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Heart failure with preserved ejection fraction: A moving target
Insuficiência cardíaca com fração de ejeção preservada: um alvo em movimento
Brenda Moura
Serviço de Cardiologia, Hospital Regional Militar n.° 1, Porto, Portugal
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However, some patients with hypertrophic cardiomyopathy or coronary artery disease presented normal ejection fraction and a clinical setting compatible with HF; these were considered to have diastolic HF.</p><p id="par0010" class="elsevierStylePara elsevierViewall">However, in the last twenty years, our understanding of HF has changed radically, a significant percentage of patients presenting HF with preserved ejection fraction (HFPEF), but who do not fit into previously established categories. Although such individuals account for an increasing proportion of HF patients (rising from 38% to 54% between 1987 and 2001, and increasing by around 1% a year),<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> little is known concerning this entity.</p><p id="par0015" class="elsevierStylePara elsevierViewall">What is reasonably sure is that such patients are predominantly female and older, are more likely to have hypertension and atrial fibrillation but less likely to have coronary artery disease, and have more comorbidities, than patients with HF with reduced ejection fraction (HFREF). Beyond that, little is known for certain.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Despite the large number of patients with HFPEF, there is still no consensus on the mortality associated with this entity. For years, it was considered to be similar to that of patients with HFREF,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> but a 2012 meta-analysis of randomized clinical trials involving over 40 000 patients showed lower mortality in HFPEF (adjusted for age, gender, etiology, and history of hypertension, diabetes and atrial fibrillation).<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> However, a presentation by the Canadian Heart Failure Network at the European Society of Cardiology's Heart Failure Congress 2013 reported no difference in survival between HFPEF and HPREF patients in a study of approximately 10 000 individuals.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Although these results appear contradictory, certain considerations should be borne in mind. HFPEF patients tend to have more comorbidities, which may affect mortality, and in fact cardiac death is less common in this patient group. The variability of results may thus be due to differences in the number and severity of comorbidities.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The prognosis of HFPEF has not changed in recent years, in contrast to that of HFREF, in which advances in medical therapy and devices have led to reductions in morbidity and mortality. There is as yet no evidence that any drug or device reduces mortality in HFPEF.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–6</span></a> There are various possible reasons for the failure of randomized clinical trials to demonstrate any benefit, but inappropriate patient selection will certainly have played a part. In the PEP-CHF (Perindopril in Elderly People with Chronic HF) study, the diagnosis of diastolic dysfunction was established by pulsed Doppler, and the mean age of the population was 78 years, which calls into question the reliability of this assessment. In the CHARM-Preserved Trial (Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction), an echocardiographic sub-study showed diastolic dysfunction in only 67% of the patients. In the I-PRESERVE trial (Outcome of heart failure with preserved ejection fraction in a population-based study), which included patients with dyspnea compatible with HF in NYHA class II-IV, the fact that 41% of patients had a body mass index of ≥30 kg/m<span class="elsevierStyleSup">2</span> and that the 25th percentile of N-terminal pro-brain natriuretic peptide (NT-proBNP) was 139 vs. 131 pg/ml (irbesartan vs. placebo) raises the possibility that etiologies other than HF may have caused dyspnea.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Review of the characteristics of patients included in these large studies suggests that there was considerable potential for inappropriate patient selection. Nevertheless, a more important problem is the limited understanding of HFPEF.</p><p id="par0040" class="elsevierStylePara elsevierViewall">There is growing evidence that it is not merely a question of diastolic dysfunction. Tan et al.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> found that, following thorough echocardiographic evaluation at rest and during exercise, HFPEF patients presented multiple changes in systolic (lower radial and longitudinal strain, apical rotation and mitral annular velocities) and diastolic function (reduced and delayed untwisting and reduced LV suction) at rest, which were more marked during exercise.</p><p id="par0045" class="elsevierStylePara elsevierViewall">However, abnormalities in this syndrome are not limited to systolic and diastolic function; there are other changes that are manifested during exercise, including chronotropic incompetence,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> vasodilatory disturbances and pulmonary hypertension.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> During physical exertion, cardiac output increases through integrated enhancements in venous return, contractility, heart rate, peripheral vasodilation and diastolic function. Borlaug et al., in a landmark article published in <span class="elsevierStyleItalic">Circulation</span> in 2006, described HFPEF as a syndrome of impaired cardiac reserves, since all these parameters are altered.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">This lends weight to the idea that HF should be considered a syndrome rather than a diagnosis, and that patients with HFPEF have a variety of clinical and risk profiles, far more heterogeneous than those with HFREF. Decision trees that reflect the above-mentioned alterations may be more successful in arriving at a correct diagnosis, as well as in guiding appropriate treatment.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Natriuretic peptide measurement is now widely used and its value in HFREF patients is undisputed. Recent studies suggest that it may also be useful in diagnosis and prognostic assessment of HFPEF.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Until the publication of the latest European guidelines on HF, the BNP and NT-proBNP cutoffs for exclusion of HF were 100 and 400 pg/ml, respectively. According to some studies, these values are too high and have low sensitivity for a diagnosis of HF. However, it should be noted that most studies on BNP measurement have focused on patients with acute symptoms seen in the emergency department, whose BNP levels reflected a different setting from that of outpatients with milder symptoms.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The latest ESC guidelines (2012) suggest different cutoffs for BNP and NT-proBNP depending on whether dyspnea is of acute or non-acute onset (100 and 300 pg/ml for acute onset, and 35 and 125 pg/ml for non-acute situations, respectively). However, the data on which these recommended values are based are limited and not specific to patients with preserved ejection fraction. Krishnaswamy et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> assessed 400 individuals with HF and showed that a BNP cutoff of 57 pg/ml identified 100% of patients with diastolic dysfunction.</p><p id="par0070" class="elsevierStylePara elsevierViewall">In a study presented in this issue of the <span class="elsevierStyleItalic">Journal</span>, Jorge et al. assessed 161 outpatients with suspected HFPEF and analyzed the correlation between clinical, electrocardiographic and echocardiographic characteristics and BNP levels. HFPEF was confirmed in 49 individuals, and the best BNP cutoff for the diagnosis was 51 pg/ml. These results are in agreement with other studies in similar patients. The interest of the study lies in its suggestion that lower BNP levels should be used for screening outpatients with suspected HF. However, these levels are higher than those used for a diagnosis of HFREF.</p><p id="par0075" class="elsevierStylePara elsevierViewall">To summarize, after more than twenty years of research into this entity, few results with clinical impact have been forthcoming. Recent discoveries concerning the pathophysiology and diagnosis of HFPEF may prove fruitful in the near future. In the meantime, it will continue to be termed heart failure with preserved ejection fraction, as the latter is the only characteristic common to all such patients.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-06-25" "fechaAceptado" => "2013-06-25" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Moura B. Insuficiência cardíaca com fração de ejeção preservada: um alvo em movimento. Rev Port Cardiol. 2013;32:653–655.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:12 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C.W. Yancy" 1 => "M. Lopatin" 2 => "L.W. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 6 | 14 |
| 2024 October | 41 | 36 | 77 |
| 2024 September | 37 | 27 | 64 |
| 2024 August | 35 | 30 | 65 |
| 2024 July | 28 | 28 | 56 |
| 2024 June | 33 | 21 | 54 |
| 2024 May | 40 | 29 | 69 |
| 2024 April | 26 | 21 | 47 |
| 2024 March | 59 | 19 | 78 |
| 2024 February | 23 | 15 | 38 |
| 2024 January | 33 | 26 | 59 |
| 2023 December | 29 | 16 | 45 |
| 2023 November | 24 | 33 | 57 |
| 2023 October | 30 | 16 | 46 |
| 2023 September | 18 | 20 | 38 |
| 2023 August | 29 | 20 | 49 |
| 2023 July | 18 | 14 | 32 |
| 2023 June | 29 | 16 | 45 |
| 2023 May | 40 | 32 | 72 |
| 2023 April | 21 | 7 | 28 |
| 2023 March | 31 | 24 | 55 |
| 2023 February | 22 | 28 | 50 |
| 2023 January | 15 | 15 | 30 |
| 2022 December | 24 | 19 | 43 |
| 2022 November | 31 | 19 | 50 |
| 2022 October | 22 | 19 | 41 |
| 2022 September | 16 | 38 | 54 |
| 2022 August | 23 | 24 | 47 |
| 2022 July | 37 | 28 | 65 |
| 2022 June | 16 | 16 | 32 |
| 2022 May | 21 | 26 | 47 |
| 2022 April | 26 | 19 | 45 |
| 2022 March | 31 | 28 | 59 |
| 2022 February | 26 | 13 | 39 |
| 2022 January | 23 | 20 | 43 |
| 2021 December | 17 | 23 | 40 |
| 2021 November | 34 | 38 | 72 |
| 2021 October | 34 | 42 | 76 |
| 2021 September | 25 | 26 | 51 |
| 2021 August | 37 | 23 | 60 |
| 2021 July | 19 | 26 | 45 |
| 2021 June | 30 | 16 | 46 |
| 2021 May | 32 | 36 | 68 |
| 2021 April | 30 | 21 | 51 |
| 2021 March | 63 | 20 | 83 |
| 2021 February | 66 | 11 | 77 |
| 2021 January | 34 | 10 | 44 |
| 2020 December | 31 | 3 | 34 |
| 2020 November | 34 | 8 | 42 |
| 2020 October | 17 | 12 | 29 |
| 2020 September | 53 | 10 | 63 |
| 2020 August | 12 | 9 | 21 |
| 2020 July | 41 | 6 | 47 |
| 2020 June | 33 | 3 | 36 |
| 2020 May | 29 | 4 | 33 |
| 2020 April | 47 | 17 | 64 |
| 2020 March | 40 | 7 | 47 |
| 2020 February | 43 | 27 | 70 |
| 2020 January | 36 | 6 | 42 |
| 2019 December | 38 | 8 | 46 |
| 2019 November | 25 | 6 | 31 |
| 2019 October | 46 | 2 | 48 |
| 2019 September | 21 | 11 | 32 |
| 2019 August | 32 | 6 | 38 |
| 2019 July | 40 | 10 | 50 |
| 2019 June | 24 | 7 | 31 |
| 2019 May | 51 | 10 | 61 |
| 2019 April | 23 | 8 | 31 |
| 2019 March | 88 | 11 | 99 |
| 2019 February | 61 | 15 | 76 |
| 2019 January | 82 | 9 | 91 |
| 2018 December | 79 | 12 | 91 |
| 2018 November | 81 | 13 | 94 |
| 2018 October | 80 | 20 | 100 |
| 2018 September | 54 | 14 | 68 |
| 2018 August | 38 | 14 | 52 |
| 2018 July | 27 | 5 | 32 |
| 2018 June | 44 | 8 | 52 |
| 2018 May | 61 | 3 | 64 |
| 2018 April | 42 | 3 | 45 |
| 2018 March | 75 | 10 | 85 |
| 2018 February | 28 | 2 | 30 |
| 2018 January | 56 | 5 | 61 |
| 2017 December | 83 | 7 | 90 |
| 2017 November | 39 | 8 | 47 |
| 2017 October | 38 | 5 | 43 |
| 2017 September | 26 | 5 | 31 |
| 2017 August | 44 | 10 | 54 |
| 2017 July | 35 | 8 | 43 |
| 2017 June | 49 | 10 | 59 |
| 2017 May | 49 | 12 | 61 |
| 2017 April | 25 | 4 | 29 |
| 2017 March | 33 | 32 | 65 |
| 2017 February | 31 | 2 | 33 |
| 2017 January | 21 | 4 | 25 |
| 2016 December | 27 | 11 | 38 |
| 2016 November | 14 | 6 | 20 |
| 2016 October | 20 | 6 | 26 |
| 2016 September | 20 | 8 | 28 |
| 2016 August | 9 | 3 | 12 |
| 2016 July | 14 | 4 | 18 |
| 2016 June | 10 | 6 | 16 |
| 2016 May | 10 | 9 | 19 |
| 2016 April | 32 | 1 | 33 |
| 2016 March | 61 | 11 | 72 |
| 2016 February | 70 | 25 | 95 |
| 2016 January | 43 | 6 | 49 |
| 2015 December | 47 | 10 | 57 |
| 2015 November | 49 | 10 | 59 |
| 2015 October | 44 | 11 | 55 |
| 2015 September | 42 | 12 | 54 |
| 2015 August | 54 | 21 | 75 |
| 2015 July | 47 | 8 | 55 |
| 2015 June | 26 | 3 | 29 |
| 2015 May | 38 | 9 | 47 |
| 2015 April | 55 | 16 | 71 |
| 2015 March | 46 | 10 | 56 |
| 2015 February | 47 | 6 | 53 |
| 2015 January | 49 | 11 | 60 |
| 2014 December | 45 | 13 | 58 |
| 2014 November | 35 | 10 | 45 |
| 2014 October | 60 | 6 | 66 |
| 2014 September | 38 | 10 | 48 |
| 2014 August | 32 | 6 | 38 |
| 2014 July | 34 | 15 | 49 |
| 2014 June | 19 | 5 | 24 |
| 2014 May | 31 | 12 | 43 |
| 2014 April | 35 | 5 | 40 |
| 2014 March | 51 | 10 | 61 |
| 2014 February | 55 | 22 | 77 |
| 2014 January | 56 | 12 | 68 |
| 2013 December | 38 | 13 | 51 |
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