Surgical management of aortic valve disease in elderly patients with and without coronary artery disease: influence on quality of life.

AIM: The feasibility of coronary artery bypass grafting (CABG) concomitant with aortic valve replacement (AVR) is well established. However, its impact on long-term patient-perceived quality of life (QoL) in the elderly remains undefined. METHODS: Retrospective analysis was conducted on 866 patients 65 years of age and over who underwent AVR between October 1976 and December 1999 with a Carpentier-Edwards porcine bioprosthesis. This cohort was divided between those who underwent isolated AVR (n=438) and those with AVR and concomitant CABG (AVR+CABG; n=428). Mean age was 77.0+/-6.1 years (range, 65 to 91) in the AVR group and 78.2+/-5.5 years (range, 65 to 93) in the AVR+CABG group. QoL was assessed with the Short Form-36 health survey for survivors at follow-up, which was 97% complete. RESULTS: Operative mortality (OM) was 6.2% (27/438) for the AVR group and 8.9% (38/428) for the AVR+CABG group (P=0.130). The occurrence of hospital complications (P=0.162) and postoperative length of stay (P=0.980) was similar for the 2 groups. Actuarial survival at 10 years was 37.1+/-3.4% for AVR and 38.7+/-4% for AVR+CABG patients (P=0.088). On multivariate analyses, CABG was not a predictor of either OM or long-term survival. QoL was similar for the 2 groups on the summary components: physical health (39.4+/-11.4 versus 40.2+/-12.1; P=0.461) and mental health (50.2+/-10.8 versus 51.9+/-10.1; P=0.103). CONCLUSIONS: Despite the presence of severe coronary artery disease, CABG preserved the long-term QoL in elderly patients undergoing AVR.

Myocardial homing and neovascularization by human bone marrow angioblasts is regulated by IL-8/Gro CXC chemokines.

In the adult, new blood vessel formation can occur either through angiogenesis from pre-existing mature endothelium or vasculogenesis mediated by bone marrow-derived endothelial precursors. We recently isolated endothelial progenitor cells, or angioblasts, in human adult bone marrow which have selective migratory properties for ischemic tissues, including myocardium, to where they home and induce vasculogenesis. Here we show that myocardial production of the IL-8/Gro-alpha CXC chemokine family is significantly increased after acute ischemia, and that this provides a chemoattractant gradient for bone marrow-derived endothelial progenitors, or angioblasts. This chemokine-mediated homing of bone marrow angioblasts to the ischemic heart regulates their ability to induce myocardial neovascularization, protection against cardiomyocyte apoptosis, and functional cardiac recovery. Together, our results indicate that CXC chemokines play a central role in regulating vasculogenesis in the adult, and suggest that manipulation of interactions between chemokines and their receptors on autologous human bone marrow-derived angioblasts could augment neovascularization of ischemic myocardial tissue.

Efficacy of single versus bilateral internal mammary artery grafting in women: a long-term study.

BACKGROUND: Coronary artery bypass grafting carries a higher operative mortality and less favorable long-term benefit in women than in men. Bilateral internal mammary artery grafting (BIMA) has been shown to yield excellent perioperative and long-term results in both women and men. However, controversy continues to exist as to the benefits of a second internal mammary artery graft in women. METHODS: A retrospective analysis was performed comparing 261 consecutive women from a single surgical practice receiving BIMA and supplemental vein grafts between January 1972 and October 1994 with a computer-matched cohort of 261 women receiving single internal mammary artery (SIMA) and vein grafts during the same period. Univariate analysis confirmed the homogeneity of the two groups based on nine preoperative variables. RESULTS: Operative mortality was comparable in the two groups, 3.8% (10 of 261 patients) in the SIMA and 3.4% (9 of 261 patients) in the BIMA group, with a markedly reduced mortality in both groups since 1990, 2.3% (2 of 86 patients) in the SIMA and 1.3% (1 of 78 patients) in the BIMA group. The mean number of distal grafts (2.78, SIMA; 3.14, BIMA), perfusion time (104 minutes, SIMA; 108 minutes, BIMA), and cross-clamp time (58 minutes, SIMA; 66 minutes, BIMA) were all comparable. There was no significant difference in the incidence of postoperative complications, including sternal wound infection. Patient follow-up ranged from 1 month to 27 years, with a mean of 10.0 years in the SIMA group and 9.1 years in the BIMA group. Clinical results were excellent, with 100% (136 of 136 patients) of the SIMA and 100% (167 of 167 patients) of the BIMA patients in Canadian Cardiovascular Society class I or II at follow-up. Rates of late myocardial infarction, percutaneous transluminal coronary angioplasty, and reoperation were similarly low in both groups: 3.7% (5 of 136 patients) versus 1.8% (3 of 166 patients), 5.4% (7 of 136 patients) versus 4.8% (8 of 166 patients), and 3.7% (5 of 136 patients) versus 1.8% (3 of 166 patients), for SIMA versus BIMA survivors, respectively. No significant difference was found in the long-term and event-free survival or in any of the eight subscales of the SF-36 quality of life survey for the two groups. CONCLUSIONS: Excellent short- and long-term results have been demonstrated with internal mammary artery grafting in women. However, the addition of a second internal mammary artery graft does not appear to confer any additional clinical benefits in a comparably matched cohort of patients.

Bilateral internal mammary artery grafting in women: a 21-year experience.

BACKGROUND: Coronary artery bypass grafting traditionally has carried a higher mortality rate in women than in men. It remains the leading cause of death in women despite major advances in diagnosis and treatment over the past 2 decades. METHODS: A retrospective analysis was conducted to identify risk factors that adversely influence hospital mortality, morbidity, and long-term clinical results in women undergoing bilateral internal mammary artery grafting. From January 1972 through October 1994, 327 consecutive women received bilateral internal mammary artery grafts and supplemental vein grafts. Patient age ranged from 32 to 84 years (mean, 65.7 years). There were 262 patients (80.1%) with three-vessel disease; 71 (21.7%) had substantial (> 50%) stenosis of the left main coronary artery, 65 (19.9%) had a moderately reduced (0.30 to 0.50) ejection fraction, and 11 (3.4%) had a severely reduced (< 0.30) ejection fraction. Preoperatively, 316 patients (96.6%) were in New York Heart Association class III or IV. RESULTS: There were 1,016 coronary artery grafts (mean, 3.1 per patient). The overall hospital mortality rate was 3.4% (11 of 327). Postoperative complications included myocardial infarction in 18 patients (5.5%), stroke in 5 (1.5%), pulmonary insufficiency in 11 (3.4%), reoperation for bleeding in 7 (2.1%), and sternal infection in 8 (2.4%). Independent predictors of operative death were postoperative cardiac arrest (p < 0.001), use of intraaortic balloon pump (p < 0.001), and reoperation for bleeding (p < 0.050). Follow-up was completed on 316 hospital survivors (100%) and ranged from 6 months to 21 years (mean, 5.1 years). Actuarial survival (mean +/- standard error of the mean) was 90.5% +/- 1.9% at 5 years and 65.6% +/- 6.1% at 10 years. At follow-up, 252 patients (94.0%) were asymptomatic in New York Heart Association class I, and 12 (4.5%) were in class II. CONCLUSIONS: This longitudinal study demonstrates that bilateral internal mammary artery grafting, though technically demanding, can be achieved in women with low hospital mortality and morbidity rates. Patients experienced reduced late cardiac events, excellent functional improvement, and enhanced long-term survival.

Coronary bypass grafting in the elderly. Single versus bilateral internal mammary artery grafts.

A surgical experience between October 1983 and December 1990, with 1467 consecutive patients 65 years of age and over, was used to compare patients receiving single internal mammary artery grafts (n = 736) with those receiving bilateral internal mammary artery grafts (n = 731). The mean age in the single-graft group was 73.2 years and 70.9 years in the bilateral-graft group (p < 0.001). Various clinical parameters were analyzed that revealed that the single-graft group had more women and more patients with unstable angina, a history of previous myocardial infarction, and emergency surgery (p < 0.05). There was no significant difference in cigarette smoking, hypertension, diabetes mellitus, hyperlipidemia, triple vessel coronary artery disease, left main coronary artery stenosis, or left ventricular function between the two groups. Hospital mortality for the single-graft group was 6.4% (47 patients) and 3.1% (23 patients) for the bilateral-graft group (p < 0.004). No significant difference was observed between the groups in the rate of reoperation for bleeding, sternal infection, respiratory failure, stroke, or perioperative infarction. Follow-up was obtained in 663 hospital survivors (96.4%) in the single-graft group and in 691 (97.7%) in the bilateral-graft group. Mean follow-up in the single-graft group was 42.5 months (range, 1 to 92.4 months) and 43.0 months (range, 1 to 90.3 months) in the bilateral-graft group. In the single-graft group, survival was 60.7% +/- 4.8% (+/- standard error of the mean) at 8 years (60 patients at risk); it was 67.9% +/- 8.1% (18 patients at risk) for the bilateral-graft group (p < 0.028). This comparative study demonstrates that bilateral internal mammary artery grafting can be accomplished in elderly patients with low operative risk and hospital morbidity. Moreover, patients in both groups had a reduction in cardiac events and significant functional improvement.

Bilateral internal mammary artery grafts in patients with left main coronary artery disease.

The use of the internal mammary artery (IMA) in myocardial revascularization has been expanded with bilateral and sequential grafting. However, its application in the presence of left main coronary artery stenosis (LMCAS) has not been well established. From September 1983 through December 1990, 280 patients with LMCAS greater than 50% were revascularized (3.4 mean grafts per patient) with bilateral IMA and saphenous vein grafts. Eighty-one were sequential IMA grafts. There were 234 males (83.6%) and 46 females (16.4%) with a mean age of 64.4 years (range 39 to 84 years). Preoperatively, there were six patients (2.1%) in New York Heart Association (NYHA) Class I, 30 patients (10.7%) in Class II, 130 patients (46.4%) in Class III, and 114 patients (40.7%) in Class IV. Fifty-six patients (20.0%) had an ejection fraction less than 50%. Intraaortic balloon counterpulsation was used preoperatively in 26 patients (9.3%) and intraoperatively in 11 patients (3.9%). There were four hospital deaths (1.4%). Hospital complications included: reoperation for bleeding, 7 patients (2.5%); pulmonary insufficiency, 21 patients (7.5%); perioperative infarction, 14 patients (5.0%); and stroke, 4 patients (1.4%). Follow-up was obtained in 276 hospital survivors (100.0%) with a mean of 33.4 months. There were 20 late deaths (7.1%): seven cardiac related and 12 noncardiac related. Postoperative assessment reveals substantial functional improvement. These results furnish evidence that bilateral IMA grafts can be accomplished with a low operative risk and can provide excellent functional results in patients with LMCAS.

Bilateral internal mammary artery grafts in reoperative and primary coronary bypass surgery.

Bilateral internal mammary artery grafting is recognized as a preferred method of myocardial revascularization. However, its efficacy in coronary bypass reoperation has not been clearly established. From January 1982 through June 1989, 88 patients underwent coronary bypass reoperation with bilateral internal mammary artery grafts. Results were compared with those for a subset of 88 patients receiving primary revascularization with bilateral internal mammary artery grafts who were computer matched for sex, age, left ventricular function, anginal classification, and left main coronary artery disease. In each group, 62.5% (55 patients) had unstable angina, 43.2% (38 patients) had reduced ejection fraction, and 21.6% (19 patients) in the reoperation group and 20.5% (18 patients) in the reference group had left main coronary artery disease. Hospital mortality for the reoperation group was 6.8% (6 patients) and for the reference group, 3.4% (3 patients). No significant difference was found in the incidence of reoperation for bleeding, sternal infection, or stroke in the two groups. The incidence of respiratory insufficiency in the reoperation group was 13.6% (12 patients) and in the reference group, 3.4% (3 patients) (p less than 0.015). Recurrent angina occurred in 13.7% (10 patients) of patients in the reoperation group and 13.3% (10 patients) in the reference group. The long-term survival at 5 years for the reoperation group was 85.3% +/- 5.6% (+/- standard error of the mean) and for the reference group, 91.6% +/- 3.1%. No significant difference was found in the equality of survival distribution for the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Seventeen-year experience with bilateral internal mammary artery grafts.

The internal mammary artery (IMA) is being recognized as the conduit of choice for myocardial revascularization. From January 1972 through June 1988, 1,087 patients received bilateral IMA and supplemental vein grafts. There were 917 men (84.4%) and 170 women (15.6%) with a mean age of 62.4 years (range, 29 to 84 years). Three hundred ninety-four patients (36.2%) had unstable angina, and 194 (17.8%) had left main coronary artery stenosis greater than 50%. In all, 3,741 coronary grafts were performed, with a mean of 3.4 per patient. Hospital mortality was 2.7% (29 patients). Hospital complications included reoperation for bleeding, 19 patients (1.7%); sternal infection, 16 patients (1.5%); respiratory failure, 35 patients (3.2%); perioperative myocardial infarction, 22 patients (2.0%); and stroke, 20 patients (1.8%). Post-operative arteriography in 53 patients (mean postoperative time, 53.0 months) showed that 92.1% (58/63) of the left IMA and 84.9% (45/53) of the right IMA grafts were patent. Follow-up was completed on 1,058 hospital survivors. There were 82 late deaths (7.8%). The actuarial survival for patients discharged from the hospital was 80.0 +/- 3.2% (plus or minus standard error of the mean) at 10 years and 60.0% +/- 5.0% at 15 years. At follow-up, 866 patients (90.3%) were asymptomatic and in New York Heart Association class I and 68 (7.1%) were in class II. This longitudinal analysis demonstrates that bilateral IMA grafting has a low operative risk and provides excellent long-term functional improvement and survival.

Cardiac xenotransplantation in primates.

Successful cardiac xenotransplantation would alleviate the severe shortage of donor organs that presently limits the availability of cardiac transplantation. Early attempts at human xenotransplantation achieved minimal success. However, the effectiveness of cyclosporine in nonhuman xenotransplant models has received little experimental investigation. We have therefore studied the effect of cyclosporine-based immunosuppression in primate cardiac xenograft models using cynomolgus monkey donors and baboon recipients. Donor hearts were transplanted heterotopically into the necks of recipients or in the orthotopic position. Recipients were treated with no immunosuppression (controls), cyclosporine and steroids, or cyclosporine, steroids, azathioprine, and antithymocyte globulin. Statistically significant prolongation of graft survival compared to the control group was observed in the heterotopic groups. Mean survival time of the cyclosporine-treated and steroid-treated heterotopic grafts was 61 days compared to 6 days for grafts in the control group (p = 0.01); the addition of azathioprine and antithymocyte globulin yielded a mean survival of 84 days (p less than 0.01). No significant increase in graft survival was noted in the orthotopic groups treated with either immunosuppressive regimen. Although long-term use of human xenografts as an alternative for heart replacement is not supported by these data, further investigation of the orthotopic model is clearly justified.

Role of the carrier solution in cyclosporine pharmacokinetics in the baboon.

Although numerous investigational models have demonstrated the potent immunosuppressive properties of cyclosporine, the effectiveness of any given dosage may vary with the metabolism of the animal, the route of administration, and the carrier solution of the drug. We investigated the pharmacokinetics of intramuscular cyclosporine administration in the baboon using three carriers: polyoxethylated castor oil (Cremophor), a mixture of octanoic and decanoic acids (Miglyol), and olive oil. Cyclosporine prepared in Cremophor, Miglyol, or olive oil was injected intramuscularly into the hindlegs of baboons. Specimens for cyclosporine assay were obtained 2, 4, 6, 12, 18, and 24 hours after single intramuscular injection of 10 mg/kg or 15 mg/kg. In addition, weekly, then monthly, levels were obtained on animals receiving daily intramuscular injections following heterotopic heart xenografts. Attempts at oral administration proved unreliable and were discontinued. Cyclosporine assay was performed on stored serum using the RIA-KIT (Sandoz Pharmaceuticals Corporation, East Hanover, N.J.). Cremophor provides a more bioavailable form of cyclosporine than Miglyol when administered intramuscularly. (Area under curve = 7776 +/- 1437 for Cremophor 15 mg/kg vs 1837 +/- 726 for Miglyol 15 mg/kg; 2579 +/- 694 for Cremophor 10 vs 1123 +/- 393 for Miglyol 10.) Long-term daily intramuscular administration of Cremophor provides a sustained drug serum trough level with wide variability between individual animals (80 to 825 ng/ml). Toxicity was limited to injection site inflammation. There was no biochemical evidence of renal toxicity; however, some animals did demonstrate early histologic changes of cyclosporine effect.(ABSTRACT TRUNCATED AT 250 WORDS)