Multi-site lactate kinetics during moderate intensity resistance and endurance exercise in definitive and probable arrhythmogenic cardiomyopathy

Background Arrhythmogenic cardiomyopathy (ACM) is a hereditary disease with a considerable risk of premature heart failure and malignant arrhythmias. High-intensity endurance exercise may increase adverse events, which has led to recommendations of no more than 20 minutes of low-to moderate intensity endurance exercise daily. The safety and metabolic effects of prolonged moderate-intensity endurance or resistance exercise are largely unknown. Methods 20 individuals with a definitive or probable diagnosis of ACM following the revised Padua criteria (mean age: 42.6±10.7 years, 12 females, 14 bearing a pathogenic plakophilin-2 mutation, 11 with an implantable cardioverter-defibrillator, mean left ventricular ejection fraction 59.2±9.2 %; mean right ventricular fractional area change 42.15±13.2 %) were included. Lactate concentration was analyzed simultaneously in the radial (RA), pulmonary (PA), and femoral vein (FV) at the end of moderate-intensity isometric handgrip and dynamic bicep curl (both for 1 minute at 70% of 1 repetition maximum), 20 and 40 minutes of moderate-intensity supine bicycle ergometry (50-60% of peak oxygen consumption). A 5min break was taken after each exercise mode. We hypothesized that a combination of moderate-intensity resistance and prolonged endurance exercise would be safe and maintain aerobic metabolism. Results Lactate concentrations differed across exercise modes at all sites (Figure 1, all p<.001). Compared to rest (RA: 0.93±0.30 mmol/L; PA: 0.87±0.26 mmol/L; FV: 1.06±0.30 mmol/L), lactate concentration consistently increased in HG and BC resistance exercise, peaking at the end of 20min cycling (Figure 1A to C). At rest, lactate concentration was slightly higher in FV (Figure 2A, p=0.009), while it was higher in RA during HG (1.58±0.58 mmol/L vs. PA: 1.19±0.47 mmol/L, FV:1.30±0.39 mmol/L; p<.001, Figure 2B) and BC (2.09±0.56 mmol/L vs. PA: 1.69±0.46 mmol/L, FV:1.56±0.47 mmol/L, p<.001, Figure 2C). No site-specific differences were found during 20 (RA: 2.25±1.08 mmol/L vs. PA: 2.20±1.02 mmol/L vs. FV: 2.21±1.27 mmol/L, p=0.829, Figure 2D) and 40 minutes (RA: 1.61±0.65 mmol/L vs. PA: 1.59±0.58 mmol/L vs. FV: 1.60±0.59 mmol/L, p=0.766, Figure 2E) of aerobic cycling. Notably, all exercise modes displayed predominant aerobic metabolism. No malignant arrhythmias were observed during exercise. Conclusion Moderate-intensity resistance and prolonged endurance exercise was safe and feasible in ACM patients. Although lactate concentration increased slightly from rest across exercise modes, aerobic metabolism was predominant throughout the exercise modes. While these acute effects are reassuring, optimal dosage of exercise in ACM still warrants further long-term investigation to prevent disease progression and facilitate cardiovascular prevention.