Exercise-induced Atrial Fibrillation Research Articles

Atrial fibrosis and local right atrial inflammation are characteristic of strenuous, but not moderate exercise, and underlie increased AF inducibility in heavily trained rats

Abstract Introduction The U-shaped relationship between exercise load and atrial fibrillation (AF) risk, where moderate exercise is protective but strenuous training increases the risk of AF, is currently well accepted (1, 2). Clinical and experimental data suggest that atrial fibrosis and parasympathetic tone (PT) enhancement may underlie the excess risk of AF in endurance athletes (3). Delving into the atrial differences between moderate exercise and strenuous training may be important to understand the pathophysiology of exercise-induced AF. Purpose To compare the atrial structural, electrophysiological and molecular remodelling occurring after long-term moderate and strenuous exercise. Methods Male Wistar rats were randomly assigned to sedentary (SED), moderate (MOD, 35 cm/s, 45 minutes) or high intensity exercise (INT, 60 cm/s, 60 minutes) for 16 weeks. An electrocardiogram (ECG) and electrophysiological study (EPS) were performed before sacrifice. Left (LA) and right (RA) atrial samples were collected for fibrosis assessment and a mRNA array. Results After the exercise protocol, weight of SED rats was higher (486±77 g) compared with both the MOD (377±28 g) and INT groups (385±43 g). In the ECG (Figure 1), INT rats presented a prolonged P-wave compared with SED and MOD. Both trained groups presented with significant bradycardia compared with SED, along with enhanced PT (heart rate variability: low to high frequency ratio). The remaining ECG parameters were similar between groups. Consistent with an enhanced PT, the Wenckebach cycle length was similarly prolonged in both trained groups in the EPS. Conversely, the sinus node recovery time was prolonged in INT rats compared with SED and MOD. AF inducibility increased from SED to MOD to INT. Myocardial fibrosis was measured in atrial samples stained with Sirius red. In both the RA and LA, fibrosis was significantly higher in the INT group (6,3±0.8 %) compared with the SED (4,4±0.2 %) and MOD (4,3±0.5 %) groups. An mRNA array showed large differences between atria. 384 and 419 genes were deregulated between INT and MOD (nominal p<0.05) in the RA and LA, respectively. Only 19 genes were consistent between both atria. In pathway analyses, the inflammatory response pathway was enriched (upregulation) in the RA, but not in the LA, of INT rats compared with MOD (Figure 2). Conclusions In healthy rats, strenuous training promoted a differential, pathological remodelling involving atrial fibrosis and sinus node dysfunction, compared with moderate exercise. Local inflammation may play a role in strenuous exercise-induced fibrosis in the RA. PT enhancement was similar in both groups.Figure 1.Figure 2.

Temporal relationship between training and episodes of atrial fibrillation in endurance athletes

Abstract Background Prolonged endurance training promotes exercise-induced cardiac remodeling and atrial fibrillation (AF), the most common arrhythmia among middle-aged endurance athletes. However, there is a lack of data on the impact of training sessions on the recurrence of AF episodes and current guidelines do not provide specific training recommendations for athletes diagnosed with AF. Both sympathetic stimulation during exercise and parasympathetic activity after exercise are possible mechanisms for recurrent episodes of AF. Purpose To assess the temporal relationship of training sessions with recurrent AF episodes among endurance athletes with paroxysmal AF. Methods The Effects of Detraining in Endurance Athletes with Atrial Fibrillation Trial is an international multicenter randomized controlled trial that includes athletes engaged in regular endurance sports ≥five hours per week, diagnosed with paroxysmal AF. AF episodes lasting ≥30 seconds were registered using wireless insertable cardiac monitors (ICM) and reviewed by an experienced cardiologist. Training sessions were registered using sports watches. We analyzed AF episodes and training data for the period from ICM implantation to randomization, and report event rates and rate ratios with 95% confidence intervals (CIs) for recurrent AF episodes during or within 3 hours after training sessions, compared to >3 hours after training. Results Eighteen athletes (1 female, 17 male) with a median age of 55 years (range 44-74) were included. The combined duration of monitoring was 845 days/20,280 hours (median 38.5, range 12-97 days). The athletes performed a total of 619 hours of training during 559 training sessions. In total, 66 AF episodes (median 1, range 0-15) were registered, of which 37 (56%) occurred within 24 hours after the start of a training sessions. Ten AF episodes (15%) occurred during a training session, 12 (18%) occurred within 3 hours after a training session and 44 (67%) occurred >3 hours after training. Figure 1 shows recurrent AF episodes during training (red bars) and within 24 hours from the start of a training session (blue bars) and smoothed density estimates. The event rate per 24 hours was 0.39 for AF during training, 0.17 the first 3 hours after training and 0.06 >3 hours after training. As compared to >3 hours after training, the rate ratio was 6.6 (95% CI 3.8 to 11.6) for recurrent AF episodes during training sessions and 3.9 (95% CI 2.2 to 6.9) for AF episodes during or within 3 hours after training. Conclusion Among middle-aged endurance athletes with paroxysmal AF, the rate of recurrent AF episodes was highest during and within 3 hours after training sessions. The impact of training and the pathophysiology of exercise-induced AF should be investigated further, with the aim of developing preventive strategies specific to athletic populations.Figure 1

Abstract 12307: Exercise-Induced Ventricular Fibrillation in Patients with Brugada Syndrome Phenotype

Introduction: Ventricular fibrillation (VF) in Brugada syndrome (BS) patients are thought to be triggered by vagal nerve activation, which leads to sudden cardiac arrest (SCA) at rest or while asleep. Generally, exercise is not considered as trigger of SCA in BS patients. Aim: To report 2 rare cases of patients with BS phenotype developing exercise-induced ventricular (VF). Case reports: Case 1: 48 year-old male developed SCA during marathon running and was successfully resuscitated with cardiopulmonary resuscitation (CPR). The stored automatic external defibrillator (AED) electrogram (ECG) showed VF. The 12-lead ECG did not show abnormal morphology, however sodium channel blocker challenge test (intravenous injection of pilsicainide, a pure sodium channel blocker 1mg/Kg) unmasked typical type-1 BS ECG. The treadmill stress test induced single premature ventricular contraction by Bruce protocol, and ventricular tachycardia by a flat-out dash without a run-up. Genetic analysis did not show mutation of SCN5A gene. Case 2: 18 year-old male experienced SCA while playing basketball and was successfully resuscitated with CPR. The stored ECG record of AED showed VF. The 12-lead ECG showed normal result, then we performed the drug challenge test. Pilsicainide unmasked typical type-1 BS ECG. He also had exercise-induced atrial fibrillation (AF) and experienced inappropriate shock delivery from implantable cardioverter defibrillator. The treadmill stress test by Bruce protocol did not induce any ventricular arrhythmias. We avoided a flat-out dash protocol because of possibility of exercise-induced AF. Genetic analysis did not show SCN5A mutation. Conclusion: These 2 rare cases of drug-induced BS phenotype developing exercise-induced VF highlight important role of exercise testing as risk stratification tool in certain BS patients.

Exercise and atrial fibrillation: how health turns harm, and how to turn it back.

Exercise is, together with diet, a powerful health-promoting habit. However, an association of intense physical activity with the onset of atrial and ventricular arrhythmias, and sudden death has been described. Although initially questioned, the atrial pro-arrhythmic role of endurance physical activity is now well accepted in the scientific community. Atrial fibrillation is common among endurance athletes, being a source of morbidity in otherwise healthy young and middle-aged individuals. The mechanisms for its development are still poorly understood, but likely involve some components of the athlete's heart (e.g., bradycardia, atrial enlargement) and some clearly pathological factors (e.g., atrial fibrosis). Its management must be a careful balance between exercise moderation and cessation, as extremes in exercise practice have both been related to atrial fibrillation. In this article, we review the current knowledge on exercise-induced atrial fibrillation through different perspectives, each focusing on the epidemiological evidence, the associated risk, the identification of individuals at risk, the potential approach to reduce its impact and how should these athletes be informed.

Excessive exercise in endurance athletes: Is atrial fibrillation a possible consequence?

Moderate physical activity levels are associated with increased longevity and lower risk of atrial fibrillation (AF). However, the relative risk of lone AF is 3-5-fold higher in intensive endurance-trained athletes compared with healthy adults. There is growing concern that "excessive" endurance exercise may promote cardiac remodelling, leading to long-term adverse consequences. The pathogenesis of exercise-induced AF is thought to arise from an interplay of multiple acute and chronic factors, including atrial enlargement, pro-fibrotic tendency, high vagal tone, and genotypic profile, which collectively promote adverse atrial remodelling. Clinical management of athletes with AF, while challenging, can be achieved using various strategies that may allow continued, safe exercise. Based on the overall risk-benefit evidence, it is premature to suggest that excessive exercise is unsafe or should be curtailed. Evidence-based assessment and treatment guidelines are required to ensure optimal and safe exercise among the growing number of endurance athletes with AF.

Mechanisms of atrial fibrillation in athletes: what we know and what we do not know.

Exercise is an emerging cause of atrial fibrillation (AF) in young individuals without coexisting cardiovascular risk factors. The causes of exercise-induced atrial fibrillation remain largely unknown, and conclusions are jeopardised by apparently conflicting data. Some components of the athlete’s heart are known to be arrhythmogenic in other settings. Bradycardia, atrial dilatation and, possibly, atrial premature beats are therefore biologically plausible contributors to exercise-induced AF. Challenging findings in an animal model suggest that exercise might also prompt the development of atrial fibrosis, possibly due to cumulative minor structural damage after each exercise bout. However, there is very limited, indirect data supporting this hypothesis in athletes. Age, sex, the presence of comorbidities and cardiovascular risk factors, and genetic individual variability might serve to flag those athletes who are at the higher risk of exercise-induced AF. In this review, we will critically address current knowledge on the mechanisms of exercise-induced AF.

Implementation of a Physician-Prescribed Exercise Program As Standard of Care in Allogeneic Stem Cell Transplant (SCT) Patients (pts) in British Columbia: A Pilot Study

Background: There is compelling evidence that physical activity positively influences quality of life (QoL), and health-related outcomes including improved muscle mass and physical functioning in cancer pts. SCT pts however have unique barriers to exercise including isolation, restriction of activities, and treatment toxicity. In the early post SCT period, pts describe worsening fatigue, physical capacity and QoL. We sought to determine whether a partially supervised exercise intervention early post SCT would address these issues. Our primary objective was to determine the feasibility of delivering such an intervention at our institution. Secondary objectives were to assess changes as a result of the intervention in QoL, muscle mass and physical functioning.Methods: From Aug 2015-Jun 2016, we conducted a prospective single-arm study to evaluate feasibility of a 12 week partially supervised exercise program (1 supervised, 2 unsupervised sessions/week) for alloSCT pts with hematologic malignancies. The program consisted of 3 progressive endurance (stationary bike, walking) and 2 resistance training sessions/week, from hospital discharge (D/C) to Day (D) 100. Feasibility was defined as ability to recruit >65% of eligible pts, ≥70% retention and ≥70% adherence. Secondary outcomes were measured pre SCT (T0), at D/C (T1) and D100 (T2) and included QoL, muscle strength, mobility, aerobic fitness and body composition. Changes from T0 to T1 and T1 to T2 were compared using a paired sample t-test.Results: Of 43 consecutive alloSCT pts assessed for eligibility, 30 (70%) entered the study: 17 male (57%), median age 48 yrs (range 19-66 yrs). Transplants characteristics were: related 6; unrelated 24; myeloablative 23; reduced intensity 7. At baseline, SCT comorbidity index was 0 in 43%, 1-2 37%, ≥ 3 20%. Pts self-reported exercising enough to break a sweat (Godin et al) never 60%, sometimes 33%, often 7%. Median hospitalization was 29d (range 15-141); 9 pts developed grade II-IV acute graft-versus-host disease (skin 7, gut 5, liver 1).Overall retention to D100 was 80% (Figure 1). Two pts had complications during hospitalization and did not enter the program. Of the 24 pts who entered the program, adherence was 72% for supervised and 89% for unsupervised sessions. Logistics with scheduling around multiple medical appointments in the early post SCT period were the most common reasons for non-adherence. Other reasons included nausea, fatigue and weakness. One pt developed exercise-induced atrial fibrillation in week 3 requiring cessation of exercise.When comparing secondary outcomes from T0 to T1 (Table 1), pts had significantly decreased muscle strength (grip strength, 30-second chair stand), mobility (timed up-and-go [TUG]) and aerobic capacity (6-min walk test [6MWT]). At T2 after completion of the program, these measures all increased significantly when compared to T1. Global QoL scores on the EORTC measure decreased from T0 to T1 (P=.011) and were significantly improved by T2 (P<.001). Similar trends were seen across functional and symptom measure scales. Body composition comparisons between T0 and T2 demonstrated a trend towards increased appendicular lean mass (P<.059).Conclusion: Results of this pilot study demonstrate feasibility of a partially supervised exercise program post-alloSCT deemed by achieving the target recruitment rate, ≥70% adherence and ≥70% retention. Logistics were the most common reason for non-adherence, highlighting need for a multidisciplinary team with knowledge of the post SCT setting. Prior observational studies have shown significant declines in physical functioning and QoL within the first 100 days of SCT. In contrast we demonstrate significant improvements in these measures. Furthermore, we demonstrate a trend towards increased lean muscle mass, which is a novel secondary outcome that warrants further evaluation in this setting. Our findings support the need for this clinical intervention and will be evaluated in a larger randomized trial. [Display omitted] [Display omitted] DisclosuresGerrie:Roche Canada: Research Funding. Plantinga:BCCA: Employment. Broady:Lotte & John Hecht Memorial Foundation: Research Funding.

Diagnosis, pathophysiology, and management of exercise-induced arrhythmias.

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.

Increased atrial arrhythmia susceptibility induced by intense endurance exercise in mice requires TNFα

Atrial fibrillation (AF) is the most common supraventricular arrhythmia that, for unknown reasons, is linked to intense endurance exercise. Our studies reveal that 6 weeks of swimming or treadmill exercise improves heart pump function and reduces heart-rates. Exercise also increases vulnerability to AF in association with inflammation, fibrosis, increased vagal tone, slowed conduction velocity, prolonged cardiomyocyte action potentials and RyR2 phosphorylation (CamKII-dependent S2814) in the atria, without corresponding alterations in the ventricles. Microarray results suggest the involvement of the inflammatory cytokine, TNFα, in exercised-induced atrial remodelling. Accordingly, exercise induces TNFα-dependent activation of both NFκB and p38MAPK, while TNFα inhibition (with etanercept), TNFα gene ablation, or p38 inhibition, prevents atrial structural remodelling and AF vulnerability in response to exercise, without affecting the beneficial physiological changes. Our results identify TNFα as a key factor in the pathology of intense exercise-induced AF.

Atrial Fibrillation Through the Years

Information about a real patient is presented in stages (boldface type) to an expert clinician (Dr Valentin Fuster), who responds to the information, sharing his reasoning with the reader (regular type). A discussion by the authors follows. A 61-year-old man presents with 2 weeks of exertional dyspnea. Pertinent medical history includes hypertension, nephrolithiasis, and internal hemorrhoids. He takes no medications and has no known drug allergies. His father died after a myocardial infarction at 57 years of age. He formerly smoked 1 pack of cigarettes daily for 15 years but ceased tobacco use 10 years before presentation. He ingests 2 glasses of alcohol weekly and denies illicit drug use. His caffeine intake is limited. He is an architect and is married, with healthy children. On physical examination, his temperature is 98.0°F, blood pressure is 130/85 mm Hg bilaterally, pulse is irregular at 130 beats per minute, and respiratory rate is 18 breaths per minute with an oxygen saturation of 97% while breathing room air. He is a slender white man in no distress. His jugular venous pressure is elevated at 14 cm H 2 O. There is no thyromegaly, and the carotid upstrokes are brisk, without bruits. Cardiovascular examination reveals a rapid and irregular heart rhythm with variation in the intensity of the first heart sound. The point of maximal impulse is not displaced. The remainder of the chest and abdominal examination is within normal limits. The extremities are warm and show mild pitting edema. Laboratory testing is significant for normal renal function and electrolytes, but a hemogram reveals a mild thrombocytopenia of 90 000 platelets/μL. ECG demonstrates atrial fibrillation (AF) with an average ventricular rate of 123 bpm ( Figure 1 ). Figure 1. The 12-lead ECG showing atrial fibrillation with a rapid ventricular rate. Dr Valentin Fuster : This is a …

P-Wave Durations in Patients Experiencing Atrial Fibrillation During Exercise Testing

Augmented sympathoadrenal activity during exercise may contribute to occurrence of various arrhythmias including atrial fibrillation (AF). The prolongation of intraatrial and interatrial conduction times and inhomogeneous propagation of sinus impulses are well-known characteristics of the atrium prone to fibrillate and are evaluated by maximum P-wave duration (P max), P-wave dispersion (PWD). To show the increased P max and PWD values in patients experiencing AF during exercise testing and the role of beta blockade on treatment of exercise-induced AF, 22 of these patients were compared with a control group consisting of 41 patients without AF attacks. P max (p = 0.001) and PWD (p = 0.001) values were significantly higher in patients with AF compared to those without AF. The development of AF during exercise testing was found to be positively correlated with P max (r = 0.87, p < 0.001), PWD (r = 0.83, p = 0.001), and work load (r = 0.34, p = 0.002) and negatively correlated with ejection fraction (r = -0.26, p=0.02). After the treatment with beta-blocking agents for 2 weeks, the decrease in P max and PWD values was accompanied by a much lower prevalence of exercise-induced AF. Consequently, the patients with AF had greater P max and PWD values compared to control subjects, and these simple parameters were well correlated with the occurrence of AF during exercise testing. Furthermore, treatment of these patients with beta blockers would appear to decrease the recurrence of exercise-induced AF and to be associated with a decrease in P-wave durations.

The prognostic significance of exercise-induced atrial arrhythmias

ObjectivesThe purpose of the study was to determine if atrial ectopy (AE) or atrial arrhythmias during exercise are predictive of an increased risk of cardiac events and death. BackgroundAlthough stress-induced atrial arrhythmias are common during exercise testing, there is a paucity of data regarding the correlation with underlying heart disease and cardiovascular outcomes. Atrial arrhythmias may reflect underlying left atrial enlargement and diastolic dysfunction, which are prognostic of mortality. We hypothesized that these stress-induced arrhythmias are associated with long-term adverse cardiac events. MethodsExercise echocardiography was performed in 5,375 patients (age 61 ± 12 years) with known or suspected coronary artery disease. An abnormal result was defined as exercise-induced atrial fibrillation (AF)/atrial flutter, supraventricular tachycardia (SVT), or AE. ResultsA total of 311 (5.8%) patients died (132 [2.5%] from cardiac causes) over a period of 3.1 ± 1.7 years. In addition, 193 (3.6%) patients experienced a myocardial infarction (MI) and 531 (9.9%) patients required revascularization. During exercise testing, 1,272 (24%) patients developed AE, 185 (3.4%) developed SVT, and 43 (0.8%) developed AF. The five-year cardiac death rate was not statistically different between groups (none [3.8%], AE [4.3%], SVT [3.7%], AF [0%], p = 0.43). The five-year rate of MI was significantly different between groups (none [5.7%], AE [8.3%], SVT [0%], AF [9.0%], p = 0.005). The five-year rate of revascularization between groups was not significantly different (none [14.2%], AE [17.0%], SVT [11.8%], AF [14.8%], p = 0.50). A composite of all five-year adverse end points was similar between groups (none [22.7%], AE [27.8%], SVT [17.7%], AF [25.7%], p = 0.10). In stepwise multivariate analysis, AE was not predictive of myocardial infarction when taking into account traditional clinical variables and exercise test results. ConclusionsIn this large cohort of patients, the occurrence of AE was predictive of an increased risk of MI. However, the association did not persist after adjustment for clinical and exercise variables known to predict adverse long-term cardiovascular outcomes. The rate of long-term cardiac death or revascularization was not influenced by the development of stress-induced atrial arrhythmias.

Cardiac adverse effects and acute exercise in elderly subjects.

Cardiac arrhythmias, ST segment depressions and other cardiac adverse effects are occasionally seen in relation to physical exercise in elderly people. However, the magnitude, quality, and time-dependence of these events need to be clarified. During voluntary maximal cycle ergometer exercise (CEE), immediate cardiac disturbances as a reason for exercise termination were registered in a sample of 75-year-old men and women (N=203) (population group, PG). Any referrals to hospital following cardiac incidents within 24 hours post-CEE were obtained from patient records. Ambulatory ECG was recorded 24 hours before and after CEE in 23 elderly subjects (12 men, 11 women) capable of maximal effort (Holter group, HG). In the PG, 23.4% of the men and 6.4% of the women had to terminate CEE because of cardiac disturbances. One subject was referred to hospital because of exercise-induced atrial fibrillation. In the HG, no long-lasting effect of exercise on the occurrence of cardiac disturbances was found in elderly subjects capable of maximal effort.

Clinical and Electrocardiographic Correlates of Exercise-Induced Atrial Fibrillation: A Case-Control Study

Clinical and electrocardiographic correlates of atrial fibrillation (AF) induced during routine exercise testing were examined in a case-control study. With the use of a prospective data base 11,730 consecutive exercise tests in 7,273 patients were reviewed. AF developed in 14 patients during exercise and in 9 patients during recovery (total incidence 0.3%). The mean age was 62 (range 36-76) years, and most patients were male (87%). AF was sustained (>30 s) in 17 patients. The median duration of AF was 233 s. Atrial premature activity, including atrial tachycardia, often (13 patients) preceded AF. In 6 patients (26%) no structural heart disease was apparent. Compared with controls, matched for age, sex, and test indication, AF patients used less beta blockers (9 vs. 43%; p < 0.05) and had a higher maximal heart rate (144 vs. 127 beats/ min; p < 0.05). Also, ischemic responses to exercise were observed more often in these patients (26 vs. 6%; p < 0.05). These findings indicate that most patients with exercise-induced AF have associated cardiac disorders, foremost ischemic heart disease. In a subset of patients, however, symphathetic activation per se appears to play an important role.

Exercise-Induced Atrial Fibrillation

Exercise-Induced Atrial Fibrillation