One-year clinical outcomes of different coronary drug eluting stents—Data from a prospective registry

We compared one-year clinical outcomes of different drug eluting stents (DES) used in a prospective observation registry maintained in two hospitals over three years. The primary endpoint was combination of all-cause mortality, stent thrombosis and revascularization. There was no significant difference among different DES. We grouped DES into well-evaluated Imported DES (Imported group), which used to be expensive prior to price control and economical Indian DES (Indigenous group) that lack supportive clinical trials. One-year follow-up data was available in 99% of Indigenous group (n=1856) and 98.5% of Imported group (n = 1539). After propensity score matching, there were 1310 matched pairs. There was no significant difference between two groups in the primary end-point or each of the components.

Epistatic interactions in idiopathic pulmonary arterial hypertension.

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a poorly understood complex disorder, which results in progressive remodeling of the pulmonary artery that ultimately leads to right ventricular failure. A two-hit hypothesis has been implicated in pathogenesis of IPAH, according to which the vascular abnormalities characteristic of PAH are triggered by the accumulation of genetic and/or environmental insults in an already existing genetic background. The multifactor dimensionality reduction (MDR) analysis is a statistical method used to identify gene–gene interaction or epistasis and gene–environment interactions that are associated with a particular disease. The MDR method collapses high-dimensional genetic data into a single dimension, thus permitting interactions to be detected in relatively small sample sizes. AIM: To identify and characterize polymorphisms/genes that increases the susceptibility to IPAH using MDR analysis. MATERIALS AND METHODS: A total of 77 IPAH patients and 100 controls were genotyped for eight polymorphisms of five genes (5HTT, EDN1, NOS3, ALK-1, and PPAR-γ2). MDR method was adopted to determine gene–gene interactions that increase the risk of IPAH. RESULTS: With MDR method, the single-locus model of 5HTT (L/S) polymorphism and the combination of 5HTT(L/S), EDN1(K198N), and NOS3(G894T) polymorphisms in the three-locus model were attributed to be the best models for predicting susceptibility to IPAH, with a P value of 0.05. CONCLUSION: MDR method can be useful in understanding the role of epistatic and gene–environmental interactions in pathogenesis of IPAH.

t-plasminogen activator inhibitor-1 polymorphism in idiopathic pulmonary arterial hypertension.

AIM: The aim of the present study was to identify the possible genotypic association of 3’UTR Hind III polymorphism of Plasminogen activator Inhibitor-1 (PAI-1) gene with idiopathic pulmonary arterial hypertension (IPAH). BACKGROUND: IPAH is a disorder with abnormally raised mean pulmonary arterial pressure and increase in the resistance to blood flow in pulmonary artery. One of the pathological features seen is development of intraluminal thrombin deposition leading to thrombosis. Plasminogen activator inhibitor-1 is an important inhibitor of the fibrinolytic system; its up-regulation may suppress fibrinolysis and result in an increased risk of thrombosis. METHOD: Blood samples from 54 IPAH patients and 100 healthy voluntary donors were analyzed by PCR-RFLP method for 3’UTR Hind III polymorphism. RESULTS AND DISSCUSSION: A significant association of Hd2 allele with the disease was observed. Raised mean level of right ventricular systolic pressure was observed in the Hd2/Hd2 genotypic patients, strengthening the role of Hd2 allele in the disease progression. Our data suggests an association of Hd2/Hd2 genotype, which may lead to the up-regulation of PAI-1 gene leading to increased levels of PAI-1, which is seen in IPAH. PAI-1 competes with plasminogen activators and hinders the normal mechanism of plasminogen activation system and leads to thrombosis and formation of plexiform lesions in the lung tissue, further strengthening its role in tissue remodeling and disease progression.

Sildenafil improves survival in idiopathic pulmonary arterial hypertension.

AIMS AND OBJECTIVES: Idiopathic Pulmonary Arterial Hypertension (IPAH) is a serious disorder of unknown etiology with limited therapeutic options. Sildenafil has been shown to decrease symptoms, improve hemodynamics and quality of life. Its impact on survival is uncertain. We studied the efficacy of sildenafil in improving survival in patients with IPAH. METHODS AND RESULTS: Data on survival of patients with IPAH was collected from prospectively maintained registry at our hospital from January 1999 to December 2005. Thirty nine patients who were treated with conventional therapy including digoxin, diuretics, anticoagulants and calcium channel blockers prior to January 2001 served as historical controls (control group). One hundred and thirty nine patients received sildenafil additionally from January 2001 (sildenafil group). All patients in sildenafil group showed improvement in symptoms. Survival of patients in sildenafil group was significantly better compared to historical controls receiving only conventional therapy. It was 89%, 43% and 19% in the control group Vs 93%, 75% and 54% in the sildenafil group at the end of 1, 3 and 5 years respectively (P Value=0.0002). Sildenafil was well tolerated and none of the patients had to discontinue the treatment. CONCLUSION: Sildenafil when added to conventional therapy improves symptoms as well as survival significantly compared to conventional therapy alone. Further randomized controlled trials are needed to evaluate its impact on survival when used either alone or in combination with other drugs.

Non-surgical transpericardial catheter ablation of post-infarction ventricular tachycardia.

Non-surgical transpericardial approach for catheter-based epicardial radiofrequency ablation of post-infarction left ventricular tachycardia has been described as an alternative and additive procedure to standard endocardial technique for delivery of radiofrequency energy in difficult situations. We report our initial experience with this approach in three patients of post-infarction recurrent ventricular tachycardia, refactory to multiple antiarrhythmic drugs. Ablation was successful in terminating the tachycardia in two and in modifying the circuit to be amenable for control with single antiarrhythmic drug in one patient. There were no serious acute or long-term complications related to the procedure. Epicardial approach is an effective and safe adjunct to standard endocardial ablative technique for patients of post-infarction ventricular tachycardia.

Plasma Lipoprotein (a) levels in patients with untreated essential hypertension.

Lipoprotein (a) [Lp (a)] is considered as a risk factor for vascular diseases, especially those associated with renal failure. Adequate studies have not been conducted on the lipoprotein (a) in essential hypertensive patients. There is a controversy on the mechanisms by which Lp (a) is associated with essential hypertension. It is unclear whether Lp (a) contributes to atherogenesis or to thrombogenesis or both. Recent studies suggest that Lp (a) can act as a marker for determining vascular or tissue injury. Reports on Indian population indicate elevated levels of Lp (a), together with other serum lipoproteins emphasizing an important role in Coronary Heart Disease (CHD) and peripheral atherosclerosis. In the present study we aimed to evaluate the relation between plasma levels of Lp (a) and the parameters of the lipid profile in a group of essential hypertensive patients, who are not receiving pharmacological treatment and with no clinical signs of associated pathologies or organ damage. A total of 37 essential hypertensive patients (27 men and 10 women) were compared with 50 controls (32 men and 18 women). It was observed that the hypertensive patients had higher plasma concentrations of Lp (a), Total Cholesterol (TC), Low-Density Lipoprotein-Cholesterol (LDL-C), and Triglycerides (TG) as compared to controls (P< 0.01). Hypertensive patients were also observed to have significantly low levels of High-Density Lipoprotein Cholesterol levels (HDL-C) as compared to controls (P<0.01). Only 14 hypertension patients and 4 controls had plasma concentrations of Lp (a) of over 30 mg/dl. Lp (a) values correlated significantly ( P<0.05 ) with systolic blood pressure (SBP), diastolic blood pressure (DBP) and the main parameters of the lipid profile. We conclude that elevated plasma Lp (a) levels were associated with hypertension and show significant correlation with lipid levels. However higher plasma concentrations of Lp (a), albeit with in the normal range, could be an independent risk factor for atherosclerosis, and could contribute towards increasing the risk for cardiovascular disease in persons with essential hypertension.

Prevalence of risk factors for coronary atherosclerosis in a cross-sectional population of Andhra Pradesh.

BACKGROUND: The prevalence of risk factors for atherosclerosis is increasing in India due to changing socioeconomic factors and lifestyles. Data for the state of Andhra Pradesh are scanty in this regard. METHODS AND RESULTS: The prevalence of conventional risk factors for atherosclerosis was prospectively assessed in a unique sample of 3307 workers of a political party drawn from all over the state of Andhra Pradesh. Demographic, anthropometric, clinical and laboratory data were collected prospectively over a period of 6 months. The mean age of the subjects was 43.12+/-9.5 years, 2955 (88%) were males and 385 (12%) females. The prevalence of risk factors was as follows: diabetes in 810 (24%); hypertension in 924 (28%); lipid abnormality in 1908 (58%); smoking in 805 (24%) and positive family history in 555 (17%). Obesity was prevalent in 1178 (36%) of the population. All coronary risk factors, excepting family history, were significantly more prevalent in males [diabetes: 777 (26%) v. 34 (9%), p<0.001; hypertension: 833 (28%) v. 72 (19%), p<0.001; lipid abnormality: 1729 (59%) v. 172 (45%), p<0.001; smoking: 801 (27%) v. 7 (2%), p<0.001; and family history: 497 (17%) v. 60 (16%), p=0.54]. Region-wise analysis showed a high prevalence of diabetes in the Andhra and Rayalaseema regions, hypertension in the Andhra region, and smoking in the Rayalaseema region. Lipid disorders were equally prevalent in all the regions. CONCLUSIONS: The present report shows a disturbing burden of coronary risk factors in the study population. There is an urgent need to undertake population-based measures to reverse the trend.

A study of clinical efficacy of sildenafil in patients with primary pulmonary hypertension.

BACKGROUND: Primary pulmonary hypertension is a disorder with limited treatment options and poor outcome. Sildenafil, a pulmonary vasodilator, is likely to be beneficial in primary pulmonary hypertension. We studied the clinical efficacy of sildenafil in patients with primary pulmonary hypertension. METHODS AND RESULTS: A registry of patients with primary pulmonary hypertension has been maintained in our hospital since January 1999. Of a total of 60 patients. 29 (M:16, F:13) consented to try sildenafiL. New York Heart Association functional class, six-minute walk test and Doppler echocardiographic evaluation of pulmonary artery pressure was done before and after treatment with sildenafil. Sildenafil was initiated at a dose of 25 mg thrice a day and increased up to 100 mg thrice a day as tolerated. There was a significant improvement in the functional class. The six-minute walked distance increased from 297.07+/-130.69 m at baseline to 427.68+/-85.35 m after 3 months of sildenafil therapy (p<0.0003). The mean of the pulmonary artery systolic pressure before starting sildenaffil was 109.26+/-24.15 mmHg (mean+/-SD) and it decreased to 95.15+/-24.64 mmHg (p<0.008). While 19 of the 31 historical controls in whom sildenafil was not given died during follow-up (11-44 months), only 1 of the 29 patients given sildenafil died (in an accident) during follow-up (5-20 months). CONCLUSIONS: Sildenafil, a pulmonary vasodilator, has a beneficial effect in patients with primary pulmonary hypertension in improving the functional class, six-minute walked distance and in decreasing the pulmonary artery pressures.

A case-control study of plasma homocysteine levels in South Indians with and without coronary artery disease.

BACKGROUND: An increased level of plasma homocysteine is being recognized as a new risk factor for coronary artery disease. Since there are not enough data about its importance in Indians with coronary artery disease, we aimed to assess the significance of plasma homocysteine as a coronary risk factor in South Indian patients. METHODS AND RESULTS: In a case-control study, fasting plasma homocysteine levels were estimated in 565 subjects, of whom 221 were cases and 344 were controls. Of the 221 clinically defined cases, 112 underwent coronary angiography while 107 of the 344 controls had angiographically proven normal coronary arteries. Ninety healthy volunteers from the community were also included as controls. Fluorescent polarization immunosorbent assay was used to measure plasma homocysteine levels. In 12 patients, this method was compared to high pressure liquid chromatography and was found to give comparable results. The mean plasma homocysteine level was 18.30 +/- 10.08 micromol/L in clinically defined cases and 18.04 +/- 10.69 micromol/L in controls. Similarly, in angiographicallyproven coronary arterydisease patients, the mean plasma homocysteine levelwas 18.49 +/- 10.04 micromol/L and in individuals with angiographically normal coronary arteries, it was 19.16 +/- 11.38 micromol/L. CONCLUSIONS: There is no statistically significant difference in plasma homocysteine levels between controls and cases with coronary artery disease. The mean plasma homocysteine levels in controls as assessed by fluorescent polarization immunosorbent assay in the present study population are higher as compared to other published reports.

Brugada syndrome with monomorphic ventricular tachycardia in a one-year-old child.

A one-year-old child with a structurally normal heart presented with monomorphic ventricular tachycardia. Electrocardiogram in sinus rhythm showed right bundle branch block with ST segment elevation suggesting a diagnosis of Brugada syndrome. At a later date, when the ST segment was isoelectric. intravenous procainamide caused ST elevation typical of Brugada syndrome.

Prospective observational study of primary angioplasty of the infarct-related artery for acute myocardial infarction.

Primary angioplasty has been shown to reduce rates of in-hospital mortality, recurrent ischaemia and infarction. However, the role of primary stenting and abciximab is presently undergoing evaluation. This study attempted to examine the feasibility, safety and outcomes of primary angioplasty in the treatment of acute myocardial infarction. Data in 100 patients who underwent primary angioplasty for evolving acute myocardial infarction was prospectively analysed to assess the safety and efficacy of various modalities. Twenty patients were in Killip class III and above. Multivessel (2 or more vessels) disease was noted in more than 52 cases. Procedural success was 99 percent; 86 patients received primary stenting, majority of them had Kalam-Raju stent implantation. Adjunct treatment included abciximab infusion in 22 and intra-aortic balloon pump support in 12. Overall mortality rate was six percent with a mortality of 2.2 percent in non-cardiogenic shock patients. Recurrent ischaemic events were noted in five, three of them had successful reperfusion with repeat angioplasty. None of the patients had emergency coronary artery bypass surgery. It is concluded that primary angioplasty is safe and effective with high procedural success. Recurrent ischaemic events are low, possibly due to routine use of stenting and selective use of abciximab.

Clinical evaluation of new balloon mountable coil stent: in-hospital and follow-up results.

The purpose of this study was to determine the feasibility, safety and efficacy of elective deployment of a new coil-stent (KR stent) in patients with coronary artery disease. KR stent deployment was attempted in 100 patients (135 lesions) enrolled prospectively at a single centre from December 1996 to March 1997. Ten, 15, 18, 24, and 32 mm long KR stents were manually crimped onto balloons and deployed in native coronary artery lesions. Majority of the patients had recent acute coronary syndromes (unstable angina 30% and post-myocardial infarction angina 56%). Diabetes was present in 34 percent of the patients. Fifty-six percent had single-vessel and 44 percent multi-vessel disease. In 38 percent, the lesions were located in proximal segments and 40 percent of lesions were long. KR stents were successfully deployed in 98 percent of patients. Mean minimal luminal diameter increased by 2.89 +/- 0.63 mm (from 0.57 +/- 0.38 mm before to 3.45 +/- 0.56 mm after the procedure). Mean percent diameter stenosis decreased from 83.33 +/- 10.84 percent before to 3.38 +/- 5.74 percent after the stent deployment. Mean reference vessel diameter was 3.45 +/- 0.56 mm. There were occasional technical complications including balloon rupture (1), stent migration (2) and distal embolisation of atheromatous material (1). One patient developed subacute stent thrombosis. There were no other major in-hospital cardiovascular events. At the end of six-month follow-up, there were no myocardial infarction or death. Six patients presented with recurrence of symptoms within six-months of the procedure, four of whom underwent target vessel revascularisation procedure. In conclusion, the in-hospital and six-month follow-up clinical results were highly encouraging with KR stent. Successful deployment rates were high despite unfavourable clinical and angiographic background. Low clinical events on follow-up will make it suitable for elective stenting.