Design and rationale for a comparison study of Olmesartan and Valsartan On myocardial metabolism In patients with Dilated cardiomyopathy (OVOID) trial: study protocol for a randomized controlled trial

Background Dilated cardiomyopathy (DCMP) is characterized by ventricular chamber enlargement and systolic dysfunction which may cause heart failure. Patients with DCMP have overactivation of the renin-angiotensin-aldosterone systems, which can also adversely affect myocardial metabolism in heart failure. The impairment of myocardial metabolism can contribute to the progression of left ventricular remodeling and contractile dysfunction in heart failure. Although angiotensin II receptor blockers (ARBs) have been used to treat patients with DCMP, there has been no direct comparison of the efficacy of these agents. The objective of this study is to compare the effects of olmesartan and valsartan on myocardial metabolism in patients with DCMP. Methods/design The OVOID study (a comparison study of Olmesartan and Valsartan On myocardial metabolism In patients with Dilated cardiomyopathy) is designed as a non-blinded, open-label, parallel-group, prospective, randomized, controlled, multicenter clinical trial. A total of 40 DCMP patients aged between 20 and 85 years will be randomly allocated into the olmesartan or the valsartan group. 18F-fluoro-2-deoxyglucose (FDG) cardiac positron emission tomography (PET) will be performed at baseline and six months after receiving the study agent. The primary endpoint is myocardial glucose consumption per square meter, measured using 18F-FDG PET 6 months after receiving the study agent. Discussion The purpose of this trial is to compare the efficacy between olmesartan and valsartan in improving myocardial metabolism in DCMP patients. This will be the first randomized comparative study investigating the differential effects of ARBs on heart failure. Trial registration ClinicalTrials.govNCT04174456. Registered on 18 November 2019

Pathophysiology, Diagnosis, and Management of Coronary No-Reflow Phenomenon

Coronary no-reflow phenomenon is a lethal mechanism of ongoing myocardial injury following successful revascularization of an infarct-related coronary artery. Incidence of this phenomenon is high following percutaneous intervention and is associated with adverse in-hospital and long-term outcomes. Several mechanisms such as ischemia-reperfusion injury and distal microthromboembolism in genetically susceptible patients and those with preexisting endothelial dysfunction have been implicated. However, the exact mechanism in humans is still poorly understood. Several investigative and treatment strategies within and outside the cardiac catheterization laboratory have been proposed, but they have not uniformly shown success in reducing mortality or in preventing adverse left ventricular remodeling resulting from this condition. The aim of this article is to provide a brief and concise review of the current understanding of the pathophysiology, clinical predictors, and investigations and management of coronary no-reflow phenomenon.

Effects of Levosimendan Preconditioning on Left Ventricular Remodeling after Myocardial Reperfusion in Acute Myocardial Infarction Patients Receiving Percutaneous Coronary Intervention

Objective: Levosimendan is a novel drug often used to treat heart failure. We aimed to explore the effects of levosimendan preconditioning on left ventricular remodeling (LVR) after myocardial reperfusion in acute myocardial infarction (AMI) patients receiving the percutaneous coronary intervention (PCI). Methods: A total of 258 AMI patients treated from January 2018 to September 2020 were randomly divided into control and observation groups. Based on conventional drug therapy, levosimendan was given 30 min before PCI for the observation group, and dobutamine was intravenously injected for the control group. Baseline data, thrombolysis in myocardial infarction (TIMI) blood flow grade, myocardial injury markers, and LVR indices were compared, and the influencing factors for LVR were analyzed. Results: After treatment, various degrees of blood perfusion were found, and the TIMI grade was better than that before treatment in both groups (P < .05). The levels of aspartate aminotransferase, creatine kinase-MB, cardiac troponin T, and brain natriuretic peptide (BNP) declined in both groups, more significantly in the observation group (P < .05). Left ventricular end-systolic diameter, left ventricular end-diastolic diameter and left ventricular end-diastolic volume declined, whereas left ventricular ejection fraction rose in both groups, more significantly in the observation group (P < .05). Age and BNP were risk factors for LVR, whereas levosimendan preconditioning was a protective factor (P < .05). Conclusion: Levosimendan preconditioning can protect cardiac function and promote the recovery of the left ventricular structure. Age and BNP are risk factors for LVR after myocardial reperfusion in AMI patients undergoing PCI, and levosimendan preconditioning is a protective factor.

Nrf2 attenuates the innate immune response after experimental myocardial infarction

Objectives: We aimed to investigate the contribution of the transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2) to the inflammatory response after experimental myocardial infarction (MI. Background: There is compelling evidence implicating dysregulated inflammation in the mechanism of ventricular remodeling and heart failure (HF) after MI. The transcription factor Nrf2 (encoded by Nfe2l2) is a promising target in this context. It impedes transcriptional upregulation of pro-inflammatory cytokines and is anti-inflammatory in various murine models. Methods: We subjected Nrf2-/- mice and wild type (WT) controls to permanent left coronary artery (LCA) ligation. The inflammatory response was investigated with fluorescence-activated cell sorting (FACS) analysis of peripheral blood and heart cell suspensions, together with qRT-PCR of infarcted tissue for chemokines and their receptors. To investigate whether Nrf2-mediated transcription is a dedicated function of leukocytes, we interrogated publicly available RNA-sequencing (RNA-seq) data from mouse hearts after permanent LCA ligation for Nrf2-regulated gene (NRG) expression. Results: FACS analysis demonstrated a profoundly inflamed phenotype in the hearts of global Nrf2-/- mice as compared to WT mice after MI. Moreover, infarcted tissue from Nrf2-/- mice displayed higher expression of inflammatory cytokines, chemokines, and their receptors, including IL6, Ccl2, and Cxcr4. RNA-seq analysis showed upregulated NRG expression in WT mice after MI compared to untreated mice, which was significantly higher in bioinformatically isolated CCR2+ cells. Conclusions: Taken together, the results suggest that Nrf2 signalling in leukocytes, and possibly CCR2+ monocyte-derived cardiac resident macrophages, may be potential targets to prevent post-MI ventricular remodeling.

The Effects of Fish Oil on Cardiovascular Diseases: Systematical Evaluation and Recent Advance

Fish oil is rich in unsaturated fatty acids, i.e., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both of which are widely distributed in the body such as heart and brain. In vivo and in vitro experiments showed that unsaturated fatty acids may have effects of anti-inflammation, anti-oxidation, protecting vascular endothelial cells, thrombosis inhibition, modifying autonomic nerve function, improving left ventricular remodeling, and regulating blood lipid. Given the relevance to public health, there has been increasing interest in the research of potential cardioprotective effects of fish oil. Accumulated evidence showed that fish oil supplementation may reduce the risk of cardiovascular events, and, in specific, it may have potential benefits in improving the prognosis of patients with hypertension, coronary heart disease, cardiac arrhythmias, or heart failure; however, some studies yielded inconsistent results. In this article, we performed an updated systematical review in order to provide a contemporary understanding with regard to the effects of fish oil on cardiovascular diseases.

Guanxin V Acts as an Antioxidant in Ventricular Remodeling

Background: Our previous studies have shown that Guanxin V (GXV) is safe and effective in the treatment of ventricular remodeling (VR), but its mechanism related to oxidative stress has not been studied deeply.Methods: We applied integrating virtual screening and network pharmacology strategy to obtain the GXV-, VR-, and oxidative stress-related targets at first, and then highlighted the shared targets. We built the networks and conducted enrichment analysis. Finally, the main results were validated by molecular docking and solid experiments.Results: We obtained 251, 11,425, and 9,727 GXV-, VR-, and oxidative stress-related targets, respectively. GXV-component-target-VR and protein–protein interaction networks showed the potential mechanism of GXV in the treatment of VR. The following enrichment analysis results gathered many biological processes and “two GXV pathways” of oxidative stress-related to VR. All our main results were validated by molecular docking and solid experiments.Conclusion: GXV could be prescribed for VR through the mechanism, including complex interactions between related components and targets, as predicted by virtual screening and network pharmacology and validated by molecular docking and solid experiments. Our study promotes the explanation of the biological mechanism of GXV for VR.

Attenuation of Adverse Postinfarction Left Ventricular Remodeling with Empagliflozin Enhances Mitochondria-Linked Cellular Energetics and Mitochondrial Biogenesis

Sodium–glucose cotransporter 2 (SGLT2) inhibitors such as empagliflozin are known to reduce the risk of hospitalizations related to heart failure irrespective of diabetic state. Meanwhile, adverse cardiac remodeling remains the leading cause of heart failure and death in the USA. Thus, understanding the mechanisms that are responsible for the beneficial effects of SGLT2 inhibitors is of the utmost relevance and importance. Our previous work illustrated a connection between adverse cardiac remodeling and the regulation of mitochondrial turnover and cellular energetics using a short-acting glucagon-like peptide-1 receptor agonist (GLP1Ra). Here, we sought to determine if the mechanism of the SGLT2 inhibitor empagliflozin (EMPA) in ameliorating adverse remodeling was similar and/or to identify what differences exist, if any. To this end, we administered permanent coronary artery ligation to induce adverse remodeling in wild-type and Parkin knockout mice and examined the progression of adverse cardiac remodeling with or without EMPA treatment over time. Like GLP1Ra, we found that EMPA affords a robust attenuation of PCAL-induced adverse remodeling. Interestingly, unlike the GLP1Ra, EMPA does not require Parkin to improve/maintain mitochondria-related cellular energetics and afford its benefits against developing adverse remodeling. These findings suggests that further investigation of EMPA is warranted as a potential path for developing therapy against adverse cardiac remodeling for patients that may have Parkin and/or mitophagy-related deficiencies.