Hal S. Wasserman

Elevated Levels of Plasma C-Reactive Protein Are Associated With Decreased Graft Survival in Cardiac Transplant Recipients

BackgroundInflammation may be involved in the origin of transplant coronary artery disease. We hypothesized that plasma levels of C-reactive protein (CRP) and interleukin-6 (IL-6), markers for systemic inflammation, would correlate with cardiac transplant graft survival. Methods and ResultsWe studied 99 consecutive cardiac transplant recipients who were referred for routine endomyocardial biopsy and/or surveillance coronary angiography. Plasma levels of CRP and IL-6 were measured by their respective ELISAs. Patients were divided into 2 groups: those who died or required retransplantation and those who survived without the need for retransplantation. During the follow-up period of 5.0±2.7 years (range, 0.2 to 15.1 years) after transplant, 20 patients died and 9 required retransplantation. There was no significant difference in age, race, sex, cause of native myopathy, presence of diabetes, or use of aspirin, statins, or calcium channel blockers between the 2 groups. Although IL-6 did not relate to graft failure, CRP level was predictive of allograft failure (P =0.003). The risk of allograft failure increased 36% for every 2-fold increase in CRP level. Moreover, CRP levels also correlated significantly with the frequency of grade 3 rejection (P =0.02). In multivariate analysis, when combined with other significant predictors such as donor age and sex mismatching of the graft, CRP still significantly predicted graft failure (P =0.025) with a 32% increase in the risk of graft failure for every 2-fold increase in CRP level. ConclusionsThese findings suggest that elevated plasma levels of CRP are associated with subsequent allograft failure in cardiac transplant recipients.

Mitral valve hemodynamic effects of percutaneous edge-to-edge repair with the MitraClip™ device for mitral regurgitation

Introduction: The Endovascular Valve Edge‐to‐Edge REpair STudies (EVEREST) are investigating a percutaneous technique for edge‐to‐edge mitral valve repair with a repositionable clip. The effects on the mitral valve gradient (MVG) and mitral valve area (MVA) are not known. Methods: Twenty seven patients with moderate to severe or severe mitral regurgitation (MR) were enrolled. Echocardiography was performed preprocedure, at discharge, and at 1, 6, and 12 months. Mean MVG was measured by Doppler and MVA by planimetry and pressure half‐time, and evaluated in a central core laboratory. Pre‐ and postclip deployment, simultaneous left atrial/pulmonary capillary wedge and left ventricular pressures were obtained in eight patients. Results: Three patients did not receive a clip, six patients had their clip(s) explanted by 6 months (none for mitral stenosis), and four were repaired with two clips. Results are notable for a slight increase in mean MVG by Doppler postclip deployment (1.79 ± 0.89 to 3.31 ± 2.09 mm Hg, P < 0.01) and an expected decrease in MVA by planimetry (6.49 ± 1.61 to 4.46 ± 2.14 cm2, P < 0.001) and by pressure half time (4.35 ± 0.98 to 3.01 ± 1.42 cm2, P < 0.05). There were no significant changes in hemodynamic parameters postclip deployment by direct pressure measurements. There was no change in MVA by planimetry from discharge to 12 months (3.90 ± 1.90 to 3.79 ± 1.54 cm2, P = 0.78). Conclusions: Echocardiographic and hemodynamic measurements after percutaneous mitral valve repair with the MitraClip show an expected decrease in mitral valve area with no evidence of clinically significant mitral stenosis either immediately after clip deployment or after 12 months of follow‐up.

Cost-effectiveness of coronary artery bypass surgery in octogenarians.

OBJECTIVE The objective of this retrospective cohort study was to determine whether coronary artery bypass graft (CABG) surgery is effective and cost-effective relative to medical management of coronary artery disease (CAD) in the elderly. SUMMARY BACKGROUND DATA The aging of the U.S population and the improvements in surgical techniques have resulted in increasing numbers of elderly patients who undergo this surgery. The three randomized, controlled trials (RCTs) that established the efficacy of CABG surgery completed patient enrollment from 19 to 24 years ago excluded patients older than 65 years. Although information regarding outcomes of CABG in this population is mainly available in case series, a major lacuna exists with respect to information on quality of life and cost effectiveness of surgery as compared with medical management. METHODS The authors retrospectively formed surgical and medically managed cohorts of octogenarians with significant multivessel CAD. More than 600 medical records of patients older than 80 years who underwent angiography at our institution were reviewed to identify 48 patients who were considered reasonable surgical candidates but had not undergone surgery. This cohort was compared with 176 patients who underwent surgery. RESULTS The cost per quality-adjusted life year saved was

Plasma Levels of Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 Are Correlated With the Presence of Transplant Coronary Artery Disease in Cardiac Transplant Recipients

10,424. At 3 years, survival in the surgical group was 80% as compared with 64% in the entire medical cohort and 50% in a smaller subset of the medical cohort. Quality of life in patients who underwent surgery was measurably better than that of the medical cohort with utility index scores, as measured by the EuroQoL, (a seven-item quality of life questionnaire) of 0.84, 0.61, and 0.74, respectively. CONCLUSIONS Performing CABG surgery in octogenarians is highly cost-effective. The quality of life of the elderly who elect to undergo CABG surgery is greater than that of their cohorts and equal to that of an average 55-year-old person in the general population.

Percutaneous mitral valve repair using the edge-to-edge technique: six-month results of the EVEREST Phase I Clinical Trial.

Hemostatic factors are involved in the pathogenesis of native coronary artery disease. However, their role in transplant coronary artery disease is less established. To assess the role of hemostatic factors in transplant coronary artery disease we studied 52 consecutive cardiac transplant patients. The presence of transplant coronary artery disease was determined by angiography. Plasma levels of tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von Willebrand Factor (vWF), and fibrin D-dimer were determined by enzyme-linked immunosorbent assays. Serum lipids were measured by enzymatic methods. Patients with transplant coronary artery disease had higher circulating t-PA (8.6 +/- 0.8 vs. 5.4 +/- 0.6 ng/ml, p = 0.021) and PAI-1 antigen concentrations (38.0 +/- 3.4 vs 25.8 +/- 2.2 ng/ml, p = 0.037). t-PA and PAI-1 antigen concentrations correlated with the severity of angiographic disease (R = 0.34; p = 0.014 for t-PA, and R = 0.45; p = 0.001 for PAI-1). Serum cholesterol levels were higher in patients with transplant coronary artery disease (221 +/- 7.6 vs 191 +/- 9.2 mg/dl, p = 0.039). Serum triglycerides were also higher in patients with transplant coronary artery disease by angiography (246 +/- 38.3 vs 139 +/- 20.8 mg/dl, p = 0.050). Multivariate analysis identified t-PA antigen (p = 0.003) and triglyceride levels (p = 0.038) as independent predictors for the presence of transplant coronary artery disease. We conclude that cardiac transplant patients with evidence of transplant coronary artery disease on coronary angiography have altered hemostatic function which is reflected by elevated levels of circulating t-PA and PAI-1 antigens. The interaction of the hemostatic system and serum lipids in the development of transplant coronary artery disease warrants further study.