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Biomedical subjects

Debabrata Mukherjee

Publications and source records attributed to Debabrata Mukherjee.

At least 37 records · Page 2Linked to original sources

Variation in outcomes after percutaneous coronary intervention in the United States and predictors of periprocedural mortality.

The objective of this study was to characterize variation in mortality rates across hospitals performing percutaneous coronary intervention (PCI) in the United States. For this purpose, data (n = 735,022) from the Nationwide Inpatient Sample from 1996 to 2001 were analyzed. The primary outcome for the analysis was postprocedural in-hospital mortality. Mortality rates were calculated by race, gender, geographic region, comorbid status and hospital volume. There were significant variations in mortality across gender groups, comorbid status, regions and by hospital volume status. Independent predictors of mortality in this large cohort were older age, female gender, lower income and lower hospital volume. The data suggests targets for quality improvement initiatives for patients undergoing PCI particularly in the elderly, females, lower income patients and low volume hospitals. Even in the contemporary era of adjunctive pharmacological therapies and ubiquitous use of stents, hospital volume remains a significant independent predictor of in-hospital mortality.

Age Factors↗

Acute intramural hematoma of the aorta: a mystery in evolution.

BACKGROUND: The definition, prevalence, outcomes, and appropriate treatment strategies for acute intramural hematoma (IMH) continue to be debated. METHODS AND RESULTS: We studied 1010 patients with acute aortic syndromes who were enrolled in the International Registry of Aortic Dissection (IRAD) to delineate the prevalence, presentation, management, and outcomes of acute IMH by comparing these patients with those with classic aortic dissection (AD). Fifty-eight (5.7%) patients had IMH, and this cohort tended to be older (68.7 versus 61.7 years; P<0.001) and more likely to have distal aortic involvement (60.3% versus 35.3%; P<0.001) compared with 952 patients with AD. Patients with IMH described more severe initial pain than did those with AD but were less likely to have ischemic leg pain, pulse deficits, or aortic valve insufficiency; moreover, they required a longer time to diagnosis and more diagnostic tests. Overall mortality of IMH was similar to that of classic AD (20.7% versus 23.9%; P=0.57), as was mortality in patients with IMH of the descending aorta (8.3% versus 13.1%; P=0.60) and the ascending aorta (39.1% versus 29.9%; P=0.34) compared with AD. IMH limited to the aortic arch was seen in 7 patients, with no deaths, despite medical therapy in only 6 of the 7 individuals. Among the 51 patients whose initial diagnostic study showed IMH only, 8 (16%) progressed to AD on a serial imaging study. CONCLUSIONS: The IRAD data demonstrate a 5.7% prevalence of IMH in patients with acute aortic syndromes. Like classic AD, IMH is a highly lethal condition when it involves the ascending aorta and surgical therapy should be considered, but this condition is less critical when limited to the arch or descending aorta. Fully 16% of patients have evidence of evolution to dissection on serial imaging.

Acute Disease↗

Development of a multicenter peripheral arterial interventional database: the PVD-QI2.

BACKGROUND: The number of peripheral vascular intervention (PVI) procedures performed is steadily increasing in the United States. PVD-QI 2 is a prospective, multicenter observational study designed to improve the quality of care for patients undergoing PVI and to better understand the effectiveness and appropriateness of PVI in improving outcomes of peripheral arterial disease. The registry aims to elucidate which comorbid conditions and procedure-related variables are associated with beneficial or adverse outcomes after vascular interventions. METHODS: Five centers are currently prospectively collecting data on consecutive PVIs performed at their institutions and will include patients with both claudication and critical limb ischemia. A common data collection form and a standard set of definitions were developed during several planning meetings. Information on patient demographics, clinical history, comorbid conditions, treatment approaches, and in hospital outcomes are being collected. Patients will be followed up at 30 days, 6 months, and 1 year after each procedure to identify recurrent vascular events, medication use, lifestyle modifications (regular exercise, dietary modification), self-reported walking scores, and mortality. Data validity will be assured through review of data form accuracy by a trained nurse, by automatic database diagnostic routines, and by site visits that include review of angiography suite logs and randomly selected charts. CONCLUSIONS: The development of a quality-controlled PVI registry requires the commitment and collaboration of clinician-investigators and hospital systems devoted to understanding factors that contribute to quality outcomes. Central to achievement of this goal is the creation of a careful diagnostic and data quality assessment system. This registry will provide important clinical insights into patient demographic and clinical characteristics, procedural characteristics, and current practice patterns that foster or impede achievement of long-term quality-based clinical outcomes for patients with peripheral arterial disease.

Databases, Factual↗

Percutaneous coronary intervention versus coronary artery bypass grafting in diabetic patients.

Revascularization with CABG or angioplasty in diabetic patients is associated with a less favor-able outcome. The value of early intervention will be assessed in the ongoing BARI 2D trial. It remains to be determined whether the widespread use of GP IIb/IIIa drugs and prolonged dual antiplatelet therapy in diabetic patients who receive stents, and possibly drug-eluting stents, will alter results significantly so that outcomes become comparable or even better than CABG (Fig. 3). It seems prudent to consider CABG with LIMA grafting in diabetic patients who have severe multi-vessel disease and to consider angioplasty in selected patients who have more discrete and less severe disease.

Angioplasty, Balloon, Coronary↗

Aortic dissection--an update.

Acute aortic dissection is a medical emergency with high morbidity and mortality requiring emergent diagnosis and therapy. Rapid advances in noninvasive imaging technology have facilitated the early diagnosis of this condition and should be considered in the differential diagnosis of any patient with chest, back, or abdominal pain. Emergent surgery is the treatment for patients with type A dissection while optimal medical therapy is appropriate in patients with uncomplicated type B dissection. Adequate beta-blockade is the cornerstone of medical therapy. Patients who survive acute aortic dissection need long-term medical therapy with beta-blockers and statins and appropriate serial imaging follow-up. Future advances in this field include biomarkers in the early diagnosis of acute aortic dissection and presymptomatic diagnosis with genetic screening. Overall patients with aortic dissection are at high risk for an adverse outcome and need to be managed aggressively in hospital and long term with frequent follow-up.

Acute Disease↗

Role of PPAR- gamma agonist thiazolidinediones in treatment of pre-diabetic and diabetic individuals: a cardiovascular perspective.

The peroxisome proliferator-activated receptors (PPARs) are nuclear fatty acid receptors, which contain a type II zinc finger DNA binding motif and a hydrophobic ligand binding pocket. These receptors are thought to play an important role in metabolic diseases such as obesity, insulin resistance, and coronary artery disease. Three subtypes of PPAR receptors have been described: PPARalpha, PPARdelta/beta, and PPARgamma. PPARalpha is found in the liver, muscle, kidney, and heart. In the liver, its role is to up-regulate genes involved in fatty acid uptake (beta-oxidation and omega-oxidation). PPARdelta/beta is involved in fatty acid oxidation in muscle. PPARgamma has high expression in fat, low expression in the liver, and very low expression in the muscle. The thiazolidinediones (TZD) are synthetic ligands of PPARgamma. By activating a number of genes in tissues, PPARgamma increases glucose and lipid uptake, increases glucose oxidation, decreases free fatty acid concentration, and decreases insulin resistance. There is a sound rationale for the use of TZDs in patients with type 2 diabetes mellitus and promising preliminary data in patients with patients with pre-diabetes. In patients with type 2 diabetes, thiazolidinediones had been shown to decrease mean HbA(1c)by 1.5% and lower HbA(1c) to less than 7% in 30% of patients. Decreased muscle insulin resistance primarily mediates the glucose lowering effect. In addition, there are several nonhypoglycemic effects of TZDs which may be beneficial to both diabetics and patients with pre-diabetes. These include effects on lipid metabolism, blood pressure, endothelial function, atherosclerotic plaque, coagulation, and albuminuria. In a pilot study, we recently demonstrated that insulin sensitizers such as thiazolidinediones appear to be associated with better clinical outcomes compared to insulin providers in diabetic patients presenting with acute coronary syndromes. In another study, we showed that the prediabetic state is a marker for worse prognosis in patients with acute coronary syndromes. In this article, we review the existing literature on the effectiveness of PPAR-gamma agonists in patients with either overt diabetes or a prediabetic state.

Diabetes Mellitus, Type 2↗

Implementation of the ACC/AHA guidelines for preoperative cardiac risk assessment in a general medicine preoperative clinic: improving efficiency and preserving outcomes.

BACKGROUND: The American College of Cardiology/American Heart Association (ACC/AHA) publishes recommendations for cardiac assessment of patients undergoing noncardiac surgery with the intent of promoting evidence-based, efficient preoperative screening and management. We sought to study the impact of guideline implementation for cardiac risk assessment in a general internal medicine preoperative clinic. METHODS: The study was an observational cohort study of consecutive patients being evaluated in an outpatient preoperative evaluation clinic before and after implementation of the ACC/AHA guideline. Data was gathered by retrospective abstraction of hospital and clinic charts using standard definitions. 299 patients were reviewed prior to guideline implementation and their care compared to 339 consecutive patients after the guideline was implemented in the clinic. RESULTS: Guideline implementation led to a reduction in exercise stress testing (30.8% before, 16.2% after; p<0.001) and hospital length of stay (6.5 days before, 5.6 days after; p=0.055). beta-Blocker therapy increased after the intervention (15.7% before; 34.5% after; p<0.001) and preoperative test appropriateness improved (86% before to 94.1% after; p<0.001). CONCLUSIONS: Implementation of the ACC/AHA guidelines for cardiac risk assessment prior to noncardiac surgery in an internal medicine preoperative assessment clinic led to a more appropriate use of preoperative stress testing and beta-blocker therapy while preserving a low rate of cardiac complications.

Adrenergic beta-Antagonists↗

Comparison of outcomes in acute coronary syndrome in patients receiving statins within 24 hours of onset versus at later times.

The clinical benefits of statins in acute coronary syndromes are well established, but the optimal time for administration in this setting has not been well studied. In this study, patients who had acute coronary syndrome and received statins <24 hours of presentation had lower incidences of death, stroke, reinfarction, heart failure, and pulmonary edema compared with delayed administration. Prompt administration of statins appears to be significantly beneficial in patients who present with an acute coronary syndrome.

Adrenergic beta-Antagonists↗

Clinical association between renal insufficiency and positive troponin I in patients with acute coronary syndrome.

BACKGROUND: Whether renal insufficiency (RI) influences troponin levels in patients with acute coronary syndromes (ACS) is controversial. We attempted to determine whether there is an association between RI and troponin I (TnI) elevation in patients presenting with ACS. METHODS: We studied 764 consecutive patients with ACS admitted to our institution from January 1999 to June 2000. Patients were identified prospectively and data were collected through chart review of all cases with an admission diagnosis of ACS. In order to assess the relationship of TnI and RI, we calculated the creatinine clearance (Cr-Cl) for all patients. We conducted an analysis of variance comparing TnI in quintiles of patients with lowest to highest Cr-Cl. RESULTS: Among 764 patients, 173 patients had a discharge diagnosis of ST elevation myocardial infarction and 591 had non-ST elevation myocardial infarction. There was no correlation between peak TnI levels and renal function as measured by Cr-Cl in the entire cohort with ACS and in the subgroups with ST elevation myocardial infarction and non ST elevation myocardial infarction. CONCLUSIONS: This large cohort study demonstrates that there appears to be no association between RI and positive TnI in patients with ACS.

Adult↗

Impact of combination evidence-based medical therapy on mortality in patients with acute coronary syndromes.

BACKGROUND: Several individual pharmacological agents, such as antiplatelet drugs, beta-blockers, ACE inhibitors, and lipid-lowering agents, have proven efficacy in reducing mortality in patients with acute coronary syndromes. However, the impact of the combination of these agents on clinical outcomes has not been studied before. METHODS AND RESULTS: A total of 1358 consecutive patients presenting with acute coronary syndromes between January 1999 and March 2002 were identified, and data on baseline demographics, comorbidities, and in-hospital management were collected. On the basis of discharge use of evidence-based therapies, we created a composite appropriateness score depending on the number of the drugs used divided by the number of the drugs potentially indicated for each patient. The impact of the composite score on 6-month mortality was analyzed using a risk-adjusted logistic regression model. The odds ratio for death for all indicated medications used (appropriateness level IV) versus none of the indicated medications used (appropriateness level 0) was 0.10 (95% CI, 0.03 to 0.42; P<0.0001); similarly, odds ratio for appropriateness level III versus level 0 was 0.17 (95% CI, 0.04 to 0.75; P=0.0018), odds ratio for appropriateness level II versus level 0 was 0.18 (95% CI, 0.04 to 0.77; P=0.01), and odds ratio for appropriateness level I versus level 0 was 0.36 (95% CI, 0.08 to 1.75; P=0.20). CONCLUSIONS: Use of combination evidence-based medical therapies was independently and strongly associated with lower 6-month mortality in patients with acute coronary syndromes. Such therapies, most of which are generic and inexpensive today, seem to offer a marked survival advantage compared with patients in whom such therapies are omitted.

Acute Disease↗

Cardiac overexpression of myotrophin triggers myocardial hypertrophy and heart failure in transgenic mice.

Cardiac hypertrophy and heart failure remain leading causes of death in the United States. Many studies have suggested that, under stress, myocardium releases factors triggering protein synthesis and stimulating myocyte growth. We identified and cloned myotrophin, a 12-kDa protein from hypertrophied human and rat hearts. Myotrophin (whose gene is localized on human chromosome 7q33) stimulates myocyte growth and participates in cellular interaction that initiates cardiac hypertrophy in vitro. In this report, we present data on the pathophysiological significance of myotrophin in vivo, showing the effects of overexpression of cardio-specific myotrophin in transgenic mice in which cardiac hypertrophy occurred by 4 weeks of age and progressed to heart failure by 9-12 months. This hypertrophy was associated with increased expression of proto-oncogenes, hypertrophy marker genes, growth factors, and cytokines, with symptoms that mimicked those of human cardiomyopathy, functionally and morphologically. This model provided a unique opportunity to analyze gene clusters that are differentially up-regulated during initiation of hypertrophy versus transition of hypertrophy to heart failure. Importantly, changes in gene expression observed during initiation of hypertrophy were significantly different from those seen during its transition to heart failure. Our data show that overexpression of myotrophin results in initiation of cardiac hypertrophy that progresses to heart failure, similar to changes in human heart failure. Knowledge of the changes that take place as a result of overexpression of myotrophin at both the cellular and molecular levels will suggest novel strategies for treatment to prevent hypertrophy and its progression to heart failure.

Animals↗

Feasibility of simultaneous bilateral carotid artery stenting.

Due to the progressive aging of the population, severe bilateral carotid stenosis has become a more frequent condition. On occasion, simultaneous revascularization may be appropriate. There is increased evidence that for these high-risk patients, a percutaneous revascularization may be the best approach. However, there are concerns that simultaneous bilateral carotid stenting may be associated with cerebral hyperperfusion, excessive bradycardia, and hypotension. We report a series of 10 consecutive patients who underwent simultaneous bilateral carotid stenting. All of these patients were not deemed to be surgical candidates due to high-risk comorbidities. All but one of the lesions were successfully stented. There were no procedural deaths, myocardial infarctions, or strokes. Thus, among carefully selected patients, simultaneous bilateral carotid artery stenting is a promising, technically feasible option.

Adrenergic alpha-Agonists↗

Elevated leukocyte count and adverse hospital events in patients with acute coronary syndromes: findings from the Global Registry of Acute Coronary Events (GRACE).

OBJECTIVE: To examine the association between elevated leukocyte count and hospital mortality and heart failure in patients enrolled in the multinational, observational Global Registry of Acute Coronary Events (GRACE). BACKGROUND: Elevated leukocyte count is associated with adverse hospital outcomes in patients presenting with acute myocardial infarction (AMI). The association of this prognostic factor with hospital mortality and heart failure in patients with other acute coronary syndromes (ACS) is unclear. METHODS: We examined the association between admission leukocyte count and hospital mortality and heart failure in 8269 patients presenting with an ACS. This association was examined separately in patients with ST-segment elevation AMI, non-ST-segment elevation AMI, and unstable angina. Leukocyte count was divided into 4 mutually exclusive groups (Q): Q1 <6000, Q2 = 6000-9999, Q3 = 10,000-11,999, Q4 >12,000. Multiple logistic regression analysis was performed to examine the association between elevated leukocyte count and hospital events while accounting for the simultaneous effect of several potentially confounding variables. RESULTS: Increasing leukocyte count was significantly associated with hospital death (adjusted odds ratio [OR] 2.8, 95% CI 2.1-3.6 for Q4 compared to Q2 [normal range]) and heart failure (OR 2.7, 95% CI 2.2-3.4) for patients presenting with ACS. This association was seen in patients with ST-segment elevation AMI (OR for hospital death 3.2, 95% CI 2.1-4.7; OR for heart failure 2.4, 95% CI 1.8-3.3), non-ST-segment elevation AMI (OR for hospital death 1.9, 95% CI 1.2-3.0; OR for heart failure 1.7, 95% CI 1.1-2.5), or unstable angina (OR for hospital death 2.8, 95% CI 1.4-5.5; OR for heart failure 2.0, 95% CI 0.9-4.4). CONCLUSION: In men and women of all ages with the spectrum of ACS, initial leukocyte count is an independent predictor of hospital death and the development of heart failure.

Adult↗

Patients undergoing infrainguinal bypass to treat atherosclerotic vascular disease are underprescribed cardioprotective medications: effect on graft patency, limb salvage, and mortality.

INTRODUCTION: Established American Heart Association guidelines recommend the use of statin drugs, angiotensin converting enzyme (ACE) inhibitors, and antiplatelet agents in patients with systemic atherosclerosis, such as those undergoing operative intervention to treat peripheral atherosclerotic disease. Many of these patients have not received treatment of coronary heart disease and have not been prescribed these medications. Whether statin drugs and ACE inhibitors confer an improvement in graft patency, limb salvage, and operative mortality is unknown. METHODS: Consecutive patients who underwent infrainguinal bypass between 1997 and 2002 were evaluated for demographic data, comorbid disease, medication use, as well as cumulative graft patency, limb salvage, and mortality. Univariate, multivariate logistical regression, and Kaplan-Meier analyses were performed. P <.05 was considered significant. RESULTS: Two hundred ninety-three patients (mean age, 64 years; 67% men) underwent 338 infrainguinal bypass procedures with autologous vein (n = 218), prosthetic grafts (n = 88), or composite prosthetic-vein grafts (n = 32). Limb salvage was the operative indication in 75% of procedures. Coexisting diseases included hypertension (70%), diabetes (52%), hyperlipidemia (37%), coronary heart disease (51%), congestive heart failure (14%), and active tobacco use (30%). Statin drugs were taken by 56% of patients, ACE inhibitors by 54% of patients, and antiplatelet agents or warfarin sodium (Coumadin) by 93% of patients. Postoperative graft surveillance was done in 39% of patients. Cumulative graft patency was 73%, limb salvage was 85%, and mortality was 9%, with a mean follow-up of 17 months. Factors independently associated with increased graft patency included statin drug use (odds ratio [OR], 3.7; 95% confidence interval [CI], 2.1-6.4), male sex (OR, 2.8; 95% CI, 1.6-5.0), and graft surveillance (OR, 2.4; 95% CI, 1.3-4.5). Factors associated with decreased amputation rate were statin drug use (OR, 0.34; 95% CI, 6.15-0.77) and graft surveillance (OR, 0.23; 95% CI, 6.1-0.63). Factors associated with decreased mortality included graft surveillance (OR, 0.18; 95% CI, 0.1-0.56), whereas congestive heart failure (OR, 6.5; 95% CI, 2.5-17) and hemodialysis-dependent renal failure (OR, 29; 95% CI, 6.1-140) were associated with increased mortality. Kaplan-Meier analysis showed that only ACE inhibitors were associated with lower mortality (P =.05) CONCLUSIONS: Patients undergoing infrainguinal bypass are undertreated with respect to cardioprotective medications. ACE inhibitor use is associated with lower mortality, and statin drug use is associated with improved graft patency and limb salvage. Institution of consensus guidelines concerning these medications should be considered by all vascular specialists, including vascular surgeons.

Angiotensin-Converting Enzyme Inhibitors↗