ROCK (RhoA/Rho Kinase) Activation in Atrial Fibrillation: Molecular Pathways and Clinical Implications.

Among the complex mechanisms of AF pathogenesis, intracellular calcium overload and oxidative stress play a major role, both triggered by inflammatory processes. The additional basic event taking place in AF is atrial fibrotic remodeling, again triggered by oxidative stress, which is determined by connexins rearrangement and differentiation of fibroblasts into active collagensecreting myofibroblasts. RhoA/ROCK system is the final pathway of a wide spectrum of molecular effectors such as Angiotensin II, platelet-derived growth factor, connective tissue growth factor and transforming growth factor ß, that overall determine calcium dysregulation and pro-fibrotic remodeling. Both in experimental and clinical studies, RhoA/ROCK activation has been linked to superoxide ion production, fibrotic remodeling and connexins rearrangement, with important consequences for AF pathogenesis. ROCK pathway inhibition may therefore be a therapeutic or preventive target for special AF subgroups of patients.

Therapeutic vs. prophylactic anticoagulation in COVID-19 patients: a systematic review and meta-analysis of real-world studies.

INTRODUCTION: Coagulopathy, in the form of either venous or arterial thromboembolism, is one of the most severe sequelae of coronavirus disease (COVID-19) and has been associated with poorer outcomes. However, the role of therapeutic anticoagulation (tAC) or prophylactic anticoagulation (pAC) in COVID-19 patients has not been definitely established. Therefore, the aim of this systematic review and meta-analysis was to gather all the available real-world data in the field and to provide a reliable effect size of the effect on mortality of tAC compared to pAC in COVID-19 patients. EVIDENCE ACQUISITION: Real-world studies (RWS) were identified by searching electronic databases from inception to 31st October, 2021. Randomized controlled trials were excluded. Mortality and bleedings were considered as primary and secondary outcomes, respectively. EVIDENCE SYNTHESIS: 10 RWS and 5541 patients were included in the analysis. Overall, tAC was associated with lower mortality (HR=0.62, 95% CI: 0.54-0.71). There was asymmetry at the funnel plot suggesting publication bias, that was not confirmed at the Egger test (P=0.07). For the secondary endpoint, there was a non-statistically significant tendency for more bleedings in patients treated with tAC compared to pAC (RR=1.75, 95% CI: 0.81-3.81). CONCLUSIONS: Our meta-analysis, based on RWS and adjusted estimates of risk, suggests a survival benefit of tAC over pAC in COVID-19 patients in the real world.

Arterial stiffness and atrial fibrillation: shared mechanisms, clinical implications and therapeutic options.

Arterial stiffness (AS) and atrial fibrillation (AF) share commonalities in molecular and pathophysiological mechanisms and numerous studies have analyzed their reciprocal influence. The gold standard for AS diagnosis is represented by aortic pulse wave velocity, whose measurement can be affected by arrhythmias characterized by irregularities in heart rhythm, such as AF. Growing evidence show that patients with AS are at high risk of AF development. Moreover, the subset of AF patients with AS seems to be more symptomatic and rhythm control strategies are less effective in this population. Reducing AS through de-stiffening interventions may be beneficial for patients with AF and can be a new appealing target for the holistic approach of AF management. In this review, we discuss the association between AS and AF, with particular interest in shared mechanisms, clinical implications and therapeutic options.

Prevalence of asymptomatic atrial fibrillation among multimorbid elderly patients: diagnostic implications.

Advancing age of the global population is one of the main reasons for the uprising trend in atrial fibrillation (AF) prevalence worldwide leading to a proper "AF epidemic". Strictly related to the increasing prevalence of AF in the elderly is the relevant burden of cardiac end extra-cardiac comorbidities that these patients show. Patients with AF are frequently asymptomatic (i.e., asymptomatic or silent AF) and thus the arrhythmia is generally underdiagnosed. Detainment of proper treatment in elderly and comorbid patients may potentially result in significant morbidity and mortality. Therefore, in recent years, several screening strategies (systematic vs opportunistic screening) for asymptomatic AF have been developed and early diagnosis of AF is an important treatment goal that can improve prognosis. This review will focus on the prevalence of asymptomatic AF in the elderly, frequently associated comorbidities, screening strategies, and implications for a correct AF diagnosis.

Management of myocarditis in clinical practice.

Myocarditis is an inflammatory heart muscle disease characterized by heterogeneous clinical presentation and outcome. Clinical heterogeneity of myocarditis, ranging from acute onset chest pain with electrocardiographic changes resembling an acute coronary syndrome, to arrhythmic storm and chronic decompensated heart failure, makes diagnosis challenging. However, a correct diagnosis is fundamental to proper patients' management and should always be seeked. Although a definite diagnosis is only provided by endomyocardial biopsy, the European Society of Cardiology task force on myocardial and pericardial diseases provided specific criteria for the diagnosis of clinically suspected myocarditis, which has been facilitated by the advent of noninvasive imaging tests (i.e. cardiovascular magnetic resonance based myocardial tissue characterization). Due to the heterogeneous presentation and disease course of myocarditis, a tailored treatment would be the best strategy, but a standardized management is still not available. However, over the years, new, promising therapies, such as antiviral and immune-suppressive treatment, have come side by side to the standard pharmacological heart treatment, i.e. antiheart failure medications. In this paper we will review the basic principles of myocarditis management in clinical practice, including diagnostic work-up, conventional and disease-specific therapy and patients' follow-up.

A rare cause of effusive-constrictive pericarditis.

Effusive-constrictive pericarditis (ECP) is an uncommon diagnosis, frequently missed due to its heterogeneous presentation, but a potentially reversible cause of heart failure. A 62-year-old Caucasian male presented with remittent right heart failure and mild-moderate pericardial effusion. Following an initial diagnosis of idiopathic pericarditis, indomethacin was started, but the patient shortly relapsed, presenting with severe pericardial effusion and signs of cardiac tamponade, requiring pericardiocentesis. ECP was diagnosed on cardiac catheterization. Cardiac computed tomography showed non-calcified, mildly thickened and inflamed parietal pericardium. Pericardiectomy was performed with symptoms remission. On histological examination of pericardium, chronic non-necrotizing granulomatous inflammation was noted. Polymerase chain reaction assay was positive for non-tuberculous mycobacteria. This case represents a rare finding of ECP with unusual presentation due to atypical mycobacteriosis in a non-immunocompromised patient and in a non-endemic area. Pericardiectomy can be an effective option in cases unresponsive to anti-inflammatory treatment, even in the absence of significant pericardial thickening or calcification.

Characteristics and hospital course of patients admitted for acute cardiovascular diseases during the coronavirus disease-19 outbreak.

INTRODUCTION: During the coronavirus disease-19 (COVID-19) outbreak in spring 2020, people may have been reluctant to seek medical care fearing infection. We aimed to assess the number, characteristics and in-hospital course of patients admitted for acute cardiovascular diseases during the COVID-19 outbreak. METHODS: We enrolled all consecutive patients admitted urgently for acute myocardial infarction, heart failure or arrhythmias from 1 March to 31 May 2020 (outbreak period) and 2019 (control period). We evaluated the time from symptoms onset to presentation, clinical conditions at admission, length of hospitalization, in-hospital medical procedures and outcome. The combined primary end point included in-hospital death for cardiovascular causes, urgent heart transplant or discharge with a ventricular assist device. RESULTS: A similar number of admissions were observed in 2020 (N = 210) compared with 2019 (N = 207). Baseline characteristics of patients were also similar. In 2020, a significantly higher number of patients presented more than 6 h after symptoms onset (57 versus 38%, P < 0.001) and with signs of heart failure (33 versus 20%, P = 0.018), required urgent surgery (13 versus 5%, P = 0.004) and ventilatory support (26 versus 13%, P < 0.001). Hospitalization duration was longer in 2020 (median 10 versus 8 days, P = 0.03). The primary end point was met by 19 (9.0%) patients in 2020 versus 10 (4.8%) in 2019 (P = 0.09). CONCLUSION: Despite the similar number and types of unplanned admissions for acute cardiac conditions during the 2020 COVID-19 outbreak compared with the same period in 2019, we observed a higher number of patients presenting late after symptoms onset as well as longer and more complicated clinical courses.