Heart failure with preserved ejection fraction (HFpEF) has grown to become the dominant form of heart failure worldwide, in tandem with ageing of the general population and the increasing prevalences ...of obesity, diabetes mellitus and hypertension. The clinical syndrome of HFpEF is heterogeneous and must be distinguished from heart failure with reduced ejection fraction as well as other aetiologies that have different treatment strategies. The diagnosis of HFpEF is challenging and ultimately relates to the conceptual definition of heart failure as a clinical syndrome characterized by symptoms that are associated with a reduced capacity of the heart to pump blood adequately at normal filling pressures during diastole. Clinical trials to date have been largely unsuccessful in identifying effective treatments for HFpEF but evidence supports the use of diuretics, mineralocorticoid antagonists and lifestyle interventions. Pathophysiological heterogeneity in the presentation of HFpEF is substantial, and ongoing studies are underway to evaluate the optimal methods to classify patients into phenotypically homogeneous subpopulations to facilitate better individualization of treatment.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Approximately half of all patients with heart failure have preserved ejection fraction (HFpEF) and, as life expectancies continue to increase in western societies, the prevalence of HFpEF will ...continue to grow. In contrast to heart failure with reduced ejection fraction (HFrEF), no treatment has been proven in pivotal clinical trials to be effective for HFpEF, largely because of the pathophysiological heterogeneity that exists within the broad spectrum of HFpEF. This syndrome was historically considered to be caused exclusively by left ventricular diastolic dysfunction, but research has identified several other contributory factors, including limitations in left ventricular systolic reserve, systemic and pulmonary vascular function, nitric oxide bioavailability, chronotropic reserve, right heart function, autonomic tone, left atrial function, and peripheral impairments. Multiple individual mechanisms frequently coexist within the same patient to cause symptomatic heart failure, but between patients with HFpEF the extent to which each component is operative can differ widely, confounding treatment approaches. This Review focuses on our current understanding of the pathophysiological mechanisms underlying HFpEF, and how they might be mechanistically related to typical risk factors for HFpEF, including ageing, obesity, and hypertension.
IMPORTANCE: Heart failure with preserved ejection fraction (HFpEF), defined as HF with an EF of 50% or higher at diagnosis, affects approximately 3 million people in the US and up to 32 million ...people worldwide. Patients with HFpEF are hospitalized approximately 1.4 times per year and have an annual mortality rate of approximately 15%. OBSERVATIONS: Risk factors for HFpEF include older age, hypertension, diabetes, dyslipidemia, and obesity. Approximately 65% of patients with HFpEF present with dyspnea and physical examination, chest radiographic, echocardiographic, or invasive hemodynamic evidence of HF with overt congestion (volume overload) at rest. Approximately 35% of patients with HFpEF present with “unexplained” dyspnea on exertion, meaning they do not have clear physical, radiographic, or echocardiographic signs of HF. These patients have elevated atrial pressures with exercise as measured with invasive hemodynamic stress testing or estimated with Doppler echocardiography stress testing. In unselected patients presenting with unexplained dyspnea, the H2FPEF score incorporating clinical (age, hypertension, obesity, atrial fibrillation status) and resting Doppler echocardiographic (estimated pulmonary artery systolic pressure or left atrial pressure) variables can assist with diagnosis (H2FPEF score range, 0-9; score >5 indicates more than 95% probability of HFpEF). Specific causes of the clinical syndrome of HF with normal EF other than HFpEF should be identified and treated, such as valvular, infiltrative, or pericardial disease. First-line pharmacologic therapy consists of sodium-glucose cotransporter type 2 inhibitors, such as dapagliflozin or empagliflozin, which reduced HF hospitalization or cardiovascular death by approximately 20% compared with placebo in randomized clinical trials. Compared with usual care, exercise training and diet-induced weight loss produced clinically meaningful increases in functional capacity and quality of life in randomized clinical trials. Diuretics (typically loop diuretics, such as furosemide or torsemide) should be prescribed to patients with overt congestion to improve symptoms. Education in HF self-care (eg, adherence to medications and dietary restrictions, monitoring of symptoms and vital signs) can help avoid HF decompensation. CONCLUSIONS AND RELEVANCE: Approximately 3 million people in the US have HFpEF. First-line therapy consists of sodium-glucose cotransporter type 2 inhibitors, exercise, HF self-care, loop diuretics as needed to maintain euvolemia, and weight loss for patients with obesity and HFpEF.
Approximately half of the patients with signs and symptoms of heart failure have a left ventricular ejection fraction that is not markedly abnormal. Despite the historically initial surprise, ...heightened risks for heart failure specific major adverse events occur across the broad range of ejection fraction, including normal. The recognition of the magnitude of the problem of heart failure with preserved ejection fraction in the past 20 years has spurred an explosion of clinical investigation and growing intensity of informative outcome trials. This article addresses the historic development of this component of the heart failure syndrome, including the epidemiology, pathophysiology, and existing and planned therapeutic studies. Looking forward, more specific phenotyping and even genotyping of subpopulations should lead to improvements in outcomes from future trials.
Diabesity is a term used to describe the combined adverse health effects of obesity and diabetes mellitus. The worldwide dual epidemic of obesity and type 2 diabetes is an important public health ...issue. Projections estimate a sixfold increase in the number of adults with obesity in 40 years and an increase in the number of individuals with diabetes to 642 million by 2040. Increased adiposity is the strongest risk factor for developing diabetes. Early detection of the effects of diabesity on the cardiovascular system would enable the optimal implementation of effective therapies that prevent atherosclerosis progression, cardiac remodelling, and the resulting ischaemic heart disease and heart failure. Beyond conventional imaging techniques, such as echocardiography, CT and cardiac magnetic resonance, novel post-processing tools and techniques provide information on the biological processes that underlie metabolic heart disease. In this Review, we summarize the effects of obesity and diabetes on myocardial structure and function and illustrate the use of state-of-the-art multimodality cardiac imaging to elucidate the pathophysiology of myocardial dysfunction, prognosticate long-term clinical outcomes and potentially guide treatment strategies.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Half of patients with heart failure (HF) have a preserved left ventricular ejection fraction (HFpEF). Morbidity and mortality in HFpEF are similar to values observed in patients with HF and reduced ...EF, yet no effective treatment has been identified. While early research focused on the importance of diastolic dysfunction in the pathophysiology of HFpEF, recent studies have revealed that multiple non-diastolic abnormalities in cardiovascular function also contribute. Diagnosis of HFpEF is frequently challenging and relies upon careful clinical evaluation, echo-Doppler cardiography, and invasive haemodynamic assessment. In this review, the principal mechanisms, diagnostic approaches, and clinical trials are reviewed, along with a discussion of novel treatment strategies that are currently under investigation or hold promise for the future.
The incidence and prevalence of heart failure with preserved ejection fraction (HFpEF) continue to rise in tandem with the increasing age and burdens of obesity, sedentariness, and cardiometabolic ...disorders. Despite recent advances in the understanding of its pathophysiological effects on the heart, lungs, and extracardiac tissues, and introduction of new, easily implemented approaches to diagnosis, HFpEF remains under-recognized in everyday practice. This under-recognition presents an even greater concern given the recent identification of highly effective pharmacologic-based and lifestyle-based treatments that can improve clinical status and reduce morbidity and mortality. HFpEF is a heterogenous syndrome and recent studies have suggested an important role for careful, pathophysiological-based phenotyping to improve patient characterization and to better individualize treatment. In this JACC Scientific Statement, we provide an in-depth and updated examination of the epidemiology, pathophysiology, diagnosis, and treatment of HFpEF.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic ...abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3-9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0-9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7-10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6-34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1-7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05-2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01-1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
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