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array:23 [ "pii" => "S2254887416300625" "issn" => "22548874" "doi" => "10.1016/j.rceng.2016.07.003" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "1300" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "copyrightAnyo" => "2016" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Rev Clin Esp. 2017;217:46-54" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2 "PDF" => 2 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0014256516301254" "issn" => "00142565" "doi" => "10.1016/j.rce.2016.07.004" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "1300" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Rev Clin Esp. 2017;217:46-54" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 110 "formatos" => array:2 [ "HTML" => 61 "PDF" => 49 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">REVISIÓN</span>" "titulo" => "Neuropatía autonómica cardiovascular en pacientes con diabetes mellitus" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "46" "paginaFinal" => "54" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Cardiovascular autonomic neuropathy in patients with diabetes mellitus" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1344 "Ancho" => 2497 "Tamanyo" => 151358 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Evolución de la neuropatía autonómica cardiovascular en la diabetes mellitus.</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">SBR: sensibilidad barorrefleja;VFC: variabilidad de la frecuencia cardiaca.</p>" ] ] ] "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." "apellidos" => "Ena" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2254887416300625" "doi" => "10.1016/j.rceng.2016.07.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887416300625?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256516301254?idApp=WRCEE" "url" => "/00142565/0000021700000001/v1_201701170139/S0014256516301254/v1_201701170139/es/main.assets" ] ] "itemAnterior" => array:19 [ "pii" => "S2254887416300716" "issn" => "22548874" "doi" => "10.1016/j.rceng.2016.10.003" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "1302" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Rev Clin Esp. 2017;217:35-45" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 3 "PDF" => 3 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Consensus Document of the Spanish Society of Cardiology and the Spanish Society of Internal Medicine on the diagnosis and treatment of iron deficiency in heart failure" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "35" "paginaFinal" => "45" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Documento de consenso de la Sociedad Española de Cardiología y la Sociedad Española de Medicina Interna sobre el diagnóstico y tratamiento del déficit de hierro en la insuficiencia cardíaca" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1571 "Ancho" => 2822 "Tamanyo" => 268864 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Treatment options for heart failure with iron deficiency. Abbreviations: Fe, iron; Hb, hemoglobin; HF, heart failure; TSAT, transferrin saturation index.</p>" ] ] ] "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" => "<span class="elsevierStyleTextfn">Review</span>" "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" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J." "apellidos" => "Ena" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "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" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Progression of cardiovascular autonomic neuropathy in diabetes mellitus.</p>" ] ] ] "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. 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.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The physical examination revealed a blood pressure (BP) of 130/70<span class="elsevierStyleHsp" style=""></span>mmHg, 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 76.2<span class="elsevierStyleHsp" style=""></span>kg and 1.60<span class="elsevierStyleHsp" style=""></span>m, 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 60<span class="elsevierStyleHsp" style=""></span>bpm, 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 162<span class="elsevierStyleHsp" style=""></span>mg/dL, an HbA1c of 8%, a low-density lipoprotein cholesterol level of 135<span class="elsevierStyleHsp" style=""></span>mg/dL, a creatinine level of 1.13<span class="elsevierStyleHsp" style=""></span>mg/dL, an estimated glomerular filtration rate (CKD-EPI formula) of 65.24<span class="elsevierStyleHsp" style=""></span>mL/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and an albumin/creatinine ratio <3<span class="elsevierStyleHsp" style=""></span>mg/g.</p><p id="par0015" class="elsevierStylePara elsevierViewall">In terms of the suspected cardiovascular autonomic neuropathy (CVAN), what diagnostic strategy should be performed? What treatment should be established?</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. It is estimated that approximately 7% of patients with a recent diagnosis of DM experience CVAN.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">1</span></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.</p><p id="par0025" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The earliest finding with CVAN is reduced heart rate variability (HRV).<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. 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>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">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.</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, performing an ECG and testing cardiovascular autonomic reflexes.<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">4–7</span></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"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Clinical manifestations (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>)</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, governed by the interaction between the sympathetic and parasympathetic nervous system.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">9</span></a> A wide variability reflects the heart's ability to adapt to the body's metabolic needs.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">9,10</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 (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</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 90–100<span class="elsevierStyleHsp" style=""></span>bpm 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.</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, 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.</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. 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"><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, 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"><span class="elsevierStyleSup">8</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Some patients can experience deep hypotension 1–2<span class="elsevierStyleHsp" style=""></span>h after meals (postprandial hypotension).<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 >20<span class="elsevierStyleHsp" style=""></span>mmHg or a reduction in diastolic BP >10<span class="elsevierStyleHsp" style=""></span>mmHg after 2<span class="elsevierStyleHsp" style=""></span>min of standing, after a previous period of 5<span class="elsevierStyleHsp" style=""></span>min 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"><span class="elsevierStyleSup">13</span></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"><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, 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 >30<span class="elsevierStyleHsp" style=""></span>bpm compared with baseline when standing up or the presence of a standing HR >120<span class="elsevierStyleHsp" style=""></span>bpm.</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. 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"><span class="elsevierStyleSup">15–17</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 (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 >450<span class="elsevierStyleHsp" style=""></span>ms in men and >460<span class="elsevierStyleHsp" style=""></span>ms 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"><span class="elsevierStyleSup">2</span></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"><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. Other mechanisms include QTc interval prolongation, increased sympathetic activity and oxidative stress.<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">18–22</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, in the absence of coronary artery disease, hypertension or valvular heart disease.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">17</span></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"><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 (microalbuminuria and renal failure progression) and cerebrovascular events in both type 1 and type 2 DM.<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">25–27</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,<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">24</span></a> CVAN screening should be performed for the following circumstances:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1.</span><p id="par0115" class="elsevierStylePara elsevierViewall">Type 2 DM at the time of diagnosis.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2.</span><p id="par0120" class="elsevierStylePara elsevierViewall">Type 1 DM in the first 5 years of the diagnosis.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3.</span><p id="par0125" class="elsevierStylePara elsevierViewall">In the presence of compatible symptoms or microvascular complications.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4.</span><p id="par0130" class="elsevierStylePara elsevierViewall">As part of the preoperative assessment.</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5.</span><p id="par0135" class="elsevierStylePara elsevierViewall">Before starting an intensive physical activity program.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">6.</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.</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, both in terms of glycemic control and cardiovascular risk factors.</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. 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"><span class="elsevierStyleSup">25</span></a><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">1.</span><p id="par0155" class="elsevierStylePara elsevierViewall">HR response to respiration.</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">2.</span><p id="par0160" class="elsevierStylePara elsevierViewall">HR response to standing.</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">3.</span><p id="par0165" class="elsevierStylePara elsevierViewall">HR and BP behavior during the Valsalva maneuver.</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">4.</span><p id="par0170" class="elsevierStylePara elsevierViewall">BP changes during orthostatism.</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">5.</span><p id="par0175" class="elsevierStylePara elsevierViewall">BP changes during isometric exercise.</p></li></ul></p><p id="par0180" class="elsevierStylePara elsevierViewall"><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"><span class="elsevierStyleLabel">1.</span><p id="par0185" class="elsevierStylePara elsevierViewall">Clinically stable patient.</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">2.</span><p id="par0190" class="elsevierStylePara elsevierViewall">No tobacco, caffeine or insulin consumption in the previous 2<span class="elsevierStyleHsp" style=""></span>h.</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">3.</span><p id="par0195" class="elsevierStylePara elsevierViewall">No intense exercise in the previous 24<span class="elsevierStyleHsp" style=""></span>h.</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">4.</span><p id="par0200" class="elsevierStylePara elsevierViewall">Withdraw drugs that could interfere with the results, such as antidepressants, antihistamines, vasodilators and diuretics.</p></li></ul></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0205" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">6</span></a><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">1.</span><p id="par0210" class="elsevierStylePara elsevierViewall">One abnormal test result: possible CVAN.</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">2.</span><p id="par0215" class="elsevierStylePara elsevierViewall">At least 2 abnormal test results: confirmed CVAN.</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">3.</span><p id="par0220" class="elsevierStylePara elsevierViewall">Presence of orthostatic hypotension<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>1 test result of abnormal HR: severe advanced CVAN.</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: 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"><span class="elsevierStyleSup">8,26</span></a> However, their implementation in clinical practice is limited.</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. The proposed therapeutic strategies are as follows:</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,<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">27–31</span></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"><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. 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"><span class="elsevierStyleSup">33,34</span></a> There is evidence of the favorable effect of physical exercise on the functioning of the autonomic nervous system.<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">35–37</span></a> Nevertheless, exercise should be performed progressively to allow the patients’ cardiovascular system to adapt, attenuating the physiological response to exercise.</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, 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"><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:<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">•</span><p id="par0250" class="elsevierStylePara elsevierViewall">Avoid standing abruptly, especially first thing in the morning.</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">•</span><p id="par0255" class="elsevierStylePara elsevierViewall">Perform dorsiflexion exercises of the feet before sitting up.</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">•</span><p id="par0260" class="elsevierStylePara elsevierViewall">Raise the head of the bed by 10–20°.</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">•</span><p id="par0265" class="elsevierStylePara elsevierViewall">Avoid certain drugs, such as vasodilators, diuretics, phenothiazines and tricyclic antidepressants, which promote hypotension.</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">•</span><p id="par0270" class="elsevierStylePara elsevierViewall">Increase fluid intake to 2–3<span class="elsevierStyleHsp" style=""></span>l 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"><span class="elsevierStyleSup">39</span></a> although it is not appropriate for patients with arterial hypertension.</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">•</span><p id="par0275" class="elsevierStylePara elsevierViewall">Avoid standing up in hot environments.</p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">•</span><p id="par0280" class="elsevierStylePara elsevierViewall">Avoid maneuvers that increase intrathoracic and intraabdominal pressure, given that these can reduce venous reflux.</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">•</span><p id="par0285" class="elsevierStylePara elsevierViewall">A number of preventive physical maneuvers, such as crossing the legs, tensing the buttocks, and squatting, can attenuate the BP reduction when standing.</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. 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.</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, 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"><span class="elsevierStyleSup">44</span></a> It is important to improve symptoms and minimize the adverse effects. Progressive treatment starting with fludrocortisone is typically employed.</p><p id="par0300" class="elsevierStylePara elsevierViewall">The main objective of drug treatment is to increase plasma volume using a mineralocorticoid agent (fludrocortisone at a starting dosage of 0.1<span class="elsevierStyleHsp" style=""></span>mg/day in the morning, with weekly increases to a maximum of 0.3<span class="elsevierStyleHsp" style=""></span>mg/day depending on the response). The treatment can promote hypertension and peripheral edema. Potassium levels should be monitored a week after each dosage adjustment.</p><p id="par0305" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">41,42</span></a> although the drug's efficacy is low.<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">43</span></a> The dosage should be titrated from 2.5 to 10<span class="elsevierStyleHsp" style=""></span>mg 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.</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. These treatments include pyridostigmine, nonsteroidal anti-inflammatory drugs, caffeine and erythropoietin for patients with concomitant anemia.<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">48</span></a> Other agents undergoing research include fluoxetine,<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">45</span></a> oral or intranasal desmopressin, subcutaneous octreotide, yohimbine, somatostatin and dihydroergotamine.</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 1–2<span class="elsevierStyleHsp" style=""></span>h 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"><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, 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"><span class="elsevierStyleSup">39,40</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, 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.</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. 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"><span class="elsevierStyleSup">46</span></a> Drugs such as fludrocortisone and midodrine and, in more severe cases, beta-blockers and ivabradine may be used,<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">47</span></a> although none of them have been specifically studied in the diabetic population.</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, 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"><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. 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"><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.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">9</span></a> The Toronto consensus proposed spectral analysis (3 tests) as a diagnostic method, along with the 4 traditional tests.<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, 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.</p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Final recommendations</span><p id="par0340" class="elsevierStylePara elsevierViewall">In 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"><span class="elsevierStyleLabel">(1)</span><p id="par0345" class="elsevierStylePara elsevierViewall">CVAN screening in DM: to whom?<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">-</span><p id="par0350" class="elsevierStylePara elsevierViewall">Type 2 DM: at the time of diagnosis.</p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">-</span><p id="par0355" class="elsevierStylePara elsevierViewall">Type 1 DM: in the first 5 years of the diagnosis.</p></li><li class="elsevierStyleListItem" id="lsti0150"><span class="elsevierStyleLabel">-</span><p id="par0360" class="elsevierStylePara elsevierViewall">Annually for inadequate blood glucose control, high cardiovascular risk or microangiopathy.</p></li><li class="elsevierStyleListItem" id="lsti0155"><span class="elsevierStyleLabel">-</span><p id="par0365" class="elsevierStylePara elsevierViewall">In the presence of compatible symptoms.</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0160"><span class="elsevierStyleLabel">(2)</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 (subclinical phase) using the hyperventilation or standing test.</p></li><li class="elsevierStyleListItem" id="lsti0170"><span class="elsevierStyleLabel">-</span><p id="par0380" class="elsevierStylePara elsevierViewall">In the advanced phase: orthostatism test (orthostatic hypotension).</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0175"><span class="elsevierStyleLabel">(3)</span><p id="par0385" class="elsevierStylePara elsevierViewall">What is the approach when the diagnosis is CVAN?<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, as well as lifestyle changes.</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, supine hypertension and orthostatic tachycardia.</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, the presence of orthostatic hypotension was suspected as the cause of recurrent syncope. An orthostatism test was performed, with a systolic BP drop of 40<span class="elsevierStyleHsp" style=""></span>mmHg 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 5<span class="elsevierStyleHsp" style=""></span>bpm 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.</p><p id="par0405" class="elsevierStylePara elsevierViewall">Based on the results of the 2 tests and the presence of orthostatic hypotension, the patient was diagnosed with advanced and probably irreversible CVAN.</p><p id="par0410" class="elsevierStylePara elsevierViewall">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.</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.</p></span></span>" "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" => "<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. 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.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">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.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Lozano T, Ena J. Neuropatía autonómica cardiovascular en pacientes con diabetes mellitus. Rev Clin Esp. 2017;217:46–54.</p>" ] ] "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" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Progression of cardiovascular autonomic neuropathy in diabetes mellitus.</p>" ] ] 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" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: bpm, beats per minute; BP, blood pressure.</p>" "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 >100<span class="elsevierStyleHsp" style=""></span>bpm \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" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Clinical manifestations of the cardiovascular autonomic neuropathy of diabetes mellitus.</p>" ] ] 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" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">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.</p>" "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"><span class="elsevierStyleItalic">HR variability beat to beat</span> \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 6<span class="elsevierStyleHsp" style=""></span>bpm. \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 >15<span class="elsevierStyleHsp" style=""></span>bpm \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>– 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 <10<span class="elsevierStyleHsp" style=""></span>bpm \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"><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> \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"><span class="elsevierStyleHsp" style=""></span>– 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<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>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"><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> \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 \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"><span class="elsevierStyleHsp" style=""></span>– 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"><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> \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. 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 ≤10<span class="elsevierStyleHsp" style=""></span>mmHg 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"><span class="elsevierStyleHsp" style=""></span>– 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 ≥30<span class="elsevierStyleHsp" style=""></span>mmHg \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> \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 5<span class="elsevierStyleHsp" style=""></span>min. \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 ≥16<span class="elsevierStyleHsp" style=""></span>mmHg 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"><span class="elsevierStyleHsp" style=""></span>– 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 ≤10<span class="elsevierStyleHsp" style=""></span>mmHg 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"><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>: 1 abnormal test result<span class="elsevierStyleHsp" style=""></span>→<span class="elsevierStyleHsp" style=""></span>possible CVAN; at least 2 abnormal test results<span class="elsevierStyleHsp" style=""></span>→<span class="elsevierStyleHsp" style=""></span>confirmed CVAN; presence of orthostatic hypotension<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>1 test result of abnormal HR<span class="elsevierStyleHsp" style=""></span>→<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>:</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>– 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>– 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>– 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"><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.</span></td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1319702.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Assessment tests of autonomic reflexes.</p>" ] ] 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" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nondrug treatment of orthostatic hypotension.</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. 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