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the most widely used of which is the Charlson index&#44; as it has been validated to predict mortality at 1 year&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">3</span></a> The index is calculated by adding up the score assigned to the various diseases&#44; and its total score ranges from 0 to 30 points&#46; However&#44; despite the high prevalence and prognostic implications of comorbidity&#44; the scientific evidence on the treatment recommendations for these patients is scarce&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">To what degree do patients with heart failure have comorbidity&#63;</span><p id="par0010" class="elsevierStylePara elsevierViewall">Most patients with heart failure &#40;HF&#41; treated in internal medicine departments are elderly and have a high degree of comorbidity&#46; A study conducted by the HF Workgroup of the Spanish Society of Internal Medicine reported that patients who were admitted for HF were elderly &#40;77 years&#41;&#44; had a median of 2 comorbidities &#40;range&#44; 0&#8211;9&#41; per patient and a mean score of 5&#46;4 points &#40;range&#44; 2&#8211;11&#41; on the Charlson index&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">2</span></a> The most commonly associated diseases were diabetes and chronic obstructive pulmonary disease &#40;COPD&#41; in 39&#37; and 31&#37; of cases&#44; respectively&#46; Only one-third of patients with greater comorbidity had echocardiogram results &#40;compared with 68&#37; for patients with less comorbidity&#41;&#46; The etiology of HF was established in only 30&#37; of those with greater comorbidity &#40;compared with 70&#37; of patients with less comorbidity&#41;&#46; Additionally&#44; comorbidity was associated with a greater frequency of hospital admissions&#44; longer mean stays&#44; greater disability and higher mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">2</span></a> Recently&#44; the same workgroup analyzed the comorbidity of patients with HF from the Spanish HF registry &#40;RICA registry&#41; and found similar results&#58; a mean age of 78 years and an average of 2 comorbidities per patient &#40;36&#37; of patients had 3 or more associated comorbidities&#41;&#46; The most common comorbidities were atrial fibrillation &#40;AF&#41; &#40;53&#46;2&#37;&#41;&#44; anemia &#40;53&#46;2&#37;&#41; diabetes &#40;44&#46;3&#37;&#41;&#44; obesity &#40;36&#37;&#41;&#44; chronic renal failure &#40;30&#46;8&#37;&#41; and COPD &#40;27&#46;4&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">5</span></a> This same profile of an elderly patient with numerous comorbidities is also common in primary care consultations&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">How is the diagnosis of heart failure achieved&#63;</span><p id="par0015" class="elsevierStylePara elsevierViewall">The diagnosis of HF is established based on the presence of typical signs and symptoms &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; and objective evidence of ventricular dysfunction&#46; In the event of uncertainty&#44; the clinical response to a specific treatment could help establish the diagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">7&#8211;10</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Signs and symptoms</span><p id="par0020" class="elsevierStylePara elsevierViewall">Despite advances in imaging tests and laboratory markers&#44; the medical history and physical examination are still the essential tools for diagnosing HF&#46; Even so&#44; many signs and symptoms of HF are nonspecific and do not help discriminate this condition from other clinical problems&#46; The signs and symptoms secondary to sodium and water retention &#40;e&#46;g&#46;&#44; edema&#41; are highly nonspecific and can be secondary to other disorders&#46; Moreover&#44; the more specific symptoms such as orthopnea and paroxysmal nocturnal dyspnea are less common&#44; especially when the HF is moderate&#46; Signs such as increased jugular vein pressure&#44; lateral displacement of the apex beat and auscultation of a third heart sound&#44; although very specific&#44; are more difficult to objectify and reproduce among various observers&#46; For this reason&#44; the value of the medical history and physical examination for the diagnosis of HF has been occasionally questioned<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">7</span></a>&#59; however&#44; we should consider that these clinical tools are still indispensable&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">8&#8211;10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In the context of elderly patients with comorbidity&#44; especially obesity and COPD&#44; the diagnosis of HF based on signs and symptoms is especially difficult&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Electrocardiogram and chest radiography</span><p id="par0030" class="elsevierStylePara elsevierViewall">It is very common to find electrocardiographic abnormalities in patients with HF &#40;e&#46;g&#46;&#44; 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natriuretic peptides</span><p id="par0035" class="elsevierStylePara elsevierViewall">Given that most signs and symptoms of HF are nonspecific&#44; it is not uncommon for the results of an echocardiogram performed in the context of a diagnostic suspicion to be normal&#46; To avoid this situation or when echocardiography is not immediately available&#44; measurement of natriuretic peptides can be a diagnostic alternative&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">9</span></a> The release of these peptides increases when there is a myocardial lesion or when one of the cardiac cavities is overloaded &#40;e&#46;g&#46;&#44; pulmonary embolism&#44; AF&#41;&#46; Natriuretic peptide levels also increase with age and renal failure&#59; conversely&#44; the levels can decrease in patients with obesity &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; As with electrocardiograms&#44; natriuretic peptides have a high negative predictive value&#46; Thus&#44; normal concentrations in a patient without specific treatment makes a diagnosis of HF highly unlikely&#44; thereby obviating the need for an echocardiogram and requiring the search for other noncardiac causes to explain the symptoms&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">9&#44;12&#8211;14</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">The exclusion cutoffs for acute HF are 300<span class="elsevierStyleHsp" style=""></span>pg&#47;mL and 100<span class="elsevierStyleHsp" style=""></span>pg&#47;mL for NT-proBNP and BNP&#44; respectively&#46; When the clinical presentation is not acute&#44; the diagnostic sensitivity and specificity of natriuretic peptides decrease&#44; and the cutoffs for NT-proBNP and BNP decrease to 125<span class="elsevierStyleHsp" style=""></span>pg&#47;mL and 35<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">9</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Echocardiogram</span><p id="par0045" class="elsevierStylePara elsevierViewall">Despite its limitations&#44; the echocardiogram is still the imaging test of choice for assessing patients with a clinical suspicion of HF&#46; The technique helps us gain information on the cardiac anatomy and function &#40;volumes&#44; left ventricular systolic and diastolic function&#44; valvular function&#44; pulmonary artery pressure&#44; and pericardium&#41;&#46; Although systolic function can be determined by measuring the left ventricular ejection fraction &#40;LVEF&#41;&#44; there is no echocardiographic parameter that&#44; in isolation&#44; determines the diastolic function sufficiently accurately to ensure the diagnosis of HF with preserved LVEF&#46; Instead&#44; the echocardiogram must identify structural &#40;left ventricular hypertrophy and left atrial dilation&#41; and functional &#40;e&#46;g&#46;&#44; e&#8217;&#44; E&#47;e&#8217; ratio&#44; E&#47;A ratio&#41; abnormalities&#46; The presence of 2 or more of these abnormalities increases the diagnostic probability of HF with preserved LVEF&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">9&#44;10</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Diagnostic algorithm</span><p id="par0050" class="elsevierStylePara elsevierViewall">For the diagnosis of HF&#44; the European Society of Cardiology proposes a clinical assessment&#44; an ECG and&#44; typically&#44; a chest radiograph &#40;especially when the presentation is acute&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">9</span></a> For acute HF&#44; particularly if there are signs of severity&#44; an echocardiogram should be performed&#46; In the event natriuretic peptide levels are measured&#44; we will use the higher cutoff &#40;300<span class="elsevierStyleHsp" style=""></span>pg&#47;mL and 100<span class="elsevierStyleHsp" style=""></span>pg&#47;mL for NT-proBNP and BNP&#44; respectively&#41;&#46; When the severity is lower&#44; especially in outpatients&#44; the measurement of natriuretic peptide levels can be very useful for discriminating which patients should undergo an echocardiogram &#40;e&#46;g&#46;&#44; those with an abnormal ECG and natriuretic peptide levels above 125<span class="elsevierStyleHsp" style=""></span>pg&#47;mL and 35<span class="elsevierStyleHsp" style=""></span>pg&#47;mL for NT-proBNP and BNP&#44; respectively&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">9</span></a></p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Diagnosis of heart failure in patients with multiple diseases</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Elderly patients</span><p id="par0055" class="elsevierStylePara elsevierViewall">Elderly patients commonly present numerous comorbidities&#44; which already impede the diagnosis of HF&#46; The most common comorbidities are AF&#44; arterial hypertension&#44; ischemic heart disease&#44; diabetes&#44; renal failure&#44; anemia&#44; obesity&#44; COPD&#44; sleep apnea and lower extremity venous insufficiency&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">15</span></a> The presence of physical or cognitive impairment&#44; reduced mobility&#44; greater difficulty visiting the doctor or accessing the healthcare system and a lower demand for additional examinations by health professionals are factors that contribute to the underdiagnosis of HF in this type of patient&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">16</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In the elderly&#44; any disease can manifest with atypical signs and symptoms&#46; Symptoms of HF can be confused with or can resemble other comorbidities such as chronic respiratory diseases&#44; obesity and venous insufficiency&#46; However&#44; and as with the general nonelderly population&#44; signs and symptoms will continue to be an essential part of the initial assessment of elderly patients with HF&#46; There are a number of special considerations for elderly patients&#46; For example&#44; the absence of arterial hypertension&#44; diabetes or previous coronary artery disease and a completely normal ECG do not support the diagnosis of HF&#44; while the presence of a valve murmur &#40;especially aortic stricture and mitral regurgitation&#41; and the coexistence of AF support the diagnosis of HF in patients older than 80 years&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">15</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Additional examinations are needed for elderly patients to confirm the diagnosis of HF&#46; As with the nonelderly population&#44; ECG has a good negative predictive value while chest radiography can be misleading&#59; echocardiograms and the measurement of natriuretic peptide levels are therefore especially useful&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">15</span></a> The negative predictive value of natriuretic peptides is also very high in the elderly&#44; although the cutoffs have been validated for younger populations&#46; Therefore&#44; high concentrations of these peptides in the elderly population should be interpreted with greater caution because both age and some concomitant conditions can contribute to their increase &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Thus&#44; using the same diagnostic cutoffs for BNP in elderly patients can lead to an incorrect diagnosis of HF and&#44; as a result&#44; unnecessary treatment&#46; A number of studies have attempted to adapt these cutoffs to age &#40;especially NT-proBNP&#41;&#44; but for now these cutoffs should be used with prudence and clinical sense&#44; especially in elderly patients with concomitant comorbidities&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">17&#44;18</span></a> Nevertheless&#44; a number of authors still recommend the same cutoffs used for younger patients&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">19</span></a> In short&#44; natriuretic peptide concentrations should not be interpreted in isolation&#44; but rather with the other clinical&#44; laboratory and echocardiographic data&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">12</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The echocardiogram is necessary in virtually all cases&#44; except when the natriuretic peptide levels are below the cutoff points&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">9&#44;15</span></a> The echocardiogram&#39;s indications&#44; parameters to assess and interpretation are similar to those for the younger population&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">9&#44;15</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The proposed algorithm for the diagnosis of HF in the elderly is similar to that of the general nonelderly population &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#59; however&#44; there are a number of considerations when the signs and symptoms are nonspecific or unclear and when the ejection fraction is preserved&#44; a very common situation in the elderly population&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">15</span></a> Thus&#44; the echocardiogram findings will be more difficult to interpret when faced with a preserved ejection fraction&#44; especially when the cardiac rhythm is AF&#46; A practical approach for indirectly determining the diastolic function is measuring the size of the left atrium&#44; which will be increased when there is a persistent pressure increase in this cavity&#44; a reflection of the telediastolic pressure of the left ventricle&#46; Left atrial dilation is associated &#40;in the absence of mitral regurgitation&#41; with the duration and intensity of the diastolic dysfunction and can obviate the need to measure other&#44; much more complex parameters of diastolic dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">15</span></a> Left ventricular hypertrophy can also be a useful indirect marker of diastolic dysfunction&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">20&#44;21</span></a> The echocardiographic diagnosis can be more complex when there is AF&#44; because AF by itself can cause left atrial dilation without diastolic dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">22</span></a> When faced with this condition and if the HF diagnosis is in doubt&#44; we should consider the presence of other disorders such as left ventricular hypertrophy&#44; the greater increase in natriuretic peptide levels &#40;BNP<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>400<span class="elsevierStyleHsp" style=""></span>pg&#47;mL or NT-proBNP<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2000<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#44; respectively&#41; and&#47;or specific parameters of diastolic dysfunction &#40;mainly an E&#47;E&#8217; ratio<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>15&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">15</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patient with chronic obstructive pulmonary disease</span><p id="par0080" class="elsevierStylePara elsevierViewall">HF and COPD often coexist&#46; The prevalence of COPD in patients with HF varies between 9&#37; and 52&#37; and is higher in older studies that were based on clinical data or diagnostic codifications than in those based on the spirometric diagnosis of COPD&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">23&#44;24</span></a> In patients with stable COPD&#44; the prevalence of HF &#40;previously undiagnosed&#41; is approximately 20&#37;&#44; and the relative risk of developing HF is 4&#46;5 &#40;95&#37; CI 4&#46;25&#8211;4&#46;95&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">23&#44;24</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Pulmonary function studies should be interpreted with caution in patients with acute HF&#44; because a &#8220;dynamic&#8221; obstructive pattern can be observed&#44; which disappears by treating the HF itself&#46; Therefore&#44; it is recommended that&#44; in order to achieve a proper diagnosis of COPD&#44; pulmonary function studies should be performed when the patient with HF is in a stable phase and in an euvolemic condition&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">23</span></a> Moreover&#44; in some patients with COPD the diagnosis of HF will be difficult to establish through echocardiography due to the poor acoustic window caused by air trapping&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">24&#8211;26</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The high prevalence of HF in patients with COPD can be partially explained by the addition of vascular risk factors&#44; especially smoking&#46; Myocardial ischemia is one of the main causes of death in these patients&#44; in whom left ventricular systolic dysfunction is common&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">23&#44;27</span></a> It has been postulated that the presence of a &#8220;certain inflammatory condition&#8221; in COPD could be responsible for the progression of atherosclerosis&#44; including that of coronary arteries&#44; and ultimately of the greater prevalence of dilated ischemic cardiomyopathy in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">28</span></a> Moreover&#44; COPD causes chronic pressure overload in the right ventricle&#44; which translates into restricted left ventricular filling&#44; due to displacement of the interventricular septum towards the left&#44; which can lead to HF&#44; even in the absence of contractility depression&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">29</span></a> There is growing evidence relating diastolic dysfunction to COPD&#44; especially in those patients who experience multiple decompensations&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">30</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Of the various comorbidities that accompany HF&#44; COPD usually causes the most delays in the diagnosis&#46; When patients with COPD have dyspnea or fatigability&#44; these symptoms are usually attributed to the COPD itself&#59; ventricular dysfunction&#44; if it coexists&#44; remains hidden&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">31</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The diagnostic utility of natriuretic peptides in patients with COPD is increasingly well established &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; In the context of a COPD exacerbation&#44; a BNP concentration &#62;500<span class="elsevierStyleHsp" style=""></span>pg&#47;mL alerts us to presence of concomitant exacerbated HF&#44; regardless of whether the heart disease was known or unknown&#46; Although this high BNP concentration does not help us differentiate whether the cause of the clinical impairment was cardiac or pulmonary&#44; it should lead us to administer treatment for HF&#44; in addition to the treatment for COPD&#46; In contrast&#44; BNP values &#60;100<span class="elsevierStyleHsp" style=""></span>pg&#47;mL makes the presence of HF very unlikely as the cause of the worsening symptoms&#46; Intermediate values &#40;100&#8211;500<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41; can be indicative of the presence of right HF &#40;cor pulmonale&#41;&#44; left HF to a more moderate degree or both&#46; Once the patient with COPD has overcome the decompensation and is in stable clinical condition&#44; an echocardiogram should be performed to document the presence of underlying heart disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">23&#44;32</span></a> Moreover&#44; when we assess a patient with stable COPD&#44; the BNP concentrations are usually &#60;100<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#46; The echocardiogram will therefore have better performance for the diagnosis of HF&#46; When we need to obtain information on cardiac function but there is a poor acoustic window&#44; we can resort to isotopic ventriculography&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">23&#44;33</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">The NT-proBNP cutoffs have also been validated in patients with COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">34</span></a> A concentration &#60;300<span class="elsevierStyleHsp" style=""></span>pg&#47;mL allows us to rule out the diagnosis of HF&#44; with a sensitivity of 94&#37;&#46; When the concentration is &#62;450<span class="elsevierStyleHsp" style=""></span>pg&#47;mL in patients younger than 50 years and &#62;900<span class="elsevierStyleHsp" style=""></span>pg&#47;mL in those older than 50 years&#44; the specificity for establishing the diagnosis of HF is 84&#37;&#46; The diagnostic performance is better when the measurement of these peptides is performed based on clinical judgment&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patients with obesity</span><p id="par0110" class="elsevierStylePara elsevierViewall">The diagnosis of HF&#44; particularly the acute form&#44; is more difficult in patients with obesity&#46; Although the pathophysiological mechanisms that contribute to dyspnea associated with obesity are not completely known&#44; disorders in respiratory mechanics have been implicated&#44; both at rest and during exercise&#46; Patients with obesity must exert greater respiratory effort due to the lower &#8220;compliance&#8221; of their thoracic cage&#44; secondary to the restriction that the adipose tissue exerts on the chest and abdomen&#46; This increased respiratory effort requires greater activation of the respiratory muscles&#44; mainly the diaphragm&#44; and therefore greater metabolic demand&#46; This explains why the dyspnea these patients feel &#40;mainly effort dyspnea&#41; is frequently attributed to the obesity itself&#44; thereby delaying or omitting the diagnosis of HF&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">36</span></a> The dyspnea experienced by patients with obesity can also be explained by their poor physical condition and orthopnea due to the size of the abdominal wall&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Although studies have not been conducted to confirm it&#44; cardiopulmonary examinations of patients with obesity are less accurate in clinical practice due to the interference of the panniculus and respiratory mechanics disorders&#46; The examinations are further hindered by the difficulties in obtaining quality images&#44; both echocardiographic and radiological&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In this context&#44; the use of natriuretic peptides can be particularly useful&#44; although their interpretation has a number of peculiarities in patients with obesity&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">37</span></a> There is an inverse relationship between obesity &#40;using body mass index as the measure&#41; and natriuretic peptide concentrations&#46;<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">38&#44;39</span></a> It is believed that a higher glomerular filtration rate in patients with obesity increases peptide clearance<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">40</span></a> and that adipocytes express natriuretic peptide receptors that contribute to their clearance from the circulation&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">41</span></a> It is also believed that hyperinsulinism attenuates the secretion and activity of natriuretic peptides&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">42</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Therefore&#44; the cutoff points for the diagnosis of HF in patients with obesity should be lower than for patients with normal weight&#46; For example&#44; using the cutoff established at 100<span class="elsevierStyleHsp" style=""></span>pg&#47;mL for BNP&#44; we would obtain a rate of up to 20&#37; of false negatives&#46; Consequently&#44; it is suggested that the cutoff be reduced to <span class="elsevierStyleUnderline">&#60;</span>54<span class="elsevierStyleHsp" style=""></span>pg&#47;mL to rule out HF in patients with a body mass index <span class="elsevierStyleUnderline">&#62;</span>35 &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Similarly&#44; it has been proposed that the BNP cutoff be increased to <span class="elsevierStyleUnderline">&#62;</span>170<span class="elsevierStyleHsp" style=""></span>pg&#47;mL for thin participants&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">13&#44;43</span></a> In contrast to what happens with BNP&#44; NT-proBNP concentrations &#60;300<span class="elsevierStyleHsp" style=""></span>pg&#47;mL still have a good negative predictive value for patients with excess weight or obesity&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">44</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Some of the peculiarities of patients with obesity help explain&#44; at least in part&#44; the obesity paradox in HF&#59; i&#46;e&#46;&#44; why patients with excess weight or obesity have better prognoses than patients with normal weight&#46; First&#44; excess weight can cause symptoms such as dyspnea &#40;due to lung restriction&#41; and edema &#40;due to venous insufficiency&#41;&#46; Although these symptoms are not necessarily related directly to HF&#44; they can lead to its diagnosis in earlier stages&#44; even for mild forms of the disease&#46; It has been suggested that the reduction in natriuretic peptide levels&#44; which is common in obesity&#44; is accompanied by increased sodium and water retention&#44; which promotes the earlier onset of dyspnea&#44; regardless of ventricular dysfunction severity&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">45</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Patients with multiple comorbidities</span><p id="par0135" class="elsevierStylePara elsevierViewall">Patients with HF&#44; regardless of age&#44; the presence of obesity and concomitant COPD have other associated comorbidities that further hinder the diagnosis&#46; For example&#44; dementia<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">5</span></a> can contribute to diagnostic delays&#44; poorer treatment adherence and poorer prognoses&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">46</span></a> If there is also anemia and renal failure&#44; which are very common&#44;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">5&#44;6</span></a> the symptoms can be confused with those of HF&#44; and the interpretation of natriuretic peptide levels will be much more difficult&#46; For patients with multiple comorbidities&#44; there is no diagnostic recommendation based on scientific evidence&#44; and only clinical experience will help adequately reach a diagnosis of HF&#46;</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusions</span><p id="par0140" class="elsevierStylePara elsevierViewall">The diagnosis of HF in patients with comorbidities is more complex&#44; especially in elderly patients and when there is concomitant COPD or obesity&#46; Despite its limitations&#44; the medical history and physical examination are still essential tools for the diagnostic suspicion&#46; Echocardiograms and natriuretic peptide measurements are the main additional tests for confirming the diagnosis&#46; Natriuretic peptide levels are influenced by multiple comorbidities&#44; and the echocardiography data can be difficult to interpret when the LVEF is preserved&#46; Therefore&#44; none of these examinations in isolation &#40;if not accompanied by clinical judgment&#41; help to reach an accurate diagnosis&#46;</p></span></span>"
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      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Heart failure &#40;HF&#41; patients present frequently comorbidities and the diagnosis of HF in this setting is a challenge&#46; The symptoms and signs of HF may be atypical and can be simulated or disguised by co-morbidities such as respiratory disease and&#47;or obesity&#46; For this reasons&#44; confirmation of the diagnosis always requires further tests&#46; Natriuretic peptides accurately exclude cardiac dysfunction as a cause of symptoms&#44; but the optimal cut-off levels for ruling out and ruling in HF diagnosis are influenced by different co-morbidities&#46; Echocardiography should be performed in all patients to confirm the diagnosis of HF&#44; except in those cases with low clinical probability and a concentration of brain natriuretic peptides below the exclusion cut-off&#46; This review aims to provide a practical clinical approach for the diagnosis of HF in patients with comorbidity&#44; focusing in older patients and patients with chronic obstructive pulmonary disease and&#47;or obesity&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con insuficiencia cardiaca &#40;IC&#41; con frecuencia presentan comorbilidades que pueden dificultar su diagn&#243;stico&#46; Los signos y s&#237;ntomas de la IC pueden ser at&#237;picos o dif&#237;ciles de distinguir de los de otras comorbilidades&#44; como las enfermedades respiratorias o la obesidad&#46; Por ello&#44; para confirmar el diagn&#243;stico suelen ser precisas exploraciones complementarias&#46; Los p&#233;ptidos natriur&#233;ticos permiten excluir de forma adecuada la disfunci&#243;n card&#237;aca&#44; pero los puntos de corte &#243;ptimos&#44; tanto para la exclusi&#243;n como para la confirmaci&#243;n diagn&#243;stica de la IC&#44; est&#225;n influenciados por las distintas comorbilidades&#46; El ecocardiograma deber&#225; realizarse a todos los pacientes para confirmar el diagn&#243;stico de IC&#44; excepto cuando la probabilidad cl&#237;nica sea muy baja y la concentraci&#243;n de p&#233;ptidos natriur&#233;ticos est&#233; por debajo del punto de corte de exclusi&#243;n&#46; En esta revisi&#243;n se proponen recomendaciones pr&#225;cticas para el diagn&#243;stico de IC en pacientes con comorbilidades&#44; especialmente en el paciente anciano&#44; con enfermedad pulmonar obstructiva cr&#243;nica u obesidad&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; Trull&#224;s JC&#44; Casado J&#44; Morales-Rull JL&#46; Dificultad del diagn&#243;stico de insuficiencia card&#237;aca en el paciente con comorbilidad&#46; Rev Clin Esp&#46; 2016&#59;216&#58;276&#8211;285&#46;</p>"
      ]
    ]
    "multimedia" => array:4 [
      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "Modified from Manzano et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">15</span></a>"
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2636
            "Ancho" => 1637
            "Tamanyo" => 258639
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Algorithm diagnosis of heart failure in the elderly&#46; LVEF&#44; ejection fraction of the left ventricle&#59; HFDEF&#44; heart failure with depressed ejection fraction&#59; HFPEF&#44; heart failure with preserved ejection fraction&#46; <span class="elsevierStyleSup">a</span>Si no availability to determine natriuretic peptides can be an echocardiogram&#46; <span class="elsevierStyleSup">b</span>Diameter<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>cm&#44; area<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">2</span>&#44; volume<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>mL&#47;m<span class="elsevierStyleSup">2</span>&#46; <span class="elsevierStyleSup">c</span>Other parameters may support the diagnosis&#58; ratio E&#47;E&#8242; by dopper tisular<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>15&#44; left ventricular hypertrophy or BNP&#47;NT-proBNP above 400<span class="elsevierStyleHsp" style=""></span>pg&#47;mL and 2&#46;000<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#44; respectively&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "Adapted from Mc Murray et al&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">9</span></a> and Manzano et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">15</span></a>"
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">In elderly patients &#40;&#62;80 years&#41;&#44; the diagnosis of HF is strongly favored&#58; the presence of a murmur suggestive of valvular heart disease &#40;especially aortic stricture and mitral regurgitation&#41;&#44; irregular pulse &#40;possible coexistence of atrial fibrillation&#41; and improved dyspnea in response to diuretic treatment&#46; The absence of dyspnea&#44; no previous history of AHT&#44; the lack of diabetes and the lack of coronary artery disease&#44; as well as a completely normal ECG strongly suggest against the diagnosis of HF&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">AHT&#44; arterial hypertension&#59; ECG&#44; electrocardiogram&#59; HF&#44; heart failure&#46;</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">Symptoms&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">Signs&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">Typical</span><br><span class="elsevierStyleHsp" style=""></span>Dyspnea<br><span class="elsevierStyleHsp" style=""></span>Orthopnea<br><span class="elsevierStyleHsp" style=""></span>Paroxysmal nocturnal dyspnea<br><span class="elsevierStyleHsp" style=""></span>Lower exercise tolerance<br><span class="elsevierStyleHsp" style=""></span>Fatigue&#44; difficulty recovering from exercise<br><span class="elsevierStyleHsp" style=""></span>Ankle edema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">More specific</span><br><span class="elsevierStyleHsp" style=""></span>Increased jugular vein pressure &#40;engorgement&#41;<br><span class="elsevierStyleHsp" style=""></span>Hepatojugular reflux<br><span class="elsevierStyleHsp" style=""></span>Third heart sound &#40;gallop rhythm&#41;<br><span class="elsevierStyleHsp" style=""></span>Lateral displacement of the apex beat<br><span class="elsevierStyleHsp" style=""></span>Heart murmurs&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="2" 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">Less typical</span><br><span class="elsevierStyleHsp" style=""></span>Night-time cough<br><span class="elsevierStyleHsp" style=""></span>Wheezing<br><span class="elsevierStyleHsp" style=""></span>Weight gain &#40;&#62;2<span class="elsevierStyleHsp" style=""></span>kg&#47;week&#41;<br><span class="elsevierStyleHsp" style=""></span>Weight loss &#40;in advanced HF&#41;<br><span class="elsevierStyleHsp" style=""></span>Sensation of fullness<br><span class="elsevierStyleHsp" style=""></span>Anorexia<br><span class="elsevierStyleHsp" style=""></span>Confusion &#40;especially in the elderly&#41;<br><span class="elsevierStyleHsp" style=""></span>Depression<br><span class="elsevierStyleHsp" style=""></span>Palpitations<br><span class="elsevierStyleHsp" style=""></span>Syncope&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Less specific</span><br><span class="elsevierStyleHsp" style=""></span>Peripheral edema &#40;sacral&#44; scrotal&#44; ankle&#41;<br><span class="elsevierStyleHsp" style=""></span>Pulmonary crackles<br><span class="elsevierStyleHsp" style=""></span>Tachycardia<br><span class="elsevierStyleHsp" style=""></span>Irregular pulse<br><span class="elsevierStyleHsp" style=""></span>Tachypnea<br><span class="elsevierStyleHsp" style=""></span>Hepatomegaly<br><span class="elsevierStyleHsp" style=""></span>Ascites<br><span class="elsevierStyleHsp" style=""></span>Cachexia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1095846.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Signs and symptoms of heart failure&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "Adapted from Yancy et al&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">10</span></a>"
        "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"><span class="elsevierStyleItalic">Increased natriuretic peptide levels due to cardiac causes</span>&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>Heart failure &#40;including right-sided heart failure&#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"><span class="elsevierStyleHsp" style=""></span>Acute coronary syndrome&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>Cardiac muscle disease &#40;including left ventricular hypertrophy&#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"><span class="elsevierStyleHsp" style=""></span>Heart valve disease&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>Pericardial disease&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>Atrial fibrillation and other atrial 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"><span class="elsevierStyleHsp" style=""></span>Ventricular 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"><span class="elsevierStyleHsp" style=""></span>Myocarditis&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>Cardiac surgery&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>Cardioversion&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="elsevierStyleVsp" style="height:0.5px"></span>&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="elsevierStyleItalic">Increased natriuretic peptide levels due to noncardiac causes</span>&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>Advanced age &#40;&#62;75 years&#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"><span class="elsevierStyleHsp" style=""></span>Anemia&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>Renal failure&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>Obstructive sleep apnea&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>Chronic obstructive pulmonary d&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>Pulmonary thromboembolism&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>Pulmonary 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"><span class="elsevierStyleHsp" style=""></span>Severe pneumonia&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>Sepsis&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>Critical patients&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>Severe burns&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>Toxic-metabolic &#40;including chemotherapy&#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"><span class="elsevierStyleVsp" style="height:0.5px"></span>&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="elsevierStyleItalic">Decreased natriuretic peptide levels</span>&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>Overweight&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>Obesity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1095845.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Causes of changes in natriuretic peptide levels&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Note</span>&#58; The exclusion cutoff points help minimize the rate of false negatives and should always be used at the clinician&#39;s discretion&#44; especially if the levels drop into the &#8220;grey area&#8221;&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">BMI&#44; body mass index&#59; COPD&#44; chronic obstructive pulmonary disease&#59; HF&#44; heart failure&#46;</p>"
          "tablatextoimagen" => array:2 [
            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="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Symptom presentation form</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">BNP</th><th class="td" title="table-head  " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NT-pro-BNP<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&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">Exclusion cutoffs&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">Grey area&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">Inclusion cutoffs&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">Exclusion cutoffs&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">Inclusion cutoffs&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" title="table-entry  " rowspan="2" align="left" valign="top">General population<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">9&#44;12</span></a></td><td class="td" title="table-entry  " align="left" valign="top">Acute&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Highly unlikely &#40;2&#37;&#41;&#58;<br>&#60;100<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Likely<br>&#40;75&#37;&#41;&#58;<br>100&#8211;400<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Highly likely &#40;95&#37;&#41;&#58;<br>&#62;400<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Highly unlikely&#58;<br>&#60;300<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Use inclusion cutoffs adjusted for age&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">Nonacute&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;35<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">&#62;35<span class="elsevierStyleHsp" style=""></span>pg&#47;mL perform echocardiogram</td><td class="td" title="table-entry  " align="left" valign="top">&#60;125<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;125<span class="elsevierStyleHsp" style=""></span>pg&#47;mL perform echocardiogram&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="7" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Age<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">17&#44;18</span></a></td><td class="td" title="table-entry  " align="left" valign="top">Acute&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="2" align="left" valign="top" colspan="3">The same cutoffs used for the general population</td><td class="td" title="table-entry  " align="left" valign="top">&#60;300<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;50 years&#58; &#62;450<span class="elsevierStyleHsp" style=""></span>pg&#47;mL<br>50&#8211;75 years&#58; &#62;900<span class="elsevierStyleHsp" style=""></span>pg&#47;mL<br>&#62;75 years&#58; &#62;1800<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&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">Nonacute&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;50 years&#58; &#60;50<span class="elsevierStyleHsp" style=""></span>pg&#47;mL<br>50&#8211;75 years&#58; &#60;75<span class="elsevierStyleHsp" style=""></span>pg&#47;mL<br>&#62;75 years&#58; &#60;250<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;125<span class="elsevierStyleHsp" style=""></span>pg&#47;mL perform echocardiogram&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            1 => array:2 [
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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  " colspan="7" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Special circumstances</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">BNP</th><th class="td" title="table-head  " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NT-proBNP<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&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">Exclusion cutoffs&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">Grey area&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">Inclusion cutoffs&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">Exclusion cutoffs&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">Inclusion cutoffs&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" title="table-entry  " rowspan="2" align="left" valign="top">COPD<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">23&#44;31&#8211;34</span></a></td><td class="td" title="table-entry  " align="left" valign="top">Exacerbation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Highly unlikely&#58; &#60;100<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Right-sided or moderate left-sided HF&#58;<br>100&#8211;500<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Highly likely left-sided HF&#58; &#62;500<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;300<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;450<span class="elsevierStyleHsp" style=""></span>pg&#47;mL &#40;age &#60;50 years&#41;<br>&#62;900<span class="elsevierStyleHsp" style=""></span>pg&#47;mL &#40;age &#62;50 years&#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">Stable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="5" align="left" valign="top">BNP and NT-proBNP levels are usually low for stable COPD&#59; therefore&#44; the echocardiogram will have better diagnostic performance&#46;</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" 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">Obesity<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">13&#44;42&#44;43</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BMI<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>25<br>BMI 25&#8211;35<br>BMI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;170<span class="elsevierStyleHsp" style=""></span>pg&#47;mL<br>&#60;110<span class="elsevierStyleHsp" style=""></span>pg&#47;mL<br>&#60;54<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">No conclusive data</td><td class="td" title="table-entry  " align="left" valign="top">&#60;300<span class="elsevierStyleHsp" style=""></span>pg&#47;mL<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No conclusive data&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="7" 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">Atrial fibrillation<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">15</span></a>&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  " colspan="2" align="left" valign="top">No conclusive data</td><td class="td" title="table-entry  " align="left" valign="top">&#62;400<span class="elsevierStyleHsp" style=""></span>pg&#47;mL<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No conclusive data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;2000<span class="elsevierStyleHsp" style=""></span>pg&#47;mL<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&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="7" 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">Renal failure<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">12</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="6" align="left" valign="top">The cutoffs need to be increased when the GFR is &#60;60<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#46; Currently&#44; there are no data for recommending GFR-adjusted cutoff points&#46; The reading of BNP&#47;NT-proBNP levels is not recommended for patients in dialysis&#46;</td></tr></tbody></table>
                  """
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            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">NT-proBNP levels &#60;300<span class="elsevierStyleHsp" style=""></span>pg&#47;mL are considered an appropriate exclusion cutoff for ruling out HF &#40;acute presentation&#41; in all age categories and for patients with COPD or obesity&#46; The cutoff points for confirming the diagnosis are age dependent&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">In contrast to BNP&#44; low levels of NT-proBNP in patients with excess weight or obesity do not appear to reduce the diagnostic ability of this biomarker&#46; Thus&#44; the cutoff of 300<span class="elsevierStyleHsp" style=""></span>pg&#47;mL continues to have good negative predictive value for patients with excess weight or obesity&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">When the LVEF is preserved and there is atrial fibrillation&#44; there can be reasonable doubts about the HF diagnosis&#46; The use of higher cutoff points might therefore be advisable&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Recommended cutoffs for BNP and NT-proBNP for suspected heart failure&#46;</p>"
        ]
      ]
    ]
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Journal Information
Vol. 216. Issue 5.
Pages 276-285 (June - July 2016)
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Vol. 216. Issue 5.
Pages 276-285 (June - July 2016)
Symposium. Heart Failure
Difficulties in the diagnosis of heart failure in patients with comorbidities
Dificultad del diagnóstico de insuficiencia cardíaca en el paciente con comorbilidad
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J.C. Trullàsa,
Corresponding author
jctv5153@comg.cat

Corresponding author.
, J. Casadob, J.L. Morales-Rullc
a Servicio de Medicina Interna, Hospital de Olot (Girona), Universitat de Girona, Girona, Spain
b Servicio de Medicina Interna, Hospital de Getafe, Madrid, Spain
c Servicio de Medicina Interna, Hospital Universitario Arnau de Vilanova , Lleida, Spain
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Tables (3)
Table 1. Signs and symptoms of heart failure.
Table 2. Causes of changes in natriuretic peptide levels.
Table 3. Recommended cutoffs for BNP and NT-proBNP for suspected heart failure.
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Abstract

Heart failure (HF) patients present frequently comorbidities and the diagnosis of HF in this setting is a challenge. The symptoms and signs of HF may be atypical and can be simulated or disguised by co-morbidities such as respiratory disease and/or obesity. For this reasons, confirmation of the diagnosis always requires further tests. Natriuretic peptides accurately exclude cardiac dysfunction as a cause of symptoms, but the optimal cut-off levels for ruling out and ruling in HF diagnosis are influenced by different co-morbidities. Echocardiography should be performed in all patients to confirm the diagnosis of HF, except in those cases with low clinical probability and a concentration of brain natriuretic peptides below the exclusion cut-off. This review aims to provide a practical clinical approach for the diagnosis of HF in patients with comorbidity, focusing in older patients and patients with chronic obstructive pulmonary disease and/or obesity.

Keywords:
Heart failure
Diagnosis
Comorbidity
Natriuretic peptides
Resumen

Los pacientes con insuficiencia cardiaca (IC) con frecuencia presentan comorbilidades que pueden dificultar su diagnóstico. Los signos y síntomas de la IC pueden ser atípicos o difíciles de distinguir de los de otras comorbilidades, como las enfermedades respiratorias o la obesidad. Por ello, para confirmar el diagnóstico suelen ser precisas exploraciones complementarias. Los péptidos natriuréticos permiten excluir de forma adecuada la disfunción cardíaca, pero los puntos de corte óptimos, tanto para la exclusión como para la confirmación diagnóstica de la IC, están influenciados por las distintas comorbilidades. El ecocardiograma deberá realizarse a todos los pacientes para confirmar el diagnóstico de IC, excepto cuando la probabilidad clínica sea muy baja y la concentración de péptidos natriuréticos esté por debajo del punto de corte de exclusión. En esta revisión se proponen recomendaciones prácticas para el diagnóstico de IC en pacientes con comorbilidades, especialmente en el paciente anciano, con enfermedad pulmonar obstructiva crónica u obesidad.

Palabras clave:
Insuficiencia cardiaca
Diagnóstico
Comorbilidad
Péptidos natriuréticos

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