Marlene Goormastic

Influence of the Internal-Mammary-Artery Graft on 10-Year Survival and Other Cardiac Events

We compared patients who received an internal-mammary-artery graft to the anterior descending coronary artery alone or combined with one or more saphenous-vein grafts (n = 2306) with patients who had only saphenous-vein bypass grafts (n = 3625). The 10-year actuarial survival rate among the group receiving the internal-mammary-artery graft, as compared with the group who received the vein grafts (exclusive of hospital deaths), was 93.4 percent versus 88.0 percent (P = 0.05) for those with one-vessel disease; 90.0 percent versus 79.5 percent (P less than 0.0001) for those with two-vessel disease; and 82.6 percent versus 71.0 percent (P less than 0.0001) for those with three-vessel disease. After an adjustment for demographic and clinical differences by Cox multivariate analysis, we found that patients who had only vein grafts had a 1.61 times greater risk of death throughout the 10 years, as compared with those who received an internal-mammary-artery graft. In addition, patients who received only vein grafts had 1.41 times the risk of late myocardial infarction (P less than 0.0001), 1.25 times the risk of hospitalization for cardiac events (P less than 0.0001), 2.00 times the risk of cardiac reoperation (P less than 0.0001), and 1.27 times the risk of all late cardiac events (P less than 0.0001), as compared with patients who received internal-mammary-artery grafts. Internal-mammary-artery grafting for lesions of the anterior descending coronary artery is preferable whenever indicated and technically feasible.

Sternal wound complications after isolated coronary artery bypass grafting: Early and late mortality, morbidity, and cost of care ☆

Of 6,504 consecutive patients who underwent isolated coronary bypass grafting in 1985 to 1987, 72 (1.1%) patients experienced sternal wound complications. Ten patients (14%) with wound complications died of multi-system failure. Only the patients with negative cultures fared well; of the bacterial culture categories, polymicrobial infection carried the worst prognosis. Effects of recurring infection were seen throughout the first year. Patients, grouped according to conduits received, experienced these wound complication rates: vein grafts only, 11/1,085 (1.0%); one internal thoracic artery, 38/4,073 (0.9%); and bilateral internal thoracic artery grafts, 23/1,346 (1.7%). There were no significant differences in wound complication rates between primary and reoperation patients or among conduit groups. By logistic regression analysis, the relative risk for patients with diabetes and bilateral internal thoracic artery grafting was 5.00 (95% confidence interval, 2.4 to 10.5). Operation time as a continuous variable increased the relative risk of wound complication 1.47 times per hour (1.3 to 1.7); obesity, 2.90 times (1.8 to 4.8); and blood units as continuous variable, 1.05 times per unit (1.01 to 1.10). Bilateral internal thoracic artery grafting in nondiabetic patients carried no greater risk of wound complication than that in patients with vein grafts only or with one internal thoracic artery graft.

Apolipoprotein A-I is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular disease

In recent studies we demonstrated that systemic levels of protein-bound nitrotyrosine (NO(2)Tyr) and myeloperoxidase (MPO), a protein that catalyzes generation of nitrating oxidants, serve as independent predictors of atherosclerotic risk, burden, and incident cardiac events. We now show both that apolipoprotein A-I (apoA-I), the primary protein constituent of HDL, is a selective target for MPO-catalyzed nitration and chlorination in vivo and that MPO-catalyzed oxidation of HDL and apoA-I results in selective inhibition in ABCA1-dependent cholesterol efflux from macrophages. Dramatic selective enrichment in NO(2)Tyr and chlorotyrosine (ClTyr) content within apoA-I recovered from serum and human atherosclerotic lesions is noted, and analysis of serum from sequential subjects demonstrates that the NO(2)Tyr and ClTyr contents of apoA-I are markedly higher in individuals with cardiovascular disease (CVD). Analysis of circulating HDL further reveals that higher NO(2)Tyr and ClTyr contents of the lipoprotein are each significantly associated with diminished ABCA1-dependent cholesterol efflux capacity of the lipoprotein. MPO as a likely mechanism for oxidative modification of apoA-I in vivo is apparently facilitated by MPO binding to apoA-I, as revealed by cross-immunoprecipitation studies in plasma, recovery of MPO within HDL-like particles isolated from human atheroma, and identification of a probable contact site between the apoA-I moiety of HDL and MPO. To our knowledge, the present results provide the first direct evidence for apoA-I as a selective target for MPO-catalyzed oxidative modification in human atheroma. They also suggest a potential mechanism for MPO-dependent generation of a proatherogenic dysfunctional form of HDL in vivo.

Restenosis After Experimental Angioplasty: Intimal, Medial, and Adventitial Changes Associated With Constrictive Remodeling

Predicting and preventing arterial restenosis after angioplasty has failed despite considerable research into mechanisms and techniques. We examined the roles of chronic constriction, neointimal-medial growth, and adventitial changes in restenosis in atherosclerotic rabbits. Angioplasty was performed on femoral artery lesions 4 weeks after lesion induction by air drying and cholesterol-supplemented diet. Angiographic and histological evaluation was conducted 3 to 4 weeks after angioplasty. The angiographic minimum luminal diameter (MLD) increased from 1.31 +/- 0.21 to 1.73 +/- 0.41 mm after angioplasty. Loss in MLD by 3 to 4 weeks was 0.95 +/- 0.64 mm. Initial gain and late loss correlated (P = .008). Late residual stenosis, defined histologically as the difference between the luminal areas of a proximal reference site and lesion site normalized by the luminal area of the reference site, was 52 +/- 32%. Histological indices of chronic constriction, neointimal-medial growth, and adventitial growth were defined on the basis of the areas of these arterial wall layers at the lesion site relative to the reference site. Another parameter defined as the ratio of adventitial area to the area of intima+media at the lesion site allowed evaluation of the relative importance of these layers. Surprisingly, late residual stenosis correlated with chronic constriction (P = .0003) but not with neointimal-medial growth or adventitial growth. The ratio of adventitial area to the area of intima+media at the lesion site also correlated with chronic constriction (P = .01). These findings suggest that factors related to arterial remodeling rather than neointimal-medial growth may dominate the response to angioplasty.

Serum Myeloperoxidase Levels Independently Predict Endothelial Dysfunction in Humans

Background—In vitro and animal studies demonstrate that myeloperoxidase catalytically consumes nitric oxide as a substrate, limiting its bioavailability and function. We therefore hypothesized that circulating levels of myeloperoxidase would predict risk of endothelial dysfunction in human subjects. Methods and Results—Serum myeloperoxidase was measured by enzyme-linked immunoassay, and brachial artery flow–mediated dilation and nitroglycerin-mediated dilation were determined by ultrasound in a hospital-based population of 298 subjects participating in an ongoing study of the clinical correlates of endothelial dysfunction (age, 51±16; 61% men, 51% with cardiovascular disease). A strong inverse relation between brachial artery flow–mediated dilation and increasing quartile of serum myeloperoxidase level was observed (11.0±6.0%, 9.4±5.3%, 8.6±5.8%, and 6.4±4.5% for quartiles 1 through 4, respectively; P<0.001 for trend). Using the median as a cut point to define endothelial dysfunction, increasing quartile of myeloperoxidase predicted endothelial dysfunction after adjustment for classic cardiovascular disease risk factors, C-reactive protein levels, prevalence of cardiovascular disease, and ongoing treatment with cardiovascular medications (OR, 6.4; 95% CI, 2.6 to 16; P=0.001 for highest versus lowest quartile). Conclusions—Serum myeloperoxidase levels serve as a strong and independent predictor of endothelial dysfunction in human subjects. Myeloperoxidase-mediated endothelial dysfunction may be an important mechanistic link between oxidation, inflammation, and cardiovascular disease.

One hundred patients with the heartmate left ventricular assist device: Evolving concepts and technology

BACKGROUND Implantable left ventricular assist devices are common as a bridge to transplantation but are just reaching their goal as an alternative to transplantation. METHODS From December 1991 until December 1996, 97 left ventricular assist devices were implanted as a bridge to transplantation, one as an alternative to transplantation, and two as a bridge to recovery. Included were 64 pneumatic devices and 36 electric devices. Most patients (69%) had ischemic cardiomyopathy and most (53%) had had previous cardiac surgery. Preoperative circulatory support (extracorporeal membrane oxygenation) was used in 25. RESULTS Perioperative insertion of a right ventricular assist device was unusual (11%). The mean duration of support with a left ventricular assist device (bridge to transplantation) was 70 +/- 41 days (up to 206 days). Survival to transplantation was 76%. Cause of death included multiple organ failure (n = 13), perioperative stroke (n = 5), device failure (n = 5), and controller disconnect (n = 1). Significant risk factors for death included (1) preoperative need for ventilator or extracorporeal membrane oxygenation, (2) elevated blood urea nitrogen, creatinine, or bilirubin, and (3) low pulmonary artery pressures. Risks after insertion of the left ventricular assist device were reoperation for bleeding, support with a right ventricular assist device, dialysis, or device failure. Catastrophic failure of the device occurred 14 times in 12 patients and was treated by emergency pump exchange in six instances. Only two device-related thromboembolic episodes were detected. Positive blood cultures were found in 59% of patients, driveline infection in 28%, and pump infection in 11%. CONCLUSIONS The HeartMate device provided excellent hemodynamic support with low device-related thromboembolic events. Infection and reliability of the device contributed to the high cost of therapy. These areas need to be improved for the left ventricular assist device to attain its goal as a viable alternative to transplantation.

Early results with partial left ventriculectomy

OBJECTIVE We sought to determine the role of partial left ventriculectomy in patients with dilated cardiomyopathy. METHODS Since May 1996 we have performed partial left ventriculectomy in 53 patients, primarily (94%) in heart transplant candidates. The mean age of the patients was 53 years (range 17 to 72 years); 60% were in class IV and 40% in class III. Preoperatively, 51 patients were thought to have idiopathic dilated cardiomyopathy, one familial cardiomyopathy, and one valvular cardiomyopathy. As our experience accrued we increased the extent of left ventriculectomy and more complex mitral valve repairs. For two patients mitral valve replacement was performed. For 51 patients the anterior and posterior mitral valve leaflets were approximated (Alfieri repair); 47 patients also had ring posterior annuloplasty. In 27 patients (51%) one or both papillary muscles were divided, additional left ventricular wall was resected, and the papillary muscle heads were reimplanted. RESULTS Echocardiography showed a significant decrease in left ventricular dimensions after resection (8.3 cm to 5.8 cm), reduction in mitral regurgitation (2.8+ to 0), and increase in forward ejection fraction (15.7% to 32.7%). Cardiac index did not increase significantly (2.2 to 2.4 L/min per square meter). Eight patients (15%) required a perioperative left ventricular assist device; one died and was the only perioperative mortality (1.9%). At 11 months, actuarial survival was 87% and freedom from relisting for transplantation was 72%. CONCLUSIONS Improved selection criteria are necessary to avoid early failures, and much more follow-up and analyses of data are mandatory. However, the operation may become a biologic bridge, or even alternative, to transplantation.

Laparoscopic restorative proctocolectomy: case-matched comparative study with open restorative proctocolectomy.

PURPOSE: A laparoscopic approach to restorative proctocolectomy is new and has not been compared recently with the traditional open procedure. By using prospectively gathered data, laparoscopic and open restorative proctocolectomy procedures in mucosal ulcerative colitis and familial adenomatous polyposis patients were compared by using a case-matched design. METHODS: Forty patients, composing 20 consecutive laparoscopic cases (13 mucosal ulcerative colitis, 7 familial adenomatous polyposis), were matched for age, gender, and body mass index with 20 open cases (13 mucosal ulcerative colitis, 7 familial adenomatous polyposis) performed during the same time period. Mucosal ulcerative colitis patients were also matched for severity of disease by using hemoglobin and albumin levels, whole blood count, and steroid dependency. A loop ileostomy was made in 12 of 13 laparoscopic mucosal ulcerative colitis patients, all open mucosal ulcerative colitis patients, and no familial adenomatous polyposis patients. RESULTS: The median age was 25 (range, 9–61) years. There were no intraoperative complications in either group and no conversions in the laparoscopic group. The operative times (median, range) were significantly longer in laparoscopic cases (330, 180–480 minutes)vs. open cases (230, 180–300 minutes),P<0.001. Bowel function returned more quickly in laparoscopic cases (2, 1–8 days)vs. open cases (4, 1–13 days),P=0.03; and the length of stay was shorter in laparoscopic cases (7, 4–14 days)vs. open cases (8, 6–17 days),P=0.02. For diverted patients, the median length of stay was reduced by two days in laparoscopic cases (6, 4–14 days)vs. open cases (8, 6–17 days),P=0.01. Complications occurred in 4 of 20 laparoscopic patients (3 obstruction/ileus and 1 pelvic abscess) and 5 of 20 open patients (2 obstruction and ileus, 1 each anastomotic leak and abscess, peptic ulceration, and episode of dehydration). CONCLUSIONS: Return of intestinal function and length of stay are reduced in the laparoscopic group compared with open group. A laparoscopic approach to restorative proctocolectomy has the potential of becoming an appealing alternative to conventional restorative proctocolectomy surgery.

Nephron Sparing Surgery in Incidental Versus Suspected Renal Cell Carcinoma

From 1956 to 1992 nephron sparing surgery was performed in 216 patients with sporadic renal cell carcinoma. Renal cell carcinoma was suspected in 121 patients and was an incidental finding in 95. Compared to suspected renal cell carcinoma, incidental tumors were smaller (p = 0.0004), more often unilateral (p = 0.001) and of lower pathological stage (p = 0.001). Incidental tumors were also associated with improved 5-year cancer-specific survival (p = 0.003) and a lower rate of postoperative tumor recurrence (p = 0.001). The overall 5-year cancer-specific survival rate was improved in patients with stage I versus higher stage renal cell carcinoma (p = 0.0002), unilateral versus bilateral disease (p = 0.0001), a single versus multiple tumors in the operated kidney (p = 0.01) and tumors smaller than 4 cm. versus larger tumors (p = 0.03). There were no postoperative tumor recurrences and the 5-year cancer-specific survival rate was 100% in patients with unilateral, stage I tumors smaller than 4 cm. These data define specific eligibility criteria for nephron sparing surgery in patients with localized unilateral renal cell carcinoma and a normal contralateral kidney.

RENAL OUTCOME 25 YEARS AFTER DONOR NEPHRECTOMY

PURPOSE The extended outcome after kidney donation has been a particular concern ever since the recognition of hyperfiltration injury. Few published reports have examined donor renal outcome after 20 years or greater. Kidney transplantation has been performed at the Cleveland Clinic Foundation since 1963, at which there is extensive experience with live donor transplantation. We assess the impact of donor nephrectomy on renal function, urinary protein excretion and development of hypertension postoperatively to examine whether renal deterioration occurs with followup after 20 years or greater. MATERIALS AND METHODS From 1963 to 1975, 180 live donor nephrectomies were performed at the Cleveland Clinic. We attempted to contact all patients to request participation in our study. Those 70 patients who agreed to participate in the study were mailed a package containing a 24-hour urine container (for assessment of creatinine, and total protein and albumin), a vial for blood collection (for assessment of serum creatinine) and a medical questionnaire. All specimens were returned to and processed by the Cleveland Clinic medical laboratories. Blood pressure was taken and recorded by a local physician. A 24-hour creatinine clearance and the Cockcroft-Gault formula were used to estimate renal function, and values were compared with an age adjusted glomerular filtration rate for a solitary kidney. RESULTS Mean patient followup was 25 years. The 24-hour urinary creatinine clearance decreased to 72% of the value before donation. For the entire study cohort serum creatinine and systolic blood pressure after donation were significantly increased compared with values before, although still in the normal range. The overall incidence of hypertension was comparable to that expected in the age matched general population. There was no gender or age difference (younger or older than 50 years) for 24-hour urinary creatinine clearance, or change in serum creatinine before or after donation. Urinary protein and albumin excretion after donation was significantly higher in males compared with females. There were 13 (19%) subjects who had a 24-hour urinary protein excretion that was greater than 0.15 gm./24 hours, 5 (7%) of whom had greater than 0.8. No gender difference was noted in blood pressure, and there were no significant changes in diastolic pressure based on gender or age. CONCLUSIONS Overall, renal function is well preserved with a mean followup of 25 years after donor nephrectomy. Males had significantly higher protein and albumin excretion than females but no other clinically significant differences in renal function, blood pressure or proteinuria were noted between them or at age of donation. Proteinuria increases with marginal significance but appears to be of no clinical consequence in most patients. Patients with mild or borderline proteinuria before donation may represent a subgroup at particular risk for the development of significant proteinuria 20 years or greater after donation. The overall incidence of proteinuria in our study is in the range of previously reported values after donor nephrectomy.