Clopidogrel resistance and its effect on clinical outcomes in acute coronary syndrome.

AIM: The genetic polymorphism of CYP2C19 influences clopidogrel metabolism and resistance. Aim was to assess the association between CYP2C19 loss of function variation, clopidogrel resistance based on platelet reactivity units and clinical outcomes. METHODS: A total of 668 patients of Acute Coronary Sundrome (ACS) who underwent Percutaneous Coronary Intervention (PCI) were subjected to genetic screening and 143 patients undrewent platelet function test to study the association between drug metabolization and its effects based on platelet reactivity unit values. RESULTS: Clopidogrel resistance with CYP2C 19 loss of function variation was noted in 54.64% of patients. Clinical outcomes, such as target vessel revascularization, target lesion revascularization, in-stent restenosis, and stent thrombosis, were also studied. CONCLUSION: CYP2C19 loss of function variation is strongly associated with clopidogrel resistance and adverse clinical outcomes.

Pharmacogenomic evaluation of CYP2C19 alleles linking low clopidogrel response and the risk of acute coronary syndrome in Indians.

BACKGROUND: Clopidogrel is an antiplatelet drug widely prescribed to prevent atherothrombotic events in coronary artery disease patients. However, there is evidence to suggest that the effectiveness of clopidogrel varies owing to genetic diversity in CYP2C19. This heterogeneity in South Asians, who are also known to have high risk of cardiac events than other population groups, highlights the importance of investigating CYP2C19 variants to estimate the risk proportion in the groups. METHODS: Given the high prevalence and genetic heterogeneity, the population-based case control was conducted in a cohort of 1191 subjects comprising 645 acute coronary syndrome (ACS) cases (unstable angina, ST-elevation myocardial infarction, and non-ST-elevation myocardial infarction) and 546 healthy controls of South Asian Indian origin. The metabolization status of CYP2C19 was assessed using *2, *3 and *17 variants in the stated cohorts to determine the prevalence of metabolization and its association with phenotypes. RESULTS: The results suggest a possible genetic association between studied CYP2C19 polymorphisms and ACS, since there was a higher proportion of intermediate and poor metabolizers present in the studied cohorts. The association analyses revealed that the *2 allele of CYP2C19 confers a significant risk for ACS, while the *17 allele provides protection. CONCLUSIONS: These findings contribute to the understanding of CYP2C19 genetic variants and their impact on clopidogrel response in South Asian Indians. Additionally, they underline the significance of assessing CYP2C19 variations in patients receiving clopidogrel therapy in order to improve therapeutic outcomes.

Preliminary genome wide screening identifies new variants associated with coronary artery disease in Indian population.

AIM: Coronary artery disease (CAD) is a major health problem in developed and developing nations. Development of CAD involves a complex interaction between genetics and lifestyle factors. Individuals with high-risk genetic predisposition along with poor lifestyle are more inclined to the development of CAD. Advancement in genotyping technologies and increase in genome wide studies has provided a platform to identify new risk factors associated with CAD and associated complexities. METHODOLOGY: In this study we performed genome wide screening in 76 well-defined CAD cases and 77 control samples in Indian population. Interestingly, new variants are identified in three genes viz, VLDLR, IFITM2 and C2CD4C. RESULTS: The odds ratios observed for variant rs1869592 (VLDLR), rs1059091 (IFITMI) and rs7247159 (C2CD4C) were 2.6 (1.4-4.8 95% CI), 1.9 (95% CI 1.2-3.1) and 2.1 (1.2-3.7 95% CI), respectively with significant P value <0.01. These variants that are associated with pathogenesis of CAD were not previously reported in literature. Moreover, we anticipate that these variants will be further validated using a larger sample size.

Minimizing scattered radiation dose in cardiac catheterization laboratory during interventional procedures using lead free drape - MILD study.

OBJECTIVE: RADPAD is a lead-free sterile drape that reduces scattered radiation during fluoroscopic procedures. We aimed to study the effect of using RADPAD on primary operator (PO) and secondary operator (SO) during coronary angiography (CAG) as well as percutaneous coronary intervention (PCI). METHODS: 137 patients undergoing elective CAG and PCIwere randomized in a 1:1 pattern with or without the RADPAD. The ratio of PO received dose in mrem to total Air Kerma (AK) in mGy, Dose Area Product (DAP) in mGycm2 and Cine Adjusted Screening Time (CAST) in minute, at the end of the procedure with or without RADPAD were measured and designated as dose relative to AK, DAP and CAST. The exposure ratios were compared for both cohorts. RESULTS: There was no significant difference in CAST, DAP and AK between the two patient cohorts. PO radiation dose relative to CAST was 0.15 ± 0.18 mrem/min for RADPAD cohort and 0.43 ± 0.31 mrem/min for No RADPAD cohort (p < 0.00001). PO dose relative to DAP was 0.00042 ± 0.00049 mrem/mGycm2 for RADPAD cohort and 0.0011 ± 0.0013 mrem/mGycm2 for No RADPAD cohort (p = 0.000014). PO dose relative to AK was 0.0030 ± 0.0037 mrem/mGy for RADPAD cohort and 0.0071 ± 0.0049 mrem/mGy for No RADPAD cohort (p < 0.00001). All PO doses relative to CAST, DAP and AK were significantly reduced in the RADPAD cohort compared to the No RADPAD cohort. Similar findings were observed for the SO also. CONCLUSION: RADPAD significantly reduces radiation exposure to both PO and SO during CAG and PCI.

Femoral artery access site closure with perclose suture mediated device in coronary interventions.

OBJECTIVE: To compare the outcome of suture mediated vascular closure device Perclose Proglide (PP) with manual compression (MC) following transfemoral access for coronary interventions (CI). METHODS: It is a retrospective, observational, single centre study from January 2018 to September 2019. Consecutive patients undergoing interventions through transfemoral access were divided into PP and MC groups. Those with less than 3 months follow up were excluded. Two groups were compared for baseline characteristics and various complications at 24 h and at 30 days. RESULTS: Out of 1743 patients studied, PP group included 1343 and MC group, 400 patients. Both groups were comparable in baseline characteristics, sheath size and use of antiplatelets and anticoagulation. PP group had significantly less minor bleeding (P = .01, CI 0.34-4.03) and hematoma (P = .0007, CI 0.95-5.10) at 24 h. At 30 days, minor bleeding (P < .0001, CI 0.97-4.25), hematoma (P = .0002, CI 1.05-4.93) and pseudo-aneurysm (P = .0095, CI 0.03-1.18) were also significantly less in PP group. Obesity (OR 3.5, CI 1.29-9.49) and hypertension (OR 2.41, CI 1.12-5.19) were associated with increased minor bleeding at 24 h. Device failure rate was 2.38%. CONCLUSIONS: PP device is safe, effective and is associated with fewer complications than MC in CI. Device failure rate is low. Obesity and hypertension are associated with increased minor bleeding in both groups.

A case of cholesterol embolization syndrome mimicking rapidly progressive renal failure causing end-stage kidney disease.

Cholesterol embolization syndrome is an uncommon complication of coronary angioplasty. Its clinical manifestations are nonspecific and may be ascribed to other causes mimicking vasculitis syndrome. In an appropriate clinical setting, the diagnosis can be confirmed by tissue biopsy. In this case report, we present a middle-aged male who presented with cutaneous and renal manifestations within two weeks of primary angioplasty. The patient had progressive clinical deterioration in the form of dry gangrene of toes and end-stage renal disease requiring surgical amputation and maintenance hemodialysis respectively within two months of symptoms onset.

Hypertension and Obesity Among Civil Aviation Pilots.

BACKGROUND: Raised blood pressure (BP) is a risk factor for cardiovascular disease, which is a common cause of sudden in-flight incapacitation among pilots. Prevalence of hypertension (HT) among pilots as per new criteria is largely unknown. This study aims to understand the prevalence of hypertension and obesity in civil aviation pilots and their correlation.METHODS: Enrolled were 1185 civilian pilots reporting for medical evaluation to a regulatory medical establishment in India. Their height, weight, and blood pressure (BP) were measured. Pilots were categorized as hypertensive or normotensive as per JNC VIII criteria and hypertensive, having elevated BP, or normotensive as per new ACC/AHA criteria of 2017. Data were analyzed for prevalence of obesity and overweight as per both WHO and Asia Pacific criteria. Results were analyzed using SPSS version 17.RESULTS: Prevalence of hypertension was 4.1%. Maximum hypertensives were in the 26-35 yr age group. Under the new ACC/AHA guidelines, prevalence of HT was 18.7%. Prevalences of overweight and obesity as per WHO criteria were 39% and 7.3% and as per Asia Pacific guidelines were 23.3% and 46.3%, respectively. As BMI increased above 23, risk of developing hypertension or white coat hypertension as per JNC VIII criteria increased by 6.86 times (OR 6.86, 95% CI 0.9-52.58).CONCLUSIONS: Prevalence of HT rose from 4.1% to an alarmingly high 18.7% when new criteria were applied. Prevalence of obesity was 7.3% but increased to 46.3% when Asia Pacific guidelines were applied. Risk of hypertension increased as BMI increased above 23 kg · m-2.Bhat KG, Verma N, Pant P, Marwaha MPS. Hypertension and obesity among civil aviation pilots. Aerosp Med Hum Perform. 2019; 90(8):703-708.