Increased incidence and mortality associated with skin cancers after cardiac transplant.

Skin cancer incidence has been shown to be increased in the context of transplant-associated immunosuppression. There is, however, limited information specifically about the incidence of skin cancer after cardiac transplantation in the United States. A 10-year retrospective cohort study of 6271 heart transplants at 32 US transplant centers revealed increased postprocedure incidence of nonmelanoma and melanoma skin cancers, especially cutaneous squamous cell carcinoma, for which the incidence increased from 4- to 30-fold compared to the age and gender equivalent general population. Incidence of skin cancer in this study was consistent with prior single-center data regarding cardiac transplant patients. Comparison of all-cause mortality statistics for patients with basal cell carcinoma, squamous cell carcinoma and melanoma, respectively, demonstrated increased mortality associated with melanoma. Skin cancer screening and prophylaxis may be of some utility in reducing morbidity and mortality in cardiac transplant patients.

Five-year follow-up of hepatitis C-naïve heart transplant recipients who received hepatitis C-positive donor hearts.

BACKGROUND: Due to the risk of transmission of hepatitis C virus, the use of hepatitis C seropositive donors in heart transplantation is controversial. The transmission rate of hepatitis C in this patient population is estimated to range from 67% to 80%. Long-term clinical outcomes of heart transplant recipients of hepatitis C-positive donor hearts are not well described. We report the 5-year long-term outcome of seven hepatitis C-naïve heart transplant recipients who received hepatitis C-positive donor hearts. METHODS: Retrospective analysis of clinical course, liver biochemistry, serology, and hepatitis C virology data. RESULTS: Seven hearts transplant recipients, six men and one woman were included in our study. After a mean follow-up of 63.3 +/- 20.4 months (range 28.2 to 85.9), four of seven (57.1%) patients are hepatitis C-negative, have normal liver function tests, and no clinical evidence of hepatitis. Three of seven (43%) have been diagnosed with hepatitis C by liver biopsy or the HCV-RNA reverse transcriptase polymerase chain reaction at a mean follow-up of 35.1 months (18.8 months posttransplantation). One had an accelerated course of hepatitis that was ultimately fatal, one was successfully treated with interferon, and the third died from other causes than liver injury. Overall, the 5-year survival was 71.4%. CONCLUSIONS: The 5-year survival of hepatitis C-naïve recipients of hearts from hepatitis C-positive donors is similar to heart transplant recipients with hepatitis-negative donor hearts. Nevertheless, the transmission rate is high and hepatitis C infection in this population can lead to considerable morbidity and accelerated, fatal hepatitis.

Asymmetry of right ventricular enlargement in response to tricuspid regurgitation.

BACKGROUND: Analysis of right ventricular adaptation to tricuspid regurgitation was studied in 10 heart transplant recipients following inadvertent endomyocardial biopsy disruption of the tricuspid apparatus. METHODS AND RESULTS: Echocardiography demonstrated progressive diastolic right ventricular cavity enlargement (19.5+/-5.0 to 30.3+/-5.4 cm(2), P<0.0002), with disproportionate elongation along the midminor axis (3.5+/-0.6 to 5. 0+/-0.5 cm, P<0.001). As the right ventricle remodeled to more spherical (and less elliptical) proportions, the end-diastolic right ventricular midminor axis/long axis ratio increased significantly from 0.52+/-0.10 to 0.68+/-0.07, P<0.005. CONCLUSIONS: Ventricular enlargement due to right ventricular volume overload results in disproportionate dilation along the free wall to septum minor axis.

Aggressive treatment for postcardiac transplant lymphoproliferation.

Posttransplant lymphoproliferative disorder (PTLD) is a frequently fatal complication of organ transplantation, occurring in 2% to 6% of cardiac recipients. Treatment remains poorly defined. Reduction in immunosuppression is effective in a proportion of cases, but mortality on the order of 80% is reported for patients requiring chemotherapy. The reason for such poor outcomes is unclear, but may be partly caused by the concomitant use of immunosuppressives. Nineteen consecutive cardiac recipients with PTLD were studied retrospectively in terms of clinical features and outcome. Patients were managed according to a uniform treatment approach. Initial therapy was a trial of reduced immunosuppression with concomitant acyclovir followed, if unsuccessful, by aggressive combination chemotherapy. The regimen used was predominantly ProMACE-CytaBOM. Six patients with phenotypically polyclonal PTLD presented less than 6 months after transplantation (median 6 weeks). Only 1 of 4 (25%) treated patients responded to reduced immunosuppression; the remainder died of multiorgan failure. Thirteen patients presented with phenotypically monoclonal disease > or = 6 months after transplantation. In 8 of 12 (75%) treated patients initial therapy was reduction in immunosuppression. None achieved complete remission (CR) and 2 experienced fatal rejection. Two patients achieved durable surgical CR. The remaining 8 patients received chemotherapy; 2 of 8 (25%) died during treatment, 6 of 8 (75%) achieved CR. None have relapsed, at a median duration of follow-up of 38 months. Neutropenic sepsis and subclinical doxorubicin cardiotoxicity at a mean cumulative dose of 63 mg/m2 were the principal toxicities. Our data indicate that aggressive chemotherapy is both feasible and effective in phenotypically monoclonal PTLD refractory to reduced immunosuppression. ProMACE-CytaBOM is well suited to cardiac recipients, minimizing doxorubicin exposure and obviating the need for concurrent immunosuppressives.

Intracoronary ultrasound assessment of morphological and functional abnormalities associated with cardiac allograft vasculopathy.

BACKGROUND: The diffuse nature of cardiac allograft vasculopathy makes early detection of the disease by traditional noninvasive methods or coronary angiography difficult. The aim of this study was to determine if there is a relation between abnormalities in vessel wall morphology, as assessed by intracoronary ultrasound, and a decreased vasodilatory response to the endothelium-dependent vasodilator papaverine hydrochloride and if cardiac allograft vasculopathy detected by coronary angiography is associated with specific intracoronary ultrasound findings. METHODS AND RESULTS: Twenty-three heart transplant recipients underwent 25 intracoronary ultrasound studies and 24 studies of coronary vasomotor tone 10 days to 8.3 years after surgery using a 20-mHz intracoronary ultrasound catheter. The studies were divided in two groups according to the presence (n = 7, group 1) or absence (n = 18, group 2) of angiographically evident cardiac allograft vasculopathy. Qualitative assessment of vessel wall morphology and quantitative analysis of the vasodilator response to the injection of papaverine hydrochloride into the coronary artery distal to the imaging site were performed off-line, and results for the two study groups were compared. A significantly higher percentage of patients with than without angiographic evidence of cardiac allograft vasculopathy had a three-interface vessel wall morphology by intracoronary ultrasound (100% versus 11%, P < .001). In two recipients who underwent two serial studies, the appearance of three interfaces in the vessel wall or a progressive thickening of the inner interface of the vessel wall occurred in conjunction with the appearance of angiographic cardiac allograft vasculopathy. The vasodilator response to papaverine was less in patients with than in those without angiographically evident cardiac allograft vasculopathy both in terms of absolute and relative increases in lumen diameter (+0.1 +/- 0.12 mm versus +0.3 +/- 0.17 mm, P < .05, and +5.1 +/- 5.3% versus +8.2 +/- 5.3%, P = NS) and lumen cross-sectional area (+0.5 +/- 0.6 mm2 versus +1.7 +/- 1.1 mm2, P < .02, and +7.1 +/- 8.8% versus 16.6 +/- 11.0%, P = .055), respectively. CONCLUSIONS: Intracoronary ultrasound assessment of vessel wall morphology and evaluation of vascular response to endothelium-dependent vasodilators are useful techniques for detecting cardiac allograft vasculopathy.

Endocardial infiltrates in the transplanted heart: clinical significance emerging from the analysis of 5026 endomyocardial biopsy specimens.

UNLABELLED: To further elucidate the significance of endocardial infiltrates in heart transplant patients, the presence, frequency, and type of endocardial infiltrates were evaluated in 5026 endomyocardial biopsy specimens obtained from 200 heart transplant patients 0 to 75 months after heart transplantation. The relationship of endocardial infiltrates to immunologic, clinical, and demographic variables was then explored. Endocardial infiltrates were detected in 557 endomyocardial biopsy specimens (11%) from 117 heart transplant patients (58%) at 6.3 +/- 9.4 months (mean +/- SD; range, 0 to 49 months) after heart transplantation. Heart transplant patients with endocardial infiltrates were younger (p = 0.03), had a greater incidence of idiopathic dilated cardiomyopathy before heart transplantation (p = 0.05), and included a greater percentage of females (p < 0.05). Both total and treated rejection rates were significantly higher in patients with endocardial infiltrates versus those without endocardial infiltrates (p = 0.0001). Rejection on the subsequent endomyocardial biopsies was more often present in endocardial biopsy specimens with endocardial infiltrates than in those without endocardial infiltrates, both in the presence (37% versus 24%; p < 0.001) and absence (33% versus 19%; p < 0.0001) of concomitant findings of rejection. No association was identified between endocardial infiltrates and posttransplantation lymphoproliferative disorder, cytomegalovirus infection, Epstein-Barr virus infection, or cardiac allograft vasculopathy. Multivariate regression analysis confirmed that the occurrence of endocardial infiltrates is associated with rejection when adjustment is made for patient's age, gender, heart disease before transplantation, follow-up time, and number of endomyocardial biopsies after heart transplantation (p = 0.0001). CONCLUSIONS: (1) Endocardial infiltrates may occur with or without associated endomyocardial biopsy findings of rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart transplantation as a treatment option for end-stage heart disease in patients older than 65 years of age.

Because of the critical donor organ shortage for heart transplantation, selection of recipients should be based on the potential for maximum benefit. To evaluate the effects of advancing age on outcome after heart transplantation, we compared the clinical variables of 12 recipients aged 65 years or older (66.1 +/- 0.9 years [x +/- standard deviation]; range, 65 to 67 years) with those of 57 patients aged 55 to 64 years (59.3 +/- 2.7 years) at the time of the procedure. The two study groups were similar in sex, race, pretransplantation heart disease, immunocompatibility, maintenance immunosuppression, and length of first hospitalization at the time of the procedure. Groups were also similar regarding the incidence of malignancies, fractures, diabetes, neurologic complications, and renal dysfunction occurring over the follow-up period. Patients 65 years of age or older had a significantly higher number of hospital days (36 +/- 29 versus 15 +/- 18 days; p < 0.02) and increased frequency of infections/month (0.7 +/- 0.3 versus 0.3 +/- 0.4 infections/month; p < 0.03) during the first postoperative year. Older patients had a higher incidence of cytomegalovirus infections (50% versus 19%; p < 0.06), lower rates of rejection at 1 and 6 months after operation (p < 0.03), and more severe functional limitation (p < 0.002) than patients aged 55 to 64 years. One-year actuarial survival was not significantly different in the two groups. The results of our study suggest that, because of lower rejection and higher infection rates, heart transplantation recipients older than 65 years of age should receive less intense immunosuppression.(ABSTRACT TRUNCATED AT 250 WORDS)

High-risk cardiac operation: a viable alternative to heart transplantation.

To determine if high-risk heart operation with circulatory support standby is an acceptable alternative to direct heart transplantation, we reviewed 21 patients who were accepted as heart transplant candidates but offered a heart operation because of the availability of circulatory support. Preoperative left ventricular ejection fraction was 0.25 +/- 0.08 (mean +/- standard deviation), and New York Heart Association functional class was 3.4 +/- 0.7. The patients underwent 16 bypass graft operations, 4 mitral and 2 aortic valve replacements, and 4 defibrillator implantations (combined procedures in 5 patients). An intraaortic balloon pump was placed in 12 patients. One patient required biventricular assist device support but was weaned in 11 days. Twenty patients were discharged 14.8 +/- 11.5 days postoperatively. One patient died 15 days postoperatively of amiodarone-induced respiratory failure, and 1 died suddenly 2 months postoperatively. At 10.5 +/- 6 months postoperatively, 19 patients (90%) are alive. Mean functional class is 1.9 +/- 0.9. None of the patients has undergone transplantation, but 2 are awaiting donor organs. We conclude that in selected heart transplant candidates high-risk heart operation is a viable alternative to direct heart transplantation.

Cytomegalovirus infections in heart transplant recipients: relationship to immunosuppression.

To determine the relationship of cytomegalovirus infections (CMVI) to immunosuppression in heart transplants, we retrospectively compared demographic and clinical variables in 154 consecutive heart transplant patients. Forty-one CMVI were compared; of these, 30 (73%) were identified in tissue, and nine (22%) were identified by blood or urine culture. Twenty (49%) of the CMVI were self-limited, and 21 (51%) were progressive, requiring treatment. When comparing patients with and without CMVI, demographic variables, mean preexisting heart disease, cyclosporine level, cumulative corticosteroid dose, and the use of anti-T-cell antibodies were examined. Only the use of OKT3 was significantly associated with the subsequent development of CMVI. Although CMVI subsequently developed in 30 of 79 (38%) patients who had received OKT3, CMVI developed in only 11 of 75 (15%) patients who had not received OKT3 (p = 0.01). Furthermore, the incidence of CMVI increased with increasing total OKT3 dose (none, 11 of 64 [17%]; < or = 75 mg, 23 of 66 [35%]; > 75 mg, 6 of 14 [43%]; p = 0.01). Logistic regression showed that the only two variables predictive of CMVI were the use of OKT3 (p = 0.0023) and ischemic rather than idiopathic heart disease before transplantation (p = 0.0098). Rejection rates, incidence of allograft vasculopathy, and 1-year actuarial survival were not influenced by previous CMVI. Pneumocystis carinii pneumonia occurred more frequently in patients with CMVI than in those without (13 of 41 [32%] patients versus 3/113 [3%] patients; p < 0.001). No correlation existed between CMVI and lymphoproliferative disorder (p = 0.84).(ABSTRACT TRUNCATED AT 250 WORDS)

Successful treatment of heart transplant rejection with photopheresis.

Photopheresis is a potential therapy for rejection in which reinfusion of mononuclear cells exposed to ultraviolet-A light ex vivo, after treatment with 8-methoxypsoralen in vivo, initiates host immune responses that specifically inhibit the cytotoxicity of the photomodulated mononuclear cells. Between May 1990 and January 1991, 7 heart transplant (HT) patients (age 42.2 +/- 16.7 [mean +/- SD] years) on triple immunosuppression (cyclosporine, corticosteroids, and azathioprine) had 9 episodes of non-hemodynamically compromising moderate rejection that were treated with photopheresis. These episodes of rejection occurred at an average of 114.4 +/- 180.5 (range 8-575) days after HT. After oral administration the mean serum level of 8-methoxypsoralen achieved was 129.0 +/- 72.4 ng/ml. An average of 10.4 +/- 9.6 x 10(9) mononuclear cells were treated with each photopheresis procedure. Photopheresis was performed twice when less than 5 x 10(9) mononuclear cells had been treated with the first procedure. Of 9 rejection episodes treated with photopheresis, 5 required 1 procedure and 4 required 2 procedures. Photopheresis was used to treat a single episode of rejection in 5 pts. and 2 separate rejection episodes in 2 additional pts. Eight of 9 episodes of rejection were successfully reversed by photopheresis as assessed by endomyocardial biopsy (EMB) performed 7 days after treatment. Immunohistochemical analysis of EMB samples revealed that postphotopheresis cell counts for T cells, B cells, and macrophages were reduced compared to pretreatment values and correlated with the histopathologic resolution of rejection. Hemodynamics were normal prephotopheresis and remained unchanged at the time when the postphotopheresis EMB showed no evidence rejection No adverse effects have been observed with photopheresis. Over a follow-up period of 5.3 +/- 4.0 months, rejection and infection rates/pt./follow-up months were 0.3 +/- 0.4 and 0.04 +/- 0.07, respectively. The preliminary, short term results of this pilot study indicate that photopheresis may be efficacious in the treatment of moderate rejection in hemodynamically stable HT patients and thus may be an alternative to corticosteroid pulses.

Primary lymphoma of the heart. Prolonged survival with early systemic therapy in a patient.

Primary lymphoma of the heart is an uncommon malignancy usually recognized at autopsy or fatal within a few weeks of diagnosis. Recently, it was reported in patients with acquired immune deficiency syndrome. A patient with diffuse large cell lymphoma of the heart is reported who had chest pain and rapidly evolving cardiac arrhythmias. The human immune deficiency virus antibody test was negative. Because of an aggressive diagnostic approach, therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone was started on the third day after diagnosis. The patient has survived 18 months with an objective response. To the authors' knowledge, this is the longest reported survival in primary cardiac lymphoma. The diagnosis in this patient was aided by excellent tumor delineation by nuclear magnetic resonance scanning. The authors believe that better survival in this patient was a result of prompt diagnosis and treatment because the behavior of the lymphoma was similar to aggressive lymphomas arising elsewhere.