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Background: Valve replacement in small aortic root remains a surgical challenge. The objective of this study was to compare results of the 19-mm bioprosthesis with those of larger prostheses in the elderly., Methods: The 443 patients, 70 years of age and older, who underwent aortic valve replacement with Carpentier-Edwards pericardial bioprostheses were reviewed., Results: There were 93 patients with a mean age of 76+/-4 years with implantation of 19-mm prostheses and 350 patients with a mean age of 75+/-4 years with larger bioprostheses. Associated aortoplasty was performed in 10 patients (11%) with 19-mm bioprostheses and in 8 patients (2%) with larger bioprostheses (p = 0.001). There were 11 deaths (12%) within 30 days of surgery in patients with 19-mm prostheses and 22 deaths (6%) among those with larger prostheses (p = 0.1). The 7-year survival rate averaged 61%+/-7% in patients with 19-mm prostheses and 67%+/-4% in those with larger prostheses (p = 0.8). The 7-year freedom rates from all valve-related events averaged 96%+/-2% and 93%+/-2%, respectively (p = 0.6)., Conclusions: Aortic valve replacement with the 19-mm Carpentier-Edwards pericardial bioprosthesis offers excellent midterm results in the elderly.

Background: Mechanical prostheses are used in young patients and bioprostheses in the elderly because of the higher rate of structural failure of bioprostheses. The objective of the present study was to compare results after aortic valve replacement with mechanical (Carbo-Medics) and biologic (Carpentier-Edwards pericardial) in middle-aged patients., Methods: Five hundred twenty-one patients, aged between 55 and 65 years, who underwent aortic valve replacement with mechanical (n = 363) or biologic (n = 158) prostheses were reviewed., Results: The 10-year actuarial survival rate averaged 66%+/-6% in patients implanted with mechanical valves compared with 75%+/-4% in patients implanted with biologic valves (p = 0.2). The 10-year freedom rate from thromboembolism, hemorrhage, and endocarditis averaged 92%+/-7%, 97%+/-2%, and 99%+/-1%, respectively, in patients with mechanical valves compared with 91%+/-3% (p = 0.03), 99%+/-1% (p = 0.4), and 95%+/-2% (p = 0.01), respectively, in those with biologic valves. The 10-year freedom rate from all valve-related complications averaged 90%+/-7% and 83%+/-4%, respectively (p = 0.01)., Conclusions: The freedom rate from all valve-related complications was higher among patients with mechanical valves compared with biologic valves 10 years after aortic valve replacement in middle-aged patients.

Background: This multicenter study concerning the mitral PERIMOUNT valve previously reported clinical results at 12 years; this report updates the performance to 15 years postoperatively., Methods: The 435 patients (mean age 60.7+/-11.6 years; 41.1% male) underwent implantation with the PERIMOUNT valve between 1984 and 1989 at seven institutions. Follow-up was complete for 96.1% of the cohort. The mean follow-up was 8.1+/-4.4 years (range 0 to 15.4 years) for a total of 3492 patient-years., Results: There were 34 (7.8%) operative deaths, one (0.2%) valve related. The late mortality rate was 5.3%/patient-year (2.2%/patient-year valve related). At 14 years, the overall actuarial survival rate was 37.1%+/-3.3% (63.1%+/-4.4% valve related). Actuarial freedom from complications at 14 years was as follows: thromboembolism, 83.8%+/-3.2% (1.1%/patient-year); hemorrhage, 86.6%+/-3.2% (1.1%/patient-year); and explant due to structural valve deterioration (SVD), 68.8%+/-4.7%. Actual freedom from explant due to SVD was 83.4%+/-2.3%. Rates of structural failure decreased with increasing age at implant., Conclusions: The Carpentier-Edwards PERIMOUNT Pericardial Bioprosthesis is a reliable choice for a tissue valve in the mitral position, especially in patients more than 60 years of age.

Background: The objective of the present study was to compare current results of prosthetic valve replacement following acute infective native valve endocarditis (NVE) with that of prosthetic valve endocarditis (PVE). Prosthetic valve replacement is often necessary for acute infective endocarditis. Although valve repair and homografts have been associated with excellent outcome, homograft availability and the importance of valvular destruction often dictate prosthetic valve replacement in patients with acute bacterial endocarditis., Methods: A retrospective analysis of the experience with prosthetic valve replacement following acute NVE and PVE between 1988 and 1998 was performed at the Montreal Heart Institute., Results: Seventy-seven patients (57 men and 20 women, mean age 48 +/- 16 years) with acute infective endocarditis underwent valve replacement. Fifty patients had NVE and 27 had PVE. Four patients (8%) with NVE died within 30 days of operation and there were no hospital deaths in patients with PVE. Survival at 1, 5, and 7 years averaged 80% +/- 6%, 76% +/- 6%, and 76% +/- 6% for NVE and 70% +/- 9%, 59% +/- 10%, and 55% +/- 10% for PVE, respectively (p = 0.15). Reoperation-free survival at 1, 5, and 7 years averaged 80% +/- 6%, 76% +/- 6%, and 76% +/- 6% for NVE and 45% +/- 10%, 40% +/- 10%, and 36% +/- 9% for PVE (p = 0.003). Five-year survival for NVE averaged 75% +/- 9% following aortic valve replacement and 79% +/- 9% following mitral valve replacement. Five-year survival for PVE averaged 66% +/- 12% following aortic valve replacement and 43% +/- 19% following mitral valve replacement (p = 0.75). Nine patients underwent reoperation during follow-up: indications were prosthesis infection in 4 patients (3 mitral, 1 aortic), dehiscence of mitral prosthesis in 3, and dehiscence of aortic prosthesis in 2., Conclusions: Prosthetic valve replacement for NVE resulted in good long-term patient survival with a minimal risk of reoperation compared with patients who underwent valve replacement for PVE. In patients with PVE, those who needed reoperation had recurrent endocarditis or noninfectious periprosthetic dehiscence.

Background: The objective of this study was to evaluate serum cardiac troponin T and I levels in patients in whom electrocardiogram, myocardial scan, and serum CK-MB levels of the MB isoenzyme of creatine kinase indicated perioperative myocardial infarction (MI) after coronary artery bypass grafting (CABG)., Methods: We studied 590 patients who underwent CABG at the Montreal Heart Institute between 1992 and 1996. Postoperative cardiac troponin T levels (493 patients), troponin I levels (97 patients), and activity of the MB isoenzyme of creatine kinase, electrocardiograms, clinical data, and clinical events were recorded prospectively. The diagnosis of perioperative PMI was defined by a new Q wave on the electrocardiogram, by serum levels of the MB isoenzyme of creatine kinase higher than 100 IU/L within 48 hours after operation, or both., Results: After CABG, 22 patients in whom troponin T levels (22/493, 4.5%) and 6 patients in whom troponin I levels (6/97, 6.2%) were measured had sustained a perioperative MI according to current diagnostic criteria. In these patients, troponin T levels higher than 3.4 microg/L 48 hours after CABG best detected the presence of perioperative MI, with an area under the receiver operating characteristic curve of 0.95, a sensitivity of 90%, a specificity of 94%, a positive predictive value of 41%, a negative predictive value of 99%, and a likelihood ratio of 15. Serum troponin I levels higher than 3.9 microg/L 24 hours after CABG confirmed the perioperative MI with an area under the receiver operating curve of 0.86, a sensitivity of 80%, a specificity of 85%, a positive predictive value of 24%, a negative predictive value of 99%, and a likelihood ratio of 5., Conclusions: Serum troponin T levels higher than 3.4 microg/L 48 hours after CABG correlated best with the diagnosis of perioperative MI. Serum troponin T levels greater than 3.9 microg/L 24 hours after CABG also correlated with the diagnosis of perioperative MI, although a larger experience is needed to confirm the validity of the chosen cutoff value.

Background: From 1994 to 1996, 75 patients undergoing valve replacement were randomized to antegrade (36 patients, group 1) or antegrade/retrograde (39 patients, group 2) administration of cold blood cardioplegia., Methods: Groups were comparable for age, sex, valve disease, and ventricular dysfunction. The aortic valve was replaced in 27 patients from group 1 and 24 patients from group 2, the mitral valve in 8 and 15 patients, and 1 patient in group 1 underwent double valve replacement (p = not significant)., Results: Lengths of cardiopulmonary bypass and aortic cross-clamp averaged, respectively, 10 minutes (p = not significant) and 12 minutes (p = < 0.05) shorter in group 2. Total amount of cardioplegia solution infused averaged 1,279 +/- 406 mL and 1,341 +/- 379 mL (p = not significant), respectively, in groups 1 and 2, and the period of infusion averaged 44% and 72% (p = < 0.01) of the total period of aortic cross-clamping. No death occurred in group 1 compared to two in group 2 (p = not significant). The perioperative myocardial infarction and stroke rates were comparable in both groups. Peak enzyme release at 24 hours was similar both for creatine kinase-MB fraction (26 versus 37 IU/L) and for troponin T (2.1 versus 2.5 IU/L)., Conclusions: Our study shows no significant advantage of the antegrade/retrograde administration of cardioplegia over the antegrade route in routine valvular replacement, other than a slightly shorter aortic cross-clamping time.

Background: The long-term benefits of double versus single internal mammary artery (IMA) coronary bypass grafting have not yet been established., Methods: Six hundred patients were studied retrospectively 10 years after coronary revascularization using saphenous vein grafts (SVGs) only or single or double IMA grafts., Results: Patients with double IMA grafts were younger and were more likely to have diabetes, left main coronary stenosis, and three-vessel coronary artery disease than patients with SVGs or single IMA grafts. Patients with SVGs and double IMA grafts had a greater number of diseased coronary vessels and a greater number of coronary bypass grafts per patient than patients with single IMA grafts (mean +/- SEM, 2.8 +/- 1.0, 2.8 +/- 0.7, 2.1 +/- 0.8 grafts per patient, respectively, p < 0.0001). Actuarial survival rates 10 years after placement of SVGs and single and double IMA grafts averaged 83% +/- 6%, 90% +/- 4%, and 87% +/- 8%, respectively (p = 0.03). Cox regression analysis showed that diabetes (relative risk, 2.03; 95% confidence interval, 1.55 to 2.66) and chronic pulmonary obstructive disease (relative risk, 2.20; 95% confidence interval, 1.58 to 3.80) increased, whereas an IMA graft on the left anterior descending coronary artery significantly decreased, the risk of death after operation (relative risk, 0.45; 95% confidence interval, 0.36 to 0.57) throughout the follow-up period., Conclusions: Use of an IMA graft on the left anterior descending coronary artery improves survival compared with use of an SVG. Although patients with double IMA grafts had a greater number of poor prognosis risk factors before operation, their 10-year survival rate was similar to that of patients with a single IMA graft.

Background: The Mitroflow pericardial bioprosthesis (model 11), a second-generation pericardial prosthesis, has clinical performance assessment to 10 years. The authors previously recommended the prosthesis for aortic valve replacement in patients 70 years or older. The purpose of the current assessment is to report on performance in patients 60 years or older undergoing aortic valve replacement., Methods: This bioprosthesis was implanted in 161 patients (mean age, 69.5+/-6.3 years; range, 60 to 94 years) with aortic valve replacement from 1982 to 1992. There were 84 patients 60 to 69 years (mean, 64.5+/-3.1 years) and 77 patients 70 years or older (mean, 74.8+/-4.3 years). Of the total population, concomitant procedures were performed in 63 patients (39.1%); of these, coronary artery bypass grafting was performed in 39 (24.2%)., Results: The early mortality was 4.8% (4 patients) for the 60 to 69-year age group and 10.4% (8) for those 70 years or older (not significant). The late mortality was 4.4%/patient-year (27) for those 60 to 69 years and 6.9%/ patient-year (35) for those 70 years or older (not significant). The patient survival for those 60 to 69 years was 58.0%+/-6.3% and for those 70 years or older, 45.3%+/-5.9% at 10 years (p < 0.05). The valve-related mortality for those 60 to 69 years was 0.82%/patient-year (5) and for those 70 years or older, 1.58%/patient-year (8) (not significant). The reoperation rate for those 60 to 69 years was 3.29%/patient-year (20) and for those 70 years or older, 1.0%/patient-year (5) (p < 0.05). The structural valve deterioration rate for those 60 to 69 years was 3.13%/ patient-year (19) and for those 70 years or older, 1.2%/ patient-year (6) (p < 0.05)., Conclusions: The Mitroflow pericardial bioprosthesis remains recommended for aortic valve replacement in patients 70 years and older.

Background: The aim of the study was to evaluate the late results of the Carpentier-Edwards pericardial bioprosthesis, which we have been implanting since 1981., Methods: The 812 patients who underwent heart valve replacement with a Carpentier-Edwards pericardial bioprosthesis between 1981 and 1996 were reviewed. Their clinical, operative, and follow-up data were prospectively recorded in a computerized database. All but 29 patients were available for follow-up (96% completeness), which averaged 58 months and totaled 3,000 patient-years., Results: There were 598 aortic valve replacements (74%), 149 mitral valve replacements (18%), and 65 double valve replacements (8%). The mean age at the time of surgery was 65 years (range, 18 to 88 years), with 24% of the patients under the age of 60 years. Preoperatively, 558 patients (69%) were in New York Heart Association functional class III or IV. Associated surgical procedures included coronary artery bypass grafting in 219 patients (27%) and tricuspid or mitral valve repair in 40 (5%). Previous cardiac operations had been performed in 149 patients, including 134 valve-related procedures. There were 49 early deaths overall (6%): 29 after aortic valve replacement (4.8%), 11 after mitral valve replacement (7.4%), and 9 with double valve replacement (13.8%). There were 120 late deaths for a 10-year actuarial survival rates of 69%+/-3%, 58%+/-7%, and 38%+/-10% for aortic, mitral, and double valve replacement, respectively. The 14-year survival rate for aortic valve replacement patients is 68%+/-3%. The 10-year and 14-year actuarial freedom rates from events after aortic valve replacement are 92% +/-2% and 88%+/-4% for thromboembolism, 96%+/-1% and 92%+/-4 for endocarditis, 91%+/-2 and 72%+/-6% for reoperation, and 93%+/-2% and 80%+/-5% for structural dysfunction of the valve. The 10-year actuarial freedom rates from events after mitral and double valve replacement are 93%+/-3% and 89%+/-4% for thromboembolism, 95%+/-3% and 88%+/-5% for endocarditis, 76%+/-7% and 70%+/-14% for reoperation, and 81%+/-7% and 72%+/-15% for structural dysfunction. No primary tissue failure of the prosthesis in any position was observed in the 357 patients aged 70 years or more at the time of valve implantation., Conclusions: The Carpentier-Edwards pericardial valve offers excellent clinical results and durability, particularly in the aortic position and for patients older than 70 years of age.

Background: L-arginine appears to improve myocardial protection during cardioplegic arrest in animal models., Methods: To study the clinical effect and safety of L-arginine in humans, a phase I pilot study was performed with 50 patients who underwent coronary artery bypass grafting. We randomly assigned half to a treatment group, which received 1 g of L-arginine administered during the first 30 minutes of cardioplegic arrest induced by either warm or cold blood cardioplegia, and half to a control group, which did not receive L-arginine supplementation., Results: Age, sex, and preoperative clinical status were similar in both groups. Seventeen patients of each group were administered intermittent warm antegrade blood cardioplegia, whereas the solution needed to be cooled to obtain complete standstill of the remaining eight hearts in each group. An internal thoracic artery graft to the left anterior descending coronary artery was performed in all patients. There was no death and no myocardial infarction in the treatment group, but there were one death and two infarctions in the control group. The amount of serial release of troponin I during the first 72 hours after the operation was similar between the L-arginine group and the control group (p > 0.05). Peak serum troponin levels averaged 4.9 +/- 1.0 microg/L in the arginine group and 3.9 +/- 1.0 microg/L in the control group (p > 0.05). A multivariate analysis of variance showed no effect of L-arginine (p > 0.05) but a significant effect of the temperature of the cardioplegic solution on the release of troponin I (p < 0.05). Serum troponin I levels averaged 2.2 +/- 0.4 microg/L, 4.5 +/- 0.4 microg/L, and 6.9 +/- 0.4 microg/L in the patients with cold cardioplegia and 1.4 +/- 0.3 microg/L, 2.4 +/- 0.3 microg/L, and 3.3 +/- 0.3 microg/L in the patients with warm cardioplegia 1, 2, and 6 hours, respectively, postoperatively., Conclusions: The administration of 1 g of L-arginine during the first 30 minutes of blood cardioplegic arrest did not result in a decrease in the postoperative release of cardiac enzyme; however, cold cardioplegic arrest significantly increased the release of cardiac troponin I postoperatively. There was no significant side effect related to the addition of L-arginine to the cardioplegic solution.

Background: The objective of this study was to evaluate the value of retrograde blood cardioplegia in coronary artery bypass grafting., Methods: In 1994 and 1995, 224 patients undergoing first-time isolated coronary artery bypass grafting were randomized to antegrade (112 patients, group 1) or retrograde (112 patients, group 2) administration of blood cardioplegia. In group 1, 76 patients were given warm cardioplegia (at 33 degrees C) and 36 had cold cardioplegia (< 20 degrees C), whereas in group 2 cardioplegia was warm in 77 patients and cold in 35. The two randomization groups had similar demographic and angiographic characteristics. The number of grafted coronary arteries averaged 2.9 +/- 0.7 in group 1 and 2.8 +/- 0.7 in group 2. Total duration of cardiopulmonary bypass (78 +/- 23 and 75 +/- 21 minutes) and of aortic cross-clamping (47 +/- 16 and 46 +/- 16 minutes), total volume of infusion of the crystalloid component of cardioplegia (988 +/- 297 and 1016 +/- 595 mL), and total duration of infusion of cardioplegia (23 +/- 10 and 22 +/- 11 minutes) were similar (p > 0.05)., Results: There was no death in group 1 and one in group 2 as a result of a pulmonary embolus, for a global early mortality of 0.45%. The numbers of perioperative myocardial infarction (5 versus 3), congestive heart failure (4 versus 5), postoperative hemorrhage (4 versus 4), and stroke (1 versus 2) were also similar (p > 0.05). Release curves of total creatine kinase, creatine kinase-MB by serum activity and mass concentration, and troponin T were not significantly different (p > 0.05) between the two groups. For the 216 patients without perioperative myocardial infarction, peak enzyme release of creatine kinase-MB at 24 hours averaged 23 +/- 22 and 20 +/- 18 IU/L, and that of troponin T averaged 1.1 +/- 1.1 and 1.3 +/- 1.5 micrograms/L at 6 hours for the antegrade and the retrograde groups, respectively (p > 0.05)., Conclusions: Our results indicate no evidence that the retrograde method of cardioplegic infusion improves myocardial protection during first operation for isolated coronary revascularization compared with the usual antegrade route.

Background: Cyclosporin A is known to alter endothelium-dependent responses to different agonists. Few data are available concerning the effect of cyclosporin A on the pulmonary vascular bed., Methods: The endothelium-dependent responses to acetylcholine (20 micrograms), bradykinin (5 micrograms), and substance P (5 micrograms) were investigated in a dog model of left lung autoperfusion at constant flow., Results: The vasodilator response to bradykinin and substance P was significantly decreased with cyclosporin A (20 mg) administration. The average decreases in pulmonary arterial pressure with bradykinin were 5.4 +/- 1.5 mm Hg and 2.4 +/- 0.4 mm Hg before and after cyclosporin A administration, respectively (p = 0.04). The average decreases in pulmonary arterial pressure with substance P were 4.4 +/- 1.0 mm Hg and 1.8 +/- 0.5 mm Hg before and after cyclosporin A administration, respectively (p = 0.04). The responses to acetylcholine and the endothelium-independent relaxing agent nitroglycerin were not significantly affected by cyclosporin A. The effects of cyclosporin A on endothelium-dependent responses to bradykinin and substance P were overcome by the administration of L-arginine (200 mg/kg intravenously). The decreased response to bradykinin and substance P after cyclosporin A administration was not significantly affected by indomethacin, a cyclooxygenase inhibitor. The pulmonary angiotensin-converting enzyme activity was also measured using [3H]benzoyl-phenylalanyl-glycyl-proline, an inactive angiotensin-converting enzyme substrate. There was an average [3H]benzoyl-phenylalanyl-glycyl-proline hydrolysis of 54% +/- 2% and 55% +/- 2% before and after cyclosporin A administration, respectively (not significant)., Conclusions: The present study suggests that cyclosporin A selectively decreases endothelium-dependent responses to bradykinin and substance P without affecting the cyclic guanosine monophosphate-dependent pathway in the canine pulmonary vascular bed. The decreased endothelium-dependent responses to bradykinin and substance P are not related to increased angiotensin-converting enzyme activity. The toxic effect of cyclosporin A on endothelium-dependent responses is reversible by the administration of L-arginine, a source of substrate for nitric oxide.

Background: The release of nitric oxide is decreased after myocardial ischemia and reperfusion. Whereas the precursor L-arginine can stimulate the release of nitric oxide, its effect on metabolic recovery after myocardial ischemia is unknown., Methods: To study the effect of L-arginine on metabolic recovery after myocardial ischemia, cardioplegia infusion, and reperfusion, 33 dogs were placed on cardiopulmonary bypass and subjected to a sequence of 30 minutes of normothermic global ischemia, 30 minutes of warm blood cardioplegic arrest, and 30 minutes of reperfusion. A pH probe was inserted in the anterior wall of the left ventricle, and tissue pH was measured throughout the experiment. Coronary blood flow in the left anterior descending coronary artery and the circumflex coronary artery was measured. Blood samples from the coronary sinus were taken to measure blood pH and levels of lactate, creatine kinase, and troponin T., Results: In the control group of 9 dogs, tissue pH averaged 6.4 +/- 0.1, 6.5 +/- 0.1, and 6.8 +/- 0.1 after the end of global ischemia, cardioplegia, and reperfusion, respectively. Tissue pH averaged 6.4 +/- 0.1, 6.6 +/- 0.1, and 6.9 +/- 0.1, respectively, in the experimental group of 9 animals with 2 mmol/L of L-arginine added to the cardioplegic solution. Tissue pH averaged 6.2 +/- 0.1, 6.7 +/- 0.1, 7.1 +/- 0.1, respectively, in the third group of 9 animals that received an additional infusion of L-arginine (10 mg.kg-1.min-1) during reperfusion. Tissue pH recovered faster in groups with L-arginine (p = 0.00001). A hyperemic response of coronary blood flow was shown at reperfusion in animals in the control group only. In 6 dogs, L-NAME (N-nitroarginine methyl ester), an inhibitor of nitric oxide synthesis, was injected and resulted in a slower pH recovery on reperfusion compared with that of animals that received L-arginine., Conclusions: The addition of L-arginine to the cardioplegic solution and the systemic circulation during reperfusion resulted in a significant increase in coronary blood flow during cardioplegia infusion and in a faster recovery of myocardial tissue pH, possibly by increasing coronary blood flow through the release of nitric oxide.

Background: A prospective, randomized clinical study involving 34 patients undergoing heart transplantation compared myocardial preservation of donor hearts maintained with continuous reperfusion with retrograde warm blood cardioplegia during surgical implantation versus the standard cold topical irrigation., Methods: Hearts in both groups were arrested with a standard crystalloid solution and maintained in a cold saline solution during transportation. In the retrograde group, cardioplegia was administered through a catheter in the coronary sinus during surgical implantation. An average of 471 +/- 30 mL of hyperkalemic crystalloid solution diluted 1:4 in warm blood from the oxygenator was infused. In the standard group, the heart was kept cold by topical irrigation of cold saline solution and was reperfused only when the ascending aorta was unclamped., Results: Preoperative characteristics of donors and recipients were similar in the two cohorts. Ischemic time average 139 +/- 12 minutes in the retrograde group compared with 130 +/- 11 minutes in the standard group (p = 0.57). Cardiopulmonary bypass time averaged 89 +/- 4 minutes in the retrograde group and 110 +/- 12 minutes in the standard group (p = 0.12). Defibrillation at reperfusion was performed in 4 patients (4/17, 24%) in the retrograde group and 12 patients (12/18, 67%) in the standard group (p = 0.01). There were no deaths in the retrograde group (0/17), whereas in the standard group, 3 patients (3/17) died of early graft failure (p = 0.11). Four early graft failures occurred in the standard group (p = 0.06). Two patients (2/17, 12%) were weaned from bypass with ventricular assist devices in the standard group. The number of subendocardial necrotic cells in the first two weekly endomyocardial biopsy specimens averaged 2.7 +/- 0.8 cells/mm2 in the retrograde group and 5.9 +/- 2.4 cells/mm2 in the standard group (p = 0.12)., Conclusions: Retrograde warm blood reperfusion appears to improve the initial recovery of transplanted hearts. The technique is easy to use and may be a useful approach to graft protection during surgical implantation.

Background: The treatment of severe or persistent acute rejection remains difficult despite newer immunosuppressive agents available., Methods: To evaluate the effectiveness of rabbit antithymocyte globulin and methotrexate as therapy for severe or persistent acute cardiac allograft rejection, we conducted a retrospective analysis of clinical and laboratory data from 150 consecutive heart transplant recipients between 1983 and 1994., Results: Thirteen episodes of severe or refractory acute rejection were treated with rabbit antithymocyte globulin in 10 patients. Rabbit antithymocyte globulin (125 mg/day for 3 consecutive days) was effective in 90% of patients. Therapy was well tolerated, and contributed to one infectious complication, no malignancy, and long-term survival in 8 of 10 patients. Recurrent rejection developed in 60% of patients. Methotrexate (7.5 to 15 mg/wk for 16 weeks) was administered to 8 patients with persistent rejection documented on three consecutive endomyocardial biopsies. Therapy was effective in 6 of the 8 patients, with one infectious complication and no malignancy on follow-up. White blood cell count decreased significantly during therapy (p = 0.008). Seven of the 8 patients in the methotrexate group are long-term survivors., Conclusions: Rabbit antithymocyte globulin is a valuable alternative in patients with severe or refractory acute rejection. Methotrexate is an important adjunct in patients with persistent rejection unresponsive to conventional immunosuppressive regimens.

Carpentier-Edwards pericardial bioprostheses were implanted in 600 patients: 416 aortic valve replacement, 115 mitral valve replacement, 6 isolated tricuspid, and 63 multiple valve replacements. The survival rates were 70% at 10 years after aortic valve replacement, 62% 8 years after mitral valve replacement, and 57% at 8 years with multiple valve replacement. Overall, 69 patients suffered one or more valve-related complications. The 10-year freedom rates from embolism were 91% (aortic valve replacement), 92% (mitral valve replacement), and 89% (multiple valve replacement), and those from endocarditis were 95%, 93%, and 85%, respectively. In 18 of the 35 patients, reoperation was due to primary valve dysfunction. Freedom from primary dysfunction was 87% at 10 years with aortic valve replacement, and at 8 years, it was 79% with mitral valve replacement and 77% with multiple valve replacement. A direct correlation was found between freedom from valve dysfunction and age of the patient at operation, with a 10-year-free rate of 90% among patients older than 59 years. This bioprosthesis has an excellent durability up to 10 years in the aortic position. More data regarding its long-term durability in the mitral position are needed. It is currently our valve substitute of choice when a bioprosthesis is indicated.

The Mitroflow pericardial bioprothesis, a second generation pericardial prosthesis, has clinical performance assessment to 10 years. This bioprosthesis was used in 445 operations in 445 patients between 1982 and 1992 inclusive (mean age, 59.1 years; age range, 19 to 94 years). There were 253 aortic valve replacements (AVR), 155 mitral valve replacements (MVR), 31 multiple valve replacements (MR), and 6 tricuspid valve replacements. Concomitant procedures were performed in 40 patients (14.2%). The age group distributions (years) were less than or equal to 35 years, 28 patients; 36 to 50 years, 79; 51 to 64 years, 167; 65 to 69 years, 70; and 70 years or more, 101 patients. The total follow-up was 1,524 patient-years (mean, 5.4 years), 96% complete. The early mortality was 6.3%/patient-year (28 patients) and the late mortality was 4.1%/patient-year (96 patients). Concomitant procedures did not influence either early or late mortality (p = not significant [NS]). The overall patient survival at 10 years was 58% +/- 5% (p = NS by valve position). The overall freedom from structural valve deterioration (SVD) at 8 years was 69% +/- 3% and at 10 years, 45% +/- 7%; and at 8 years AVR 80% +/- 4%, MVR 58% +/- 6%, and MR 38% +/- 11% (p < 0.05, AVR > MVR > MR). The freedom from thromboembolism (TE) was 87% +/- 2%, overall at 10 years, and was not different by valve position (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

The optimal temperature of blood cardioplegia remains controversial. Interstitial myocardial pH was monitored online with a probe that was inserted in the anterior wall of the left ventricle. Venous pH, lactate production, and creatine kinase and troponin T release were measured in coronary sinus blood obtained in 14 dogs after ischemic arrest periods of 5, 10, 20, and 40 minutes with warm (n = 7; mean myocardial temperature, 35 degrees +/- 2 degrees C) and cold (n = 7; mean myocardial temperature, 12 degrees +/- 1 degree C) blood cardioplegic protection. Blood cardioplegic solution was delivered at a rate of 100 mL/min during the 10 minutes between each ischemic arrest. The interstitial myocardial pH decreased significantly (p < 0.05) from 7.1 +/- 0.3 to 6.53 +/- 0.3 after ischemia in animals perfused with warm blood cardioplegia and from 7.04 +/- 0.3 to 6.64 +/- 0.1 in those receiving cold blood cardioplegic protection; however, the difference between the groups was not significant (p > 0.05). Lactate production and creatine kinase and troponin T release increased significantly after ischemia, but there was no difference in the changes between the warm and cold blood cardioplegia groups. In conclusion, ischemia caused significant changes in all variables measured, and these changes were directly proportional to the duration of ischemia. However, there was no significant difference (p > 0.05) in the myocardial metabolic changes between the warm and cold blood cardioplegia groups in terms of the duration of ischemic arrest studied.(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective, randomized study was performed in 200 patients undergoing coronary artery bypass grafting to compare the myocardial protection obtained with intermittent antegrade warm versus cold blood cardioplegia. Preoperative and surgical characteristics of the two cohorts were similar. Intermittent antegrade infusion of warm blood cardioplegia failed to achieve sustained electromechanical arrest of the heart in 13%. The only difference in clinical outcomes was the more frequent spontaneous return to sinus rhythm after the unclamping of the aorta in the warm group (88% versus 70%, p = 0.002). Mortality (1% each) and myocardial infarction (2% and 4%) rates were similar. Rates of increase in serum activity of the isoenzyme of creatine kinase (CK-MB), CK-MB mass concentration, and cardiac troponin-T level as well as total release of troponin T were significantly lower in the warm group, and fewer patients in this group had a clinically significant increase in serum CK-MB mass (20% versus 39%, p = 0.005) and troponin T (20% versus 56%, p = 0.00001). Thus, intermittent antegrade warm blood cardioplegia is appropriate and clinically safe; the lower release of biochemical markers of myocardial damage suggests improved protection during first-time coronary artery bypass grafting.

Allograft coronary artery disease is a major threat to long-term survival after cardiac transplantation. It has been suggested that hyperlipidemia plays a major role in allograft coronary disease. The objective of the present study was to evaluate the effect of a lipid-lowering intervention with diet and drug therapy after cardiac transplantation. Forty-six patients who underwent transplantation between 1988 and 1991 and who were treated with the American Heart Association phase 1 diet and an HMG coenzyme A reductase inhibitor (lovastatin or simvastatin) when low-density lipoprotein cholesterol levels were higher than 3.4 mmol/L were compared with 35 untreated patients having transplantation between 1983 and 1988. Annual coronary angiograms were obtained in both groups. Cholesterol, triglyceride, and low-density lipoprotein levels were significantly lower in the treated group. Actuarial survival and event-free survival (survival free from allograft coronary artery disease) were similar in both groups. Low-density lipoprotein levels lower than 3 mmol/L at the last follow-up had a positive effect on event-free survival. The cholesterol-lowering intervention was not effective in decreasing the prevalence of allograft coronary artery disease. This study suggests that more aggressive measures to lower low-density lipoprotein levels may be necessary to significantly affect allograft disease. Clinical trials should be developed to address this hypothesis.

The excellent long-term results with the internal mammary artery for coronary artery bypass grafting have prompted the search for other conduits with similar characteristics. From December 1989 to December 1991, the right gastroepiploic artery (RGEA) has been used as an in situ graft to the posterior descending coronary artery in 51 patients at the Montreal Heart Institute. The patients' age averaged 50 +/- 11 years. Three-vessel coronary artery disease was present in 41 patients and two-vessel disease in the remaining 10 patients. In all but 1 patient, bilateral internal mammary artery grafting was performed in addition to RGEA grafting. The number of grafts per patient averaged 3.2 +/- 0.8. There was no operative mortality. Morbidity was minimal with only myocardial infarction and a pleural effusion in 1 patient. In 1 patient, a splenectomy had to be performed because of iatrogenic tear during dissection of the RGEA. The average hospital stay was 8.2 +/- 2.6 days. Enteral nutrition was resumed on average 2 days after operation. Angiographic evaluation of RGEA grafts was performed before discharge or within the first month after surgery in 31 patients. In 28 patients (28/31, 90%) the RGEA graft was patent, two grafts were occluded, and in the remaining patient, the graft could not be visualized due to technical difficulties during angiography. A second angiographic evaluation was performed in 5 patients, 1 year after operation. Four RGEAs were patent and 1 was occluded. Clinical follow-up averaged 4 months (range 1 to 15 months).(ABSTRACT TRUNCATED AT 250 WORDS)

From January 1987 to January 1992, 11 patients underwent percutaneous transluminal angioplasty (PTA) for the treatment of subclavian artery stenosis before or after coronary artery bypass grafting (CABG) using the internal mammary artery (IMA). There were 8 men and 3 women, with a mean age of 57 +/- 7 years. Four patients had PTA 1 to 4 months before undergoing CABG with IMA grafts, because of either asymptomatic supraclavicular murmurs or neurologic symptoms. Seven patients underwent PTA 2 to 37 months after CABG with IMA grafts, because of recurrent angina. Subclavian artery stenosis was on the left side in 9 patients, the right side in 1 patient, and bilateral in 1 patient. Ten PTA procedures were successful in 9 patients. All patients with post-CABG angina had reversal of the ischemia. There were three complications: one femoral artery thrombosis, one brachial plexus hematoma after an axillary approach, and one acute pulmonary edema after the procedure. Follow-up after PTA ranged from 1 to 60 months (mean, 38 +/- 17 months). Nine patients had no angina at follow-up and 2 had stable angina (class II) upon exertion. Upper-limb Doppler studies showed no evidence of restenosis in any of these patients at a mean follow-up of 38 months. Subclavian artery PTA is a useful alternative to IMA bypass grafting in patients with subclavian artery stenosis discovered preoperatively, and it is the treatment of choice for those presenting with post-CABG angina due to subclavian artery stenosis proximal to an IMA graft.

Infusions of crystalloid hyperkalemic cardioplegic solutions (CHCSs) are known to impair endothelium-dependent coronary relaxation. This impairment might also be influenced by high perfusion pressure and duration of CHCS infusion. To verify this hypothesis, we designed experiments to study the influence of pressure and duration of CHCS infusion as modulating factors in CHCS-related endothelial impairment. Isolated hearts of Sprague-Dawley rats were studied in a Langendorff apparatus for coronary endothelial function. Hearts (n = 6) were exposed to four different CHCSs containing 12, 24, 40, or 100 mmol/L of potassium chloride (KCl). Endothelial and smooth muscle functions were respectively tested by infusion of 5-hydroxytryptamine (1 x 10(-6) mol/L) and sodium nitroprusside (1 x 10(-5) mol/L) before and after CHCS perfusion. In group I (n = 24), 37 degrees C CHCSs were perfused at 80 cm H2O of pressure for 30 minutes. In group II (n = 24), the same CHCSs were perfused at 160 cm H2O for 30 minutes. In group III (n = 18), CHCSs containing 24, 40, and 100 mmol/L of KCl were infused at 160 cm H2O for 10 minutes. In all groups, response to sodium nitroprusside was unaltered by CHCS infusion, indicating that smooth muscle function was preserved. However, in group II, 5-hydroxytryptamine-induced vasodilation was significantly impaired in hearts perfused with CHCS containing 24 mmol/L of KCl or more, suggesting endothelial damage. This study demonstrates that, in addition to KCl concentration, pressure and duration of infusion are two major determinants in CHCS-mediated endothelial damage.

Internal mammary artery (IMA) dissection may cause sternal devascularization and ischemia resulting in sternal wound complication. To evaluate the effect of median sternotomy and IMA dissection on sternal vascular supply, sternal bone tomography was performed 7 days and 1 month after cardiac operation in 67 patients. Seventeen nondiabetic patients had single IMA grafts, 18 had double IMA grafts, and 12 had only saphenous vein grafts or valve replacement. Twenty diabetic patients were studied after any one of these operations. Seven patients were restudied 1 month after the operation. Sternal technetium-99m-methylene diphosphate tomography was performed. The sternum was visualized and focal zones of hypoactivity represented sternal hypoperfusion. The ratio of hypoactivity area over total sternal area was calculated for every patient. After median sternotomy without single or double IMA grafts, the averaged hypoperfusion ratio was 4% +/- 1% compared with 13% +/- 3% after single IMA grafts and 24% +/- 6% after double IMA grafts (p less than 0.0001). Diabetic patients without IMA, with single IMA, and with double IMAs showed hypoperfusion areas of 5% +/- 3%, 15% +/- 5%, and 23% +/- 9%, respectively, a result similar to that of nondiabetic patients. One month after operation the hypoperfusion area decreased to 2% +/- 2% (p less than 0.05) in restudied patients. Our results indicate that IMA dissection causes a significant although partial and temporary sternal ischemia, which is more severe after double IMA than single IMA mobilization and which may be incriminated in the development of sternal wound infection. This vascularization defect was not greater among patients with diabetes mellitus.

Prolactin, a pituitary hormone, has been shown to have an active role in the regulation of the immune system. Prolactin receptors have been described on the membrane of lymphocyte cells, and competitive binding to these receptors by cyclosporine and circulating prolactin has been demonstrated. Experimental evidence suggests a synergistic effect of cyclosporine and bromocriptine, an inhibitor of pituitary release of prolactin, on immunosuppression. Between July 1986 and January 1988, 54 patients were randomly assigned to two groups of immunosuppression treatment. Thirty patients (group 1) were administered cyclosporine, azathioprine, and prednisone and 24 patients (group 2), a modified protocol aimed at decreasing the level of circulating prolactin by adding bromocriptine to the immunosuppression regimen. The two groups were similar in regard to age, preoperative diagnosis, and duration of follow-up. Minimal side effects related to bromocriptine were observed. The overall incidences of rejection and infection were similar, although actuarial analysis showed that freedom from these complications among patients treated with bromocriptine was significantly higher throughout the first 2 months after heart transplantation compared with that of patients in the control group. Other variables such as serum cyclosporine levels and lymphocyte counts were similar in both groups. In conclusion, suppression of circulating prolactin by bromocriptine appears to improve the immunosuppressive effect of cyclosporine, at least during the early postoperative period when the risk of rejection and infection is higher, and could be a promising avenue to successful hormonal manipulations of the immune process after organ transplantation.

Circulating lymphocyte subpopulations were studied in 18 consecutive patients treated with cyclosporine-prednisone immunosuppression during the first month following heart transplantation. Eleven patients showed no evidence of graft rejection. There were eight episodes of acute rejection demonstrated at endomyocardial biopsy in 7 patients. Three patients were treated with corticosteroids, 3 were treated with rabbit antithymocyte globulin (RATG), and 1 died before treatment (early mortality: 5.6%). Using the monoclonal antibody technique, 150 determinations of lymphocyte subpopulations were performed and were correlated with 72 endomyocardial biopsy specimens. Cyclosporine immunosuppression caused a significant (p less than 0.05) decrease in total lymphocyte count (38%) and in the number of OKT3 (52%) and OKT4 cells (55%). During acute rejection, total lymphocytes and OKT3, OKT4, and OKT8 cells all increased significantly, but the T4 to T8 ratio did not change significantly. Treatment of rejection with corticosteroids resulted in a moderate but not significant decrease in all T-cell types, whereas RATG caused a marked but not selective decrease in all T-cell groups. In conclusion, T cells decrease with cyclosporine immunosuppression and with treatment of rejection and increase at onset of rejection, but the T4 to T8 ratio has no predictive value for the diagnosis and severity of rejection, and the sensitivity of the method does not permit its use to assess the degree of immunosuppression with cyclosporine following heart transplantation.

From January, 1977, to December, 1983, 102 patients aged 70 years or more underwent isolated aortocoronary bypass surgery. They were compared with a group of 100 consecutive patients of less than 70 years of age who underwent the same surgical procedure in 1983. The older group was consistently more diseased in regard to clinical incapacity, unstable angina, the number of coronary arteries involved, and the number of coronary bypasses performed. The incidence of substantial stenosis of the left main coronary artery among the older patients was twice that in the younger ones. There were 7 early deaths in the older group and none in the younger patients. The cause of death was cardiac in 3 patients and noncardiac in 4. A total of 54 complications occurred in 39 older patients and 32 in 27 younger patients. The incidence of cardiac complications was similar in both groups (18 in the older and 17 in the younger). However, noncardiac complications were significantly (p less than 0.0001) more common in older patients (32) than in the younger patient group (7). The most frequent in the older group were cerebral (14), sternal (6), and respiratory (5) complications. Thus, the operative risk of aortocoronary bypass grafting is increased after the age of 70 years, particularly because of noncardiac complications, which are responsible for more than half of the early deaths. Careful selection of candidates for surgical treatment in this age group is mandatory, and particular attention should be given preoperatively to the search for noncardiac disorders to decrease the incidence of these operative complications.

Clinical data on the Omniscience cardiac valve prosthesis (sizes 19 to 31 mm) were obtained from 326 patients (155, aortic valve replacement [AVR]; 125, mitral valve replacement [MVR]; and 46, double-valve replacement) during a five-year period (650 patient-years) with 96% accountability. Mean age was 56 +/- 12 years, and 40% (130) of the patients were 61 years old or older. Thirty-one percent (101) had prior or concomitant coronary artery bypass grafting procedures, 9% (28) had a previous malfunctioning prosthesis, and 17% (57) had other cardiac surgical procedures. Eighty percent were in New York Heart Association (NYHA) Functional Class III or IV preoperatively. Early mortality was 10% (34). Five-year actuarial thrombus-free rate is 96% for patients who underwent AVR and 95% for patients having MVR. Postoperatively, 89% (172/193) were in NYHA Class I or II, and 84% (163/193) improved by at least one Functional Class. A significantly high proportion of the postoperative hematological values fall within normal ranges: red blood cell count, 94% (176/187); hematocrit, 88% (166/188); and hemoglobin, 93% (176/190). Ninety-eight percent (287/292) are free from clinical anemia. Four of the 5 patients with clinical anemia had a preoperative history of this condition. Levels of lactic dehydrogenase in 3 patients suggested the probable presence of clinically significant hemolysis, although all 3 have normal hematological values. Actuarial five-year survival for patients who underwent AVR or MVR are similar (82% and 80%, respectively), indicating satisfactory and comparable levels of safety and performance.(ABSTRACT TRUNCATED AT 250 WORDS)

From 1976 to 1988, 1,593 patients underwent valve replacement with a porcine (878 patients) or a pericardial bioprosthesis (715 patients). There were 701 aortic, 678 mitral, and 214 multiple-valve replacements. Follow-up was obtained for 1,559 patients (98%). Early mortality was 9% (79 patients) in the porcine valve group and 5% (37 patients) among patients with a pericardial valve (p less than 0.01). Late survival after replacement with porcine valves was 80% +/- 1% and 62% +/- 3% at 5 and 10 years, respectively. With pericardial valves, 5-year survival was 79% +/- 2%. Among valve-related complications, rates of freedom from thromboembolism, endocarditis, and hemorrhage after 6 years were similar for both valve groups. Freedom from reoperation at 6 years was also similar after aortic (96% versus 91%) or multiple-valve replacement (95% versus 88%). However, for mitral valve replacement, freedom from reoperation was significantly better with porcine valves than with pericardial valves at 6 years (92% versus 68%; p less than 0.001). This difference was mainly due to the Ionescu-Shiley valve, which accounted for 83% of primary tissue failures among pericardial bioprostheses implanted in the mitral position (10/12 patients). After 6 years, freedom from primary tissue failure of mitral valves was 92% +/- 2% with porcine and 70% +/- 11% with pericardial bioprostheses (p less than 0.0001). The degree of clinical improvement among survivors was similar with both valve types. Thus, in the aortic position, pericardial valves compare with porcine valves up to 6 years, whereas in the mitral position, the durability of the former is significantly less, mainly because of the suboptimal performance of the Ionescu-Shiley pericardial bioprosthesis.

In a series of 226 patients with spontaneous pneumothorax, 167 (74%) were managed successfully on an outpatient basis by observation (20%) or by intercostal tube drainage and a flutter valve (54%). Only 59 patients (26%) were hospitalized, and 42 of these were treated surgically (18.6%). Outpatient management with a flutter valve has proved to be safe, efficient, and economical.