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Biomedical subjects

G Sethi

Publications and source records attributed to G Sethi.

At least 19 recordsLinked to original sources

Assessment of left ventricular compliance during heart preservation.

There is critical need for a greater number of donor hearts for transplantation. The demand can be relieved, in part, by an extension of preservation time. This necessitates new methods of preservation and development of means to assess the functional condition of the preserved heart. We report a heart-preservation system designed for long-term preservation support and discuss issues specifically related to extended heart preservation. This article presents methodology to assess ventricular compliance and to quantify coronary flow distribution during the use of microperfusion preservation. Ventricular adenosine triphosphate (ATP) concentrations are directly related to the immediate post-preservation function: however, direct measurement of ATP is not clinically available. Based on the premise that ventricular compliance relates directly to the ventricular ATP concentrations, we performed sequential ventricular compliance measurements using a simple left ventricular balloon during a 24 h preservation period. A porcine heart model was employed using a continuous, hypothermic, antegrade, microperfusion system for 24 h and measurements were made at specific intervals during the preservation time. The compliance measurements were ascertained by pressure-volume curves using a flaccid balloon inserted into the left ventricle through the mitral valve. In addition, to assess microvascular function during the preservation interval, regional coronary flow measurements were performed using a microsphere technique. We report that after 12 h of preservation there was a twofold reduction in ventricular compliance which decreased further by fivefold at 18 h. In contrast, there was a time-dependent decrease in left ventricular coronary flow, especially with the left-ventricular subendocardial region significantly decreasing by 50% at 12 h. In conclusion, a simple ventricular-compliance balloon provided a direct measurement of ventricular compliance of the preserved heart which may provide an indirect estimate of the ventricular high-energy phosphates of the preserved heart prior to transplantation.

Animals

Predictors of graft patency 3 years after coronary artery bypass graft surgery. Department of Veterans Affairs Cooperative Study Group No. 297.

OBJECTIVES: The purpose of this analysis was to define the factors that predict 3-year graft patency. BACKGROUND: The success of coronary artery bypass graft surgery (CABG) is dependent on vein graft patency after the operation. It has been well established by a series of Department of Veterans Affairs Cooperative Trials that aspirin (325 mg daily) improves saphenous vein graft patency early (7 to 10 days) and at 1 year, but not at 3 years after CABG. This analysis, based on one of these trials, defined factors that predict 3-year graft patency. METHODS: This analysis consisted of 266 patients, with 656 grafts that were patent 7 to 10 days after the operation, who underwent 3-year catheterization. To determine which patient-specific and/or graft-specific factors, or both, predict graft occlusion, a multivariate logistic regression analysis in terms of latent variables was used. It yielded a model that also took into account possible intraclass correlations. RESULTS: For a vein graft that was patent at 7 to 10 days after the operation, the positive predictors, according to univariate analysis, for that graft being patent at 3 years were cross-clamp time < or = 80 min (p < 0.001), vein preservation solution temperature < or = 5 degrees C (p = 0.009), bypass time < or = 2 h (p = 0.042), number of proximal anastomoses < or = 2 (p = 0.018), operation time < or = 5 h (p = 0.044) and continuous versus intermittent cross-clamp technique (p = 0.024). There was also a trend with regard to recipient artery diameter > 1.5 mm (p = 0.063), serum cholesterol < or = 225 mg/dl (p = 0.084) and single versus sequential or Y vein graft (p = 0.060). Factors not predictive of 3-year patency were age, race, smoking history, high density lipoprotein cholesterol, vein source (thigh vs. calf), coronary artery grafted and aspirin treatment. Of all the predictors obtained in the univariate analysis, the only variables that were sufficient to yield a good model within the multivariate analysis were solution temperature (p = 0.004), serum cholesterol (p = 0.024), number of proximal anastomoses (p = 0.032) and recipient artery diameter (p = 0.034). CONCLUSIONS: For a patient with patent vein grafts 7 to 10 days after the operation, predictors of 3-year graft patency are more closely related to operative techniques and underlying disease and not to aspirin treatment.

Coronary Artery Bypass

Pharmacotherapeutic education through problem based learning and its impact on cognitive and motivational attitude of Indian students.

OBJECTIVE: The cognitive and motivational attitudes to problem based learning (i.e., simple didactic problem stated in written form and Programmed Patient) has been compared with those to didactic lectures (DL), the traditional teaching method. The change in recall performance measured in MCQ tests was considered as a change in the cognitive domain. The first test was conducted one week after completion of the topic and second test was taken 3 months later, without prior information. The motivational change was recorded by open-ended questions about the learning method. Three groups of students at second MBBS professional year level consisting of 55, 57 and 59 people, were assigned a simple didactic problem stated in written form (SDP), programmed patients (PP), and didactic lecture (DL), respectively. RESULTS: The average scores obtained by the learners in problem based learning (PBL) groups were similar to the students in the DL group in both the tests. Most of the students in PBL groups appreciated the exercise and suggested including more such exercises in the curriculum. These exercises helped them to better understand patient problems and prescribing behaviour as well as in development of communication skills. However, these exercises were time consuming and were not examination oriented. CONCLUSION: Pharmacotherapeutic teaching through PBL could be used within a traditional curriculum to develop relevant and rational use of drugs, provided the evaluation method was also modified.

Association Learning

Use of cumulative meta-analysis in the design, monitoring, and final analysis of a clinical trial: a case study.

From 1983 to 1987, the Department of Veterans Affairs (DVA) Cooperative Studies Program (CSP) conducted a multicenter clinical trial (CSP #207) to determine whether four different antiplatelet regimens compared to placebo could prevent the occlusion of grafts following coronary artery bypass surgery. The study showed that all of the active regimens tended to be better than placebo and that the three regimens containing aspirin were statistically significantly better. A cumulative meta-analysis of 12 trials performed shortly before the end of CSP #207 raised the issue as to whether the meta-analysis, if done earlier, would have changed the conduct of the trial. At the start of the planning period, one trail of size n = 37 had been published with a nonsignificant odds ratio (OR) of 0.74 (95% CI: 0.18, 3.12). At the time that CSP # 207 was approved by the DVA Cooperative Studies Evaluation Committee, two trials had been published (cumulative n = 150, OR = 0.44, 95% CI 0.19, 0.99). At the time patient intake started, five trials showed cumulative n = 769, OR = 0.42, 95% CI = 0.26, 0.68. Although the first 6-month CSP #207 progress report showed no treatment effect, by the time of the 12-month review by the Data Monitoring Board (DMB) a trend was developing in favor of active treatment. If the results of the meta-analysis had been available to the DMB at that time, conceivably the Board would have recommended stopping the placebo arm because of a convincing treatment effect based on the totality of the evidence. Cumulative meta-analysis could be useful as an adjunct in the planning, conduct, and final analysis of a clinical trial. It could also be used as one piece of evidence in the monitoring of the ongoing phase of a trial.

Anti-Inflammatory Agents, Non-Steroidal

Long-term graft patency (3 years) after coronary artery surgery. Effects of aspirin: results of a VA Cooperative study.

BACKGROUND: The long-term success of coronary bypass surgery is dependent on graft patency after surgery. This trial was designed to determine if aspirin improved saphenous vein graft or internal mammary artery (IMA) graft patency between 1 and 3 years after coronary artery bypass grafting (CABG). METHODS AND RESULTS: After receiving aspirin 325 mg/d for 1 year after CABG and undergoing a 1-year postoperative cardiac catheterization, patients were randomized to receive either aspirin (325 mg) or placebo for 2 additional years. Angiography was performed 3 years after surgery to determine the primary end point-saphenous vein graft patency in 288 patients and IMA graft patency in 167 patients. At 3 years after CABG, the saphenous vein graft occlusion rate was 17.0% (62 of 365) for patients treated with aspirin compared with 19.7% (74 of 376) for those who received placebo (P = .404). For saphenous vein grafts that were patent at 1 year, the occlusion rate at 3 years was 4.8% (15 of 313) for patients treated with aspirin compared with 4.2% (13 of 310) for patients who received placebo (P = .757). At 3 years, the IMA graft occlusion rate was 10.3% (8 of 78) for patients treated with aspirin compared with 7.9% (7 of 89) for patients who received placebo (P = .594). For IMA grafts that were patent at 1 year, the occlusion rate was 4.3% (3 of 70) for patients treated with aspirin compared with 2.5% (2 of 81) for patients who received placebo (P = .541). CONCLUSIONS: These data suggest that aspirin treatment does not improve saphenous vein graft or IMA graft patency between 1 and 3 years after CABG.

Aspirin

Determinants of the occurrence of and survival from prosthetic valve endocarditis. Experience of the Veterans Affairs Cooperative Study on Valvular Heart Disease.

For the determination of the risk factors associated with the development of and death caused by prosthetic valve endocarditis, data were reviewed from 66 patients who were prospectively entered into the Veterans Affairs Cooperative Study on Valvular Heart Disease and in whom prosthetic valve endocarditis subsequently developed. Data were recorded at 13 medical centers between October 1977 and September 1982 in patients randomized to receive a mechanical valve (Bjork-Shiley spherical disc, n = 510 patients) or a bioprosthetic valve (Hancock porcine heterograft, n = 522 patients). The average rate of prosthetic valve endocarditis development was 0.8% per year over an average follow-up period of 7.7 years. Of the 66 patients in whom prosthetic valve endocarditis developed (5.8%), 15 cases occurred within 2 months of operation (early) and 51 occurred after operation (late). The most significant preoperative predictor of prosthetic valve endocarditis was active endocarditis at the time of operation (7.4% versus 0.9%) (p = 0.001). Early prosthetic valve endocarditis occurred more frequently in patients who underwent operation for multivalvular disease (p = 0.023). Significantly related perioperative variables were coma, prolonged mechanical ventilation, deep postoperative wound infection, postoperative jaundice, ventricular tachycardia, ventricular fibrillation, and replacement of more than one valve (p < 0.05). Multivariate predictors were hypoxia (p = 0.001), preoperative endocarditis (p = 0.003), preoperative valve lesion (p = 0.020), and resident surgeon (p = 0.05). Significant preoperative variables predictive of late prosthetic valve endocarditis were mitral stenosis and mixed mitral stenosis-regurgitation. The only multivariate predictor of late prosthetic valve endocarditis was superficial wound infection (p = 0.004). Of deaths attributable to prosthetic valve endocarditis, 41% occurred in patients treated with antibiotics alone, 48% occurred in patients treated with surgical intervention and antibiotics, and death resulted in both patients who received no treatment. No difference was found in the risk of early or late postoperative prosthetic valve endocarditis developing in patients receiving the mechanical valve versus those receiving the bioprosthetic valve.

Actuarial Analysis

Mitral valve replacement six years after cardiac transplantation.

A 33-year-old man found to have increasing mitral regurgitation and decreasing exercise tolerance 6 years after cardiac transplantation received a mitral bioprosthesis. For 8 months he has been without complications from the valve replacement and is clinically and hemodynamically considerably improved.

Adult

Long-term bridge to transplantation with the Symbion acute ventricular assist device system.

A 48-year-old man was supported for 164 days with Symbion biventricular assist devices. During that time, his cytotoxic antibody screen fell from 97% positivity to less than 10%, enabling cardiac transplantation. Complications during the implantation included a 3-minute episode of amaurosis fugax, one positive blood culture, and anemia, which responded to decreased frequency of blood drawing. He is now alive 7 months after transplantation.

Coronary Artery Bypass

Conditional power for arbitrary survival curves to decide whether to extend a clinical trial.

This article describes a computer simulation methodology to calculate conditional power for comparing two arbitrary survival curves as an aid in deciding whether or not to extend a clinical trial. The method is a modification of that by Halpern and Brown, which computes unconditional power for comparing arbitrary survival curves at the beginning of a study. The advantage of this method is that it permits conditional power calculations for comparisons of distribution-free survival curves. Power is computed for two commonly used statistical tests, the log-rank test and Gehan's generalization of the Wilcoxon test, and for a modified Kolmogorov-Smirnov test, which is particularly sensitive to crossing survival curves. This method for estimating conditional power should be useful in the situation in which a decision must be made regarding the benefit of continuing a clinical trial. The application of this method is shown using VA Cooperative Study No. 90, "Prognosis and Outcome Following Heart Valve Replacement."

Aortic Valve

Starting aspirin therapy after operation. Effects on early graft patency. Department of Veterans Affairs Cooperative Study Group.

BACKGROUND: Although aspirin therapy started before operation improves vein graft patency after coronary artery bypass grafting, it also causes bleeding. The objective of this prospective, centrally directed, randomized, double-blind, placebo-controlled trial was to compare the effects of aspirin therapy started before operation with aspirin started 6 hours after operation on early (7-10-day) graft patency. METHODS AND RESULTS: Patients were randomized to receive either aspirin 325 mg or placebo the night before surgery; after operation, all patients received aspirin 325 mg daily, with the first dose administered through the nasogastric tube 6 hours after operation. Angiography was performed in 72% of the analyzed patients an average of 8 days after operation, and the primary end point was saphenous vein graft patency in 351 patients. Internal mammary artery graft patency was also assessed in 246 patients because many individuals received both internal mammary artery and vein grafts. In the patients given preoperative aspirin, the vein graft occlusion rate was 7.4 +/- 1.3% compared with 7.8 +/- 1.5% in those who received preoperative placebo (p = 0.871). In the subgroup of patients receiving Y grafts, 0.0% of the grafts were occluded in the preoperative aspirin group compared with 7.0 +/- 3.6% in the preoperative placebo group (p = 0.066). The internal mammary artery occlusion rate was 0.0% (0 of 131) in the aspirin group compared with 2.4 +/- 1.4% (three of 125) in the placebo group (p = 0.081). Patients in the aspirin group received more transfusions than those in the placebo group (median, 900 versus 725 ml, p = 0.006). The reoperation rate for bleeding in the aspirin group was 6.3% compared with 2.4% in the placebo group (p = 0.036). Median chest tube drainage within the first 6 hours after operation was 500 ml in the aspirin group compared with 448 ml in the placebo group (p = 0.011). CONCLUSIONS: Thus, preoperative aspirin is associated with increased bleeding complications and offers no additional benefit in early vein graft patency compared with starting aspirin therapy 6 hours after operation. There was a trend, although not significant, toward improved early patency for Y grafts and internal mammary artery grafts with preoperative aspirin.

Aged

Successful coronary artery bypass grafting for high-risk left main coronary artery atherosclerosis after cardiac transplantation.

Severe stenosis of the left main coronary artery developed in a 58-year-old woman 9 years after orthotopic heart transplantation. Because of serious reversible myocardial ischemia and the high-risk nature of the coronary disease, coronary artery bypass grafting was performed, with no complications. Possible risk factors for the development of coronary arterial disease and its management in the transplant population are discussed.

Coronary Artery Bypass

Determinants of survival and left ventricular performance after mitral valve replacement. Department of Veterans Affairs Cooperative Study on Valvular Heart Disease.

To determine how survival and clinical status were related to left ventricular (LV) size and systolic function after mitral valve replacement, 104 patients (48 mitral regurgitation [MR], 33 mitral stenosis [MS], and 23 MS/MR) with isolated mitral valve replacement were evaluated before and after surgery. Preoperative hemodynamic abnormalities by cardiac catheterization were improved 6 months after surgery in all three patient groups. The patients with MR exhibited reductions in LV end-diastolic volume index (EDVI) (117 +/- 51 to 89 +/- 27 ml/m2, p less than 0.001) and ejection fraction (EF) (0.56 +/- 0.15 to 0.45 +/- 0.13, p less than 0.001); however, the ratio of forward stroke volume to end-diastolic volume increased (0.32 +/- 0.21 to 0.45 +/- 0.17, p less than 0.001) because of the elimination of regurgitant volume. Survival analysis revealed that mortality was significantly higher in MS or MS/MR patients with postoperative EDVI more than 101 ml/m2 (p less than 0.001 and p less than 0.042, respectively) and in MR patients with postoperative EF less than or equal to 0.50 (p less than 0.031). Also, the majority of patients with MR or MS/MR and postoperative EDVI more than 101 ml/m2 and EF less than or equal to 0.50 were in New York Heart Association class III or IV. Multivariate logistic regression analysis in the patients with MR revealed that the strongest predictor of postoperative EF was preoperative EF (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography

Heart transplantation: current status.

Two hundred ninety-three patients transplanted between March 1979 and October 1990 are reviewed. A comparison of survival curves suggests that our current triple therapy results in a half-life (15 years) which is twice that anticipated with either conventional or CsA and P therapy. Rejection occurs primarily in the first 1-3 months after transplantation and with our current therapy, is rarely seen thereafter. Infection, however, continues to be a threat with an incidence of approximately 10% per year. The major threats to long-term survival appear to be graft arteriosclerosis, infection, and malignancy.

Drug Therapy, Combination

Internal mammary artery and saphenous vein graft patency. Effects of aspirin.

As part of two Department of Veterans Affairs Cooperative Trials, we obtained angiographic patency data for internal mammary artery (IMA) and saphenous vein grafts to the left anterior descending (LAD) coronary artery at 1 year after coronary artery bypass surgery. Patients received either aspirin 325 mg q.d., aspirin 325 mg t.i.d., aspirin 325 mg and dipyridamole 75 mg t.i.d., or placebo. Aspirin was initiated either 12 hours before or 6 hours after operation. Patients were stratified preoperatively for extent of disease and randomized to the therapies outlined above. There was no randomization to IMA versus saphenous vein grafts to the LAD. When the patients taking placebo were compared with those taking aspirin, there were no differences in the IMA (100.0% versus 92.1%, p = 0.385) or vein graft (88.8% versus 90.4%, p = 0.675) patency rates. The patency rate, irrespective of treatment, for all IMA grafts was 92.8% (220 of 237) versus 90.1% (345 of 383) for all vein grafts to the LAD (p = 0.309). Thus, both the IMA and vein grafts had excellent patency rates at 1 year. Aspirin did not alter this at 1 year, and there were no differences between IMA and vein graft patency to the LAD.

Aspirin

Complications of cardiac catheterization and angiography in patients with valvular heart disease. VA Cooperative Study on Valvular Heart Disease.

Complications were surveyed prospectively in 2,029 catheterizations performed on 1,483 patients from the 13 centers participating in the VA Cooperative Study on Valvular Heart Disease. Complications were reported in 6.9% of 1,559 preoperative procedures of which 2.6% were major and 0.2% fatal. Clinical predictors of complications were hypertension and the precatheterization diagnosis of aortic stenosis. Nevertheless, patients with aortic stenosis successfully tolerated left ventriculography, which was routinely performed regardless of the magnitude of gradient. Procedural predictors of complication were brachial arteriotomy (vascular occlusion) and transseptal catheterization (tamponade). Among the 470 postoperative catheterizations performed solely for research purposes, there were six complications, of which five were bleeding events in patients taking warfarin. Transseptal catheterization was safer in postoperative patients with no cases of tamponade in 125 procedures.

Cardiac Catheterization

Preoperative identification of patients likely to have left ventricular dysfunction after aortic valve replacement. Participants in the Veterans Administration Cooperative Study on Valvular Heart Disease.

The purpose of this study was to identify preoperative and intraoperative variables predictive of left ventricular dysfunction 6 months after aortic valve replacement. Patients were considered to have postoperative left ventricular dysfunction if the end-diastolic-volume index was greater than or equal to 101 ml/m2 or if the ejection fraction was less than or equal to 0.50. Data from 180 patients entered into the Veterans Administration Cooperative Study on Valvular Heart Disease who had technically satisfactory cardiac catheterizations 6 months postoperatively were analyzed by a series of univariate and multivariate analyses. For the 88 patients with preoperative aortic stenosis, the most powerful predictor of postoperative left ventricular dysfunction in the final multivariate model was preoperative left ventricular ejection fraction (p = 0.0001), followed by preoperative myocardial infarction (p = 0.012), aortic valve gradient (p = 0.020), and incomplete coronary revascularization (p = 0.059). Abnormal preoperative left ventricular ejection fraction had a sensitivity of 72% and a specificity of 82% in identifying patients with postoperative left ventricular dysfunction. Preoperative left ventricular systolic-volume index greater than or equal to 40 ml/m2 had a similar sensitivity and specificity (79% and 84%, respectively). For the 36 patients with aortic regurgitation, preoperative left ventricular ejection fraction was again the most powerful predictor of postoperative left ventricular dysfunction (p = 0.013), followed by left ventricular systolic pressure (p = 0.038) and arteriovenous oxygen difference (p = 0.054). For the 56 patients with mixed aortic stenosis and regurgitation, left ventricular systolic pressure (p = 0.007) and preoperative myocardial infarction (p = 0.022) were the variables predictive of postoperative left ventricular dysfunction. Although many patients with preoperative left ventricular dysfunction experience improved left ventricular performance after aortic valve replacement, performance does not always return to normal. For patients with either aortic stenosis or regurgitation, the strongest predictor of postoperative left ventricular dysfunction is preoperative dysfunction. These data support the concept that patients with moderate or severe aortic stenosis or regurgitation should be operated on before the onset of significant left ventricular dysfunction.

Aortic Valve