BackgroundOptimal treatment for stable repaired tetralogy of Fallot (rTOF) patients with pulmonary regurgitation (PR) and related right ventricular (RV) dilatation, including timing of valve implantation, remains uncertain. We sought to study tolerability of the angiotensin-converting-enzyme (ACE) inhibitor ramipril and its effects on cardiovascular function in these patients.MethodsClinically stable rTOF patients with moderate/severe PR were included. A double-blinded, placebo-controlled study of 6months of ramipril vs placebo was performed. All patients underwent cardiovascular magnetic resonance (CMR), echocardiography, neurohormonal analysis, and objective cardiopulmonary exercise testing at baseline and follow-up.Primary endpointThe main aim was to detect changes in RV function (primary endpoint CMR-derived RV ejection fraction).ResultsSeventy-two patients were enrolled and 64 qualified for the final analysis.There was no difference in the primary endpoint RV ejection fraction. RV long-axis shortening significantly improved in the ramipril group compared to placebo (RV: 2.3±3.8 vs 0.02±2.7mm; P=0.017) as did LV long-axis shortening (1.9±4.5 vs −0.2±3.7mm respectively; P=0.030). No clear differences were detected between ramipril and placebo for other measures. In a subgroup of patients with restrictive RV physiology, ramipril resulted in decrease in LV end-systolic volume index and increase in LVEF (−2.4±5.0 vs 2.7±3.6mL/m2; P=0.005, 2.5±5.0 vs −1.3±3.5%; P=0.03). Ramipril did not cause adverse events and was well tolerated.ConclusionsRamipril is a well tolerated therapy, improves biventricular function in patients with rTOF and may have a particular role in patients with restrictive RV physiology. Larger, longer-term studies are needed to determine if ACE inhibitors can improve both ventricular remodelling and clinical outcomes. (ISRCTN: 97515585)

Objective: The effects of obstructive sleep apnoea (USA) on the markers of glucose metabolism and other hormones are of interest, particularly since there is growing evidence that USA may be a risk factor for disorders such as insulin resistance. However, interpreting these studies depends on the target hormone not having a diurnal rhythm and the circadian rhythm not being altered by the sleep fragmentation that occurs in USA. Therefore, the aim of our study was to test the hypothesis that USA displaces the circadian rhythm.Methods: We carried out a prospective, observational, controlled, parallel study in 22 USA patients (mean [SD] age: 45.1 [8.8] years; apnoea/hypopnoea index (AHI): 37 [24] events/h) and 22 age matched healthy subjects (age: 47.9 [7.9] years; AHI: 3 [1] events/h). Saliva samples for the measurement of melatonin were collected from participants resting in dim light at 30 min intervals between 19:30 and 22:30 h. Dim light melatonin onset (DLMO), a marker of the circadian phase, was taken at the end of the 30 min interval in which the greatest rise in melatonin occurred.Results: The group median (interquartile range) DLMO did not differ in USA patients compared to healthy subjects (USA patients: 90 [60-150] min; healthy subjects: 135 [90-150] min, p = 0.19).Conclusion: The circadian phase is the same in USA patients and healthy subjects using salivary melatonin concentration as a marker of the circadian phase. (C) 2011 Published by Elsevier B.V.

Objective: The objective of this study was to assess natriuretic peptide release following acute myocardial infarction, and its relationship with ventricular function.Methods: A total of 44 patients with acute myocardial infarction were studied;, 13 anterior, age (57 +/- 12 years) and 31 inferior, age (58 +/- 12 years). Peptide levels and left ventricular function by echocardiography were assessed at admission and on days 7 and 30 after thrombolysis. Healthy volunteers (n = 21) served as controls.Results: Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) levels rose from admission to day 7 (p = 0.002). While ANP remained elevated at day 30 in both groups, BNP levels fell in patients with anterior myocardial infarction (p = 0.03). Left ventricular fractional shortening was reduced at admission in the two groups (p = 0.01) but returned towards normal in 7 days (p = 0.001) in inferior myocardial infarction and in 30 days in anterior myocardial infarction (p = 0.02). Left ventricular long axis amplitude was universally reduced at admission (p = 0.01) and remained abnormal at day 30 (p = 0.01) in both groups, At day 7, BNP and ANP levels inversely correlated with long axis amplitude of lateral wall in anterior myocardial infarction; (r = -0.7, p = 0.01). BNP correlated inversely with fractional shortening in anterior myocardial infarction (r = - 0.7, p = 0.01) at day 30.Conclusion: The elevated peptide levels at 7 days post-myocardial infarction correlate with reduced mechanical activity of the adjacent noninfarcted segment. Natriuretic peptides release seem to be related to failure of compensatory hyperdynamic activity of the noninfarcted area rather than directly from the injured myocardial segments. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

BACKGROUND:Acute right ventricular (RV) restrictive physiology after tetralogy of Fallot repair results in low cardiac output and a prolonged stay in the intensive care unit (ICU). However, its mechanism remains uncertain.METHODS AND RESULTS:In the first 24 hours after tetralogy of Fallot repair (n=11 patients), serial prospective measurements were performed of cardiac troponin T, indexes of NO production (NO(2)(-) and NO(3)(-) combined as NOx), and iron metabolism and antioxidants. RV diastolic function was assessed by transthoracic Doppler echocardiography. Patients who had a long stay in the ICU were characterized by restrictive RV physiology (nonrestrictive group [n=7]: 3.0+/-0.6 days [mean+/-SD]; restrictive group [n=4]: 10.7+/-3.1 days). Troponin T peak concentration and the area under its concentration-time curve (AUC) were higher in the restrictive RV group (peak: restrictive group 17. 0+/-2.8 microg/L, nonrestrictive group 10.4+/-4.6 microg/L, P<0.03; AUC: restrictive group 268.8+/-73.6 microg. h(-1). L(-1), nonrestrictive group 136.2+/-48.3 microg. h(-1). L(-1), P<0.03). Plasma NOx/creatinine concentrations were higher in the restrictive group than the nonrestrictive group at 2 hours after bypass (restrictive group 1.3+/-0.4, nonrestrictive group 0.8+/-0.2; P=0. 04) but were similar by 24 hours. Iron loading peaked 2 to 10 hours after bypass and was more severe in the restrictive group (peak transferrin saturation: restrictive group 83.9+/-13.0%, nonrestrictive group 58.3+/-16.2%, P=0.05; minimum total iron-binding capacity: restrictive group 0.59+/-0.21%, nonrestrictive group 0.76+/-0.06%, P=0.04; minimum iron-binding antioxidant activity to oxyorganic radicals: restrictive group 9. 5+/-22.4%, nonrestrictive group 50.6+/-11.4%, P=0.01).CONCLUSIONS:After tetralogy of Fallot repair, acute restrictive RV physiology is associated with greater intraoperative myocardial injury and postoperative oxidative stress with severe iron loading of transferrin.