The clinical risk in heart transplantation: is it evaluable?

At the moment, there is no score to evaluate clinical risk in heart transplantation. There is a need for such an instrument due to the extended criteria for donations and for recipient evaluation for transplantation. We divided the 203 consecutive patients who underwent heart transplantation (HTx). Between January 1999 and December 2007 into two groups: high and low risk based on several common well-defined variables. Donors were also divided into high- and low-risk groups. We matched the four groups to obtain risk cohorts: GA (high risk), GB and GC (intermediate risk) versus GD (low risk). We analyzed the 30 day-mortality showing a significant difference between GD and the other groups (P = .05) in contrast to no significant difference in 1- and 3-year survival rates among GA, GB, GC, and GD. Although the development of a specific score for heart transplantation is desirable and would be useful, a careful, case-by-case evaluation is indispensable.

Validation of limited sampling strategy for estimation of mycophenolic acid exposure during the first year after heart transplantation.

BACKGROUND: Individualization of mycophenolate mofetil (MMF) dosing based on mycophenolic acid (MPA) therapeutic drug monitoring may minimize the risk of organ transplant rejection. The MPA area under the 12-hour concentration-time curve (MPA-AUC(0-12h)) is a more powerful predictor of rejection than are MPA trough levels. Measurement of MPA-AUC(0-12h,) however, is difficult and clinically impractical. The limited sampling strategy (LLS) has been proposed to overcome this problem. OBJECTIVE: To validate the predictive performance of MPA LSS algorithms previously published for heart transplant (HTx) recipients (initial group) when applied to a new independent group of 29 HTx recipients (validation group) during the first year after transplantation. PATIENTS AND METHODS: In a previous study, we established 2 algorithms using a LSS in HTx recipients: (1) 5.568 + 0.902 x C(1.25) + 2.022 x C(2) + 4.594 x C(6) and (2) 3.8 + 1.025 . C(1.25) + 1.819 x C(2) + 1.566 x C(4) + 3.479 x C(6). Agreement between abbreviated AUC and the full AUC(0-12h) was tested using the Bland-Altman method. The validation group was used to test and assess bias and precision. RESULTS: The 2 LSS algorithms used predicted the corresponding MPA-AUC(0-12h) with a mean bias of -4.85% and -3.6% and mean precision of 15.9% and 14%, respectively. CONCLUSIONS: The MPA-AUC(0-12h) obtained using the LSS may be useful to guide clinical management and dosing. This study prospectively validates 2 algorithms for calculation of MPA-AUC(0-12h) using an LSS calculated in HTx recipients. Bias and precision values suggest that our algorithms could be used for MPA therapeutic drug monitoring predictions in HTx recipients who share the same characteristics.

Therapeutic mycophenolic acid monitoring by means of limited sampling strategy in orthotopic heart transplant patients.

Therapeutic drug monitoring (TDM) is essential to maintain the efficacy of many immunosuppressant drugs while minimizing their toxicity. TDM of mycophenolate mofetil requires area under the curve AUC determinations but appears laborious, costly, and clinically impractical. To overcome these problems, limited sampling strategies (LSS) have been proposed in adult and pediatric renal transplant patients. The purpose of this study was to develop an LSS in heart transplant patients. Forty-four mycophenolic acid (MPA) full AUC(0-12h) profiles were generated by high-performance liquid chromatography in nine heart transplant patients during the first 12 weeks posttransplant. Each patient received concomitant cyclosporine and prednisone therapy. Multiple stepwise regression analysis was used to define the time points of MPA levels to explain the MPA AUC(0-12h). Agreement between abbreviated AUC and the full AUC(0-12h) was tested by means of a Bland and Altman analysis. The highest coefficient of determination r(2) among MPA AUC and single concentrations (r(2) = .610) was observed with C(2), while C(12) provided the lowest one (r(2) = .003). Stepwise linear regression showed that the minimal model with the best estimation of MPA AUC(0-12h) was obtained at timed values of 1.25, 2, and 6 hours. The corresponding estimated model was AUC = 5.568 + 0.902 * C(1.25) + 2.022 * C(2) + 4.594 * C(6) (r(2) = .926). Bland and Altman analysis revealed good agreement between predicted AUC and full AUC. A further interesting model equation obtained by four samples was AUC = 3.800 + 1.015 * C(1.25) + 1.819 * C(2) + 1.566 * C(4) + 3.479 * C(6) (r(2) = .948).

Left ventricular mass regression after aortic valve replacement with CryoLife-O'Brien stentless aortic bioprosthesis.

BACKGROUND AND AIM OF THE STUDY: Left ventricular (LV) hypertrophy has been shown adversely to affect LV function and late outcome after aortic valve replacement (AVR). The study aim was to assess the time course of LV mass regression (LVMR) after AVR with a CryoLife-O'Brien stentless bioprosthesis, and to identify factors affecting late reduction of myocardial hypertrophy. METHODS: In total, 113 patients (60 males, 73 females; mean age 70.9+/-6.5 years) were studied by echocardiography preoperatively, at discharge, at six and 12 months postoperatively, and yearly thereafter. LV diameter and thickness were measured using M-mode echocardiography; LV mass was calculated using the Devereux formula and indexed by body surface area (BSA). RESULTS: LV end-systolic diameter, end-diastolic diameter, septal thickness and wall thickness decreased significantly after surgery (p <0.001). LV mass index (LVMI) was reduced by 16.6, 13.6, 10.1, 3.1, 3.3, 1.7, 2.6, and 1.8% at discharge and at 6 months and 1, 2, 3, 4, 5, and 6 years, respectively. Most LVMR occurred within the first year, with further (not significant) reductions at later examinations. Male sex (p = 0.002), arterial blood pressure > or =150 mmHg (p <0.001), LV ejection fraction (LVEF) < or =35% (p = 0.01), NYHA functional class > or = III (p = 0.01), atrial fibrillation (p <0.001), mean transvalvular gradient > or =40 mmHg (p = 0.001), and prevalent aortic incompetence (p <0.001) were factors influencing LVMR, independently of baseline effective orifice area and prosthesis size. CONCLUSION: AVR with the CryoLife-O'Brien stentless prosthesis resulted in significant LVMR. These findings encourage the use of this bioprosthesis in appropriate patients.

Extracorporeal photochemotherapy after cardiac transplantation: a new therapeutic approach to allograft rejection.

UNLABELLED: Photopheresis (ECP) is a new immunomodulatory therapy in which recipient lymphocytes are treated extracorporeally with 8-methoxypsoralen and ultraviolet light. The treatment seems to induce an inhibition of both humoral and cellular rejection after transplantation. OBJECTIVE: Since recurrent rejection (RR) continues to be a severe complication after heart transplantation (HTx) and the immunosuppressive regimes used for the treatment are often associated with increased morbidity and mortality, we investigated whether ECP could have a beneficial effect on the number and severity of rejection episodes. METHODS: Eleven HTX recipients (5 M and 6 F, mean age 48.5 yrs) with RR were enrolled in the study. ECP was performed at weekly intervals during the 1st month, at 2 week intervals during the 2nd and 3rd month, and then monthly for another 3 months. RESULTS: The fraction of biopsies (EMB) with a grade 0/1A rejection increased during ECP from 46% to 72% while the EMB showing a 3A/3B rejection decreased from 42% to 18%. It is also noteworthy that out of the 78 EMB performed during ECP only one showed a 3B rejection in comparison with 13 out of 110 EMB in the pre-ECP period. Six rejection relapses were observed in a total follow-up of 60 months, two of them occurring during the tapering of oral steroid. Four relapses were reversed by ECP, one by i.v. steroids and the last by methotrexate after the failure of both i.v. steroids and ECP. The mean doses of immunosuppressive drugs resulted lower after 6 months of ECP: steroids were reduced from 13 to 8.25 mg/day, cyclosporine from 375 to 285 mg/day, azathioprine from 55 to 35 mg/day. CONCLUSIONS: ECP is a well tolerated treatment. Its administration allows better RR control and significant reduction in immunosuppressive therapy.

Mid-term results of heart transplantation for end-stage valvular disease.

The results of heart transplantation in a consecutive series of 19 end-stage valvular disease patients (15 male, aged 48 +/- 8 years) were analysed retrospectively. The indication for heart transplantation was heart failure due to left and/or right ventricular dysfunction; 16 patients had undergone previous valve surgery, but prosthetic dysfunction was present in only one patient. All patients were in NYHA class IV, 15 were on oral anticoagulants and 5 on i.v. catecholamine support. There were four in-hospital deaths (21%) and one late death (5%), resulting in a 1-year mortality rate slightly, but not significantly, higher than that of patients transplanted for other indications (16%). Mean follow-up of the survivors was 48 +/- 33 months (range 9-95); 5-year actuarial survival was similar to that observed among the other heart transplantation patients (74 +/- 10% vs 77 +/- 3%, P = NS). The incidence of acute rejection and infection was also similar in valvular disease and non-valvular disease patients. Kidney and liver function at 1 year post-heart transplantation was preserved in all cases; cardiac catheterization revealed normal graft function in all patients and the absence of coronary lesions in all but two. In conclusion, in our limited experience morbidity and mortality in patients transplanted for end-stage valvular disease seem to be similar to those of patients undergoing heart transplantation for other etiologies.

Tricuspid valve endocarditis: repair with the use of artificial chordae.

We report on a patient who developed tricuspid valve endocarditis on a permanent endocardial pacemaker lead. At operation the endocardial lead was removed and accurate debridement of the tricuspid tissue was performed. Tricuspid valve reconstruction included commissural plication and the construction of artificial polytetrafluoroethylene chordae from the anterior leaflet to the anterior papillary muscle to obtain valve competence.

Discrete subaortic stenosis. Operative age and gradient as predictors of late aortic valve incompetence.

Between January 1969 and May 1990, 100 patients were operated on for discrete subaortic stenosis. Three patients died in the perioperative period. Patients with intrinsic lesions, prosthetic replacement, or extensive operative remodeling of the aortic valve were excluded from the analysis. The 67 remaining patients had a median follow-up of 62 months. Preoperatively, 8 patients had aortic valve competence, 51 had mild incompetence, and 8 patients moderate aortic valve incompetence. At follow-up mild incompetence persisted in 27 and moderate incompetence in 6 patients. In 1 patient it worsened from no incompetence to mild and in another patient from mild to moderate. The probability of aortic incompetence at follow-up was significantly and simultaneously related (multivariate ordinal logistic model) to (1) older age at operation (logarithm of months, p = 0.007), (2) higher preoperative gradient (third power of milligrams of mercury, p = 0.0004), (3) preoperative cardiomegaly (p = 0.04), and (4) surgical myectomy (p = 0.002). There was an interaction between age and gradient (p = 0.03). Two nomograms are proposed as a generalizable aid to decision making. The data support the policy of early repair of subaortic stenosis.

Fatal obstruction of the left ventricular outflow tract caused by low-profile bioprostheses in the mitral valve position.

Two cases of fatal left ventricular outflow tract obstruction following mitral valve replacement with low-profile bioprostheses are described. This unfortunate experience shows that correct orientation of the prosthesis is mandatory also when using low-profile bioprosthetic valves to avoid this complication, particularly in patients with a small left ventricular cavity.

Does Down syndrome affect prognosis of surgically managed atrioventricular canal defects?

The appropriateness of surgical correction of complete atrioventricular canal defect in patients with Down syndrome has been questioned on a cost-benefit basis. Our experience with nonselective correction of all patients with atrioventricular canal defects gave us the opportunity to evaluate the impact of Down syndrome on postoperative survival. Between January 1, 1975, and December 31, 1989, we operated on 94 patients with Down syndrome and on 127 genetically normal patients. One hundred thirty-four patients had partial or intermediate atrioventricular canal defect (28% Down patients) and 87 had complete atrioventricular canal defect (74% Down patients). Thirty-two patients died perioperatively and 10 patients died during the 15-year follow-up. The actuarial survival was 90% in the genetically normal patients and 57% in patients with Down syndrome (p < 0.0001). Nonetheless, when the confounding effects of pulmonary vascular resistance and the prevalence of more severe anatomic forms in patients with Down syndrome were eliminated with a multivariable analysis in the hazard domain, Down syndrome was not a significant independent incremental risk factor. This was verified by fitting parametric survival to actuarial survival graphically and by a testing of fit. Patients with Down syndrome underwent fewer reoperations and fared as well as or even better, on clinical and echocardiographic investigation, than their genetically normal counterparts.

Influence of type of prosthesis on late results after combined mitral-aortic valve replacement.

The influence of type of prosthesis on the late outcome of patients with combined mitral-aortic valve replacement was analyzed by comparing, at a 14-year follow-up, patients receiving two biological prostheses (group 1; n = 135), two mechanical prostheses (group 2; n = 221), or a mechanical prosthesis in the aortic position and a bioprosthesis in the mitral position (group 3; n = 97). No difference was found among the three groups in terms of actuarial survival and incidence of and freedom from valve-related deaths, thromboemboli, and hemorrhages. Patients with biological prostheses had a significantly greater incidence of structural valve deterioration, reoperations, and overall complications when compared with patients with only mechanical prostheses. The results of an extended follow-up of patients with combined mitral-aortic valve replacement indicate that mechanical prostheses perform better in the long-term owing to their superior durability when compared with biological valves. The use of bioprostheses should be confined to old patients with limited life expectancy because of their cardiac disease, provided that anticoagulants are not used. Combination of mechanical and biological prostheses in the same patient should be avoided because the advantages of each type of prosthesis are lost.

Constrictive epicarditis after open heart surgery: the turtle cage operation.

A 60-year-old man developed constrictive epicarditis within 1 year after isolated mitral valve replacement (MVR). At reoperation, decortication of the thick epicardial layer resulted, impossible without a high risk of injury of the myocardium and major coronary arteries. Therefore, multiple longitudinal and transverse incisions were performed on the epicardial peel, which at the end acquired a turtle cage appearance allowing myocardial reexpansion, relief of constriction, and restoration of adequate hemodynamics.

Intracardiac metastatic melanoma: report of a case mimicking a right atrial myxoma, with a review of the literature.

A 49-year-old patient, referred with a diagnosis of right atrial myxoma, was found at surgery to have extensive cardiac metastases from a previously undetected cutaneous melanoma. In reviewing the literature, we found 5 other patients with a clinical diagnosis of melanoma metastatic to the heart, all of whom had a previous history of melanoma. In no other case has cardiac involvement been the 1st manifestation of a malignant cutaneous melanoma.