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Background: There is limited information on ethnic differences between patients with Brugada syndrome (BrS) and arrhythmic events (AEs).Objective: The purpose of this study was to compare clinical, electrocardiographic (ECG), electrophysiological, and genetic characteristics between white and Asian patients with BrS and AEs.Methods: The Survey on Arrhythmic Events in Brugada Syndrome is a multicenter survey from Western and Asian countries, gathering 678 patients with BrS and first documented AE. After excluding patients with other (n = 14 [2.1%]) or unknown (n = 30 [4.4%]) ethnicity, 364 (53.7%) whites and 270 (39.8%) Asians comprised the study group.Results: There was no difference in AE age onset (41.3 ± 16.1 years in whites vs 43.3 ± 12.3 years in Asians; P = .285). Higher proportions of whites were observed in pediatric and elderly populations. Asians were predominantly men (98.1% vs 85.7% in whites; P < .001) and frequently presented with aborted cardiac arrest (71.1% vs 56%; P < .001). Asians tended to display more spontaneous type 1 BrS-ECG pattern (71.5% vs 64.3%; P = .068). A family history of sudden cardiac death was noted more in whites (29.1% vs 11.5%; P < .001), with a higher rate of SCN5A mutation carriers (40.1% vs 13.2% in Asians; P < .001), as well as more fever-related AEs (8.5% vs 2.9%; P = .011). No difference was observed between the 2 groups regarding history of syncope and ventricular arrhythmia inducibility.Conclusion: There are important differences between Asian and white patients with BrS. Asian patients present almost exclusively as male adults, more often with aborted cardiac arrest and spontaneous type 1 BrS-ECG. However, they have less family history of sudden cardiac death and markedly lower SCN5A mutation rates. The striking difference in SCN5A mutation rates should be tested in future studies. [ABSTRACT FROM AUTHOR]

Background: Information on young patients with Brugada syndrome (BrS) and arrhythmic events (AEs) is limited.Objectives: The purpose of this study was to describe their characteristics and management as well as risk factors for AE recurrence.Methods: A total of 57 patients (age ≤20 years), all with BrS and AEs, were divided into pediatric (age ≤12 years; n = 26) and adolescents (age 13 to 20 years; n = 31).Results: Patients' median age at time of first AE was 14 years, with a majority of males (74%), Caucasians (70%), and probands (79%) who presented as aborted cardiac arrest (84%). A significant proportion of patients (28%) exhibited fever-related AE. Family history of sudden cardiac death (SCD), prior syncope, spontaneous type 1 Brugada electrocardiogram (ECG), inducible ventricular fibrillation at electrophysiological study, and SCN5A mutations were present in 26%, 49%, 65%, 28%, and 58% of patients, respectively. The pediatric group differed from the adolescents, with a greater proportion of females, Caucasians, fever-related AEs, and spontaneous type-1 ECG. During follow-up, 68% of pediatric and 64% of adolescents had recurrent AE, with median time of 9.9 and 27.0 months, respectively. Approximately one-third of recurrent AEs occurred on quinidine therapy, and among the pediatric group, 60% of recurrent AEs were fever-related. Risk factors for recurrent AE included sinus node dysfunction, atrial arrhythmias, intraventricular conduction delay, or large S-wave on ECG lead I in the pediatric group and the presence of SCN5A mutation among adolescents.Conclusions: Young BrS patients with AE represent a very arrhythmogenic group. Current management after first arrhythmia episode is associated with high recurrence rate. Alternative therapies, besides defibrillator implantation, should be considered. [ABSTRACT FROM AUTHOR]

Background: There is limited information on gender differences in patients with Brugada syndrome (BrS) who experienced arrhythmic events (AEs).Objective: The purpose of this study was to compare clinical, electrocardiographic (ECG), electrophysiological, and genetic characteristics between males and females in patients with BrS with their first AE.Methods: The multicenter Survey on Arrhythmic Events in BRUgada Syndrome collected data on the first AE in 678 patients with BrS including 619 males (91.3%) and 59 females (8.7%) aged 0.27-84 years (mean age 42.5 ± 14.1 years) at the time of AE occurrence.Results: After excluding pediatric patients, it was found that females were older than males (49.5 ± 14.4 years vs 43 ± 12.7 years, respectively; P = .001). Higher proportions of females were observed in the pediatric and elderly populations. In Asians, the male to female ratio for AEs was ≈9-fold higher than that in White. Spontaneous type 1 BrS ECG was associated with an earlier onset of AEs in pediatric females. A similar prevalence (≈65%) of spontaneous type 1 BrS ECG was present in males and females above the age of 60 years. Females less frequently showed spontaneous type 1 BrS ECG (41% vs 69%; P < .001) or arrhythmia inducibility at electrophysiology study (36% vs 66%; P < .001). An SCN5A mutation was more frequently found in females (48% vs 28% in males; P = .007).Conclusion: This study confirms that female patients with BrS are much rarer, display less type 1 Brugada ECG, and exhibit lower inducibility rates than do males. It shows for the first time that female patients with BrS with AE have higher SCN5A mutation rates as well as the relationship between gender vs age at the onset of AEs and ethnicity. [ABSTRACT FROM AUTHOR]

Background: The literature on fever-related arrhythmic events (AEs) in Brugada syndrome (BrS) is currently limited to few case reports and small series.Objective: The present study aimed to describe the characteristics of fever-related AE in a large cohort of patients with BrS.Methods: The Survey on Arrhythmic Events in Brugada Syndrome is a multicenter study on 678 patients with BrS with first AE documented at the time of aborted cardiac arrest (n = 426) or after prophylactic implantable cardioverter-defibrillator implantation (n = 252).Results: In 35 of 588 patients (6%) with available information, the AE occurred during a febrile illness. Most of the 35 patients were male (80%), Caucasian (83%), and proband (70%). The mean age at the time of AE was 29 ± 24 years (range 0.3-76 years). Most patients (80%) presented with aborted cardiac arrest and 6 (17%) with arrhythmic storm. Family history of sudden death, history of syncope, and spontaneous type 1 Brugada electrocardiogram were noted in 17%, 40%, and 71% of patients, respectively. Ventricular fibrillation was induced at electrophysiology study in 9 of 19 patients (47%). An SCN5A mutation was found in 14 of 28 patients (50%). The highest proportion of fever-related AE was observed in the pediatric population (age <16 years), with a disproportionally higher event rate in the very young (age 0-5 years) (65%). Males were involved in all age groups and females only in the pediatric and elderly groups. Fever-related AE affected 17 Caucasians aged <24 years, but no Asians aged <24 years.Conclusion: The risk of fever-related AE in BrS markedly varies according to age group, sex, and ethnicity. Taking these factors into account could help the clinical management of patients with BrS with fever. [ABSTRACT FROM AUTHOR]

Verapamil-sensitive left fascicular monomorphic ventricular tachycardia (LF-VT) was first described ~4 decades ago. Our knowledge regarding this arrhythmia is evolving continuously. The current review aims to highlight up to date aspects of this arrhythmia focusing on its ECG recognition, new considerations of the reentrant circuit, ablation targets in inducible and non-inducible patients and the approach to LF-VT with multiform morphology. [ABSTRACT FROM AUTHOR]

Background: During radiofrequency (RF) ablation of paroxysmal atrial fibrillation, a circular multielectrode recording “lasso” catheter is generally positioned within each pulmonary vein (PV) to determine when pulmonary vein potentials (PVPs) are present and when they have been ablated. The new irrigated multipolar nMARQ circular ablation catheter is positioned within the left atrium to create contiguous circular ablation lines around each PV ostium. Objective: To determine whether the recordings obtained from the nMARQ catheter position around the PV ostium accurately reproduce the recordings obtained from a lasso catheter positioned within that vein. Methods: In 10 patients undergoing RF ablation of paroxysmal atrial fibrillation, we placed an nMARQ and a lasso catheter around and within each PV, respectively. Recordings obtained from both catheters at baseline and after RF ablation were compared. Results: At baseline, recordings of PVPs in both catheters were concordant in 92% of all PVs. However, after RF delivery, the concordance between the nMARQ and lasso recordings was poor. The discordant result most commonly observed was disappearance of “PVPs” from the nMARQ catheter with persistence of PVPs in the lasso catheter (12 of 39 [30%]). Conversely, the delivery of RF frequently resulted in fragmented electrograms (pseudo-PVPs) on the nMARQ catheter despite evidence of PV isolation by lasso catheter recordings. Conclusions: The use of an nMARQ catheter alone, as currently recommended, may lead to underestimation and overestimation of the number of RF applications required to achieve PV isolation. [Copyright &y& Elsevier]

Transcatheter aortic valve implantation (TAVI) frequently requires postprocedural permanent pacemaker (PPM) implantation. We evaluated clinical and hemodynamic impact of PPM after TAVI. Clinical and echocardiographic data were retrospectively analyzed in 230 consecutive patients who underwent TAVI and echocardiography at baseline and after 6 months. Echocardiographic parameters included left ventricular ejection fraction (LVEF), left ventricular (LV) stroke volume, early mitral velocity/annulus velocity ratio (E/e0), right ventricular index of myocardial performance, systolic pulmonary artery pressure (SPAP), and aortic, mitral, and tricuspid regurgitation grades. Clinical outcomes included 2-year survival and cardiovascular and PPM-related event-free survival. The Medtronic CoreValve and Edwards Sapien prosthesis were used in 201 and 29 patients, respectively. PPM was required in 58 patients (25.4%). Two-year and event-free survival rates were similar between patients with and without PPM. At 6 months, patients with PPM demonstrated attenuated improvement in LVEF (-0.9 ± 8.7% vs 2.3 ± 10.8%, respectively, p = 0.03) and LV stroke volume (-2 ± 16 vs 4 ± 10 ml/m², respectively, p = 0.015), a trend toward smaller reduction in systolic pulmonary artery pressure (-1 ± 12 vs -6 ± 10 mm Hg, respectively, p = 0.09), and deterioration of right ventricular index of myocardial performance (-3 ± 17% vs 5 ± 26%, respectively, p = 0.05). The differences in post-TAVI aortic, mitral, and tricuspid regurgitation grades were insignificant. In conclusion, PPM implantation after TAVI is associated with reduced LVEF and impaired LV unloading. However, this unfavorable hemodynamic response does not affect the 2-year clinical outcome. The maintenance of clinical benefit appears to be driven by TAVI-related recovery of LV and right ventricular performance that mitigates unfavorable impact of PPM. [ABSTRACT FROM AUTHOR]

Background: Epicardial ablation has been shown to be a useful adjunct for treatment of ventricular tachycardia (VT). Objective: To report the trends, safety, and efficacy of epicardial mapping and ablation at a single center over an 8-year period. Methods: Patients referred for VT ablation (June 2004 to July 2011) were divided into 3 groups: ischemic cardiomyopathy (ICM), nonischemic cardiomyopathy (NICM), and idiopathic ventricular arrhythmias (VA). Patients with scar-mediated VT who underwent combined epicardial and endocardial (epi-endo) mapping and ablation were compared with those who underwent endocardial-only (endo-only) ablation with regard to patient characteristics, acute procedural success, 6- and 12-month clinical outcomes. Results: Among 144 patients referred for VT ablation, 95 patients underwent 109 epicardial procedures (94% access rate). Major complications were seen in 8 patients (8.8%) with pericardial bleeding (>80 cm3) in 6 cases (6.7%), although no tamponade, surgical intervention, or procedural mortality was seen. Patients with ICM who underwent a combined epi-endo ablation had improved freedom from VT compared with those who underwent endo-only ablation at 12 months (85% vs 56%; P = .03). In patients with NICM, no differences were seen between those who underwent epi-endo ablation and those who underwent endo-only ablation at 12 months (36% vs 33%; P = 1.0). In idiopathic VA, only 2 of 17 patients were successfully ablated from the epicardium. Conclusions: In this large tertiary single-center experience, complication rates are acceptably low and improved clinical outcomes were associated with epi-endo ablation in patients with ICM. Patients with NICM represent a growing referred population, although clinical recurrence remains high despite epicardial ablation. Epicardial ablation has a low yield in idiopathic VA. [ABSTRACT FROM AUTHOR]

Background: Prior chest surgery limits the ability to obtain epicardial access in patients referred for catheter ablation of ventricular tachycardia (VT). Objective: The purpose of this study was to describe the utility of different surgical approaches to access the epicardium for VT ablation. Methods: Clinical data of 14 patients with drug-refractory VT who underwent hybrid surgical epicardial access for catheter mapping and ablation in the electrophysiology lab were reviewed. Baseline patient and procedural characteristics including access, exposure, mapping techniques, and ablation were analyzed. Results: Of a total of 14 patients (age 63.2 ± 10.3 years), 11 had a subxiphoid window performed, and three patients underwent limited anterior thoracotomy to access the epicardium. The indication for surgical access was prior cardiac surgery (n = 12), previous failed epicardial access (n = 1), and ablation in close proximity to the coronary arteries and phrenic nerve (n = 1). Mapping in patients with subxiphoid surgical access was limited to the inferior and diaphragmatic surface of the heart extending posteriorly to the basal lateral wall. With limited anterior thoracotomy, access to the apex, anterior, and mid to apical anterolateral walls was obtained. In these regions, adhesions were more severe and repeat entry into the epicardial region at a different intercostal level was needed in two of three patients. Conclusion: Surgical access with subxiphoid window and limited anterior thoracotomy in the electrophysiology lab is feasible and safe. The surgical approach can be tailored to the region of interest in the ventricle to be mapped and ablated. [ABSTRACT FROM AUTHOR]

Background: Management of ventricular tachycardia (VT) in patients with hypertrophic cardiomyopathy (HCM) is challenging. Objective: The purpose of this study is to assess the value of radiofrequency catheter ablation (RFCA) for the treatment of the VTs in the setting of HCM. Methods: Twenty-two patients (18 with ICD) with HCM and multiple episodes of VTs resistant to medical therapy underwent RFCA with an open irrigation catheter. Epicardial access was obtained if required. All patients were followed for at least 1 year after RFCA. Results: Mean age was 50.4 ± 15.3, and mean ejection fraction was 34.3% ± 9.8%. RFCA was performed endocardially in all patients, while epicardial radiofrequency applications were needed in 13 patients. A previous endocardial ablation was unsuccessful in six patients. At 20 ± 9 months of follow-up, elimination of VTs reached 73%. No major complication was observed during and after the procedures in all patients. Conclusion: Catheter ablation of VTs in patients with hypertrophic cardiomyopathy refractory to medical therapy is safe, feasible, and successful in eliminating VT. Epicardial VT mapping and ablation should be considered as an important access option for the treatment of these patients to increase the success rate. [Copyright &y& Elsevier]

Background: Catheter ablation of the left atrium (LA) is associated with potential collateral injury to surrounding structures, especially the esophagus and the right phrenic nerve (PN). Objectives: The purpose of this study was to evaluate the efficacy and feasibility of intrapericardial balloon placement (IPBP) for the protection of collateral structures adjacent to the LA. Methods: Electroanatomic mapping was performed in porcine hearts using a transseptal endocardial approach in eight swine weighing 40–50 kg. An intrapericardial balloon was inflated in the oblique sinus, via percutaneous epicardial access, to displace the esophagus. Similarly, with the balloon positioned in the transverse sinus, IPBP was used to displace the right PN. Esophageal temperature was monitored while endocardial radiofrequency (RF) energy was delivered to the distal inferior PV. Results: In all cases, balloon placement was successful with no significant effects on hemodynamic function. Balloon inflation increased the distance between the esophagus and posterior LA by 12.3 ± 4.0 mm. IPBP significantly attenuated increases in luminal esophageal temperature during endocardial RF application (6.1 ± 2.4°C vs. 1.2 ± 1.1°C; P<.0001). High-output endocardial pacing from the right superior pulmonary vein ostium stimulated PN activity. After displacement of the right PN with IPBP, PN capture was abolished in 30 (91%) of 33 sites. Conclusions: These findings demonstrate that in an animal model, IPBP is feasible in the setting of catheter ablation procedures and has the potential to decrease the risk of collateral damage to the esophagus and PN during LA ablation. [Copyright &y& Elsevier]

Abstract: Background: C-reactive protein (CRP) has been tested in patients with systolic heart failure (HF) and mixed results have been obtained with regards to its potential predictive value. However, the role of C-reactive protein (CRP) in patients with diastolic HF is not established. We studied the predictive role of high sensitivity CRP (hsCRP) in patients with diastolic HF. Methods: HsCRP levels were measured in a cohort of CHF outpatients, 77 patients with diastolic HF and 217 patients with systolic HF. Concentrations were compared to a large cohort of healthy population (n =7701) and associated with the HF admissions and mortality of the patients. Results: Levels of hsCRP did not differ between patients with systolic and diastolic HF and were significantly elevated compared to the cohort of healthy subjects even after adjustment to various clinical parameters (p <0.0001). In patients with diastolic HF, hsCRP levels associated with New York Heart Association functional class (NYHA-FC) (r =0.31 p =0.01). On univariate Cox regression model hsCRP levels independently predicted hospitalizations in patients with systolic but not diastolic HF (p =0.047). Conclusion: HsCRP concentrations are elevated in patients with diastolic HF and correlate with disease severity; their prognostic value in this patient population should be further investigated. [Copyright &y& Elsevier]

Objectives: Herein, we determined the significance of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in atherosclerotic vascular disease. Background: Inflammation is associated with the pathogenesis of atherosclerosis. The TNF-related apoptosis-inducing ligand/APO-2L, a member of the TNF superfamily, has a role in apoptosis induction and is recognized for its immunomodulatory properties. Methods: Stable and vulnerable atherosclerotic human plaques and aortas from atherosclerotic mice were assayed for the presence of TRAIL, and its inducibility was assayed by immunoblot and real-time polymerase chain reaction on peripheral mononuclear cells incubated with oxidized low-density lipoprotein (oxLDL). Enzyme-linked immunosorbent assay was used for the determination of soluble TRAIL levels in atherosclerotic patients. Results: Tumor necrosis factor-related apoptosis-inducing ligand is present in stable atherosclerotic lesions, is increased in vulnerable plaques, and is found to colocalize with CD3 cells and oxLDL. The TNF-related apoptosis-inducing ligand messenger ribonucleic acid (mRNA) and protein expression was up-regulated in peripheral blood mononuclear cells after incubation with oxLDL. Serum levels of soluble TRAIL but not TNF-alpha or Fas-ligand were reduced significantly in patients with unstable angina as compared with patients with stable atherosclerotic disease and healthy subjects. A negative correlation was demonstrated between soluble TRAIL and C-reactive protein levels but not with levels of mRNA of TRAIL in peripheral blood mononuclear cells. Conclusions: Tumor necrosis factor-related apoptosis-inducing ligand is expressed in plaque-infiltrating CD3 cells and induced by oxLDL, whereas levels of soluble TRAIL are reduced in patients with acute coronary syndromes and negatively correlate with C-reactive protein levels. These results support a possible role for TRAIL in atherosclerosis. [Copyright &y& Elsevier]

Abstract: Background:: The prevalence of coronary ectasia (CE) appears to rise in recent years. However, the pathogenetic mechanisms that underlie this entity are not understood. We hypothesized that dysregulation of circulating matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) contributes to ectasia formation. We also evaluated the association of MMP with inflammatory or the neurohormonal markers. Methods:: We screened coronary angiographic procedures conducted in our hospital. Thirty-four patients with CEs were identified; 17 with a single ectasia and 17 with generalized ectasias. Two control groups; patients with atherosclerotic coronary disease (n =26) and patients with normal coronary arteries (n =27) were chosen randomly. Serum levels of MMP-2, MMP-3 and TIMP-1 were determined by ELISA. Pro B-type natriuretic peptide (proBNP) and high sensitivity C-reactive protein (hsCRP) serum levels were also measured. Results:: Serum levels of MMP-2, MMP-3, TIMP-1, proBNP and hsCRP did not differ between the three groups of patients. However, subgroup analysis demonstrated that MMP-3 level is significantly lower in patients with generalized CEs compared to those with single vessel ectasia. We also found a statistically significant correlation between proBNP and MMP-2/TIMP-1 (for MMP-2: r 2 =0.3, p =0.003 and for TIMP-1 r 2 =0.42, p &#60; 0.000l). By performing subgroup analysis we found that this correlation is only demonstrated in patients with CEs. No correlation was demonstrated between hsCRP and MMPs/TIMP. Conclusions:: These observations suggest that MMP/TIMP imbalance is present in patients with generalized CE and may contribute to ectasia formation. This imbalance could be mediated by BNP. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to compare the characteristics and prevalence of late potentials (LP) in patients with nonischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM) etiologies and evaluate their value as targets for catheter ablation.Background: LP are frequently found in post-myocardial infarction scars and are useful ablation targets. The relative prevalence and characteristics of LP in patients with NICM is not well understood.Methods: Thirty-three patients with structural heart disease (NICM, n = 16; ICM, n = 17) referred for catheter ablation of ventricular tachycardia were studied. Electroanatomic mapping was performed endocardially (n = 33) and epicardially (n = 19). The LP were defined as low voltage electrograms (<1.5 mV) with onset after the QRS interval. Very late potentials (vLP) were defined as electrograms with onset >100 ms after the QRS.Results: We sampled an average of 564 +/- 449 points and 726 +/- 483 points in the left ventricle endocardium and epicardium, respectively. Mean total low voltage area in patients with ICM was 101 +/- 55 cm(2) and 56 +/- 33 cm(2), endocardial and epicardial, respectively, compared with NICM of 55 +/- 41 cm(2) and 53 +/- 28 cm(2), respectively. Within the total low voltage area, vLP were observed more frequently in ICM than in NICM in endocardium (4.1% vs. 1.3%; p = 0.0003) and epicardium (4.3% vs. 2.1%, p = 0.035). An LP-targeted ablation strategy was effective in ICM patients (82% nonrecurrence at 12 +/- 10 months of follow-up), whereas NICM patients had less favorable outcomes (50% at 15 +/- 13 months of follow-up).Conclusions: The contribution of scar to the electrophysiological abnormalities targeted for ablation of unstable ventricular tachycardia differs between ICM and NICM. An approach incorporating LP ablation and pace-mapping had limited success in patients with NICM compared with ICM, and alternative ablation strategies should be considered. [ABSTRACT FROM AUTHOR]