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Background-Pharmacological blockade of the renin-angiotensin system improves exercise tolerance in patients with left ventricular dysfunction, yet its impact on patients with systemic right ventricles (RVs) remains unknown. Methods and Results-A multicenter, randomized, double-blind, placebo-controlled, crossover clinical trial was performed to assess the effects of losartan on exercise capacity and neurohormonal levels in patients with systemic RVs. Of 29 patients studied (age, 30.3Ϯ10.9 years), 21 had transposition of the great arteries with a Mustard baffle, and 8 had congenitally corrected transposition of the great arteries. Baseline values were as follows: V O 2 max, 29.8Ϯ5.6 mL · kg Ϫ1 · min Ϫ1 (73.5Ϯ12.9% predicted value); RV ejection fraction, 41.6Ϯ9.3%; N-terminal pro brain natriuretic peptide (NT-proBNP), 257.7Ϯ243.4 pg/mL (normal Ͻ125 pg/mL); and angiotensin II, 5.7Ϯ4.9 pg/mL (normal Ͻ5.0 pg/mL). Comparing losartan to placebo showed no differences in V O 2 max (29.9Ϯ5.4 versus 29.4Ϯ6.2 mL · kg Ϫ1 · min Ϫ1 ; Pϭ0.43), exercise duration (632.3Ϯ123.0 versus 629.9Ϯ140.7 seconds; Pϭ0.76), and NT-proBNP levels (201.2Ϯ267.8 versus 229.7Ϯ291.5 pg/mL; Pϭ0.10), despite a trend toward increased angiotensin II levels (15.2Ϯ13.8 versus 8.8Ϯ12.5 pg/mL; Pϭ0.08). Conclusions-In adults with systemic RVs, losartan did not improve exercise capacity or reduce NT-proBNP levels.Minimal baseline activation of the renin-angiotensin system may explain this lack of benefit and imply an alternative pathophysiological mechanism for the progressive ventricular dysfunction and impaired exercise capacity observed in such patients. Key Words: angiotensin Ⅲ exercise Ⅲ transposition of great vessels P atients with congenitally corrected transposition of the great arteries (L-TGA) or intra-atrial baffle repair for complete transposition of the great arteries (D-TGA) function with a morphological right ventricle (RV) supporting a systemic circulation. Overall, excellent long-term survival is reported, with most young adults remaining symptom free. 1,2 However, long-term sequelae include progressive RV dilatation, systolic ventricular dysfunction, 2-5 impaired exercise tolerance, 6,7 arrhythmias, 1,2,5 and sudden death, 1 raising concern over the suboptimal capacity of the RV to endure against a systemic afterload.In both symptomatic and asymptomatic patients with left ventricular (LV) dysfunction, pharmacological blockade of the renin-angiotensin system (RAS) improves LV filling pressures, 8 -10 cardiac index, 8,9 exercise tolerance, 8 -12 and overall survival. [13][14][15] Results of such studies are often extrapolated to patients with systemic RVs, and therapy frequently is empirically initiated. However, beneficial effects of inhibiting the RAS in patients with systemic RVs have not yet been demonstrated. This study therefore was designed to assess the effects of losartan on exercise capacity and neurohormonal levels in adults with systemic RVs. Methods Study PopulationThe study population was derived from patients having L-TGA or ...

Background-Transposition of the great arteries with intra-atrial baffle repair is among the congenital heart defects at highest risk of sudden death. Little is known about mechanisms of sudden death and the role of implantable cardioverter defibrillators. Methods and Results-We conducted a multicenter cohort study in patients with transposition of the great arteries to determine actuarial rates of implantable cardioverter defibrillator shocks, identify risk factors, assess underlying arrhythmias, and characterize complications. Overall, 37 patients (age, 28.0Ϯ7.6 years; 89.2% male) were enrolled from 7 sites. Implantable cardioverter defibrillators were implanted for primary prevention in 23 (62.1%) patients and secondary prevention in 14 patients (37.8%). Annual rates of appropriate shocks were 0.5% and 6.0% in primary and secondary prevention, respectively (Pϭ0.0366). Independent predictors were a secondary prevention indication (hazard ratio, 18.0; Pϭ0.0341) and lack of ␤-blockers (hazard ratio, 16.7; Pϭ0.0301). In patients with appropriate shocks, intracardiac electrograms documented supraventricular tachycardia preceding or coexisting with ventricular tachycardia in 50%. No patient with inducible ventricular tachycardia received an appropriate shock in comparison with 37.5% of noninducible patients (Pϭ0.0429). Inappropriate shocks occurred in 6.6% per year, more so in patients of lesser weight (hazard ratio, 0.91 per kg; Pϭ0.0168). Additionally, 14 patients (37.8%) experienced complications: 5 (13.5%) acute, 1 (2.7%) late generator related, and 12 (32.4%) late lead related. Conclusion-In

Background— The risk of systemic thromboemboli associated with transvenous leads in the presence of an intracardiac shunt is currently unknown. Methods and Results— To define this risk, we conducted a multicenter, retrospective cohort study of 202 patients with intracardiac shunts: Sixty-four had transvenous leads (group 1), 56 had epicardial leads (group 2), and 82 had right-to-left shunts but no pacemaker or implantable cardioverter defibrillator leads (group 3). Patient-years were accrued until the occurrence of systemic thromboemboli or study termination. Censoring occurred in the event of complete shunt closure, death, or loss to follow-up. Mean ages for groups 1, 2, and 3 were 33.9±18.0, 22.2±12.6, and 22.9±15.0 years, respectively. Respective oxygen saturations were 91.2±9.1%, 88.1±8.1%, and 79.7±6.7%. During respective median follow-ups of 7.3, 9.3, and 17.0 years, 24 patients had at least 1 systemic thromboembolus: 10 (15.6%), 5 (8.9%), and 9 (11.0%) in groups 1, 2, and 3, respectively. Univariate risk factors were older age (hazard ratio [HR], 1.05; P =0.0001), ongoing phlebotomy (HR, 3.1; P =0.0415), and an transvenous lead (HR, 2.4; P =0.0421). In multivariate, stepwise regression analyses, transvenous leads remained an independent predictor of systemic thromboemboli (HR, 2.6; P =0.0265). In patients with transvenous leads, independent risk factors were older age (HR, 1.05; P =0.0080), atrial fibrillation or flutter (HR, 6.7; P =0.0214), and ongoing phlebotomy (HR, 14.4; P =0.0349). Having had aspirin or warfarin prescribed was not protective. Epicardial leads were, however, associated with higher atrial ( P =0.0407) and ventricular ( P =0.0270) thresholds and shorter generator longevity (HR, 1.9; P =0.0176). Conclusions— Transvenous leads incur a >2-fold increased risk of systemic thromboemboli in patients with intracardiac shunts.

Background-Controversy exists as to whether secundum atrial septal defects (ASDs) in asymptomatic or mildly symptomatic New York Heart Association (NYHA) class I or II adult patients should be closed.