Pharmacogenetic variants influence vitamin K anticoagulant dosing in patients with mechanical prosthetic heart valves.

Background: Vitamin K antagonists (VKAs) are class I oral anticoagulants that are widely prescribed following surgical heart valve implantation. The objective of this study was to quantify the relative effects of VKORC1, CYP2C9 and CYP4F2 genotypes in predicting VKA dosing. Materials & methods: A total of 506 South Indian patients with mechanical prosthetic heart valves who were prescribed oral VKAs, such as warfarin or acenocoumarol, were genotyped. The discriminatory ability of mutant genotypes to predict dose categories and bleeding events was assessed using regression analysis. Results: The VKORC1 rs9923231, CYP2C9*3 and CYP4F2*3 mutant genotypes significantly influenced VKA-dose requirements and explained 27.47% of the observed dose variation. Conclusion: These results support pharmacogenetic screening for initial VKA dosing among South Indian patients with mechanical prosthetic heart valves.

Pulmonary Hypertension Registry of Kerala, India (PRO-KERALA): One-year outcomes.

BACKGROUND: Short term outcomes of patients with pulmonary hypertension are not available from low and middle-income countries including India. METHODS: We conducted a prospective study of 2003 patients with pulmonary hypertension, from 50 centres (PROKERALA) in Kerala, who were followed up for one year. Pulmonary hypertension (PH) was mainly diagnosed on the basis of Doppler echocardiography. The primary outcome was a composite end-point of all-cause death and hospital admission for heart failure. All cause hospitalisation events constituted the secondary outcome. RESULTS: Mean age of study population was 56 ± 16 years. Group 1 and Group 2 PH categories constituted 21.2% and 59% of the study population, respectively. Nearly two-thirds (65%) of the study participants had functional class II symptoms. 31% of Group 1 PH patients were on specific vasodilator drugs.In total, 83 patients (4.1%) died during the one-year follow-up period. Further, 1235 re-hospitalisation events (61.7%) were reported. In the multivariate model, baseline NYHA class III/IV (OR 1.87, 95% C.I. 1.35-2.56), use of calcium channel blockers (OR 0.18, 95% C.I. 0.04-0.77), vasodilator therapy (OR 0.5, 95% C.I. 0.28-0.87) and antiplatelet agents (OR 1.80, 95% C.I. 1.29-2.51) were associated with primary composite outcome at one-year (p < 0.05). CONCLUSION: In the PROKERALA registry, annual mortality rate was 4%. More than half of the patients reported re-hospitalisation events on follow up. Uptake of guideline directed therapies were suboptimal in the study population. Quality improvement programmes to improve guideline directed therapy may improve clinical outcomes of PH patients in India.

Conduction abnormalities post alcohol septal ablation for hypertrophic cardiomyopathy - A single center experience.

Conduction abnormalities are commonly noted after alcohol septal ablation (ASA). This was a retrospective, observational study where we studied the incidence of new onset conduction abnormalities post ASA. 23 patients, who underwent ASA over a period of 5 years, were included in the study. Baseline conduction abnormalities were noted in 26% patients (n = 6). Transient complete heart block (CHB) was noted in 21.7% (n = 5) whereas new onset right bundle branch block (RBBB) was seen in 60.8% (n = 14). Left bundle branch block was uncommon (4.3%,n = 1). Permanent pacemaker implantation was done in 4.3% (n = 1) for CHB. Conduction anomalies are frequent after ASA with RBBB being most common.

Prognostic value of late gadolinium enhancement in cardiac MRI of non-ischemic dilated cardiomyopathy patients.

BACKGROUND: The role of late gadolinium enhancement (LGE) in cardiac MRI (CMR) as prognostic marker in non-ischemic dilated cardiomyopathy (NIDCM) is evolving. OBJECTIVE: To study the effect of LGE in the prognosis of NIDCM patients. METHODS: 112 consecutive NIDCM patients, who underwent CMR, were prospectively followed up for 745 ± 320 days. Primary end point was occurrence of MACE {composite of all-cause mortality, resuscitated cardiac arrest, sustained ventricular tachycardia (VT)/appropriate ICD shock, heart failure (HF) hospitalization}. RESULTS: LGE was present in 44 out of 112 patients (39%). The primary end point (MACE) was significantly higher in LGE + ve group compared to the LGE -ve group (72.7% vs. 29.4%; p < 0.0001). Similarly, cardiac mortality (9.1% vs 2.9%; p < 0.049), VT (13.6% vs. 2.9%; p < 0.031), HF hospitalization (63.6% vs. 30.9%; p < 0.001) were significantly more in LGE + ve group. In univariate model, LGE demonstrated the strongest association with MACE (Hazard ratio [HR] = 2.96 [95% CI 1.685 to 5.201; p < 0.0001). LGE extent of >14% of LV predicted MACE with 90.6% sensitivity and 86% specificity. HR of LGE extent >14% of LV for MACE is 6.12; p < 0.01. LGE was associated with MACE irrespective of its location, pattern or distribution. Multivariate model showed LGE and its extent >14% of LV volume were strongest predictor of MACE. CONCLUSION: LGE and its extent >14% predicts adverse cardiac events in NIDCM irrespective of LVEF and LGE location, pattern or distribution. This study emphasises the role of CMR in risk stratification of NIDCM patients and guiding therapy.