The Role of Rehabilitation in Arterial Function Properties of Convalescent COVID-19 Patients.

Coronavirus disease (COVID-19) is a respiratory disease, although arterial function involvement has been documented. We assess the impact of a post-acute COVID-19 rehabilitation program on endothelium-dependent vasodilation and arterial wall properties. We enrolled 60 convalescent patients from COVID-19 and one-month post-acute disease, who were randomized at a 1:1 ratio in a 3-month cardiopulmonary rehabilitation program (study group) or not (control group). Endothelium-dependent vasodilation was evaluated by flow-mediated dilation (FMD), and arterial wall properties were evaluated by carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AIx) at 1 month and at 4 months post-acute disease. FMD was significantly improved in both the study (6.2 ± 1.8% vs. 8.6 ± 2.4%, p < 0.001) and control groups (5.9 ± 2.2% vs. 6.6 ± 1.8%, p = 0.009), but the improvement was significantly higher in the study group (rehabilitation) (p < 0.001). PWV was improved in the study group (8.2 ± 1.3 m/s vs. 6.6 ± 1.0 m/s, p < 0.001) but not in the control group (8.9 ± 1.8 m/s vs. 8.8 ± 1.9 m/s, p = 0.74). Similarly, AIx was improved in the study group (25.9 ± 9.8% vs. 21.1 ± 9.3%, p < 0.001) but not in the control group (27.6 ± 9.2% vs. 26.2 ± 9.8 m/s, p = 0.15). Convalescent COVID-19 subjects of the study group (rehabilitation) with increased serum levels of circulating IL-6 had a greater reduction in FMD. Conclusively, a 3-month cardiopulmonary post-acute COVID-19 rehabilitation program improves recovery of endothelium-dependent vasodilation and arteriosclerosis.

Vaccination Against SARS-CoV-2 Protects from COVID-19-induced Endothelial Dysfunction.

BACKGROUND: Coronavirus Disease-19 (COVID-19) is implicated in endotheliitis, which adversely affects cardiovascular events. The impact of vaccination with COVID-19 on the clinical outcome of patients is documented. OBJECTIVE: To evaluate the impact of vaccination with COVID-19 on the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) infection-related endothelial impairment. METHODS: We enrolled 45 patients hospitalized for COVID-19 (either vaccinated or not against SARS-CoV-2). Clinical and laboratory data were collected, and brachial artery flow-mediated dilation (FMD) was evaluated. Subjects without COVID-19 were used as the control group. RESULTS: There was no difference in age (64.7 ± 7.5 years vs. 61.2 ± 11.1 years vs. 62.4 ± 9.5, p = 0.28), male sex (49% vs. 60% vs. 52%, p = 0.71), control subjects, vaccinated, and unvaccinated subjects with COVID-19, respectively. Of the patients with COVID-19, 44% were vaccinated against SARS-CoV-2. Unvaccinated COVID-19 patients had significantly impaired FMD compared to vaccinated COVID-19 patients and Control subjects (2.05 ± 2.41 % vs. 7.24 ± 2.52% vs. 7.36 ± 2.94 %, p <0.001). Importantly, post hoc tests revealed that unvaccinated COVID-19 patients had significantly impaired FMD from both Vaccinated COVID-19 subjects (p <0.001) and from Control subjects (p <0.001). There was no difference in FMD between the control group and the vaccinated COVID-19 group (p = 0.99). CONCLUSION: Hospitalized patients with COVID-19 present endothelial dysfunction in the acute phase of the disease. Endothelial function in unvaccinated patients with COVID-19 is impaired compared to control subjects as well compared to vaccinated patients with COVID-19. Vaccinated hospitalized subjects with COVID-19 do not show endothelial dysfunction, strengthening the protective role of vaccination against SARS-CoV-2.

Atrial Fibrillation: Biomarkers Determining Prognosis.

Atrial fibrillation (AF) is a common cardiac arrhythmia known to incite increased thromboembolic and mortality risks, especially among patients not under anticoagulant therapy when indicated. Several routine scores exist to help stratify AF patients, such as the CHAD2DS2-VASc score and upon which physicians are based to decide whether to administer anticoagulant therapy. Being that anticoagulant regimen is a double- edged situation with both benefits and risks, decision-making process demands a definite and reliable, evidence-based set of data to rely on. Blood-based biological elements known as biomarkers are measurable indices that can provide crucial insights concerning not only underlying disease mechanisms but also prognostic and risk stratifying information. As AF is constituted by an overwhelming range of pathophysiological aspects such as inflammation, fibrosis, hypercoagulable states and myocardial damage, identifying and assessing relevant biomarkers will evidently support the clinician's prognostication efforts. The current reviewpresents studied biomarkers with proven prognostic potential in AF as well as possible enhancement of risk-scores when incorporated to them.

Biomarkers in Atrial Fibrillation and Heart Failure.

Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice and an important contributor to cardiovascular morbidity and mortality. Although the exact mechanisms behind AF are not completely elucidated, the underlying pathophysiological changes have been well described. Predisposal factors for AF include the older age, the increased left atrial size, the decreased left atrial function, the presence of heart failure and left ventricular systolic dysfunction and the presence of coronary heart disease or pulmonary or mitral valve disease. In addition to these factors, emerging evidence demonstrate that myocardial strain, fibrosis and inflammation, are associated with AF as well as the pathogenesis of the arrhythmia. The natruretic peptide system including Atrial Natriuretic Peptide (ANP), Brain Natriuretic Peptide (BNP) and C-type Natriuretic Peptide (CNP) is indicative of the level of myocardial strain which may predispose to AF. As a result, the aforementioned peptides are increased in AF patients. The levels of myocardial fibrosis biomarkers, such as ST2 and Galectin-3, are elevated suggesting atrial structural abnormalities, while the increased levels of CRP and Interleukin-6 supplement the inflammatory profile of AF patients. Emerging data for the aforementioned biomarkers are discussed in the present review.

Redox State in Atrial Fibrillation Pathogenesis and Relevant Therapeutic Approaches.

BACKGROUND: Myocardial redox state is a critical determinant of atrial biology, regulating cardiomyocyte apoptosis, ion channel function, and cardiac hypertrophy/fibrosis and function. Nevertheless, it remains unclear whether the targeting of atrial redox state is a rational therapeutic strategy for atrial fibrillation prevention. OBJECTIVE: To review the role of atrial redox state and anti-oxidant therapies in atrial fibrillation. METHOD: Published literature in Medline was searched for experimental and clinical evidence linking myocardial redox state with atrial fibrillation pathogenesis as well as studies looking into the role of redoxtargeting therapies in the prevention of atrial fibrillation. RESULTS: Data from animal models have shown that altered myocardial nitroso-redox balance and NADPH oxidases activity are causally involved in the pathogenesis of atrial fibrillation. Similarly experimental animal data supports that increased reactive oxygen / nitrogen species formation in the atrial tissue is associated with altered electrophysiological properties of atrial myocytes and electrical remodeling, favoring atrial fibrillation development. In humans, randomized clinical studies using redox-related therapeutic approaches (e.g. statins or antioxidant agents) have not documented any benefits in the prevention of atrial fibrillation development (mainly post-operative atrial fibrillation risk). CONCLUSION: Despite strong experimental and translational data supporting the role of atrial redox state in atrial fibrillation pathogenesis, such mechanistic evidence has not been translated to clinical benefits in atrial fibrillation risk in randomized clinical studies using redox-related therapies.

Interrelationship between diabetes mellitus and heart failure: the role of peroxisome proliferator-activated receptors in left ventricle performance.

Heart failure (HF) is a common cardiac syndrome, whose pathophysiology involves complex mechanisms, some of which remain unknown. Diabetes mellitus (DM) constitutes not only a glucose metabolic disorder accompanied by insulin resistance but also a risk factor for cardiovascular disease and HF. During the last years though emerging data set up, a bidirectional interrelationship between these two entities. In the case of DM impaired calcium homeostasis, free fatty acid metabolism, redox state, and advance glycation end products may accelerate cardiac dysfunction. On the other hand, when HF exists, hypoperfusion of the liver and pancreas, b-blocker and diuretic treatment, and autonomic nervous system dysfunction may cause impairment of glucose metabolism. These molecular pathways may be used as therapeutic targets for novel antidiabetic agents. Peroxisome proliferator-activated receptors (PPARs) not only improve insulin resistance and glucose and lipid metabolism but also manifest a diversity of actions directly or indirectly associated with systolic or diastolic performance of left ventricle and symptoms of HF. Interestingly, they may beneficially affect remodeling of the left ventricle, fibrosis, and diastolic performance but they may cause impaired water handing, sodium retention, and decompensation of HF which should be taken into consideration in the management of patients with DM. In this review article, we present the pathophysiological data linking HF with DM and we focus on the molecular mechanisms of PPARs agonists in left ventricle systolic and diastolic performance providing useful insights in the molecular mechanism of this class of metabolically active regiments.

Antiplatelet Therapy in Acute Coronary Syndromes. Evidence Based Medicine.

BACKGROUND: Acute coronary syndromes (ACS) represent the final step in the chronic process of atherothrombotic coronary disease which begins early in life as thickening of intima layer and progresses to fibroatheroma and fibrocalcific lesions with vulnerable characteristics. METHODS: As abrupt occlusion in the settings of ACS happens due to platelet aggregation and mobilization antiplatelet treatment has gained significant interest especially in the settings of primary percutaneous intervention and the aim of this review article is to understand the current evidence justifying the use and combination of different antiplatelet agents. RESULTS: Beyond aspirin, several antiplatelet agents (ADP receptor inhibitors, Glycoprotein IIb/IIIa inhibitors and varopaxar) are used in combination to effectively inhibit platelet activity. However the best choice, initiation, combination and duration of antithrombotic treatment, in order to maximize the effectiveness of therapy and reduce the hazard of bleeding, depends on the clinical setting and patient specific characteristics and is an issue of intense scientific interest. CONCLUSION: Early and potent platelet inhibition with safety reassurance can be achieved by a combination of antiplatelet agents and is essential for the management of ACS. Therefore in this review article we focus on the current evidence regarding rational, safety and effectiveness of current antiplatelet approaches in acute coronary syndromes.

The Interaction Between Gender and Diabetes Mellitus in the Coronary Heart Disease Risk.

BACKGROUND: Cardiovascular disease (CVD) despite the advances in medical management keeps on as the primary cause of morbidity and mortality for both genders in Western societies. Sex differences though modify the clinical picture as well as the effectiveness of treatment. METHODS AND RESULTS: In this literature review article we searched publications in Englishlanguage on MEDLINE and the Cochrane Database from the beginning of the databases to January 2016. Among the specific key words and phrases we used were Diabetes Mellitus; Gender; Coronary artery disease; Stroke and Cardiovascular disease. Various studies have found that diabetic women have increased risk of coronary heart disease than their male counterparts; however, further research into this field has questioned this finding and there is much controversy among many researchers. Women have a different risk factor profile, are usually treated less effectively than men, and have a variance in the levels of sex hormones throughout their life which complicate the study and understanding of the mechanisms involved in insulin resistance, diabetes mellitus and cardiovascular risk profile. CONCLUSION: The connection between diabetes mellitus and cardiovascular disease is variable according to gender and further studies are needed to elucidate the lenient differentiations in gender specific hormones, risk factor profile, and therapeutic implications between genders.