Ventricular Arrhythmia and Cardiac Fibrosis in Endurance Experienced Athletes (VENTOUX)

Abstract

Background: Sudden cardiac death due to primary arrhythmia is a leading cause of mortality in athletes, predominantly affecting older male athletes. Myocardial fibrosis is strongly associated with arrhythmogenesis in nonischemic cardiomyopathy, but its clinical significance in asymptomatic endurance athletes is unknown. We aimed to investigate whether myocardial fibrosis on cardiovascular magnetic resonance in asymptomatic veteran male athletes was associated with incident ventricular arrhythmia on long-term implantable loop recorder.

Methods: Prospective observational cohort study involving 106 asymptomatic male competitive cyclists/triathletes (aged ≥50 years) who undertook ≥10 h/wk of exercise for ≥15 years. Exclusion criteria were any preexisting cardiovascular disease. Participants underwent clinical assessment, stress-perfusion late gadolinium enhancement-cardiovascular magnetic resonance, exercise testing, and implantable loop recorder implantation to detect ventricular arrhythmia. Athletes were followed up for the primary end point of incident ventricular arrhythmia.

Results: A total of 50/106 (47.2%) athletes had focal myocardial fibrosis (all nonischemic distribution) on cardiovascular magnetic resonance predominantly affecting the basal inferolateral left ventricular segment. During follow-up (median 720 days), 23/106 (21.7%) athletes experienced ≥1 ventricular arrhythmic episode; 3/106 (2.8%) sustained ventricular tachycardia, and 20/106 (18.9%) nonsustained ventricular tachycardia. Myocardial fibrosis (hazard ratio, 4.7 [95% CI, 1.8-12.8]; P=0.002) and greater left ventricular end-diastolic volume indexed (hazard ratio, 1.4 [95% CI, 1.1-1.9]; P=0.02) were associated with an increased risk of incident ventricular arrhythmia, but right ventricular insertion point late gadolinium enhancement was not (hazard ratio, 1.7 [95% CI 0.6-5.1]; P=0.32). Myocardial fibrosis remained predictive after adjusting for left ventricular end-diastolic volume indexed (hazard ratio, 4.7 [95% CI, 1.7-12.7]; P=0.002).

Conclusions: In male veteran endurance athletes, myocardial fibrosis was independently associated with the onset of ventricular arrhythmia, even after adjusting for left ventricular dilatation. Right ventricular insertion point late gadolinium enhancement was not associated with ventricular arrhythmia. Further studies are needed to establish whether myocardial fibrosis itself is arrhythmogenic or a marker of an underlying cardiomyopathic process.

Keywords: athletes; dilatation; fibrosis; perfusion.

Figure 1.

CONSORT diagram. Flowchart of participants; 139 athletes were screened, of which 33 were excluded due to prior cardiovascular disease (CVD) or ineligibility based on age. A total of 106 athletes were included, of which 50 had myocardial fibrosis and 56 did not have myocardial fibrosis on cardiovascular magnetic resonance (CMR). During follow-up, 4 athletes underwent implantable loop recorder (ILR) removal in the no fibrosis group and 2 athletes in the fibrosis group.

Figure 2.

Athletes with late gadolinium enhancement (LGE). Bright blood LGE-cardiovascular magnetic resonance (CMR) images of left ventricular (LV) short-axis (SAX; top) with corresponding LV long-axis (LAX; bottom) images demonstrating fibrosis (white arrow) of the lateral LV segments of a 56-year-old male cyclist (left), a 75-year-old triathlete (middle), and a 64-year-old cyclist (right).

Figure 3.

Onset of ventricular arrhythmia on implantable loop recorder (ILR) monitoring. ECG readings from athletes who developed ventricular arrhythmia during ILR monitoring. A, A 60-year-old cyclist who experienced nonsustained ventricular tachycardia (NSVT) at rest. B, A 64-year-old cyclist who developed asymptomatic NSVT at rest.

Figure 4.

Kaplan-Meier curve of probability of ventricular arrhythmia by myocardial fibrosis over time. Kaplan-Meier curve demonstrating the increased risk of ventricular arrythmia in athletes with myocardial fibrosis (top, red) compared with those without myocardial fibrosis (bottom, blue line). aHR indicates adjusted hazard ratio.