginaFinal" => "423"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9562345"
                            "web" => "Medline"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes"
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                          "etal" => false
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                            0 => "P&#46; Gaede"
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                            2 => "N&#46; Larsen"
                            3 => "G&#46;V&#46; Jensen"
                            4 => "H&#46;H&#46; Parving"
                            5 => "O&#46; Pedersen"
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "N Eng J Med"
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                        "volumen" => "348"
                        "paginaInicial" => "283"
                        "paginaFinal" => "293"
                      ]
                    ]
                  ]
                ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria&#58; the Steno type 2 randomised study"
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                        "tituloSerie" => "Lancet"
                        "fecha" => "1999"
                        "volumen" => "353"
                        "paginaInicial" => "617"
                        "paginaFinal" => "622"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10030326"
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                ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Recovery pattern of baroreflex sensitivity after exercise"
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                            3 => "J&#46;A&#46; Salmi"
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                            5 => "M&#46;P&#46; Tulppo"
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                        "tituloSerie" => "Med Sci Sport Exerc"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Exercise and type 2 diabetes&#58; the American College of Sports Medicine and the American Diabetes Association&#58; joint position statement"
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                          "issn" => "0022202X"
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                      "titulo" => "Exercise improves cardiac autonomic function in obesity and diabetes"
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                      "titulo" => "Alpha sympathomimetic treatment of autonomic insufficiency with orthostatic hypotension"
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                        "paginaInicial" => "604"
                        "paginaFinal" => "610"
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                            1 => "T&#46; Brannan"
                            2 => "L&#46; Krakoff"
                            3 => "M&#46;D&#46; Yahr"
                            4 => "J&#46; Mandeli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "1998"
                        "volumen" => "38"
                        "paginaInicial" => "951"
                        "paginaFinal" => "956"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2452997"
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                      ]
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                ]
              ]
            ]
            42 => array:3 [
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Midodrine for orthostatic hypotension and recurrent reflex syncope&#58; a systematic review"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46; Izcovich"
                            1 => "C&#46; Gonz&#225;lez Malla"
                            2 => "M&#46; Manzotti"
                            3 => "H&#46;N&#46; Catalano"
                            4 => "G&#46; Guyatt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/WNL.0000000000000815"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2014"
                        "volumen" => "83"
                        "paginaInicial" => "1170"
                        "paginaFinal" => "1177"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25150287"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0460"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of orthostatic hypotension with erythropoietin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46;D&#46; Hoeldtke"
                            1 => "D&#46;H&#46; Streeten"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM199308263290904"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "1993"
                        "volumen" => "329"
                        "paginaInicial" => "611"
                        "paginaFinal" => "615"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8341335"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0465"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fluoxetine hydrochloride for the treatment of severe refractory orthostatic hypotension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "B&#46;P&#46; Grubb"
                            1 => "D&#46; Samoil"
                            2 => "D&#46; Kosinski"
                            3 => "D&#46; Wolfe"
                            4 => "M&#46; Lorton"
                            5 => "E&#46; Madu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Med"
                        "fecha" => "1994"
                        "volumen" => "97"
                        "paginaInicial" => "366"
                        "paginaFinal" => "368"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7942939"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0470"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Postural tachycardia syndrome &#40;POTS&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46;R&#46; Raj"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIRCULATIONAHA.112.144501"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2013"
                        "volumen" => "127"
                        "paginaInicial" => "2336"
                        "paginaFinal" => "2342"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23753844"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0475"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Single centre experience of ivabradine in postural orthostatic tachycardia syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "C&#46; McDonald"
                            1 => "J&#46; Frith"
                            2 => "J&#46;L&#46; Newton"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/europace/euq390"
                      "Revista" => array:6 [
                        "tituloSerie" => "Europace"
                        "fecha" => "2011"
                        "volumen" => "13"
                        "paginaInicial" => "427"
                        "paginaFinal" => "430"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21062792"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0480"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Validation of a computerised measurement system for guided routine evaluation of cardiovascular autonomic neuropathy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Vespasiani"
                            1 => "M&#46; Bruni"
                            2 => "I&#46; Meloncelli"
                            3 => "L&#46; Clementi"
                            4 => "R&#46; Amoretti"
                            5 => "S&#46; Branca"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Comput Methods Programs Biomed"
                        "fecha" => "1996"
                        "volumen" => "51"
                        "paginaInicial" => "211"
                        "paginaFinal" => "216"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8955589"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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