Health-Related Quality of Life in Heart Failure With Preserved Ejection Fraction

Recognition that heart failure (HF) is a major global health problem has led to widespread study of its causes, underlying mechanisms, associated co-morbidities and clinical characteristics. Most importantly, it has resulted in the development of therapies that greatly improve outcomes, particularly for patients with HF with reduced ejection fraction (HFrEF). Progress in understanding and treating HF, however, has been uneven with less robust advances seen in some areas than in others. One area that is lagging is the understanding of differences between men and women in several facets of HF, including pathophysiology, clinical presentation, management decisions and response to therapy. In this issue of the Journal, Frigerio and colleagues present an interesting case of a patient in whom the diagnosis and treatment of HF were greatly delayed. 1 While their lucid discussion attributes this to the patient's past history, her young age, and the presence of somewhat atypical symptoms, it is also possible that the patient's sex played a role. In this article, we discuss some of the gender differences in HF and their clinical implications.As summarized in Table 1, 2-6 there are important differences between men and women in the prevalence of risk factors for HF. Coronary artery disease (CAD) is, in general, the most strongly associated risk factor for HF with a population attributable risk (PAR) of 61%. 7 When gender differences are incorporated, however, the PAR for CAD is more than doubled in men compared to women at 39% and 18%, respectively. 8 In contrast, the PAR for hypertension, another common risk factor for HF, is higher in women than for men (59% compared to 39%). 8 Hypertension disproportionately affects women after the age of 65 years, with a threefold increase in risk of developing HF in this group, compared to a twofold increase in risk in men. 8 These differences play a role in determining well known sex and age differences in HF phenotype with HFrEF being more common and presenting at a younger age in males while HF with preserved ejection fraction (HFpEF) is more common in older women. Moreover, there is an interaction between sex and development of HF for some risk factors. Although diabetes mellitus is more common in men than in women, it has been associated with a fivefold increase in HF risk in women compared to only a twofold increase in risk in men. 9 In women with CAD, diabetes has been identified as the strongest predictor of HF. 10 Differences in the prevalence of risk factors have *Corresponding author. Advanced Heart Failure Treatment Program,

Section: Prevalence Of Cardiovascular and Non‐cardiovascular Risk Facmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Considering the gender gap in heart failure

Lin

Greenberg

2019

“…Nevertheless, when considering an intervention in a given patient, this apparent dichotomy should be considered. Finally, although patient‐oriented outcomes were not evaluated in this paper, existing evidence would suggest that the benefits in quality of life that accompany the use of at least some of these medications are also largely independent of LVEF …”

Section: Therapeutic Decisions According To Left Ventricular Ejectionmentioning

confidence: 99%

Evolving towards a more realistic approach to the importance of left ventricular ejection fraction and sex in heart failure and its therapy

Bouabdallaoui

Rouleau

2020

“…However, as overall mortality and the relative proportion of cardiovascular deaths in HFpEF are lower compared with HFrEF, 16 new endpoints and analytic approaches have been considered. As a result, the primary efficacy endpoint chosen PARAGON-HF reflected a further evolution of thinking 18 As adverse quality of life is similar or worse among HFpEF compared with HFrEF (especially in women 19,20 ), ongoing HFpEF trial programmes should continue to target measures of health status. Modest average differences in the Kansas City Cardiomyopathy Questionnaire clinical summary score (1.0, 95% confidence interval 0-2.1) may be reflective of high individual patient-level responses.…”

Section: Endpoint Selection In Emerging Heart Failure With Preserved mentioning

confidence: 99%

Angiotensin receptor–neprilysin inhibition in heart failure with preserved ejection fraction: lessons from PARAGON‐HF

Vaduganathan

McMurray

Solomon

2020

Self Cite

Identifying effective therapies for patients living with heart failure (HF) with preserved ejection fraction (HFpEF) has remained challenging. The recently completed PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction), 1 the largest HFpEF trial conducted to date, examined a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI), sacubitril/valsartan, compared with valsartan among 4822 patients with signs and symptoms of HF, left ventricular ejection fraction (LVEF) ≥45%, elevated natriuretic peptides, and evidence of structural heart disease. Patients allocated to sacubitril/valsartan experienced modestly lower rates of composite cardiovascular death and total HF hospitalizations compared with patients randomized to valsartan after a median follow-up of 35 months, but this treatment effect did not meet pre-specified statistical significance thresholds (Figure 1). We contextualize these trial findings, including learnings from subsequent secondary analyses, and reflect on key trial elements that may inform the next phase of therapeutic development in HFpEF. Were the intended biological pathways affected and anticipated haemodynamic responses achieved in PARAGON-HF? Irrespective