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Dharam J Kumbhani

Publications and source records attributed to Dharam J Kumbhani.

15 recordsLinked to original sources
PubMed2006

Benefit of early invasive therapy in acute coronary syndromes: a meta-analysis of contemporary randomized clinical trials.

OBJECTIVES: This study sought to systematically determine whether early invasive therapy improves survival and reduces adverse cardiovascular events in the management of non-ST-segment elevation acute coronary syndromes. BACKGROUND: Although early invasive therapy reduces recurrent unstable angina, the magnitude of benefit on other important adverse outcomes is unknown. METHODS: Clinical trials that randomized non-ST-segment elevation acute coronary syndrome patients to early invasive therapy versus a more conservative approach were included for analysis. RESULTS: In all there were 7 trials with 8,375 patients available for analysis. At a mean follow-up of 2 years, the incidence of all-cause mortality was 4.9% in the early invasive group, compared with 6.5% in the conservative group (risk ratio [RR] = 0.75, 95% confidence interval [CI] 0.63 to 0.90, p = 0.001), and at 1 month (RR = 0.82, 95% CI 0.50 to 1.34, p = 0.43). At 2 years of follow-up, the incidence of nonfatal myocardial infarction was 7.6% in the invasive group, versus 9.1% in the conservative group (RR = 0.83, 95% CI 0.72 to 0.96, p = 0.012), and at 1 month (RR = 0.93, 95% CI 0.73 to 1.19, p = 0.57). At a mean of 13 months of follow-up, there was a reduction in rehospitalization for unstable angina (RR = 0.69, 95% CI 0.65 to 0.74, p < 0.0001). CONCLUSIONS: Managing non-ST-segment elevation acute coronary syndromes by early invasive therapy improves long-term survival and reduces late myocardial infarction and rehospitalization for unstable angina.

Acute Disease↗
PubMed2006

A meta-analysis of randomized trials of rescue percutaneous coronary intervention after failed fibrinolysis.

Previous trials have suggested clinical benefit with rescue percutaneous coronary intervention (PCI) after failed fibrinolysis, but more recent, larger studies are conflicting. Therefore, we designed a meta-analysis to determine whether rescue PCI improves outcomes compared with conservative therapy in the setting of early failure of fibrinolysis. We searched MEDLINE for randomized trials by using the Medical Subject Heading terms "angioplasty," "myocardial infarction," "thrombolytic therapy," and "fibrinolysis." The inclusion criteria were (1) acute ST-elevation myocardial infarction initially treated with fibrinolytics, (2) randomization of patients with failed fibrinolysis to immediate PCI or conservative therapy, and (3) available short-term clinical outcome data. The primary end point was short-term mortality and secondary end points were thromboembolic stroke and heart failure. Numbers of events were tabulated for each trial and risk ratios (RRs) were computed. Five trials were included for analysis. The pooled RR estimates showed a 36% decrease in the risk of death in the rescue arm (RR 0.64, 95% confidence interval 0.41 to 1.00, p=0.048) and a marginally significant 28% decrease in the risk of heart failure (RR 0.72, 95% confidence interval 0.51 to 1.01, p=0.06). We also found a marginally increased risk of thromboembolic stroke in the rescue arm (RR 3.61, 95% confidence interval 0.91 to 14.27, p=0.07). In conclusion, rescue PCI in the setting of early fibrinolytic failure improves mortality, but this is tempered by a possible increase in the risk of thromboembolic stroke.

Angioplasty, Balloon, Coronary↗
PubMed2006

Intracoronary shunt-induced endothelial cell damage in porcine heart.

BACKGROUND: Injury to and dysfunction of the endothelium can compromise the patency of coronary arteries and lead to impaired perfusion of the heart. Such injury can occur after the application of an intravascular shunt and/or a snare to a coronary artery during bypass surgery. In this study, multiphoton microscopy was used to assess the integrity of endothelium in porcine coronary arteries subjected to shunting and snaring during off-pump coronary artery bypass grafting (OPCAB). MATERIALS AND METHODS: In open chest porcine, the left anterior descending artery was manipulated in different regions using snare and shunt to simulate OPCAB. Sections of left anterior descending artery were labeled with fluorescent dyes to evaluate the viability of the endothelium. The structural integrity of the endothelium was evaluated by calcein- and ethidium homodimer-mediated fluorescence. Endothelial functional viability was assessed by measuring cellular esterase activity, calcium mobilization, and endothelial nitric oxide synthase-mediated generation of nitric oxide using fluorescence dyes and multiphoton microscopy. RESULTS: Substantial endothelial damage was observed in shunted region of the coronary arteries. In contrast, endothelium remained structurally viable in regions that were snared, similar to control regions of the coronary arteries that were not manipulated. Esterase activity, calcium mobilization, and nitric oxide generation was greater in the control and snared regions of the coronary arteries in comparison to the shunted region. CONCLUSIONS: The use of intracoronary shunts led to structural damage and attenuation of endothelial function in porcine coronary arteries, whereas snared vessels maintained their viability and integrity, similar to the control sections. The routine use of shunts in OPCABG may lead to endothelial damage and possibly to long-term graft failure.

Anastomosis, Surgical↗
PubMed2006

Late thrombosis of drug-eluting stents: a meta-analysis of randomized clinical trials.

PURPOSE: Drug-eluting stents are commonly used for percutaneous coronary intervention. Despite excellent clinical efficacy, the association between drug-eluting stents and the risk for late thrombosis remains imprecisely defined. METHODS: We performed a meta-analysis on 14 contemporary clinical trials that randomized 6675 patients to drug-eluting stents (paclitaxel or sirolimus) compared with bare metal stents. Eight of these trials have reported more than a year of clinical follow-up. RESULTS: The incidence of very late thrombosis (>1 year after the index procedure) was 5.0 events per 1000 drug-eluting stent patients, with no events in bare metal stent patients (risk ratio [RR]=5.02, 95% confidence interval [CI], 1.29 to 19.52, P=.02). Among sirolimus trials, the incidence of very late thrombosis was 3.6 events per 1000 sirolimus stent patients, with no events in bare metal stent patients (RR=3.99, 95% CI, .45 to 35.62, P=.22). The median time of late sirolimus stent thrombosis was 15.5 months, whereas with bare metal stents it was 4 months. Among paclitaxel trials, the incidence of very late thrombosis was 5.9 events per 1000 paclitaxel stent patients, with no events in bare metal stent patients (RR=5.72, 95% CI, 1.08 to 32.45, P=.049). The median time of late paclitaxel stent thrombosis was 18 months, whereas it was 3.5 months in bare metal stent patients. CONCLUSIONS: Although the incidence of very late stent thrombosis more than 1 year after coronary revascularization is low, drug-eluting stents appear to increase the risk for late thrombosis. Although more of this risk was seen with paclitaxel stents, it remains possible that sirolimus stents similarly increase the risk for late thrombosis compared with bare metal stents.

Coronary Disease↗
PubMed2005

Risk of thrombosis with the use of sirolimus-eluting stents for percutaneous coronary intervention (from registry and clinical trial data).

We conducted a meta-analysis on 6 studies in 2,963 patients who had coronary artery disease and received a sirolimus-eluting stent or a bare metal stent for revascularization. Compared with bare metal stents, sirolimus-eluting stents did not appear to increase the risk for thrombosis up to 13.5 months after coronary intervention (risk ratio 0.49, 95% confidence interval 0.22 to 1.12, p = 0.09).

Angioplasty, Balloon, Coronary↗
PubMed2005

What is the risk of stent thrombosis associated with the use of paclitaxel-eluting stents for percutaneous coronary intervention?: a meta-analysis.

OBJECTIVES: This study investigated the risk of stent thrombosis associated with the use of paclitaxel-eluting stents (PES) compared to bare-metal stents (BMS). BACKGROUND: Clinical experience with coronary drug-eluting stents (DES) is relatively limited. There is concern that DES used for percutaneous coronary intervention may result in subsequent thrombosis. METHODS: We conducted a meta-analysis on eight trials (total of 13 study arms) in 3,817 patients with coronary artery disease who were randomized to either PES or BMS. RESULTS: As compared with BMS, PES do not increase the hazard for thrombosis up to 12 months (risk ratio [RR] = 1.06, 95% confidence interval [CI] 0.55 to 2.04, p = 0.86]). There was no evidence of heterogeneity among the studies (chi-square value for Q-statistic = 5.90 [10 degrees of freedom], p = 0.82). Similar results were obtained when the analysis was restricted to trials with a polymeric stent platform (Treatment of de novo coronary disease using a single pAclitaXel elUting Stent [TAXUS]-I, -II, -IV, and -VI) (RR = 1.01, 95% CI 0.40 to 2.53, p = 0.99), trials with longer lesions (TAXUS-IV and -VI) (RR = 0.62, 95% CI 0.2 to 1.91, p = 0.41), and trials that used a higher dose of paclitaxel (ASian Paclitaxel-Eluting Stent Clinical trial [ASPECT], European evaLUaTion of paclitaxel Eluting Stents [ELUTES], and DELIVER-I) (RR = 1.87, 95% CI 0.52 to 6.81, p = 0.34). CONCLUSIONS: Current evidence suggests that standard dose PES do not increase the hazard of stent thrombosis compared to BMS.

Aged↗
PubMed2005

Adverse 30-day outcomes after cardiac surgery: predictive role of intraoperative myocardial acidosis.

BACKGROUND: Regional myocardial acidosis in patients undergoing cardiac surgery has been shown to be reflective of regional myocardial ischemia. This study elucidates the relationship between intraoperative regional myocardial acidosis and 30-day postoperative outcomes after cardiac surgery. METHODS: Intramyocardial tissue pH in the anterior and posterior left ventricular walls was measured in 397 adult patients undergoing valve replacement or coronary revascularization surgery between 1987 and 2001. Dedicated nurses and research assistants prospectively collected preoperative, intraoperative, and outcomes data. Regional myocardial acidosis was defined in terms of pH thresholds identified by recursive partitioning. Adverse 30-day outcome, defined as death or any one of six complications, was the dependent variable in a multivariate logistic regression analysis. A morbidity score was developed on the basis of the sensitivity of each of the six complications in predicting death, and was the dependent variable in a multivariate linear regression analysis. RESULTS: During the period of aortic clamping, a mean intramyocardial tissue pH less than 6.85 was identified to be significant by recursive partitioning, and was encountered in either the anterior or posterior left ventricular wall in 85.4% of patients. After adjusting for preoperative and intraoperative variables, this pH threshold was found to be significantly associated with increased adverse outcomes within 30 days after surgery (p = 0.045). It was also significantly associated with increase in the morbidity score (p = 0.05). CONCLUSIONS: Regional myocardial acidosis of a magnitude frequently encountered during aortic clamping is an independent determinant of adverse 30-day outcomes after cardiac surgery. Its reversal by pH-guided myocardial management has the potential of improving postoperative patient outcomes.

Acidosis↗
PubMed2005

Intraoperative regional myocardial acidosis and reduction in long-term survival after cardiac surgery.

BACKGROUND: Regional myocardial acidosis, as measured with tissue pH electrodes during cardiac surgery, has been shown to be reflective of regional myocardial ischemia. This study examined the relationship between intraoperative regional myocardial acidosis and long-term survival of patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: A total of 496 adult patients who underwent valve replacement, coronary artery revascularization, or both with intraoperative myocardial pH monitoring in the anterior and posterior left ventricular walls were followed up for 3 to 17 years (average 10.2 +/- 4.9 years) for all cause mortality. Regional myocardial acidosis in each patient was defined by the lower of the anterior and posterior wall pH values. RESULTS: A bivariate automatic interaction detection analysis identified three significant regional myocardial acidosis thresholds that affected long-term mortality: pH 37C less than 6.63 before aortic crossclamping, integrated mean pH 37C less than 6.34 during the period of aortic crossclamping, and pH 37C less than 6.73 at discontinuation of cardiopulmonary bypass. Cox proportional hazard regression analysis identified each of these thresholds to be independently determinant of survival, with pH 37C during aortic crossclamping having the highest risk ratio (risk ratio 2.15, 95% confidence interval 1.37-3.37). Raising pH 37C from lower than threshold before aortic crossclamping to higher than threshold during clamping increased the median survival by 40.2%. CONCLUSION: In adult patients undergoing cardiac surgery with cardiopulmonary bypass, regional myocardial ischemic acidosis before aortic crossclamping, during aortic crossclamping, and at discontinuation of cardiopulmonary bypass are independently associated with reduced long-term postoperative survival. Reversing or avoiding myocardial acidosis during cardiac surgery improves long-term patient survival.

Acidosis↗
PubMed2005

Determinants of long-term survival after major surgery and the adverse effect of postoperative complications.

OBJECTIVE: The objective of this study was to identify the determinants of 30-day postoperative mortality and long-term survival after major surgery as exemplified by 8 common operations. SUMMARY BACKGROUND DATA: The National Surgical Quality Improvement Program (NSQIP) database contains pre-, intra-, and 30-day postoperative data, prospectively collected in a standardized fashion by a dedicated nurse reviewer, on major surgery in the Veterans Administration (VA). The Beneficiary Identification and Records Locator Subsystem (BIRLS) is a VA file that depicts the vital status of U.S. veterans with 87% to 95% accuracy. METHODS: NSQIP data were merged with BIRLS to determine the vital status of 105,951 patients who underwent 8 types of operations performed between 1991 and 1999, providing an average follow up of 8 years. Logistic and Cox regression analyses were performed to identify the predictors of 30-day mortality and long-term survival, respectively. RESULTS: The most important determinant of decreased postoperative survival was the occurrence, within 30 days postoperatively, of any one of 22 types of complications collected in the NSQIP. Independent of preoperative patient risk, the occurrence of a 30-day complication in the total patient group reduced median patient survival by 69%. The adverse effect of a complication on patient survival was also influenced by the operation type and was sustained even when patients who did not survive for 30 days were excluded from the analyses. CONCLUSIONS: The occurrence of a 30-day postoperative complication is more important than preoperative patient risk and intraoperative factors in determining the survival after major surgery in the VA. Quality and process improvement in surgery should be directed toward the prevention of postoperative complications.

Databases as Topic↗
PubMed2004

Invasive therapy along with glycoprotein IIb/IIIa inhibitors and intracoronary stents improves survival in non-ST-segment elevation acute coronary syndromes: a meta-analysis and review of the literature.

Current evidence suggests that routine invasive therapy in the setting of unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI) reduces the incidence of composite end points (i.e., death, myocardial infarction, or angina.). The 2002 American College of Cardiology/American Heart Association guidelines recommend invasive therapy in high-risk patients, although it is unknown if such an approach improves survival. We conducted a meta-analysis on 5 studies in 6,766 UA/NSTEMI patients who were randomized to either routine invasive versus conservative therapy in the era of glycoprotein IIb/IIIa inhibitors and intracoronary stents. Compared with conservative therapy, an invasive approach suggested a reduction in mortality at 6 to 12 months (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.63 to 1.03) and at 24 months (RR 0.77, 95% CI 0.60 to 0.99). The composite end point of death or myocardial infarction was reduced throughout all periods of follow-up: at 30 days (RR 0.61, 95% CI 0.45 to 0.84), at 6 months (RR 0.75, 95% CI 0.63 to 0.89), and at 12 months (RR 0.78, 95% CI 0.65 to 0.92). For the same composite end point at 6 to 12 months, men benefited from invasive therapy (RR 0.68, 95% CI 0.57 to 0.81), as did troponin-positive patients (RR 0.74, 95% CI 0.59 to 0.94). The results for women (RR 1.07, 95% CI 0.82 to 1.41) and troponin-negative patients (RR 0.82, 95% CI 0.59 to 1.14) were equivocal. Routine invasive therapy in UA/NSTEMI patients along with adjunctive use of glycoprotein IIb/IIIa inhibitors and intracoronary stents improves survival. Enhanced risk stratification is needed in women and troponin-negative patients so that invasive therapy may be more effectively recommended in these groups.

Acute Disease↗
PubMed2004

Intraoperative regional myocardial acidosis predicts the need for inotropic support in cardiac surgery.

OBJECTIVE: To determine the impact of regional myocardial acidosis encountered during cardiac surgery on the need for inotropic and intra-aortic balloon (IAB) support. METHODS: Intramyocardial tissue pH(37C) was measured in 247 patients undergoing cardiopulmonary bypass (CPB). Inotropic support (INO) was defined as requiring one or more of norepinephrine/epinephrine/amrinone/dobutamine/>2.5 mug/kg/min dopamine, for at least 45 minutes intraoperatively, and intraoperative or postoperative IAB use. PH (corrected to 37 degrees C, pH(37C)) during surgery was compared in patients who needed INO versus those who did not. Multivariate logistic regression models identified the determinants of INO. RESULTS: Fifty patients (20.2%) required INO intraoperatively. pH(37C) was significantly lower throughout reperfusion in patients needing INO. Preoperative ejection fraction and pH(37C) during reperfusion were identified as independent predictors of INO. CONCLUSIONS: This is the first study to show that intraoperative regional myocardial acidosis, a preventable condition, independently determines the need for intraoperative INO. Increased INO is associated with greater postoperative mortality and morbidity.

Acidosis↗
PubMed2004

Determinants of regional myocardial acidosis during cardiac surgery.

BACKGROUND: Intraoperative regional myocardial acidosis (RMA) during cardiac surgery has been shown to be reflective of regional myocardial ischemia and an independent predictor of adverse postoperative outcomes. This study identifies the determinants of intraoperative RMA. METHODS: Intramyocardial tissue pH(37C) in the anterior and posterior LV walls was measured in 641 adult patients during cardiac surgery. RMA at two intraoperative periods was quantified as integrated mean pH(37C) < 6.35 during aortic clamping (AC) and pH(37C) < 6.73 at the end of cardiopulmonary bypass (CPB). These pH thresholds were chosen because of their demonstrated relationship to long-term patient survival. Multivariate logistic regression models were constructed. An acidosis prediction score was constructed based on the factors determining RMA at the end of CPB. RESULTS: Independent determinants of RMA during AC were preoperative New York Heart Association class III/IV (P = .007), current smoker (P = .0088), pH(37C) < 6.63 prior to AC (P < .0001), and intraoperative myocardial management technique (P = .0001). Independent determinants of RMA at end of CPB were ASA class IV/V (P = .0042), pH(37C) < 6.63 prior to AC (P = .035), pH(37C) < 6.35 during AC (P = .001), and total duration of CPB > or = 212 minutes (P = .001). CONCLUSIONS: RMA during cardiac surgery is determined by patient risk factors, the magnitude of preceding regional myocardial acidosis, and the duration of CPB.

Acidosis↗
PubMedDate not supplied

Fascicular conduction disturbances after coronary artery bypass surgery: a review with a meta-analysis of their long-term significance.

Fascicular conduction abnormalities are frequently reported following adult cardiac surgery, but their pathogenesis and long-term outcomes remain unclear. In this article, we review the epidemiological features, pathogenesis, diagnosis, and management, and the short-term and long-term significance of fascicular conduction abnormalities following coronary artery bypass graft (CABG) surgery, based on data from 30 studies. Conduction disturbances have an incidence of 3.4% to 55.8% after CABG surgery, the most common being right bundle branch block (RBBB). RBBB is usually transient and benign. Although a slew of factors have been implicated in the pathogenesis of fascicular conduction disturbances, the two most important factors are myocardial ischemia and type of cardioplegia. While a 12-lead electrocardiogram is the gold standard for diagnosis, additional tests such as myocardial enzymes or echocardiography may have additional diagnostic and prognostic value. Short-term prognosis after RBBB is good, but its impact on long-term survival is unclear. We conducted a meta-analysis, the first of its kind in this area, using long-term survival data from five studies. There was no difference in long-term survival between patients who developed conduction disturbances after CABG surgery, and those who did not, indicating a benign influence of conduction disturbances on long-term survival, and the lack of the necessity for monitoring or pacing. While the older literature reported an adverse impact of fascicular conduction disturbances on long-term survival, the more recent studies report a substantially reduced mortality after CABG surgery, despite a higher incidence of conduction disturbances, pointing to the effect of improved surgical techniques.

Bundle-Branch Block↗