Impacto pronóstico de la enfermedad pulmonar obstructiva crónica y el asma bronquial en pacientes con insuficiencia cardiaca / Prognostic impact of chronic obstructive pulmonary disease and bronchial asthma in patients with heart failure

Propósito Analizar el impacto de la enfermedad pulmonar obstructiva crónica (EPOC) y el asma bronquial sobre el manejo terapéutico y el pronóstico de los pacientes con insuficiencia cardiaca (IC). Métodos Análisis de la información contenida en un registro clínico de pacientes remitidos a una unidad especializada de IC entre enero de 2010 y junio de 2022. Se compararon su perfil clínico, el tratamiento y el pronóstico en base a la presencia de EPOC o asma bronquial. El análisis de supervivencia se realizó mediante los métodos de Kaplan-Meier y Cox. La mediana de seguimiento fue de 1.493 días. Resultados Se estudiaron 2.577 pacientes, de los cuales 251 (9,7%) presentaban EPOC y 96 (3,7%), asma bronquial. Observamos diferencias significativas entre los tres grupos con respecto a la prescripción de betabloqueantes (EPOC=89,6%; asma=87,5%; no broncopatía=94,1%; p=0,002) e inhibidores del cotransportador de sodio-glucosa tipo2 (EPOC=35,1%; asma=50%; no broncopatía=38,3%; p=0,036). Además, los pacientes con patología bronquial recibieron con menor frecuencia un desfibrilador (EPOC=20,3%; asma=20,8%; no broncopatía=29%; p=0,004). La presencia de EPOC se asoció de forma independiente con mayor riesgo de muerte por cualquier causa (HR=1,64; IC95%: 1,33-2,02), muerte u hospitalización por IC (HR=1,47; IC95%: 1,22-1,76) y muerte cardiovascular o trasplante cardiaco (HR=1,39; IC95%: 1,08-1,79) en comparación con la ausencia de broncopatía. La presencia de asma bronquial no se asoció a un impacto significativo sobre los desenlaces analizados. Conclusiones La EPOC, pero no el asma bronquial, es un factor pronóstico adverso e independiente en pacientes con IC. (AU)

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=.002) and SGLT2 inhibitors (COPD=35.1%; asthma=50%; no bronchopathy=38.3%; P=.036). Also, patients with bronchial disease received less frequently a defibrillator (COPD=20.3%; asthma=20.8%; no broncopathy=29%; P=.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. (AU)

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.

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.

Perfil clínico y causas de muerte de los pacientes con insuficiencia cardíaca atendidos en una unidad especializada de Cardiología según su fracción de eyección / Clinical profile and causes of death according to ejection fraction in patients with heart failure cared for in a specialized Cardiology unit

Antecedente y objetivo: Los pacientes con insuficiencia cardíaca se caracterizan en 3 fenotipos en función de su fracción de eyección ventricular izquierda. El propósito de este estudio fue comparar el perfil clínico, el tratamiento, el pronóstico y las causas de muerte de los pacientes con insuficiencia cardíaca y fracción de eyección ventricular izquierda reducida (<40%, IC-FEr), preservada (≥50%, IC-FEp) o en rango medio (40-49%, IC-FErm). Metodología: Análisis de la información clínica recogida en un registro prospectivo de pacientes con insuficiencia cardíaca remitidos a una consulta monográfica de Cardiología entre 2010 y 2019. Resultados: Se estudiaron 1.404 pacientes con IC-FEr, 239 pacientes con IC-FErm y 266 pacientes con IC-FEp. Se observaron diferencias significativas entre los 3 grupos en relación con diversas características clínicas, y en cuanto a la tasa de prescripción de fármacos moduladores de la respuesta neurohormonal. La regresión de Cox multivariante reveló un incremento del riesgo de muerte por cualquier causa en los pacientes con IC-FEp (hazard-ratio 1,36; intervalo de confianza al 95% 1,03-1,80; p=0,028) e IC-FErm (hazard-ratio 1,36; intervalo de confianza al 95% 1,03-1,78; p=0,029) en comparación con los pacientes con IC-FEr. La insuficiencia cardíaca fue la causa más frecuente de muerte en los 3 grupos; se observó un mayor peso relativo de la muerte súbita en los pacientes con IC-FEr, mientras que las causas no cardiovasculares de muerte tuvieron un peso relativo mayor en los pacientes con IC-FEp e IC-FErm. Conclusiones: El estudio confirma la existencia de diferencias significativas en el perfil clínico, manejo terapéutico, pronóstico y causas de muerte de los pacientes con IC-FEr, IC-FErm e IC-FEp (AU)

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 1,404 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 (AU)

Clinical characteristics and long-term outcomes of patients undergoing combined heart-kidney transplantation: a single-center experience.

BACKGROUND: The purpose of the study was to describe clinical characteristics and long-term survival of patients undergoing combined heart-kidney transplant in a single center. METHODS: We conducted a retrospective analysis of 22 consecutive patients who underwent combined heart-kidney transplant at our institution between 1995 and 2013. Long-term outcomes were analyzed by means of the Kaplan-Meier method. RESULTS: Four patients underwent re-do transplant (2 cardiac re-transplants, 1 kidney re-transplant, and 1 combined heart-kidney re-transplant). Most frequent underlying cardiac conditions were coronary artery disease (54%), dilated cardiomyopathy (23%), and chronic rejection of a previous heart graft (18%). Known causes of chronic renal dysfunction were nephroangioesclerosis (23%), drug-related toxicity (14%), and Wegener granulomatosis (5%). Non-specified chronic renal dysfunction was present in 50% patients. In-hospital postoperative mortality rate was 5 of 22 (23%). Causes of early death were directly related to kidney transplant surgery in 4 of 5 (80%) patients. Among the remaining 17 patients who surmounted the postoperative period, long-term survival rates 1 year, 5 years, and 10 years after HKT were 88%, 82%, and 65%, respectively. Over a mean follow-up of 6.7 ± 6.4 years, cumulative incidences of cytomegalovirus infection, coronary allograft vasculopathy, malignancy, and acute cardiac graft rejection were 41%, 6%, 24%, and 41%, respectively. There was no episode of acute renal graft rejection. At the end of follow-up, all survivors (n = 11) were in functional New York Heart Association class I. Mean creatinine serum level was 1.68 mg/dL. CONCLUSIONS: In our experience, combined heart-kidney transplant is a feasible therapeutic option that yielded favorable long-term outcomes, with a low cumulative incidence of cardiac graft dysfunction. These results were obtained at the expense of a significant risk of early postoperative mortality, which was mainly related to complications of kidney transplant surgery.

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.

Steroid withdrawal during 5 years following heart transplantation, and the relationship between steroid dosage at 1-year follow-up and complications during the next 2 years: results from the RESTCO study.

BACKGROUND: Little information is available regarding the controversial issue of steroid withdrawal following heart transplantation (HT), or instead in the incidence of adverse steroid effects at dosages typically employed in Spain. METHODS: We analyzed the 5-year follow-up records of 1209 patients (82.5% men, aged ≥ 18 years) who underwent HT between 2000 and 2005 and survived at least 1 month in 13 Spanish centers. The incidences of first steroid withdrawal before 1, 3, and 5 years post-HT were expressed as Kaplan-Meier probability estimates. Three patient groups defined in accordance with steroid dosage at 1-year follow-up (0, ≤ 5, and >5 mg/d; groups A, B, and C, respectively) were compared with regard to the incidence of de novo hypertension, diabetes, and bone fractures over the following 2 years. RESULTS: The 5-year incidence of withdrawal was 28%, 21% of whom required reintroduction of steroids. Kaplan-Meier probabilities of withdrawal before 1, 3, and 5 years post-HT were 8.8% (95% confidence interval ([CI] 7.3%-10.7%), 27.8% (CI 25.2%-30.6%), and 30.2% (CI 27.5%-33.2%), respectively. At 1-year follow-up, 9.9% of patients were steroid-free, 28.9% were taking ≤ 5 mg/d, and 61.3% >5 mg/d. The 2-year incidence of de novo hypertension increased significantly (P = .012) from 13.5% to 29.6% to 35.3% in groups A, B, and C respectively. These groups did not differ significantly in regard to the 2-year incidence of diabetes or bone fractures. CONCLUSIONS: Reintroduction of steroids was required by 21% of the 28% of Spanish HT patients who has been weaned from steroids within 5 years of HT. The incidence of de novo hypertension between 1 and 3 years post-HT increased with steroid dosage at 1-year follow-up. De novo diabetes and bone fractures showed no similar significant association.

Indoleamine, 2-3 dioxygenase activity could be an early marker of graft rejection in heart transplantation.

BACKGROUND: The indoleamine, 2-3 dioxygenase (IDO) is an inducible intracellular enzyme with immunosuppressive effects mainly on lymphocyte populations. It has been postulated that indirect determination of IDO serum activity may be a marker of renal graft rejection, but its potential usefulness in heart transplantation (HT) is unknown. METHODS: This longitudinal study included 98 HT patients (83% males) who survived ≥1 year. Mean age was 54.14 ± 11.57 years. Serum IDO activity was analyzed one month after HT by means of high performance liquid chromatography and correlated with the cumulative incidence of acute rejection (AR) during one-year follow-up. AR was defined as biopsy-proven ≥ ISHLT grade 2R rejection or empirically treated non-biopsy-proven rejection. The study sample was divided into two groups: AR group (n = 51), including patients who experienced at least one AR episode during the first year after HT; No-AR group (N = 47), including the remaining patients. RESULTS: Mean serum IDO activity one month after HT was significantly higher (P = .021) in the AR group (3.32 ± 1.56) than in the no-AR group (2.62 ± 1.35). No significant association between serum IDO activity and gender (male: 3.1 ± 1.56, women: 2.43 ± 0.99, P = .092), recipient age (r = -.07, P = .943) or donor age (r = 0.108, P = 0.293) was observed. By means of binary logistic regression, an odds ratio of 1.4 [CI 95%: 1.033-1.876, P = .03] per unit increase of act-IDO was estimated, with no significant modification upon forced adjustment for age and sex. Mean glomerular filtration rate 1 month after HT was 67.01 ± 28.51 mL/min/m(2). No significant correlation between this parameter and serum IDO activity was observed (r = .160, P = .117). CONCLUSIONS: Our study suggests that serum IDO activity one month after HT might be associated with a higher risk of AR during one-year follow-up. This association seems to be independent of recipient gender, age or renal function.

Percutaneous coronary interventions and bypass surgery in patients with cardiac allograft vasculopathy: a single-center experience.

INTRODUCTION: Cardiac allograft vasculopathy (CAV) remains a major impediment to long-term survival after heart transplantation (HT). Limited data exist regarding the impact of coronary revascularization in these patients. OBJECTIVE: To evaluate the outcomes of revascularization procedures in patients with CAV compared with patients who did not undergo revascularization. METHODS: Retrospective analysis of 249 patients who underwent HT at our center between June 1998 and December 2009 and who were examined by coronary angiography after HT. We included patients with moderate or severe CAV according to the International Society for Heart and Lung Transplantation (ISHLT) nomenclature to evaluated outcomes after revascularization or diagnostic angiography. Major adverse cardiovascular events (MACE) comprised death, acute coronary syndrome, coronary revascularization, admission because of heart failure not due to an acute rejection episode, and cardiac retransplantation. RESULTS: Moderate or severe CAV was detected in 43 patients. Twelve (27.9%) underwent coronary revascularization: eight percutaneous interventions and four bypass surgeries. Indications for revascularization were symptomatic ischemia or noninvasive evidence of ischemia (n = 6, 14.0%) or high-risk asymptomatic CAV (n = 6; 14.0%), namely, lesions located in the left main or proximal anterior descending arteries or multivessel disease with left ventricular dysfunction. The remaining 31 (72.1%), who did not undergo revascularization showed an absence of ischemia during exercise echocardiography (n = 11; 25.6%) or diffuse disease not amenable to revascularization (n = 20; 46.5%). During a mean follow-up of 3.0 ± 2.4 years, MACE occurred in three revascularized patients (25.0%), in one with absence of stress-induced ischemia (9.1%) and in 13 with nonrevascularizable disease (65%; P = .012). CONCLUSIONS: Revascularization procedures were effective in HT patients with evidence of ischemia or high-risk CAV. Patients with absence of stress-induced ischemia have a good prognosis without revascularization. On the other hand, diffuse nonrevascularizable CAV is associated with a poor prognosis.

Cumulative incidence of cytomegalovirus infection and disease after heart transplantation in the last decade: effect of preemptive therapy.

INTRODUCTION: Infection by cytomegalovirus (CMV) is a major concern in solid organ transplant (SOT). It increases morbidity and mortality. The prevalence of CMV asymptomatic infection and disease is variable among centers, partially related to immunosuppressive protocols and therapeutic strategies to treat CMV. Induction therapy with basiliximab is associated with fewer CMV infections than therapy with OKT3. In our center, universal prophylaxis is used in the first month post-heart transplant (HT) and preemptive therapy (PET) is used later, according to viral load monitoring. OBJECTIVE: To analyze the short- and long-term incidence of CMV infection and disease post-HT according to CMV status of recipient (R)/donor (D) in a cohort of patients who received induction therapy with basiliximab. MATERIALS AND METHODS: Retrospective analysis of 201 consecutive patients over 18 years of age who underwent HT between February 2001 (when induction therapy with basiliximab was initiated) and June 2011. Patients were divided in two risk subgroups of developing CMV disease: high-risk (D+/R- or D-/R- who received blood transfusions or R-, or donor with unknown serostatus) and low-risk (any other combination). RESULTS: Of 201 patients (mean age 53.81 ± 11.61 years, 81.1% men). 165 patients were classified in the low-risk and 36 in the high-risk group. The cumulative incidence of asymptomatic CMV infection during the first year post-HT was 47%: 46% in the low-risk and 50% in the high-risk group (P = .668). The incidence of CMV disease during the first year post-HT was 7.5%: 3.6% in the low-risk versus 25% in the high-risk group (P < .001). CONCLUSIONS: In our series, asymptomatic CMV infection after HT is frequent, affecting almost 50% of patients. However, the incidence of CMV disease is very low (7.5%), which confirms the effectiveness of PET. The higher incidence of disease in the high-risk group recommends closer monitoring of viral load in these patients or performing more prolonged universal prophylaxis.

Influence of steroid dosage, withdrawal, and reinstatement on survival after heart transplantation: results from the RESTCO study.

BACKGROUND: Little information is available regarding the consequences of steroid withdrawal following heart transplantation (HT) in Spain. METHODS: We analyzed the records of 1068 patients (81.6% men) who underwent HT between 2000 and 2005 in 13 Spanish centers who were aged ≥ 18 years and who survived at least 1 year. Death rates and Kaplan-Meier survival curves for 1 to 5 years post-HT were compared among four groups: groups A and B, patients on steroids throughout the first 5 years post-HT at dosages of ≤ 5 mg/d between 1-year and 5-year follow-up (group A; n = 148), or >5 mg/d for some part of this period (group B; n = 578). Groups C and D were patients from whom steroids were at some point withdrawn including group D (n = 73) with and group C (n = 269) without subsequent reintroduction into the maintenance regimen. RESULTS: Steroids were withdrawn at 1.6 ± 0.9 years post-HT in group C, and 1.7 ± 1.2 years post-HT in group D. The death rate between 1- and 5-year follow-up (deaths per 1000 person-years) was 44.3% (95% confidence interval 26.2-62.5) in group A, 42.6% (33.7-51.4) in group B, 30.5% (19.6-41.4) in group C, and 47.8% (21.8-73.7) in group D. There was no significant difference among them or among Kaplan-Meier survival curves of the four groups (P = .34 in both cases). Comparison of combined groups C + D with groups A + B showed no evidence of a greater mortality among combined groups C + D. CONCLUSIONS: The late withdrawal of steroids following HT was not associated with increased mortality.

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.

Prevalence of donor-transmitted coronary artery disease and its influence on heart transplant outcomes.

BACKGROUND: It is uncertain whether donor-transmitted coronary artery disease (DTCAD) affects heart transplant (HT) recipients. METHODS: This retrospective analysis includes records of all patients who underwent a HT at our center over an 8-year period, who survived for at least 1 month, and who were examined by coronary angiography within 2 months post-HT. We distinguished angiographically from keep ultrasonography (IVUS) detected DTCAD. Major adverse cardiovascular events (MACE) comprised death, myocardial infarction, unstable angina, coronary revascularization, and admission because of heart failure not due to an acute rejection episode. RESULTS: Among the 171 patients of mean age 53±13 years and including 83% men, 65 (38%) were evaluated by IVUS. Donors were aged 40±14 years (range=14-73). Angiographic DTCAD affected seven patients (4.1%), and IVUS-detected DTCAD, 35 (53.8% of those examined by IVUS). DTCAD donors were older than non-DTCAD donors, by an average of 13 years (P=.001) for angiographic DTCAD and 18 years (P<.0001) for IVUS-detected DTCAD. Two patients underwent percutaneous revascularization upon detection of angiographic DTCAD. The angiographic- and IVUS-detected DTCAD groups did not differ significantly from the corresponding non-DTCAD groups as regards MACE incidence during 54±41 and 38±20 months follow-up, respectively. Cox regression analysis with adjustment for relevant confounders confirmed that IVUS-detected DTCAD was not a predictor of MACE (hazard ratio 1.2, 95% confidence interval 0.2-8.1). CONCLUSIONS: Among HT patients surviving≥1 month, angiographic- and IVUS-detected DTCAD showed prevalences of <10% and >50%, respectively. Neither detection method was associated with a greater long-term incidence of MACE.

Conversion of heart transplant patients from standard to sustained-release tacrolimus requires a dosage increase.

INTRODUCTION: It has been suggested that for adequate maintenance of tacrolimus levels, the total daily dosage should be increased when switching from the conventional twice-daily regimen tacrolimus (CT) to once-daily sustained-release tacrolimus (SR-T). OBJECTIVE: To evaluate the safety and efficacy of a 25% increase in daily dosage when switching heart transplant (HT) patients from CT to SR-T. METHODS: We switched 75 HT patients including 72% males and an overall mean age of 55.6 years from CT to SR-T using a 25% increase in daily dosage. We screened for adverse events by measurements of lipids, creatinine, glycemia, and tacrolimus in blood samples taken at 1, 3, 7, and 12 weeks after the conversion, as well as by repeated echocardiography and routine clinical examinations. RESULTS: Just two patients (2.7%) were returned to CT because of failure of SR-T to attain therapeutic levels. In the remainder of subjects, tacrolimus levels remained stable, with trough values of 8.7±3.2, 8.7±2.9, 8.3±2.6, and 7.5±2.0 mg/dL, respectively. Twenty-three patients (31%) required no dosage change in the first 3 months, but 44 (33%) required one or two changes. No departure from therapeutic levels was associated with rejection; there was no case of severe intercurrent infection. We did not observe significant changes in glycemia, creatinine, lipid profile, or blood pressure. CONCLUSIONS: Administration of SR-T at a dosage 25% higher than the daily dosage of CT was safe. It ensured adequate tacrolimus levels in one-third of patients. Nevertheless, strict analytical surveillance is necessary during the initial months to allow dosage adjustments and to detect the minority of patients for whom SR-T does not achieve therapeutic tacrolimus levels.

Long-term outcome in heart transplant patients with pretransplant malignancies.

INTRODUCTION: Neoplasms have classically been considered a contraindication for heart transplantation (HT) because of the possibility of recurrence during immunosuppressive therapy. There are few cases of patients who suffered a pretransplant malignancy (PTM); however the appropriate interval free of a malignancy (IFoM) before heart transplantation is unclear. Our study sought to determine the long-term outcomes after transplantation among patients who had suffered a prior neoplasm compared with our overall cohort. METHODS: This retrospective, single-center study included 595 heart transplant recipients ungrafted between 1991 and 2009. We determined PTM location, histology, and IFoM. We examined donor and recipient factors and post-HT data of rejections, infections, neoplasms, and survival associated with a poor prognosis. RESULTS: Twelve patients with different types, locations, and histological grades of PTM represented 66.7% women versus 16.1% women in the overall series (P<.01). There were no differences in recipient age or clinical characteristics (diabetes mellitus, arterial hypertension, previous renal failure, or New York Heart Association class), number of emergency cases, or graft ischemia time. Mean IFoM was 114.3 months (range=5.3-350.4). After heart transplantation, there were no significant differences between the number of infections (47.9%; n=[279] vs 33.3% n=4; P=.39), rejection episodes (44.4% [259] vs 50% [6], P=0.77) or post-HT malignancies (12.2% [70] vs 0%, P=0.37) between the overall series and the patients with PTM. None of the patients with PTM suffered a recurrence of the neoplasm. Actuarial survivals at 1, 3, and 5 years were 82%, 76%, and 70% among patients without PTM and 75%, 75%, and 56% among those with PTM (P=.70). CONCLUSION: Patients with PTM and an appropriate IFoM with regard to tumor lineage showed similar rates of survival and complications as those of the overall series. This series suggested that appropriately selected patients with a cured PTM can be candidates for HT.

Efficacy and tolerance of different types of prophylaxis for prevention of early aspergillosis after heart transplantation.

BACKGROUND: The incidence of aspergillosis (ASP) after heart transplantation (HTx) is low (<4%-5%), but the mortality is high (>78%). AIM: To determine the incidence of ASP in the first 3 months post-HTx according to the type of prophylaxis and assess the tolerance to these regimens. METHODS: This retrospective study of 571 adult HTx patients engrafted from 1991 to December 2009 included 83% males with an overall group age of 54.9±11 years. Three types of prophylaxis were compared: group A was no prophylaxis (n=99; 1991-1994); group B, itraconazole for 3 months (n=352; 1995-November 2004); and group C, inhaled amphotericin for 3 months (n=120; December 2004-2009). The dependent variables were the presence and severity or tracheobronchitis and invasive/disseminated disease as well as, prognosis of Aspergillus infection and tolerance to the regimen. RESULTS: The incidences of aspergillosis were 5% in group A (n=5); 1.4% in group B (n=5); and 0% in group C. Significant differences were observed between groups A versus B (P=.030) and between groups A versus C (P=.013), but there were no differences between groups B versus C. In terms of severity, there were no significant differences among the five cases of tracheobronchitis (20% group A/80% group B), five of invasive/disseminated disease (80% group A/20% group B). There were two deaths (20%) from invasive/disseminated ASP at 0.67 months after diagnosis. The mean time from HTx to ASP was 0.98±0.40 months. There were no adverse effects associated with itraconazole, but they occurred in 3/120 patients (2.5%) treated with inhaled amphotericin, all of whom were on mechanical ventilation, developing respiratory failure requiring amphotericin withdrawal. CONCLUSIONS: Prophylaxis with itraconazole or inhaled amphotericin was effective for the prevention and severity of pulmonary ASP in the first 3 months post-HTx. Although the incidence of early ASP was low in our series, the 20% mortality rate justified the use of preventive measures. Tolerance to both prophylactic treatments was good.

Gene expression profiling for monitoring graft rejection in heart transplant recipients.

Heart transplantation is a life-prolonging therapy for many patients with stage D heart failure and other forms of advanced heart disease. However, graft rejection and/or immunosuppression-related side effects are major causes of morbidity and death among heart transplant patients. Graft rejection monitoring remains a challenge. It would be desirable to be able to detect rejection early enough and specifically enough to prevent allograft dysfunction without unnecessary overimmunosuppression. Hitherto, the main technique employed in monitoring the rejection status of a transplanted heart has been endomyocardial biopsy (EMB), which allows rejection to be screened for and monitored on the basis of the extent and distribution of lymphocytic infiltrates and associated myocardial damage. However, EMB has significant limitations: it is invasive, its sensitivity is limited by sampling efficacy, and it suffers from considerable between-observer variability. Although many noninvasive techniques have been investigated, none so far has proved able to match the performance of EMB. Currently, a multiparametric approach is employed that comprises clinical examination for signs or symptoms of heart failure, EMBs, drug level monitoring, allograft function tests (mainly echocardiographic studies), and screening for allograft vasculopathy. Gene expression profiling may be a promising tool for this purpose.

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.

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.