VT Recurrence After Ablation: Incomplete Ablation or Disease Progression? A Multicentric European Study.

AIM: To determine whether ventricular tachycardia (VT) recurrences in arrhythmogenic RV cardiomyopathy (ARVC) and nonischemic cardiomyopathy (NICM) are related to incomplete ablation or disease progression. METHODS: ARVC and NICM patients with two substrate maps of the same diseased ventricle with an interprocedural delay of ≥12 months were included. Disease progression was defined as ≥1 factor: scar area progression (PROG, +5%), ventricular remodeling (dilatation [+25 mL] or decreased ejection fraction [-5%EF]). Incomplete ablation was defined as index VT recurrence or ablation in previously unablated regions inside index scar without PROG. RESULTS: Twenty patients from nine centers were included (80% male 55 ± 16 years, 7 ARVC and 13 NICM, LVEF 43 ± 14%). Mean delay was 28 ± 18 months. Disease progression occurred in 75% with ventricular remodeling in 70%: ventricular dilation in 45% (ARVC [71%]; NICM [38%]), decreased EF in 60% [RVEF in ARVC (71%); LVEF in NICM (54%)], and scar progression in 50% (in ARVC [57%] and NICM [46%]). Index VT recurrence was observed in 40%. Redo ablation sites were located in previously unablated regions inside the index scar in 70% of patients. VT recurrence following the second procedure was seen in 25%. Fifteen percent died during a follow-up of 17 ± 17 months. CONCLUSION: Disease progression is the rule in ARVC and NICM while scar progression occurs in half. However, even if disease progression is frequently observed, incomplete index ablation is the most common finding, strongly suggesting the need for more extensive ablation.

Associations between cardiac fibrosis and permanent atrial fibrillation in advanced heart failure.

Atrial fibrosis is considered as the basis in the development of long-standing atrial fibrillation (AF). However, in advanced heart failure (HF), the independent role of fibrosis for AF development is less clear since HF itself leads to atrial scarring. Our study aimed to differentiate patients with AF from patients without AF in a population consisting of patients with advanced HF. Myocardial samples from the right atrial and the left ventricular wall were obtained during heart transplantation from the explanted hearts of 21 male patients with advanced HF. Long-standing AF was present in 10 of them and the remaining 11 patients served as sinus rhythm controls. Echocardiographic and hemodynamic measurements were recorded prior to heart transplantation. Collagen volume fraction (CVF), transforming growth factor-beta (TGF-beta), and connective tissue growth factor (CTGF) expression in myocardial specimens were assessed histologically and immunohistochemically. The groups were well matched according to age (51.9+/-8.8 vs. 51.3+/-9.3 y) and co-morbidities. The AF group had higher blood pressure in the right atrium (13.6+/-7.7 vs. 6.0+/-5.0 mmHg; p=0.02), larger left atrium diameter (56.1+/-7.7 vs. 50+/-5.1 mm; p=0.043), higher left atrium wall stress (18.1+/-2.1 vs. 16.1+/-1.7 kdynes/m(2); p=0.04), and longer duration of HF (5.0+/-2.9 vs. 2.0+/-1.6 y, p=0.008). There were no significant differences in CVF (p=0.12), in CTGF (p=0.60), and in TGF-beta expression (p=0.66) in the atrial myocardium between the two study groups. In conclusions, in advanced HF, atrial fibrosis expressed by CVF is invariably present regardless of occurrence of AF. In addition to atrial wall fibrosis, increased wall stress might contribute to AF development in long-standing AF.

Role of the PPARalpha Leu162Val and PPARgamma2 Pro12Ala gene polymorphisms in weight change after 2.5-year follow-up in Czech obese women.

The aim of this study was to investigate the possible effect of PPARalpha and PPARgamma2 variants on weight and eating attitudes as well as on their changes after 2.5-year follow-up. The study was carried out in 246 Czech non-diabetic obese women (age 49.0 +/- 11.9 years; BMI 38.1 +/- 7.0 kg/m(2)). The comprehensive weight management programme included lowenergy diet, increased physical activity and lifestyle modification. Anthropometric parameters (body weight and height, waist and hip circumferences) and body composition were measured. The Three-Factor Eating Questionnaire and Beck Depression Inventory were evaluated. At baseline and after the follow-up period, fasting levels of serum glucose, plasma adiponectin, ghrelin, leptin, and lipid profile were determined. The dependence of monitored parameters on the Pro12Ala in PPARgamma2 and Leu162Val in PPARalpha and stage of the treatment (baseline; 2.5- year follow-up) was evaluated using the repeated measures ANOVA model. The cohort was re-examined after 2.5 years, independent of regular checkups and adherence to lifestyle recommendation. Significant favourable changes in anthropometric indexes, lipid profile, leptin, ghrelin and adiponectin levels as well as in dietary restraint and hunger scores were revealed at 2.5-year check-up. However, no changes in the scores of disinhibition and depression were demonstrated. Despite several observed significant differences between carriers and non-carriers of the minor alleles at baseline and at the follow-up, the repeated measures ANOVA did not reveal any significant effect of the PPARalpha and PPARgamma2 polymorphisms on anthropometric, biochemical, hormonal and psycho-behavioural characteristics, neither at baseline nor at the 2.5-year follow-up.

New insights into mechanisms of atrial fibrillation.

Although atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, precise mechanisms that lead to the onset and persistence of AF have not completely been elucidated. Over the last decade, outstanding progress has been made in understanding the complex pathophysiology of AF. The key role of ectopic foci in pulmonary veins as a trigger of AF has been recognized. Furthermore, structural remodeling was identified as the main mechanism for AF persistence, confirming predominant role of atrial fibrosis. Systemic inflammatory state, oxidative stress injury, autonomic balance and neurohormonal activation were discerned as important modifiers that affect AF susceptibility. This new understanding of AF pathophysiology has led to the emergence of novel therapies. Ablative interventions, renin-angiotensin system blockade, modulation of oxidative stress and targeting tissue fibrosis represent new approaches in tackling AF. This review aims to provide a brief summary of novel insights into AF mechanisms and consequent therapeutic strategies.

Neuromedin beta: P73T polymorphism in overweight and obese subjects.

Neuromedin beta (NMB) is a member of the bombesin-like peptide family expressed in brain, gastrointestinal tract, pancreas, adrenals and adipose tissue. The aim of our study was to compare the frequency of P73T polymorphism in overweight and obese patients (37 men: age 50.6+/-11.7 years, BMI 41.1+/-7.8 kg/m(2); 255 women: age 49.0+/-11.9 years, BMI 37.9+/-6.8 kg/m(2)) with that of healthy normal weight subjects (51 men: age 28.2+/-7.1 years, BMI 22.3+/-2.0 kg/m(2); 104 women: age 29.1+/-9.1 years, BMI 21.5+/-1.9 kg/m(2)) and to investigate the polymorphism's influence on anthropometric, nutritional and psychobehavioral parameters in overweight/obese patients both at the baseline examination and at a control visit carried out 2.5 years later, regardless of the patient s compliance with the weight reduction program. No significant differences in the genotype distribution were demonstrated between normal weight and overweight/obese subjects. Male T allele non-carriers compared to T allele carriers had higher energy (p=0.009), protein (p=0.018) and fat (p=0.002) intakes and hunger score (p=0.015) at the beginning of treatment. Male T allele non-carriers had a more favorable response to weight management at the follow-up, as they exhibited a significant reduction in waist circumference, energy intake and depression score as well as a significant increase in dietary restraint. No significant differences between carriers and non-carriers were demonstrated in women at the baseline examination. Both female T allele carriers and non-carriers demonstrated similar significant changes in nutritional parameters and in restraint score at the follow-up. Nevertheless, only female non-carriers showed a significant decrease in the hunger score.

Role of hereditary factors in weight loss and its maintenance.

The prevalence of obesity is increasing worldwide at an alarming rate in both developed and developing countries. Obesity is a chronic complex disease of multifactorial origin resulting from a long-term positive energy balance, in which both genetic and environmental factors are involved. Genetically prone individuals are the first to accumulate fat in the present obesogenic environment. Obesity increases the risks of type 2 diabetes, hypertension, cardiovascular disease, dyslipidemia, arthritis, and several cancers and reduces the average life expectancy. Implementation of effective strategies in prevention and management of obesity should become an important target in health care systems. Weight changes throughout life depend on the interaction of behavioral, genetic and environmental factors. Weight loss in response to weight management shows a wide range of interindividual variation which is largely influenced by genetic determinants. The strong control of weight loss by genotype was confirmed by twin and family studies. Recently, special attention has been paid to nutritional, hormonal, psychobehavioral and genetic factors which can predict the response to weight reduction programme. In this article currently available data on the role of obesity candidate gene polymorphisms in weight loss and maintenance are reviewed. It is believed that an elucidation of the genetic component in the prognosis of weight management could assist in the development of more effective and individually tailored therapeutic strategies.