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.

Health-related quality of life, social support, and caregiver burden between six and 120 months after heart transplantation: a Spanish multicenter cross-sectional study.

A multicenter cross-sectional study was conducted to determine the current heart transplant (HTx) outcomes in Spain. Clinical and functional status, health-related quality of life (HRQoL), social support, and caregiver burden were analyzed in 303 adult transplant recipients (77.9% males) living with one functioning graft. Mean age at time of HTx (SD) was 56.4 (11.4) years, and the reason for transplantation in all patients was congestive heart failure. All patients had received a first heart transplant 6 (± 1), 12 (± 2), 36 (± 6), 60 (± 10), or 120 (± 20) months previously. Participants completed the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ-5D, the Duke-UNC Functional Social Support Questionnaire, and the Zarit Caregiver Burden Scale. Reasonable HRQoL, social support, and caregiver burden levels were found at all time points, although a slight decrease in HRQoL was recorded at 120 months (p ≤ 0.033). Multivariate regression analyses showed that complications, comorbidities, and hospitalizations were associated with HRQoL (EQ-5D: 48.4% of explained variance, F4,164 = 38.46, p < 0.001; KCCQ overall summary score: 45.0%, F3,198 = 54.073, p < 0.001). Patient functional capabilities and complications affected caregiver burden (p < 0.05). In conclusion, HTx patients reported reasonable levels of HRQoL with low caregiver burden. Clinical variables related to these outcomes included functional status, complications, and number of admissions.

Sirolimus conversion after heart transplant: risk factors for acute rejection and predictors of renal function response.

In a randomized, comparative study of cardiac transplant patients with mild-to-moderate renal insufficiency, conversion from calcineurin inhibitors (CNIs) to sirolimus improved renal function at 1 year versus continuing CNIs, with an attendant risk of biopsy-confirmed acute rejection (BCAR). Post hoc analyses were conducted to identify predictors of BCAR and GFR improvement associated with conversion. Patients with proteinuria >500 mg/day were excluded. Univariate and multivariate regression analyses tested 13 parameters for BCAR and six for GFR improvement. In 57 sirolimus-treated patients, mean daily mycophenolate mofetil (MMF) dose was lower in those with versus without BCAR (1000 vs. 1420 mg; p = 0.014). Receiver operating characteristic analysis identified MMF dose ≤1000 mg/day as the optimal cutoff to predict BCAR. Multivariate analysis confirmed low MMF dose (odds ratio: 9.94; p = 0.007) and non-white race (odds ratio: 15.3; p = 0.06) were independently associated with BCAR. GFR improvement was evaluated in intent-to-treat patients (n = 116). Significant interaction was detected between treatment effect and preexisting diabetes status (univariate p = 0.077; multivariate p = 0.022), indicating greater beneficial effect of sirolimus in those without preexisting diabetes. These findings suggest that sirolimus is more effective in improving GFR in patients without preexisting diabetes, and adequate MMF doses are needed for sirolimus conversion.

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.

Prognostic impact of chronic obstructive pulmonary disease and bronchial asthma in patients with heart failure.

PURPOSE: To analyze the impact of chronic obstructive pulmonary disease (COPD) and bronchial asthma on therapeutic management and prognosis of patients with heart failure (HF). METHODS: Analysis of the information collected in a clinical registry of patients referred to a specialized HF unit from January-2010 to June-2012. Clinical profile, treatment and prognosis of patients was evaluated, according to the presence of COPD or asthma. Survival analyses were conducted by means of Kaplan-Meier and Cox's methods. Median follow-up was 1493 days. RESULTS: We studied 2577 patients, of which 251 (9.7%) presented COPD and 96 (3.7%) bronchial asthma. Significant differences among study groups were observed regarding to the prescription of beta-blockers (COPD=89.6%; asthma=87.5%; no bronchopathy=94.1%; p=0.002) and SGLT2 inhibitors (COPD=35.1%; asthma=50%; no bronchopathy=38.3%; p=0.036). Also, patients with bronchial disease received less frequently a defibrillator (COPD=20.3%; asthma=20.8%; no broncopathy=29%; p=0.004). COPD was independently associated with increased risk of all-cause mortality (HR=1.64; 95% CI 1.33-2.02), all-cause death or HF admission (HR=1.47; 95% CI 1.22-1.76) and cardiovascular death or heart transplantation (HR=1.39; 95% CI 1.08-1.79) as compared with patients with no bronchopathy. Bronchial asthma was not significantly associated with increased risk of adverse outcomes. CONCLUSIONS: COPD, but not asthma, is an adverse independent prognostic factor in patients with HF.

Randomized controlled trial of sirolimus conversion in cardiac transplant recipients with renal insufficiency.

This randomized, comparative, multinational phase 3b/4 study of patients 1-8 years postcardiac transplantation (mean 3.9 years) evaluated the effect of conversion from a calcineurin inhibitor (CNI) to sirolimus on renal function in patients with renal insufficiency. In total, 116 patients on CNI therapy with GFR 40-90 mL/min/1.73 m(2) were randomized (1:1) to sirolimus (n = 57) or CNI (n = 59). Intent-to-treat analysis showed the 1-year adjusted mean change from baseline in creatinine clearance (Cockcroft-Gault) was significantly higher with sirolimus versus CNI treatment (+3.0 vs. -1.4 mL/min/1.73 m(2) , respectively; p = 0.004). By on-therapy analysis, values were +4.7 and -2.1, respectively (p < 0.001). Acute rejection (AR) rates were numerically higher in the sirolimus group; 1 AR with hemodynamic compromise occurred in each group. A significantly higher treatment discontinuation rate due to adverse events (AEs; 33.3% vs. 0%; p < 0.001) occurred in the sirolimus group. Most common treatment-emergent AEs significantly higher in the sirolimus group were diarrhea (28.1%), rash (28.1%) and infection (47.4%). Conversion to sirolimus from CNI therapy improved renal function in cardiac transplant recipients with renal impairment, but was associated with an attendant AR risk and higher discontinuation rate attributable to AEs.

Clinical profile and causes of death according to ejection fraction in patients with heart failure cared for in a specialized Cardiology unit.

BACKGROUND AND OBJECTIVE: Patients with heart failure are classified into three phenotypes based on left ventricular ejection fraction. This work aimed to compare the clinical profile, treatment, prognosis, and causes of death of patients with heart failure and reduced (<40%, HF-rEF), preserved (≥50%, HF-pEF), or mid-range (40-49%, HF-mrEF) left ventricular ejection fraction. METHODS: An analysis was conducted on the clinical data included in a prospective registry of patients with heart failure who were referred to a specific Cardiology unit from 2010 to 2019. RESULTS: A total of 1404 patients with HF-rEF, 239 patients with HF-mrEF, and 266 patients with HF-pEF were analyzed. Significant differences were observed among the groups in regard to several clinical characteristics and the frequency of prescription of neurohormonal blocking drugs. A multivariate Cox regression revealed an increased risk of all-cause mortality in patients with HF-pEF (hazard ratio 1.36; 95% confidence interval 1.03-1.80; p = 0.028) and patients with HF-mrEF (hazard ratio 1.36; 95% confidence interval 1.03-1.78; p = 0.029) as compared to patients with HF-rEF. Heart failure was the most frequent cause of death in the three subgroups. A higher relative weight of sudden death as a cause of death was observed among patients with HF-rEF while the relative weight of non-cardiovascular causes of death was higher among patients with HF-pEF and HF-mrEF. CONCLUSIONS: This study confirms the existence of significant differences among patients with HF-rEF, HF-mrEF, and HF-pEF with regard to their clinical profile, therapeutic management, prognosis, and causes of death.

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.

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.

Reversal of cardiac cirrhosis following orthotopic heart transplantation.

Irreversible hepatic cirrhosis greatly increases the risks attending heart transplantation (HT), and is accordingly considered to be an absolute contraindication for HT unless combined heart and liver transplantation can be performed. It is now recognized that hepatic cirrhosis can undergo regression if the source of insult is removed, but no cases of post-HT regression of cirrhosis of cardiac origin have hitherto been reported. Here we report a case of cardiac cirrhosis that underwent complete regression following orthotopic HT, and we discuss the implications of this case.

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.

The efficacy and safety of ezetimibe for treatment of dyslipidemia after heart transplantation.

INTRODUCTION: Statins, although the treatment of choice for dyslipidemia after heart transplantation (HT), are not always well tolerated or effective. In such cases, administration of ezetimibe may be useful. AIM: The aim of this study was to assess the efficacy and safety of ezetimibe, with or without statins, after HT. METHOD: Thirty-six HT patients, 97% of whom were males of overall mean age of 57 +/- 13 years, were all unable to reach target lipid levels with statins alone and/or were intolerant of statins. They were prescribed ezetimibe, with or without a statin. Efficacy and safety were evaluated after 1, 3, 6, and 12 months. RESULTS: Thirty-four patients were evaluated at 1 month and 12 months. Ezetimibe was prescribed to 27 patients (75%) because of statin inefficacy, and to 9 patients (25%) because of statin intolerance, manifested by myalgia in 4 cases (11%), hepatotoxicity in 2 cases (6%), and rhabdomyolysis in 3 cases (8%). Lipid levels (mg/dL; baseline vs 1 year) were as follows: cholesterol, 235 +/- 49 versus 167 +/- 32 (P = .013); LDL cholesterol, 137 +/- 47 versus 89 +/- 29 (P = .001); HDL cholesterol, 54 +/- 13 versus 51 +/- 10 (P = .235); and triglycerides, 243 +/- 187 versus 143 +/- 72 (P = .022). There were no cases of liver toxicity, renal dysfunction, or significant alteration of immunosuppressive pharmacokinetics. Ezetimibe was withdrawn from 2 patients because of hand edema or asymptomatic recurrence of rhabdomyolysis first caused by statins. CONCLUSIONS: With or without a statin, ezetimibe was generally well tolerated, reducing total cholesterol, LDL cholesterol, and triglyceride levels with no long-term alteration of HDL cholesterol levels. CPK surveillance is recommended because of a slight continued risk of adverse effects. Further studies should evaluate the benefit for survival.

Adverse effects of mammalian target of rapamycin inhibitors during the postoperative period after cardiac transplantation.

INTRODUCTION: Safety of treatment with mammalian target of rapamycin inhibitors (mTORi) in the postoperative period after heart transplantation (HT) is controversial. METHODS: We evaluated the incidence of postoperative complications (pericardial, pleural, and surgical wound complications) among nine de novo heart transplant recipients treated with mTORi compared with 19 patients who did not receive them during the same period (control group). RESULTS: No significant differences were observed between the two groups regarding sex, age, body mass index, pretransplant diagnosis, history of diabetes mellitus, prior cardiac surgery, or baseline renal function. The main laboratory parameters at 1 month were also similar. During the first 2 months after HT, four patients (44%) in the mTORi group developed severe pericardial effusions requiring drainage, compared to 1 (5%) in the control group (P = .026). All patients presenting this complication in the mTORi group received everolimus. In addition, two cases of sternal dehiscence were observed in the mTORi group, compared to none in the control group (P = .09); one patient on everolimus required sternal reopening and debridement for clinically suspected mediastinitis. Duration of chest tube drainage, quantity of collected pleural fluid, and need for thoracentesis were similar in both groups. CONCLUSIONS: In our series, patients receiving mTORi-particularly everolimus-during the postoperative period after HT showed a higher incidence of severe pericardial effusion requiring drainage, as well as a trend toward a higher incidence of sternal dehiscence, as compared to a group not receiving mTORi. The use of mTORi during the early postcardiac transplant period should be individualized.

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.

Late steroid withdrawal after heart transplantation and incidence of acute rejection.

BACKGROUND: Steroid withdrawal (SW) after heart transplantation (HT) reduces steroid-associated side effects, although it can increase acute rejection episodes (ARE). Patient selection criteria for SW and the time elapsed after HT for this maneuver are controversial issues. The objective of this study was to assess the safety of late SW after HT with regard to the occurrence of ARE and to analyze risk factors resulting in a poor evolution. METHODS: We studied a cohort of 24 patients who underwent SW late after HT. All of them had gone at least 4 years without any ARE. Independent variables were time after HT, general recipient and donor data, risk factors for ARE, and immunosuppression. The dependent variables were occurrence of ARE (proven or not proven with endomyocardial biopsy) and time and severity of ARE. RESULTS: Among 24 HT patients including 96% men with an overall mean age of 57 years who underwent SW, the mean follow-up was 2.32 +/- 0.86 years. Six patients (25%) displayed an ARE >or=2R according to the International Society for Heart and Lung Transplantation (ISHLT) at 5 +/- 3 months after SW. There were no deaths. Time from the last rejection episode to SW was 6.6 +/- 2 years. All ARE were treated with steroid boluses (mean total dose 1583 +/- 1044 mg). Among the HT patients with ARE, 5 (85%) had never experienced ARE after HT. Upon long-term follow-up, there were 2 deaths: 1 sudden death at 30 months after SW and 1 due to allograft vasculopathy at 20 months post-SW. Currently 92% are New York Heart Association (NYHA) functional class I with a mean left ventricular ejection fraction of 67% +/- 10%. CONCLUSIONS: In our series of HT with late SW after HT (even among an HT population with a low risk of rejection), there was a 25% rate of ARE. This study did not allow us to identify risk factors for ARE after SW. We believe that based upon these observations SW should be implemented with caution.

Late noncardiac surgery in heart transplant patients.

OBJECTIVE: Because of improved long-term survival of heart transplants (HT), patients often need noncardiac surgery (NCS). Immunosuppression may increase the infection rate. Inadequate management may increase the risk of dysfunction or acute rejection episodes (ARE). Long-term outcomes of NCS and optimal immunosuppressive management in the perioperative period are not well known. The objective of this study was to analyze the incidence, morbidity, and mortality of late NCS after HT. METHODS: We retrospectively evaluated the incidence and type of late NCS as well as the risk factors for complications and the mortality among 207 HT patients. Immunosuppression and ARE rates were also analyzed. RESULTS: One hundred and sixteen late NCS (84.5% elective) were performed in 72 HT patients (34.8%). Interventions were: 35 urologic (30.2%), 29 abdominal (25%), 14 vascular (12.1%), 13 ENT (11.2%), 11 skin and soft tissue (9.5%), and 7 orthopedic (6%). Malignancy was the main indication for NCS (33.6%). Only 4 patients (5.6%) died preoperatively. Mortality was higher among emergent vs elective procedures (16.6% vs 1%; P = .012) and among patients with preoperative high vs middle/low risk (26.6% vs 0%). Postsurgical infection was the most frequent complication (6.9%). However, there were no relevant complications in 82.8% of HT patients. Hospitalization time was <15 days in two thirds of patients. Immunosuppression was modified in 33 patients (28.4%), especially when the surgical indication was neoplasia (P < .001). None of the patients with NCS displayed allograft dysfunction or an ARE. CONCLUSIONS: More than one-third of HT patients needed a late NCS. In our experience, elective surgical procedures with middle/low preoperative cardiovascular risk are safe. In this context, the risk of rejection was low when immunosuppression was carefully monitored to reduce the risk of infection.

Bone fractures after cardiac transplantation.

OBJECTIVE: Bone loss and bone fractures are disabling complications after heart transplantation. Severe bone loss happens mainly during the first year posttransplantation. Steroids and cyclosporine alter bone metabolism in several ways. To counterbalance these effects, antiresorptive therapy is provided to these patients. The objective of this study was to assess the frequency of bone fractures after heart transplantation, considering previous comorbidities, immunosuppressive therapy, and osteoprotective treatment. METHODS: From 1993 to 2005, 443 consecutive heart transplant recipients were followed for the occurrence of bone fractures, immunosuppressive therapy, clinical conditions, and antiresorptive treatment. RESULTS: There were 41 fractures in 34 patients (7.6%, group I). The remainder of patients formed group II. Fractures commonly involved the lumbar spine. Postmenopausal women had more fractures than other patients (20.6% vs 7.8%, P = .02). When the initial immunosuppressive regimen included tacrolimus, fractures did not happen (P = .01, vs other regimens). Osteoprotective therapy was administered to 91.2% of patients in group I and 79% in group II (P = .08). Mean interval from transplantation to the first fracture was 1131.5 days. Overweight patients had a 61.8% incidence of fracture. CONCLUSIONS: Our series showed a low frequency of bone fractures. Postmenopausal women and overweight patients had more fractures. An initial immunosuppressive regimen using tacrolimus was associated with lower fracture rates.

Calcineurin inhibitors in heart transplantation.

The calcineurin inhibitors (CNIs) cyclosporine and tacrolimus are routinely used for immunosuppression following heart transplantation in conjunction with an antiproliferative agent with or without maintenance steroids. In randomized multicenter trials both agents showed similar efficacies to prevent rejection and death within the first year after transplant. Neither cyclosporine nor tacrolimus have been shown to prevent coronary allograft vasculopathy. Their use is limited by many side effects like kidney damage, hypertension, new-onset diabetes, and hyperlipidemia, although they may have different cardiovascular side effect profiles. The choice of CNIs seems to be currently dictated by their adverse effect profiles, by the results obtained for the individual patient, and possibly by institutional preference.

Long-term results of heart transplant in recipients older and younger than 65 years: a comparative study of mortality, rejections, and neoplasia in a cohort of 445 patients.

BACKGROUND: Whether being older than 65 years should be considered an absolute counterindication to heart transplant (HT), as it is in some centers, is controversial. In our centre, patients older than 65 years are accepted for HT if they satisfy stringent conditions. The aim of this study was to examine whether heart recipients older than 65 years have a greater risk of rejection, neoplasia, or mortality than younger ones. METHODS: We studied 445 patients who underwent HT between April 1991 and December 2003, 42 of whom were older than 65 years and 403 who were 65 years or younger. The parameters evaluated were the cumulative incidences of neoplasias and rejections (ISHLT grade > or = 3A), and the survival rates 1 month, 1 year, and 5 years post-HT. RESULTS: The two groups had similar percentages of patients with at least one rejection episode (< or =65 years 56.9%, >65 years 51.3%; P > .05), and although there were proportionally almost twice as many tumors in the older group (14.2%) as in the younger (7.9%), this difference was not statistically significant either. Nor were there any significant differences in survival, the 1-month, 1-year, and 5-year rates being 87.8%, 82.1%, and 68.8%, respectively, in the younger group and 85.7%, 78.6%, and 73.4%, respectively, in the older. CONCLUSIONS: Among carefully selected patients aged more than 65 years, HT can be performed without incurring greater risk of rejection, malignancy, or death than is found among recipients younger than 65 years.

Safety of statins when response is carefully monitored: a study of 336 heart recipients.

BACKGROUND: Statins are used as first-line drugs against hypercholesterolemia after heart transplantation. Randomized clinical trials have shown that they reduce cholesterol levels, and the incidence of rejection and coronary vasculopathy. Adverse effects have been related to the use of certain statins, high statin dosages, comorbidities, and coadministration with cyclosporine. However, estimation of the risk of adverse effects for a given patient is difficult. The aims of this study were to determine the incidence of various kinds of adverse effect of statins; to evaluate certain potential risk factors; and to assess the efficacy of early response to signs of adverse effects. METHODS: Between April 1991 and December 2003, we retrospectively evaluated 336 heart transplant patients (including 55 women) with regard to the occurrence of possible adverse effects of statins (rhabdomyolysis, myalgia, hepatotoxicity, high CK without muscle symptoms, and others). Resolution on reduction of dosage or discontinuance and/or change of statin were deemed to constitute confirmation of cause. Relations were sought between adverse effects and age, sex, immunosuppressive therapy, kidney failure, body mass index (BMI), arterial hypertension, and diabetes mellitus. RESULTS: Possible adverse events of statins were suffered by 60 patients, all of them men. The causal role of statins was confirmed in 41 (12.2% of all 336): hepatotoxicity was suffered by 13, high CK without muscle ache or weakness by 18, rhabdomyolysis by 5, myalgia by 3, and other effects by 2. The incidence of confirmed statin-related complications was higher among patients with BMI >29 kg/m(2) than among those with lower BMI (P = .055). None of the patients with confirmed statin-related complications needed dialysis, none died, and permanent suspension of statin treatment was only necessary in 13 cases (3.9% of the 336). CONCLUSIONS: Some 10% to 20% of HT patients appear to suffer adverse side effects of initial statin therapy. However, early detection of such effects through diligent clinical and analytical monitoring allows the therapy to be modified in time to minimize the appearance of severe complications. In only a minority of cases permanent suspension of statin therapy is necessary.