Cancer Incidence in Heart Transplant Recipients With Previous Neoplasia History.

Neoplasm history increases morbidity and mortality after solid organ transplantation and has disqualified patients from transplantation. Studies are needed to identify factors to be considered when deciding on the suitability of a patient with previous tumor for heart transplantation. A retrospective epidemiological study was conducted in heart transplant (HT) recipients (Spanish Post-Heart Transplant Tumor Registry) comparing the epidemiological data, immu-nosuppressive treatments and incidence of post-HT tumors between patients with previous malignant noncardiac tumor and with no previous tumor (NPT). The impact of previous tumor (PT) on overall survival (OS) was also assessed. A total of 4561 patients, 77 PT and 4484 NPT, were evaluated. The NPT group had a higher proportion of men than the PT group (p < 0.001). The incidence of post-HT tumors was 1.8 times greater in the PT group (95% confidence interval [CI] 1.2-2.6; p < 0.001), mainly due to the increased risk in patients with a previous hematologic tumor (rate ratio 2.3, 95% CI 1.3-4.0, p < 0.004). OS during the 10-year posttransplant period was significantly lower in the PT than the NPT group (p = 0.048) but similar when the analysis was conducted after a first post-HT tumor was diagnosed. In conclusion, a history of PT increases the incidence of post-HT tumors and should be taken into account when considering a patient for HT.

Temporal trends in the use of proliferation signal inhibitors in maintenance heart transplantation: a Spanish multicenter study.

Proliferation signal inhibitors (PSI; sirolimus, everolimus) are being increasingly used in heart transplantation. We performed an observational, retrospective, multicenter study in 9 Spanish centers seeking to describe the clinical context in which a PSI was used among maintenance heart recipients and its evolution over time. We collected a cohort of 548 patients in whom a PSI was prescribed from October 2001 to March 2009. The group was divided into 3 time periods. The use of PSI steeply increased in the 2005-2006 period, remaining stable thereafter. There were no significant differences over time with regard to age, gender, or time from transplantation to the introduction of the PSI. Everolimus usage overtook sirolimus from 2005 on; currently, >90% of the subjects with PSI indications are prescribed everolimus. Compared with earlier periods, patients in the more recent period (October 2006-March 2009) showed less vascular graft disease and better basal renal function, irrespective of the primary indication for the PSI prescription. Also, skin cancer overtook solid cancer as the main type of neoplasm in patients for whom malignancy was the primary indication for the use of the PSI. The actuarial incidence of PSI withdrawal owing to adverse effects did not change significantly over time.

Incidence and risk factors for nonmelanoma skin cancer after heart transplantation.

INTRODUCTION: The incidence of skin cancer in heart transplant (HT) patients is higher than in the general population, reversing the proportion of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with a predominance of the former. The etiologic role of new immunosuppressants is not well known. We sought to ascertain the incidence of SCC and BCC in HT patients and the risk factors for its occurrence. PATIENTS AND METHODS: We report the incidence of all types of post-HT skin cancer, SCC, and BCC among adult HT patients in Spain (4089 subjects) as well as the influence of gender, age at heart transplant, immunosuppression, and sunlight exposure. RESULTS: The incidence rates of SCC and BCC, per 1000 persons/year, were 8.5 and 5.2, respectively. Males had a higher risk of SCC but not BCC. Induction therapy increased the risk of SCC and BCC. The relative risk of mycophenolate mofetil (MMF) was 0.3 (0.2-0.6; P<.0005) and azathioprine (AZA) 1.8 (1.2-2.7; P<.0032) for SCC, whereas tacrolimus and cyclosporine showed no difference. The relative risk of BCC was not affected by any immunosuppressant. CONCLUSION: Age at transplantation>45 years, induction therapy use, and high sunshine zone were risk factors for both SCC and BCC. Different immunosuppressive agents have different risks of nonmelanoma skin cancer, as AZA increases the risk of SCC and MMF is a protective factor. The relative risk of BCC was not affected by any immunosuppressor.

Steroid use in heart transplant patients in Spain in the current era: a multicenter survey.

OBJECTIVE: Steroid withdrawal (SW) from maintenance therapy in heart transplant patients is still a controversial subject. We designed a questionnaire to ascertain the attitudes and procedures of a number of Spanish heart transplant units (16) regarding the use/withdrawal of steroids as part of the immunosuppressive maintenance therapy. MATERIALS AND METHODS: We sent an 11-item questionnaire to the clinical director in charge of each unit. The questionnaire was completed and returned by 14 units. RESULTS: In 21.5% of the centers SW was performed in all patients, while 78.5% of the centers only performed SW in selected patients. In 57% of units SW was performed at 12 months posttransplantation and between 6 and 12 months in the rest. Fewer than 20% of patients were steroid-free in 46% of units while in 23% of units this proportion was >50%. In 11 units, the minimum prednisone dose administered was

Outcomes of heart transplantation for cardiac amyloidosis: subanalysis of the spanish registry for heart transplantation.

Amyloidosis (Am), a systemic disease, has poor prognosis because of organ damage produced by protein deposition in the extracellular space. Although heart transplantation (HTx) is possible, donor availability concerns and high mortality make this approach controversial. The Spanish Registry for Heart Transplantation includes 25 Am patients (54 +/- 9 years): 13 with AL type, 2 with AA and 10 with TTR mutation. Fifteen patients (60%) died during follow-up (4.9 +/- 1.3 years): 9 AL-Am patients, both AA-Am patients and 4 with TTR-Am. HTx survival for Am patients was similar to patients without Am at 1 month but significantly worse at 5 years: 46% versus 78% (p < 0.02). Of 10 AL-Am patients undergoing successful HTx, 4 died of systemic Am. Stem cell transplantation was performed in 3 (1 died of acute rejection). Five of 10 patients with TTR-Am underwent liver transplant; 4 remained alive at the last follow-up. Findings include poor outcome for AL-Am patients despite HTx and better survival for TTR-Am patients if HTx is associated with liver transplantation. Given the shortage of donors and poor outcome for Am patients, we would recommend that HTx be reserved for patients without or with mild systemic Am and be supplemented by additional therapies as indicated.

Malignancy after heart transplantation: incidence, prognosis and risk factors.

The Spanish Post-Heart-Transplant Tumour Registry comprises data on neoplasia following heart transplantation (HT) for all Spanish HT patients (1984-2003). This retrospective analysis of 3393 patients investigated the incidence and prognosis of neoplasia, and the influence of antiviral prophylaxis. About 50% of post-HT neoplasias were cutaneous, and 10% lymphomas. The cumulative incidence of skin cancers and other nonlymphoma cancers increased with age at HT and with time post-HT (from respectively 5.2 and 8.9 per 1000 person-years in the first year to 14.8 and 12.6 after 10 years), and was greater among men than women. None of these trends held for lymphomas. Induction therapy other than with IL2R-blockers generally increased the risk of neoplasia except when acyclovir was administered prophylactically during the first 3 months post-HT; prophylactic acyclovir halved the risk of lymphoma, regardless of other therapies. Institution of MMF during the first 3 months post-HT reduced the incidence of skin cancer independently of the effects of sex, age group, pre-HT smoking, use of tacrolimus in the first 3 months, induction treatment and antiviral treatment. Five-year survival rates after first tumor diagnosis were 74% for skin cancer, 20% for lymphoma and 32% for other tumors.

Role of orthotopic liver transplant in the treatment of homozygous familial hypercholesterolemia.

UNLABELLED: Homozygous familial hypercholesterolemia is an inherited metabolic disease that leads to decreased catabolism of low-density lipoprotein cholesterol. As a result coronary artery disease ensues by the first or second decade. Because most low-density lipoprotein receptors (50-75%) are located in the liver, liver transplantation has been introduced as a therapeutic option in this disorder. AIMS: To report our experience in the treatment of homozygous familial hypercholesterolemia with ortothopic liver transplantation. We evaluated metabolic results and patient survival. METHOD: We treated two affected siblings. One of them received a sequenced heart-liver transplantation because of cardiac failure due to severe coronary disease. RESULTS: The operative and postoperative course was favourable in both patients, with a decrease in cholesterol levels to normal values. Four years later both were alive and both had normal liver and heart functions. Neither patient needed cholesterol-lowering drugs, and the disease had not progressed. CONCLUSIONS: As shown by our results and those reported by others, liver transplantation is the treatment of choice for homozygous familial hypercholesterolemia until gene therapy becomes a viable option. Transplantation should be done before of cardiovascular complications develop.

[Primary cardiac lymphoma: presentation of a case and review of the literature]. / Linfoma cardíaco primario: presentación de un caso y revisión de la literatura.

We describe a case of primary cardiac lymphoma presenting with chest pain, complete AV block, negative T waves, and infiltration of the basal segments and right free ventricular wall on echocardiography, interpreted initially as hypertrophy. One month later the patient was readmitted with systemic disease and cardiac insufficiency. Furthermore multicentric myocardial infiltration with a nodular mass in the right atrium producing severe tricuspid stenosis was demonstrated. Surgical biopsy was performed and a high grade non-Hodgkin's lymphoma diagnosed. The patient died during the immediate post-operative period without receiving specific chemotherapeutic treatment. Reviewing the published cases, we found that primary cardiac lymphomas are fast growing tumors that infiltrate predominantly the right cavities and have limited therapeutic options.

[The incidence, mechanisms and clinical factors predictive of sudden death in patients with severe heart failure evaluated in anticipation of heart transplantation]. / Incidencia, mecanismos y factores clínicos predictores de muerte súbita en pacientes con insuficiencia cardíaca severa evaluados con vistas a trasplante cardíaco.

INTRODUCTION AND OBJECTIVES: Sudden death is not uncommon in patients with severe congestive heart failure. The aim of our study was to assess the incidence, mechanisms and clinical predictors of sudden death in a large series of patients with severe congestive heart failure evaluated for heart transplantation. METHODS: With this aim we have reviewed our experience on 240 consecutive patients with severe heart failure studied in our hospital from May 1986 to June 1992. Heart failure was due to ischemic heart disease in 35% of patients and idiopathic dilated cardiomyopathy in 65%. Age was 47 +/- 12 years, left ventricular ejection fraction was 20 +/- 6%, and symptom class was IV in 88% of patients and III in 12%. RESULTS: Sixty-eight of the 240 patients (28%) died without transplantation. Death was sudden in 21 patients (31% of deaths, and 9% of all patients), due to heart failure in 41 (68%), and due to malignancy (ampuloma) in 1 (1%). Mechanism of sudden death could be identified in 12 cases: ventricular tachycardia/fibrillation in 8 and bradycardia/electromechanical dissociation in 4. On multivariate analysis (stepwise logistic regression), a lower tolerated captopril dosage (p = 0.004), a lower systolic blood pressure (p = 0.079) and a history of a ventricular tachycardia/fibrillation (p = 0.073) were independent predictors of sudden death. CONCLUSIONS: It seems possible to identify, between patients with severe heart failure, a subgroup of patients at higher risk for sudden death by means of such simple clinical parameters.

Visceral Kaposi's sarcoma without mucocutaneous involvement in a heart transplant recipient.

Kaposi's sarcoma has been occasionally reported in heart transplant recipients, but its occurrence without mucocutaneous involvement is extremely rare. In these uncommon cases, the tumor can be indistinguishable from opportunistic infections, making diagnosis difficult. The case of a patient in whom visceral Kaposi's sarcoma was diagnosed by necropsy 6 months after heart transplantation is reported.

[Infectious endocarditis due to Q fever. A report of 4 new cases]. / Endocarditis infecciosa por fiebre Q. Descripción de 4 nuevos casos.

Q fever (Coxiella burnetii) is an uncommon cause of culture-negative infective endocarditis. Four cases of Q fever endocarditis diagnosed at our hospital in the last 7 years are reported (8% of all infective endocarditis). Infection involved a prosthetic heart valve in 3 cases (15% of all prosthetic valve endocarditis), and one patient with single ventricle and pulmonary stenosis in the remaining case. Important complications developed in all cases, and 3 patients underwent cardiac surgery. Mortality was 50%. Some diagnostic and therapeutical aspects of this disease are discussed.

Noninvasive radioisotopic diagnosis of acute heart rejection.

In a prospective protocol for noninvasive diagnosis and follow-up of acute heart rejection 162 examinations were performed in 36 patients who underwent heart transplantation. The follow-up period ranged from 15 days to 44 months. The protocol comprised multiple gated acquisition ventriculography with albumin labeled with 99mTc (740 MBq), acquired using a forward/backward by thirds framing mode, 32 frames/cycle, and 10 million total counts. Parameters of left ventricular diastolic function were analyzed. Antimyosin antibody labeled with indium 111 (74 MBq) was injected, and myocardium/lung uptake ratios were obtained at 48 hours in counts per pixel. Endomyocardial biopsy was performed in all patients within 48 hours. The results were evaluated by comparison of mean values of each parameter and global and individual correlation analysis in relation to the presence or absence of rejection and treatable (moderate or severe) or nontreatable (mild or absent) rejection. Antimyosin and diastolic function parameters showed significant differences (p less than 0.001) between patients with and without rejection and between patients with treatable and nontreatable rejection. Global correlation with biopsy existed (p less than 0.05) for antimyosin (r = 0.75), average filling rate (r = 0.61), and peak filling rate (r = 0.56). Individual correlation exhibited significance in all patients only for antimyosin (r = 0.78 to 0.98). In eight patients average filling rate also showed significant correlation (r = 0.65 to 0.88). In conclusion, these results provide a noninvasive diagnosis of cardiac allograft rejection episodes and allow an accurate selection between treatable and nontreatable rejection. Individual patient follow-up is possible with antimyosin. The study of diastolic function is also useful in this setting.

The activation antigen CD69 is selectively expressed on CD8+ endomyocardium infiltrating T lymphocytes in human rejecting heart allografts.

We analyzed the presence of T-cell subsets (CD4/CD8) and the activation markers CD25 and CD69 in the cellular infiltrates of endomyocardium biopsies taken from transplanted human hearts. The results indicate that CD25 was present within specimens mainly infiltrated by CD4+ cells. In contrast, CD69 was found in infiltrated biopsies by CD8+ cells, as determined by single immunofluorescence. Double immunoenzymatic staining was used to investigate the cellular distribution of the activation markers studied in some representative cases. Thus, CD25 was found on both CD4+ and CD8+ cells while CD69 molecule was selectively expressed on CD8+ T-cell subset. These results suggest that CD69 is a surface molecule relevant to the CD8+ cell-mediated graft rejection events of allografted human hearts.