ABSTRACT
Data on post-heart transplant (HT) survival of patients with Chagas cardiomyopathy (CC) are scarce. We sought to evaluate post-HT survival in patients with CC as compared with other causes of heart failure across different eras of HT. Methods: We conducted a retrospective, cohort study of 376 adult HT recipients between October 1997 and November 2019. Participants were classified according to the etiology of heart failure as CC (N = 66), nonischemic cardiomyopathy (N = 214), and ischemic cardiomyopathy (N = 96), and according to the era of HT as early (1997-2009), recent (2010-2014), and current era (2015-2019). Results: After a mean follow-up of 5.0 y (0-20.5 y), post-HT survival rates at 1, 5, and 10 y were comparable between groups. One-y survival improved from 70% in the early eras to 80% in the current era (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.41-0.97; P = 0.034). After adjustment for sex, age, and mechanical circulatory support, time-related improvement in survival was observed only in patients without CC (HR, 0.54; 95% CI, 0.32-0.91; P = 0.019) but not in those with CC (HR, 0.99; 95% CI, 0.36-2.73; P = 0.98). Causes of death were similar between patients with CC and the other etiological subgroups. Conclusions: Posttransplant survival is comparable between patients with CC, nonischemic cardiomyopathy, and ischemic cardiomyopathy. Although survival has improved significantly over years for most HT recipients, it has remained unchanged for those with Chagas disease. These trends underscore the importance of scientific research, policy discussions and a collaborative registry of heart transplantation in Chagas cardiomyopathy.
ABSTRACT
Introduction: Recurrent hypoxia (HPX), a hallmark of the obstructive sleep apnea (OSA), impairs autonomic balance, and increases arterial blood pressure (BP). Oxidative stress is one of the mechanisms involved in these alterations. The cumulative effect of acute intermittent HPX and the chronicity may determine whether the response crosses the threshold from having protective value to pathology. However, the impact of acute intermittent HPX-reoxygenation on markers of oxidative stress in healthy individuals remains to be fully understood. Objective: To analyze the effects of the acute intermittent HPX on the generation of neutrophil-derived superoxide, sympathovagal balance, and vascular function in healthy subjects. Methods: We applied six cycles of intermittent HPX (10% O2 and 90% N2) for 5 min followed by 2 min of room-air in 15 healthy volunteers (34 ± 2 years; 22.3 ± 0.46 kg/m2), without OSA (polysomnography), during wakefulness. During the experimental protocol, we recorded O2 saturation, end-tidal CO2, heart rate (HR), systolic, and diastolic BP, cardiac output (CO) and peripheral resistance (PR). Cardiac sympathovagal balance was determined by HR variability analysis (low frequency and high frequency bands, LF/HF). Superoxide generation in polymorphonuclear neutrophil cells were established using relative luminescence units (PMNs RLU) at baseline (pre-HPX) and immediately after hypoxia induction (post-HPX6). Results: The studied subjects had normal levels of BP, plasma glucose, lipid profile, and inflammatory marker (C-reactive protein). Acute intermittent HPX increased HR, systolic BP, CO, and decreased PR. Additionally, acute intermittent HPX increased PMNs RLU, measured post-HPX6 (470 ± 50 vs. 741 ± 135, P < 0.05). We found a similar increase in LF/HF post-HPX6 (0.91 ± 0.11 vs. 2.85 ± 0.40, P < 0.05). PR was diminished from pre-HPX to post-HPX6 (1.0 ± 0.03 vs. 0.85 ± 0.06, P < 0.05). Further analysis showed significant association between O2 saturation and PMNs RLU (R = -0.62, P = 0.02), and with LF/HF (R = -0.79, P = 0.02) post-HPX6. In addition, an association was found between PMNs RLU and PR post-HPX6 (R = 0.58, P = 0.04). Conclusion: Acute exposure to intermittent HPX not only increased superoxide generation in neutrophils, but also impaired cardiac sympathovagal balance in healthy subjects. These data reinforce the role of intermittent HPX in superoxide generation on neutrophils, which may lead to an impairment in peripheral vascular resistance.
