Plasma Testosterone and Arrhythmic Events in Male Patients with Arrhythmogenic Right Ventricular Cardiomyopathy

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Abstract
Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with life‐threatening ventricular arrhythmia and progressive ventricular dysfunction. Previous studies suggested that sex hormones play an important role in the onset and prognosis of ARVC. This study aimed to investigate the role of testosterone in predicting major adverse cardiac events in the Chinese ARVC cohort. Methods and results Ninety‐nine ARVC patients (median age, 40 years; 70.7% male) and 96 healthy controls (median age, 41 years; 62.5% male) were enrolled. The circulating levels of testosterone were measured by enzyme‐linked immunosorbent assays (ELISA). The median follow‐up time of all ARVC male patients was 17 months (interquartile range/IQR 9–29). Cox proportional hazards regression was used to analyse the effect of plasma testosterone and other well‐described risk factors on malignant arrhythmic events in male ARVC patients. The male ARVC patients had significantly elevated levels of total testosterone [TT, 6.390 (4.438–8.768) ng/mL vs. 3.617 (2.073–4.479) ng/mL, P < 0.0001, data shown as the median with IQR], bioavailable testosterone [BT, 4.11 (1.990–6.545) ng/mL vs. 1.32 (0.7965–2.0350) ng/mL, P < 0.0001, median with IQR], and free testosterone [FT, 0.2055 (0.1000–0.4073) ng/mL vs. 0.0768 (0.0405–0.1105) ng/mL, P < 0.0001, median with IQR] than healthy male volunteer, whereas no differences were observed among female counterparts. There was no significant correlation between the baseline clinical characteristics and testosterone levels in male ARVC patients (Spearman's correlation test, P > 0.05). During the follow‐up, the levels of testosterone were higher in male patients who experienced malignant arrhythmic events (N = 22) than in those who did not (N = 25) [TT, 9.034 (7.222–15.370) ng/mL vs. 4.633 (3.363–6.375) ng/mL, P < 0.001; BT, 7.485 (2.070–9.163) ng/mL vs. 3.300 (1.685–4.690) ng/mL, P < 0.05; FT, 0.453 (0.221–0.758) ng/mL vs. 0.161 (0.075–0.337) ng/mL P < 0.05, data expressed as median (IQR) and adjusted by Dunn's multiple comparisons test], whereas such distinction was not observed among patients with significant structural progression events (N = 16). Through multivariable adjustments, the Cox regression analysis showed the level of plasma total testosterone (HR = 1.325, 95% confidence interval = 1.171–1.498, P < 0.001) was an independent predictor for malignant arrhythmic events. Conclusions The levels of plasma testosterone in ARVC male patients are higher than those in healthy males. Testosterone level, without relation to the baseline cardiac function and future significant structural progression events, is a strong predictor of future adverse arrhythmic events in male patients with ARVC. Therefore, our results suggest that testosterone may be a useful biomarker in arrhythmic risk prediction in the ARVC.
Funding Information
  • Shanghai Municipal Science and Technology Major Project (2017SHZDZX01)
  • PUMC Youth Fund, and the Fundamental Research Funds for the Central Universities (3332018140)
  • National Natural Science Foundation of China (81670376)
  • CAMS Innovation Fund for Medical Sciences (2016-I2M-1-015)
  • Chinese Academy of Medical Sciences (2017SHZDZX01)
  • National Natural Science Foundation of China (81670376)

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