Effect of Flecainide on Multifocal Ectopic Purkinje-Related Premature Contractions in an R814W SCN5A Carrier.

Multifocal ectopic Purkinje-related premature contraction (MEPPC) is an autosomal dominant SCN5A channelopathy characterized by frequent multiform premature ventricular contractions originating from the His-Purkinje system. We present a patient with an MEPPC phenotype whose genetic testing identified a pathogenic SCN5A (HGNC:10593) variant amenable to precision antiarrhythmic therapy with flecainide.

Identification of high-risk imaging features in hypertrophic cardiomyopathy using electrocardiography: A deep-learning approach.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) are at risk of sudden death, and individuals with ≥1 major risk markers are considered for primary prevention implantable cardioverter-defibrillators. Guidelines recommend cardiac magnetic resonance (CMR) imaging to identify high-risk imaging features. However, CMR imaging is resource intensive and is not widely accessible worldwide. OBJECTIVE: The purpose of this study was to develop electrocardiogram (ECG) deep-learning (DL) models for the identification of patients with HCM and high-risk imaging features. METHODS: Patients with HCM evaluated at Tufts Medical Center (N = 1930; Boston, MA) were used to develop ECG-DL models for the prediction of high-risk imaging features: systolic dysfunction, massive hypertrophy (≥30 mm), apical aneurysm, and extensive late gadolinium enhancement. ECG-DL models were externally validated in a cohort of patients with HCM from the Amrita Hospital HCM Center (N = 233; Kochi, India). RESULTS: ECG-DL models reliably identified high-risk features (systolic dysfunction, massive hypertrophy, apical aneurysm, and extensive late gadolinium enhancement) during holdout testing (c-statistic 0.72, 0.83, 0.93, and 0.76) and external validation (c-statistic 0.71, 0.76, 0.91, and 0.68). A hypothetical screening strategy using echocardiography combined with ECG-DL-guided selective CMR use demonstrated a sensitivity of 97% for identifying patients with high-risk features while reducing the number of recommended CMRs by 61%. The negative predictive value with this screening strategy for the absence of high-risk features in patients without ECG-DL recommendation for CMR was 99.5%. CONCLUSION: In HCM, novel ECG-DL models reliably identified patients with high-risk imaging features while offering the potential to reduce CMR testing requirements in underresourced areas.

Cytochrome P450 2C19 Polymorphisms and Its Association With Major Adverse Cardiac Events in Post-coronary Intervention Patients on Clopidogrel in the Tertiary Care Center.

Background Clopidogrel has become essential in managing coronary artery disease and other atherothrombotic diseases. It is an inactive prodrug that needs biotransformation in the liver by various cytochrome P (CYP) 450 isoenzymes for its active metabolite formation. However, 4-30% of patients on clopidogrel have shown no or decreased antiplatelet response. This condition is called 'clopidogrel non-responsiveness' or 'clopidogrel resistance.' This is attributed to genetic heterogeneity causing interindividual variation and increased risk of major adverse cardiac events (MACEs). This study aimed to assess MACEs and their association with CYP450 2C19 polymorphisms in post-coronary intervention patients on clopidogrel. Methods This prospective observational study was conducted on acute coronary syndrome patients, started on clopidogrel following coronary intervention. After considering inclusion and exclusion criteria, 72 patients were enrolled, and a genetic analysis was done. Based on genetic analysis, patients were divided into two groups, normal (CYP2C19*1) and abnormal phenotypes (CYP2C19*2 & *3). These patients were followed for two years, and the MACE during the first year and second year was compared between these two groups. Results Of 72 patients, 39 (54.1%) were normal, and 33 (45.8%) were abnormal genotypes. The mean age of patients is 67.71 ± 9.968. A total of 19 and 27 MACEs were seen during first- and second-year follow-ups. During the first-year follow-up, three (9.1%) patients with abnormal phenotypes developed ST-elevation myocardial infarction (STEMI), and none of the phenotypically normal patients developed STEMI (p-value = 0.183). Non-ST elevation myocardial infarction (NSTEMI) was seen in three (7.7%) normal and seven (21.2%) abnormal phenotype patients (p-value=0.19). Other events, such as thrombotic stroke, stent thrombosis, and cardiac death, were seen in two (6.1%) abnormal phenotypic patients (p-value=0.401). During the second-year follow-up, STEMI was seen in one (2.6%) normal and three (9.7%) abnormal phenotypic patients (p-value=0.183). NSTEMI was seen in four (10.3%) normal and nine (29%) abnormal phenotype patients (p=0.045). Comparison of total MACEs between normal and abnormal phenotypic groups at the end of the first year (p-value=0.011) and second year (p-value=<0.01) has statistical significance. Conclusion We can infer that the risk of developing a recurrent MACE in post-coronary intervention patients on clopidogrel is significantly high in the abnormal phenotypic group (CYP2C19*2 & *3) than in normal phenotypic patients.

Mutation of the MYL3 gene in a patient with mid-ventricular obstructive hypertrophic cardiomyopathy.

In this study, we discuss a female patient referred to cardiology with left ventricular hypertrophy at mid-ventricular segments resulting in a mid-cavitary obstruction and a left ventricular apical aneurysm. The patient had normal epicardial coronary arteries, but presented with recurrent cerebrovascular events. The patient had a positive family history for sudden cardiac death. Cardiac MRI detected positive features of left ventricular mid-cavity obstruction, left ventricular apical aneurysm and delayed gadolinium enhancement, with Holter monitoring assessment displaying segments of non-sustained ventricular tachycardia. Genetic analysis detected an myosin light chain 3 (MYL3) gene mutation. The patient will be referred to receive an implantable cardioverter defibrillator.The MYL3 gene mutation is a rare variant in patients with familial hypertrophic cardiomyopathy. To our knowledge, the presence of a left ventricular apical aneurysm has not been previously reported in literature concerning the MYL3 gene mutation. The presence of this abnormality further increases the risk of sudden cardiac death.

Do alternative approaches work in surgical septal myectomy?

Trans-aortic septal myectomy is the gold standard for septal reduction therapy. This technique has low peri-procedural mortality and excellent long-term survival. Moreover, it relieves the heart failure symptoms and improves the quality of life. Secondary chordal cutting along with septal myectomy has shown to improve the outcome but can potentially cause deterioration of left ventricular function. In patients with relatively thin inter-ventricular septum, abnormalities of mitral valve apparatus may be the main reason for systolic anterior motion and left ventricular outflow tract obstruction. These patients may require additional procedures on the mitral valve to shift the coaptation plane away from outflow tract. Mitral valve replacement should be performed only in patients with intrinsic mitral valve abnormalities that are not suitable for repair and its routine use along with limited septal myectomy should be discouraged. Minimal access surgery although attractive in concept requires more robust data before universal application.

Cardiac tamponade as a presentation of COVID-19 after cardiac surgery.

We present two patients who turned positive for coronavirus disease 2019 (COVID-19) after elective cardiac surgery, developing postoperative pericardial effusion with tamponade. One of the patients who presented with tamponade had no other symptoms of COVID-19 infection. COVID-19 can rarely present with cardiac manifestations including pericardial effusion and tamponade. In the post cardiac surgery setting, this effect of the virus may be accentuated. Hence, a high index of suspicion and prompt management are the keys for a successful outcome.

Posterior mitral leaflet plication with extended septal myectomy for hypertrophic obstructive cardiomyopathy.

Abnormalities of the mitral valve apparatus are a phenotypical expression of hypertrophic cardiomyopathy and can contribute to systolic anterior motion and left ventricular outflow tract obstruction. In patients with significant abnormalities of the mitral apparatus, adjunct procedures like plication of the anterior mitral leaflet and/or release of papillary muscles may be required to obtain sufficient relief of obstruction. Very rarely, an elongated posterior mitral leaflet is the main culprit for systolic anterior motion. In such cases, plication of the posterior mitral leaflet is a useful technique, in addition to septal myectomy, to abolish left ventricular outflow tract obstruction. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12055-021-01213-1.

Familial left ventricular noncompaction cardiomyopathy due to a novel mutation in the MYH 7 gene.

Left Ventricular Non Compaction (LVNC) is considered a unique cardiomyopathy according to the American Heart Association guidelines. The genetic ethology of LVNC in children is not completely understood although upto 41% of LVNC are thought to be genetic. We report a family with LVNC due to a novel mutation in the MYH 7 gene.

Fabry disease in India: A multicenter study of the clinical and mutation spectrum in 54 patients.

Fabry disease (FD) is a treatable X linked lysosomal storage disorder with a wide phenotypic spectrum. There is a scarcity of published data on the burden of FD in India. This study evaluates the clinical and molecular spectrum of Indian patients with FD. In this multicentric study involving 10 tertiary referral centers in India, we analyzed the clinical course and genotype of 54 patients from 37 families. Family screening identified 19 new patients (35%) from 12 index cases. Then, 33 GLA gene variants were identified in 49/54 (90.7%) which included 11 novel and 22 known pathogenic variants. Of the 54 patients in our cohort, 40 patients had "classical" and 10 patients had a "nonclassical" presentation. The symptoms and signs included kidney dysfunction in 38/54 (70.3%), neuropathic pain in 34/54 (62.9%), left ventricular hypertrophy in 22/49 (44.8%) and stroke in 5/54 (9.2%). Female heterozygotes were 10/54 (18.5%) of whom 2 were index cases. There was a significant delay in reaching the diagnosis of 11.7 years. Enzyme replacement therapy was initiated in 28/54 (51.8%) patients with significant improvement of neuropathic pain and gastrointestinal symptoms. This study highlights the clinical presentation and mutational spectrum of FD in India and suggests that family screening and screening of high-risk groups (hypertrophic cardiomyopathy, idiopathic chronic renal failure and cryptogenic stroke) could be the most cost-effective strategies for early identification of FD.

Phenotypic expression and clinical outcomes in a South Asian PRKAG2 cardiomyopathy cohort.

The PRKAG2 syndrome is a rare autosomal dominant phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM), characterized by ventricular pre-excitation, progressive conduction system disease and left ventricular hypertrophy. This study describes the phenotype, genotype and clinical outcomes of a South-Asian PRKAG2 cardiomyopathy cohort over a 7-year period. Clinical, electrocardiographic, echocardiographic, and cardiac MRI data from 22 individuals with PRKAG2 variants (68% men; mean age 39.5 ± 18.1 years), identified at our HCM centre were studied prospectively. At initial evaluation, all of the patients were in NYHA functional class I or II. The maximum left ventricular wall thickness was 22.9 ± 8.7 mm and left ventricular ejection fraction was 53.4 ± 6.6%. Left ventricular hypertrophy was present in 19 individuals (86%) at baseline. 17 patients had an WPW pattern (77%). After a mean follow-up period of 7 years, 2 patients had undergone accessory pathway ablation, 8 patients (36%) underwent permanent pacemaker implantation (atrio-ventricular blocks-5; sinus node disease-2), 3 patients developed atrial fibrillation, 11 patients (50%) developed progressive worsening in NYHA functional class, and 6 patients (27%) experienced sudden cardiac death or equivalent. PRKAG2 cardiomyopathy must be considered in patients with HCM and progressive conduction system disease.

Right ventricular dysfunction in stress cardiomyopathy: The prognostic value of fractional area change.

BACKGROUND: There are limited data on the impact of right ventricular dysfunction (RVD) on the clinical outcomes in patients with stress cardiomyopathy (SC). The purpose of this study was to evaluate the impact of RVD on outcomes and to characterize the prognostic value of RV fractional area change (FAC). METHODS: This study retrospectively analyzed data from 111 consecutive patients with SC. The primary endpoint, major cardiac events (MCE), was a composite of 30-day mortality, cardiogenic shock, life threatening arrhythmias, and stroke. Regression analysis was used to identify independent predictors of short (30 days)- and long-term MCE. RESULTS: Among the 111 patients (80.2% females, mean age 45.8 ± 11.5 years), RVD was present in 17(15.3%) patients. MCE occurred in 18(16.2%) and 22(19.8%) patients at 30 days and during long-term follow-up, respectively. RVD was an independent predictor of short (HR 1.88(1.21-15.67), P = .036)- and long (HR 1.65(1.11-9.67), P = .016)-term MCE. Compared with tricuspid annular plane systolic excursion < 15 mm (TAPSE) (sens 72.2%, spec 94.1%, AUC 0.75) and tricuspid annulus pulsed TDI-derived peak systolic velocity (S') < 9.5 cm/s (sens 67.2%, spec 94.5%, AUC 0.72), RV FAC < 30% (sens 89.1%, spec 100%, AUC 0.92) had the highest accuracy and discriminative ability to predict MCE. Furthermore, RV FAC < 30% was a significant predictor of recurrence (29.4% vs 2.1%, P = .002) and delayed recovery time (21.4 ± 6.8 vs 8.5 ± 4.3 days, P < .001). CONCLUSIONS: The presence of RVD in stress cardiomyopathy identifies patients at higher risk of mortality, complications, delayed recovery, and recurrence. Compared with other indices, RV FAC has the highest prognostic ability to predict these outcomes.

Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians.

BACKGROUND: Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population. OBJECTIVES: This analysis used summary statistics from a prior genome-wide association study to derive a new GPSCAD for South Asians. METHODS: This GPSCAD was validated in 7,244 South Asian UK Biobank participants and tested in 491 individuals from a case-control study in Bangladesh. Next, a static ancestry and GPSCAD reference distribution was built using whole-genome sequencing from 1,522 Indian individuals, and a framework was tested for projecting individuals onto this static ancestry and GPSCAD reference distribution using 1,800 CAD cases and 1,163 control subjects newly recruited in India. RESULTS: The GPSCAD, containing 6,630,150 common DNA variants, had an odds ratio (OR) per SD of 1.58 in South Asian UK Biobank participants and 1.60 in the Bangladeshi study (p < 0.001 for each). Next, individuals of the Indian case-control study were projected onto static reference distributions, observing an OR/SD of 1.66 (p < 0.001). Compared with the middle quintile, risk for CAD was most pronounced for those in the top 5% of the GPSCAD distribution-ORs of 4.16, 2.46, and 3.22 in the South Asian UK Biobank, Bangladeshi, and Indian studies, respectively (p < 0.05 for each). CONCLUSIONS: The new GPSCAD has been developed and tested using 3 distinct South Asian studies, and provides a generalizable framework for ancestry-specific GPS assessment.

The prognostic value of dispersion of repolarization in stress cardiomyopathy.

INTRODUCTION: Although abnormalities of ventricular repolarization are a hallmark of SC, their clinical impact on management remains to be determined. This study sought to evaluate the prognostic value of dispersion of repolarization in stress cardiomyopathy (SC) with regards to major cardiac events (MCE), recovery time, and recurrence. METHODS: This study analyzed data from258 patients with SC, from January 2009 to January 2018. Standard 12 lead ECG recordings during the acute, subacute, and recovery phases were collected for each eligible patient. Logistic regression was used to identify independent predictors of MCE, a composite of 30 day all-cause mortality, cardiogenic shock, life-threatening ventricular arrhythmias, and stroke. RESULTS: Among the 101 eligible patients (80.2% females, mean age 45.8 ± 11.5 years) in the study cohort, MCE occurred in 16 patients (15.8%). Cox regression analysis identified two independent predictors of MCE: increased ΔQT dispersion ≥ 40 ms (HR 1.31, 95% CI 1.05-9.77, p = 0.029) and increased Δnegative T wave amplitude dispersion ≤ -2.0 mV (HR 1.25, 95% CI 1.11-11.93, p = 0.018) during the subacute phase. The final regression model had good accuracy (sensitivity 81.3%, specificity 96.5%) and discriminative power (AUC 0.89, 95% CI 0.83-0.95). Kaplan-Meier analysis revealed that there was increasing MCE in patients with zero, one, or two predictors (log rank p < 0.001). In addition, patients with increased dispersion also had a significantly longer time to achieve complete recovery (21.4 ± 6.8 vs. 8.5 ± 4.3 days, p = 0.012) and a higher incidence of recurrence (31.3% vs. 2.4%, p = 0.011) of SC. CONCLUSION: Evaluation of dynamic changes of dispersion of repolarization is a simple bed-side tool with high predictive accuracy for prognostication of short term adverse outcomes, delayed recovery, and recurrence in patients with SC.

Posterior mitral leaflet plication for hypertrophic obstructive cardiomyopathy.

Anomalies of the mitral valve apparatus in hypertrophic cardiomyopathy are an important cause of systolic anterior motion. Patients with significant residual obstruction due to systolic anterior motion after myectomy and anterior mitral leaflet plication may end up having mitral valve replacement. We describe the case of a 52-year-old man who underwent posterior mitral leaflet plication to correct residual systolic anterior motion after anterior mitral leaflet plication.