Heart failure highlights in 2011

Heart failure (HF) remains a major medical problem, and the European Journal of Heart Failure is dedicated to publishing research further investigating its pathophysiology and diagnosis in order to help clinicians alleviate symptoms and improve patient outcomes. 1 This review reports on important studies in the field of HF published in 2011. All research areas are addressed, including experimental studies, biomarkers, clinical trials, arrhythmias, and new insights into the role of device therapy.     

CONSENSUS to EMPHASIS: the overwhelming evidence which makes blockade of the renin-angiotensin-aldosterone system the cornerstone of therapy for systolic heart failure

We will shortly celebrate the 25th anniversary of the publication of the Co‐operative North Scandinavian Enalapril Survival Study (CONSENSUS), a clinical trial which revolutionized the treatment of heart failure and highlighted the importance of the renin–angiotensin–aldosterone system (RAAS) in the pathophysiology of heart failure (Figure 1). In this article I will give a brief, historical overview of this exciting quarter‐century of discovery related to the RAAS. My focus is on the treatment of heart failure in patients with a low left ventricular ejection fraction.     

Systems Biology Applied to Heart Failure With Normal Ejection Fraction

Heart failure with normal ejection fraction (HFNEF) is currently the most prevalent clinical phenotype of heart failure. However, the treatments available have shown no reduction in mortality so far. Advances in the omics sciences and techniques of high data processing used in molecular biology have enabled the development of an integrating approach to HFNEF based on systems biology.This study aimed at presenting a systems-biology-based HFNEF model using the bottom-up and top-down approaches.A literature search was conducted for studies published between 1991 and 2013 regarding HFNEF pathophysiology, its biomarkers and systems biology. A conceptual model was developed using bottom-up and top-down approaches of systems biology.The use of systems-biology approaches for HFNEF, a complex clinical syndrome, can be useful to better understand its pathophysiology and to discover new therapeutic targets.     

Serelaxin in acute heart failure: Most recent update on clinical and preclinical evidence

Heart failure continues to be a widely prevalent disease across the world, affecting millions of Americans annually. Acute heart failure (AHF) has a substantial effect on rising healthcare costs and is one of the major causes of morbidity and mortality. The search for new drugs for symptom relief and to improve long‐term outcomes in heart failure has led to development of serelaxin, a recombinant human relaxin‐2 hormone. Relaxin was discovered in pregnancy, but eventually found to have a number of other physiological actions, not only in pregnancy, but also in nonpregnant women and men. The actions of serelaxin are primarily via nitric oxide, leading to the observed vasodilatory effects, and increase in renal plasma flow. It has also been found to increase expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)‐2 and MMP‐9. The antifibrotic and antiinflammatory effects of the drug also play a role in heart failure. In Phase II studies, serelaxin has shown reduction in pulmonary arterial pressure, pulmonary capillary wedge pressure, and NT‐proBNP. The recently published results of the RELAX‐AHF, a phase III clinical trial on serelaxin, has opened new avenues into our understanding of its effects in heart failure. The trial showed improvement in short‐term dyspnea scores and 180‐day mortality, but, interestingly, failed to show any improvement of the secondary endpoints of death or readmission at 60 days. Ongoing Phase III trials like RELAX‐AHF‐2 and RELAX‐AHF‐ASIA would explain these data better and improve understanding of the use of serelaxin in clinical practice. This article summarizes the most updated published preclinical and clinical study data on serelaxin, including pharmacokinetic, pharmacodynamic, safety studies in hepatic, renal impaired patients, Phase II and Phase III trials.     

Clinical trials update from the European Society of Cardiology–Heart Failure meeting 2015: AUGMENT‐HF,TITRATION, STOP‐HF,HARMONIZE, LION HEART,MOOD‐HF,and renin–angiotensin inhibitors in patients with heart and renal failure

This article provides an overview on the key trials relevant to the pathophysiology, prevention, and treatment of heart failure (HF) presented at the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) annual meeting held in Seville, Spain in May 2015. Trials reported include AUGMENT‐AF (myocardial injections of calcium‐alginate hydrogel), a propensity score‐matched study of renin–angiotensin system antagonists in patients with HF and severe renal dysfunction, HARMONIZE (sodium zirconium cyclosilicate used to bind potassium), TITRATION, comparing two regimes for introducing LCZ696, STOP‐HF, a trial of intramyocardial stromal cell‐derived factor‐1, MOOD‐HF (escitalopram for patients with heart failure and depression), and LION HEART, a trial of intermittent levosimendan therapy. Unpublished reports should be considered as preliminary, since analyses may change in the final publication.     

Heart failure in women

Increasingly high mortality from cardiovascular disease in women has sparked nationwide campaigns to raise awareness of this significant threat to women’s health. Heart failure has the most lethal prognosis of the major cardiovascular diseases, yet women demonstrate an apparent survival advantage compared with men. Sex-linked disparities in heart failure risk factors and pathophysiology contribute to this divergent clinical outcome. Heart failure etiology and clinical manifestations unique to female sex exist. At age 40, the lifetime risk of developing heart failure is equal for men and women, whereas the lifetime risk of developing coronary heart disease is one in two for men and one in three for women. Understanding sex-inherent characteristics related to heart failure may help determine whether the optimal therapy for this prevalent syndrome should be modified according to sex. Until prospective trial data prove otherwise, heart failure treatment guidelines should be uniformly applied to both women and men.     

2022 ACC/AHA/HFSA Guideline for the Management of Heart Failure: Executive Summary

BackgroundThe 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America (AHA/ACC/HFSA) Guideline for the Management of Heart Failure replaces the 2013 ACCF/AHA Guideline for the Management of Heart Failure and the 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose and manage patients with heart failure.MethodsA comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews and other evidence conducted in human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies published through September 2021 were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021.Results and ConclusionsHeart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients’ interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments that have high-quality published economic analyses.     

Heart failure highlights in 2010

Heart failure is still a large medical problem, and the European Journal of Heart Failure remains dedicated to further investigating its pathophysiology and diagnosis, as well as alleviating the symptoms and improving outcome for patients with this disorder.(1) In 2010, a large number of important studies have been published, many with exciting results. In this overview, we discuss the results of many of these studies, which have been conducted in a broad range of areas, ranging from pre-clinical research, to co-morbidities, new insights in the genetics of heart failure, and novel guidelines in the field of device therapy.     

The HEART FAILURE Journal Club: a review of publications on heart failure in American Heart Journal

The following paper reviews the heart failure literature that has been published by the American Heart Journal over the last year. Specifically the literature has been divided up into the areas of epidemiology, pathophysiology, autonomic function, neuroendocrine activation, exercise, imaging, surgery, pharmacological therapies and prognosis.     

Comparison of midregional pro‐atrial natriuretic peptide with N‐terminal pro‐B‐type natriuretic peptide in the diagnosis of heart failure

Objectives. The concentration of atrial natriuretic peptide (ANP) in the circulation is approximately 10‐ to 50‐ fold higher than B‐type natriuretic peptide (BNP). We sought to compare the accuracy of midregional pro‐atrial natriuretic peptide (MRproANP) measured with a novel sandwich immunoassay with N‐terminal pro‐B‐type natriuretic peptide (NTproBNP) in the diagnosis of heart failure. Design. The diagnosis of heart failure was adjudicated by two independent cardiologists using all available clinical data (including BNP levels) in 287 consecutive patients presenting with dyspnoea to the emergency department (ED). MRproANP and NTproBNP levels were determined at presentation in a blinded fashion. Results. Heart failure was the adjudicated final diagnosis in 154 patients (54%). Median MRproANP was significantly higher in patients with heart failure as compared to patients with other causes of dyspnoea (400 vs. 92 pmol L^?1, P < 0.001). The diagnostic accuracy of MRproANP was very high with an area under the receiver operating characteristic curve of 0.92 and was comparable with that of NTproBNP (0.92, P = 0.791). Moreover, MRproANP provided incremental diagnostic information to BNP and NTproBNP in patients presenting with BNP levels in the grey zone between 100 and 500 pg mL^?1. Conclusion. Midregional pro‐atrial natriuretic peptide is as accurate in the diagnosis of heart failure as NTproBNP. MRproANP seems to provide incremental information on top of BNP or NT‐proBNP in some subgroups and should be further investigated in other studies.     

2022 ACC/AHA/HFSA Guideline for the Management of Heart Failure

AimThe “2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure” replaces the “2013 ACCF/AHA Guideline for the Management of Heart Failure” and the “2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure.” The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure.MethodsA comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021.StructureHeart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients’ interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.     

Resveratrol in cardiovascular disease: what is known from current research?

Resveratrol is a well-known antioxidant that exists in grape skin/seed, red wine, and the root of Polygonum cuspidatum, a traditional Chinese and Japanese medicinal material. Studies have found that resveratrol has many interesting properties, including anti-carcinogenic properties, anti-microbial and antiviral effects, the ability to reverse dyslipidemia and obesity, the ability to attenuate hyperglycemia and hyperinsulinemia, and the ability to protect endothelial function. Heart failure is the final consequence of the majority of cardiovascular diseases, and resveratrol has been shown to directly attenuate heart contraction. The cardiovascular protective capacities of resveratrol are associated with multiple molecular targets and may lead to the development of novel therapeutic strategies for atherosclerosis, ischemia/reperfusion, metabolic syndrome, and heart failure. This article will mainly review recently published basic researches about the protective cardiovascular effects of resveratrol because these results may lead to the development of new clinical therapeutics in patients.     

Imaging in patients with suspected acute heart failure: timeline approach position statement on behalf of the Heart Failure Association of the European Society of Cardiology

Acute heart failure is one of the main diagnostic and therapeutic challenges in clinical practice due to a non‐specific clinical manifestation and the urgent need for timely and tailored management at the same time. In this position statement, the Heart Failure Association aims to systematize the use of various imaging methods in accordance with the timeline of acute heart failure care proposed in the recent guidelines of the European Society of Cardiology. During the first hours of admission the point‐of‐care focused cardiac and lung ultrasound examination is an invaluable tool for rapid differential diagnosis of acute dyspnoea, which is highly feasible and relatively easy to learn. Several portable and stationary imaging modalities are being increasingly used for the evaluation of cardiac structure and function, haemodynamic and volume status, precipitating myocardial ischaemia or valvular abnormalities, and systemic and pulmonary congestion. This paper emphasizes the central role of the full echocardiographic examination in the identification of heart failure aetiology, severity of cardiac dysfunction, indications for specific heart failure therapy, and risk stratification. Correct evaluation of cardiac filling pressures and accurate prognostication may help to prevent unscheduled short‐term readmission. Alternative advanced imaging modalities should be considered to assist patient management in the pre‐ and post‐discharge phase, including cardiac magnetic resonance, computed tomography, nuclear studies, and coronary angiography. The Heart Failure Association addresses this paper to the wide spectrum of acute care and heart failure specialists, highlighting the value of all available imaging techniques at specific stages and in common clinical scenarios of acute heart failure.     

Atrial Support Pacing in Heart Failure: Results from the Multicenter PEGASUS CRT Trial

Atrial Pacing in Heart Failure. Introduction: Cardiac resynchronization therapy (CRT) efficacy trials to date used atrial‐synchronous biventricular pacing wherein there is no or minimal atrial pacing. However, bradycardia and chronotropic incompetence are common in this patient population. This trial was designed to evaluate the effect of atrial support pacing among heart failure patients receiving a CRT defibrillator. Methods and Results: PEGASUS CRT was a multicenter, 3‐arm, randomized study. At 6 weeks, patients were randomized to DDD mode at a lower rate of 40 bpm (DDD‐40; control arm), or one of the following 2 treatment arms: DDD‐70, or DDDR‐40. The primary endpoint was a clinical composite endpoint that included all‐cause mortality, heart failure events, NYHA functional class, and patient global self‐assessment. Subjects were classified as improved, unchanged, or worsened at 12 months. There were 1,433 patients randomized, of whom 66% were male, mean age was 67 ± 11 years, and mean left ventricular ejection fraction was 23 ± 7%. The average follow‐up time was 10.5 ± 3.5 months and 1,309 patients contributed to the primary endpoint. No significant differences were observed in the composite endpoint between either of the 2 treatment arms compared to the control arm (P>0.05 for both comparisons). Additionally, there were no differences among the groups in mortality or heart failure events. Conclusion: In advanced heart failure patients treated with CRT, atrial support pacing did not improve clinical outcomes compared to atrial tracking. However, atrial pacing did not adversely affect mortality or heart failure events. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1317‐1325, December 2012)     

Clinical trials update from the Heart Failure Society of America and the American Heart Association meetings in 2008: SADHART-CHF,COMPARE, MOMENTUM,thyroid hormone analogue study,HF-ACTION,I-PRESERVE, β-interferon study,BACH, and ATHENA

This article provides information and a commentary on trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the Heart Failure Society of America and the American Heart Association meetings in 2008. Unpublished reports should be considered as preliminary, as analyses may change in the final publication. (i) SADHART-CHF showed no difference in outcome for heart failure patients with depression treated with sertraline compared with placebo. (ii) A controlled release carvedilol formulation showed similar LV haemodynamic effects to the standard carvedilol formulation in the COMPARE study. (iii) A post hoc analysis of the MOMENTUM study suggested that patients with less severe heart failure may be more likely to benefit from a continuous aortic flow augmentation device. (iv) A thyroid hormone analogue was poorly tolerated in patients with heart failure. (v) HF-ACTION showed that exercise training is safe and offers modest clinical benefits in patients with heart failure. (vi) Irbesartan failed to improve outcomes in patients with preserved ejection fraction in the I-PRESERVE study. (vii) A phase II study of beta-interferon administration in patients with dilated cardiomyopathy showed encouraging results. (viii) The BACH study showed that mid-regional pro-adrenomedullin was more accurate than BNP or NT-proBNP at predicting outcome at 90 days in patients with acute heart failure. (ix) A secondary analysis from ATHENA showed a reduction in cardiovascular hospitalizations and strokes for patients with atrial fibrillation receiving dronedarone compared with placebo.     

The Heart Failure Journal Club: a review of publications on Heart Failure in the European Heart Journal

This is one of a series of articles reviewing the literature on heart failure from the world's leading cardiovascular journals. All articles published in the European Heart Journal during the year 2000 were identified and those relevant to heart failure were reviewed. This includes all original scientific articles, systematic reviews and key editorials. This may prove a valuable resource for keeping up to date with the literature on heart failure.     

Clinical trials update from the European Society of Cardiology heart failure meeting 2009: CHANCE,B‐Convinced,CHAT, CIBIS‐ELD,and Signal‐HF

This paper provides information and a commentary on trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the annual meeting of the Heart Failure Association of the European Society of Cardiology held in Nice. The CHANCE study showed a substantial reduction in morbidity and mortality in a randomized controlled trial (RCT) of a multidisciplinary management programme for patients with chronic heart failure in Russia. Data from the B‐Convinced study, also an RCT, suggest that continuation of beta‐blocker (BB) therapy in patients hospitalized with worsening heart failure may be associated with improved outcomes when compared with treatment discontinuation. The CHAT study suggests that telephone support can improve prognosis in heart failure patients living in remote rural locations. CIBIS‐ELD showed that titration of BBs to target doses in older patients with heart failure is more difficult; but tolerance levels were similar for bisoprolol and carvedilol. Signal‐HF randomized elderly heart failure patients to treatment guided by NT‐proBNP levels or usual care, and showed no effect of NT‐proBNP‐guided treatment on outcomes.     

Epidemiology of acute heart failure syndromes

Acute Heart Failure is a heterogeneous set of syndromes associated with significant morbidity and mortality. There are several classifications of acute heart failure syndromes (AHFS) based on pathophysiology or clinical presentation. In the USA and in Europe, AHFS are the first cause of hospitalization of the elderly, and the leading health care cost. Despite this clinical and social importance, AHFS have received little attention from clinicians and researchers. Recently published epidemiological studies described clinical presentation, characteristics and treatment of over 100,000 patients hospitalized with AHFS. These studies also underlined the poor, short, and medium term prognosis, especially for the most severe patients admitted to an intensive care unit, with in-hospital mortality of 28%. Further epidemiological and clinical research is needed to improve our understanding of AHFS, thereby enhancing patient care.     

Sex differences in the causes and natural history of heart failure

Heart failure is a clinical syndrome of increasing prevalence in the United States, with significant morbidity and mortality. Although men have a higher annual mortality rate, more women than men die from heart failure each year. Optimal disease management is critical in limiting the impact of heart failure on life quality, quantity, and health care expenditures. Women have a unique risk-factor profile and different clinical manifestations of heart failure than men. Understanding inherent sex differences in heart failure epidemiology, pathophysiology, and natural history is imperative in determining whether the optimal therapy for this prevalent and important syndrome is affected by sex.     

Right side of heart failure

The function of the right ventricle (RV) in heart failure (HF) has been mostly ignored until recently. A 2006 report of the National Heart, Lung, and Blood Institute identified a gap between RV research efforts and its clinical importance compared with that of the left ventricle. This recent shift in paradigm is fueled by the prognostic value ascribed to RV failure in HF and morbidity/mortality after myocardial infarction and surgery. In this review, we examine the significance of RV failure in the HF setting, its clinical presentation and pathophysiology, and ways to evaluate RV function using echocardiographic measurements. Furthermore, we discuss the medical management of RV failure including traditional therapies like beta-blockers and newer options like nitric oxide, phosphodiesterase inhibitors, and calcium sensitizers. Mechanical support is also examined. Finally, this review places an emphasis on RV failure in the setting of left ventricular assist devices and heart transplantation.