Imaging predictors of incident heart failure: a systematic review and meta-analysis

BACKGROUND: Preventing the evolution of subclinical cardiac disease into overt heart failure is of paramount importance. Imaging techniques, particularly transthoracic echocardiography (TTE), are well suited to identify abnormalities in cardiac structure and function that precede the development of heart failure. METHODS: This meta-analysis provides a comprehensive evaluation of 32 studies from 11 individual cohorts, which assessed cardiac indices from TTE (63%), cardiovascular magnetic resonance (CMR; 34%) or cardiac computed tomography (CCT; 16%). Eligible studies focused on measures of left ventricular geometry and function and were highly heterogeneous. RESULTS: Among the variables that could be assessed through a meta-analytic approach, left ventricular systolic dysfunction, defined as left ventricular ejection fraction (LVEF) lower than 50%, and left ventricular dilation were associated with a five-fold [hazard ratio (HR) 4.76, 95% confidence interval (95% CI) 1.85-12.26] and three-fold (HR 3.14, 95% CI 1.37 -7.19) increased risk of heart failure development, respectively. Any degree of diastolic dysfunction conveyed an independent, albeit weaker, association with heart failure (HR 1.48, 95% CI 1.11-1.96), although there was only a trend for left ventricular hypertrophy in predicting incident heart failure (hazard ratio 2.85, 95% CI 0.82-9.85). CONCLUSION: LVEF less than 50%, left ventricular dilation and diastolic dysfunction are independent predictors of incident heart failure among asymptomatic individuals, while left ventricular hypertrophy seems less predictive. These findings may serve as a framework for implementing imaging-based screening strategies in patients at risk of heart failure and inform future studies testing preventive or therapeutic approaches aiming at thwarting or halting the progression from asymptomatic (preclinical) to overt heart failure

The role of antithrombotic therapy in heart failure

Heart failure is a major contributor to global morbidity and mortality burden affecting approximately 1-2% of adults in developed countries, mounting to over 10% in individuals aged >70 years old. Heart failure is characterized by a prothrombotic state and increased rates of stroke and thromboembolism have been reported in heart failure patients compared with the general population. However, the impact of antithrombotic therapy on heart failure remains controversial. Administration of antiplatelet or anticoagulant therapy is the obvious (and well-established) choice in heart failure patients with cardiovascular comorbidity that necessitates their use, such as coronary artery disease or atrial fibrillation. In contrast, antithrombotic therapy has not demonstrated any clear benefit when administered for heart failure per se, i.e. with heart failure being the sole indication. Randomized studies have reported decreased stroke rates with warfarin use in patients with heart failure with reduced left ventricular ejection fraction, but at the expense of excessive bleeding. Non-vitamin K oral anticoagulants have shown a better safety profile in heart failure patients with atrial fibrillation compared with warfarin, however, current evidence about their role in heart failure with sinus rhythm is inconclusive and further research is needed. In the present review, we discuss the role of antithrombotic therapy in heart failure (beyond coronary artery dis-ease), aiming to summarize evidence regarding the thrombotic risk and the role of antiplatelet and anticoagulant agents in patients with heart failure. © 2020 Bentham Science Publishers

Aortic valve: anatomy and structure and the role of vasculature in the degenerative process

Aortic valve stenosis is a degenerative disease affecting increasing number of individuals and characterised by thickening, calcification and fibrosis of the valve resulting in restricted valve motion. Degeneration of the aortic valve is no longer considered a passive deposition of calcium, but an active process that involves certain mechanisms, that is endothelial dysfunction, inflammation, increased oxidative stress, calcification, bone formation, lipid deposition, extracellular matrix (ECM) remodelling and neoangiogenesis. Accumulating evidence indicates an important role for neoangiogenesis (i.e. formation of new vessels) in the pathogenesis of aortic valve stenosis. The normal aortic valve is generally an avascular tissue supplied with oxygen and nutrients via diffusion from the circulating blood. In contrast, presence of intrinsic micro-vasculature has been demonstrated in stenotic and calcified valves. Importantly, presence and density of neovessels have been associated with inflammation, calcification and bone formation. It remains unclear whether neoangiogenesis is a compensatory mechanism aiming to counteract hypoxia and increased metabolic demands of the thickened tissue or represents an active contributor to disease progression. Data extracted mainly from animal studies are supportive of a direct detrimental effect of neoangiogenesis, however, robust evidence from human studies is lacking. Thus, there is inadequate knowledge to assess whether neoangiogenesis could serve as a future therapeutic target for a disease that no effective medical therapy exists. In this review, we present basic aspects of anatomy and structure of the normal and stenotic aortic valve and we focus on the role of valve vasculature in the natural course of valve calcification and stenosis. © 2020 Belgian Society of Cardiology

Imaging predictors of incident heart failure: a systematic review and meta-analysis

BACKGROUND: Preventing the evolution of subclinical cardiac disease into overt heart failure is of paramount importance. Imaging techniques, particularly transthoracic echocardiography (TTE), are well suited to identify abnormalities in cardiac structure and function that precede the development of heart failure. METHODS: This meta-analysis provides a comprehensive evaluation of 32 studies from 11 individual cohorts, which assessed cardiac indices from TTE (63%), cardiovascular magnetic resonance (CMR; 34%) or cardiac computed tomography (CCT; 16%). Eligible studies focused on measures of left ventricular geometry and function and were highly heterogeneous. RESULTS: Among the variables that could be assessed through a meta-analytic approach, left ventricular systolic dysfunction, defined as left ventricular ejection fraction (LVEF) lower than 50%, and left ventricular dilation were associated with a five-fold [hazard ratio (HR) 4.76, 95% confidence interval (95% CI) 1.85-12.26] and three-fold (HR 3.14, 95% CI 1.37 -7.19) increased risk of heart failure development, respectively. Any degree of diastolic dysfunction conveyed an independent, albeit weaker, association with heart failure (HR 1.48, 95% CI 1.11-1.96), although there was only a trend for left ventricular hypertrophy in predicting incident heart failure (hazard ratio 2.85, 95% CI 0.82-9.85). CONCLUSION: LVEF less than 50%, left ventricular dilation and diastolic dysfunction are independent predictors of incident heart failure among asymptomatic individuals, while left ventricular hypertrophy seems less predictive. These findings may serve as a framework for implementing imaging-based screening strategies in patients at risk of heart failure and inform future studies testing preventive or therapeutic approaches aiming at thwarting or halting the progression from asymptomatic (preclinical) to overt heart failure. Copyright © 2020 Italian Federation of Cardiology - I.F.C. All rights reserved

Usefulness of F2-isoprostanes in early prognostication after cardiac arrest: a topical review of the literature and meta-analysis of preclinical data

Prognostication after cardiac arrest (CA) represents a challenging issue, and several biomarkers have been proposed in the attempt to predict outcome. Among these, F2-isoprostanes stand out as potential biomarkers for early prognostication, providing information on the magnitude of global oxidative injury after return of spontaneous circulation (ROSC). We performed a topical review searching PubMed and Scopus databases to identify studies evaluating the modifications of F2-isoprostanes in the early period after CA, and a meta-analysis of studies providing curves of F2-isoprostanes plasma levels seeking to describe the biomarker’s kinetics after CA. Evidence suggests that plasma levels of F2-isoprostanes increase in the early post-resuscitation period and seem well correlated with the burden of ischaemia-reperfusion injury. Our meta-analysis shows a possible increase as early as 5 minutes after ROSC, which persists at 2 hours and is attenuated at 4 hours. Clinical studies are warranted to evaluate the utility of this biomarker for prognostication purposes in CA survivors. © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group

Skeletal muscle mass in acute coronary syndrome prognosis: Gender-based analysis from Hellenic Heart Failure cohort

Background and aims: Predictive and prognostic ability of muscle mass in CVD settings is increasingly discussed. The gender-specific effect of skeletal muscle mass index (SMI) on 10-year recurrent fatal/non fatal cardiovascular disease (CVD) event of acute coronary syndrome (ACS) patients was evaluated. Methods and results: In 2006–2009, n = 1000 consecutive patients (n = 222 women), hospitalized at the First Cardiology Clinic of Athens with ACS diagnosis and with symptoms and left ventricular function indicative of heart failure were selected. SMI was created to reflect skeletal muscle mass through appendicular skeletal muscle mass (indirectly calculated through population formulas) divided by body mass index (BMI). In the 10-year follow-up (2016), 55% of ACS patients experienced recurrent fatal/non fatal CVD events (53% in women vs.62% in men, p = 0.04). Patients in the 2nd SMI tertile (mostly overweight) had 10% lower risk for CVD recurrence (women:men rate ratio = 0.87) over their counterparts in the 1st (mostly normalweight) and 3rd tertile (mostly obese). Multivariate analysis revealed that ACS patients in the 2nd SMI tertile presented 46% and 85% lower CVD event risk over their counterparts in the 1st tertile (Hazard Ratio (HR) = 0.54, 95% Confidence Interval (95% CI) 0.30, 0.96, p = 0.002) and 3rd tertile (HR = 1.85, 95%CI 1.05, 2.94, p = 0.03). Gender-based analysis revealed that this trend remained significant only in women. Inflammatory markers had strong confounding effect. Conclusion: A U-shape association between SMI and 10-year CVD event especially in women was highlighted. This work reveals gender-specific remarks for “obesity-lean paradox” in secondary prevention, implying that high muscle mass accompanied by obesity and excess adiposity may not guarantee better prognosis. © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II Universit

The Role of Arterial Hypertension in Mitral Valve Regurgitation

Purpose of Review: To review medical literature for evidence of association between hypertension and mitral regurgitation (MR) and summarize potential favorable effects of antihypertensive drugs on MR natural history and treatment. Recent Findings: Hypertension and MR are common diseases affecting a large proportion of the general population. Contemporary evidence suggests that hypertension may worsen the progression and prognosis of MR through augmented mechanical stress and increased regurgitation volume. Renin-angiotensin axis inhibitors, beta-blockers, and vasodilators have been tested in order to prevent or decrease primary or secondary MR. Summary: Although antihypertensive agents may improve hemodynamic parameters and left ventricular remodeling in primary MR, there is no strong evidence of benefit on clinical outcomes. On the other hand, a beneficial effect of these drugs on secondary MR is better established. Moreover, there are no studies evaluating a possible benefit of lower blood pressure targets in MR. Randomized controlled trials are warranted to elucidate the precise role of antihypertensive therapy on treatment of MR. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

Orthostatic hypertension: From pathophysiology to clinical applications and therapeutic considerations

Orthostatic hypertension (OHT), that is, sustained increase in blood pressure after standing, is an increasingly recognized cardiovascular disorder having been examined in much fewer studies compared with orthostatic hypotension (OH). However, in both OHT and OH, dysfunction of the autonomous nervous system is considered to be the primary pathophysiological disturbance, while significant associations with essential hypertension have been observed. Although in many studies OHT has been related to subclinical or clinical target organ damage, there is also evidence denying such an association. Because OHT is defined variably across different studies, the comparison of relevant outcomes is at least problematic. Since evidence about OHT treatment is exclusively based on limited non-randomized studies, no specific recommendations have been developed. Therefore, both the prognostic role and the clinical significance of OHT remain largely undefined. The aim of the present review is to summarize the available evidence regarding the definition, diagnosis, pathophysiology, prognostic role and treatment of OHT and highlight potential clinical implications of this underestimated condition. ©2019 Wiley Periodicals, Inc

Cardiac resynchronisation therapy and cellular bioenergetics: Effects beyond chamber mechanics

Cardiac resynchronisation therapy is a cornerstone in the treatment of advanced dyssynchronous heart failure. However, despite its widespread clinical application, precise mechanisms through which it exerts its beneficial effects remain elusive. Several studies have pointed to a metabolic component suggesting that, both in concert with alterations in chamber mechanics and independently of them, resynchronisation reverses detrimental changes to cellular metabolism, increasing energy efficiency and metabolic reserve. These actions could partially account for the existence of responders that improve functionally but not echocardiographically. This article will attempt to summarise key components of cardiomyocyte metabolism in health and heart failure, with a focus on the dyssynchronous variant. Both chamber mechanics-related and -unrelated pathways of resynchronisation effects on bioenergetics - stemming from the ultramicroscopic level - and a possible common underlying mechanism relating mechanosensing to metabolism through the cytoskeleton will be presented. Improved insights regarding the cellular and molecular effects of resynchronisation on bioenergetics will promote our understanding of non-response, optimal device programming and lead to better patient care. © RADCLIFFE CARDIOLOGY 2019

Vitamins in heart failure: Friend or enemy?

Background: The failing heart is characterized by a depleted metabolic energy reserve and the upregulation of several molecular mechanisms leading to cardiac hypertrophy, inflammation, fibrosis, angiogenesis, and apoptosis. Dietary or non-dietary supplementation of vitamins could potentially benefit energy balance. Objective: The objective of the present study was to evaluate all available information on vitamins supplementation in patients with chronic HF for possible beneficial effect on metabolic, inotropic, chronotropic and hemodynamic indices. Method: We searched MEDLINE via Pubmed by using the following terms: “chronic heart failure” OR “cardiomyopathy” AND “vitamins”, “vitamin A”, “B complex vitamins”, “vitamin C”, “ascorbic acid”, “vitamin D”, “retinol”, “vitamin E”, “thiamine”, “riboflavin”, “niacin”, “pyridoxine”, “cobalamin”, “folate”, “pantothenic acid”, “biotin”, “tocopherol” and combinations of them. Results: Data regarding supplementation of micronutrients in HF for most vitamins were sparse, and the inference about cardiovascular outcomes was obscured by the heterogeneity of studies, high inherent morbidity, and mortality of this group of high-risk patients, limited sample sizes in certain studies, unclear design and lack of head to head comparisons. Most vitamins in human trials failed to offer survival, or robust beneficial effect. Mostly indirect favorable evidence is derived from patients with deficiencies of certain micronutrients rather than their ad hoc supplementation. Conclusion: While vitamins and micronutrients are promising compounds for optimizing myocardial metabolism and homeostasis in HF, additional randomized clinical trials of larger scale are warranted to demonstrate the benefits of their supplementation in this high risk group of patients. © 2017 Bentham Science Publishers