Faculty Bibliography

BACKGROUND: With recent improvements in medical and device therapy, the benefit of cardiac transplantation for UNOS Status 2 patients has been questioned. No randomized trial has been performed to compare transplantation versus contemporary medical therapy. METHODS: Between January 1996 and December 2003, 203 patients were listed at our institution for heart transplantation as UNOS Status 2. We performed a retrospective review to determine outcomes in these patients. RESULTS: Demographics of this cohort revealed a mean age of 52 years, female sex in 28%, and ischemic etiology in 47%. Eighty-one patients (40%) had an implantable cardiac defibrillator. A total of 64 patients (32%) had to be upgraded in their UNOS status, with 9 requiring a left ventricular assist device. Of the entire group, 95 (47%) underwent transplantation at a mean time of 303 days, 45 (22%) died while waiting at a mean time of 397 days, and 24 (12%) were removed from the waiting list due to deterioration in medical condition such that transplantation was no longer an option. The remaining patients continue to wait or have been removed from consideration due to improved condition. Survival at 1- and 3-years postlisting was 94% and 87% for patients who received transplants compared to 81% and 57% for patients who did not receive transplants (P < .01). CONCLUSION: A significant number of patients listed as Status 2 are upgraded in UNOS status or die while on the waiting list. Early and midterm survival is significantly better with transplantation. Identification of variables associated with deterioration may allow for better risk stratification in the future. At this point, transplantation offers the best outcome

Reoperations during ventricular assist device (VAD) explantation and subsequent heart transplantation are difficult procedures because of dense adhesions, obliterated planes of dissection, and proximity of the right ventricle to the sternum. We present our approach for left VAD explantation to minimize potential complications that may occur during this procedure.

Despite advances in mechanical circulatory support, cardiogenic shock continues to have a high mortality. We reviewed our experience with pulsatile versus non-pulsatile temporary mechanical support at our institution to determine optimal strategy for survival. From January 2001 to December 2003, mechanical support for cardiogenic shock was instituted in 38 patients. Non-pulsatile devices (NP group) were used in 22 patients and pulsatile devices (P group) in 16 patients. Indications for the NP group were post-cardiotomy shock (PCS) in 17, myocardial infarction in 2, and isolated post-cardiotomy right ventricular failure in 3 patients. In the P group, 9 had the device placed for PCS, 3 for viral myocarditis, 1 after myocardial infarction, and 3 for right ventricular (RV) failure. Overall, bleeding, limb ischemia, and multi-system organ failure were higher in NP group with 5 weaned and 3 surviving to discharge (14%). In the P group, survivors included 7 weaned and 3 transplanted patients (63%). With the exception of isolated RV failure, we obtained a dismal survival result with ECMO/centrifugal circuits for treatment of cardiogenic shock. For refractory pump failure, improved survival was achieved by using intermediate-term pulsatile devices with early transition to a chronic device and/or heart transplantation.

Both heart failure (HF) and cardiac surgery with cardiopulmonary bypass result in a release of neurohormones, with a variety of physiologic effects. Administration of exogenous B-type natriuretic peptide (BNP) has beneficial hemodynamic effects and reduces the level of several neurohormones in HF patients. BNP is currently being investigated in the perioperative management of cardiac surgery patients and may be especially beneficial for patients with ventricular dysfunction, pulmonary hypertension, or renal dysfunction. Using a neurohormonal approach to supportive therapy may enhance future strategies for patients undergoing cardiac surgery, especially those at greatest risk for complications.

Recent studies have shown an increased expression of several matrix metalloproteinases (MMP) during cardiac, renal and pulmonary allograft rejection. To further define the roles of MMP-2 and MMP-9 in the pathogenesis of cardiac allograft rejection, BALB/c cardiac allografts were transplanted into MMP-2-deficient (-/-) and MMP-9-/- mice. Allografts rejected by wild-type mice revealed a significant increase in MMP-2 and MMP-9 expression. MMP-2-deficiency significantly prolonged allograft survival time. Functioning allografts harvested from MMP-2-/- mice showed lower cellular infiltration and fibrosis than rejected allografts harvested from MMP-2+/+ mice at the same time. In contrast, MMP-9-deficiency significantly decreased allograft survival time. Functioning allografts harvested from MMP-9+/+ mice showed lower cellular infiltration and fibrosis than rejected allografts harvested from MMP-9-/- mice at the same time. MMP-2-/- recipients showed decreased T-cell alloreactivity mediated by a defect in dendritic cell stimulatory and T-cell responsive capacities. In contrast, MMP-9-/- recipients showed increased T-cell alloreactivity mediated by a significant increased in dendritic cell stimulatory and T-cell responsive capacities. These results indicate that MMP2 and MMP-9 play significantly different roles in the process of cardiac allograft rejection.

BACKGROUND: Methods that can improve the accuracy of application of directed intervention in the treatment of coronary artery disease deserve investigation. Magnetic resonance imaging with tissue tagging allows for noninvasive, quantitative determination of regionally varying minimum principal strain. Because the directional vector of minimum principal strain has been shown to be sensitive to ischemic involvement, my colleagues and I sought to fully characterize the normal range of vector direction in the in vivo human left ventricle at rest and during inotropic stimulation. METHODS: Tagged magnetic resonance imaging image sets were acquired in 20 healthy volunteers at rest and during dobutamine infusion. Strain was computed from the measured displacement data by using finite element software. Orientation of minimum principal strain was characterized by measuring the angle (principal strain angle) between the minimum principal strain vector and the local circumferential-longitudinal plane. Values of this angle were computed in 6 ventricular regions and globally. RESULTS: Resting values of the principal strain angle were small in every region, confirming that maximal normal myocardial contraction occurs primarily in the circumferential-longitudinal plane. Angles were similar during dobutamine infusion. Comparisons between ventricular walls, both at rest and with dobutamine, revealed no marked regional differences in the principal strain angle. CONCLUSIONS: The direction of maximal myocardial contraction is known to change with ischemic injury to the myocardium and can be a sensitive, regionally varying index of myocardial ischemia. The critical first step in the clinical application of this technology is to accurately characterize normal ranges of principal strain angles.

BACKGROUND: Complete revascularization is important in young patients undergoing coronary artery bypass grafting, but this principle remains less absolute in elderly patients. The purpose of this study was to determine how complete revascularization influenced long-term survival after coronary artery bypass grafting in octogenarians. METHODS: From 1986 to 2003, 500 consecutive patients 80 to 94 years of age underwent coronary artery bypass grafting. Complete revascularization was defined as placement of at least one graft to each of the three major vascular regions that included a 50% diameter lesion. Revascularization was complete in 400 (80%) patients and incomplete in 100 (20%) patients. Mean (+/- standard deviation) follow-up was 51 +/- 41 months and was 99% complete (2,102 total patient-years). RESULTS: Operative mortality was 8% +/- 2% (+/-95% confidence interval) and was statistically lower with complete (7% +/- 3%) versus incomplete (13% +/- 7%) revascularization (p < 0.05). Of 459 operative survivors, there were 261 late deaths. Multivariate regression analysis identified six independent predictors of late death: earlier operative year, male sex, peripheral or cerebrovascular disease, congestive heart failure, and incomplete revascularization (p < 0.03 for all). Excluding operative deaths, mean survival (Kaplan-Meier) was 82 months with complete revascularization compared with 65 months with incomplete revascularization (p < 0.008). Survival was 62% +/- 3% with complete versus 45% +/- 6% with incomplete revascularization at 5 years and 39% +/- 3% with complete versus 25% +/- 6% with incomplete revascularization at 8 years (p < 0.008). CONCLUSIONS: In octogenarians undergoing coronary artery bypass grafting, complete revascularization correlated with improved long-term survival, increasing mean survival by almost 25% compared with incomplete revascularization.

BACKGROUND: Cardiac transplant recipients frequently receive a large number of transfusions. The objective of this study was to determine whether there is an association between total number of blood transfusions and cardiac allograft rejection. METHODS: A retrospective analysis of all cardiac transplants between October 1, 1997, and December 31, 2001, was performed. Total number of transfusions, total number of rejection episodes Grade 3A or more, rejection-free survival, and overall survival were analyzed. Comparisons between patients bridged to transplantation with a Novacor left ventricular assist device (LVAD) and the primary transplant group were also made. RESULTS: Eighty-two patients were transplanted. Fifteen were bridged to transplantation, and 67 underwent primary heart transplantation. Age and sex were similar for the LVAD group and the primary transplant group (45 +/- 11 vs 47 +/- 15 years and 67% vs 58% male sex, respectively). Mean follow-up was 658 +/- 486 days for the LVAD group and 708 +/- 548 days for the primary transplant group. Transfusions received were 50 +/- 34 U of packed red blood cells for the LVAD group and 7 +/- 12 for the primary transplant group (p < 0.001). There were no differences in donor characteristics between the 2 groups. The incidence of acute rejection within 1 year was 27% for the LVAD group and 39% for the primary transplant group (p = .28). Freedom from rejection was 71% at 1 year in the LVAD group compared with 59% for the primary transplant group (p = 0.39). In all 82 patients, the total number of transfusions was inversely correlated with the development of acute rejection (p = 0.011). Survival was 80% and 62% for the LVAD group at 1 and 3 years after transplantation and 88% and 85%, respectively, for the primary transplant group (p = 0.045). CONCLUSIONS: The number of blood transfusions received by heart transplant recipients is inversely related with the number of acute rejection episodes.

BACKGROUND: Despite a known survival benefit with the use of the left internal mammary artery, it is used less frequently in women when compared with men. This study evaluated the hypotheses that the radial artery graft is used less frequently in women compared with men, that the radial artery is smaller in women compared with men, and that the use of the radial artery influences operative mortality and long-term survival in women. METHODS: The use of a radial artery graft was evaluated in 2,633 patients who underwent isolated coronary artery bypass. Radial artery size and flow were compared in 207 patients who had intraoperative radial artery diameter and flow measurements. Propensity scoring was utilized to compare short- and long-term outcomes in a matched cohort of 588 women. RESULTS: Of 862 women (33%) who had isolated coronary artery bypass grafting, only 301 (35%) received a radial artery graft versus 44% of men (786 of 1,771, p < 0.001). Radial artery size and flow were significantly less in women. Operative mortality was not different between women with a radial artery graft and women without; however, 5-year survival was significantly better in women with a radial artery graft than in those without. CONCLUSIONS: Women received fewer radial artery grafts than men. Radial artery size and flow were significantly less in women than in men. Use of a radial artery graft did not influence operative mortality among women. However, 5-year survival among women who received a radial artery graft was significantly better than among women who did not.