P.E. Oyer

Treatment of endocarditis with valve replacement: the question of tissue versus mechanical prosthesis

BACKGROUND It remains unknown whether there is any important clinical advantage to the use of either a bioprosthetic or mechanical valve for patients with native or prosthetic valve endocarditis. METHODS Between 1964 and 1995, 306 patients underwent valve replacement for left-sided native (209 patients) or prosthetic (97 patients) valve endocarditis. Mechanical valves were implanted in 65 patients, bioprostheses in 221 patients, and homografts in 20 patients. RESULTS Operative mortality was 18+/-2% and was independent of replacement valve type (p > 0.74). Long-term survival was superior for patients with native valve endocarditis (44+/-5% at 20 years) compared with those with prosthetic valve endocarditis (16+/-7% at 20 years) (p < 0.003). Survival was independent of valve type (p > 0.27). The long-term freedom from reoperation for patients who received a biologic valve who were younger than 60 years of age was low (51+/-5% at 10 years, 19+/-6% at 15 years). For patients older than 60 years, however, freedom from reoperation with a biological valve (84+/-7% at 15 years) was similar to that for all patients with mechanical valves (74+/-9% at 15 years) (p > 0.64). CONCLUSIONS Mechanical valves are most suitable for younger patients with native valve endocarditis; however, tissue valves are acceptable for patients greater than 60 years of age with native or prosthetic valve infections and for selected younger patients with prosthetic valve infections because of their limited life expectancy.

Post-transplantation lymphoproliferative disease in heart and heart–lung transplant recipients: 30-year experience at Stanford University

BACKGROUND Post-transplantation lymphoproliferative disease (PTLD) is an important source of morbidity and mortality in transplant recipients, with a reported incidence of 0.8% to 20%. Risk factors are thought to include immunosuppressive agents and viral infection. This study attempts to evaluate the impact of different immunosuppressive regimens, ganciclovir prophylaxis and other potential risk factors in the development of PTLD. METHODS We reviewed the records of 1026 (874 heart, 152 heart-lung) patients who underwent transplantation at Stanford between 1968 and 1997. Of these, 57 heart and 8 heart-lung recipients developed PTLD. During this interval, 4 different immunosuppressive regimens were utilized sequentially. In January 1987, ganciclovir prophylaxis for cytomegalovirus serologic-positive patients was introduced. Other potential risk factors evaluated included age, gender, prior cardiac diagnoses, HLA match, rejection frequency and calcium-channel blockade. RESULTS No correlation of development of PTLD was found with different immunosuppression regimens consisting of azathioprine, prednisone, cyclosporine, OKT3 induction, tacrolimus and mycophenolate mofetil. A trend suggesting an influence of ganciclovir on the prevention of PTLD was not statistically significant (p = 0.12). Recipient age and rejection frequency, as well as high-dose cyclosporine immunosuppression, were significantly (p < 0.02) associated with PTLD development. The prevalence of PTLD at 13.3 years was 15%. CONCLUSIONS The overall incidence of PTLD was 6.3%. It was not altered by sequential modifications in treatment regimens. Younger recipient age and higher rejection frequency were associated with increased PTLD occurrence. The 15% prevalence of PTLD in 58 long-term survivors was unexpectedly high.

Durability of the hancock MO bioprosthesis compared with standard aortic valve bioprostheses

To compare the durability of the Hancock modified orifice (Hancock MO, model 250 [H-MO]) valve with two other commonly used standard aortic valve bioprostheses, a cohort of 1,602 patients undergoing aortic valve replacement using porcine valves between 1971 and 1990 (excluding simultaneous mitral valve replacement) was analyzed retrospectively using Cox model multivariate techniques. Five hundred sixty-one patients received a composite H-MO valve, 652 received a standard Hancock model 242 (H) valve, and 389 received a Carpentier-Edwards model 2625 (C-E) valve. Mean age was 60 +/- 15 years (+/- 1 standard deviation) (71% male). Follow-up (10,247 patient-years) extended to 15 years and was 97% complete. The main focus of this study was bioprosthetic durability, using The American Association for Thoracic Surgery/The Society of Thoracic Surgeons guidelines to define structural valve deterioration (SVD). Multivariate analysis revealed that (younger) age (p < 10(-5), liver disease (p = 0.02), and 1981 to 1985 operative period (p = 0.012) were the only significant, independent predictors of SVD. In concordance with previous reports, the SVD freedom estimate was greater than 90% at 15 years for patients older than 70 years of age. Hepatic dysfunction had an adverse effect on SVD (estimated freedom from event at 10 years was 34 +/- 17% [standard error of mean] versus 78 +/- 2% for those without liver disease), but this affected only 3% of patients. Interestingly, one operative period (1981 to 1985) was associated with a slightly higher risk of SVD compared to the three other 5-year time windows. Valve type did not emerge as a significant risk factor for SVD.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction therapy for pediatric and adult heart transplantation: comparison between OKT3 and daclizumab.

Background. Induction therapy can reduce morbidity and early mortality in pediatric and adult heart transplant recipients. Monoclonal and polyclonal agents are most widely used; they nonspecifically deplete the T-cell pool and are thus associated with drug-induced side effects. The cytokine release syndrome is one of the most problematic events associated with induction. Daclizumab, a highly humanized, specific interleukin-2 receptor blocker, may be efficacious to the monoclonal agent, OKT3. Due to its specific action and properties, the safety profile of this agent may be superior to OKT3. Methods. Forty subjects received daclizumab and their clinical outcomes were compared against a historical group of 40 subjects who received OKT3. Three- and six-month outcome measures included survival, rejection history, steroid burden, and complications. Results. Mortality was low between the groups with equivalent 6-month survival. No differences in rejection profile or time to the first significant rejection event were detected; no subject had severe acute rejection within the first 180 days. Steroid requirement for maintenance immunosuppression and treatment of rejection was also similar between the groups. Six-month prevalence for complications were significantly different; 55% of OKT3-treated subjects having at least one event compared to 33% of daclizumab-treated subjects (P = 0.04). The likelihood of complications occurred within the first month after transplantation. Conclusions. Daclizumab induction therapy is as efficacious as OKT3 in the prevention of early acute rejection after heart transplantation among pediatric and adult subjects. Complications related to the induction agent are significantly lower in the humanized product.

Cardiac retransplantation in the cyclosporine era

Between December 1980, when immunosuppression with cyclosporine was introduced, and May 1988, 288 patients underwent primary transplantation for end-stage cardiac disease (group TX). Fourteen patients underwent retransplantation for accelerated graft atherosclerosis (group RTXAGA), and 9 underwent retransplantation for intractable acute allograft rejection (group RTXREJ). Cumulative patient follow-up was 724 patient-years (range, 1 month to 7.5 years; mean, 2.3 years). Within the first 3 postoperative months, no differences were noted between groups for linearized rates of infection or rejection except between the rate of rejection for group TX (1.69 +/- 0.09 events/100 patient-days) and group RTXAGA (0.94 +/- 0.3 events/100 patient-days) (p less than 0.02). No significant differences existed between groups for actuarial rates of remaining rejection-free or infection-free for more than 7.5 years. No significant differences in actuarial survival existed except between group TX (81% +/- 2% at 1 year and 58% +/- 4% at 5 years) and group RTXREJ (44% +/- 17% at 1 year and 44% +/- 0% at 5 years) (p less than 0.05). We conclude that patients who undergo retransplantation for accelerated graft atherosclerosis experience a lower rate of early rejection and similar rates of infection and survival compared with patients who receive primary transplants. Cardiac retransplantation for rejection incurs rejection and infection at rates similar to those of primary procedures. However, patients who undergo retransplantation for rejection survive these complications significantly less often than do patients who receive primary transplants. This information should be considered when scarce donor hearts become available and retransplantation is contemplated.

Cardiovascular physiology in a case of heterotopic cardiac transplantation

Successful heterotopic cardiac transplantation in a 24 year old man with end stage cardiomyopathy provided an opportunity to study cardiovascular physiology. The donor and native hearts, functioning independently in parallel, were studied by serial physical examination, electrocardiography, echocardiography, nuclear angiography and cardiac catheterization. Results indicated that the donor left heart assumed the predominant role in supplying systemic output, possibly contributing to decreasing function of the patients own (native) heart. Analysis of serial nuclear angiograms revealed an initial postoperative ejection fraction of 52 and 21 percent in the donor and the native left ventricle, respectively; repeat studies 3 months postoperatively showed values of 50 and 9 percent, respectively, indicating significant deterioration in native left ventricular cardiac function. Observation of valve motion of the native heart showed major irregularities of the aortic valve in contrast to seemingly normal, regular mitral valve motion. These data rise interesting questions regarding interpretation of valve motion as an indicator of ventricular function.

Response to Letter Regarding Article Entitled “Heart and Combined Heart–Kidney Transplantation in Patients With Concomitant Renal Insufficiency and End-Stage Heart Failure”

We thank Dr. Rajagopalan et al for their letter (1) discussing our recent publication (2). The dilemmahere is that although left ventricular assist devices (LVADs) can clearly improve renal function in patients with end-stage heart failure (ESHF) and concomitant nondialysis-dependent renal insufficiency (NDDRI) secondary to a type I or II cardiorenal syndrome, having NDDRI is a significant risk factor for postLVAD morbidity and mortality. Furthermore, no evidence has indicated that LVAD therapy in ESHF/NDDRI patients improves long-term survival (3,4). Hasin et al (3) showed that in a group of 54 patients with NDDRI (GFR <60mL/ min) who underwent LVAD implantation, 8 (15%) required chronic hemodialysis postimplant and 4 of those patients died within 3 months of LVAD implantation. Unfortunately, Hasin et al did not provide data regarding the incidence of mortality for all 54 patients with NDDRI, but we can infer from their data that fewer patients with NDDRI before LVAD placement were available at 6-month follow-up (34/54; 63%) than were patients without NDDRI (23/29; 79%) (3). Similarly, an analysis of the INTERMACS database revealed a roughly 10% absolute decrease in the survival of LVAD recipients with NDDRI (1-year survival <80%) and a 20% absolute decrease in the survival of LVAD recipients who were dialysis dependent or had severe renal dysfunction (1-year survival <70%) (4). Furthermore, our study of waitlist outcomes in ESHF/ NDDRI patients has shown a 17–19% incidence of mortality in patients with NDDRI who are waiting for an isolated heart transplant or a combined heart–kidney transplant an outcome comparable to the results of the INTERMACS database analysis (2).

Bridge to cardiac transplantation: comparison of LVAD versus inotropic support

isolated RV dysfunction and severe hemodynamic compromise at our institution. Overall survival, duration of mechanical support, postRVAD hemodynamics, and RV function measured by echocardiography were analyzed. Results: Post-cardiotomy RV failure developed in patients after coronary artery bypass surgery alone or in combination with valve surgery (12), valvular surgery alone (5), aortic surgery (6), heart or lung transplantation (3), and pulmonary endarterectomy (4). Mean age was 58 15 years and 17 (57%) were female. Initial operation was emergent in 22 (73%) cases. Centrifugal pumps were used in 29 and Abiomed pump in one patient. Overall, 17 (57%) patients died on the assist device: 3 from sepsis, 2 from stroke, and 12 from an inability to wean from the RV device. RVAD was successfully weaned in 13 (43%) patients with a median duration of 5 days (range 2-8). Ten survived to hospital discharge. At post-RVAD removal, mean pulmonary artery pressure was 25 6 mmHg, cardiac output was 4 2L, and central venous pressure was 16 3 mmHg. Echocardiogram after RVAD removal showed normal RV function in 2 patients and 11 demonstrated improvement of RV hypokinesis. Our most recent experience, from 1997 to present, demonstrated an improved postoperative survival of 44% compared to 18% from the five preceding years. Conclusion: Post-cardiotomy RV failure patients requiring mechanical support continue to have high mortality. Survival has improved over the last several years due to advances in pharmacological treatment and RVAD support. For patients successfully weaned from the RVAD, residual RV dysfunction is compatible with survival. More liberal use of RV mechanical support may be indicated for patients with acute RV failure.