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

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

The Role of Arterial Hypertension in Mitral Valve Regurgitation

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

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

Arterial hypertension in patients under antineoplastic therapy: a systematic review

BACKGROUND: Cardio-oncology aims to mitigate adverse cardiovascular manifestations in cancer survivors, but treatment-induced hypertension or aggravated hypertension has received less attention in these high cardiovascular risk patients. METHODS: In this systematic review, we searched literature for contemporary data on the prevalence, pathophysiologic mechanisms, treatment implications and preventive strategies of hypertension in patients under antineoplastic therapy. RESULTS: Several classes of antineoplastic drugs, including mainly vascular endothelial growth factor inhibitors, proteasome inhibitors, cisplatin derivatives, corticosteroids or radiation therapy were consistently associated with increased odds for new-onset hypertension or labile hypertensive status in previous controlled patients. Moreover, hypertension constitutes a major risk factor for chemotherapy-induced cardiotoxicity, which is the most serious cardiovascular adverse effect of antineoplastic therapy. Despite the heterogeneity of pooled studies, the pro-hypertensive profile of examined drug classes could be attributed to common structural and functional disorders. Importantly, certain antihypertensive drugs are considered to be more effective in the management of hypertension in this population and may partially attenuate indirect complications of cancer treatment, such as progressive development of cardiomyopathy and/or cardiovascular death. Nonpharmacological approaches to alleviate hypertension in cancer patients are also described, albeit adjudicated as less effective in general. CONCLUSION: A growing body of evidence suggests that multiple antineoplastic agents increase the rate of progression of hypertension. Physicians need to balance the life-saving cancer treatment and the inflated risk of adverse cardiovascular events due to suboptimal management of hypertension in order to achieve improved clinical outcomes and sustained survival for their patient

A Bayesian meta-analysis on early tobacco exposure and vascular health:From childhood to early adulthood

Background: Smoking has been consistently associated with increased cardiovascular risk in adults. Although exposure to tobacco products often starts in early life, evidence for the possible adverse effects on the cardiovascular system of the young is scarce. We sought to derive pooled estimates of smoking effects on indices of early vascular damage in children and adolescents. Design and methods: We performed a systematic review and meta-analysis of clinical studies involving young individuals up to 21 years old that provided data on smoking exposure (active or passive) and flow-mediated dilatation, carotid to femoral pulse wave velocity and maximum carotid intima-media thickness. We employed three distinct methodologies of random-effects data synthesis, including the Sidik-Jonkman estimator, the Hartung and Knapp correction and a Bayesian method with a well-informed prior on the level of between-study variance. Results: In 12 studies and 5279 individuals in total, smoking exposure was related to deterioration in all three outcomes (mean adjusted flow-mediated dilatation decrease: −0.77%, 95% confidence interval −1.38–−0.15, mean adjusted pulse wave velocity increase: 0.1 m/s, 95% confidence interval 0.02–0.17 and mean adjusted carotid intima-media thickness increase: 0.35 mm, 95% confidence interval 0.16–0.55, for the Sidik-Jonkman estimator). No difference was established between active and passive smoking on associations with arterial damage. Conclusions: Exposure to tobacco products is associated with subclinical vascular damage early in life, even from childhood. Public health initiatives should target these very young age groups to prevent early smoking exposure and associated arterial damage and its sequelae

Multipoint left ventricular pacing effects on hemodynamic parameters and functional status: HUMVEE single-arm clinical trial (NCT03189368)

Objectives: The aim of this study was to assess the capacity of optimized multipoint pacing (MPP) over optimized cardiac resynchronization therapy (CRT), in terms of clinical, functional, and echocardiographic parameters among patients with dyssynchronous heart failure (HF). Methods: Eighty patients (Caucasian, 77.5% male, 68.4 +/- 10.1 years, and 53.8% ischemic cardiomyopathy) sequentially received optimized CRT and optimized MPP over 6-and 12-month periods in a single-arm clinical trial. Clinical, laboratory, and echocardiographic assessment was conducted at baseline and after the completion of each step. Results: Significant additive effects of optimized MPP over optimized CRT were noted with regard to 6 min walking distance (baseline/optCRT/optMPP: 293 +/- 120 m vs 367 +/- 94 m vs 405 +/- 129 m and p < 0.001), NYHA class (2.36 vs 2.19 vs 1.45 and p < 0.001), VTIlvot (14.25 +/- 3.2 cm vs 16.2 +/- 4 cm vs 17.5 +/- 3.4 cm and p < 0.001), stroke volume (48 +/- 13.5 ml vs 55 +/- 15 ml vs 59 +/- 15 ml and p < 0.001), left ventricular ejection fraction (LVEF) (29% +/- 7.1% vs 33% +/- 7.3% vs 37% +/- 7.7% and p < 0.001), maximal left atrial volume (77.2 +/- 34.2 ml vs 74.2 +/- 39.5 ml vs 67.7 +/- 32 ml and p = 0.02), pulmonary artery systolic pressure (35.9 mmHg vs 33.5 mmHg vs 31 mmHg and p < 0.001), and right ventricular strain (-8.3% +/- 6.9% vs-8.8% +/- 6.6% vs-11.8% +/- 6.1% and p = 0.022). With regard to VAC, stroke work (SW), and CP as percentages of maximal, there was a significant difference detected as compared to baseline for both CRT and MPP. Additive effects persisted only if suitable MPP dipoles were present. Exploratory analysis revealed that ischemic cardiomyopathy continued to exhibit significant differences that favor MPP, whereas nonischemic cardiomyopathy had similar findings with regard to total left atrial strain and quality of life. Conclusions: Optimized MPP showed significant improvements in hemodynamic parameters and ventricular function in patients with HF over optimized CRT. The beneficial effect was more prominent in men and in those with rather reduced LVEF, consistent with findings that suggest a beneficial trend in VAC and CP with more homogeneous depolarization offered by optimized MPP. (c) 2021 Hellenic Society of Cardiology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Left ventricular mass versus pulse wave velocity as predictors of coronary artery disease in hypertensive patients: data from a 6-year-follow-up study

In treated hypertensive patients, there is a substantial residual cardiovascular (CV) risk that cannot be assessed by the available prediction models. This risk can be associated with subclinical organ damage, such as increased left ventricular mass (LVM) and arterial stiffness. However, it remains unknown which of these two CV markers better predicts coronary artery disease (CAD). A prospective cohort study was used to answer the above question. The study sample consisted of 1033 patients with hypertension (mean age 55.6 years, 538 males) free of CAD at baseline, who were followed for a mean period of 6 years. At baseline, all subjects underwent a complete echocardiographic study and pulse wave velocity (PWV) measurement. Hypertensive individuals who developed CAD (2.8%) compared to those without CAD at follow-up, had a higher baseline LVM index (by 16.7 g/m(2), p < 0.001), higher prevalence of left ventricular hypertrophy (LVH) (21% greater, p = 0.027) and greater prevalence of high PWV levels at baseline (21% greater, p = 0.019). Multivariate Cox regression analysis revealed that baseline age >65 years (HR = 2.067, p = 0.001), male gender (HR = 3.664, p = 0.001), baseline chronic kidney disease (HR = 2.020, p = 0.026), baseline diabetes mellitus (HR = 1.952, p = 0.015) and baseline LVH (HR = 2.124 p = 0.001) turned out to be independent predictors of CAD, whereas high PWV levels were not. LVH proved to be an independent prognosticator of CAD in contrast to arterial stiffness that was not related to CAD after accounting for established confounders. Therefore, LVM can reliably help physicians to identify high-risk hypertensives in whom an intensified therapeutic management is warranted