Genetics can contribute to the prognosis of Brugada syndrome: a pilot model for risk stratification

Brugada syndrome is an inherited arrhythmogenic disorder leading to sudden death predominantly in the 3–4 decade. To date the only reliable treatment is the implantation of a cardioverter defibrillator; however, better criteria for risk stratification are needed, especially for asymptomatic subjects. Brugada syndrome genetic bases have been only partially understood, accounting for <30% of patients, and have been poorly correlated with prognosis, preventing inclusion of genetic data in current guidelines. We designed an observational study to identify genetic markers for risk stratification of Brugada patients by exploratory statistical analysis. The presence of genetic variants, identified by SCN5A gene analysis and genotyping of 73 candidate polymorphisms, was correlated with the occurrence of major arrhythmic events in a cohort of 92 Brugada patients by allelic association and survival analysis. In all, 18 mutations were identified in the SCN5A gene, including 5 novel, and statistical analysis indicated that mutation carriers had a significantly increased risk of major arrhythmic events (P=0.024). In addition, we established association of five polymorphisms with major arrhythmic events occurrence and consequently elaborated a pilot risk stratification algorithm by calculating a weighted genetic risk score, including the associated polymorphisms and the presence of SCN5A mutation as function of their odds ratio. This study correlates for the first time the presence of genetic variants with increased arrhythmic risk in Brugada patients, representing a first step towards the design of a new risk stratification model.     

环肺静脉消融治疗慢性房颤

背景：进行一项关于环肺静脉消融治疗慢性房颤的随机对照试验。方法：共纳入146例年龄为57±9岁的慢性房颤患者，将其随机分人头3个月仅接受胺碘酮及两次心脏复率治疗组（对照组）或联合环肺静脉消融治疗组。每天通过电话联系以评估心脏节律，共持续1年。在12个月时评估左房直径和症状严重程度。结果：77例接受环肺静脉消融术的患者中，26％因房颤复发再次行消融治疗，6％因非典型房扑而再次行消融治疗。意向治疗分析显示，在未服用抗心律失常药物的情况下，1年内消融组74％的患者和对照组58％的患者未出现房颤复发或房扑（P=0．05）。在对照组的69例患者中，1年内有53例（77％）因房颤复发转而行环肺静脉消融治疗，仅有3例（4％）在不服用抗心律失常药物且未行消融术的情况下维持窦性节律。     

The effect of concomitant radiofrequency ablation and surgical technique (repair versus replacement) on release of cardiac biomarkers during mitral valve surgery

All patients undergoing heart surgery experience a certain amount of nonspecific myocardial injury documented by the release of cardiac biomarkers and associated with poor outcome. We investigated the role of unipolar radiofrequency ablation of atrial fibrillation on the release of cardiac biomarkers in 71 patients undergoing mitral valve surgery and concomitant left atrial ablation case-matched with 71 patients undergoing isolated mitral surgery. The study was powered to detect a 3 ng/mL difference. There was no difference between the 2 groups in terms of cardiac troponin I (10 +/- 5.3 versus 12 + 10.4 ng/mL; P = 0.7) or creatine kinase-MB (50 +/- 21.8 versus 57 +/- 62.0 ng/mL; P = 0.5) release. Postoperative peak cardiac troponin I levels had univariate associations with the duration of cardiopulmonary bypass (P = 0.002) and aortic cross-clamping (P = 0.001) and with the surgical technique (15 +/- 12 ng/mL for mitral valve replacement versus 9 +/- 4.8 for mitral valve repair; P = 0.0007) at univariate analysis. Mitral valve replacement was the only independent predictor of postoperative peak release of cardiac troponin I identified with multivariate analysis (P = 0.005). Radiofrequency ablation of atrial fibrillation does not significantly increase cardiac biomarker release compared with isolated mitral surgery; mitral valve repair is associated with less release of cardiac biomarkers compared with mitral valve replacement.     

Intervertebral disc lesions in diffuse idiopathic skeletal hyperostosis (DISH).

OBJECTIVE: In order to evaluate the relationships between DISH and vertebral osteochondrosis (degenerative disc disease), the radiographs of the spine of 69 DISH patients were compared to those of 68 controls. METHODS: Radiographs of 69 patients affected by DISH according to Resnick's criteria and of 68 control subjects affected by diseases other than DISH, were evaluated in order to determine the prevalence of vertebral osteochondrosis, diagnosed by the occurrence of moderate to severe reduction in the intervertebral disc height and of the extensive radiographic changes typical of degenerative disc disease, including vacuum phenomena and vertebral body marginal sclerosis. The rate ratios with 95% confidence intervals were computed, with stratification by age groups. RESULTS: Thirty-eight DISH patients (55.1%) and 34 controls (50%) showed vertebral osteochondrosis. Stratification by age revealed an increased prevalence of vertebral osteochondrosis in younger DISH patients with respect to controls (p < 0.05). CONCLUSION: Our results show that vertebral osteochondrosis may be associated with DISH and underline the differences between classification and diagnostic criteria. Moreover, it could be hypothesized that DISH plays a predisposing role in the development of vertebral osteochondrosis during the early stages of the disease, causing an early modification in the physiological curves of the spine.     

Endocardial impedance mapping during circumferential pulmonary vein ablation of atrial fibrillation differentiates between atrial and venous tissue

BACKGROUND: Circumferential pulmonary vein ablation (CPVA) is an effective treatment for atrial fibrillation (AF). Accurate left atrial (LA) mapping is essential for creating lesions at the LA-pulmonary vein (PV) junction, avoiding PV stenosis. OBJECTIVES: The purpose of this study was to establish whether endocardial impedance varies within the LA and PVs and whether it is a useful tool for mapping and ablation. METHODS: Pilot Phase: Three-dimensional LA maps were created using CARTO. Impedance (Z) was measured using a radiofrequency generator at multiple points in the LA, PV ostia (PVO), and deep PVs in 79 patients undergoing their first AF ablation (group 1) and 29 patients undergoing repeat CPVA (group 2). Prospective Phase: In an additional 20 patients, using pilot phase data, one operator defined catheter tip location as either LA or PVO based on CARTO and fluoroscopy. A second operator blinded to CARTO simultaneously did the same based on impedance at 15 +/- 4 points per patient. RESULTS: Group 1: Z(LA) was 99.4 +/- 9.0 omega. Z(PVO) was higher (109.2 +/- 8.5 omega), rising further as the catheter advanced into deep PV (137 omega +/- 18). Z(PVO) differed from Z(LA) by 9 +/- 4 omega. Group 2 had a lower Z(LA) and Z(PVO) compared with group 1 (P <.05). Impedance monitoring differentiated between LA and PVO, with 91% specificity and sensitivity, 96% positive predictive value, and 81% negative predictive value. At 3-month follow-up, no patients had evidence of PV stenosis on magnetic resonance imaging. CONCLUSION: Impedance mapping reliably identifies the LA-PV transitional zone, facilitating AF ablation, and its use is associated with a low incidence of PV stenosis.     

Utility of a new left ventricular asynchrony index as a predictor of reverse remodelling after cardiac resynchronization therapy.

AIMS: The majority of tissue Doppler indexes proposed to predict left ventricular (LV) reverse remodelling in cardiac resynchronization therapy (CRT) reflects LV asynchrony as assessed in ejection phase. We evaluated the predictive value of a new strain-imaging parameter reflecting the total amount of time spent by 12 LV segments in contracting after aortic valve closure. METHODS AND RESULTS: Fifty-nine patients who fulfilled current treatment recommendations were studied before and 6 months after CRT. Time to tissue Doppler systolic peak velocity (Ts) and time exceeding aortic closure (ExcT) in strain curves were measured in 12 LV segments. Ts standard deviation (Ts-SD) and sum of ExcT of overall 12 LV segments (oExcT) were analysed. After 6 months, responders were defined according to > or =15% LV end-systolic volume reduction. Responders (47%) when compared with non-responders (53%) had significantly higher baseline Ts-SD and oExcT values. Receiver operating characteristic (ROC) curve analysis demonstrated that an optimal cutoff value of 760 ms for oExcT yielded 93.5% sensitivity and 82.8% specificity. For Ts-SD at the cutoff of 32 ms, 82% sensitivity and 39% specificity were obtained. Area under ROC was significantly larger for oExcT than for Ts-SD. CONCLUSION: o-ExcT is able to predict LV reverse remodelling after CRT.     

Mapping and ablation: A worldwide perspective

Currently, many ablative techniques have reported excellent long-term results in restoring and maintaining sinus rhythm among patients with paroxysmal and persistent AF. Catheter ablation of AF should not be performed too late over time when recurrent paroxysmal AF progresses to the persistent or to the permanent form. Among patients with permanent AF, the stepwise approach requires very extensive lesions in both the left and right atrium to obtain the same success rate as reported by CPVA as performed in Milan many years ago. Long-term prospective multicenter randomized studies comparing the impact of medical therapy with catheter ablation strategy on “hard” outcomes such as morbidity and mortality are required to better define the patient population that may mostly benefit from ablation at the lowest risk and acceptable cost.