Clinical safety profile of ticagrelor compared to clopidogrel in 1208 patients: Real world evidence.

INTRODUCTION: Dual antiplatelet treatment is recommended by current clinical practice guidelines for patients undergoing PCI. The PLATO trial showed superiority of ticagrelor to clopidogrel in reducing the rate of death from vascular causes, myocardial infarction and stroke without increase in the rate of overall major bleeding in ACS patients. However, real world evidence in Indian patients is limited. The objective of this study is to compare safety profile of ticagrelor with clopidogrel in real world settings. METHODOLOGY: In this single centered retrospective observational study, a total of 1208 serial patient records undergoing PCI (ACS and stable angina patients as well) treated with Ticagrelor or Clopidogrel were collected and analyzed to look into in hospital outcomes. We excluded the patient's data that were incomplete. RESULTS: In total of 1208 patients, 604 patients received ticagrelor and similarly 604 patient received clopidogrel. No significant differences in the rates of major life threatening bleeding and any major bleeding were observed between ticagrelor and clopidogrel group (0.2% (n = 1) vs. 0.7% (n = 4), p = 0.18 and 2.8% (n = 17) vs. 3% (n = 18), p = 0.86 respectively). There was increase in minor bleeding rate with ticagrelor compared to clopidogrel (21.4% & 13.6%, p = 0.00). CONCLUSION: In the real world settings, patients undergoing PCI treated with ticagrelor showed similar safety profile compared to clopidogrel but with increase in minor bleeding rate. The observed results were in alignment with PLATO clinical trial.

Traumatic Fracture of Pacemaker Lead by Suture Transfixation to Pectoral Muscle.

We report acute lead fracture during pacemaker implantation. Suturing the lead without the sleeve might damage the lead. To avoid this result, we suggest tying knots tightly, but not too vigorously.

Qualitative Analysis of the Most Cited Publications from Leading Indian Medical Institutions.

BACKGROUND AND OBJECTIVES: The most important responsibility of physicians is research - advancement of medical knowledge is the core on which the other responsibilities, patient care and research, are based. This study was planned to conduct a qualitative analysis of the major publications from the the country's leading medical institutions. METHODS: We used Scopus to generate a list of total number of publications from the topmost institutions, the number of citations, and citations per article. We calculated the h-index, g-index, i-10 index, and h5-index for these institutions. A more detailed analysis was carried out for the top 20 most cited papers in each of the institutions. Only descriptive statistics were used. RESULTS: Among the top 10 medical institutions included, AIIMS, Delhi and PGIMER, Chandigarh were the top institutes, accounting for more publications and citations than the next eight institutions combined. The other institutions also managed to publish a large number of highly-cited papers. AIIMS was the leading institution when other indices were calculated. Among the most-cited articles, >80% had first/corresponding authors from outside India. A large number papers remained uncited, even after many years of publication. INTERPRETATION AND CONCLUSIONS: Uncited papers could be a result research conducted with the purpose of getting the numbers needed for promotion (NNP). Importance of collaborative research was seen to be an important factor when citations are considered. Even with the huge resource deficit, our institutes managed to publish a decent number of highly cited articles, which can be boosted if funding situation is improved.

Genetic polymorphisms, Biochemical Factors, and Conventional Risk Factors in Young and Elderly North Indian Patients With Acute Myocardial Infarction.

This study compared genetic polymorphisms (factor V Leiden [FVL] 1691G/A, factor VII [FVII] 10976G/A, FVII HVR4, platelet membrane glycoproteins GP1BA 1018C/T, GP1BA VNTR, integrin ITGB3 1565T/C, ITGA2 807C/T and methylenetetrahydrofolate reductase [MTHFR] 677C/T), biochemical (fibrinogen and homocysteine), and conventional risk factors in 184 young and 166 elderly north Indian patients with acute myocardial infarction (AMI). Univariate analysis revealed higher prevalence of hypertension and obesity in elderly patients while smoking, alcohol intake, and low socioeconomic status in young patients (P < .001). Although mean fibrinogen predominated (P = .01) in elderly patients, mean homocysteine was higher (P < .001) among young patients. Prevalence of hyperhomocysteinemia was greater in young than in elderly patients (odds ratio: 2.8, 95% confidence interval: 1.8-4.4, P < .001); however, genetic polymorphisms were equally prevalent in young and elderly patients. Multiple logistic regression analysis showed smoking (P < .001), alcohol intake (P = .046), and hyperhomocysteinemia (P = .001) to be associated with AMI in the young patients while hypertension (P = .006) in elderly patients. To conclude, smoking, alcohol intake, and elevated homocysteine are the risk factors for AMI among young while hypertension among elderly patients.

Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction--MI3 Trial.

BACKGROUND & OBJECTIVES: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. METHODS: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). RESULTS: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 10 [8] (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. INTERPRETATION & CONCLUSIONS: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

Heart failure in children in tropical regions.

With the ever increasing younger population in tropical countries, the number of children with heart failure is increasing. However, the etiology of heart failure in this region varies considerably from that in the temperate region, with infectious causes leading the list. In this review, we have summarized the important causes of heart failure seen in the pediatric population in tropical regions.

Putting the humanities back into medicine: some suggestions.

The practice of medicine is an art as well as a science. As doctors diagnose illness and treat patients day after day, they constantly interweave the social, psychological, ethical and scientific aspects of clinical practice. However, the humanistic values necessary for this approach are generally perceived to be lacking in today's medical practice. The Medical Council of India (MCI) believes that a course in medical humanities can help students cultivate a humane attitude towards their patients, as well as give them the knowledge and skills to deal with the complex challenges they will face as they practise medicine. The new Graduate Medical Regulations being formulated by the MCI provide time for teaching this aspect of medical practice. This paper contains some suggestions for the implementation of a medical humanities course in medical colleges.

Association of thrombomodulin gene polymorphisms and plasma thrombomodulin levels with acute myocardial infarction in north Indian patients.

This is the first study from north India that investigated the association of thrombomodulin (TM) polymorphisms with acute myocardial infarction (AMI) in 350 patients (≤ 40 years, n = 184 and ≥ 60 years, n = 166) and 350 matched-controls. The TM polymorphisms were determined by polymerase chain reaction-single-stranded conformational polymorphism and DNA sequencing. The TM 1418TT genotype (odds ratio [OR] 2.8; 95% confidence interval [CI] 1.3-6.4; P = .012) was independent risk predictor of young AMI as were hypertension (OR 3.3; 95% CI 1.8-5.9; P < .001), diabetes mellitus (OR 14.3; 95% CI 2.9-44.6; P = .001), smoking (OR 13.8; 95% CI 7.7-24.7; P < .001), family history (OR 1.8; 95% CI 1.1-3.3; P = .045), high body mass index (OR 2.2; 95% CI 1.3-3.6; P = .002), and high waist-hip ratio (OR 4.1; 95% CI 2.4-7.1; P < .001). Mean plasma TM also showed association with young AMI (P < .001). Smoking carriers of TM 1418CT + TT genotype had significantly higher risk of AMI (OR 12.8; 95% CI 6.0-27.3; P < .001) when compared with nonsmoking noncarriers. In conclusion, TM 1418C/T polymorphism is independent predictor of AMI and synergies with smoking.

Prothrombotic gene polymorphisms and plasma factors in young North Indian survivors of acute myocardial infarction.

The aim of this study was to evaluate the association of prothrombotic gene polymorphisms [factor V Leiden (FVL) 1691GA, factor VII (FVII) 10976GA, FVII HVR4, platelet membrane glycoproteins GP1BA 1018CT, GP1BA VNTR, integrin ITGB3 1565TC, integrin ITGA2 807CT and methylenetetrahydrofolate reductase (MTHFR) 677C/T], plasma factors (fibrinogen and homocysteine) and traditional risk factors with acute myocardial infarction (AMI) in 184 patients ≤ 40 years of age and 350 controls (≤ 40 years) from north India. Multiple logistic-regression analysis showed that hypertension (OR 1.9, 95 % CI 1.1-3.8, p = 0.042), diabetes mellitus (OR 10.5, 95 % CI 2.0-56.7, p = 0.006), smoking (OR 7.1, 95 % CI 3.7-13.6, p < 0.001), low socio-economic status (OR 13.5, 95 % CI 2.3-78.4, p = 0.004), high waist-hip ratio (OR 35.6, 95 % CI 11.1-53.7, p < 0.001) and FVL 1691GA (OR 6.0, 95 % CI 1.2-13.4, p = 0.03) were independent risk predictors of AMI in young. Elevated plasma fibrinogen also showed association with increased AMI risk. ITGA2 807C/T polymorphism showed protection against AMI in univariate analysis only, while GP1BA VNTR-ac (OR 0.4, 95 % CI 0.2-0.9, p = 0.033) showed significant protection even after adjusting for age and sex. Multinominal logistic-regression analysis showed gene-gene (GP1BA 1018C/T with GP1BA VNTR and ITGA2 807C/T with ITGB3 1565T/C polymorphisms) and gene-environment interactions (gene polymorphisms with smoking) operating in the occurrence of AMI in young. In conclusion, the role of inherited predisposition to thrombosis in complex, polygenic and multifactorial disease like AMI is limited to certain genetic factors, in combination with environmental factor like smoking.

Synergistic effect of angiotensin II type-1 receptor 1166A/C with angiotensin-converting enzyme polymorphism on risk of acute myocardial infarction in north Indians.

INTRODUCTION: This first study from north India investigated the synergistic effect of AT1R 1166A/C with the ACE I/D polymorphism on risk of acute myocardial infarction (AMI). MATERIALS AND METHODS: Traditional coronary risk factors, ACE I/D and AT1R 1166A/C polymorphism were analyzed in 350 patients with AMI and 350 matched controls. RESULTS: In univariate analysis, hypertension (52.9% vs. 11.1%; OR=8.9; 95%CI 6.0-13.3), diabetes mellitus (16.0% vs. 0.6%; OR=33.1; 95%CI 8.0-137), smoking (43.7% vs. 20.9%; OR=2.9; 95%CI 2.1-4.1), family history of coronary artery disease (22.3% vs. 14.0%; OR=1.8; 95%CI 1.2-2.6), high body mass index (64.3% vs. 51.4%; OR=1.7; 95%CI 1.3-2.3), high waist-hip ratio (46.2% vs. 2.3%; OR=37; 95%CI 16-85.8) and AT1R 1166AC genotype (20.6% vs. 12%; OR=1.9; 95%CI 1.3-2.9) were associated with AMI. In multivariate analysis, all these factors were found to be independent risk predictors for AMI. Subjects carrying the AT1R 1166AC+CC and ACE ID+DD combined genotype showed a twofold increased association (OR=2.1; 95%CI 1.2-3.5) compared with the AT1R 1166AA-ACE II combined genotype. Patients who smoked and who carried the ACE ID+DD genotype had 2.4-fold (OR=2.4; 95%CI 1.5-3.8), and with the AT1R 1166AC+CC genotype had 15-fold (OR=14.9; 95%CI 5.2-42.8) increased risk of AMI compared with non-smoking non-carriers. CONCLUSIONS: The AT1R 1166A/C polymorphism has association with AMI among north Indian patients, particularly if integrated with ACE I/D polymorphism and smoking.

Adhesion molecule expression and ventricular remodeling in chronic rheumatic heart disease: a cause or effect in the disease progression--a pilot study.

BACKGROUND: Rheumatic fever and chronic rheumatic heart disease (RHD) remains one of the most important causes of cardiovascular morbidity leading to a major public health problem, especially in developing countries. This was a pilot study to assess the presence of inflammation and expression of adhesion molecules by immunohistochemistry (IHC) in endomyocardial biopsy specimens of patients with chronic RHD. METHODS: Endomyocardial biopsy was obtained from 14 patients of chronic RHD with no features of activity clinically. Biopsies were processed for histology and IHC. IHC was carried using monoclonal antibodies against CD3, CD4, CD8, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. RESULTS: Histomorphologically, varying degree of interstitial and perivascular fibrosis was seen in all the 13 patients (100%). Mild fibrosis (1+) was seen in five patients (38.5%); moderate interstitial fibrosis (2+) was present in four patients (30.8%).There was no Aschoff nodule or evidence of active myocarditis in any of the biopsy specimens. IMMUNOHISTOCHEMISTRY: Moderate positivity of (2+) and intense positivity of (3+) for intercellular adhesion molecule-1 was seen in 11 and 2 patients, respectively. With vascular cell adhesion molecule-1, four showed mild positivity (1+), and three showed intense positivity (3+). The phenotypic analysis of the inflammatory cells in our study revealed CD8(+) cells in 77%, CD4(+) in 23.1%, and CD3(+) in 38.5% of total patients, which suggests chronicity. CONCLUSION: The nonspecific histomorphological changes and increased adhesion molecules expression could be a part of the ventricular remodeling due to the hemodynamic stress by the stenotic or regurgitant lesions of RHD itself.

Congestive heart failure in Indians: how do we improve diagnosis & management?

Heart failure is a common cardiovascular disease with high morbidity and mortality. Unlike western countries where heart failure is predominantly a disease of the elderly, in India it affects younger age group. Important risk factors include coronary artery disease, hypertension, diabetes mellitus, valvular heart disease and cardiomyopathies. Plasma brain natriuretic peptide levels are helpful in the diagnosis of heart failure. Echocardiography is the primary imaging modality of choice, through recently cardiac magnetic resonance imaging (MRI) has been found to play an increasing role. Aim of management is to improve symptoms & enhance survival. Diuretics are important in relieving symptoms. Beta-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers and adosterone antagonists improve survival in patients with impaired systolic function. Device therapy including cardiac resynchronization therapy and implantable cardiac defibrillators, though expensive are useful in selected patients. Unlike in patients with systolic heart failure where several therapies have been shown to improve survival, clinical trial results in diastolic heart failure have been disappointing and therapy in these patients is restricted to symptom improvement and risk factor control. Therapies like stem cell therapy are being evaluated in clinical trials and appear promising. Early diagnosis and appropriate therapy helps in reversing the process of remodelling and clinical improvement in most of the patients.

Association of ACE and FACTOR VII gene variability with the risk of coronary heart disease in north Indian population.

The angiotensin converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin. Chronic exposure to high levels of circulating and tissue ACE predispose to vascular wall thickening and atherosclerosis. Factor VII (FACTOR VII) is the first enzyme in the extrinsic pathway of the blood coagulation system and plays a key role in hemostasis; it also contributes to the occurrence of thrombotic events. In this study, we have examined the association of ACE and FACTOR VII gene in coronary heart disease patients (n = 300) and their age-matched controls (n = 300). Genotyping was done by PCR-RFLP method. No significant difference was observed in the distribution of I/D genotypes of ACE between cases and controls. In case of FACTOR VII R353Q polymorphism, there was not much difference in the distribution of alleles. AA genotype had protective effect for CHD (OR 0.56, 95% CI 0.37-0.83, P = 0.001). In case of FACTOR VII VNTR, there was difference in the distribution of alleles, H6 (73.5) and H7 (25.5) in cases, and H6 (70.5) and H7 (30.5) in controls. H6H7 and H7H7 genotypes had a protective effect for CHD with OR 0.27, 95% CI 0.18-0.41, P < 0.001, and OR 0.18, 95% CI 0.09-0.36, P < 0.001. Our study showed D allele of ACE to be associated with marginal risk of CHD, AA genotype of FACTOR VII R353Q and H6H7 and H7H7 genotypes of FACTOR VII VNTR showed protective effect for CHD.