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 ...

The pacemaking activity of specialized tissues in the heart and gut results in lifelong rhythmic contractions. Here we describe a new syndrome characterized by Chronic Atrial and Intestinal Dysrhythmia, termed CAID syndrome, in 16 French Canadians and 1 Swede. We show that a single shared homozygous founder mutation in SGOL1, a component of the cohesin complex, causes CAID syndrome. Cultured dermal fibroblasts from affected individuals showed accelerated cell cycle progression, a higher rate of senescence and enhanced activation of TGF-β signaling. Karyotypes showed the typical railroad appearance of a centromeric cohesion defect. Tissues derived from affected individuals displayed pathological changes in both the enteric nervous system and smooth muscle. Morpholino-induced knockdown of sgol1 in zebrafish recapitulated the abnormalities seen in humans with CAID syndrome. Our findings identify CAID syndrome as a novel generalized dysrhythmia, suggesting a new role for SGOL1 and the cohesin complex in mediating the integrity of human cardiac and gut rhythm.

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Most cases of PVE post-TVR involved male patients, with a very high-risk profile (TAVR) or underlying stenotic conduit/valve (TPVR). Typical, but different, microorganisms of PVE were involved in one-half of the TAVR and TPVR cases. Most TPVR-PVE patients were managed surgically as opposed to TAVR patients, and the mortality rate was high, especially in the TAVR cohort.

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