The falling incidence of hematologic cancer after heart transplantation.

BACKGROUND: A number of changes in the management of heart transplantation (HT) patients have each tended to reduce the risk of post-HT hematologic cancer, but little information is available concerning the overall effect on incidence in the HT population. METHODS: Comparison of data from the Spanish Post-Heart-Transplantation Tumour Registry for the periods 1991-2000 and 2001-2010. RESULTS: The incidence among patients who underwent HT in the latter period was about half that observed in the former, with a particularly marked improvement in regard to incidence more than five yr post-HT. CONCLUSIONS: Changes in HT patient management have jointly reduced the risk of hematologic cancer in the Spanish HT population. Long-term risk appears to have benefited more than short-term risk.

Lung cancer after heart transplantation: results from a large multicenter registry.

In this study we analyzed Spanish Post-Heart-Transplant Tumour Registry data for adult heart transplantation (HT) patients since 1984. Median post-HT follow-up of 4357 patients was 6.7 years. Lung cancer (mainly squamous cell or adenocarcinoma) was diagnosed in 102 (14.0% of patients developing cancers) a mean 6.4 years post-HT. Incidence increased with age at HT from 149 per 100 000 person-years among under-45s to 542 among over-64s; was 4.6 times greater among men than women; and was four times greater among pre-HT smokers (2169 patients) than nonsmokers (2188). The incidence rates in age-at-diagnosis groups with more than one case were significantly greater than GLOBOCAN 2002 estimates for the general Spanish population, and comparison with published data on smoking and lung cancer in the general population suggests that this increase was not due to a greater prevalence of smokers or former smokers among HT patients. Curative surgery, performed in 21 of the 28 operable cases, increased Kaplan-Meier 2-year survival to 70% versus 16% among inoperable patients.

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.

[Peritoneal dialyisis role in heart failure treatment, experience in our center]. / Papel de la diálisis peritoneal en el tratamiento de la insuficiencia cardíaca. Experiencia en nuestro centro.

Peritoneal dialysis is a renal replacement therapy indicated in patients with an unstable hemodynamic status. It has been used, by ultrafiltration, preferably in those patients with congestive heart failure refractory to conventional medical therapy. We present the experience of our center with five patients who were affected by severe congestive heart failure [Class IV on the New York Heart Association (NYHA) scale] and diverse stages of chronic renal failure, who received this therapy. Icodextrin has been used as an osmotic agent to induce ultrafiltration. The follow-up period ranged between 5 and 14 months (9.8 +/- 3.7 months). The results that we have found are similar to those of other studies: we observed a significant improvement in quality of life and a reduction in morbidity and hospitalization rates in all our patients. But it seems to be necessary to make a prospective randomized controlled trial with more number of individuals to confirm these promising facts, to clarify the impact on the survival, and to analyze the cost-benefit for treating patients suffering from refractory, end stage congestive heart failure.

Study of the renal function in nonrenal organ transplantation.

Kidney disease after transplantation of a nonrenal organ has been described to be the result of the nephrotoxicity from the commonly used calcineurin-inhibitors as well as other factors. The aim of this study was to evaluate renal function and potential risk factors for the development of chronic renal failure among nonrenal organ recipients. We designed a single-center retrospective study including all 165 of our cardiac and liver recipients between February 1998 and October 2003, collecting clinical, analytic, and therapeutic data. We excluded double transplants and patients with survival less than 6 months. Creatinine clearance was calculated according to the Cockcroft-Gault and the Levey Modification of Diet in Renal Disease (MDRD)-5 equations. Although 165 patients received a cardiac or liver transplantation, 17 died in the first 6 months and three were double transplants; therefore we analyzed 145 patients: 107 (74%) cardiac transplantations and 38 (26%) liver transplantations. There were 106 male and 39 female recipients. The mean age (+/-SD) at the time of transplantation was 54 +/- 10 years and the mean follow-up was 2.9 +/- 1.7 years. Urinalysis before transplantation was only performed in 33 patients (22.8%) including three (2.1%) who had proteinuria. Serum creatinine increased until 12 months after transplantation (P < .001), then it recovered its average level. Creatinine clearance calculated using the aforementioned equations showed a similar pattern, with a progressive decline to 12 months (P < .05), with eventual stabilization or even improvement. The factors that we observed to increase the risk of renal damage were age, female sex, obesity, and the presence of proteinuria prior to transplantation. There was a good correlation (r = 0.96) between cyclosporine but not tacrolimus trough levels and serum creatinine at 48 hours after transplantation.

Quality of Life According to Urgency Status in De Novo Heart Transplant Recipients.

INTRODUCTION: Elective heart transplantation (HTX) aims to improve physical ability, increase survival, and improve health-related quality of life (HRQoL) in patients with chronic heart failure. Nevertheless, most patients who undergo urgent HTX are previously healthy, and a transplant could be perceived as a limitation. The aim of this study is to compare HRQoL between elective and urgent heart transplant recipients. METHODS: Cohort study including patients undergoing heart transplantation between January 1998 and March 2012 in a single center. Patients with retransplantation or multiorgan transplantation were excluded. Clinical variables including comorbidities were collected. For assessment of HRQoL, the Kansas City Cardiomyopathy Questionnaire (KCCQ) was completed by the survivors on March 2013. Univariate analysis (Mann-Whitney U test) was performed. RESULTS: Questionnaires were collected from 95 of 106 elective recipients and 28 of 33 urgent recipients. Urgent heart recipients were younger, with more cardiovascular risk factors, and ischemic etiology was the leading cause of transplant. All domain results were higher in elective heart transplant recipients, but after univariate analysis only the punctuation of the self-efficacy domain remained superior in the elective HTX group (87.5 vs 79.7, P = .034). CONCLUSION: Both urgent and elective heart transplant patients reported a good HRQoL, and there were no significant differences between their scores.

Effect of early conversion to everolimus together with prophylaxis with valganciclovir in the prevention of cytomegalovirus infection in heart transplant recipients.

INTRODUCTION: Viral infections, especially cytomegalovirus (CMV), are a leading cause of early death and morbidity after heart transplantation. Several strategies have been used to minimize the risk, including universal prophylaxis with ganciclovir or valganciclovir and preemptive therapy. Lately, everolimus (EVE) efficacy studies have shown a protective effect against CMV infection. METHODS: We studied retrospectively a series of 223 heart transplant patients, dividing them into 5 groups according to CMV prevention strategy: 16 patients were at low risk for infection (negative recipient [R-]/negative donor [D-]) and received no treatment; 26 patients received prophylactic therapy with ganciclovir, 8 patients prophylaxis with valganciclovir, 145 patients received preemptive therapy and 28 patients prophylaxis with valganciclovir and early conversion to EVE. RESULTS: There were no cases of CMV infection in the low-risk group. There was 1 case of CMV infection in the group that received valganciclovir and conversion to EVE. Among the patients who received prophylaxis with ganciclovir or valganciclovir or preemptive therapy, CMV infection was detected in 68 patients (37%). CONCLUSIONS: Early conversion to EVE in addition to valganciclovir prophylaxis was superior to other strategies in our series for the prevention of CMV infection.

[Acute myocardial infarction related to cocaine use]. / Infarto agudo de miocardio en relación con consumo de cocaína.

Cocaine is a drug capable of potentiating the response to catecholamines. Acute myocardial infarction is the most frequently reported cardiac consequence of cocaine abuse, usually in those patients who had used cocaine in a habitual basis. We report a 30-year-old man, first-time cocaine user, that suffered an acute myocardial infarction.

Use of mTOR inhibitors in chronic heart transplant recipients with renal failure: calcineurin-inhibitors conversion or minimization?

BACKGROUND: In the last decade, mTOR inhibitors (mTOR-is) have become the cornerstone of the calcineurin inhibitor (CNI)-reduced/free regimens aimed to the preservation of post-transplant renal function. We compared utility and safety of the total replacement of calcineurin inhibitors with a mTOR-i with a strategy based on calcineurin inhibitor minimization and concomitant use of m-TOR-i. METHODS: In a retrospective multi-center cohort of 394 maintenance cardiac recipients with renal failure (GFR<60 mL/min/1.73 m(2)), we compared 235 patients in whom CNI was replaced with a mTOR-i (sirolimus or everolimus) with 159 patients in whom mTOR-is were used to minimize CNIs. A propensity score analysis was carried out to balance between group differences. RESULTS: Overall, after a median time of 2 years from mTOR-i initiation, between group differences for the evolution of renal function were not observed. In a multivariate adjusted model, improvement of renal function was limited to patients with mTOR-i usage within 5years after transplantation, particularly with the conversion strategy, and in those patients who could maintain mTOR-i therapy. Significant differences between strategies were not found for mortality, infection and mTOR-i withdrawal due to drug-related adverse events. However, conversion group tended to have a higher acute rejection incidence than the minimization group (p=0.07). CONCLUSION: In terms of renal benefits, our results support an earlier use of mTOR-is, irrespective of the strategy. The selection of either a conversion or a CNI minimization protocol should be based on the clinical characteristics of the patients, particularly their rejection risk.

Effect of CYP3A5, CYP3A4, and ABCB1 genotypes as determinants of tacrolimus dose and clinical outcomes after heart transplantation.

BACKGROUND: Tacrolimus (Tac) is mainly metabolized by cytochrome P450 3A isoenzymes. In a cohort of heart transplant recipients, we investigated the effect of CYP3A5, CYP3A4, and ABCB1/MDR1 polymorphisms on Tac dose requirements and the risk of developing new-onset diabetes after transplantation (NODAT). METHODS: A total of 65 heart transplant recipients were genotyped for 3 single nucleotide polymorphisms (SNPs) in the CYP3A5 (SNP rs776746), CYP3A4 (SNP rs2740574), and ABCB1 (SNP rs104564). The mean Tac dose values were compared between the genotypes. RESULTS: CYP3A5 3 homozygotes (nonexpressers; n = 55, 85%) received significantly higher Tac dose compared with CYP3A5 1 carriers (expressers). No different NODAT frequencies were found between the genotypes. CONCLUSIONS: The CYP3A5 polymorphism was the main determinant of Tac dose requirements among heart transplant recipients. This common functional polymorphism had no influence on the risk of developing NODAT.

The prognosis of noncutaneous, nonlymphomatous malignancy after heart transplantation: data from the Spanish Post-Heart Transplant Tumour Registry.

INTRODUCTION: Malignancy is a major complication in the management of solid organ transplant patients. Skin cancers show a better prognosis than other neoplasms, but not all others are equal: Ideally, patient management must take into account the natural history of each type of cancer in relation to the transplanted organs. We sought to determine the prognosis of various groups of noncutaneous nonlymphomatous (NCNL) cancers after heart transplantation (HT). METHODS: We retrospectively analyzed the records of the Spanish Post-Heart-Transplant Tumour Registry, which collects data on posttransplant tumors in all patients who have undergone HT in Spain since 1984. Data were included in the study up to December 2008. We considered only the first NCNL post-HT tumors. RESULTS: Of 4359 patients, 375 developed an NCNL cancer. The most frequent were cancers of the lung (n=97; 25.9%); gastrointestinal tract (n=52; 13.9%); prostate gland (n=47; 12.5%; 14.0% of men), bladder (n=32; 8.5%), liver (n=14; 3.7%), and pharynx (n=14; 3.7%), as well as Kaposi's sarcoma (n=11; 2.9%). The corresponding Kaplan-Meier survival curves differed significantly (P<.0001; log-rank test), with respective survival rates of 47%, 72%, 91%, 73%, 36%, 64%, and 73% at 1 year versus 26%, 62%, 89%, 56%, 21%, 64%, and 73% at 2 years; and 15%, 51%, 77%, 42%, 21%, 64%, and 52% at 5 years post-diagnosis, respectively. CONCLUSION: Mortality among HT patients with post-HT NCNL solid organ cancers was highest for cancers of the liver or lung (79%-85% at 5 years), and lowest for prostate cancer (23%).

The relationship of anti-MICA antibodies and MICA expression with heart allograft rejection.

The role of MICA antibodies in acute heart allograft rejection was examined utilizing 190 pre- and post-transplant serum samples from 44 patients collected during the first year after transplantation. MICA antibodies were detected by CDC test on recombinant cell lines and by the newly developed Luminex MICA antibody detection assay. Additionally, MICA expression was analyzed by 'real time' RT-PCR and by immunohistochemistry in 10 endomyocardial biopsies. Only two subjects had HLA antibodies post-transplant. Nevertheless, MICA antibodies were found in a significant number of subjects. The prevalence of MICA antibodies was significantly higher among those with severe acute rejection (AR) than in those without rejection (60.7% vs. 14.3%, p = 0.0038 by CDC; 55.5% vs. 5.7%, p = 0.0020 by Luminex). In most cases, the appearance of MICA antibodies post-transplant precedes AR. Following transplantation, MICA up-regulation correlated with histological evidence of severe rejection. Monitoring for MICA antibodies post-transplant may be useful to establish new risk factors for acute rejection.