Delayed depolarization and histologic abnormalities underlie the Brugada syndrome.

Brugada syndrome (BrS) is a controversial disease whose pathophysiology is still far from being fully understood. Unlike other cardiological disorders, a definite etiology has not yet been established so that it could be summarized under two main chapters: "functional" or "organic", "repolarization" or "depolarization" disorder. Despite initial descriptions leaned towards the organic substrate and delayed depolarization features, functional and repolarization theories have attracted most of the Cardiological attention for many years. Data from electrocardiography, endocavitary tracings, electroanatomic mapping and histopathology, however, demonstrated that BrS is mainly characterized by structural myocardial changes mostly at the right ventricular outflow tract (RVOT), but also at the right ventricle (RV) and by delayed conduction at the same sites. Conduction disorders at different levels may also be present and identify patients at high risk for major arrhythmic events. The aim of the present review is to provide the current state of art of the pathophysiology of BrS, focusing on electro-vectorcardiography and electrophysiological features, histopathology, echocardiography, and cardiac magnetic resonance imaging (CMRI).

Interpolated junctional extrasystoles mimicking complex polymorphic ventricular arrhythmias in a healthy young athlete: a case report.

Background: In young competitive athletes, ventricular arrhythmias could be a reason for concern as they may represent the sign of a serious underlying cardiac condition. On the other hand, atrial or conduction system premature beats are usually benign. However, when the properties of the His-Purkinje system lead to conduction aberrancies, there is a risk of misinterpreting benign arrhythmias as potentially at risk ventricular ectopic beats. Case summary: We described the case of a healthy young athlete with asymptomatic interpolated junctional ectopic beats interpreted as polymorphic ventricular tachycardia during pre-participation screening. Discussion: Strange and rare electrocardiogram pictures may be observed during sport pre-participation screening. The small atrioventricular (AV) junction is made up of many specialized fibres with different conduction properties. Junctional arrhythmias can have a normal anterograde conduction or can be conducted with aberrancy. Rarely, they can be interpolated and cause PR prolongation or bundle branch block by increasing the refractory period of the AV node and/or the conduction system. When aberrancy occurs, they can be mistaken for 'atypical' ventricular arrhythmias. Prognosis of these events remains uncertain.

Arrhythmic Mitral Valve Prolapse in the Young: A Rare but Concerning Entity.

Arrhythmic mitral valve prolapse (MVP) is an increasingly recognized clinical entity, characterized by the association of myxomatous mitral valve, ventricular arrhythmias (VAs) and sudden cardiac death (SCD). Prevalence of MVP is reported ranging between 2% and 5% of the general population, and risk of SCD is estimated approximately 0.3% per year. Diagnosis of MVP and the occurrence of fatal events involve generally adults aged 30 to 50 years, whereas in younger and even pediatric individuals has rarely been described. Herein, we report two clinical cases of malignant MVP in young patients, with the aim to point out the clinical features and the challenge of clinical management and risk stratification.

Role of Provocable Brugada ECG Pattern in The Correct Risk Stratification for Major Arrhythmic Events.

The so-called Brugada syndrome (BS), first called precordial early repolarization syndrome (PERS), is characterized by the association of a fascinating electrocardiographic pattern, namely an aspect resembling right bundle branch block with a coved and sometime upsloping ST segment elevation in the precordial leads, and major ventricular arrhythmic events that could rarely lead to sudden death. Its electrogenesis has been related to a conduction delay mostly, but not only, located on the right ventricular outflow tract (RVOT), probably due to a progressive fibrosis of the conduction system. Many tests have been proposed to identify people at risk of sudden death and, among all, ajmaline challenge, thanks to its ability to enhance latent conduction defects, became so popular, even if its role is still controversial as it is neither specific nor sensitive enough to guide further invasive investigations and managements. Interestingly, a type 1 pattern has also been induced in many other cardiac diseases or systemic diseases with a cardiac involvement, such as long QT syndrome (LQTS), arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM) and myotonic dystrophy, without any clear arrhythmic risk profile. Evidence-based studies clearly showed that a positive ajmaline test does not provide any additional information on the risk stratification for major ventricular arrhythmic events on asymptomatic individuals with a non-diagnostic Brugada ECG pattern.

Effects of the C825T polymorphism of the GNB3 gene on body adiposity and blood pressure in fertile and menopausal women: a population-based study.

OBJECTIVES: The 825T allele of the GNB3 gene is implicated in adipose distribution, predisposing to obesity and hypertension. Menopause is also considered a condition leading to excess adiposity and hypertension. The aim of the present study was to clarify whether the effects of menopause on body weight and blood pressure are influenced by the C825T polymorphism of the GNB3 gene. METHODS: The study involved 1339 subjects (43% men) aged 18-95 years, genotyped at the GNB3 825 locus, undergoing, in an epidemiological population-based frame, questionnaire, anthropometrics and blood examinations. RESULTS: Mean skinfold thickness (MST), truncal obesity and excess subcutaneous adiposity (MST greater than median) were higher in women than in men. A significant interaction was detected between menopausal status and the C825T polymorphism (Pint > 0.0001). MST, truncal obesity and excess subcutaneous adiposity were lower in CC fertile than menopausal women, but were comparable in TT fertile and menopausal women. In a multivariate logistic model for excess subcutaneous adiposity, the relative risk of menopause was 4.12 (95% confidence interval 2.35-7.22) in CC women but was insignificant in the other two genotypes. In fertile women only, higher systolic blood pressure (SBP) was detected in TT than in CC genotypes. CONCLUSION: An interaction exists between the C825T polymorphism and menopause in controlling body adiposity and blood pressure in women. Adiposity and SBP are higher in menopausal than in fertile women, provided they have the CC genotype. TT fertile women show the same adiposity as those in menopause. Men have the same excess adiposity as menopausal women, independent of the GNB3 genotype.

Menopause does not affect blood pressure and risk profile, and menopausal women do not become similar to men.

OBJECTIVE: Menopause is considered to be a cardiovascular risk factor, but this belief is based on opinions rather than on evidence. Confounding effects of age are often neglected. DESIGN: Population-based study with further subanalysis of case-to-case age-matched cohorts of men and fertile and menopausal women. SETTING: Epidemiology in primary, public, institutional frame. PARTICIPANTS: Nine thousand three hundred and sixty-four men and women aged 18-70 years representative of Italian general population followed-up for 18.8 +/- 7.7 years. MAIN OUTCOME MEASURES: Blood pressure (BP), prevalence and incidence of hypertension, serum total, high-density lipoprotein and low-density lipoprotein cholesterol, glucose tolerance, body adiposity, vascular reactivity, target organ damage, overall and cardiovascular mortality and morbidity, by gender and by menopausal status. RESULTS: Cross-sectional: crude BP, pressor response to cold, orthostatic BP decrease, BMI, skinfold thickness, fasting and postload blood glucose and insulin, serum lipids, left ventricular mass, serum creatinine, microalbuminuria and augmetantion index were higher in menopausal than in fertile women, and comparable in menopausal women and men, a difference that was no longer present when adjusting for age or considering age-matched cohorts. Longitudinal: BP increase during follow-up, cardiovascular mortality and morbidity were greater in menopausal than in fertile women, and comparable in menopausal women and men, a difference no longer present in age-matched cohorts. Menopausal status was rejected from multivariate Cox analysis also including age. CONCLUSION: The cardiovascular effects usually attributed to menopause seem to be a mere consequence of the older age of menopausal women.

Skinfold thickness and blood pressure across C-344T polymorphism of CYP11B2 gene.

OBJECTIVE: To ascertain whether body adiposity is associated with the C-344T polymorphism of the CYP11B2 gene codifying for aldosterone synthase. DESIGN: A cross-sectional epidemiological evaluation of a highly homogeneous unselected general population of Caucasians. METHODS: Lifestyle, medical history, anthropometrics, subscapular, triceps and suprailiac skinfold thickness, lying blood pressure and biochemical measures were recorded in a population-based study among 1386 unselected subjects (56.5% women) living in a secluded valley. All were genotyped for C-344T allele status. Continuous variables were compared across genotypes with analysis of covariance and correlations evaluated using the Pearson method. Odds ratios (OR) were calculated for the TT and CT genotype versus the CC homozygotes and compared with the T-carriers with a logistic model. RESULTS: The C-344T genotypic frequency did not deviate from Hardy-Weinberg equilibrium. In women, higher values of triceps and subscapular skinfold thickness were found in the CC homozygotes than in the T-carriers. In this sex, skinfold thickness also directly correlated with both systolic and diastolic blood pressure in the T-carriers only. The logistic regression for the dependent variable arterial hypertension showed an influence of triceps [OR 1.07, 95% confidence interval (CI) 1.02-1.12, P=0.006], subscapular (OR 1.13, 95% CI 1.06-1.20, P<0.0001) and suprailiac (OR 1.08, 95% CI 1.01-1.15, P=0.03) skinfold in T-carrier women only. These relationships were not detectable in men. The aldosterone-to-renin ratios were comparable across genotypes and sexes. CONCLUSION: The C-344T polymorphism of the CYP11B2 gene seems to exert a sex-specific influence on body adiposity, independent of adrenal aldosterone.

Reduction of cardiovascular risk and mortality: a population-based approach.

The purpose of this study was to evaluate risk pattern and mortality in a general population epidemiologic study performed by a staff of hypertension specialists working as the "good father of a family," with lifestyle and therapeutic advice and instrumental measurements. Mortality among the study population (n=856) during the 4-y study was compared with that recorded in the general population during the 4-y period before the study; those who refused to participate in the study were also recorded (n=280). Among study subjects, blood pressure decreased by 3.6/3.5 mm Hg (P<.01/P<.0001), serum total cholesterol by 3.8% (P<.0001), and low-density lipoprotein cholesterol by 10.9% (P<.01); awareness of hypertension increased by 87% (P<.0001); 20% of hypercholesterolemic patients (P<.01) and 28% of diabetic patients (P<.001) were identified; and 40% of hypertensive patients (P<.0001) were treated. Overall 4-y mortality was 12.5% in study subjects, 36.6% in renitent subjects (P<.0001 vs enrolled), and 19.9% during the period preceding the study (P<.0001 vs enrolled); cardiovascular mortality rates were 5.8%, 18.6% (P<.0001), and 11.4% (P<.0001), respectively. In particular, the frequency of fatal stroke was 0.06%, 3.8% (P<.0001), and 2.5% (P<.0001), respectively, and that of fatal coronary events was 3.4%, 7.5% (P<.0001), and 4.6% (P<.0001), respectively. In conclusion, when an epidemiologic professional staff member approaches patients in a manner similar to that of the "good father of a family," a better risk pattern and lower mortality rates (particularly cerebrovascular and coronary) are seen in those who are receptive to the care provided; those who decide not to participate in health care opportunities do not benefit.

C-344T polymorphism of the aldosterone synthase gene and blood pressure in the elderly: a population-based study.

OBJECTIVES: Whether the C-344T polymorphism of the aldosterone synthase gene is important for blood pressure control remains controversial. It has been proposed that an association between this polymorphism and blood pressure might be evident in elderly subjects. The aim of the present study was to test this hypothesis in an epidemiological context. DESIGN: A cross-sectional epidemiological evaluation of a highly homogeneous unselected general population of elderly Caucasians. METHODS: Lifestyle, medical history, anthropometrics, skinfold thickness, supine blood pressure, heart rate and biochemical measures were recorded in 437 subjects aged > or = 65 years living in a secluded valley. All were genotyped for C-344T allele status and underwent measurements of plasma aldosterone and renin. RESULTS: The C-344T genotypic frequency did not deviate from Hardy-Weinberg equilibrium. The aldosterone to renin ratio was 19% lower in the CC than in the TT genotype. Systolic blood pressure was significantly lower in subjects with the CC genotype, higher in the TT (+9.6 mmHg versus CC) and intermediate in the CT (+7.9 mmHg versus CC). Adjustment for age, gender, smoking and antihypertensive treatment did not affect this association. Diastolic blood pressure did not differ across genotypes. A significant increase of systolic blood pressure with increasing age and with increasing skinfold thickness was observed in the TT homozygotes but not in the C-carriers. CONCLUSIONS: These data support the concept that the C-344T polymorphism plays a role in controlling systolic blood pressure and the age-related increase in systolic blood pressure in response to age and to body fat, possibly through differences in modulation of aldosterone synthesis.

Right Ventricular Outflow Tract Tachycardia with Structural Abnormalities of the Right Ventricle and Left Ventricular Diverticulum.

A 43-year-old woman presented to the emergency room with a sustained ventricular tachycardia (VT). ECG showed a QRS in left bundle branch block morphology with inferior axis. Echocardiography, ventricular angiography, and cardiac magnetic resonance imaging (CMRI) revealed a normal right ventricle and a left ventricular diverticulum. Electrophysiology studies with epicardial voltage mapping identified a large fibrotic area in the inferolateral layer of the right ventricular wall and a small area of fibrotic tissue at the anterior right ventricular outflow tract. VT ablation was successfully performed with combined epicardial and endocardial approaches.

Body fat and the cognitive pattern: A population-based study.

OBJECTIVE: The relationship between body fatness and cognitive pattern at a population level was investigated. METHODS: Among 500 unselected subjects from the general population, the role of body mass index (BMI) and body fat mass (BFM) on a mini-mental state examination (MMSE) and on a battery of paper and pencil neuropsychological tests was analyzed. Multiple linear regressions, accounting for potential confounders, were used. RESULTS: In fully adjusted models, MMSE (coefficient +0.027, 95% confidence intervals, 0.017-0.177), the clock drawing test (+0.141, 0.053-0.226), and the trail making test A (+1.542, 0.478-2.607) were positively associated with BMI. Adding BFM to the models, no associations were observed. The tests were also positively associated with BFM (+0.056, 0.021-0.091; +0.063, 0.025-0.101; +0.592, 0.107-1.077; respectively). At analysis of covariance, the same tests were significantly better performed over 29.4 kg m(-2) of BMI. After adding BFM as further confounder, all differences in performance across BMI were no longer significant. The three tests were better performed over 34.6 kg of BFM. CONCLUSIONS: Higher BMI and particularly higher BFM are positively associated with better performance at the cognitive tasks exploring selective attention and executive functions.

Therapeutic profile of manidipine and lercanidipine in hypertensive patients.

Manidipine and lercanidipine are considered effective and safe in the treatment of chronic arterial hypertension and are equipotent in reducing blood pressure (BP) levels. Their main side effect is ankle-foot edema. After a 2-week placebo run-in period, these 2 drugs were compared in a controlled parallel-group study lasting 3 months, involving 53 patients with mild-to-moderate essential hypertension (26 assigned to manidipine and 27 to lercanidipine). At the end of the active treatment period, BP was significantly reduced in comparison with the end of the placebo phase in both the manidipine and the lercanidipine groups, without significant differences between the 2 drugs. Daytime BP was significantly reduced by 5.5%/5.6% with manidipine and by 3.8%/6.6% with lercanidipine, while smaller reductions were seen at nighttime. The smoothness index was the same with both drugs. Unlike lercanidipine, manidipine significantly reduced both basal (-30%) and minimal vascular resistance (-39%), qualifying it as a potent vasodilator. Despite vasodilation, heart rate was not increased but was even slightly reduced by treatment. Ankle-foot edema was observed with both drugs but was less pronounced with manidipine, probably because of greater postcapillary dilatation. In conclusion, manidipine and lercanidipine are both effective and safe in mild-to-moderate essential hypertension, although the former seems to have a more favorable tolerability profile than the latter.