Catheter ablation of ventricular tachycardia: strategies to improve outcomes.

Catheter ablation of ventricular arrhythmias has evolved considerably since it was first described more than 3 decades ago. Advancements in understanding the underlying substrate, utilizing pre-procedural imaging, and evolving ablation techniques have improved the outcomes of catheter ablation. Ensuring safety and efficacy during catheter ablation requires adequate planning, including analysis of the 12 lead ECG and appropriate pre-procedural imaging. Defining the underlying arrhythmogenic substrate and disease eitology allow for the developed of tailored ablation strategies, especially for patients with non-ischemic cardiomyopathies. During ablation, the type of anesthesia can affect VT induction, the quality of the electro-anatomic map, and the stability of the catheter during ablation. For high risk patients, appropriate selection of hemodynamic support can increase the success of VT ablation. For patients in whom VT is hemodynamically unstable or difficult to induce, substrate modification strategies can aid in safe and successful ablation. Recently, there has been an several advancements in substrate mapping strategies that can be used to identify and differentiate local late potentials. The incorporation of high-definition mapping and contact-sense technologies have both had incremental benefits on the success of ablation procedures. It is crucial to harness newer technology and ablation strategies with the highest level of peri-procedural safety to achieve optimal long-term outcomes in patients undergoing VT ablation.

A case of cardiac sarcoidosis mimicking Brugada syndrome.

A 17-year-old boy was admitted for management of ventricular fibrillation (VF) with intermittent Brugada pattern on ECG. On evaluation, cardiac MRI revealed myocardial scar and mediastinal lymphadenopathy. 18-Fluorodeoxyglucose positron emission tomography scan showed inflammation in the heart, lungs, and lymph nodes. He was diagnosed as a case of cardiac sarcoidosis (CS) and treated with steroids. However, there was a reactivation of cardiac inflammation and the development of a second VF storm. Following catheter ablation, the patient's arrhythmia improved. This report highlights the inflammation due to CS mimicking channelopathic features.

Mapping the Conduction System in Patients Undergoing Transcatheter Device Closure of Perimembranous Ventricular Septal Defect: A Proof-of-Concept Study.

Earlier studies that investigated the relation of atrioventricular (AV) conduction system to perimembranous ventricular septal defect (pmVSD) were based on cardiopathological specimens. To study the relationship of conduction system to pmVSD using 3-dimensional electroanatomic mapping system (EAMS) in patients undergoing device closure. Fifteen consecutive cases of pmVSD from January 2014 to July 2017 (age > 2 years and weight > 8 kg) were included in the study. The course of conduction system and its relationship with the pmVSD was mapped before and after device closure, with the use of EAMS. Median age and weight of the cohort was 10 years (range 4-21 years) and 25 kg (range 13-55) respectively. Device implantation was successful in all patients except 1. The course and relation of the conduction system were posteroinferior to the pmVSD in all cases (100%), and away from the defect in 67% (10/15). In patient with baseline RBBB, the right-sided conduction system was in close proximity to the pmVSD. Two patients had part of left-sided conduction system in close proximity to pmVSD or device edges. Two patients developed RBBB following device deployment, which reverted to normal on follow up. No patient developed high grade AV block during the median follow-up of 34 months (range 24-62). This experimental study has shown the feasibility of 3D EAM of conduction system during device closure of pmVSD. This novel concept can be utilized to understand the anatomy of conduction system in other congenital heart diseases.

Mitral valve tuberculoma: Role of sequential multimodality imaging of an unusual intracardiac mass.

We present an unusual intracardiac mass posing a diagnostic dilemma. A middle-aged male patient was referred for workup of a symptomatic cardiac mass involving the mitral valve. Multimodality imaging consisting of cardiac magnetic resonance (CMR) imaging and 18F-fluorodeoxyglucose positron emission computerized tomography (18FDG-PET) scan was utilized to further characterize the mass after initial echocardiographic identification. CMR imaging identified extent of valvular mass into the interatrial septum and basal portion of the interventricular septum. On 18FDG-PET scan, the intracardiac mass was found to be metabolically active. It also revealed the presence of FDG avid lymph nodes in the abdomen. Histology of the lymph node revealed active granulomatous inflammation suggestive of tuberculosis. Treatment with antitubercular therapy resulted in resolution of the mass and mitral regurgitation, avoiding surgery.

Epicardial ablation of focal atrial tachycardia arising from left atrial appendage in children.

Focal left atrial tachycardia (FLAT) although a common cause of supraventricular tachycardia(SVT) among children, the one's arising from left atrial appendage (LAA) present a unique challenge for successful ablation because of anatomical location. We present two children with FLAT arising from the epicardial LAA, successfully mapped and ablated through percutaneuous epicardial approach.

Inappropriate Detection of a Supraventricular Tachycardia as Dual Tachycardia by the PR Logic™ Algorithm.

Tachycardia detection and therapy algorithms in Implantable Cardioverter-Defibrillators (ICD) reduce, but do not eliminate inappropriate ICD shocks. Awareness of the pros and cons of a particular algorithm helps to predict its utility in specific situations. We report a case where PR logic™, an algorithm commonly used in currently implanted ICDs to differentiate supraventricular tachycardia (SVT) from ventricular tachycardia resulted in inappropriate detection and shock for an SVT, and discuss several solutions to the problem.

Novel mutations of KCNQ1 in Long QT syndrome.

BACKGROUND: Autosomal recessive Long QT syndrome is characterized by prolonged QTc along with congenital bilateral deafness depends on mutations in K(+) channel genes. A family of a Long QT syndrome proband from India has been identified with novel indel variations. METHODS: The molecular study of the proband revealed 4 novel indel variations in KCNQ1. In-silico analysis revealed the intronic variations has led to a change in the secondary structure of mRNA and splice site variations. The exonic variations leads to frameshift mutations. DNA analysis of the available family members revealed a carrier status. RESULTS AND CONCLUSION: It is thus predicted that the variations may lead to a change in the position of the splicing enhancer/inhibitor in KCNQ1 leading to the formation of a truncated S2-S3 fragment of KCNQ1 transmembrane protein in cardiac cells as well as epithelial cells of inner ear leading to deafness and aberrant repolarization causing prolonged QTc.

An in silico analysis of troponin I mutations in hypertrophic cardiomyopathy of Indian origin.

Hypertrophic Cardiomyopathy (HCM) is an autosomal dominant disorder of the myocardium which is hypertrophied resulting in arrhythmias and heart failure leading to sudden cardiac death (SCD). Several sarcomeric proteins and modifier genes have been implicated in this disease. Troponin I, being a part of the Troponin complex (troponin I, troponin C, troponin T), is an important gene for sarcomeric function. Four mutations (1 novel) were identified in Indian HCM cases, namely, Pro82Ser, Arg98Gln, Arg141Gln and Arg162Gln in Troponin I protein, which are in functionally significant domains. In order to analyse the effect of the mutations on protein stability and protein-protein interactions within the Troponin complex, an in silico study was carried out. The freely available X-ray crystal structure (PDB ID: 1JIE) was used as the template to model the protein followed by loop generation and development of troponin complex for both the troponin I wild type and four mutants (NCBI ID: PRJNA194382). The structural study was carried out to determine the effect of mutation on the structural stability and protein-protein interactions between three subunits in the complex. These mutations, especially the arginine to glutamine substitutions were found to result in local perturbations within the troponin complex by creating/removing inter/intra molecular hydrogen bonds with troponin T and troponin C. This has led to a decrease in the protein stability and loss of important interactions between the three subunits. It could have a significant impact on the disease progression when coupled with allelic heterogeneity which was observed in the cases carrying these mutations. However, this can be further confirmed by functional studies on protein levels in the identified cases.

Genetic variations of α-cardiac actin and cardiac muscle LIM protein in hypertrophic cardiomyopathy in South India.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a disease of the heart muscle, with an autosomal dominant mode of inheritance. It is also known as the 'disease of the sarcomere', and is a major cause of morbidity and mortality worldwide. Mutations in the sarcomeric genes have been largely implicated in the manifestation of HCM. Modifier genes and environmental factors, along with causative mutation, add to the cumulative effect of the disease. METHODS: In the present study, the role of the cardiac actin gene and the cardiac muscle LIM protein as contributors to HCM - through genetic variation - has been elucidated by screening the entire coding region in 100 control and 100 HCM subjects through polymerase chain reaction-based single-strand conformation polymorphism analysis and direct sequencing. RESULTS: The authors could not find any novel or reported exonic variations in any of the genes in the studied population; however, intronic variations were revealed in the cardiac actin gene through direct sequencing. A case of compound heterozygosity was observed in a patient with a variation in intron 1, along with a novel heterozygous mutation in exon 7 (S215L) of α-tropomyosin. CONCLUSIONS: The particular genes are highly conserved, and account for only 1.5% of HCM cases. They do not seem to play a major role in the genesis of HCM in the present population, thus confirming earlier reports of conserved sequences and ethnicity.

Novel mutations in arrhythmogenic right ventricular cardiomyopathy from Indian population.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive condition with right ventricular myocardium being replaced by fibro-fatty tissue. The spectrum of the expression may range from benign palpitations to the most malignant sudden death. Most of the mutations identified for the condition are localized in desmosomal proteins although three other nondesmosomal genes (cardiac ryanodine receptor-2, TGF-ß3, and TMEM43) have also been implicated in ARVC. Both desmosomal and nondesmosomal genes were screened in a set of patients from local population. MATERIALS AND METHODS: A set of 34 patients from local population were included in this study. Diagnosis was based on the criteria proposed by task force of European Society of Cardiology/International Society and Federation of Cardiology. Polymerase chain reaction-based single-strand conformation polymorphism analysis was carried out, and samples with abnormal band pattern were commercially sequenced. RESULTS: Screening of cardiac ryanodine receptor revealed an insertion of a base in the intronic region of exon-28 in a patient, leading to a creation of a cryptic splice site. Screening of plakohilin-2 for mutations revealed an abnormal band pattern in three patients. Two of them had similar abnormal band pattern for exon-3.1. Sequencing revealed a novel 2 base pair deletion (433_434 delCT), which would lead to premature truncation of the protein (L145EfsX8). Another patient showed abnormal band pattern for exon-3.2 and sequencing revealed a missense mutation C792T leading to amino acid change P244L, in N-terminal, and this substitution may cause disturbances in the various protein-protein interactions. CONCLUSION: This study reports novel cardiac ryanodine receptor (RyR-2) mutations and Pkp-2 for the first time from Indian population.

Epidemiology of sudden cardiac death in rural South India - insights from the andhra pradesh rural health initiative.

BACKGROUND: Sudden cardiac death (SCD) is a common initial presentation of coronary artery disease (CAD). Despite the growing epidemic of CAD in India, the epidemiology of SCD is largely unknown. OBJECTIVE: The objective of the study was to define the prevalence and determinants of sudden cardiac deaths in rural South India. METHODS: Prospective mortality surveillance was conducted in 45 villages (180,162 subjects) in rural South India between January 2006 and October 2007. Trained multipurpose health workers sought to do verbal autopsies within 4 weeks of any death. Detailed questionnaires including comorbidities and circumstances surrounding death were recorded. SCD was adjudicated using the modified Hinkle-Thaler classification. RESULTS: A total of 1916 deaths occurred in the study population over the 22 month time period and verbal autopsy was obtained in 1827 (95%) subjects. Overall mean age of the deceased was 62 ± 20 years and 1007 (55%) were men. Cardiovascular and cerebrovascular diseases together accounted for 559 deaths (31%), followed by infectious disease (163 deaths, 9%), cancer (126 deaths, 7%) and suicide (93 deaths, 5%). Of the 1827 deaths, after excluding accidental deaths (89 deaths), 309 deaths (17%) met criteria for SCD. Cardiovascular disease was the underlying causes in the majority of the SCD events (231/309 (75%)). On multivariate analyses, previous MI/CAD (p < 0.001, OR 14.25), hypertension (p < 0.001, OR 1.84), and age groups between 40-60 yrs (p=0.029) were significantly associated with SCD. CONCLUSION: Sudden cardiac death accounted for up to half of the cardiovascular deaths in rural Southern India. Traditional cardiovascular risk factors were strongly associated with SCD.

Ventricular dyssynchrony patterns in left bundle branch block, with and without heart failure.

BACKGROUND: Assessment of ventricular dyssynchrony in patients with heart failure is used for selecting candidates for cardiac resynchronization therapy (CRT). The patterns of regional distribution of dyssynchrony in a population with LBBB with and without heart failure have not been well delineated. This aspect forms the object of the study. METHODS: Tissue Doppler Imaging (TDI) data of consecutive patients with heart failure and LBBB (Group A) was compared with those with LBBB and normal LV function (Group B). All patients had standard 2D-echocardigraphic examination and TDI. Tissue velocity curves obtained by placing sample volumes in opposing basal and mid segments of septal, lateral, inferior, anterior and posterior walls were analyzed. Inter ventricular dyssynchrony (IVD) was assessed by the difference between aortic and pulmonary pre ejection intervals. LV dyssynchrony (LVD) was assessed by the difference in times to peak velocity. A delay of >/= 40 msec was considered significant for presence of IVD and LVD. RESULTS: There were 103 patients in Group A and 25 in Group B. The mean QRS duration and PR intervals respectively were 146 +/- 25 vs. 152+/-20 msec and 182+/- 47 vs. 165+/-36 msec. (p=NS) LVEF in the 2 groups were (32 +/- 6 % vs. 61+/- 11%; p< 0.01). Prevalence of dyssynchrony in the HF group compared to Group B was 72% vs. 16%, (P< 0.01). Lateral wall dyssynchrony in the 2 groups was 37% vs. 0% (p< 0.01) while septal dyssynchrony was 16% vs. 16% (p- NS). CONCLUSIONS: 72% of heart failure patients with LBBB have documented dyssynchrony on TDI, which has a heterogeneous regional distribution. Dyssynchrony may be seen in LBBB and normal hearts but it is does not involve the lateral wall. Septal dyssynchrony in heart failure patients may not have the same significance as lateral wall delay.

Comparison of Uhl's anomaly, right ventricular outflow tract ventricular tachycardia (RVOT VT) & arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) with an insight into genetics of ARVD/C.

Among the right ventricular conditions, Uhl's anomaly, arrhythmogenic right ventricular dysplasia / cardiomyopathy (ARVD/C) and right ventricular outflow tract ventricular tachycardia (RVOT VT) are disorders that exhibit pathogenic changes involving the right ventricular (RV) myocardium, and are expected to be severe or milder forms of the same condition. The review focuses on the aspect whether the three RV disorders are a spectrum of the same disease. ARVD/C is the only condition among these to be genetically well characterized. Also, variations in the clinical expression of ARVD/C due to the genetic heterogeneity are examined. Based on clinical manifestations, age at onset, gender ratio and the possible molecular mechanisms implicated, Uhl's anomaly, ARVD/C and RVOT VT may be considered as separate entities. Further, to differentiate between the three RV disorders, the molecular studies on ARVD/C might be helpful. An attempt was made to differentiate between the eleven different types of ARVD/Cs based on clinical symptoms presented including the progression of the disease to the left ventricle, ventricular arrhythmias and clinical characteristics like ECG, SAECG, ECHO and histopathological studies.

Hemodynamic benefit of multiple programmable pacing configurations in patients with biventricular pacemakers.

INTRODUCTION: Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure. However, one-third of the patients fail to improve with this therapy. Stimulation with different left ventricular stimulation (LVS) configurations has been used to prevent diaphragmatic capture and to decrease the capture thresholds. We evaluated the hemodynamic effects of different LVS configurations using echocardiography. METHODS: Recipients of CRT systems capable of multiple LVS configurations were studied. Biventricular capture was confirmed for each polarity and echocardiographic measurements were made. The atrioventricular and interventricular delays were optimized and kept constant during the study. The cardiac output (CO), myocardial performance index (MPI), and severity of mitral regurgitation (MR) were recorded for all LVS configurations and compared for the best and the worst configurations, determined by CO. RESULTS: We studied 10 men and four women, 55 +/- 13 years of age on average. The CO and MPI changed significantly by changing the LVS configurations. The difference in CO ranged from 0.3 to 1.5 L, and seven patients (50%) showed > or =20% difference in CO between best and worst LVS configurations. Severity of MR decreased by > or =1 grade in nine patients, while in two patients MR worsened despite improvement in CO. CONCLUSIONS: Changing the LVS configuration changes hemodynamic function in some CRT system recipients.

Clinical picture of arrhythmogenic right ventricular dysplasia / cardiomyopathy patients from Indian origin.

OBJECTIVE: Among the inherited cardiomyopathies, Arrhythmogenic right ventricular dysplasia/cardiomyopathy is unique with a peculiar pathology of fibro-fatty replacement. Studies have been carried out all over the world and several groups have reported clinical heterogeneity in manifestation of ARVD/C related symptoms. Present study is an attempt to identify the clinical profile of ARVD/C patients from Asian Indian origin. METHODS: 31 patients in the span of three years were diagnosed with ARVD/C. Diagnosis was based on proposed task force criteria. RESULTS: The mean age at diagnosis was 32.9 +/- 16.4 years with slight tilt in male to female ratio (1.46). About 80% cases had palpitations, syncope in 45.16% and dyspnea in 22.5%, whereas 16% of patients were asymptomatic. About 50% of patients revealed a family history of confirmed ARVD/C or sudden death of a family member without any known cause. ECG showed T-wave inversion in about 60% cases, prolongation of QRS was observed in 20% cases. RV dilatation was observed in 80% of patients and 66.7% showed systolic dysfunction. RV free wall motion abnormalities were found in 33% patients. Most of the early onset cases with less than 30 years of age showed family history indicative of ARVD/C. Familial study in three patients indicated early onset of condition in younger generations in two families. CONCLUSIONS: ARVD/C in India shows relatively early age at onset when compared with other Asian populations with more than half of patients showing the disease below the age of 30 years. History in most of the early onset cases revealed family history indicating strong genetic influence.

Genetic variation in exon 5 of troponin - I gene in hypertrophic cardiomyopathy cases.

BACKGROUND: Cardiomyopathies are a heterogeneous group of heart muscle disorders and are classified as 1) Hypertrophic Cardiomyopathy (HCM) 2) Dilated cardiomyopathy (DCM) 3) Restrictive cardiomyopathy (RCM) and 4) Arrhythmogenic right ventricular dysplasia (ARVD) as per WHO classification, of which HCM and DCM are common. HCM is a complex but relatively common form of inherited heart muscle disease with prevalence of 1 in 500 individuals and is commonly associated with sarcomeric gene mutations. Cardiac muscle troponin I (TNNI-3) is one such sarcomeric protein and is a subunit of the thin filament-associated troponin-tropomyosin complex involved in calcium regulation of skeletal and cardiac muscle contraction. Mutations in this gene were found to be associated with a history of sudden cardiac death in HCM patients. AIM: Therefore the present study aims to identify for mutations associated with troponin I gene in a set of HCM patients from Indian population. MATERIALS AND METHODS: Mutational analyses of 92 HCM cases were carried out following PCR based SSCP analysis. RESULTS: The study revealed band pattern variation in 3 cases from a group of 92 HCM patients. This band pattern variation, on sequencing revealed base changes, one at nt 2560 with G>T transversion in exon-5 region with a wobble and others at nt 2479 and nt 2478 with G>C and C>G transversions in the intronic region upstream of the exon 5 on sequencing. Further analysis showed that one of the probands showed apical form of hypertrophy, two others showing asymmetric septal hypertrophy. Two of these probands showed family history of the condition. CONCLUSIONS: Hence, the study supports earlier reports of involvement of TNNI-3 in the causation of apical and asymmetrical forms of hypertrophy.

Successful ablation of aortic cusp tachycardia from right ventricle outflow tract using a superior approach.

We report a case of successful radiofrequency catheter ablation of idiopathic aortic cusp tachycardia arising close to right coronary artery ostium performed safely from the right ventricular outflow tract (RVOT) by unconventional superior approach. As both activation mapping and pace mapping of the tachycardia were suboptimal from transfemoral RV endocardial approach, retrograde aortic mapping was performed. This revealed that the site of ventricular tachycardia (VT) origin to be on the right coronary sinus. Due to close proximity of VT site of origin and the right coronary ostium, an alternate approach to ablation was considered. We approached this area easily and successfully ablated the VT with an ablation catheter introduced from a right-sided superior approach (jugular vein). The patient has remained free from recurrences over an 18 month follow-up period.