A common Matrix metalloproteinase 8 promoter haplotype enhances the risk for hypertension via diminished interactions with nuclear factor kappa B.

OBJECTIVES: Matrix metalloproteinase 8 (MMP8) has a prominent role in collagen turnover in blood vessels and vascular remodeling. The contribution of regulatory single nucleotide polymorphisms in MMP8 to cardiovascular diseases is unclear. We aimed to delineate the influence of MMP8 promoter variations on hypertension. METHODS: A case-control study in unrelated individuals ( n  = 2565) was carried out. Resequencing of the MMP8 proximal promoter, linkage disequilibrium analysis, genotyping of variants and regression analyses were performed. MMP8 promoter-reporter constructs were generated and expressed in human vascular endothelial cells under various conditions. RESULTS: We identified four single nucleotide polymorphisms (SNPs) in the promoter region of MMP8 : -1089A/G (rs17099452), -815G/T (rs17099451), -795C/T (rs11225395), -763A/T (rs35308160); these SNPs form three major haplotypes. Hap3 (viz., GTTT haplotype) carriers showed significant associations with hypertension in two geographically distinct human populations (e.g., Chennai: odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.16-1.86, P  = 2 × 10 -3 ; Chandigarh: OR = 1.85, 95% CI = 1.21-2.81, P  = 4 × 10 -3 ). Hap3 carriers also displayed elevated systolic blood pressure, diastolic blood pressure and mean arterial pressure levels. Hap3 promoter-reporter construct showed lower promoter activity than the wild-type (Hap1) construct. In silico analysis and molecular dynamics studies predicted diminished binding of the transcription factor nuclear factor kappa B (NF-κB) to the functional -815T allele of Hap3 compared to the -815G wild-type allele; this prediction was validated by in-vitro experiments. Hap3 displayed impaired response to tumor necrosis factor-alpha treatment, possibly due to weaker binding of NF-κB. Notably, MMP8 promoter haplotypes were identified as independent predictors of plasma MMP8 and endothelial dysfunction markers (von Willebrand factor and endothelin-1) levels. CONCLUSION: MMP8 promoter GTTT haplotype has a functional role in reducing MMP8 expression during inflammation via diminished interaction with NF-κB and in enhancing the risk of hypertension.

STEMI India: reimagining STEMI networks in low- and middle-income countries: Reimagining STEMI.

Effective treatment for ST-elevation myocardial infarction (STEMI) includes the 24/7 availability of reperfusion therapy, which is crucial for good clinical outcomes. In low- and middle-income countries, this is hindered by disparities in resource utilisation, irregularities in access to health care and organisational gaps. Due to the inaccessibility of primary percutaneous coronary intervention (PCI) for most patients, the more feasible and practical approach of pharmacoinvasive management must be incorporated into the systems of care for STEMI. This review focuses on the development of STEMI India, a not-for-profit organisation that aims to advance the field of STEMI management by imparting and disseminating the latest information from around the world on STEMI management to all those involved in STEMI care. The STEMI India model system of care includes a 3-model framework, based on infrastructure and workforce availability, and tailored to meet the needs of the society it caters to. After the successful implementation of the "Tamil Nadu STEMI" project, a nationwide system of care for STEMI has been developed, which has been endorsed by the Cardiological Society of India (CSI) and the Association of Physicians of India (API).

Safety and feasibility of intravascular ultrasound guided zero-contrast percutaneous coronary intervention-A prospective study.

BACKGROUND: There are published reports of safety and feasibility of percutaneous coronary intervention (PCI) without contrast, using intravascular ultrasound (IVUS) and coronary physiology guidance in chronic kidney disease population. We prospectively evaluated the safety and feasibility of zero-contrast PCI technique. METHODS: In this prospective study, we hypothesized that PCI is feasible without contrast, using IVUS guidance alone without mandatory coronary physiology to rule out slow-flow or no-flow at the end of PCI in a population at risk of contrast-induced acute kidney injury (CI-AKI). In this study, we included 31 vessels in 27 patients at risk of CI-AKI and assessed the primary outcome of technical success at the end of PCI. Major adverse cardio-cerebro vascular events (MACCE) and percent change in estimated glomerular filtration rate(eGFR) one month after PCI were the secondary outcomes of the study. RESULTS: The primary outcome was met in 87.1%(n = 27) of the procedures. Technical failure was seen in 12.9%(n = 4) of the procedures. None of the patients developed MACCE at one-month follow-up. The median percent change in eGFR at one-month follow-up was -8.19%(-24.40%, +0.92%). There was no newer initiation of renal replacement therapy at one-month follow-up. CONCLUSIONS: Zero-contrast PCI is safe and feasible in selective coronary anatomies with IVUS guidance. Coronary physiology is not mandatory to rule out slow-flow or no-flow at the end of procedure. Contrast may be needed to tide over the crisis during the possible complications, namely slow-flow, geographical miss and intraprocedural thrombus.

Sex-Related Differences in Outcomes for Patients With ST Elevation Myocardial Infarction (STEMI): A Tamil Nadu-STEMI Program Subgroup Analysis.

BACKGROUND: ST elevation myocardial infarction (STEMI) represents a large proportion of the clinical presentation of coronary artery disease in Indian people. Owing to multiple factors contributing to the sex difference, women with STEMI are thought to have a higher risk of adverse outcomes than men. The aim of this study was to evaluate sex-related differences in the clinical characteristics and prognosis of patients with STEMI within a system of care. METHOD: This study was a subgroup analysis of the Tamil Nadu-STEMI (TN-STEMI) program, a multicentre, prospective, observational study of a quality-improvement program studying patients with STEMI at four hub-and-spoke clusters in the southern state of Tamil Nadu, India. In total, 2,420 patients were enrolled between 2012 and 2014, and the data from all four clusters, pre- and postimplementation of integrated STEMI systems, were combined for this analysis, with a 1-year follow-up. RESULTS: The mean ± SD age of presentation of female patients (16%) was significantly later (60.1±10.9 years) compared with males (84%; 53.7±12 years). Diabetes was more prevalent in women (35.2% vs 23.8%; p<0.001), as was hypertension (35.2% vs 22.9%; p<0.001). Symptom to first medical contact in female patients was significantly delayed compared with males (193 mins vs 170 mins; p≤0.009). Women had higher mortality, both in hospital (10.4% vs 4.8%; p≤0.001) and at 1 year (26.7% vs 13%; p≤0.001). This pattern was persistent, even in the younger STEMI (<45 years) population (in-hospital: 9.1% vs 3% [p≤0.05]; at 1 year: 18.2% vs 3% [p≤ 0.05]). In the regression model, females had a 1.8 times increased likelihood (p<0.04) of mortality after adjusting for confounders. CONCLUSIONS: Among patients with STEMI, women have an unfavourable risk profile and adverse short- and long-term prognoses when compared to men.

Radiation doses during cardiac catheterisation procedures in India: a multicentre study: Radiation dose study.

AIMS: Established, evidence-based measures of radiation are required to minimise its hazards, while maintaining adequate image quality. The aim of this study is to evaluate radiation data and generate reference radiation levels for commonly performed coronary catheterisation procedures in India. METHODS AND RESULTS: In this prospective, observational study, all procedures were performed in accordance with the established standards using Innova IGS 520/2100-IQ catheterisation laboratories. Demographic, procedural and radiation data were collected. Dose reference limits (DRL) were established as the 75th percentile of the total distribution. There were 2,906 coronary angiograms (CAG), 750 percutaneous coronary interventions (PCI) and 715 CAG+PCI. DRLs for dose area product were: 19.6 Gy·cm2 for CAG, 49.8 Gy·cm2 for PCI and 72.0 Gy·cm2 for CAG+PCI, respectively. Median cumulative air kerma levels were: 185 mGy for CAG, 533mGy for PCI, and 891 mGy for CAG+PCI. Male gender, higher BMI, combining CAG+PCI, fluoroscopy time, number of cine frames, and image acquisition settings were significant contributors to increased radiation dose. CONCLUSIONS: This study established reference radiation dose levels for diagnostic and interventional coronary procedures in India, which were comparable to and in the lower range of international standards.

A Common Tag Nucleotide Variant in MMP7 Promoter Increases Risk for Hypertension via Enhanced Interactions With CREB (Cyclic AMP Response Element-Binding Protein) Transcription Factor.

MMP (matrix metalloproteinase)-7-a potent extracellular matrix degrading enzyme-is emerging as a new regulator of cardiovascular diseases. However, potential contributions of MMP7 genetic variations to hypertension remain unknown. In this study, we probed for the association of a tag single-nucleotide polymorphism in the MMP7 promoter (-181A/G; rs11568818) with hypertension in an urban South Indian population (n=1501). The heterozygous AG genotype significantly increased risk for hypertension as compared with the wild-type AA genotype (odds ratio, 1.60 [95% CI, 1.25-2.06]; P=2.4×10-4); AG genotype carriers also displayed significantly higher diastolic blood pressure and mean arterial pressure than wild-type AA individuals. The study was replicated in a North Indian population (n=949) (odds ratio, 1.52 [95% CI, 1.11-2.09]; P=0.01). Transient transfection experiments using MMP7 promoter-luciferase reporter constructs revealed that the variant -181G allele conferred greater promoter activity than the -181A allele. Computational prediction and structure-based conformational and molecular dynamics simulation studies suggested higher binding affinity for the CREB (cyclic AMP response element-binding protein) to the -181G promoter. In corroboration, overexpression/downregulation of CREB and chromatin immunoprecipitation experiments provided convincing evidence for stronger binding of CREB with the -181G promoter. The -181G promoter also displayed enhanced responses to hypoxia and epinephrine treatment. The higher promoter activity of -181G allele translated to increased MMP7 protein level, and MMP7-181AG heterozygous individuals displayed elevated plasma MMP7 levels, which positively correlated with blood pressure. In conclusion, the MMP7 A-181G promoter polymorphism increased MMP7 expression under pathophysiological conditions (hypoxic stress and catecholamine excess) via increased interactions with CREB and enhanced the risk for hypertension in its carriers.

The impact of systems-of-care on pharmacoinvasive management with streptokinase: The subgroup analysis of the TN-STEMI programme.

OBJECTIVES: We evaluated the impact of implementation of the TN-STEMI programme on various characteristics of the pharmacoinvasive group by comparing clinical as well as angiographic outcomes between the pre- and post-implementation groups. METHODS: The TN-STEMI programme involved 2420 patients of which 423 patients had undergone a pharmacoinvasive strategy of reperfusion. Of these, 407 patients had a comprehensive blinded core-lab evaluation of their angiograms post-lysis and clinical evaluation of various parameters including time-delays and adverse cardio- and cerebro-vascular events at 1year. Streptokinase was used as the thrombolytic agent in 94.6% of the patients. RESULTS: In the post-implementation phase, there was a significant improvement in 'First medical contact (FMC)-to-ECG' (11 vs. 5min, p<0.001) and 'Lysis-to-angiogram' (98.3 vs. 18.2h, p<0.001) times. There was also a significant improvement in the number of coronary angiograms performed within 24h (20.7% vs. 69.3%, p<0.001). The 'Time-to-FMC' (160 vs. 135min, p=0.07) and 'Total ischemic time' (210 vs. 176min, p=0.22) also showed a decreasing trend. IRA patency rate (70.2% vs. 86%, p<0.001) and thrombus burden (TIMI grade 0: 49.1% vs. 73.4%, p<0.001) were superior in this group. The MACCE rates were similar except for fewer readmissions (29.8% vs. 12.6%, p=0.0002) and target revascularizations at 1year (4.8% vs. none, p=0.002) in the post-implementation group. CONCLUSION: The implementation of a system-of-care (hub-and-spoke model) in the pharmacoinvasive group of the TN-STEMI programme demonstrated shorter lysis-to-angiogram times, better TIMI flow patterns and lower thrombus burden in the post-implementation phase.

A System of Care for Patients With ST-Segment Elevation Myocardial Infarction in India: The Tamil Nadu-ST-Segment Elevation Myocardial Infarction Program.

Importance: Challenges to improving ST-segment elevation myocardial infarction (STEMI) care are formidable in low- to middle-income countries because of several system-level factors. Objective: To examine access to reperfusion and percutaneous coronary intervention (PCI) during STEMI using a hub-and-spoke model. Design, Setting, and Participants: This multicenter, prospective, observational study of a quality improvement program studied 2420 patients 20 years or older with symptoms or signs consistent with STEMI at primary care clinics, small hospitals, and PCI hospitals in the southern state of Tamil Nadu in India. Data were collected from the 4 clusters before implementation of the program (preimplementation data). We required a minimum of 12 weeks for the preimplementation data with the period extending from August 7, 2012, through January 5, 2013. The program was then implemented in a sequential manner across the 4 clusters, and data were collected in the same manner (postimplementation data) from June 12, 2013, through June 24, 2014, for a mean 32-week period. Exposures: Creation of an integrated, regional quality improvement program that linked the 35 spoke health care centers to the 4 large PCI hub hospitals and leveraged recent developments in public health insurance schemes, emergency medical services, and health information technology. Main Outcomes and Measures: Primary outcomes focused on the proportion of patients undergoing reperfusion, timely reperfusion, and postfibrinolysis angiography and PCI. Secondary outcomes were in-hospital and 1-year mortality. Results: A total of 2420 patients with STEMI (2034 men [84.0%] and 386 women [16.0%]; mean [SD] age, 54.7 [12.2] years) (898 in the preimplementation phase and 1522 in the postimplementation phase) were enrolled, with 1053 patients (43.5%) from the spoke health care centers. Missing data were common for systolic blood pressure (213 [8.8%]), heart rate (223 [9.2%]), and anterior MI location (279 [11.5%]). Overall reperfusion use and times to reperfusion were similar (795 [88.5%] vs 1372 [90.1%]; P = .21). Coronary angiography (314 [35.0%] vs 925 [60.8%]; P < .001) and PCI (265 [29.5%] vs 707 [46.5%]; P < .001) were more commonly performed during the postimplementation phase. In-hospital mortality was not different (52 [5.8%] vs 85 [5.6%]; P = .83), but 1-year mortality was lower in the postimplementation phase (134 [17.6%] vs 179 [14.2%]; P = .04), and this difference remained consistent after multivariable adjustment (adjusted odds ratio, 0.76; 95% CI, 0.58-0.98; P = .04). Conclusions and Relevance: A hub-and-spoke model in South India improved STEMI care through greater use of PCI and may improve 1-year mortality. This model may serve as an example for developing STEMI systems of care in other low- to middle-income countries.

A case of recurrent unstable angina - Insight from optical coherence tomography imaging.

Intimal tear is a rare cause of ACS and is angiographically indistinguishable. OCT provides unprecendented insight to the mechanism of ACS with its near tissue level definition. This is a case of unstable angina with non-significant RCA lesion. OCT showed intimal tear/flaps with evidence of thrombi, thus clinching the diagnosis.

Prevalence of parameters of suboptimal scaffold deployment following angiographic guided bioresorbable vascular scaffold implantation in real world practice - an optical coherence tomography analysis.

AIM: To assess the prevalence of suboptimal bioresorbable vascular scaffold (BVS, Abbott Vascular, Santa Clara, California) deployment in real world practice with intracoronary optical coherence tomography (OCT) imaging. METHODS: Consecutive patients who underwent percutaneous coronary intervention using BVS and the final optimization assessed with OCT imaging in two tertiary care centers between December 2012 and February 2015 were evaluated for parameters of suboptimal scaffold deployment by OCT. RESULTS: Overall, 36 scaffolds were implanted in 27 patients during this period. Mean age of the population was 54.7±8.2years and 19 (70.4%) were type B2/C lesions. The prevalence of parameters of suboptimal scaffold deployment were: underexpansion-22(61.1%), geographic miss-3(8.3%), tissue prolapse-7(25.9%), scaffold pattern irregularity-1(2.8%), longitudinal elongation-7(38.8%). Of the 7 overlaps imaged: excessive overlap was observed in 3 and scaffold gap in one. The median duration of follow up was 679days (range 193-963days). There were four events during this period. None were associated with suboptimal scaffold deployment. CONCLUSION: OCT based parameters of suboptimal scaffold deployment are common in real world scenario and were not associated with adverse outcomes on long term follow up. These findings need to be confirmed in larger studies.

Two-year follow-up data from the STEPP-AMI study: A prospective, observational, multicenter study comparing tenecteplase-facilitated PCI versus primary PCI in Indian patients with STEMI.

BACKGROUND: A pharmacoinvasive strategy may alleviate the logistical and geographical barriers in timely reperfusion of ST-segment elevation myocardial infarction (STEMI), especially in a developing country like India. AIM: To assess the safety and efficacy of pharmacoinvasive strategy versus primary PCI in STEMI patients at 2 years. METHODS: Patients enrolled in STEPP-AMI, an observational, multicenter, prospective study of 200 patients presenting with STEMI, were followed up for 2 years. Group 'A' comprised of patients with pharmacoinvasive strategy (n=45), and patients who underwent primary PCI (n=155) formed group 'B'. Primary endpoint was composite of death, cardiogenic shock, reinfarction, repeat revascularization of the culprit artery, or congestive heart failure at 30 days, with follow-up till 2 years. RESULTS: The primary endpoint occurred in 11.1% and 17.8% in group A and in 3.9% and 13.6% in group B, at 30 days and 2 years, respectively (p=0.07, RR=2.87; 95% CI: 0.92-8.97 at 30 days and p=0.47, RR=1.31; 95% CI: 0.62-2.76). There was no difference in bleeding risk between groups, 2.2% in group A and 0.6% in group B ('p'=0.4). The infarct-related artery patency varied at angiogram; it was 82.2% in arm A and 22.6% in arm B ('p'<0.001). In group A, failed fibrinolysis occurred in 12.1%. CONCLUSION: A pharmacoinvasive strategy resulted in outcomes that were comparable with primary PCI at 2 years, suggesting it might be a viable option in India. Larger studies are required to confirm these findings.

Framework for a National STEMI Program: consensus document developed by STEMI INDIA, Cardiological Society of India and Association Physicians of India.

The health care burden of ST elevation myocardial infarction (STEMI) in India is enormous. Yet, many patients with STEMI can seldom avail timely and evidence based reperfusion treatments. This gap in care is a result of financial barriers, limited healthcare infrastructure, poor knowledge and accessibility of acute medical services for a majority of the population. Addressing some of these issues, STEMI India, a not-for-profit organization, Cardiological Society of India (CSI) and Association Physicians of India (API) have developed a protocol of "systems of care" for efficient management of STEMI, with integrated networks of facilities. Leveraging newly-developed ambulance and emergency medical services, incorporating recent state insurance schemes for vulnerable populations to broaden access, and combining innovative, "state-of-the-art" information technology platforms with existing hospital infrastructure, are the crucial aspects of this system. A pilot program was successfully employed in the state of Tamilnadu. The purpose of this article is to describe the framework and methods associated with this programme with an aim to improve delivery of reperfusion therapy for STEMI in India. This programme can serve as model STEMI systems of care for other low-and-middle income countries.

Risk scoring system to predict contrast induced nephropathy following percutaneous coronary intervention.

BACKGROUND: Contrast induced nephropathy (CIN) is associated with significant morbidity and mortality after percutaneous coronary intervention (PCI). The aim of this study is to evaluate the collective probability of CIN in Indian population by developing a scoring system of several identified risk factors in patients undergoing PCI. METHODS: This is a prospective single center study of 1200 consecutive patients who underwent PCI from 2008 to 2011. Patients were randomized in 3:1 ratio into development (n = 900) and validation (n = 300) groups. CIN was defined as an increase of ≥25% and/or ≥0.5 mg/dl in serum creatinine at 48 hours after PCI when compared to baseline value. Seven independent predictors of CIN were identified using logistic regression analysis - amount of contrast, diabetes with microangiopathy, hypotension, peripheral vascular disease, albuminuria, glomerular filtration rate (GFR) and anemia. A formula was then developed to identify the probability of CIN using the logistic regression equation. RESULTS: The mean (±SD) age was 57.3 (±10.2) years. 83.6% were males. The total incidence of CIN was 9.7% in the development group. The total risk of renal replacement therapy in the study group is 1.1%. Mortality is 0.5%. The risk scoring model correlated well in the validation group (incidence of CIN was 8.7%, sensitivity 92.3%, specificity 82.1%, c statistic 0.95). CONCLUSION: A simple risk scoring equation can be employed to predict the probability of CIN following PCI, applying it to each individual. More vigilant preventive measures can be applied to the high risk candidates.

A prospective, observational, multicentre study comparing tenecteplase facilitated PCI versus primary PCI in Indian patients with STEMI (STEPP-AMI).

OBJECTIVE: To compare the efficacy of pharmacoinvasive strategy versus primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). Primary PCI is the preferred treatment for STEMI, but it is not a feasible option for many. A pharmacoinvasive strategy might be a practical solution in the Indian context, although few empirical data exist to guide this approach. METHODS: This is a prospective, observational, multicentre pilot study. Two hundred consecutive patients with STEMI aged 18-75 years, presenting within 12 h of onset of symptoms and requiring a reperfusion strategy, were studied from five primary PCI capable centres in South India. Patients who opted for pharmacoinvasive strategy (n=45) formed group A. Group B consisted of patients treated with primary PCI (n=155). One patient was lost to follow-up at 1 year. The primary end point was a composite of death, cardiogenic shock, reinfarction, repeat revascularisation of a culprit artery and congestive heart failure at 30 days. RESULTS: The primary end point occurred in 11.1% in group A and in 3.9% in group B, p=0.07 (RR=2.87; 95% CI 0.92 to 8.97). The infarct-related artery patency at angiogram was 82.2% in group A and 22.6% in group B (p<0.001). PCI was performed in 73.3% in group A versus 100% in group B (p<0.001), and a thrombus was present in 26.7% in group A versus 63.2% in group B (p<0.001). Failed fibrinolysis occurred in 12.1% in group A. There was no difference in bleeding risk, 2.2% in group A versus 0.6% in group B, (p=0.4). CONCLUSIONS: This pilot study shows that a pharmacoinvasive strategy can be implemented in patients not selected for primary PCI in India and hints at the possibility of similar outcomes. Larger studies are required to confirm these findings. TRIAL REGISTRATION NUMBER: TRIAL IS REGISTERED WITH CLINICAL TRIAL REGISTRY OF INDIA, CTRI NUMBER: REF/2011/07/002556.

Outcome of primary PCI - an Indian tertiary care center experience.

OBJECTIVE: To assess the feasibility and outcomes of primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) in Indian Scenario. METHODS: Between January 2005 and December 2012, consecutive STEMI patients who underwent PPCI within 12 h of onset of chest pain were prospectively enrolled in a PPCI registry. Patient demographics, risk factors, procedural characteristics, time variables and in-hospital and 30 day major adverse cardiovascular events (MACE) [death, reinfarction, bleeding, urgent coronary artery bypass surgery (CABG) and stroke] were assessed. RESULTS: A total of 672 patients underwent PPCI during this period. The mean age was 52 ± 13.4 years and 583 (86.7%) were males, 275 (40.9%) were hypertensives and 336 (50%) were diabetics. Thirty one (4.6%) patients had cardiogenic shock (CS). Anterior myocardial infarction was diagnosed in 398 (59.2%) patients. The median chest pain onset to hospital arrival time, door-to-balloon time and total ischemic times were 200 (10-720), 65 (20-300), and 275 (55-785) minutes respectively. In-hospital adverse events occurred in 54 (8.0%) patients [death 28 (4.2%), reinfarction 8 (1.2%), major bleeding 9 (1.3%), urgent CABG 4 (0.6%) and stroke 1 (0.14%)]. Nineteen patients with CS died (mortality rate - (61.3%)). At the end of 30 days, 64 (9.5%) patients had MACE [death 35 (5.2%), reinfarction 10 (2.1%), major bleeding 10 (1.5%), urgent CABG 4 (0.6%) and stroke 1 (0.1%)]. CONCLUSION: Our study has shown that PPCI is feasible with good outcomes in Indian scenario. Even though the recommended door-to-balloon time can be achieved, the total ischemic time remained long. CS in the setting of STEMI was associated with poor outcomes.

Protocol for a prospective, controlled study of assertive and timely reperfusion for patients with ST-segment elevation myocardial infarction in Tamil Nadu: the TN-STEMI programme.

INTRODUCTION: Over the past two decades, India has witnessed a staggering increase in the incidence and mortality of ST-elevation myocardial infarction (STEMI). Indians have higher rates of STEMI and younger populations that suffer from it when compared with developed countries. Yet, the recommended reperfusion therapy with fibrinolysis and percutaneous coronary intervention is available only to a minority of patients. This gap in care is a result of financial barriers, limited healthcare infrastructure and poor knowledge and accessibility of acute medical services for a majority of its population. METHODS AND ANALYSIS: This is a prospective, multicentre, 'pretest/post-test' quasi-experimental, community-based study. This programme will use a 'hub-and-spoke' model of an integrated healthcare network based on clusters of primary-care health clinics, small hospitals and large tertiary-care facilities. It is an 'all-comers' study which will enrol consecutive patients presenting with STEMI to the participating hospitals. The primary objectives of the study is to improve the use of reperfusion therapy and reduce the time from first medical contact to device or drug in STEMI patients; and to increase the rates of early invasive risk stratification with coronary angiography within 3-24 h of fibrinolytic therapy in eligible patients through changes in process of care. Outcomes will be measured with statistical comparison made before and after implementing the TN-STEMI programme. The estimated sample size is based on the Kovai Erode Pilot study, which provided an initial work on establishing this type of programme in South India. It will be adequately powered at 80% with a superiority margin of 10% if 36 patients are enrolled per cluster or 108 patients in three clusters. Thus, the enrolment period of 9 months will result in a sample size of 1500 patients. ETHICS: This study will be conducted in accordance with the ethical principles that have their origin in the current Declaration of Helsinki and 'ethical guidelines for biomedical research on human participants' as laid down by the Indian Council for Medical Research. All participating hospitals will still obtain local ethics committee approval of the study protocol and written informed consent will be obtained from all participants. DISSEMINATION AND RESULTS: Our findings will be reported through scientific publications, research conferences and public policy venues aimed at state and local governments in India. If successful, this model can be extended to other areas of India as well as serve as a model of STEMI systems of care for low-income and middle-income countries across the world. REGISTRATION: Trial is registered with Clinical trial registry of India, No: CTRI/2012/09/003002.

Door-to-balloon: where do we lose time? Single centre experience in India.

BACKGROUND/AIMS: To assess the factors causing delay in attaining DTB time of <90 min. METHODS: Eighty-five patients who underwent primary PCI from August 2008 to July 2009 were studied. From door-to-balloon, time was divided into 6 stages; any reason for delay was studied. RESULTS: The mean DTB time was 80.5 min (SD = 34.4, median time 75 min, range 30-195). DTB time was <90 min in 76.5%, and DTB time >90 min occurred in 23.5%. Mean door to ECG - 6.5 min (SD = 2.7), mean time for the decision of PCI - 7.5 min (SD = 10.5), mean time taken for the patient's consent - 19.6 min (SD = 17.6), for STEMI team activation - 6.7 min (SD = 7.6), average time for financial process - 39.2 min (SD = 22.9). Average time for sheath to balloon - 5.2 min (SD = 1.7). Hospital related delay occurred in 5%, patient related delay in 80%, both together in 15%. 89.5% of patient related delay was due to delay in giving consent and financial reasons. There was no statistically significant delay for patients presented at morning or night and during the weekdays or weekend. Total mortality was 4.7%. Mortality among <90 min was 3.1%, mortality among >90 min was 10% ('p' = 0.2). CONCLUSIONS: With effective hospital strategies, the DTB time of 90 min can be achieved in majority of patients. The chief delay in DTB time in this study was due to a delay in obtaining consent and financial reasons.

Apical ballooning syndrome in first degree relatives.

Apical ballooning syndrome (Takotsubo cardiomyopathy) is an unusual stress-related reversible cardiomyopathy occurring commonly in postmenopausal females. Genetic etiology of this condition is uncertain. A 68-year-old female and her daughter aged 43 got admitted to our institute simultaneously with acute chest pain following demise of one of their close relative. Both had features typical of Takotsubo cardiomyopathy and recovered completely. This reports point to the possible genetic predisposition to this abnormality.

Single coronary artery from the right coronary sinus with proximal origin of the left anterior descending coronary artery and left circumflex as distal continuation of the right coronary artery: a rare variant.

A single coronary artery is a rare coronary anomaly. A 68-year-old male underwent coronary angiography for recent inferior wall myocardial infarction. It revealed a common coronary trunk arising from the right sinus of Valsalva and bifurcated into the right coronary artery (RCA) and anterior descending coronary arteries. The RCA, after its usual distribution in the right atrioventricular groove, continued as the left circumflex artery in the left atrioventricular groove. There were significant stenoses in the mid and distal RCA, which were treated percutaneously.