Mitochondria are central organelles in the homeostasis of the cardiovascular system via the integration of several physiological processes, such as ATP generation via oxidative phosphorylation, synthesis/exchange of metabolites, calcium sequestration, reactive oxygen species (ROS) production/buffering and control of cellular survival/death. Mitochondrial impairment has been widely recognized as a central pathomechanism of almost all cardiovascular diseases, rendering these organelles important therapeutic targets. Mitochondrial dysfunction has been reported to occur in the setting of drug-induced toxicity in several tissues and organs, including the heart. Members of the drug classes currently used in the therapeutics of cardiovascular pathologies have been reported to both support and undermine mitochondrial function. For the latter case, mitochondrial toxicity is the consequence of drug interference (direct or off-target effects) with mitochondrial respiration/energy conversion, DNA replication, ROS production and detoxification, cell death signaling and mitochondrial dynamics. The present narrative review aims to summarize the beneficial and deleterious mitochondrial effects of common cardiovascular medications as described in various experimental models and identify those for which evidence for both types of effects is available in the literature.

Amiodarone is a potent antiarrhythmic drug and displays substantial liver toxicity in humans. It has previously been demonstrated that amiodarone and its metabolite (desethylamiodarone, DEA) can inhibit mitochondrial function, particularly complexes I (CI) and II (CII) of the electron transport system in various animal tissues and cell types. The present study, performed in human peripheral blood cells, and one liver-derived human cell line, is primarily aimed at assessing the concentration-dependent effects of these drugs on mitochondrial function (respiration and cellular ATP levels). Furthermore, we explore the efficacy of a novel cell-permeable succinate prodrug in alleviating the drug-induced acute mitochondrial dysfunction. Amiodarone and DEA elicit a concentration-dependent impairment of mitochondrial respiration in both intact and permeabilized platelets via the inhibition of both CI- and CII-supported respiration. The inhibitory effect seen in human platelets is also confirmed in mononuclear cells (PBMCs) and HepG2 cells. Additionally, amiodarone elicits a severe concentration-dependent ATP depletion in PBMCs, which cannot be explained solely by mitochondrial inhibition. The succinate prodrug NV118 alleviates the respiratory deficit in platelets and HepG2 cells acutely exposed to amiodarone. In conclusion, amiodarone severely inhibits metabolism in primary human mitochondria, which can be counteracted by increasing mitochondrial function using intracellular delivery of succinate.

Since the prevalence of heart failure (HF) increases with age, HF is now one of the most common reasons for the hospitalization of elderly people. Although the treatment strategies and overall outcomes of HF patients have improved over time, hospitalization and mortality rates remain elevated, especially in developed countries where populations are aging. Therefore, this paper is intended to be a valuable multidisciplinary source of information for both doctors (cardiologists and general physicians) and pharmacists in order to decrease the morbidity and mortality of heart failure patients. We address several aspects regarding pharmacological treatment (including new approaches in HF treatment strategies [sacubitril/valsartan combination and sodium glucose co-transporter-2 inhibitors]), as well as the particularities of patients (age-induced changes and sex differences) and treatment (pharmacokinetic and pharmacodynamic changes in drugs; cardiorenal syndrome). The article also highlights several drugs and food supplements that may worsen the prognosis of HF patients and discusses some potential drug–drug interactions, their consequences and recommendations for health care providers, as well as the risks of adverse drug reactions and treatment discontinuation, as an interdisciplinary approach to treatment is essential for HF patients.

The aim of this paper is to provide an accurate overview regarding the current recommended approach for antihypertensive treatment. The importance of DNA sequencing in understanding the complex implication of genetics in hypertension could represent an important step in understanding antihypertensive treatment as well as in developing new medical strategies. Despite a pool of data from studies regarding cardiovascular risk factors emphasizing a worse prognosis for female patients rather than male patients, there are also results indicating that women are more likely to be predisposed to the use of antihypertensive medication and less likely to develop uncontrolled hypertension. Moreover, lower systolic blood pressure values are associated with increased cardiovascular risk in women compared to men. The prevalence, awareness and, most importantly, treatment of hypertension is variable in male and female patients, since the mechanisms responsible for this pathology may be different and closely related to gender factors such as the renin–angiotensin system, sympathetic nervous activity, endothelin-1, sex hormones, aldosterone, and the immune system. Thus, gender-related antihypertensive treatment individualization may be a valuable tool in improving female patients’ prognosis.

Thrombospondin-1 (TSP-1) is a potent endogenous inhibitor of both physiological and pathological angiogenesis, widely studied as a target in drug development for treating cancer. Several studies performed in the cardiovascular field on TSP-1 are contradictory, the role of TSP-1 in the physiopathology of cardiovascular disorders (CVDs) being, for the moment, incompletely understood and may be due to the presence of several domains in its structure which can stimulate many cellular receptors. It has been reported to inhibit NO-mediated signaling and to act on the angiogenesis, tissue perfusion, endothelial cell proliferation, and homeostasis, so we aimed to quantify the effect Perindopril has on TSP-1 plasma levels in hypertensive patients with endothelial dysfunction in comparison with other antihypertensive drugs, such as beta blockers, calcium channel blockers, and diuretics, in a chronic treatment. As a conclusion, patients under treatment with Perindopril had increased plasma levels of TSP-1 compared with other hypertensive patients and with the control group. The results of this study confirms the pleiotropic properties of Perindopril: anti-proliferative, anti-inflammatory, with effects showed by quantifying a single biomarker: TSP-1.

Background: Fusion CRT pacing (FCRT) is noninferior to biventricular pacing, according to the current data. The aim of this study is to assess the response to FCRT and to identify predictors of super-responders (SRs) in a nonischemic population with normal AV conduction. Methods: LV-only CRT patients (pts) with a right atrium/left ventricle pacing system implanted in two CRT centers in Romania were included. Device interrogation, exercise tests, echocardiography, and individualized drug optimization were performed every 6 months during close follow-up. SRs pts were defined as those with left ventricular end-systolic volume (LVESV) improvement ≥30% and stable ejection fraction (LVEF) ≥45%. Results: A total of 25 out of 83 pts (31%) were SRs, with nonischemic LBBB low EF cardiomyopathy (50 male, 62 ± 9 y.o.) initially included. Mean follow-up was 5 years ± 27 months. Patients were divided in two groups: SRs and non-SRs (52 responders/6 hypo-responders). Two predictors were found in the SRs group: a higher baseline LVEF (SRs 29 ± 5% vs. non-SRs 26 ± 5%, p = 0.02) and a lower pulmonary arterial systolic pressure (SRs 38 ± 11 mm Hg vs. non-SRs 50 ± 15 mmHg, p = 0.003). Baseline severe mitral regurgitation was found in 11% of SRs vs. 64% in the non-SRs group. Conclusions: SRs in the selected NICM-FCRT group are significative high. Higher baseline LVEF and mild pulmonary arterial hypertension were independently associated with super-response.