Myocardium Metabolism in Physiological and Pathophysiological States: Implications of Epicardial Adipose Tissue and Potential Therapeutic Targets

The main energy substrate of adult cardiomyocytes for their contractility are the fatty acids. Its metabolism generates high ATP levels at the expense of high oxygen consumption in the mitochondria. Under low oxygen supply, they can get energy from other substrates, mainly glucose, lactate, ketone bodies, etc., but the mitochondrial dysfunction, in pathological conditions, reduces the oxidative metabolism. In consequence, fatty acids are stored into epicardial fat and its accumulation provokes inflammation, insulin resistance, and oxidative stress, which enhance the myocardium dysfunction. Some therapies focused on improvement the fatty acids entry into mitochondria have failed to demonstrate benefits on cardiovascular disorders. Oppositely, those therapies with effects on epicardial fat volume and inflammation might improve the oxidative metabolism of myocardium and might reduce the cardiovascular disease progression. This review aims at explain (a) the energy substrate adaptation of myocardium in physiological conditions, (b) the reduction of oxidative metabolism in pathological conditions and consequences on epicardial fat accumulation and insulin resistance, and (c) the reduction of cardiovascular outcomes after regulation by some therapies

Social media in cardiology: Reasons to learn how to use it

Social media has changed the way we learn, educate, and interact with our peers. The dynamic nature of social media and their immediate availability through our portable devices (smartphones, tablets, smartwatches, etc.) is quickly transforming the way we participate in society. The scope of these digital tools is broad as they deal with many different aspects: Teaching and learning, case discussion, congresses coverage, peer to peer interaction, research are examples worth mentioning. The scientific societies considered more innovative, are promoting these tools between their members. These new concepts need to be known by the cardiologists to stay updated, as countless information is moving rapidly through these channels. We summarize the main reasons why learning how to use these tools to be part of the conversation is essential for the cardiologist in training or fully stablished

CD5L, Macrophage Apoptosis Inhibitor, Was Identified in Epicardial Fat-Secretome and Regulated by Isoproterenol From Patients With Heart Failure

Objectives: Neurohormonal dysfunction, which can regulate epicardial fat activity, is one of the main promoters of atrial fibrillation (AF) in patients with heart failure (HF). Our aim was to study the epicardial fat mediators for AF in patients with HF and its catecholaminergic regulation. Methods: We have included 29 patients with HF who underwent cardiac surgery and were followed up for 5 years. Released proteins by epicardial adipose tissue (EAT) after isoproterenol treatment were identified by nano-high-performance liquid chromatography (HPLC) and triple time-of-flight (TOF) analysis. Common and differential identified proteins in groups of patients with AF before and after surgery were determined by the FunRich tool. Plasma and epicardial fat biopsy proteins were quantified by western blot. Results: Our results identified 17 common released proteins by EAT, after isoproterenol treatment, from HF patients who suffered AF or developed new-onset AF during follow-up. Mostly, they were involved on inflammatory response and extracellular matrix. One of them was CD5L, a macrophage apoptosis inhibitor. Its secretion by isoproterenol treatment was validated on western blot. The CD5L levels on epicardial fat were also higher in the group of male patients who present or develop AF (0.44 +/- 0.05 vs. 0.18 +/- 0.15; p < 0.016). However, there were no differences regarding plasma levels. Conclusion: Our results suggest the role of epicardial fat CD5L as a mediator of AF and its possible paracrine effect by catecholaminergic activity

Points to consider in cardiovascular disease risk management among patients with rheumatoid arthritis living in South Africa, an unequal middle income country

Background: It is plausible that optimal cardiovascular disease (CVD) risk management differs in patients with rheumatoid arthritis (RA) from low or middle income compared to high income populations. This study aimed at producing evidence-based points to consider for CVD prevention in South African RA patients. Methods: Five rheumatologists, one cardiologist and one epidemiologist with experience in CVD risk management in RA patients, as well as two patient representatives, two health professionals and one radiologist, one rheumatology fellow and 11 rheumatologists that treat RA patients regularly contributed. Systematic literature searches were performed and the level of evidence was determined according to standard guidelines. Results: Eighteen points to consider were formulated. These were grouped into 6 categories that comprised overall CVD risk assessment and management (n = 4), and specific interventions aimed at reducing CVD risk including RA control with disease modifying anti-rheumatic drugs, glucocorticoids and non-steroidal anti-inflammatory drugs (n = 3), lipid lowering agents (n = 8), antihypertensive drugs (n = 1), low dose aspirin (n = 1) and lifestyle modification (n = 1). Each point to consider differs partially or completely from recommendations previously reported for CVD risk management in RA patients from high income populations. Currently recommended CVD risk calculators do not reliably identify South African black RA patients with very high-risk atherosclerosis as represented by carotid artery plaque presence on ultrasound. Conclusions: Our findings indicate that optimal cardiovascular risk management likely differs substantially in RA patients from low or middle income compared to high income populations. There is an urgent need for future multicentre longitudinal studies on CVD risk in black African patients with RA

Cost-Effectiveness Analysis of Apixaban Versus Edoxaban in Patients with Atrial Fibrillation for Stroke Prevention

OBJECTIVE: Our objective was to assess the cost effectiveness of apixaban versus edoxaban in the prevention of stroke and systemic embolism (SE) in patients with atrial fibrillation (AF) in Spain. METHODS: We customized a Markov model with ten health states to estimate the lifetime economic and clinical outcomes in 6-week cycles. The efficacy (clinical event rates per 100 patient-years) and safety data were derived from a pairwise indirect treatment comparison. The analysis was conducted from both the national health service (NHS) and societal perspectives, and included pharmaceutical costs (retail price plus value-added tax (VAT) and applicable national deductions) according to daily dosages (apixaban 10 mg (5 mg twice daily (bid)) and edoxaban 60 or 30 mg) and complications and disease-management costs, obtained from national databases. Utilities for quality-adjusted life-year (QALY) calculations reflected EuroQoL 5-Dimension scores in patients with AF. An annual discount rate of 3% was applied for costs (euro, year 2019 values) and outcomes. RESULTS: In a 1000-patient cohort, apixaban 5 mg bid versus edoxaban 60 mg could avoid five strokes, six major bleedings and 29 clinically relevant non-major bleedings (CRNMBs). Compared with edoxaban 30 mg, apixaban could avoid 21 strokes and two SEs. An increase in bleedings was observed with apixaban (seven haemorrhagic strokes, 48 major bleedings and 17 CRNMBs). Apixaban yielded 0.04 additional QALYs compared with edoxaban 60 mg or 30 mg. Incremental costs/QALY were euro9639.33 and euro354.22 for apixaban versus edoxaban 60 mg and edoxaban 30 mg, respectively, from the NHS perspective and euro7756.62 for apixaban versus edoxaban 60 mg from the societal perspective. Apixaban was dominant versus edoxaban 30 mg from the societal perspective. Sensitivity analyses confirmed the robustness of the model. CONCLUSIONS: This study suggests that apixaban 5 mg bid is a cost-effective alternative to edoxaban for stroke prevention in the AF population in Spain

Bioelectronics-on-a-chip for cardio myoblast proliferation enhancement using electric field stimulation

Background: Cardio myoblast generation from conventional approaches is laborious and time-consuming. We present a bioelectronics on-a-chip for stimulating cells cardio myoblast proliferation during culture. Method: The bioelectronics chip fabrication methodology involves two different process. In the first step, an aluminum layer of 200 nm is deposited over a soda-lime glass substrate using physical vapor deposition and selectively removed using a Q-switched Nd:YVO4 laser to create the electric tracks. To perform the experiments, we developed a biochip composed of a cell culture chamber fabricated with polydimethylsiloxane (PDMS) with a glass coverslip or a cell culture dish placed over the electric circuit tracks. By using such a glass cover slip or cell culture dish we avoid any toxic reactions caused by electrodes in the culture or may be degraded by electrochemical reactions with the cell medium, which is crucial to determine the effective cell-device coupling. Results: The chip was used to study the effect of electric field stimulation of Rat ventricular cardiomyoblasts cells (H9c2). Results shows a remarkable increase in the number of H9c2 cells for the stimulated samples, where after 72 h the cell density double the cell density of control samples. Conclusions: Cell proliferation of Rat ventricular cardiomyoblasts cells (H9c2) using the bioelectronics-on-a-chip was enhanced upon the electrical stimulation. The dependence on the geometrical characteristics of the electric circuit on the peak value and homogeneity of the electric field generated are analyzed and proper parameters to ensure a homogeneous electric field at the cell culture chamber are obtained. It can also be observed a high dependence of the electric field on the geometry of the electrostimulator circuit tracks and envisage the potential applications on electrophysiology studies, monitoring and modulate cellular behavior through the application of electric fields

Cyclophilins in Ischemic Heart Disease: Differences Between Acute and Chronic Coronary Artery Disease Patients

Background: Cyclophilins (Cyps) are a family of peptidyl-prolyl cis/trans isomerases consistently involved in cardiovascular diseases through the inflammation pathway. This study aims to investigate the serum levels of Cyps (CypA, CypB, CypC and CypD) in patients with coronary artery disease (CAD) and the correlation with clinical characteristics and inflammation parameters. Methods: We developed an observational prospective study with a total of 125 subjects: 40 patients with acute CAD, 40 patients with chronic CAD and 45 control volunteers, in whom serum levels of Cyps (CypA, CypB, CypC and CypD), interleukins and metalloproteinases were measured. Results: CypA levels increased significantly in CAD patients compared with control subjects, but no differences were noted between acute CAD (7.80 +/- 1.30 ng/mL) and chronic CAD (5.52 +/- 0.76 ng/mL) patients (P = 0.13). No differences in CypB and CypD levels were showed between CAD patients and controls and between acute CAD and chronic CAD patients. In relation with CypC, the levels in CAD patients were significantly higher compared to controls (32.42 +/- 3.71 pg/mL vs. 9.38 +/- 1.51 pg/mL, P 17.5 pg/mL cut-off point, and it was significantly associated with older age, hypertension, dyslipidemia and more extensive CAD in acute and chronic CAD groups. Conclusions: CypA and CypC levels are increased in CAD patients. High CypC serum levels could be a novel biomarker in CAD patients correlating with a more severe disease

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

AIMS: The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin-kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (>/=1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. METHODS AND RESULTS: Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77-0.99; P = 0.032) and Type 2 (0.77, 0.61-0.97; P = 0.025), but not Type 4 MI. CONCLUSION: After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types