The continuous heart failure spectrum: moving beyond an ejection fraction classification.

Randomized clinical trials initially used heart failure (HF) patients with low left ventricular ejection fraction (LVEF) to select study populations with high risk to enhance statistical power. However, this use of LVEF in clinical trials has led to oversimplification of the scientific view of a complex syndrome. Descriptive terms such as 'HFrEF' (HF with reduced LVEF), 'HFpEF' (HF with preserved LVEF), and more recently 'HFmrEF' (HF with mid-range LVEF), assigned on arbitrary LVEF cut-off points, have gradually arisen as separate diseases, implying distinct pathophysiologies.

The role of ventricular-arterial coupling in cardiac disease and heart failure: assessment, clinical implications and therapeutic interventions. A consensus document of the European Society of Cardiology Working Group on Aorta & Peripheral Vascular Diseases, European Association of Cardiovascular Imaging, and Heart Failure Association.

Ventricular-arterial coupling (VAC) plays a major role in the physiology of cardiac and aortic mechanics, as well as in the pathophysiology of cardiac disease. VAC assessment possesses independent diagnostic and prognostic value and may be used to refine riskstratification and monitor therapeutic interventions. Traditionally, VAC is assessed by the non-invasive measurement of the ratio of arterial (Ea) to ventricular end-systolic elastance (Ees).

Cardiac Remodeling: Endothelial Cells Have More to Say Than Just NO.

The heart is a highly structured organ consisting of different cell types, including myocytes, endothelial cells, fibroblasts, stem cells, and inflammatory cells. This pluricellularity provides the opportunity of intercellular communication within the organ, with subsequent optimization of its function. Intercellular cross-talk is indispensable during cardiac development, but also plays a substantial modulatory role in the normal and failing heart of adults.

An integrative translational approach to study heart failure with preserved ejection fraction: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology.

As heart failure with preserved ejection fraction (HFpEF) rises to epidemic proportions, major steps in patient management and therapeutic development are badly needed. With the current position paper we seek to update our view on HFpEF as a highly complex systemic syndrome, from risk factors and mechanisms to long-term clinical manifestations. We will revise recent advances in animal model development, experimental set-ups and basic and translational science approaches to HFpEF research, highlighting their drawbacks and advantages.

The future of pleiotropic therapy in heart failure. Lessons from the benefits of exercise training on endothelial function.

A novel generation of drugs is introduced in the treatment of heart failure (HF). These drugs, including phosphodiesterase-5 inhibitors, guanylate cyclase stimulators and activators, share the feature that their action is either endothelial-mediated or substitutes for endothelial pathways, in particular the nitric oxide-cyclic guanosine monophosphate pathway, thereby influencing homeostatic balances in virtually each organ system in a pleiotropic fashion. Unfortunately, recent clinical trials with some of these drugs have shown disappointing results, at least in the setting of HF with a preserved ejection fraction.

Cardiac endothelium-myocyte interaction: clinical opportunities for new heart failure therapies regardless of ejection fraction.

Heart failure (HF) is an important global health problem with great socioeconomic burden. Outcomes remain sub-optimal. Endothelium-cardiomyocyte interactions play essential roles in cardiovascular homeostasis, and deranged endothelium-related signalling pathways have been implicated in the pathophysiology of HF.

Pulmonary hypertension and right heart failure in heart failure with preserved left ventricular ejection fraction: pathophysiology and natural history.

Purpose Of Review: Pulmonary hypertension and right heart failure are common findings in patients suffering from heart failure with preserved ejection fraction (HFpEF). In this review, we summarize our current understanding of the pathophysiology of pulmonary hypertension related to heart failure.

Recent Findings: HFpEF is a clinical syndrome with increasing prevalence and a mortality rate similar to heart failure with reduced ejection fraction.

Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology.

The reductions in mortality and morbidity being achieved among cancer patients with current therapies represent a major achievement. However, given their mechanisms of action, many anti-cancer agents may have significant potential for cardiovascular side effects, including the induction of heart failure. The magnitude of this problem remains unclear and is not readily apparent from current clinical trials of emerging targeted agents, which generally under-represent older patients and those with significant co-morbidities.

How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology.

Diastolic heart failure (DHF) currently accounts for more than 50% of all heart failure patients. DHF is also referred to as heart failure with normal left ventricular (LV) ejection fraction (HFNEF) to indicate that HFNEF could be a precursor of heart failure with reduced LVEF. Because of improved cardiac imaging and because of widespread clinical use of plasma levels of natriuretic peptides, diagnostic criteria for HFNEF needed to be updated.

Diastolic heart failure: a separate disease or selection bias?

Chronic heart failure (CHF) is often subdivided based on left ventricular ejection fraction (LVEF) in 2 distinct forms, usually specified as "diastolic heart failure" and "systolic heart failure." In this review, arguments are provided against an LVEF-based bimodal view, and CHF is presented as one pathophysiological identity encompassing a continuous spectrum of closely related phenotypes. Most importantly, there is currently no pathophysiological basis to support a bimodal view.

Cardiac dysfunction in heart failure: the cardiologist's love affair with time.

Translating research into clinical practice has been a challenge throughout medical history. From the present review, it should be clear that this is particularly the case for heart failure. As a consequence, public awareness of this disease has been disillusionedly low, despite its prognosis being worse than that of most cancers and many other chronic diseases.

Diastolic heart failure: perception of the syndrome and scope of the problem.

Diastolic Heart Failure: perception of the syndrome and scope of the problem. As a result of the recent publications of the CHARM-Preserved trial, the upcoming I-PRESERVE and other still ongoing clinical trials in patients with Heart Failure and Normal (or Preserved) Left Ventricular Ejection Fraction, numerous questions have arisen as for the conceptual rationale and pathophysiological basis of such trials. The present symposium is a synopsis of the most important remaining controversies.

Systolic and diastolic heart failure: different phenotypes of the same disease?

Traditional pathophysiological concepts of chronic heart failure have largely focused on the haemodynamic consequences of ventricular systolic dysfunction. How these concepts relate to the pathophysiology of diastolic heart failure, i.e.

Diastolic heart failure: a myth.

Purpose Of Review: Until recently, patients with heart failure and preserved ejection fraction (HFprEF) have been excluded from nearly all large clinical trials in heart failure. Based on the conjecture that this clinical picture of heart failure, also known as diastolic heart failure, may be different from other forms of heart failure, several recent and ongoing clinical trials have targeted more specifically this patient population. The present review critically re-evaluates the pathophysiological rationale for such trials.

Urgent need to reorganize heart failure management: from paradoxes to heart failure clinics.

Despite the decreasing incidence of ischaemic heart disease and despite major medical advances in heart failure, the prevalence and mortality of chronic heart failure in the population is rising and the prognosis remains grim. Chronic heart failure is a complex disease, which is characterized by its progressive nature. In this paper, we approach the complexity of heart failure from four paradoxes: epidemiology, diagnosis, therapy and economical impact respectively.

Neuregulin-1 induces a negative inotropic effect in cardiac muscle: role of nitric oxide synthase.

Background: Deficient cardiac neuregulin/ErbB signaling increases susceptibility to heart failure. In this study, we examined the effects of neuregulin-1 (NRG-1) on myocardial contractility.

Methods And Results: NRG-1 (alpha and beta isoforms) induced a negative inotropic effect in isolated rabbit papillary muscles and a rightward shift of the dose-response curve to isoproterenol.

Cytokines and immune activation in systolic heart failure: the role of Type D personality.

The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and its soluble receptors 1 (sTNFR1) and 2 (sTNFR2) are predictors of mortality in chronic heart failure (CHF) but the determinants of these increased levels of disease-promoting cytokines are largely unknown. Type D personality refers to the combination of the tendency to experience negative emotions (negative affectivity) and the tendency to inhibit the expression of emotions in social interaction (social inhibition). Type D is an independent predictor of cardiac events in coronary patients who are at risk for CHF.