The cardiovascular benefits of physical activity are indisputable. Nevertheless, growing evidence suggests that both atrial fibrillation and right ventricular arrhythmia can be caused by intense ...exercise in some individuals. Exercise-induced atrial fibrillation is most commonly diagnosed in middle-aged, otherwise healthy men who have been engaged in endurance training for >10 years, and is mediated by atrial dilatation, parasympathetic enhancement, and possibly atrial fibrosis. Cardiac ablation is evolving as a first-line tool for athletes with exercise-induced arrhythmia who are eager to remain active. The relationship between physical activity and right ventricular arrhythmia is complex and involves genetic and physical factors that, in a few athletes, eventually lead to right ventricular dilatation, followed by subsequent myocardial fibrosis and lethal ventricular arrhythmias. Sinus bradycardia and atrioventricular conduction blocks are common in athletes, most of whom remain asymptomatic, although incomplete reversibility has been shown after exercise cessation. In this Review, we summarize the evidence supporting the existence of exercise-induced arrhythmias and discuss the specific considerations for the clinical management of these patients.
Identification of left atrial (LA) fibrosis through late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) remains controversial due to the heterogeneity and lack of reproducibility of ...proposed methods. Our aim is to describe a normalized, reproducible, standardized method to evaluate LA fibrosis through LGE-CMR.
Electrocardiogram- and respiratory-gated 3-Tesla LGE-CMR was performed in 10 healthy young volunteers and 30 patients with atrial fibrillation (AF): 10 with paroxysmal AF, 10 with persistent AF, and 10 with a previous AF ablation procedure. Local image intensity ratio (IIR) of the LA was calculated as the absolute pixel intensity to mean blood pool intensity ratio. The healthy atrial tissue threshold was defined in young healthy volunteers (upper limit of normality set at IIR tissue mean plus 2 SDs). Dense atrial scarring was characterized in patients with previous radiofrequency-induced scarring (post-AF ablation patients). Validation groups consisted of patients with paroxysmal and persistent AFs. The upper limit of normal IIR was 1.20; IIR values higher than 1.32 (60% of mean maximum pixel intensity in post-ablation patients) were considered dense scar. Image intensity ratio values between 1.2 and 1.32 identified interstitial fibrosis. Patients with paroxysmal and persistent AFs had less atrial fibrotic tissue compared with post-ablation patients. Endocardial bipolar voltage was correlated to IIR values.
An IIR of 1.2 identifies the upper limit of normality in healthy young individuals. An IIR of >1.32 defines dense atrial fibrosis in post-ablation patients. Our results provide a consistent, comparable, and normalized tool to assess atrial arrhythmogenic substrate.
Recent clinical studies suggest that endurance sports may promote cardiac arrhythmias. The aim of this study was to use an animal model to evaluate whether sustained intensive exercise training ...induces potentially adverse myocardial remodeling and thus creates a potential substrate for arrhythmias.
Male Wistar rats were conditioned to run vigorously for 4, 8, and 16 weeks; time-matched sedentary rats served as controls. Serial echocardiograms and in vivo electrophysiological studies at 16 weeks were obtained in both groups. After euthanasia, ventricular collagen deposition was quantified by histological and biochemical studies, and messenger RNA and protein expression of transforming growth factor-β1, fibronectin-1, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, procollagen-I, and procollagen-III was evaluated in all 4 cardiac chambers. At 16 weeks, exercise rats developed eccentric hypertrophy and diastolic dysfunction, together with atrial dilation. In addition, collagen deposition in the right ventricle and messenger RNA and protein expression of fibrosis markers in both atria and right ventricle were significantly greater in exercise than in sedentary rats at 16 weeks. Ventricular tachycardia could be induced in 5 of 12 exercise rats (42%) and only 1 of 16 sedentary rats (6%; P=0.05). The fibrotic changes caused by 16 weeks of intensive exercise were reversed after an 8-week exercise cessation.
In this animal model, we documented cardiac fibrosis after long-term intensive exercise training, together with changes in ventricular function and increased arrhythmia inducibility. If our findings are confirmed in humans, the results would support the notion that long-term vigorous endurance exercise training may in some cases promote adverse remodeling and produce a substrate for cardiac arrhythmias.
Abstract
Cardiovascular research is in an ongoing quest for a superior imaging method to integrate gross-anatomical information with microanatomy, combined with quantifiable parameters of cardiac ...structure. In recent years, synchrotron radiation-based X-ray Phase Contrast Imaging (X-PCI) has been extensively used to characterize soft tissue in detail. The objective was to use X-PCI to comprehensively quantify ischemic remodeling of different myocardial structures, from cell to organ level, in a rat model of myocardial infarction. Myocardial infarction-induced remodeling was recreated in a well-established rodent model. Ex vivo rodent hearts were imaged by propagation based X-PCI using two configurations resulting in 5.8 µm and 0.65 µm effective pixel size images. The acquired datasets were used for a comprehensive assessment of macrostructural changes including the whole heart and vascular tree morphology, and quantification of left ventricular myocardial thickness, mass, volume, and organization. On the meso-scale, tissue characteristics were explored and compared with histopathological methods, while microstructural changes were quantified by segmentation of cardiomyocytes and calculation of cross-sectional areas. Propagation based X-PCI provides detailed visualization and quantification of morphological changes on whole organ, tissue, vascular as well as individual cellular level of the ex vivo heart, with a single, non-destructive 3D imaging modality.
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Cardiovascular diseases (CVDs) affect the myocardium and vasculature, inducing remodelling of the heart from cellular to whole organ level. To assess their impact at micro and macroscopic level, ...multi-resolution imaging techniques that provide high quality images without sample alteration and in 3D are necessary: requirements not fulfilled by most of current methods. In this paper, we take advantage of the non-destructive time-efficient 3D multiscale capabilities of synchrotron Propagation-based X-Ray Phase Contrast Imaging (PB-X-PCI) to study a wide range of cardiac tissue characteristics in one healthy and three different diseased rat models. With a dedicated image processing pipeline, PB-X-PCI images are analysed in order to show its capability to assess different cardiac tissue components at both macroscopic and microscopic levels. The presented technique evaluates in detail the overall cardiac morphology, myocyte aggregate orientation, vasculature changes, fibrosis formation and nearly single cell arrangement. Our results agree with conventional histology and literature. This study demonstrates that synchrotron PB-X-PCI, combined with image processing tools, is a powerful technique for multi-resolution structural investigation of the heart ex-vivo. Therefore, the proposed approach can improve the understanding of the multiscale remodelling processes occurring in CVDs, and the comprehensive and fast assessment of future interventional approaches.
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The role of high-intensity exercise and other emerging risk factors in lone atrial fibrillation (Ln-AF) epidemiology is still under debate. The aim of this study was to analyse the contribution of ...each of the emerging risk factors and the impact of physical activity dose in patients with Ln-AF.
Patients with Ln-AF and age- and sex-matched healthy controls were included in a 2:1 prospective case-control study. We obtained clinical and anthropometric data transthoracic echocardiography, lifetime physical activity questionnaire, 24-h ambulatory blood pressure monitoring, Berlin questionnaire score, and, in patients at high risk for obstructive sleep apnoea (OSA) syndrome, a polysomnography. A total of 115 cases and 57 controls were enrolled. Conditional logistic regression analysis associated height odds ratio (OR) 1.06 1.01-1.11, waist circumference (OR 1.06 1.02-1.11), OSA (OR 5.04 1.44-17.45), and 2000 or more hours of cumulative high-intensity endurance training to a higher AF risk. Our data indicated a U-shaped association between the extent of high-intensity training and AF risk. The risk of AF increased with an accumulated lifetime endurance sport activity ≥ 2,000 h compared with sedentary individuals (OR 3.88 1.55-9.73). Nevertheless, a history of <2000 h of high-intensity training protected against AF when compared with sedentary individuals (OR 0.38 0.12-0.98).
A history of ≥ 2,000 h of vigorous endurance training, tall stature, abdominal obesity, and OSA are frequently encountered as risk factors in patients with Ln-AF. Fewer than 2000 total hours of high-intensity endurance training associates with reduced Ln-AF risk.
Most cells release extracellular vesicles (EVs) that can be detected circulating in blood. We and others have shown that the microRNA contents of these vesicles induce transcriptomic changes in ...acceptor cells, contributing to the adjustment of metabolic homeostasis in response to environmental demands. Here, we explore the potential for modulating obesity- and exercise-derived EV-microRNAs to treat the metabolic dysfunction associated with obesity in mice. Treatment with EV-miRNAs alleviated glucose intolerance and insulin resistance in obese mice to an extent similar to that of high-intensity interval training, although only exercise improved cardiorespiratory fitness and decreased body weight. Mechanistically, EV-miRNAs decreased fatty acid and cholesterol biosynthesis pathways in the liver, reducing hepatic steatosis and increasing insulin sensitivity, resulting in decreased glycemia and triglyceridemia. Our data suggest that manipulation of EV-miRNAs may be a viable strategy to alleviate metabolic dysfunction in obese and diabetic patients who are unable to exercise, although actual physical activity is needed to improve cardiorespiratory fitness.
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