Prolonged Right Ventricular Ejection Delay in Brugada Syndrome Depends on the Type of SCN5A Variant　- Electromechanical Coupling Through Tissue Velocity Imaging as a Bridge Between Genotyping and Phenotyping.

BACKGROUND: Patients with Brugada syndrome (BrS) and a history of syncope or sustained ventricular arrhythmia have longer right ventricular ejection delays (RVEDs) than asymptomatic BrS patients. Different types ofSCN5Avariants leading to different reductions in sodium current (INa) may have different effects on conduction delay, and consequently on electromechanical coupling (i.e., RVED). Thus, we investigated the genotype-phenotype relationship by measuring RVED to establish whether BrS patients carrying more severeSCN5Avariants leading to premature protein truncation (T) and presumably 100%INareduction have a longer RVED than patients carrying missense variants (M) with different degrees ofINareduction.Methods and Results:There were 34 BrS patients (mean [±SD] age 43.3±12.9 years; 52.9% male) carrying anSCN5Avariant and 66 non-carriers in this cross-sectional study. Patients carrying aSCN5Avariant were divided into T-carriers (n=13) and M-carriers (n=21). Using tissue velocity imaging, RVED and left ventricular ejection delay (LVED) were measured as the time from QRS onset to the onset of the systolic ejection wave at the end of the isovolumetric contraction. T-carriers had longer RVEDs than M-carriers (139.3±15.1 vs. 124.8±11.9 ms, respectively; P=0.008) and non-carriers (127.7±17.3 ms, P=0.027). There were no differences in LVED among groups. CONCLUSIONS: Using the simple, non-invasive echocardiographic parameter RVED revealed a more pronounced 'electromechanical' delay in BrS patients carrying T variants ofSCN5A.

Prolonged right ventricular ejection delay identifies high risk patients and gender differences in Brugada syndrome.

BACKGROUND AND OBJECTIVES: Right ventricular (RV) conduction delay has been suggested as an underlying pathophysiological mechanism in Brugada syndrome (BS). In this cross-sectional study we non-invasively assessed the value of echocardiographic markers reflecting ventricular ejection delay to further assess electromechanical abnormalities in BS and to identify patients at risk for life-threatening arrhythmic events. Furthermore, we sought to assess differences in ejection delays between genders because male BS patients demonstrate a more malignant clinical phenotype. METHODS: 124 BS patients (57.3% males) and 62 controls (CTR) (48.4% males) were included. Using Tissue Velocity Imaging, the ejection delay, determined as the time from QRS onset to the onset of the sustained systolic contraction, was measured for both RV free wall (RVED) and lateral LV wall (LVED). From these parameters, the interventricular ejection delay between both walls (IVED) was calculated. RESULTS: BS patients had longer RVEDs and IVEDs compared to the CTR. BS patients with a previous history of syncope or spontaneous ventricular arrhythmia showed the longest RVEDs and IVEDs. Male BS patients demonstrated longer RVEDs and IVEDs than females. Male BS patients with malignant events had the longest delays. No significant differences regarding LVED were observed between BS patients and CTR. CONCLUSIONS: We demonstrated that a previous history of malignant events was associated with longer RVEDs. Our findings supported the RV conduction delay mechanism behind BS and demonstrated for the first time that the predominant malignant male Brugada phenotype might also be the result of a more delayed RV conduction in males.

Short course radiotherapy with simultaneous integrated boost for stage I-II breast cancer, early toxicities of a randomized clinical trial.

BACKGROUND: TomoBreast is a unicenter, non-blinded randomized trial comparing conventional radiotherapy (CR) vs. hypofractionated Tomotherapy (TT) for post-operative treatment of breast cancer. The purpose of the trial is to compare whether TT can reduce heart and pulmonary toxicity. We evaluate early toxicities. METHODS: The trial started inclusion in May 2007 and reached its recruitment in August 2011. Women with stage T1-3N0M0 or T1-2N1M0 breast cancer completely resected by tumorectomy (BCS) or by mastectomy (MA) who consented to participate were randomized, according to a prescribed computer-generated randomization schedule, between control arm of CR 25x2 Gy/5 weeks by tangential fields on breast/chest wall, plus supraclavicular-axillary field if node-positive, and sequential boost 8x2 Gy/2 weeks if BCS (cumulative dose 66 Gy/7 weeks), versus experimental TT arm of 15x2.8 Gy/3 weeks, including nodal areas if node-positive and simultaneous integrated boost of 0.6 Gy if BCS (cumulative dose 51 Gy/3 weeks). Outcomes evaluated were the pulmonary and heart function. Comparison of proportions used one-sided Fisher's exact test. RESULTS: By May 2010, 70 patients were randomized and had more than 1 year of follow-up. Out of 69 evaluable cases, 32 were assigned to CR (21 BCS, 11 MA), 37 to TT (20 BCS, 17 MA). Skin toxicity of grade ≥1 at 2 years was 60% in CR, vs. 30% in TT arm. Heart function showed no significant difference for left ventricular ejection fraction at 2 years, CR 4.8% vs. TT 4.6%. Pulmonary function tests at 2 years showed grade ≥1 decline of FEV1 in 21% of CR, vs. 15% of TT and decline of DLco in 29% of CR, vs. 7% of TT (P = 0.05). CONCLUSIONS: There were no unexpected severe toxicities. Short course radiotherapy of the breast with simultaneous integrated boost over 3 weeks proved feasible without excess toxicities. Pulmonary tests showed a slight trend in favor of Tomotherapy, which will need confirmation with longer follow-up of patients. TRIAL REGISTRATION: [corrected] ClinicalTrials.gov NCT00459628.

Screening for silent myocardial ischaemia in patients with type 2 diabetes mellitus: a quest to improve selection of the target screening population.

OBJECTIVE: Despite the association of diabetes mellitus type 2 (DM2) with silent myocardial ischaemia (SMI) and a high prevalence of death due to coronary artery disease (CAD), screening for CAD in patients with DM2 remains controversial because of a lack of proof that it improves cardiac outcome. The aim of this study was to improve the diagnostic yield of the exercise stress test (EST) by introducing recently published life expectancy tables in selecting DM2 patients for coronary screening. METHODS: 359 patients with DM2 without history or symptoms of CAD were included to perform an EST after a clinical history and brief physical examination. Cardiovascular risk factor profiling was completed with blood and urine analysis. A lower heart rate was defined as bradycardia (heart rate less than 60 bpm), a higher blood pressure as a systolic blood pressure at rest of 130 mmHg of more. RESULTS: The prevalence of SMI was 14.5% (n = 52). The average number of additional cardiovascular risk factors per subject was 4. Multivariate logistic regression yields 4 significant predictors: (i) heart rate at rest (P= 0.015), (ii) a family history of cardiovascular disease (P = 0.017), (iii) systolic blood pressure at rest (P = 0.019), and, (iv) an LDL-c of 80 mg/dL or more (P = 0.021). CONCLUSION: Known risk factors for myocardial ischaemia were identified as significantly influencing the prevalence of SMI. No improvement in diagnostic yield could be identified by selecting the screening population using predicted life expectancy tables.

Pericardial effusion in atrial fibrillation ablation: a comparison between cryoballoon and radiofrequency pulmonary vein isolation.

AIMS: Atrial fibrillation (AF) ablation is increasingly being performed in electrophysiology laboratories. Pericardial effusion (PE) is certainly one of the most frequently observed complications during AF ablation. The aim of our study was to investigate the incidence and outcome of PE following cryothermal energy balloon ablation (CBA) in comparison with conventional circumferential pulmonary vein isolation with a focal radiofrequency (RF) catheter. METHODS AND RESULTS: A total of 133 consecutive patients (105 males) with paroxysmal AF were included in this study. Forty-six patients (36 males) underwent CBA (Arctic Front, Medtronic, USA) and 87 (69 males) point-by-point RF ablation guided by electroanatomical mapping (Carto, Biosense Webster, Diamond Bar, CA, USA). Ablation was performed under general anaesthesia with both techniques. All patients underwent a 2D transthoracic echocardiogram within 24 h before and after the procedure as routinely performed in our centre. Pericardial effusion was detected in 19 (14.2%) of 133 patients. Sixteen patients presented mild effusion, one moderate effusion, and two pericardial tamponades. There was no significant difference in the incidence of PE between the cryoballoon and the RF group (11 vs. 16%). A longer procedural time, coronary artery disease, and arterial hypertension were found to be independent predictors of PE during AF ablation. CONCLUSION: Pericardial effusion occurred in a similar proportion following CBA and RF ablation for AF. Pericardial effusion was mostly mild and asymptomatic, with benign clinical outcome not requiring additional hospitalization days.

Role of echocardiography in toxic heart valvulopathy.

The notion that drugs can induce valvular heart disease (VHD) has occurred since the 1960s and has received a lot of attention in recent years. This review focuses on different aspects of this distinct valvulopathy in seven sections: (i) historical background, (ii) drug-induced VHD, is this a real entity?, (iii) its morphological and echocardiographic features, (iv) drugs associated with VHD, (v) the influence of cumulative drug dose and risk factors, (vi) the natural course of toxic valvulopathy, and (vii) practical recommendations when using potential valvulopathic drugs.

First experience with real-time three-dimensional transoesophageal echocardiography-guided transseptal in patients undergoing atrial fibrillation ablation.

AIMS: Transseptal (TS) puncture during atrial fibrillation (AF) ablation is a relatively safe procedure in experienced hands. However, major and minor complications cannot be completely ruled out. Real-time three-dimensional transeosophageal echocardiography (RT 3D TEE) is a novel imaging technology that permits direct visualization of the fossa ovalis in a 3D perspective, thereby sensibly lowering the likelihood of potential adverse effects during TS. In our study, we describe the technique and assess the feasibility, advantages, and safety of this novel imaging method in guiding TS puncture in a series of consecutive patients undergoing AF ablation. METHODS AND RESULTS: We performed TS puncture guided by RT 3D TEE under general anaesthesia in 24 consecutive patients (16 male, 55.4 +/- 8.1 years) undergoing ablation for drug refractory AF. The fossa ovalis could clearly be seen and easily be distinguished from surrounding anatomical structures in all 24 patients. All punctures required a single attempt to access left atrium. Mean orientation of the needle hub when puncturing was 4.30 o'clock (ranging from 3 o'clock to 6.30 o'clock), and mean distances from the needle tip to the aortic and to the posterior wall were, respectively, 13.5 +/- 7 and 35 +/- 7.3 mm. Total fluoroscopic time was 120.6 +/- 34 s. No major or minor complications were experienced. CONCLUSION: Real-time three-dimensional transeosophageal is a very useful tool in guiding TS puncture in patients undergoing AF ablation with the invaluable advantage of the 3D direct visualization of the fossa ovalis. This permits fast and safe transatrial access with a single puncture attempt.