A Novel TPM1 Mutation Causes Familial Hypertrophic Cardiomyopathy in an Indian Family: Genetic and Clinical Correlation.

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterised by unexplained left ventricular hypertrophy in the absence of abnormal loading conditions. The global prevalence of HCM is estimated to be 1 in 250 in the general population. It is caused due to mutations in genes coding for sarcomeric proteins. α-tropomyosin (TPM1) is an important protein in the sarcomeric thin filament which regulates sarcomere contraction. Mutations in TPM1 are known to cause hypertrophic cardiomyopathy, dilated cardiomyopathy and left ventricular non-compaction. Mutations in TPM1 causing hypertrophic cardiomyopathy are < 1%. However, some high-risk mutations causing sudden cardiac death are also known in this gene. We present a case of a novel heterozygous TPM1 mutation, NM_001018005.2:c.203A>G, p.Gln68Arg; co-segregating in an Indian family with hypertrophic cardiomyopathy. Our report expands the mutational spectrum of HCM due to TPM1 and provides the correlated cardiac phenotype.

A histological study of the atria in patients with isolated rheumatic mitral regurgitation with and without atrial fibrillation.

BACKGROUND: There is a high incidence of atrial fibrillation (AF) in patients with isolated rheumatic mitral regurgitation (MR). The histopathologic changes in the atria of patients with isolated rheumatic MR with and without AF are unknown. OBJECTIVES: We aimed to determine the histological findings in patients with isolated severe rheumatic MR with and without AF. METHODS: Patients with severe isolated rheumatic MR undergoing valve replacement surgeries underwent endocardial biopsies from right atrial appendage, left atrial appendage, right free wall, left free wall, left posterior wall, and mitral valve. Group I consisted of patients in sinus rhythm (SR), and Group II included patients with AF. We analyzed and compared these 10 histological features in the biopsies of patients in Groups I and II. RESULTS: Of the 25 patients, 12 were in Group I and 13 in Group II. In Group I, patients had severe myocyte hypertrophy (60% vs. 18%, p = .04) that was significantly more in the right atrium (22.7% vs. 11.4%, p = .059). Interstitial adipose tissue deposition was more common in Group I (30% vs. 25%, p = .06). Interstitial fibrosis was evenly distributed at all sites without significant difference between the two groups. Group II patients had a higher prevalence and severity of vacuolar degeneration (91% vs. 60%, p = .09). CONCLUSIONS: Patients with isolated severe rheumatic MR and AF have more vacuolar degeneration in the atrial tissue. Patients with SR have myocyte hypertrophy and interstitial adipose tissue deposition. Interstitial fibrosis is uniformly distributed in patients in SR and AF.

Angiography-guided mid/high septal implantation of ventricular leads in patients with congenital heart disease.

BACKGROUND: Conduction system pacing prevents pacing-induced cardiomyopathy, but it can be challenging to perform in patients with congenital heart disease (CHD), and mid/high septal lead implantation is an alternative. This study aimed to assess intraprocedural angiography's utility as a guide for mid/high-septal lead implantation in CHD patients. METHODS: The study subjects were CHD patients with Class I/IIa indications for permanent pacemaker implantation. To guide septal lead implantation, we performed an intraprocedural right ventricular angiogram in anteroposterior, 40° left anterior oblique, and 30° right anterior oblique. The primary endpoint was the lead tip in the mid/high septum on computed tomography (CT). The secondary endpoints were complications and systemic ventricular function on follow-up. RESULTS: From January 2008 to December 2018, we enrolled 27 patients (mean age: 30 ± 20 years; M:F 17:10) with CHD (unoperated: 20, operated: 7). The mean paced QRS duration was 131.7 ± 5.8 ms, and CT done in 22/27 patients confirmed the lead tip in the mid-septum in 16, high septum in 5, and apical septum in 1 patient. There were no procedural complications, and during a mean follow-up of 58 ± 35.2 months, there was no significant change in the systemic ventricular ejection fraction (56.4 ± 8.3% vs 53.9 + 5.9%, P = .08). Two patients with Eisenmenger syndrome died because of refractory heart failure. CONCLUSIONS: Intraprocedural angiography is safe and useful to guide mid/high-septal lead implantation in CHD patients. Mid/high septal lead position preserves systemic ventricular function in patients with CHD during medium-term follow-up.

Computed tomography validated right ventricular mid-septal lead implantation using right ventricular angiography.

BACKGROUND: Right ventricular (RV) mid-septal pacing has been proposed as an alternative to RV apical pacing. Fluoroscopic and electrocardiogram criteria are unreliable for predicting the RV mid-septal lead position. This study aimed to define the optimal RV mid-septal pacing site using RV angiography. METHODS: We randomized patients undergoing pacemaker implantation (PPM) to the RV angiography-guided group (Group A) or conventional fluoroscopy-guided group (Group F). In Group A, we performed an angiogram in right anterior oblique (RAO 30°), left anterior oblique (LAO 40°), and left lateral (LL) views. We made a 5-segment grid in RAO 30° and LL views and a 3-segment grid in LAO 40° on the angiographic silhouette to define the lead position. Computed tomography (CT) was used to validate the lead tip position in both groups. RESULTS: We enrolled 53 patients (Group A: 26, Group F: 27) with a mean age of 55.9 ± 12.2 years. CT images validated the lead position in the mid-septum (Group A, 23 [88.5%]; Group F, 11 [40.7%], P = .0003) and anteroseptal (Group A, 3 [11.5%]; Group F, 5 [18.5%], P = .24). In Group F, the lead was in the anterior wall in 9 patients (33.3%) and the right ventricular outflow tract in 2 (7.4%) patients and none in these two positions in Group A. The lead tip in segment one on the angiographic 5-segment grid in RAO 30° and LL views indicated a mid-septal lead position on CT. CONCLUSIONS: RV angiography is safe and may be used to confirm the mid-septal lead position during PPM.

Transvenous pacing in complex post-operative congenital heart disease guided by angiography: A case report.

Transvenous pacing in patients with postoperative complex congenital heart disease (CHD) can be challenging and pose technical challenges to lead placement because of the complex anatomy, distortions produced by the surgical procedures, and the altered relationship of cardiac chambers. We describe the utility of angiography for transvenous dual chamber pacemaker implantation in a post-operative complex congenital heart disease.

Short-term response to phenytoin sodium in Andersen-Tawil syndrome-1 with a cardiac-dominant phenotype.

BACKGROUND: Andersen-Tawil syndrome (ATS) is a rare familial periodic paralysis that typically also affects the heart and skeletal system. Ventricular arrhythmias (VAs) are profound and difficult to control, but minimally symptomatic. In this report, we describe an atypical phenotype of ATS in two related families. We also report our experience with phenytoin sodium for the control of resistant VAs in these patients. METHODS AND RESULTS: Between 2014 and 2018, seven siblings were diagnosed with ATS on the basis of cardiac arrhythmias and genetic evaluation. Heterozygous mutation with c.431G > C (p.G144A) in exon 2 of KCNJ2 gene was observed in all patients. Characteristic cardiac manifestations were noted in all patients but periodic paralysis or objective neurological involvement was distinctly absent. Phenytoin was considered for control of symptomatic VA in three patients. Intake of oral phenytoin (5 mg/kg/day) for 1 month completely suppressed VA (<1% in 24-h Holter monitoring) in two patients, and significantly in the third (8% per 24 h) patient. Phenytoin was well-tolerated in all three patients. CONCLUSIONS: We describe a cardiac-predominant phenotype in ATS. ATS should be suspected in patients with typical cardiac manifestations even in the absence of periodic paralysis. Our initial experience with short-term use of phenytoin for control of resistant VAs is encouraging.

Fosphenytoin for control of electrical storm in acute myocardial infarction and Purkinje fiber-mediated arrhythmias.

BACKGROUND: Purkinje fiber-mediated arrhythmias in the setting of acute myocardial infarction are poorly responsive to conventional antiarrhythmic therapy, increases overall mortality and often requires radiofrequency ablation (RFA) for control. In this study, we report the use of intravenous Fosphenytoin for the control of arrhythmic storm in patients with acute myocardial infarction. METHODS AND RESULTS: Six patients with acute myocardial infarction (5 AW/1 LW) and Purkinje-triggered ventricular arrhythmias refractory to conventional antiarrhythmics were treated with intravenous Fosphenytoin before considering RFA. Arrhythmia control was obtained in all patients after the initial bolus dose. Breakthrough episodes were seen in 5/6 within 24-36 hours of the initial bolus, necessitating a second bolus. Complete arrhythmia control was obtained in all patients within 72 hours and 5/6 patients were successfully discharged from the hospital. One patient succumbed to sepsis in hospital while another patient succumbed to Sub Dural Hematoma after 3 months. CONCLUSIONS: Intravenous Fosphenytoin should be considered before RFA for control of Purkinje fiber-mediated refractory arrhythmias in acute myocardial infarction patients.

'Optimized' LV only pacing using a dual chamber pacemaker as a cost effective alternative to CRT.

BACKGROUND: Cardiac Resynchronization therapy (CRT) remains largely under-used in developing countries owing to the high cost of therapy. In this pilot study, we explore 'optimized' Left Ventricle Only Pacing (LVOP) as a cost effective alternative to cardiac resynchronization therapy in selected patients with heart failure. HYPOTHESIS: In economically poorer patients with heart failure, left bundle branch block (LBBB) and intact AV node conduction, synchronization can be obtained using a dual chamber pacemaker (leads in right atrium and Left ventricle) with the help of 2D strain imaging. METHODS AND RESULTS: 4 patients underwent LVOP for symptomatic heart failure. Post procedure 'optimization' was done using 12 lead electrocardiography and 2D- Strain imaging. Difference between Time to Peak longitudinal strain and Aortic valve Closure (Diff TPL-AC) was calculated for each segment at different AV delays and the AV delay with the smallest Diff TPL-AC was programmed. The mean AV delay that resulted in electrical and mechanical synchrony was 150 ms. After a mean follow up of 6 months, all patients had improved by at least 1 NYHA class. The mean reduction in QRS duration post procedure was -54.5 ± 22.82 ms and the mean improvement in EF was 7 ± 2.75%. CONCLUSION: Optimized LVOP using 2D strain and ECG can be a cost-effective alternative to CRT in patients with LBBB, heart failure and normal AV node conduction.

Evaluation of baseline ECG in patients undergoing Oral Flecainide Challenge test for suspected Brugada Syndrome: An analysis of lead II.

BACKGROUND AND OBJECTIVES: We analyzed Lead II in patients undergoing an Oral Flecainide Challenge test (FCT), to identify any pointers that could predict a positive FCT and thereby help in recognition of latent BS. METHODS: The following parameters in lead II were retrospectively analyzed from the pre-test ECG in 62 patients undergoing FCT for suspected BS: The presence or absence of S waves, S wave amplitude, duration and upslope duration; J point parameters- Early repolarization, QRS notch, and QRS Slur; ST segment parameters-lack of isoelectric ST segment, ST duration and QT interval. RESULTS: 48 had positive FCT (Group-1) while 14 were negative for FCT(Group-2). Lack of an isoelectric ST segment (50% vs 14.29%, p = 0.018) and slurring of QRS (33.33% vs 0%, p = 0.014) was more common in Group-1 than Group-2. Group-1 had shorter ST segment duration (median 81.5 (IQR 64-103.5) vs 110 (IQR 90-132), p = 0.002) and shorter ST: QT ratio (median 0.28 (IQR 0.22-0.35) vs 0.23 (0.18-0.27), p = 0.007). QRS notch/depressed J point (87.5%), QRS slur (100%), and lack of isoelectric ST segment (92.31%) had high sensitivity for predicting an inducible Type 1 Brugada pattern. Combining two parameters- ST: QT ratio<0.24 and lack of isoelectric ST segment-considerably improved the specificity (73.3%), and the positive predictive value of the test to 76%. The results remained accurate when validated in a small prospective cohort. CONCLUSION: Shortened ST segment in Lead II, lack of isoelectric ST segment, slurred QRS and ST/QT ratio <0.24 are predictive of underlying Brugada pattern in baseline ECG.

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.

Diagnostic dilemma with a narrow QRS regular rhythm at normal rates in a patient with corrected transposition of great arteries.

A 35 year old male, known case of corrected transposition of great arteries presented with exertional dyspnea and recurrent pre-syncope. 12 lead electrocardiogram revealed a regular rhythm at 75 beats per minute, P waves occurring on the upstroke of T waves and apparent 1:1 P-QRS relationship. The possibilities to be considered - complete AV block with junctional escape, junctional rhythm with 1:1 retrograde conduction, junctional rhythm with isorhythmic AV dissociation and prolonged PR interval have been discussed.

Transvenous permanent pacemaker implantation in dextrocardia: technique, challenges, outcome, and a brief review of literature.

AIMS: Dextrocardia is a rare congenital anomaly. Pacemaker implantation in dextrocardia can be challenging because of the distorted anatomy and associated anomalies. The literature regarding implantation of pacemaker in dextrocardia is scarce. METHODS AND RESULTS: The study involved retrospective analysis of records of patients with dextrocardia who had undergone pacemaker implantation between January 2006 and July 2013 from a single centre. Six patients with dextrocardia (five males and one female) underwent permanent pacemaker implantation (PPI) between January 2006 and July 2013. Of them, three had situs solitus dextrocardia and three situs inversus dextrocardia. All three patients with situs solitus dextrocardia had associated corrected transposition of great arteries. The indication for pacemaker implantation was symptomatic complete atrioventricular (AV) block in four, high-grade AV block in one, and sinus node dysfunction in one patient. A favourable outcome was noted during a mean follow-up of 3.9 years (4 months to 7 years) with one patient needing a pulse generator replacement. CONCLUSION: Permanent pacemaker implantation in dextrocardia can be challenging because of the distorted anatomy. Use of a technique employing angiography to delineate chamber anatomy and relationship can assist the operator during such difficult PPIs. The medium- and long-term survival after a successful pacemaker implantation in dextrocardia is favourable.

Transjugular percutaneous transvenous mitral commissurotomy (PTMC) using conventional PTMC equipment in rheumatic mitral stenosis with interruption of inferior vena cava.

BACKGROUND: Isolated interruption of the inferior vena cava (IVC) is a rare anomaly. We report a series of 4 cases of isolated interruption of the IVC that coexisted with rheumatic mitral stenosis. Interrupted IVC precludes the use of the femoral approach to percutaneous transseptal mitral commissurotomy (PTMC). We describe the jugular approach to PTMC in such cases using conventional PTMC equipment. METHODS AND RESULTS: The mean pre-PTMC mitral valve area was 0.85 cm². Septal puncture was done through the right internal jugular vein with a pediatric Brokenborough needle (Medtronic) using the levophase of pulmonary artery angiogram and the pigtail as guide. The mitral valve was crossed successfully in all cases and appropriately sized Accura balloons (Vascular Concepts) were used for incremental dilatations. Successful balloon dilatation was achieved in all 4 cases (mean post-PTMC mitral valve area of 1.85 cm²) with no complications. CONCLUSION: The jugular approach appears to be a safe and effective alternative in cases of rheumatic mitral stenosis with IVC anomalies, thereby preventing an otherwise necessary surgery.

Preventing a central nervous system catastrophe in a case of Takayasu's arteritis presenting with critical stenosis of all three arch vessels.

Multifocal and bilateral involvement of the arch vessels is a common presentation of Takayasu's arteritis. Endovascular stenting of multiple supra aortic lesions in Takayasu's arteritis has been described scarcely in literature. We describe the management of a case of Takayasu's arteritis who presented with recurrent vertebro-basilar symptoms and a single surviving arch vessel. Whether routine revascularization of all three vessels is superior to symptom driven revascularization of individual lesions remains uncertain. The abundant collateral blood flow; the problems with stenting during the acute phase of the disease; the risk of restenosis that is considerably higher than atherosclerotic lesions; and the chances of progression of the disease have to be taken into account during endovascular revascularization of multiple supra aortic arch vessels.