Trainingstherapie bei Herzinsuffizienz

Exercise training in patients with chronic stable heart failure (HF) is a recommended and broadly accepted treatment strategy that is an integral part of an evidence-based management involving pharmacological and non-pharmacological therapies. There is ample scientific evidence that exercise training in HF with reduced (HFrEF) and with preserved ejection fraction (HFpEF) improves exercise capacity, HF symptoms and quality of life. This is due to an improvement of central hemodynamics, endothelial function, neurohumoral activation, skeletal muscle structure and function as well as a decrease in inflammatory markers. The largest randomized, controlled HF-ACTION study (Heart Failure-A Controlled Trial Investigating Outcomes of exercise TraiNing) demonstrated that exercise training results in a modest improvement of all-cause mortality and hospitalizations in HFrEF, depending on adequate compliance. Outcome data in HFpEF are lacking. Besides compliance, efficacy of exercise training is dependent on the intensity and type of exercise. Resistance and high intensity endurance training in addition to a standard aerobic exercise seem to be superior in improving the clinical status of HF patients. In the future, individualized exercise programs will help to improve long-term adherence to exercise training.     

Heart Failure with Preserved Ejection Fraction: Pathophysiology and Emerging Therapies

Approximately half of patients with heart failure (HF) have a preserved ejection fraction (HFpEF). Morbidity and mortality are similar to HF with reduced EF (HFrEF), yet therapies with unequivocal benefit in HFrEF have not been shown to be effective in HFpEF. Recent studies have shown that the pathophysiology of HFpEF, initially believed to be due principally to diastolic dysfunction, is more complex. Appreciation of this complexity has shed new light into how HFpEF patients might respond to traditional HF treatments, while also suggesting new applications for novel therapies and strategies. In this review, we shall briefly review the pathophysiologic mechanisms in HFpEF, currently available clinical trial data, and finally explore new investigational therapies that are being developed and tested in ongoing and forthcoming trials.     

Evolution of a Geriatric Syndrome: Pathophysiology and Treatment of Heart Failure with Preserved Ejection Fraction

The majority of older adults who develop heart failure (HF), particularly older women, have a preserved left ventricular ejection fraction (HFpEF). The prevalence of this syndrome is increasing, and the prognosis is not improving, unlike that of HF with reduced ejection fraction (HFrEF). Individuals with HFpEF have severe symptoms of effort intolerance, poor quality of life, frequent hospitalizations, and greater likelihood of death. Despite the importance of HFpEF, there are numerous major gaps in our understanding of its pathophysiology and management. Although it was originally viewed as a disorder due solely to abnormalities in left ventricular diastolic function, our understanding has evolved such that HFpEF is now understood as a systemic syndrome involving multiple organ systems, and it is likely that it is triggered by inflammation and other as‐yet‐unidentified circulating factors, with important contributions of aging and multiple comorbidities, features generally typical of other geriatric syndromes. We present an update on the pathophysiology, diagnosis, management, and future directions in this disorder in older persons.     

Current concept in the diagnosis,treatment and rehabilitation of patients with congestive heart failure

Heart failure(HF) is a major public health problem with a prevalence of 1%-2% in developed countries. The underlying pathophysiology of HF is complex and as a clinical syndrome is characterized by various symptoms and signs. HF is classified according to left ventricular ejection fraction(LVEF) and falls into three groups: LVEF ≥ 50%-HF with preserved ejection fraction(HFpEF), LVEF 40%-HF with reduced ejection fraction(HFrEF), LVEF 40%-49%-HF with mid-range ejection fraction. Diagnosing HF is primarily a clinical approach and it is based on anamnesis, physical examination, echocardiogram, radiological findings of the heart and lungs and laboratory tests, including a specific markers of HF-brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide as well as other diagnostic tests in order to elucidate possible etiologies. Updated diagnostic algorithms for HFpEF have been recommended(H2 FPEF, HFA-PEFF). New therapeutic options improve clinical outcomes as well as functional status in patients with HFrEF(e.g., sodium-glucose cotransporter-2-SGLT2 inhibitors) and such progress in treatment of HFrEF patients resulted in new working definition of the term "HF with recovered left ventricular ejection fraction". In line with rapid development of HF treatment, cardiac rehabilitation becomes an increasingly important part of overall approach to patients with chronic HF for it has been proven that exercise training can relieve symptoms, improve exercise capacity and quality of life as well as reduce disability and hospitalization rates. We gave an overview of latest insights in HF diagnosis and treatment with special emphasize on the important role of cardiac rehabilitation in such patients.     

Impact of comorbidities on health status measured using the Kansas City Cardiomyopathy Questionnaire in patients with heart failure with reduced and preserved ejection fraction

Aim

Patients with heart failure (HF) often suffer from a range of comorbidities, which may affect their health status. The aim of this study was to assess the impact of different comorbidities on health status in patients with HF and reduced (HFrEF) and preserved ejection fraction (HFpEF).

Methods and results

Using individual patient data from HFrEF (ATMOSPHERE, PARADIGM-HF, DAPA-HF) and HFpEF (TOPCAT, PARAGON-HF) trials, we examined the Kansas City Cardiomyopathy Questionnaire (KCCQ) domain scores and overall summary score (KCCQ-OSS) across a range of cardiorespiratory (angina, atrial fibrillation [AF], stroke, chronic obstructive pulmonary disease [COPD]) and other comorbidities (obesity, diabetes, chronic kidney disease [CKD], anaemia). Of patients with HFrEF (n = 20 159), 36.2% had AF, 33.9% CKD, 33.9% diabetes, 31.4% obesity, 25.5% angina, 12.2% COPD, 8.4% stroke, and 4.4% anaemia; the corresponding proportions in HFpEF (n = 6563) were: 54.0% AF, 48.7% CKD, 43.4% diabetes, 53.3% obesity, 28.6% angina, 14.7% COPD, 10.2% stroke, and 6.5% anaemia. HFpEF patients had lower KCCQ domain scores and KCCQ-OSS (67.8 vs. 71.3) than HFrEF patients. Physical limitations, social limitations and quality of life domains were reduced more than symptom frequency and symptom burden domains. In both HFrEF and HFpEF, COPD, angina, anaemia, and obesity were associated with the lowest scores. An increasing number of comorbidities was associated with decreasing scores (e.g. KCCQ-OSS 0 vs. ≥4 comorbidities: HFrEF 76.8 vs. 66.4; HFpEF 73.7 vs. 65.2).

Conclusions

Cardiac and non-cardiac comorbidities are common in both HFrEF and HFpEF patients and most are associated with reductions in health status although the impact varied among comorbidities, by the number of comorbidities, and by HF phenotype. Treating/correcting comorbidity is a therapeutic approach that may improve the health status of patients with HF.     

Medical and Interventional Options to Treat Pulmonary Embolism

Heart failure (HF) is the leading cause of hospitalization among older adults and the prevalence is growing with the aging populations in western countries. Approximately one-half of patients with HF have preserved ejection fraction (HFpEF). In contrast to HF with reduced EF (HFrEF), there is no proven effective treatment for HFpEF. The pathophysiology of HFpEF is complex, and the dominant mechanisms leading to symptoms of HF often vary between afflicted patients, confounding efforts to apply “one-size fits all” types of therapeutic approaches. Current treatment strategies focus on control of volume status and comorbidities, but future research aimed at individualized therapies holds promise to improve outcomes in this increasingly prevalent form of cardiac failure.     

心力衰竭与脑啡肽酶的研究进展

心力衰竭是一种机制复杂的临床综合征。对心力衰竭病生理机制的深入认识提示脑啡肽酶在其发生发展中起重要作用,脑啡肽酶抑制为心力衰竭治疗提供了新的方向和证据。目前血管紧张素受体脑啡肽酶抑制剂在射血分数减少心力衰竭中的治疗取得了较大进步,而射血分数保留心力衰竭尚无有效的治疗方法。2016年美国及欧洲心力衰竭指南已将血管紧张素受体脑啡肽酶抑制剂作为治疗慢性射血分数减少心力衰竭的推荐药物。本文将对心力衰竭与脑啡肽酶的研究进展作一综述。     

Acutely decompensated heart failure with preserved and reduced ejection fraction present with comparable haemodynamic congestion

Aims

Congestion is a central feature of acute heart failure (HF) and its assessment is important for clinical decisions (e.g. tailoring decongestive treatments). It remains uncertain whether patients with acute HF with preserved ejection fraction (HFpEF) are comparably congested as in acute HF with reduced EF (HFrEF). This study assessed congestion, right ventricular (RV) and renal dysfunction in acute HFpEF, HFrEF and non‐cardiac dyspnoea.

Methods and results

We compared echocardiographic and circulating biomarkers of congestion in 146 patients from the MEDIA‐DHF study: 101 with acute HF (38 HFpEF, 41 HFrEF, 22 HF with mid‐range ejection fraction) and 45 with non‐cardiac dyspnoea. Compared with non‐cardiac dyspnoea, patients with acute HF had larger left and right atria, higher E/e', pulmonary artery systolic pressure and inferior vena cava (IVC) diameter at rest, and lower IVC variability (all P < 0.05). Mid‐regional pro‐atrial natriuretic peptide (MR‐proANP) and soluble CD146 (sCD146), but not B‐type natriuretic peptide (BNP), correlated with echocardiographic markers of venous congestion. Despite a lower BNP level, patients with HFpEF had similar evidence of venous congestion (enlarged IVC, left and right atria), RV dysfunction (tricuspid annular plane systolic excursion), elevated MR‐proANP and sCD146, and renal impairment (estimated glomerular filtration rate; all P > 0.05) compared with HFrEF.

Conclusion

In acute conditions, HFpEF and HFrEF presented in a comparable state of venous congestion, with similarly altered RV and kidney function, despite higher BNP in HFrEF.

     

Cardiovascular Autonomic Disturbances in Heart Failure With Preserved Ejection Fraction

In heart failure with reduced ejection fraction (HFrEF), diminished tonic and reflex vagal heart rate modulation and exaggerated sympathetic outflow and neural norepinephrine release are evident from disease inception. Each of these disturbances of autonomic regulation has been independently associated with shortened survival, and β-adrenoceptor antagonism and therapeutic autonomic modulation by other means have been demonstrated, in clinical trials, to lessen symptoms and prolong survival. In contrast, data concerning the autonomic status of patients with heart failure with preserved ejection fraction (HFpEF) are comparatively sparse. Little is known concerning the prognostic consequences of autonomic dysregulation in such individuals, and therapies applied with success in HFrEF have in most trials failed to improve symptoms or survival of those with HFpEF. A recent HFpEF Expert Scientific Panel report emphasised that without a deeper understanding of the pathophysiology of HFpEF, establishing effective treatment will be challenging. One aspect of such pathology may be cardiovascular autonomic disequilibrium, often worsened by acute exercise or routine daily activity. This review aims to summarise existing knowledge concerning parasympathetic and sympathetic function of patients with HFpEF, consider potential mechanisms and specific consequences of autonomic disturbances that have been identified, and propose hypotheses for future investigation.     

Epidemiology and clinical characteristics of hospitalized elderly patients for heart failure with reduced,mid-range and preserved ejection fraction

Introduction: Elderly patients hospitalized with heart failure (HF) have high mortality rates and requires specific evidence based theraphy, however there are few studies which have focused on patients older than 80 years hospitalized with HF. The aim of the present study is to evaluate the overall clinical characteristics, management, and in-hospital outcomes of elderly patients hospitalized with HF.Methods: Journey-HF study was conducted in 37 different centers in Turkey and recruited 1606 patients who were hospitalized with HF between September 2015 and September 2016. In this study, clinical profile of patients ≥ 80 years old and 65-79 years old hospitalized with HF were described and compared based on EF-related classification: HFrEF (HF with reduced ejection fraction), HFmrEF (HF with mid-range ejection fraction) and HFpEF (HF with preserved ejection fraction).Results: A total of 1034 elder patients (71.6% 65–79 years old and 28.4% ≥80 years old) were recruited. Of the 65–79 years old patients 67.4% had HFrEF, 16.2% had HFmrEF and 16.3% had HFpEF. Among patients ≥80 years old 61.6% had HFrEF, 15.6% had HmrEF and 22.8% had HFpEF.When compared with patients with HFrEF and HFmrEF, patients ≥80 years old with HFpEF were more likely to be older, have atrial fibrilation (AF), and less likely to have diabetes mellitus (DM), coronary artery disease (CAD) or to be recieving an angiotensin-converting enzyme inhibitor (ACEi) or beta blocker theraphy. When compared to patients 65–79 years old with HFpEF, patients ≥80 years with HFpEF had a higher rate of AF and less likely DM. Acute coronary syndrome was the most common precipitant factor for hospitalization in both age groups with HFrEF group. Arrhythmia was a major precipitant factor for hospitalization of patients ≥80 years old with HFpEF. Non-compliance with theraphy was a major problem of patients ≥80 years old with HFrEF.Conclusion: Elderly patients with HFrEF, HFmrEF and HFpEF each had characterized unique patient profiles and the guideline recommended medications were less likely to be used in these patient populations. In hospital mortality rate is worrisome and reflects a need for more specific tretment strategy.     

Impaired Exercise Tolerance in Heart Failure: Role of Skeletal Muscle Morphology and Function

Purpose of Review

To discuss the impact of deleterious changes in skeletal muscle morphology and function on exercise intolerance in patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), as well as the utility of exercise training and the potential of novel treatment strategies to preserve or improve skeletal muscle morphology and function.

Recent Findings

Both HFrEF and HFpEF patients exhibit a reduction in percent of type I (oxidative) muscle fibers and oxidative enzymes coupled with abnormal mitochondrial respiration. These skeletal muscle abnormalities contribute to impaired oxidative metabolism with an earlier shift towards glycolytic metabolism during exercise that is strongly associated with exercise intolerance. In both HFrEF and HFpEF patients, peripheral “non-cardiac” factors are important determinants of the improvement in exercise tolerance following aerobic exercise training. Adjunctive strategies that include nutritional supplementation with amino acids and/or anabolic drugs to stimulate anabolic molecular pathways in skeletal muscle show great promise for improving exercise tolerance and treating heart failure-associated sarcopenia, but these efforts remain early in their evolution, with no immediate clinical applications.

Summary

There is consistent evidence that heart failure is associated with multiple skeletal muscle abnormalities which impair oxygen uptake and utilization and contribute greatly to exercise intolerance. Exercise training induces favorable adaptations in skeletal muscle morphology and function that contribute to improvements in exercise tolerance in patients with HFrEF. The contribution of skeletal muscle adaptations to improved exercise tolerance following exercise training in HFpEF remains unknown and warrants further investigation.

     

影响射血分数保留的心力衰竭相关疾病及心功能障碍的机制研究进展

射血分数保留的心力衰竭（HFpEF）是一种严重威胁人类健康且机制复杂的临床综合征,约占全部心力衰竭总数的一半。其发病率伴随着人口老龄化的发展而逐年上升,病死率与射血分数减少的心力衰竭（HFrEF）相当,传统的药物治疗虽能降低HFrEF患者的再住院率及死亡率,却不能有效的改善HFpEF患者的预后。目前,对HFpEF的发病机制、诊断、治疗等许多方面尚无统一的认识,加之临床医师对HFpEF的认识存在局限性,均使得HFpEF成为心血管防治领域的社会公共难题及主要挑战。为了解国内外射血分数保留的心力衰竭的病理机制及诊疗情况,现从其影响其的相关疾病、病理机制、诊断治疗等方面进行综述。     

New Drugs and Devices in the Pipeline for Heart Failure with Reduced Ejection Fraction Versus Heart Failure with Preserved Ejection Fraction

Heart failure (HF) is a growing problem in the USA and other industrialized nations. HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) each make up approximately half of the overall HF burden. Although a variety of medical and surgical therapies exist for the treatment of patients with HFrEF, morbidity and mortality remain high, and cardiac transplantation, considered the current gold standard for patients with HFrEF and severe symptoms, is reserved for relatively few eligible patients. Patients with HFpEF have more limited therapeutic options, because no medical therapy to date has been shown to improve survival in these patients. With the rising prevalence of HF and its increasing role in health care expenditure, there is a substantial need for new drug and device therapies for HFrEF and, in particular, HFpEF. This forms the topic of the current review.     

Role of Physical Training in Heart Failure with Preserved Ejection Fraction

About 50 % or more of heart failure (HF) patients living in the community have preserved left ventricular ejection fraction (HFpEF), and the proportion is higher among women and the very elderly. A cardinal feature of HFpEF is reduced aerobic capacity, measured objectively as peak exercise pulmonary oxygen uptake (peak VO₂), that results in decreased quality of life. Specifically, peak VO₂ of HFpEF patients is 30–70 % lower than age-, sex-, and comorbidity-matched control patients without HF. The mechanisms for the reduced peak VO₂ are due to cardiovascular and skeletal muscle dysfunction that results in reduced oxygen delivery to and/or utilization by the active muscles. Currently, four randomized controlled exercise intervention trials have been performed in HFpEF patients. These studies have consistently demonstrated that 3–6 months of aerobic training performed alone or in combination with strength training is a safe and effective therapy to increase aerobic capacity and endurance and quality of life in HFpEF patients. Despite these benefits, the physiologic mechanisms underpinning the improvement in peak exercise performance have not been studied; therefore, future studies are required to determine the role of physical training to reverse the impaired cardiovascular and skeletal muscle function in HFpEF patients.     

Reframing the association and significance of co‐morbidities in heart failure

Several co‐existing diseases and/or conditions (co‐morbidities) are present in patients with heart failure (HF), with diverse clinical relevance. Multiple mechanisms may underlie the co‐existence of HF and co‐morbidities, including direct causation, associated risk factors, heterogeneity, and independence. The complex inter‐relationship of co‐morbidities and their impact on the cardiovascular system contribute to the features of HF, both with reduced (HFrEF) and preserved ejection fraction (HFpEF). The purpose of this work is to provide an overview of the contribution of major cardiac and non‐cardiac co‐morbidities to HF development and outcomes, in the context of both HFpEF and HFrEF. Accordingly, epidemiological evidence linking co‐morbidities to HF and the effect of prevalent and incident co‐morbidities on HF outcome will be reviewed.     

Heart Failure With Midrange Ejection Fraction—What Is It,If Anything?

The patient cohort with left ventricular ejection fractions (LVEFs) of 41%-49%, which has been defined as heart failure with midrange ejection fraction (HFmrEF), represent a significant proportion of the heart failure (HF) population. Despite the clear cutoffs established by different society guidelines, confusion remains regarding the exact significance of midrange LVEF within the HF syndrome. Patients with LVEF 41%-49% represent a heterogeneous group of patients sharing pathophysiologic mechanisms, biomarker profiles, comorbidities, and clinical characteristics with patients with preserved and reduced LVEF. In this clinical review, we discuss the underlying pathophysiologic mechanisms that culminate in the clinical syndrome of HF and contribute to the disparities observed between HFpEF, HFrEF, and HFmrEF. We highlight differences and similarities in clinical characteristics and imaging features between HFpEF and HFrEF in an effort to disentangle the heterogeneous group of patients with midrange LVEF, but ultimately we conclude that LVEF should be seen as simply one important element of a continuum throughout the HF syndrome, and that although is useful, it is an oversimplification, because HF syndrome is more of a continuum. The underlying pathophysiology, etiology, and comorbidities of patients presenting with HF is becoming ever more important as the limitations of a classification solely based on LVEF are being better recognised, and as patient-specific personalisation of care is becoming ever more important.     

Use of sodium–glucose co‐transporter‐2 inhibitors in patients with and without type 2 diabetes: implications for incident and prevalent heart failure

Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF), with recent reports indicating that HF with preserved ejection fraction (HFpEF) may be more common than HF with reduced ejection fraction (HFrEF) in patients with T2D. T2D and HF result in worse outcomes than either disease alone. Sodium–glucose co‐transporter‐2 inhibitors (SGLT‐2is) have significantly improved HF outcomes in patients with T2D and may represent a new therapeutic alternative for patients with T2D at risk for or with HF. Current guidelines recommend prevention of HF through risk factor management. Once developed, treatment of HFrEF should include neurohormonal and haemodynamic modulations; however, there are no specific treatments available for HFpEF. SGLT‐2is are the first class of glucose‐lowering therapy to prevent HF in clinical trials and real‐world studies in patients with T2D (with or without established cardiovascular disease and with or without baseline HF). Mechanistic studies suggest that SGLT‐2is have beneficial effects on both systolic and diastolic function and additional systemic effects that could benefit HF outcomes. In patients with HFrEF, SGLT‐2i treatment as add‐on to standard HF therapy has had beneficial effects on HF outcomes, irrespective of T2D status. These results and those of ongoing outcomes trials with SGLT‐2is may help establish this drug class as a treatment for HF in patients with HFrEF and HFpEF, as well as HF in patients without T2D.     

可溶性鸟苷酸环化酶激动剂治疗射血分数保留性心力衰竭的研究进展

心力衰竭(心衰)发病率、病死率高,是多种心血管疾病的终末阶段,其中射血分数保留性心力衰竭(HFpEF)是一组常见且复杂的临床综合征,约占所有心力衰竭患者的50％.HFpEF预后差,再住院率及死亡率与射血分数降低性心力衰竭(HFrEF)相当.尽管针对HFrEF有了相对完整的指南共识,但目前尚缺乏可真正改善HFpEF患者预...     

Skeletal Muscle Myopathy in Heart Failure: the Role of Ejection Fraction

Purpose of Review

This review summarizes: (1) the structural and functional features coupled with pathophysiological factors responsible of skeletal muscle myopathy (SMM) in both heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction and (2) the role of exercise as treatment of SMM in these HF-related phenotypes.

Recent Findings

The recent literature showed two main phenotypes of heart failure (HF): (1) HFrEF primarily due to a systolic dysfunction of the left ventricle and (2) HFpEF, mainly related to a diastolic dysfunction. Exercise intolerance is one of most disabling symptoms of HF and it is shown that persists after the normalization of the central hemodynamic impairments by therapy and/or cardiac surgery including heart transplant. A specific skeletal muscle myopathy (SMM) has been defined as one of the main causes of exercise intolerance in HF.

Summary

The SMM has been well described in the last 20 years in the HFrEF; on the contrary, few studies are available in HFpEF. Recent evidences have revealed that exercise training counteracts HF-related SMM and in turn ameliorates exercise intolerance.