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Abstract Background Measures of left ventricular (LV) systolic and diastolic function are known predictors of mortality after repair of tetralogy of Fallot. We aimed to characterise LV reverse remodelling achievable with ramipril therapy. Methods and results A blinded post-hoc analysis of baseline and 6-month follow-up echocardiograms from the APPROPRIATE (ISRCTN: 97515585) randomised double-blinded placebo-controlled trial of ramipril therapy was performed in 64 patients: 32 in ramipril and 32 in placebo group. Tissue Doppler systolic and diastolic myocardial velocities, mitral inflow velocities and time intervals were measured. Left atrial area and left atrial emptying fraction were calculated. There was significant increase in long axis shortening mean (standard deviation); MAPSE [1.9 (4.2) mm vs −0.2 (3.7) mm; p = 0.030], peak lateral systolic velocity; S′ lateral [1.0 (2.0) cm/s vs −0.3 (2.2) cm/s; p = 0.025], peak lateral early diastolic velocity; E′ lateral [0.57 (2.4) cm/s vs −3.3 (3.9) cm/s; p < 0.001], transmitral to lateral mitral annular early diastolic velocity ratio; E/E′ lateral [−0.7 (1.9) vs 1.5 (1.9); p < 0.001] over the study period in the ramipril compared to the placebo group. Significantly higher measurements were observed in the ramipril arm of the subgroup of patients with right ventricular restrictive physiology in terms of peak late diastolic velocity; A [5.9 (13.5) cm/s vs −5.8 (12.5) cm/s; p = 0.041] and early to late diastolic transmitral velocity ratio; E/A [−0.18 (0.42) vs 0.23 (0.48); p = 0.037]. Conclusion Six months' ramipril treatment appears to limit progression of both diastolic and systolic LV function in adults late after tetralogy of Fallot repair. With increased appreciation that even subtle LV disease predicts tetralogy of Fallot outcomes, further clinical trials of drug therapies are justified. Highlights • Left ventricular (LV) function is a known predictor of mortality after tetralogy of Fallot repair. • We aimed to characterise LV reverse remodelling achievable with ramipril therapy. • 6-months' ramipril treatment limits progression of both diastolic and systolic LV function. [ABSTRACT FROM AUTHOR]

Background Antipsychotic agents are well known for their arrhythmigenic effect on ventricular arrhythmia. Though a few case reports observed the occurrence of atrial fibrillation (AF) after antipsychotic exposure, information about their implication in AF is limited. Methods Based on the National Health Insurance Database in Taiwan, we conducted a nested case-control study to investigate the relationship between antipsychotics and AF. From 2001 to 2010, a total of 34,053 cases of AF and 34,919 matched controls were enrolled. Antipsychotic exposure was measured and binding affinity to neurotransmitter receptors was calculated. Both medical and psychiatric comorbidities were identified and adjusted in multivariate logistic regression analysis. Results Current antipsychotic use was associated with a 17% increased risk of AF relative to nonusers (adjusted OR: 1.17, 95% CI: 1.10–1.26). A dose-dependent relationship of antipsychotic exposure and AF risk was observed ( P for trend < 0.001). Antipsychotics with higher binding affinity to muscarinic M2 receptors were associated with a higher incidence of AF. In subgroup analysis, subjects with preexisting hypertension, diabetes, or coronary artery diseases were at greater risk of developing AF following antipsychotic exposure. Conclusion Antipsychotic exposure was associated with increased risk of AF, especially for agents with higher cardiac muscarinic receptor binding affinity. Physicians should monitor the occurrence of new-onset AF, and strictly control underlying medical risk factors while prescribing antipsychotic agents to high-risk populations. [ABSTRACT FROM AUTHOR]

Background and purpose This study aims to investigate whether changes in lifestyle, added to the antihypertensive treatment, could translate to changes in cardiovascular (CV) morbidity and mortality in hypertensive patients. Methods Between October 2007 and November 2008, men or women (50–79 years) were enrolled randomly in this study when their BP was 140/90–179/109 mmHg with a 2-weeks run-in stage firstly. All participants had at least one additional CV risk factor, indicated by a history of stroke, myocardial infarction (MI), etc. Results 12,245 (90.4%) patients were eligible for our analysis. We assigned them to the lifestyle intervention group (5225) or to control group (7020). In the end of the study, weight loss at least 1 kg of the participants of the intervention group of accounted for 33.2%, control group was 24.9 (P < 0.001). Salt intake more than 6 g of the participants accounted for 29.4% in the intervention group, 38.4% in the control group (P < 0.001). The composite CV events which include non-fatal stroke, MI and CV death, happened in 133 (2.2%) participants of intervention group and 177 (2.4%) in the control group. However, the improvement of composite CV events reduced 55% (adjusted HR = 0.45, 95% CI: [0.32,0.63]), and decreased by 55% (HR = 0.45, 95% CI: [0.37,0.63]) for all CV events. Conclusions The effect of advised only lifestyle intervention used in our study is minor for CV prevention. However, the effect of improvement of lifestyle on CV prevention is indisputable even in hypertensives who receive a-hypertension drug treatment. [ABSTRACT FROM AUTHOR]

Background Angiotensin-(1-7) [Ang-(1-7)] exhibits cardiovascular effects opposite those of angiotensin II (Ang II), thus providing protection against heart disease. However, how Ang-(1-7) imparts cardioprotection is unclear, and its direct cardiac effects are controversial. Whether heart failure (HF) alters cardiac contractile responses to Ang-(1-7) remains undetermined. We tested the hypothesis that in HF, Ang-(1-7) may produce positive modulation on [Ca 2 + ] i regulation, enhancing left ventricular (LV) and myocyte contraction and relaxation via Ang-(1-7) Mas receptor coupled with nitric oxide (NO)/bradykinin (BK)-mediated mechanism. Methods and results We measured LV contractility changes after Ang-(1-7) (650 ng/kg, iv) and compared myocyte functional and [Ca 2 + ] i transient ([Ca 2 + ] iT ) responses to Ang-(1-7) superfusion in 24 normal rats and 34 rats with isoproterenol-induced HF (3 months after 170 mg/kg, s.q. for 2 days). To assess the mechanisms of altered HF responses to Ang-(1-7), subsets of HF myocytes were pretreated to inhibit NO synthase (L-NAME), BK (HOE-140), and Mas receptor (A-779) followed with Ang-(1-7). In normal rats, Ang-(1-7) produced no significant changes in LV and myocyte function. In HF rats, Ang-(1-7) significantly augmented LV contractility and relaxation with increased E ES (51%), but decreased τ compared to baseline. Ang-(1-7) also significantly increased myocyte contraction (dL/dt max , 30%), relaxation (dR/dt max , 41%), and [Ca 2 + ] iT . L-NAME increased, HOE-140 decreased, and A-779 prevented HF myocyte contractile responses to Ang-(1-7). Conclusions In a rat model of HF, Ang-(1-7) increases [Ca 2 + ] iT , and produces positive inotropic and lusitropic effects in the LV and myocytes. These effects are mediated by the Mas receptor and involve activation of NO/BK pathways. [ABSTRACT FROM AUTHOR]

Abstract: Background: Signal averaged electrocardiogram (SAECG) is a specific and non-invasive tool useful for arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis. However, its role in risk stratification of patients with ARVC remains largely undefined. Methods: Sixty-four patients fulfilling Task Force ARVC criteria (mean age: 47±14years-old, 56% male, 50% definite ARVC) were enrolled. The baseline demographic, electrocardiographic, structural, and electrophysiological characteristics were collected. Patients with SAECG fulfilling all 3 Task Force criteria (3+ SAECG) were categorized into group 1, and those fulfilled 2 or less criterion were categorized into group 2. The study endpoints were unstable ventricular arrhythmia (VA), device detectable sustained fast VA (cycle lengths <240ms) and cardiovascular death. Results: During a mean follow-up of 21±20months, 15 primary endpoints including 12 unstable VAs and 3 device-detected fast VAs were met. One patient died of electrical storm, and one patient underwent heart transplantation. The presence of 3+ SAECG predicted malignant events in all patients with definite and non-definite ARVC (p <0.01, OR=30.5, 95% CI=2.5–373.7) and in patients with definite ARVC alone (p =0.03, OR=11.1, 95% CI=1.3–93.9). Patients diagnosed with non-definite ARVC without 3+ SAECG were free from malignant events. Conclusions: SAECG fulfilling all 3 Task Force criteria was an independent risk predictor of malignant events in ARVC patients. SAECG may play a valuable role in ARVC risk stratification. [Copyright &y& Elsevier]

Abstract: Background: The impact of overload duration and age on remodelling process in human atria remains controversial. We analysed histological markers of right atrial (RA) remodelling in CHD patients in order to provide some insights into impacts of age and overload duration on substrates of atrial arrhythmias. Methods: Sixty-five CHD patients who underwent initial cardiac surgery were enrolled (median age 18years). Patients with dominant left atrial overload were excluded. RA tissues resected from CHD patients during surgery were examined by means of histology and immunohistochemistry and compared with RA tissues from age-matched control hearts from post-mortem (n=22, median age 22years). Patient histories of preoperative SVTs and echocardiography were also examined. Results: The greatest extent of fibrosis, the largest myocyte diameter and the longest capillary distance and the most CD45-positive cell infiltration was observed in CHD samples with SVT, followed by CHD without SVT and then control samples. All histological changes were correlated with age in CHD samples (r=0.462, 0.718, 0.529 and 0.447, respectively) with relatively steep and continuous manner, whereas only myocyte diameter was correlated with age in control samples (r=0.576). RA dimensions and area obtained from echocardiography also correlated with histological markers in CHD patients. Conclusions: Dominant and chronic RA overload due to CHD resulted in time-course related RA structural remodelling, which could provide the background for atrial arrhythmia. The overload duration, rather than age, seems to be a key factor for atrial histological degeneration in the cohort of CHD. [Copyright &y& Elsevier]

Abstract: Background: Ebstein''s anomaly of the tricuspid valve often results in biventricular dysfunction and functional deterioration. Little is known about the relation between exercise capacity, disease severity and outcome in adults with Ebstein''s anomaly. Methods: Data on all patients with Ebstein''s anomaly of the tricuspid valve who underwent cardiopulmonary exercise testing in our tertiary center were collected. The relation between exercise parameters, anatomic severity (Glasgow outcome score) and the combined end-point of death, non-elective hospitalization and surgical repair was studied using Cox regression analysis. Results: A total of 51 adult patients fulfilled inclusion criteria (49% male, mean age 37.8±13.6years). Mean peak oxygen uptake (peak VO2) was 63.2±18.7% of predicted, the slope of ventilation per unit of carbon dioxide output (VE/VCO2 slope) 37.4±11.4, heart rate reserve (HRR) 23.6±22.7bpm. A significantly lower peak VO2 was found in patients with a higher Glasgow outcome score, higher cardiothoracic ratio and documented atrial shunt. Peak VO2 (HR for value <60% of predicted 3.47, 95% CI: 1.28–9.44, p=0.015) and HRR (HR for value <25bpm 3.07, 95% CI: 1.24–7.61, p=0.016) were significant predictors of outcome, the former being the strongest on multivariable analysis. Conclusions: Reduced exercise capacity in patients with Ebstein''s anomaly relates to severity of the underlying disease and is a strong and independent predictor of outcome. Cardiopulmonary exercise testing should be incorporated in the follow-up and risk stratification of patients with this relatively uncommon and challenging cardiac defect. [Copyright &y& Elsevier]