Bilateral Cardiac Sympathetic Denervation for Refractory Multifocal Premature Ventricular Contractions in Patients With Nonischemic Cardiomyopathy.

BACKGROUND: Bilateral cardiac sympathetic denervation (BCSD) for refractory life-threatening ventricular arrhythmias is a neuromodulatory intervention targeting sympathetically driven focal or re-entrant ventricular arrhythmias. OBJECTIVES: This study sought to provide a more complete and successful option for intervention in patients in whom premature ventricular contraction (PVC) ablation is not feasible or has been unsuccessful. METHODS: A total of 43 patients with >5% PVC burden and concomitant nonischemic cardiomyopathy (NICM) who previously failed medical and ablation therapies were referred for BCSD. All patients underwent bilateral video-assisted thoracoscopic surgical approach with T1-T4 sympathectomy. Primary effectiveness endpoints were postprocedural PVC burden resolution, improvement in left ventricular ejection fraction (LVEF), and cessation of antiarrhythmic drugs (AADs). Safety endpoints included peri- and postprocedural complications. Outcomes were assessed over a 1-year follow-up period. RESULTS: Among the 43 patients who underwent BCSD, the mean age was 52.3 ± 14.7 years, 69.8% of whom were male patients. Presenting mean LVEF was 38.7% ± 7.8%, and PVC burden was 23.7% ± 9.9%. There were significant reductions in PVC burden postprocedurally (1.3% ± 1.1% post-BCSD, compared with 23.7% ± 9.9% pre-BCSD, P < 0.001) and improvements in LVEF (46.3% ± 9.5% post-BCSD, compared with 38.7% ± 7.8% pre-BCSD, P < 0.001). The rate of ICD therapies decreased from 81.4% (n = 35) to 11.6% (n = 5) (P < 0.001), leading to a significant reduction in use of AADs (100.0% to 11.6%, P < 0.001) and improvement in mean NYHA functional class (2.5 ± 0.5 to 1.4 ± 0.2, P < 0.001). Major intraoperative complications were seen in 4.7% of patients (hemothorax and chylothorax). Of the patients, 81.4% (n = 35) experienced no mortality or major complications over a 1-year follow-up period, with the remaining still within their first year postprocedure. CONCLUSIONS: BCSD is effective for the management of refractory PVCs and ventricular tachycardia who have failed previous ablation therapy.

The benefit of cardioneuroablation to reduce syncope recurrence in vasovagal syncope patients: a case-control study.

BACKGROUND: Adequate and effective therapy for resistant vasovagal syncope patients is lacking and the benefit of cardioneuroablation (CNA) in this cohort is still debated. The aim of this study is to assess the long-term effect of CNA versus conservative therapy (CT) in a retrospectively followed cohort. METHODS: A total of 2874 patients underwent head-up tilt test (HUT) and 554 (19.2 %) were reported as positive, with VASIS type 2B response or > 3 s asystole in 130 patients. After exclusion of 29 patients under 18 years and over 65 years of age, 101 patients were included final analysis. Fifty-one patients (50.4%) underwent CNA and 50 (49.6%) patients received CT. After propensity score matching, 19 pairs of patients were successfully matched. The recurrence rate of syncope was compared between groups. RESULTS: During a median follow-up of 22 months (IQR, 13-35), syncope was seen in 12 (11.8%) cases. In the 19 propensity-matched patients, recurrent syncope was observed in 8 patients in the CT group and in 2 patients in the CNA group, respectively. In mixed effect Cox regression analysis, CNA was associated with less syncope recurrence risk at follow-up (HR 0.23, 95% CI 0.03-0.99, p = 0.049). The 4-year Kaplan-Meier syncope free rate was 0.86 (95% CI, 0.63-1.00) for CNA group and 0.50 (95% CI, 0.30-0.82) for CT group in the matched cohort. CONCLUSIONS: In highly selected patients with HUT-induced cardioinhibitory response, CNA is associated with a significant reduction in syncope recurrence during follow-up when compared to CT.

Ribosomal protein S6 kinase beta-1 gene variants cause hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease with preserved or increased ejection fraction in the absence of secondary causes. Mutations in the sarcomeric protein-encoding genes predominantly cause HCM. However, relatively little is known about the genetic impact of signalling proteins on HCM. METHODS AND RESULTS: Here, using exome and targeted sequencing methods, we analysed two independent cohorts comprising 401 Indian patients with HCM and 3521 Indian controls. We identified novel variants in ribosomal protein S6 kinase beta-1 (RPS6KB1 or S6K1) gene in two unrelated Indian families as a potential candidate gene for HCM. The two unrelated HCM families had the same heterozygous missense S6K1 variant (p.G47W). In a replication association study, we identified two S6K1 heterozygotes variants (p.Q49K and p.Y62H) in the UK Biobank cardiomyopathy cohort (n=190) compared with matched controls (n=16 479). These variants are neither detected in region-specific controls nor in the human population genome data. Additionally, we observed an S6K1 variant (p.P445S) in an Arab patient with HCM. Functional consequences were evaluated using representative S6K1 mutated proteins compared with wild type in cellular models. The mutated proteins activated the S6K1 and hyperphosphorylated the rpS6 and ERK1/2 signalling cascades, suggesting a gain-of-function effect. CONCLUSIONS: Our study demonstrates for the first time that the variants in the S6K1 gene are associated with HCM, and early detection of the S6K1 variant carriers can help to identify family members at risk and subsequent preventive measures. Further screening in patients with HCM with different ethnic populations will establish the specificity and frequency of S6K1 gene variants.

Effects of permanent cardiac pacing on ventricular repolarization when compared to cardioneuroablation.

INTRODUCTION: The impact of cardioneuroablation (CNA) on ventricular repolarization by using corrected QT interval (QTc) measurements has been recently demonstrated. The effects of cardiac pacing (CP) on ventricular repolarization have not been studied in patients with vasovagal syncope (VVS). We sought to compare ventricular repolarization effects of CNA (group 1) with CP (group 2) in patients with VVS. METHODS: We enrolled 69 patients with age 38 ± 13 years (53.6% male), n = 47 in group 1 and n = 22 in group 2. Clinical diagnosis of cardioinhibitory type was supported by cardiac monitoring or tilt testing. QTc was calculated at baseline (time-1), at 24 h after ablation (time-2), and at 9-12 months (time-3) in the follow-up. RESULTS: In the group 1, from time-1 to time-2, a significant shortening in QTcFredericia (from 403 ± 27 to 382 ± 27 ms, p < 0.0001), QTcFramingham (from 402 ± 27 to 384 ± 27 ms, p < 0.0001), and QTcHodges (from 405 ± 26 to 388 ± 24 ms, p < 0.0001) was observed which remained lower than baseline in time-3 (373 ± 29, 376 ± 27, and 378 ± 27 ms, respectively). Although the difference between measurements in time-1 and time-2 was not statistically significant for QTcBazett, a significant shortening was detected between time-1 and time-3 (from 408 ± 30 to 394 ± 33, p = 0.005). In the group 2, there was no time-based changes on QTc measurements. In the linear mixed model analysis, the longitudinal reduction tendency in the QTcFredericia and QTcFramingham was more pronounced in group 1. CONCLUSIONS: Our results demonstrate that CNA reduces QTc levels through neuromodulation effect whereas CP has no effect on ventricular repolarization in patients with VVS.

A randomized study of yoga therapy for the prevention of recurrent reflex vasovagal syncope.

AIMS: Vasovagal syncope (VVS) is a common cardiovascular dysautonomic disorder that significantly impacts health and quality of life (QoL). Yoga has been shown to have a positive influence on cardiovascular autonomics. This study assessed the effectiveness of yoga therapy on the recurrence of VVS and QoL. METHODS AND RESULTS: We randomized subjects with recurrent reflex VVS (>3 episodes in the past 1 year) and positive head-up tilt test to guideline-directed therapy (Group 1) or yoga therapy (Group 2). Patients in Group 1 were advised guideline-directed treatment and Group 2 was taught yoga by a certified instructor. The primary endpoint was VVS recurrences and QoL. Between June 2015 and February 2017, 97 highly symptomatic VVS patients were randomized (Group 1: 47 and Group 2: 50). The mean age was 33.1 ± 16.6 years, male:female of 40:57, symptom duration of 17.1 ± 20.7 months, with a mean of 6.4 ± 6.1 syncope episodes. Over a follow-up of 14.3 ± 2.1 months Group 2 had significantly lower syncope burden compared with Group 1 at 3 (0.8 ± 0.9 vs. 1.8 ± 1.4, P < 0.001), 6 (1.0 ± 1.2 vs. 3.4 ± 3.0, P < 0.001), and at 12 months (1.1 ± 0.8 vs. 3.8 ± 3.2, P < 0.001). The Syncope functional score questionnaire was significantly lower in Group 2 compared with Group 1 at 3 (31.4 ± 7.2 vs. 64.1 ± 11.5, P < 0.001), 6 (26.4 ± 6.3 vs. 61.4 ± 10.7, P < 0.001), and 12 months (22.2 ± 4.7 vs. 68.3 ± 11.4, P < 0.001). CONCLUSION: For patients with recurrent VVS, guided yoga therapy is superior to conventional therapy in reducing symptom burden and improving QoL.

Effect of fluoroscopy frame rate on radiation exposure and in-hospital outcomes in three-dimensional electroanatomic mapping guided procedures.

BACKGROUND: Fluoroscopic imaging involves exposure of the patients and the laboratory staff to ionizing radiation. One of the strategies that reduce such exposure in an electrophysiology laboratory is using a three-dimensional electroanatomic mapping (3D EAM) system for performing these procedures. In this analysis, we have analyzed the effect of fluoroscopy frame rate on the radiation exposure and in-hospital outcomes in ablation procedures performed under 3D EAM guidance. METHODS: We retrospectively analyzed all the ablation procedures performed under 3D EAM guidance at our institute from September 2015 to December 2018. The procedures were divided into two groups based on whether the procedures were performed before (pre) or after (post) January 26, 2018. After January 2018, fluoroscopy was used at a frame rate of 3.75 frames per second (fps). Radiation exposure indices and in-hospital outcomes were compared between the two groups. RESULTS: Ablation procedures included in the analysis were ventricular arrhythmias (n = 192), atrial flutter (115), atrial tachycardia (AT) (43), and atrial fibrillation (AF) (30). Over the study period, there was a significant reduction in procedure time, fluoroscopy time, dose area product, and effective dose (ED) (P < .001). Except for AT and AF ablation procedures, there was a significant reduction in the radiation exposure indices when the "post" group was compared with the "pre" group (P ≤ .02). The decrease in the frame rate had no significant effect on in-hospital outcomes. CONCLUSION: The use of 3D EAM combined with decreasing the fluoroscopy frame rate significantly reduced the total radiation exposure without adversely affecting in-hospital outcomes.

Cardiac perforation complicating cardiac electrophysiology procedures: value of angiography and use of a closure device to avoid cardiac surgery.

BACKGROUND: Computed tomography (CT) is used for the diagnosis of cardiac perforation (CP) although it has significant limitations. We report our experience with angiography to assist in the diagnosis and management of cardiac perforation during electrophysiology procedures. METHODS: Patients with suspected CP after pacemaker lead insertion (temporary = 2, permanent = 2) or during epicardial mapping/ablation (n = 2) were included. All patients underwent initial angiography with repeat study performed post-lead repositioning/withdrawal for the pacemaker cases. Patients with CP due to permanent pacing leads underwent CT comparison. RESULTS: In 4 pacemaker patients, temporary leads caused two acute perforations, permanent active fixation leads caused one subacute right ventricular perforation and one delayed right atrial perforation. CT overdiagnosed CP in one temporary pacemaker patient, and was non-diagnostic in an atrial lead perforation, whereas angiography was accurate in both. Angiography identified an active leak in atrial lead CP, guided percutaneous closure in one case and demonstrated sealing of perforation in all cases. In the 2 epicardial ablation cases, 1 patient underwent surgical repair after a persistent right ventricular perforation, but the other avoided surgery with novel use of an Amplazter® patent ductus arteriosus (PDA) closure device (Abbott, St Paul, MN, USA). CONCLUSIONS: Angiography may be more accurate than CT in the diagnosis of CP. Angiography is easy to perform, can be done acutely, reveals active leaks and can demonstrate sealing of perforations after percutaneous lead repositioning. Utilisation of a PDA closure device may avoid the need for surgery for RV perforation.

Etiology and Outcomes of Syncope in Patients With Structural Heart Disease and Negative Electrophysiology Study.

OBJECTIVES: This study sought to determine the cause of recurrent syncope and clinical outcomes by using the head-up tilt test (HUTT) and an insertable loop recorder (ILR) in patients with structural heart disease (SHD) and negative electrophysiology study (EPS) results. BACKGROUND: Patients with syncope and SHD with negative EPS findings have a low risk of sudden cardiac arrest. Nevertheless, the cause of recurrent syncope and the outcomes in these patients are not well characterized. METHODS: This prospective study evaluated syncope patients with SHD and negative EPS results by using HUTT (with sublingual nitroglycerine [NTG] provocation as needed) and ILR. A total of 41 SHD patients (27 patients [66%] had coronary arterial disease, and 14 patients [34.15%] had dilated cardiomyopathy with mean EF of 42 ± 4.8% [range 30% to 49%]) were included. RESULTS: HUTT findings were positive in 25 patients (61%) in group A and negative in 16 patients (39%) in group B. An ILR was implanted in 21 of 25 group A patients (84%) and in 12 of 16 group B patients (75%), and they were followed for 15 ± 8 months. During follow-up, 17 of 21 patients (81%) in group A and 5 of 12 patients (41.7%) in group B had ILR evidence consistent with reflex syncope. One group B patient had documented atrioventricular block and underwent pacemaker implantation. There were no malignant ventricular arrhythmias or deaths on follow-up. CONCLUSIONS: Reflex syncope is the most common cause of syncope and accounts for approximately 60% of cases in patients with SHD, negative EPS results, left ventricular systolic dysfunction with left ventricular EF >30%, and not in heart failure.

Histopathological Study of Left and Right Atria in Isolated Rheumatic Mitral Stenosis With and Without Atrial Fibrillation.

BACKGROUND: Mitral stenosis (MS) has the highest incidence of atrial fibrillation (AF) in chronic rheumatic valvular disease. There are very few studies in isolated MS comparing histopathological changes in patients with sinus rhythm (SR) and AF. OBJECTIVES: To analyze the histological changes associated with isolated MS and compare between changes in AF and SR. METHODS: This was a prospective study in patients undergoing valve replacement surgery for symptomatic isolated MS who were divided into 2 groups, Group I AF (n = 13) and Group II SR (n = 10). Intra-operative biopsies performed from 5 different sites from both atria were analyzed for 10 histopathologic changes commonly associated with AF. RESULTS: On multivariate analysis, myocytolysis (odds ratio [OR]: 1.48, P = 0.05) was found to be associated with AF, whereas myocyte hypertrophy (OR: 0.21, P = 0.003), and glycogen deposition (OR: 0.43, P = 0.002) was associated with SR. Interstitial fibrosis the commonest change was uniformly distributed across both atria irrespective of the rhythm. CONCLUSION: In rheumatic MS, SR is associated with myocyte hypertrophy whereas AF is associated with myocytolysis. Endocardial inflammation is more common in left atrial appendage irrespective of rhythm. Interstitial fibrosis is seen in >90% of patients distributed in both the atria and is independent of the rhythm. Amyloid and Aschoff bodies are uncommon and the rest of the changes are uniformly distributed across both the atria.

Prolonged Tpeak-end and Tpeak-end/QT ratio as predictors of malignant ventricular arrhythmias in the acute phase of ST-segment elevation myocardial infarction: a prospective case-control study.

BACKGROUND: Prolonged Tpeak-end (the interval from the peak of the T wave to the end of the T wave) and Tpeak-end/QT ratio have been shown to be markers of arrhythmogenesis in various cardiac disorders. OBJECTIVES: The purpose of this study was to evaluate the utility of Tpeak-end and Tpeak-end/QT ratio at admission in patients with acute ST-segment elevation myocardial infarction (STEMI) in predicting malignant ventricular arrhythmias. METHODS: The study group included 50 patients presenting with STEMI, in whom Tpeak-end and Tpeak-end/QT ratio were measured at admission; these patients were monitored for arrhythmias with a continuous electrocardiogram in the intensive care unit for 48 hours, and 50 healthy individuals acted as controls. RESULTS: The Tpeak-end (0.11 ± 0.04 seconds vs 0.08 ± 0.006 seconds; P < .0010) and Tpeak-end/QT ratio (0.30 ± 0.06 vs 0.21 ± 0.02; P < .001) were prolonged in patients with STEMI. Three patients with STEMI who sustained ventricular fibrillation (VF) within 24 hours of admission had prolonged corrected QT interval (0.39 ± 0.04 seconds vs 0.46 ± 0.13 seconds; P = .019), Tpeak-end (0.10 ± 0.02 seconds vs 0.20 ± 0.11 seconds; P < .001), and Tpeak-end/QT ratio (0.26 ± 0.05 vs 0.41 ± 0.09; P < .001) as compared with patients with STEMI without VF. Tpeak-end > 0.1 seconds and Tpeak-end/QT ratio > 0.3 predicted VF with a sensitivity of 100%. However, the Tpeak-end/QT ratio had a higher specificity (82.9% for Tpeak-end/QT ratio vs 44.7% for Tpeak-end) and accuracy (84% for Tpeak-end/QT ratio vs 48% for Tpeak-end). CONCLUSION: Tpeak-end and Tpeak-end/QT ratio are prolonged in patients with STEMI compared with healthy individuals, and Tpeak-end > 0.1 and Tpeak-end/QT ratio > 0.3 predict malignant ventricular arrhythmias within 24 hours of STEMI.