Heart failure with preserved ejection fraction: Classification based upon phenotype is essential for diagnosis and treatment

Heart failure (HF) is classified based upon the left ventricular ejection fraction (LVEF). Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disorder with increasing prevalence in the elderly that remains incompletely understood and inadequately treated as no therapy has shown favorable effects. In this review, we summarize the current theories regarding HFpEF pathogenesis, propose a phenotype-based classification of HFpEF, discuss prevention strategies, explain why clinical trials on HFpEF treatment have failed, and make suggestions for the future.     

Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology

There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed.     

The Emerging Epidemic of Heart Failure with Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF), which currently represents approximately 50 % of heart failure (HF) cases, is common and associated with high morbidity and mortality. Understanding the epidemiology of HFpEF has been difficult due to the challenges in HFpEF diagnosis and the heterogeneous etiologies and pathophysiologies that underlie HFpEF. Nevertheless, several high-quality epidemiology and observational registry studies of HFpEF demonstrate that an increasing prevalence of HFpEF in both the outpatient and inpatient settings, coupled with a lack of evidence-based effective treatments for HFpEF, is resulting in an emerging epidemic of HFpEF. In this review, we discuss the emerging HFpEF epidemic, focusing on: (1) reasons for the rising prevalence of HFpEF; (2) the abnormalities in cardiac structure and function that dictate the transition from risk factors to HFpEF; (3) novel HFpEF mechanisms that may underlie the increase in HFpEF prevalence; (4) prognosis of HFpEF; and (5) risk prediction in HFpEF. We conclude with 10 unanswered questions on HFpEF epidemiology that will be important areas for future investigation.     

射血分数保留的心力衰竭合并慢性肾功能不全的研究进展

射血分数保留的心力衰竭(HFpEF)是发病率及死亡率均较高的一种常见疾病,慢性肾功能不全(CKD)是HFpEF患者常见的伴随疾病。HFpEF合并CKD的发病机制尚未完全阐明,HFpEF与CKD常相互影响、交互促进疾病的进展。与单纯HFpEF患者相比,合并CKD的HFpEF患者通常预后较差,且随着肾损伤程度的加重,其死亡风险增加。治疗心力衰竭的基石类药物并不能使HFpEF患者明显获益,然而建议将沙库巴曲缬沙坦等新型抗心力衰竭药物应用于合并轻中度CKD的HFpEF患者。     

射血分数保留的心力衰竭研究与治疗新进展

射血分数保留的心力衰竭(HFpEF)是一个在病理生理方面异质性很强的综合征,由于老龄化的趋势,其发生率和比例持续升高。重要的是,目前几乎缺乏针对HFpEF的有效治疗方法,因此,寻找HFpEF新的治疗方法已成为当前心力衰竭研究领域的热点。近年来,针对HFpEF的发病机制、治疗所做的研究取得了新的进展,文章将就这些新进展作一综述。     

Large animal models of heart failure with preserved ejection fraction

Heart Failure Reviews - Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction and multiple comorbidities. The number of patients is continuously...     

钠葡萄糖共转运蛋白2抑制剂治疗射血分数保留型心衰的最新进展

心衰是各种心脏疾病的严重表现或晚期阶段,死亡率和再住院率居高不下,成为正在危害人类健康的重要疾病之一。射血分数保留的心衰（HFpEF）占比达心衰患者一半以上,但目前尚无确切的可以降低HFpEF发病率和死亡率的治疗策略。近年来,新型降糖药物钠葡萄糖共转运蛋白2抑制剂（SGLT-2i）带来的心血管益处得到了广泛的关注,HFpEF患者是否可以从SGLT-2i中获益备受关注,现就这一问题作一综述。     

Cardiac mechanics in heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical entity associated with significant morbidity and mortality. Common comorbidities including hypertension, coronary artery disease, diabetes, chronic kidney disease, obesity, and increasing age predispose to preclinical diastolic dysfunction that often progresses to frank HFpEF. Clinical HFpEF is typically associated with some degree of diastolic dysfunction, but can occur in the absence of many conventional diastolic dysfunction indices. The exact biologic links between risk factors, structural changes, and clinical manifestations are not clearly apparent. Innovative approaches including deformation imaging have enabled deeper understanding of HFpEF cardiac mechanics beyond conventional metrics. Furthermore, predictive analytics through data-driven platforms have allowed for a deeper understanding of HFpEF phenotypes. This review focuses on the changes in cardiac mechanics that occur through preclinical myocardial dysfunction to clinically apparent HFpEF.     

Obesity and heart failure with preserved ejection fraction: A growing problem

Heart Failure with Preserved Ejection Fraction (HFpEF) is increasing in prevalence due to the aging of the United States population as well as the current obesity epidemic. While obesity is very common in patients with HFpEF, obesity may represent a specific phenotype of HFpEF characterized by unique hemodynamics and structural abnormalities. Obesity induces a systemic inflammatory response that may contribute to myocardial fibrosis and endothelial dysfunction. The most obese patients continue to be excluded from HFpEF clinical trials, and thus ongoing research is needed to determine the role of pharmacologic and interventional approaches in this growing population.     

Unveiling the role of exercise training in targeting the inflammatory paradigm of heart failure with preserved ejection fraction: a narrative review

Heart Failure Reviews - Heart failure with preserved ejection fraction (HFpEF) is currently lacking an effective pharmacological treatment with impact on major outcomes such as hospitalization and...     

Heart Failure with Preserved Ejection Fraction: Diagnosis and Management

Heart failure with preserved ejection fraction (HFpEF) is a prevalent condition with substantial individual and societal burden. In this article, we review the current status of understanding of HFpEF, focusing on the challenges and uncertainties regarding diagnosis and treatment. We then propose a scientific roadmap to facilitate research that may translate into improved clinical outcomes.     

Prognostic significance of T1 mapping parameters in heart failure with preserved ejection fraction: a systematic review

Heart Failure Reviews - Heart failure with preserved ejection fraction (HFpEF) accounts for almost one-half of all heart failure (HF) patients and continues to increase in prevalence. While...     

Cardiovascular magnetic resonance for the diagnosis and management of heart failure with preserved ejection fraction

Heart Failure Reviews - Heart failure with preserved ejection fraction (HFpEF) is characterized by an impaired ventricular filling resulting in the development of dyspnea and other HF symptoms....     

How to Develop and Implement a Specialized Heart Failure with Preserved Ejection Fraction Clinical Program

Heart failure with preserved ejection fraction (HFpEF), a highly prevalent and complex clinical syndrome with high morbidity and mortality, is often unrecognized and not optimally treated. Clinical trials for HFpEF have been plagued by low enrollment, and clinicians often approach HFpEF patients with “therapeutic nihilism” given the perceived lack of available therapies based on the disappointing results of these prior trials. Due to these challenges, we have pioneered the successful creation of dedicated, specialized HFpEF clinical programs. Here, we discuss (1) the rationale for the development of a specialized HFpEF clinical program; (2) strategies for the systematic identification of HFpEF patients; (3) a standardized diagnostic and therapeutic approach; (4) validation of the HFpEF clinical program paradigm; (5) staffing and reimbursement considerations; (6) HFpEF clinical trial enrollment; and (7) challenges and future directions for HFpEF clinical programs. We conclude that it is feasible to create HFpEF clinical programs that fulfill the major unmet need of identifying and caring for patients with HFpEF. These clinics are essential for confirming the HFpEF diagnosis, providing standardized treatment, and facilitating clinical trial enrollment. It is our hope that the information provided here will encourage others to establish their own specialized HFpEF programs, thereby allowing for comprehensive care for these complex patients.     

Patient phenotype profiling in heart failure with preserved ejection fraction to guide therapeutic decision making. A scientific statement of the Heart Failure Association,the European Heart Rhythm Association of the European Society of Cardiology,and the European Society of Hypertension

Heart failure with preserved ejection fraction (HFpEF) represents a highly heterogeneous clinical syndrome affected in its development and progression by many comorbidities. The left ventricular diastolic dysfunction may be a manifestation of various combinations of cardiovascular, metabolic, pulmonary, renal, and geriatric conditions. Thus, in addition to treatment with sodium–glucose cotransporter 2 inhibitors in all patients, the most effective method of improving clinical outcomes may be therapy tailored to each patient's clinical profile. To better outline a phenotype-based approach for the treatment of HFpEF, in this joint position paper, the Heart Failure Association of the European Society of Cardiology, the European Heart Rhythm Association and the European Hypertension Society, have developed an algorithm to identify the most common HFpEF phenotypes and identify the evidence-based treatment strategy for each, while taking into account the complexities of multiple comorbidities and polypharmacy.     

Treatment of heart failure with preserved ejection fraction

Opinion statement  Heart failure with preserved ejection fraction (HFpEF) is a major public health problem in the United States. However, in contrast to systolic heart failure, there are little data to guide treatment decisions in HFpEF, and no therapies have been shown to improve outcome in these patients. This review explores what is currently known about the pathophysiologic mechanisms causing HFpEF in order to frame appropriate therapeutic targets and better understand the clinical responses commonly observed in patients with HFpEF. Data from published clinical trials are reviewed, and the roles for each class of drug commonly used in practice are examined. Finally, novel therapies and future directions for basic investigation and clinical trials are discussed.     

Heart failure with a preserved ejection fraction and the EMPEROR-Preserved Trial: a review of how we got here

Heart Failure Reviews - Heart failure with a preserved ejection fraction (HFpEF), previously known as diastolic heart failure, was first recognized more than 50 years ago. In spite of all...     

The Restoration of Chronotropic CompEtence in Heart Failure PatientS with Normal Ejection FracTion (RESET) Study: Rationale and Design

BackgroundHeart failure with preserved ejection fraction (HFpEF) is the predominant form of heart failure among the elderly and in women. However, there are few if any evidence-based therapeutic options for HFpEF. The chief complaint of HFpEF is reduced tolerance to physical exertion. Recent data revealed that 1 potential mechanism of exertional intolerance in HFpEF patients is inadequate chronotropic response. Although there is considerable evidence demonstrating the benefits of rate-adaptive pacing (RAP) provided from implantable cardiac devices in patients with an impaired chronotropic response, the effect of RAP in HFpEF is unknown.Methods and ResultsThe Restoration of Chronotropic CompEtence in Heart Failure PatientS with Normal Ejection FracTion (RESET) study is a prospective, multicenter, double-blind, randomized with stratification, study assessing the effect of RAP on peak oxygen consumption and quality of life. RAP therapy will be evaluated in a crossover paired fashion for each patient within each study stratum. Study strata are based on patient β-blocker usage at time of enrollment. The study is powered to assess the impact of pacing independently in both strata.ConclusionsThe RESET study seeks to evaluate the potential benefit of RAP in patients with symptomatic mild to moderate HFpEF and chronotropic impairment. Study enrollment began in July 2008.     

生物标志物在射血分数保留的心力衰竭中的研究进展

心力衰竭是一种复杂的临床综合征,严重危害人类健康。随着对心力衰竭的不断深入研究,人们发现生物标志物在心力衰竭、尤其是在射血分数保留的心力衰竭(HFpEF)中扮演着越来越重要的角色。不同途径(包括神经激素激活、心肌损伤、炎症和纤维化等)的生物标志物对HFpEF具有超出诊断范围的临床效用。本文主要对钠尿肽和新型生物标志物如乳糖凝集素-3及转化生长因子-15等在HFpEF患者诊断及预后中的研究进展进行综述。     

Analysis of circumferential and longitudinal left ventricular systolic function in patients with non-ischemic chronic heart failure and preserved ejection fraction (from the CARRY-IN-HFpEF study)

Heart failure with preserved left ventricular ejection fraction (HFpEF) is implicitly attributed to diastolic dysfunction, often recognized in elderly patients with hypertension, diabetes, and renal dysfunction. In these patients, left ventricular circumferential and longitudinal shortening is often impaired despite normal ejection fraction. The aim of this prospective study was to analyze circumferential and longitudinal shortening and their relations in patients with nonischemic HFpEF. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (S') were measured in 60 patients (mean age 73 ± 13 years) with chronic nonischemic HFpEF in stable New York Heart Association functional class II or III and compared to the values in 120 healthy controls and 120 patients with hypertension without HFpEF. Sc-MS was classified as low if <89% and S' as low if <8.5 cm/s (the 10th-percentile values of healthy controls). Isolated low sc-MS was detected in 46% of patients with HFpEF, 27% of patients with hypertension, and 2% of controls; isolated low S' was detected in 11% of patients with HFpEF, 7% of patients with hypertension, and 5% of controls; and combined low sc-MS and low S' was detected in 26% of patients with HFpEF, 9% of patients with hypertension, and 5% of controls (HFpEF vs others, all p values <0.001). Thus, any alteration of systolic function was found in 83% of patients with HFpEF. The relation between sc-MS and S' was nonlinear (cubic). Changes in S' within normal values corresponded to negligible variations in sc-MS, whereas the progressive decrease below 8.5 cm/s was associated with substantial decrease in sc-MS. In conclusion, circumferential and/or longitudinal systolic dysfunction is present in most patients with HFpEF. Circumferential shortening normalized by wall stress identifies more patients with concealed left ventricular systolic dysfunction than longitudinal shortening.