Nakul Sinha

Primary congenital anomalies of the coronary arteries: a coronary arteriographic study

Geographic variations in the incidence of different congenital coronary anomalies are well known, but infrequently studied in the Indian population. Among 4,100 adult patients who underwent diagnostic coronary arteriography, 39 (0.95%) patients (34 males, 5 females) had one or more anomalous coronary arteries. Their mean age was 46.4 +/- 8.2 years (range, 26-68 years). Thirty-five (89.74%) had anomalies of origin and distribution, while the remaining four (10.25%) had coronary artery fistulae. Right coronary artery was the commonest anomalous vessel, involved in 19 (48.74%) patients. It was originating from the left sinus of Valsalva in 15 and from the non-facing aortic sinus in four patients. Anomalous left circumflex artery was the second commonest anomaly, seen in 14 (35.89%) patients. Anomalous left anterior descending artery and anomalous left coronary artery from pulmonary artery were seen in one patient each. Among patients with coronary fistulae, two had fistulae between the left anterior descending artery and the main pulmonary artery, one between the conal artery and the right atrium, while the fourth patient had fistulae from the right coronary as well as from the left anterior descending artery to the left atrium. Atherosclerotic plaques in the anomalous arteries were seen in only 13 (33.33%) patients, much less than the overall incidence of coronary artery disease in patients with congenital coronary anomalies in this series (66.66%). In four (10.25%) patients, only the anomalous vessels were involved in coronary artery disease. Thus, in a small subgroup there does not appear to be an increased risk for development of atherosclerotic coronary artery disease in anomalous coronary arteries. Recognition of coronary anomalies is important in patients undergoing coronary arteriography, coronary interventions and cardiac surgery. Variations in the frequency of primary congenital coronary anomalies may possibly have a genetic background.

Use of dopamine in prevention of contrast induced acute renal failure — A randomised study

We report the use of dopamine in renal doses (5 micrograms/kg/min) to prevent contrast induced nephropathy (CIN). Forty patients with diabetes mellitus who were undergoing coronary angiography were randomly divided into two groups. Gr I (20 patients) was infused with dopamine starting 30 min before cardiac catheterization and continued for 6 h thereafter. Gr II (20 patients) did not receive dopamine. Baseline blood chemistry was performed before catheterization and then repeated 24 h after the procedure. The mean age and sex distribution were similar in both the groups. Urograffin (76%; 120-150 ml) was used in all the cases. The mean serum creatinine and blood urea nitrogen (BUN) levels in Gr I patients before catheterization were 1.5 +/- 0.32 mg % and 16.3 +/- 8.05 mg %, respectively. The corresponding values for Gr II were 1.52 +/- 0.68 mg % and 19.6 +/- 13.4 mg %, respectively. After angiography, Gr I patients did not show significant changes in renal parameters (serum creatinine, 1.37 +/- 0.25 mg % and BUN, 14.7 +/- 5.5 mg %) while Gr II patients showed a significant rise (serum creatinine, 1.96 +/- 1.2 mg % and BUN, 23.25 +/- 12.7 mg %; P = 0.01 and P = 0.05, respectively). Ten patients in Gr II (50%) developed a 25% rise in serum creatinine levels within 24 h of injection of the contrast. None of the patients developed renal failure severe enough to warrant dialysis. Hence alterations of renal function are common after cardiac catheterization. Dopamine in renal doses appears to be an effective means to prevent deterioration in renal function induced by contrast.

Cellular and humoral immune responses to mycobacterial heat shock protein-65 and its human homologue in Takayasu's arteritis

Expression of heat shock protein (HSP)‐65 as well as infiltration of T‐cells in arterial lesions and raised levels of circulating antibodies against mycobacterial HSP65 (mHSP65) led us to the concept that mHSP65 or its human homologue (hHSP60) might be involved in the etiopathogenesis of Takayasus arteritis (TA). Therefore, we investigated mHSP65 and hHSP60 reactive peripheral blood T‐cell subsets by BrdU incorporation assay and flow cytometry as well as investigating the different isotypes of anti‐mHSP65 and hHSP60 antibodies by ELISA. Eighty‐four percent (22/26) of the TA patients were observed to show T‐cell proliferation to mHSP65 and hHSP60 whereas only 16% (3/18) healthy controls showed such proliferation (P < 0·001). Both HSPs induced proliferation of exclusively CD4+ T‐cells and not CD8+ T‐cells. We also observed a significantly higher prevalence of only the IgG isotype reactive to mHSP65 and hHSP60 in TA as compared to HC (mHSP65: 92% TA versus 11% HC, P < 0·0001 and hHSP60: 84% versus 22%, P < 0·001). Our data show a significant correlation between mHSP65 and hHSP60 reactive T‐cells (CD3+: r = 0·901; CD4+: r = 0·968) as well as anti‐mHSP65 and anti‐hHSP60 IgG antibodies (r = 0·814) suggesting an infection induced autoimmunity in TA, possibly induced by molecular mimicry between mHSP65 and hHSP60 or other tissue specific antigens.

Dextrocardia: an analysis of cardiac structures in 125 patients

BACKGROUND Dextrocardia is associated with multiple and complex congenital cardiac anomalies. Precise anatomical diagnosis is essential for successful surgery. Spectrum of congenital malformations in cases of dextrocardia is based primarily on two-dimensional echocardiographic studies. The purpose of the current study was to use colour Doppler echocardiography in large number of patients. METHODS Patients of dextrocardia were studied retrospectively, by reviewing database of our echocardiographic laboratory over last 10 years. Standard criteria for diagnosis of situs were used. Detailed segmental analysis for cardiac anatomy and associated malformations was done using previously suggested and well accepted terms and definitions. Cardiac anatomy was confirmed on catheterization and during surgery in few cases. RESULTS Of total 125 patients, dextrocardia was most common with situs inversus (39.2%) followed by situs solitus (34.4%) and situs ambiguous [26.4% (right isomerism in 18.4% and left isomerism in 8.0%)]. Mean age was 9.2+/-11.2 years (range; 3 days to 60 years), 82 males and 43 females. In situs inversus dextrocardia, majority (73.4%) had concordant atrioventricular (AV) connections while discordant AV connections and univentricular atrioventricular connections (UVAVC) were present in 12.2 and 14.3% patients, respectively. Majority of patients with concordant AV connections (72.2%) also had concordant VA (ventriculo-arterial) connections (conotruncal anomalies were commonest). Similarly, majority of patients with discordant AV connections (66.7%) also had discordant VA connections. Commonly (44.9%), these patients presented with decreased pulmonary blood flow (Qp). Total 28.6% patients had normal intracardiac anatomy (10.2% presented with rheumatic heart disease). In situs solitus dextrocardia, majority (51.2%) had AV concordance while discordant AV connections and UVAVC were present in 41.9 and 7.0% patients, respectively. In patients with concordant AV connections, majority (77.2%) had VA concordance (majority presented with increased Qp due to pre or post-tricuspid shunts). Similarly, majority of patients with discordant AV connections (88.9%) also had discordant VA connections (88.9% presented with decreased Qp). Only 7.0% patients with situs solitus dextrocardia had normal intracardiac anatomy. The striking features of right isomerism were male predominance (male:female ratio 2.2:1), cyanosis with decreased Qp in 86.9%, and high incidence of UVAVC and venous system anomalies (39.1% each). Striking features of left isomerism were biventricular ambiguous AV connections in all except one, presentation with increased Qp in 60.0% and presence of inferior vena caval interruption in 60.0% patients. CONCLUSIONS Present study, largest study of dextrocardia till date reconfirms that these patients have variable intracardiac anatomy depending upon their situs and types of segmental connections. These patients can present with different haemodynamic subsets, which can be correctly identified by colour Doppler echocardiography. Diagnostic accuracy and a better understanding of the various types of dextrocardia are essential, since improved surgical techniques have made it possible to correct many of these complex abnormalities.

Anti-annexin V antibodies in Takayasu's arteritis: prevalence and relationship with disease activity.

Annexin V has an important role in the regulation of apoptosis and antibodies directed against it have been shown to lead to apoptosis of vascular endothelial cells. To evaluate the role of anti‐annexin V antibodies (AA5A) in Takayasus arteritis (TA), we investigated these antibodies in the sera of 66 TA patients, 50 healthy controls and in the follow‐up sera of 12 active TA patients by enzyme‐linked immunosorbent assay. The AA5A‐positive patients were analysed further for the presence of anti‐endothelial cell antibodies (AECA) and anticardiolipin antibodies (ACLA) to determine the relationship of AA5A with these autoantibodies. AA5A were observed in 36% (24/66) of the patients versus 6% (3/50) of the controls (P < 0·001) and in 53% (19/36) of patients with active TA versus 17% (5/30) of those with inactive disease (P < 0·01). Levels of AA5A were also observed to be significantly higher in patients with TA compared to controls (0·557 ± 0·362 versus 0·259 ± 0·069; P < 0·0001) and in patients with active disease compared to those with inactive disease (0·700 ± 0·403 versus 0·385 ± 0·205; P < 0·0001). In the follow‐up study, 6/12 patients who became inactive during follow‐up also showed normalization of AA5A levels. AECA and ACLA were detected in 54% (13/24) and 12% (3/24) of the AA5A‐positive patients, respectively. Our results show that a significant proportion of TA patients have AA5A, which exhibit an association with AECA and because they have a correlation with disease activity thus appear to be involved in the disease pathogenesis.

Twelve-month outcomes in patients with diabetes implanted with a zotarolimus-eluting stent: results from the E-Five Registry

Objective To retrospectively evaluate the 12-month effectiveness of the Endeavor zotarolimus-eluting stent (ZES) in diabetic versus non-diabetic patients enrolled in the E-Five Registry. Design and Setting The E-Five Registry is a prospective, multicentre registry of 8314 patients presenting with symptomatic coronary artery disease treated with the Endeavor (ZES). Patients were treated at 188 centres located in 37 countries across Europe, Latin America and Asia Pacific. Patients There were 2721 (32.7%) patients with diabetes (DM) and among these patients 682 were insulin-treated (ITDM) and 2039 were non-insulin-treated diabetic patients (NITDM). Interventions All enrolled patients received an Endeavor ZES and were followed for 12 months. Main outcome measurements The primary outcome measure was major adverse cardiac event (MACE) at 12 months. Secondary endpoints included target lesion revascularisation (TLR), target vessel revascularisation (TVR), target vessel failure (TVF) and stent thrombosis. Results Compared with non-DM patients, DM patients had higher rates of MACE (9.7% vs 6.4%, p<0.001), TLR (5.3% vs 4.0%, p=0.028) and Academic Research Consortium (ARC) definite and probable stent thrombosis (1.5% vs 0.9%, p=0.041). Compared with non-DM patients, ITDM patients had higher rates of MACE (12.6% vs 6.4%, p<0.001). ITDM patients had higher rates of death (6.7% vs 1.7%, p<0.001), cardiac death (4.5% vs 1.2%, p<0.001) and TLR (6.5% vs 4.0%, p=0.011) than non-DM patients. Conclusions The Endeavor ZES performed well in DM patients; however, DM patients experienced higher rates of adverse clinical events compared with non-DM patients. Trial Reg No Clinical trial registration information: http://www.clinicaltrials.gov; Unique identifier: NTC00623441

Impact of alcohol on coronary heart disease in Indian men.

BACKGROUND Moderate alcohol consumption is known to be protective against coronary heart disease (CHD). However, the INTERHEART study, a case-control study of acute myocardial infarction (MI) patients, revealed that alcohol consumption in South Asians was not protective against CHD. We therefore planned to study cardiovascular risk factor and CHD prevalence among male alcohol users as compared to age matched lifetime abstainers. METHODS The subjects for this study were recruited from a cross-sectional survey carried out among employees and their family members aged 20-69 years in 10 medium-to-large industries from diverse sites in India, using a stratified random sampling technique. Information on education, behavioral, clinical and biochemical risk factors of CHD and alcohol use was obtained through standardized instruments. CHD diagnosis was based on Rose Questionnaire or a prior physician diagnosed CHD. RESULTS A total of 4465 subjects were present or past alcohol users. The mean age of alcohol users and lifetime abstainers was 42.8+/-11.0 years and 42.8+/-11.1 years, respectively (p=0.90). Systolic blood pressure and diastolic blood pressure were significantly higher in alcohol users (128.7+/-17.6 mmHg/80.1+/-11.3 mmHg) as compared to lifetime abstainers (126.9+/-15.9 mmHg/79.5+/-10.3 mmHg, p<0.01). Fasting blood sugar in alcohol users (98.7+/-30.5 mg%) was also significantly higher than lifetime abstainers (96.6+/-26.0 mg%, p<0.01). Total cholesterol was lower in alcohol users (179.1+/-41.1 mg%) as compared to lifetime abstainers (182.7+/-38.2 mg%, p<0.01). HDL cholesterol was higher in alcohol users (42.9+/-10.8 mg%) as compared to lifetime abstainers (41.3+/-10.0 mg%, p<0.01). Body mass index (BMI) was lower in alcohol users as compared to lifetime abstainers (22.7+/-4.1 kg/m2 vs. 24.0+/-3.3 kg/m2, p<0.001). Tobacco use was significantly higher in alcohol users (63.1% vs. 20.7%). The odds ratio (OR) of having CHD after adjusting for tobacco use, BMI and education was 1.4 (95%CI 1.0-1.9) in alcohol users as compared to controls. The OR was 1.2 (95%CI 0.8-1.6) in occasional alcohol users, 1.6 (95%CI 1.0-2.2) in regular alcohol users and 2.1 (95% CI 1.1-3.0) in past alcohol users as compared to controls. CONCLUSION We did not observe an inverse (protective) association between alcohol intake and the prevalence of CHD. In contrast, our study indicated an association in the reverse direction, suggesting possible harm of alcohol for coronary risk in Indian men. This relationship needs to be further examined in large, prospective study.

Paraoxonase 1 gene polymorphisms contribute to coronary artery disease risk among north Indians

BACKGROUND Polymorphisms in paraoxonase 1 (PON1) coding for PON1 enzyme have been studied as genetic markers of coronary artery disease (CAD). PON1 Q192R and PON1 L55M polymorphisms have been analyzed extensively, but data on association and role of these polymorphisms in the etiology of CAD are conflicting. In this study, we tested the genetic association between PON1 Q192R and PON1 L55M polymorphisms and CAD among north Indians. MATERIALS AND METHODS Two hundred eighty-five angiographically proven patients with coronary artery disease and 200 sex-matched and ethnically matched controls were genotyped for 2 PON1 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Genotype/ allele frequencies were compared in patients and controls using the chi-square test. RESULTS At PON1-192 locus, there were significant differences between patients and controls (P< 0.05), leading to significant odds ratios for RR genotype (OR= 1.92, CI: 1.19-3.10) and *R allele (OR= 1.30, CI: 1.00-1.70). These odds ratios were higher in the sub-sample of smokers (2.84 and 1.45, respectively). Binary logistic regression analysis also confirmed that *R allele carriers (QR and RR) have a higher risk of CAD (OR= 3.54, CI: 1.67-5.53). PON1-55 locus did not show significant differences between patients and controls, but LL genotype and *L allele were significant risk factors in the nonsmoker group. RL haplotype was also significantly associated with CAD risk (OR= 1.44, CI: 1.08-1.93). CONCLUSIONS PON1-192R allele and RR genotype are significantly associated with CAD patients from the north Indian population (Uttar Pradesh). This association was stronger in smokers, supporting the conclusion that an interaction between PON1 activity and smoking augments CAD risk. Further studies with larger sample size are warranted to confirm these associations in different Indian populations.

Digoxin or verapamil or metoprolol for heart rate control in patients with mitral stenosis--a randomised cross-over study.

The effect and choice of a drug to control heart rate for symptomatic improvement in patients with isolated mitral stenosis with normal sinus rhythm (n = 10) or atrial fibrillation (n = 10) were studied. Digoxin (0.25-0.5 mg daily), metoprolol (50-100 mg twice a day) and verapamil (40-80 mg three times a day) were evaluated for this purpose. An open randomised cross-over design was followed. The efficacy of a drug was evaluated by: (1) subjective improvement on a visual analog scale, and (2) objective improvement on repeated multi-stage symptom-limited treadmill exercise. In patients with sinus rhythm greater than or equal to 50% subjective improvement was seen in 90%, 40% and nil with metoprolol, verapamil and digoxin, respectively. The total work done by these patients was 1008 +/- 541 kpm (control), 2869 +/- 1418 kpm on metoprolol, 2369 +/- 884 kpm on verapamil and 1654 +/- 918 kpm on digoxin. In patients with atrial fibrillation greater than or equal to 50% subjective improvement was seen in 80%, 40% and 30% with verapamil, metoprolol and digoxin, respectively. The total work done by these patients was 555 +/- 232 kpm (control), 1379 +/- 553 kpm on verapamil, 1251 +/- 575 kpm on metoprolol and 716 +/- 340 kpm on digoxin. The degree of improvement on a drug appeared to be a function of its ability to control resting and exercise heart rates in two different rhythms in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Glutathione S-transferase gene polymorphism as a susceptibility factor for acute myocardial infarction and smoking in the North Indian population.

Objectives: Glutathione S-transferase (GST) plays a key role in the detoxification of xenobiotic atherogens generated by smoking. We investigated whether functional GST gene polymorphism might be associated with acute myocardial infarction (AMI) and smoking. No such investigation has previously been conducted among North Indians. Methods: 230 patients with AMI and 300 healthy controls of North Indian ethnicity were enrolled in the study. GSTM1/T1/P1 gene polymorphisms were examined using restriction fragment length polymorphism. Results: When GST polymorphism was analyzed in patients with AMI, GSTM1 null genotype frequencies were 0.24 and 0.21 among cases with coronary artery disease and controls, respectively. The respective GSTT1 null genotype frequencies were 0.10 and 0.20 (p = 0.001). GSTP1 variant Val/Val allele frequencies were 0.02 and 0.07 with p = 0.03. After risk factor adjustment, only GSTP1Val/Val was found to be protective against disease. Considering the effect of GST (T1, M1, and P1) gene polymorphism on smoking, subjects were further divided into smokers and nonsmokers. However, GSTT1 null as well as GSTP Val/Val genotypes were protective only in nonsmokers (p = 0.01 and p = 0.04). Conclusions: A significant protective effect of GSTT1 null and GSTP1 Val genotype against disease was observed in patients with AMI although protection was limited to nonsmokers.