Suspecting and diagnosing transthyretin amyloid cardiomyopathy (ATTR-CM) in India: An Indian expert consensus

Transthyretin cardiac amyloidosis (ATTR-CM) is a rare and under-recognized disorder characterized by the aggregation of transthyretin-derived insoluble amyloid fibrils in the myocardium. Heterogeneity of symptoms at presentation, makes its diagnosis often delayed. An expert panel gathered on a virtual platform across India to conduct a meeting for developing a guiding tool for ATTR-CM diagnosis. The panel recommended younger age (40 years) for suspecting ATTR-CM and thick-walled non-dilated hypokinetic ventricle was considered as one of the important red flags. Electrocardiogram (ECG) and echocardiography (ECHO) findings were recommended as primary tests to raise the suspicion while nuclear scintigraphy and hematological tests were recommended to confirm the diagnosis and rule out amyloid light-chain (AL) amyloidosis. Cardiac magnetic resonance (CMR) and biopsy were recommended in case of ambiguity in the presence of red flags. Considering the lack of expert guidelines in the Indian scenario, a standardized diagnostic algorithm was also proposed.

Interventions in the diagnosis and adoption of pacemaker therapy in sinus node dysfunction patients: Results from the IMPROVE Brady study

Aims: IMPROVE Brady assessed whether a process improvement intervention could increase adoption of guideline-based therapy in sinus node dysfunction (SND) patients. Methods: /Results: IMPROVE Brady was a sequential, prospective, quality improvement initiative conducted in India and Bangladesh. Patients with symptomatic bradycardia were enrolled. In Phase I, physicians assessed and treated patients per standard care. Phase II began after implementing educational materials for physicians and patients. Primary objectives were to evaluate the impact of the intervention on SND diagnosis and pacemaker (PPM) implant. SF-12 quality of life (QoL) and Zarit burden surveys were collected pre- and post-PPM implant. A total of 978 patients were enrolled (57.7 ± 14.8 years, 75% male), 508 in Phase I and 470 in Phase II. The diagnosis of SND and implantation of PPM increased significantly from Phase I to Phase II (72% vs. 87%, P < 0.001 and 17% vs. 32%, P < 0.001, respectively). Pacemaker implantation was not feasible in 41% of patients due to insurance/cost barriers which was unaltered by the intervention. Both patient QoL and caregiver burden improved at 6-months post-PPM implant (P < 0.001). Conclusions: A process improvement initiative conducted at centers across India and Bangladesh significantly increased the diagnosis of SND and subsequent treatment with PPM therapy despite the socio-economic constraints.

Prevalence, clinical profile, and stroke risk of atrial fibrillation in rural Andhra Pradesh, India (the AP-AF study)

The burden of atrial fibrillation (AF) is increasing worldwide. It is often asymptomatic, with stroke being the first manifestation in some. AF burden in the community and the practice of stroke prophylaxis has not been studied in India. The problem might be higher in rural regions due to poor health awareness and challenges to healthcare access. This study aimed to estimate the prevalence of AF, clinical profile and stroke risk in rural India. Methods: This is a community-based cross-sectional study done in rural Andhra Pradesh (AP). Adults from 40 villages formed the study population. We did a door-to door survey to collect information on demographics, and medical history. Electrocardiogram was recorded using a smart phone based Alivecor device. Participants diagnosed with AF underwent echocardiogram. Study cardiologists assessed the cardiovascular risk profile and collected detailed medical history. Results: Fourteen of the 4281 individuals screened had AF (0.3%). The mean age of the sampled population was 44 ± 16.5 years with 56% women. The mean age of participants with AF was 71 ±7.8 years; males were 71%. Except for one, all were non-valvular AF. Majority had a CHA2D2S2Vasc score of 2. Three had history of stroke. Two were on anticoagulant therapy but without INR monitoring. Conclusion: The prevalence of AF is lower in this study compared to studies from the developed countries. Non-rheumatic cardiovascular risk factors were primary causes for AF. Non-adherence to stroke prophylaxis is a major threat that needs to be addressed

Permanent HIS bundle Pacing Feasibility in Routine Clinical Practice: Experience from an Indian Center

There is a paucity of experience regarding His bundle pacing (HBP) at laboratories initially attempting the procedure, especially in the Indian scenario. Patient who underwent HBP were selected for pacing therapy or in lieu of cardiac resynchronization therapy (CRT) at a single center. Among 22 patients attempted, 19 patients underwent successful implant, achieving selective HBP in 14 patients. There was a significant improvement in left ventricular ejection fraction (LVEF) (49.3 ± 9.3 vs. 36.7 ± 9.2) in the LV dysfunction subgroup (n = 6). Over a follow-up of 15 ± 6.5 months, thresholds were stable in all except one patient, and there was no requirement of lead revision. In summary, we found that HBP is a feasible option for achieving physiological pacing.

Catheter ablation for electrical storm in Brugada syndrome: Results of substrate based ablation

Background Brugada syndrome (BrS) is known to cause malignant ventricular arrhythmia (VA) and sudden cardiac death (SCD). Patients with implantable cardioverter defibrillator (ICD) may experience recurrent shocks from ICD. Recent reports indicate that radiofrequency ablation (RFA) in BrS is feasible, and effective. Catheter ablation of premature ventricular complexes (PVCs) triggering VA and substrate modification of right ventricular outflow tract (RVOT) has been described. Methods and results Five patients (4 males, age-23 to 32 years) with BrS and electrical storm (ES) despite being on isoprenaline infusion and cilostazol (phosphodiestrase-3 inhibitor) underwent 3 dimensional electroanatomic mapping and RFA. Ventricular fibrillation was easily inducible in two patients. Voltage map of right ventricle was created in sinus rhythm in all patients. Substrate modification of RVOT was performed endocardially in one patient, both endocardial and epicardial in three and only epicardially in one patient. Brugada pattern gradually resolved over one week in all patients post procedure. These patients completed follow up of median 40 months (1.5–70). One patient had inappropriate shock due to atrial fibrillation, one had an episode of VF and appropriate shock 24 months after the RFA. The remaining four patients had no device therapy or VA in device log on follow up. Conclusion Abnormal myocardial substrate is observed in RVOT among patients with BrS. Substrate modification in these patients may abolish Brugada pattern on the ECG and prevents spontaneous VAs on long term follow up.

KvLQT1 and KCNE1 K+ Channel Gene Polymorphisms in Long QT Syndrome.

Long QT Syndrome (LQTS), a disorder of the cardiac repolarization process with prolongation of the QT interval (QTc ≥0.46 seconds), is an ion-channelopathy. Mutations in either KCNQ1 or KCNE1 genes are susceptible to LQTS. Hence, screening of KCNQ1 and KCNE1 genes is taken up to evaluate the genetic correlation of these genes in Long QT patients of Indian origin. A total of 33 Long QT Syndrome patients and 100 healthy subjects were enrolled for the present study. PCR-SSCP protocol was utilised for screening of KCNQ1 and KCNE1 genes followed by In-silico and statistical analysis. The clinical profile of the Long QT syndrome patients in our study revealed a higher percentage of females with the mean age also being higher in females when compared to males. The two variations (S546S and IVS13+36A>G) in KCNQ1 and the S38G polymorphism in KCNE1 gene were identified and their association with Long QT syndrome is being reported for the first time in Indian population. S546S is located in the KCNQ1 C terminus close to this domain and IVS13+36A>G is located in the intronic region in close proximity to the coding region for C-terminal domain; these may therefore affect the functional protein through non-assembly. S38G leads to a substitution of serine to glycine at 38th amino acid position (S38G) in the transmembrane domain of KCNE1. Our study reports compound heterozygosity/genetic compound ofS546S and IVS13+36A>G of KCNQ1 gene. Haplotype frequencies and linkage disequilibrium analysis revealed a significant association between the three biomarkers. Compound heterozygosity of the polymorphisms influence downstream signalling and KCNQ1- KCNE1 interactions.

Epidemiology and genetics of hypertrophic cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is a heart muscle disorder and is known to be inherited as an autosomal dominant trait. Mutations in several sarcomeric, cytoskeletal and mitochondrial genes have been reported in HCM. Though many cases of HCM are being identified, there is limited data regarding the epidemiology and genetics of HCM in India. Aim: Therefore the present study is envisaged at identifying the epidemiological variables in HCM and fitting a probability model assuming dominant mode of inheritance in HCM, which may in turn shed light on the heterogeneity of this complex disorder. Materials AND Methods: The 127 HCM cases were divided into subtypes based on pattern of hypertrophy. Chi square analysis, odds ratio, probability, relative frequency, penetrance and heritability estimates were calculated apart from epidemiological variables. Results: The HCM subtypes revealed the heterogeneous nature of the condition suggesting that the genes/mutations involved in their pathogenesis are different and this is supported by distinctive differences observed in their probability, heritability and penetrance estimates apart from epidemiological variables. An increased male preponderance was observed with the sex ratio being 3.7:1. The age at onset was found to be more than a decade early in familial cases (30 ± 10 yrs) compared to non familial cases (44 ± 14 yrs). Chi square analysis revealed obstructive HCM to be following autosomal dominant mode of inheritance where as non-obstructive HCM was significantly deviating. The level of deviation was significantly high for the middle onset group compared to early and late onset groups, therefore this group may be considered as an admixture wherein genes/gene modifiers and environmental variables may be contributing to the heterogeneity and this is further supported by odds ratio. Conclusions: The study thus brings out the complexity of HCM and suggests that modes of inheritance other than autosomal dominant may be encountered in a subset of HCM especially in asymmetric septal hypertrophy, apical, concentric and mid cavity obstruction subsets and hence a mixed model of inheritance is the best fit for such complex disorders.

Non-surgical transpericardial catheter ablation of post-infarction ventricular tachycardia.

Non-surgical transpericardial approach for catheter-based epicardial radiofrequency ablation of post-infarction left ventricular tachycardia has been described as an alternative and additive procedure to standard endocardial technique for delivery of radiofrequency energy in difficult situations. We report our initial experience with this approach in three patients of post-infarction recurrent ventricular tachycardia, refactory to multiple antiarrhythmic drugs. Ablation was successful in terminating the tachycardia in two and in modifying the circuit to be amenable for control with single antiarrhythmic drug in one patient. There were no serious acute or long-term complications related to the procedure. Epicardial approach is an effective and safe adjunct to standard endocardial ablative technique for patients of post-infarction ventricular tachycardia.