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.

Transcatheter aortic valve implantation using coplanar and cuspal overlap techniques in Indian patients.

INTRODUCTION: Transcatheter Aortic Valve Implantation (TAVI) techniques gradually evolved since 2002 and have undergone various refinements. Achieving optimal implantation depth has become crucial for good long term outcome. High implantation decreases the likelihood of conduction disturbances. Conventionally TAVI valve is positioned in a tricusp coplanar (CON) fluoroscopic projection however it does not ensure a optimal implantation. In an attempt to attain higher implantation(3 mm) and decrease rate of permanent pacemaker, cuspal overlap technique (COT) view has been developed. There is scarcity of Indian literature comparing TAVI deployment using coplanar and cuspal overlap techniques. METHODS: We included 111 patients who underwent TAVR with a self-expanding Core Valve Evolut R (Medtronic, Minneapolis, Minnesota), between January 2017 to September 2022 at our centre.Transcatheter Heart Valves (THV) were implanted using the traditional coplanar in 55 patients, while in 56 patients valves were implanted using the COT. RESULTS: Baseline characteristics including electrocardiographic findings were comparable in both groups. In all patients Evolut R or Evolut PRO valves were used. Procedure was done in conscious sedation in 90.9 % of patients in CON and 96.4 % in COT group. Predilatation and postdilatation was used in 38.8 % vs 33.9 % and 27 % vs 32 % in CON and COT groups respectively. 90 day PPI rate was less in COT group (7.3 % CON vs 3.5 % COP). Majority of patients who received permanent pacemaker implantation (PPI) had baseline ECG abnormality (RBBB in 50 %, LBBB in 16 %, Grade 1 AV block 16 %). Mean time of post procedure PPI was 5.6 days in COT group and 7.3 days in CON group. New onset LBBB was also less in COT group (21 % CON vs 12.5 % COT).There were 3.6 % intraprocedural deaths in CON group and 1.8 % in COT group. Depth of deployed valve was 4.8 ± 2.34 mm in COT and 6.6 ± 2.11 mm in CON group. Valve deployment time was more in COT group(10.40 CON vs 14.34 min COT). Average valve recapture rate was 2.58 in COP and 2.11 in CON. Stroke rate was more in COT group(3.6 % CON vs 7.14 % COT). Pericardial effusions were also more in COT group. All cause mortality at 3 months was 10.9 % in CON group and 5.3 % in COT. CONCLUSION: In this study we achieved lower rates of PPI and new onset LBBB using COT technique in Indian patients using self-expandable prostheses. However valve deployment time, stroke rate and pericardial effusion were seen more in COT group. All cause mortality was low in cuspal overlap technique.

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.

All that seems sepsis is not sepsis.

Catastrophic antiphospholipid antibody syndrome (CAPS) resembles severe sepsis in its acute presentation, with features of systemic inflammatory response syndrome (SIRS) leading to multiple organ dysfunction. Infections are the best known triggers of CAPS. This emphasizes the need for early diagnosis and aggressive treatment as the mortality is as high as 50%. We present a 42-year-old woman who developed SIRS postoperatively and was eventually diagnosed as CAPS.

Percutaneous Extraction of Deployed Coronary Stent During Retrieval of Jailed Buddy Wire.

Retrieval of a buddy wire following coronary stenting of long, tortuous, and calcified lesions runs the risk of wire entrapment and stent deformation. We report a case of successful percutaneous extraction of a longitudinally deformed coronary stent during retrieval of jailed buddy wire from the left anterior descending artery. (Level of Difficulty: Advanced.).

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.

Epidemiology and pathophysiology of vascular thrombosis in acclimatized lowlanders at high altitude: A prospective longitudinal study.

Background: Previous literature suggests that thrombosis is more common in lowlanders sojourning at high altitude (HA) compared to near-sea-level. Though the pathophysiology is partly understood, little is known of its epidemiology. To elucidate this, an observational prospective longitudinal study was conducted in healthy soldiers sojourning for months at HA. Methods: A total of 960 healthy male subjects were screened in the plains, of which 750 ascended, to altitudes above 15,000ft (4,472m). Clinical examination, haemogram, coagulogram, markers of inflammation and endothelial dysfunction, were studied at three time points during ascent and descent. The diagnosis of thrombosis was confirmed radiologically in all cases where a thrombotic event was suspected clinically. Subjects developing thrombosis at HA were labelled as Index Cases (ICs) and compared to a nested cohort of the healthy subjects (comparison group,(CG)) matched for altitude of stay. Findings: Twelve and three subjects, developed venous (incidence: 5,926/105 person-years) and arterial (incidence: 1,482/105 person-years) thrombosis at HA, respectively. The ICs had enhanced coagulation (FVIIa: p<0.001; FXa: p<0.001) and decreased levels of natural anticoagulants (thrombomodulin, p=0.016; tissue factor pathway inhibitor [TFPI]: p<0.001) and a trend to dampened fibrinolysis (tissue plasminogen activator tPA; p=0.078) compared to CG. ICs also exhibited statistically significant increase in the levels of endothelial dysfunction and inflammation markers (vascular cell adhesion molecule-1[VCAM-1], intercellular adhesion molecule-1 [ICAM-1], vascular endothelial growth factor receptor 3 [VEGFR-3], P-Selectin, CD40 ligand, soluble C-reactive protein and myeloperoxidase: p<0.001). Interpretation: The incidence of thrombosis in healthy subjects at HA was higher than that reported in literature at near sea-level. This was associated with inflammation, endothelial dysfunction, a prothrombotic state and dampened fibrinolysis. Funding: Research grants from the Armed Forces Medical Research Committee, Office of the Director General of Armed Forces Medical Services (DGAFMS) & Defence Research and Development Organization (DRDO), Ministry of Defence, India.

Spontaneous closure of grade IV coronary perforation.

Previous coronary artery bypass surgery (CABG) is an independent risk factor for coronary perforation (CP) during percutaneous coronary intervention (PCI) because of complexity of the cases. However in patients with prior CABG surgery, cardiac tamponade is rare because of local or regional pericardial adhesions.

Accidental Snapping of Right Ventricular Pacing Lead with MICRA.

Leadless Pacemaker implantation rates are increasing worldwide. These pacemakers have to be deployed, captured and redeployed in order to achieve optimal electric parameters. Various complications occur during this procedure. We herein report a unique case, where right ventricular (RV) pacing lead of the patient was accidently snapped with the tines during deployment of intracardiac pacemaker in an elderly male with pocket site infection.

Assessing safety of leadless pacemaker (MICRA) at various implantation sites and its impact on paced QRS in Indian population.

BACKGROUND: In this study we report our experience in implanting MICRA TPS (transcatheter pacing system) at various RV sites; observing its safety, and impact on paced QRS in Indian population. MATERIAL & METHODS: 35 patients with MICRA TPS deployed from March 2017 to December 2019 at Army Hospital Research and Referral, New Delhi, at RVOT, apical septum and mid septum of RV were enrolled in the study. These patents were followed up and impact of implantation site, procedure related complications, change in pacing parameters, left ventricular ejection fraction and duration of paced QRS were monitored. RESULTS: Sick sinus syndrome was the commonest indication of pacing in this study (51.5%), followed by high degree AV block (34.2%). Mean follow up of 1.4 years showed no change in left ventricular ejection fraction, electrical parameters or change in pacing thresholds after implantation. Mean pQRS was broadest (166.60 ms) in apically implanted MICRA TPS and narrowest in mid septum group 139.33 ms. Among 35 cases, in our study one patient developed pericardial effusion, and other had intermittent diaphragmatic pacing. CONCLUSION: Among these three implantation sites mid septum deployment is associated with narrowest paced QRS in Indian population.

Giant right atrial myxoma presenting as right heart failure: a rare manifestation.

A 37-year-old man was presented in outpatient clinic of cardiology department with symptoms of easy fatigability and progressive increasing generalised anasarca since 5 months. Echocardiogram showed large mass of 9.8×7.8 cm in size in right atrium, attached to interatrial septum. Urgent opinion of thoracic surgeon was taken and surgical excision of mass under cardiopulmonary bypass was done. The tumour was large, fragile and histology confirmed it as myxoma. The patient made a good recovery and his symptoms resolved completely on follow-up.

Outcomes of transcatheter closure of patent ductus arteriosus with the off-label use of large occluders (≥16 mm).

OBJECTIVE: Transcatheter closure is the first-choice strategy for the management of appropriate patients with patent ductus arteriosus (PDA). The management of large PDAs is challenging due to the limited available sizes of approved devices and the inherent risks of surgical ligation, especially in adults with calcified PDAs. This study aimed to assess the outcomes of the off-label use of large occluders at a tertiary center. METHODS: This retrospective review included patients who underwent transcatheter PDA closure with large occluders (≥16 mm) over 16 years. The baseline patient data, procedural details, angiograms, and immediate outcomes were recorded and patients were followed up at 3, 6, 12 months after the intervention and annually thereafter. RESULTS: Of the 685 patients who underwent transcatheter PDA closure, 36 patients (mean age 16.6 ± 12.5 years) needed occluders ≥ 16 mm in size. Cocoon duct occluder, Cera duct occluder, Amplatzer atrial septal occluder (ASO), and Cera muscular ventricular septal defect occluders were used for PDA closure. There was no device embolization, one patient in whom ASO was used had residual shunt with intravascular hemolysis requiring surgery, and one patient had mild left pulmonary artery narrowing after the intervention, which was managed conservatively. No patient had residual shunt and one patient had persistent pulmonary hypertension at an intermediate duration of follow-up. CONCLUSION: Transcatheter PDA closure with the use of large devices, which are available in Asia and Europe, is an effective and safe method, especially in adolescents and adults. However, a close follow-up of these patients is mandatory.

Left Atrial Myxoma from Anterior Mitral Valve.

Primary cardiac tumors are relatively rare, and myxoma, the most common variety, is found predominantly in the left atrium. Clinical presentation varies from asymptomatic incidental masses to serious life-threatening cardiovascular complications. Some cases are difficult to diagnose, as symptoms can be nonspecific. We present a case of a young female with 4 months of history of dyspnea, weight loss, and night sweats, eventually diagnosed as a case of large left atrial myxoma arising from the anterior mitral valve through transthoracic echocardiography.

Pneumocephalus Presenting as Sudden Thunderclap Headache.

Pneumocephalus is a rare condition characterized by the presence of gas within the cranial cavity. This gas arises either from a trauma, tumor, surgical procedure, or occasionally from infection. Pneumocephalus secondary to chronic otitis media is an extremely rare phenomenon. We describe here a 70-year-old male, a known case of chronic suppurative otitis media who presented with sudden onset severe thunderclap headache and was eventually diagnosed as pneumocephalus.

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 ¼ 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. © 2022 Published by Elsevier, a division of RELX India, Pvt. Ltd on behalf of Cardiological Society of India

Risk factors including prothrombotic work up in young ischemic stroke Indian patients

Background: Stroke in young poses a major health problem. Various Indian studies have shown the incidence of stroke to be 10-15%. Cerebral venous thrombosis and rheumatic heart disease are the leading causes of stroke in the young in India. Thrombophilic factors have been implicated in 4-8% of the young strokes worldwide. Protein C deficiency is the most common thrombophilia marker followed by a deficiency of protein S, Factor V Leiden mutation, and antithrombin (AT) deficiency. Aims and objectives was the study of stroke in young is important for various reasons. The etiology and risk factors are more diverse and different as compared to the elderly. Therefore, these may indicate separate therapeutic approaches. The aim is to study the profile of ischemic stroke cases among the young.Methods: The study was carried out at a tertiary care defence hospital between December 2018 to December 2019. All cases of fresh ischemic stroke who were more than 15 and less than 45 years of age were included. Following clinical evaluation, patients underwent complete haemogram, blood sugar levels, lipid profile and other metabolic parameters. All patients were subjected to chest radiography, 12 lead ECG, and 2D echocardiography, Non-contrast CT head and MRI brain. Prothrombotic work up was also done.Results: A total of 41 patients (12.69%) presented with ischemic stroke before 45 years of age. Out of these 10 (24%) were females and 31 (76%) were male. None of the women smoked or consumed alcohol. Among the males, 19 (47%) smoked more than 10 cigarettes or bidis per day and 9 (22%) were moderate-to-heavy drinkers of alcohol. Hypertension was present in 7 (18%) and diabetes mellitus in 3 (7%) patients. Serum cholesterol was elevated in 7 (18%) patients and triglycerides in 17 (42%). Protein S deficiency was found in 28.8% patients, while protein C deficiency was detected in 21% patients and antithrombin III deficiency in 12% patients.Conclusions: Although traditional risk factors, such as hypertension, diabetes, and smoking, are associated with stroke in both elderly and young, this study shows that other modifiable risk factors such as alcohol consumption were also prevalent. The most common etiological cause was found to be venous infarction followed by cardio embolic cause. Deficiency of Protein S was the most common prothrombotic defect followed by deficiency of Protein C.

Oxcarbazepine induced toxic epidermal necrolysis - a rare case report.

Carbamazepine, is well known to cause Stevens-Johnson syndrome and toxic epidermal necrolysis(TEN). Oxcarbazepine, a 10-keto analog of carbamazepine, is an anticholinergic, anticonvulsant and mood stabilizing drug, used primarily in the treatment of epilepsy. Its efficacy is similar to carbamazepine but allergic reactions and enzyme induction is low. We describe a case of oxcarbazepine induced TEN, who presented with erythematous ulcerative maculopapular rash.