Gender differences in heart transplantation: Twenty-five year trends in the nationwide Spanish heart transplant registry.

The study of gender differences may lead into improvement in patient care. We have aimed to identify the gender differences in heart transplantation (HT) of adult HT recipients in Spain and their evolution in a study covering the years 1993-2017 in which 6740 HT (20.6% in women) were performed. HT indication rate per million inhabitants was lower in women, remaining basically unchanged during the 25-year study period. HT rate was higher in men, although this decreased over the 25-year study period. Type of heart disease differed in men versus women (p < .001): ischemic heart disease 47.6% versus 22.5%, dilated cardiomyopathy 41.3% versus 34.6%, or other 36% versus 17.8%, respectively. Men were more frequently diabetics (18% vs. 13.1% p < .001), hypertensives (33.1% vs. 24% p < .001), and smokers (21.7% vs. 12.9% p < .001), respectively. Women had more pre-HT malignancies (7.1% vs. 2.8% p < .001), and their clinical status was worse at HT due to renal function and mechanical ventilation. Adjusted survival (p = .198) and most of the mortality-related variables were similar in men and women. Death occurred more frequently in women due to rejection (7.9% vs. 5.1% p < .001) and primary failure (18.2% vs. 12.5% p < .001) and in men due to malignancies (15.1% vs. 6.6% p < .001).

Myocardial deformation and acute cellular rejection after heart transplantation: Impact of inter-vendor variability in diagnostic effectiveness.

PURPOSE: Our objective was to investigate the impact of inter-vendor variability in the ability of myocardial strain analysis to detect acute cellular rejection (ACR) in heart transplant recipients. METHODS: We performed serial echocardiographic examinations in 18 consecutive adult heart transplanted patients, in their first year post-transplantation, within 3 hours of the routine surveillance endomyocardial biopsies (EMB) in a single center. Myocardial strain was analyzed using two software in two different institutions, and inter-vendor variability of strain values and its association with ACR (any grade or grade ≥2R) was investigated. The parameter of comparison was the peak value of the average curve of strain during the entire cardiac cycle. RESULTS: A total of 147 pairs of EMB-echocardiogram were performed, 65 with no ACR, 63 with ACR grade 1R, and 19 with ACR grade ≥2R. Intra-class correlation coefficients for left ventricle longitudinal, radial, and circumferential strain were 0.38, 0.39, and 0.77, respectively, and 0.32 for right ventricular longitudinal strain. Neither software found significant association of left ventricular longitudinal strain with rejection. Grade ≥2R ACR was associated with left ventricular circumferential strain measured with the first software and with left ventricular radial strain with the other; and ACR of any grade was only significantly associated with right ventricle longitudinal strain measured with the first software. CONCLUSIONS: Inter-vendor reproducibility of strain values was low in this study. Some strain parameters were associated to ACR, although these results were inconsistent between two commercially available software. Specific validation of each software is warranted for this clinical indication.

Spanish Heart Transplantation Registry. 26th Official Report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984-2014).

INTRODUCTION AND OBJECTIVES: We present the characteristics and outcomes of heart transplantation in Spain since it was first performed in 1984. METHODS: A descriptive analysis of the characteristics of recipients, donors, the surgical procedure, and the outcomes of heart transplantations performed in Spain until 31 December 2014. RESULTS: In 2014, 266 procedures were performed, making a time series of 7289 transplantations. The temporal analysis confirmed a significant worsening of the clinical profile of recipients (higher percentage of older patients, patients with severe renal failure, insulin-dependent diabetes, previous cardiac surgery, and previous mechanical ventilation), of donors (higher percentage of older donors and greater weight mismatch), and of the procedure (higher percentage of emergency transplantations, reaching 41.4% in 2014, and ischemia time>240min). Mechanical assist devices were used less than in 2013; in 2014 they were used in 18.8% of all transplant recipients. Survival at 1, 5, 10, and 15 years was 76%, 65%, 52%, and 38%, respectively, and has remained stable since 1995. CONCLUSIONS: Cardiac transplantation activity in Spain has remained stable in recent years, at around 250 procedures per year. Despite a clear deterioration in donor and recipient characteristics and surgical times, the mortality outcomes have remained comparable to those of previous periods in our environment. The growing use of circulatory assist devices before transplantation is also confirmed.

Spanish Heart Transplantation Registry. 25th official report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984-2013).

INTRODUCTION AND OBJECTIVES: The present article reports the characteristics and outcome of heart transplantation in Spain since it was first performed in May 1984. METHODS: We provide a descriptive analysis of the characteristics of the recipients, the donors, the surgical procedure, and results of the heart transplantations performed in Spain until 31 December 2013. RESULTS: During 2013, a total of 248 transplantation procedures were carried out, bringing the time series to a total of 7023 transplantations. The temporal analysis confirms a significant deterioration in the clinical profile of the recipients (higher percentage of older patients, severe renal failure, insulin-dependent diabetes mellitus, previous heart surgery, mechanical ventilation), of the donors (higher proportion of older donors and greater weight mismatch), and of the procedure (higher percentage of emergency transplantations which, in 2013, reached 49%, and with ischemia times > 240min). There was a marked increase in the use of circulatory assist devices prior to transplantation which, in 2013, were employed in 25.2% of all the patients. The survivals at 1, 5, 10, and 15 years were 76%, 65%, 52%, and 37%, respectively, and have remained stable since 1995. CONCLUSIONS: Heart transplantation activity in Spain remains stable in recent years, with around 250 procedures a year. Despite the clear deterioration in the clinical characteristics of the donors and recipients, and lengthening of the operative times, the results in terms of mortality continue to be comparable to those reported in our neighboring countries, and a growing use of circulatory assist devices prior to transplantation is confirmed.

Long-term survival in elderly patients with stable coronary disease.

BACKGROUND: This study aimed to assess long-term prognosis of stable coronary artery disease (sCAD) in patients aged ≥ 75 years and to identify clinical predictors of cardiovascular and overall mortality. MATERIALS AND METHODS: From February 2000 to January 2007, 391 outpatients aged ≥ 75 years (median 78 years, interquartile range [IQR] 76-81 years, 66% male) with sCAD were recruited in this prospective cohort study. Associations of baseline variables with long-term cardiovascular and all-cause death were investigated. RESULTS: After up to 11 years of follow-up (median 4 years, IQR 2-6 years), 89 patients died (23%, 5·45%/year), 35 from cardiovascular causes (9%, 2·14%/year). Multivariate analysis identified family history of coronary disease (HR 4·28, 95% CI 1·22-15·02, P = 0·02), baseline atrial fibrillation (HR 3·18, 95% CI 1·37-7·39, P = 0·007), age (HR 1·61 per 5 year increase, 95% CI 1·04-2·50, P = 0·03), resting heart rate (HR 1·26 per 5 bpm increase, 95% CI 1·09-1·47, P = 0·003) and previous revascularization (HR 0·17, 95% CI 0·04-0·77, P = 0·02) as independent predictors of cardiovascular death, and previous acute coronary syndrome (HR 4·93, 95% CI 1·49-16·30, P = 0·009), baseline atrial fibrillation (HR 1·96, 95% CI 1·12-3·43, P = 0·02), tobacco use (HR 1·69, 95% CI 1·00-2·84, P = 0·049 for ex-smoking and HR 6·78, 95% CI 0·89-51·47, P = 0·06 for active smoking), age (HR 1·58 per 5 year increase, 95% CI 1·18-2·11, P = 0·002), resting heart rate (HR 1·10 per 5 bpm increase, 95% CI 1·00-1·22, P = 0·05) and diastolic blood pressure (HR 0·97, 95% CI 0·94-0·99, P = 0·01) as independent predictors of overall mortality. CONCLUSIONS: In this study, 4-years overall mortality was 23% among elderly patients with sCAD. Simple clinical variables can identify patients at higher risk of mortality.

Spanish Heart Transplantation Registry. 24th official report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984-2012).

INTRODUCTION AND OBJECTIVES: The present article reports the characteristics and results of heart transplantation in Spain since this therapeutic modality was first used in May 1984. METHODS: We summarize the main features of recipients, donors, and surgical procedures, as well as the results of all heart transplantations performed in Spain until December 31, 2012. RESULTS: A total of 247 heart transplantations were performed in 2012. The whole series consisted of 6775 procedures. Recent years have seen a progressive worsening in the clinical characteristics of recipients (34% aged over 60 years, 22% with severe kidney failure, 17% with insulin-dependent diabetes, 29% with previous heart surgery, 16% under mechanical ventilation) and donors (38% aged over 45 years, 26% with recipient: donor weight mismatch>20%), and in surgical conditions (29% of procedures at >4 h ischemia and 36% as emergency transplantations). The probability of survival at 1, 5, 10, and 15 years of follow-up was 78%, 67%, 53%, and 38%, respectively. These results have remained stable since 1995. CONCLUSIONS: In recent years, the number of heart transplantations/year in Spain has remained stable at around 250. Despite the worsening of recipient and donor clinical characteristics and of time-to-surgery, the results in terms of mortality have remained stable and compare favorably with those of other countries.

Spanish registry on heart transplantation. 23rd official report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984-2011).

INTRODUCTION AND OBJECTIVES: The purpose of this article is to present the results obtained from heart transplantation since this therapeutic modality first began to be used in Spain in May 1984. METHODS: A descriptive analysis was performed of all heart transplantations performed until 31 December 2011. RESULTS: The total number of transplantations is 6528. The average clinical profile of the Spanish heart transplantation patient in 2011 was that of a 53-year-old male who had been diagnosed with nonrevascularizable ischemic heart disease accompanied by severely depressed ventricular function and poor functional status. The implanted heart was typically from a 38-year-old donor who had died from brain hemorrhage. The average waiting list time was 122 days. Mean survival time has progressively increased over the years. For the overall series, the probability of survival at 1, 5, 10, and 15 years was 77%, 66%, 53%, and 39%, respectively, whereas over the past 5 years the probability of survival at 1 and 5 years was 80% and 73%, respectively. The most frequent cause of death was acute graft failure (16%), followed by infection (15.6%), the combination of graft vascular disease and sudden death (14%), tumors (12.3%) and acute rejection (7.7%). CONCLUSIONS: The survival rates obtained in Spain from heart transplantation, especially in recent years, place heart transplantation as the treatment of choice in irreversible heart failure patients without other established medical or surgical options.

[Spanish registry on heart transplantation. 22nd official report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984-2010)]. / Registro Español de Trasplante Cardiaco. XXII Informe Oficial de la Sección de Insuficiencia Cardiaca y Trasplante Cardiaco de la Sociedad Española de Cardiología (1984-2010).

INTRODUCTION AND OBJECTIVES: The purpose of this report is to present the results obtained with heart transplantation since this therapeutic modality first began to be used in Spain in May 1984. METHODS: A descriptive analysis was performed of all heart transplantation performed until December 31, 2010. RESULTS: The total number of transplants is 6291. The average clinical profile of the Spanish heart transplant patient in 2010 was that of a 53-year-old male diagnosed with nonrevascularizable ischemic heart disease accompanied by severely depressed ventricular function and poor functional status. The implanted heart was typically from a 39-year-old donor who had died from brain hemorrhage. The average time on the waiting list was 99 days. Mean survival time has progressively increased over the years. Whereas for the overall series, the probability of survival at 1, 5, 10, and 15 years was 78%, 67%, 54%, and 40%, respectively, over the past 5 years the probability of survival at 1 and 5 years was 85% and 73%, respectively. The most frequent cause of death was acute graft failure (16.5%), followed by infection (15.9%), the combination of graft vascular disease and sudden death (13.7%), tumors (11.9%), and acute rejection (7.8%). CONCLUSIONS: The transplantation survival rates obtained in Spain, especially in recent years, position heart transplant as the treatment of choice in irreversible heart failure patients without other established medical or surgical options.

Spanish Heart Transplantation Registry. 21st Official Report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984-2009).

INTRODUCTION AND OBJECTIVES: The purpose of this report is to present the results obtained with heart transplantation in Spain from the first use of this therapeutic modality in May 1984. METHODS: A descriptive analysis of all heart transplantations performed up to December 31, 2009 is presented. RESULTS: In total, 6048 transplants were carried out. The typical clinical profile of a Spanish heart transplant patient in 2009 was that of a 53-year-old male who had been diagnosed with nonrevascularizable ischemic heart disease and who had severely impaired ventricular function and a poor functional status. The implanted heart typically came from a donor who had died from a brain hemorrhage (mean age 37 years) and the average time on the waiting list was 106 days. Mean survival time has increased progressively over the years. Whereas for the whole time series, the probability of survival at 1, 5, 10 and 15 years was 78%, 67%, 53% and 40%, respectively, for the past 5 years, the probability of survival at 1 and 5 years was 85% and 73%, respectively. The most frequent cause of death was acute graft failure (17%), followed by infection (16%), the combination of graft vascular disease and sudden death (14%), tumor (12%) and acute rejection (8%). CONCLUSIONS: The survival rates obtained in Spain with heart transplantation, especially in recent years, make the procedure the treatment of choice for patients who have irreversible heart failure and a poor functional status and for whom there are few other established medical or surgical options.

Clinical recommendations for the use of everolimus in heart transplantation.

Proliferation signal inhibitors (PSIs), everolimus (EVL), and sirolimus are a group of immunosuppressor agents indicated for the prevention of acute rejection in adult heart transplant recipients. Proliferation signal inhibitors have a mechanism of action with both immunosuppressive and antiproliferative effects, representing an especially interesting treatment option for the prevention and management of some specific conditions in heart transplant population, such as graft vasculopathy or malignancies. Proliferation signal inhibitors have been observed to work synergistically with calcineurin inhibitors (CNIs). Data from clinical trials and from the growing clinical experience show that when administered concomitantly with CNIs, PSIs allow significant dose reductions of the latter without loss of efficacy, a fact that has been associated with stabilization or significant improvement in renal function in patients with CNI-induced nephrotoxicity. The purpose of this article was to review the current knowledge of the role of PSIs in heart transplantation to provide recommendations for the proper use of EVL in cardiac transplant recipients, including indications, treatment regimens, monitoring, and management of the adverse events.

[Clinical characteristics and prognosis of infective endocarditis in women]. / Características clínicas y pronóstico de la endocarditis infecciosa en la mujer.

INTRODUCTION AND OBJECTIVES: Little is known about the prognosis of infective endocarditis in women. The objective of this study was to determine the clinical characteristics and prognosis of infective endocarditis in women diagnosed with the condition at our center during the last 20 years. METHODS: Comparative analysis of 288 patients diagnosed with infective endocarditis between 1987 and 2006. Of these, 104 (36%) were women. RESULTS: Mean age was similar in the two sexes, at 50 (18) years for men and 52 (21) years for women, as was the incidence of early and late prosthetic valve endocarditis: the incidence of early prosthetic endocarditis was 42% in men and 49% in women. Infection occurred more frequently in the mitral valve in women (54% vs. 39%) and more frequently in the aortic valve in men (50% vs. 29%; P< .01). The severe complication rate during the active disease phase was similar in the two sexes (76% for women and 73% for men). Fewer women underwent surgery during the active disease phase (44% versus 58%; P< .03), and there was a trend to higher mortality in women (24% versus 20.7%; (24% versus 20.7%; P<.1). The 5-year survival rate was similar in the two sexes, at 85% in men and 83% in women. CONCLUSIONS: The clinical characteristics of infective endocarditis were similar in men and women. However, women underwent surgery less frequently despite a similar rate of severe complications during the active disease phase.

Influence of induction therapy, immunosuppressive regimen and anti-viral prophylaxis on development of lymphomas after heart transplantation: data from the Spanish Post-Heart Transplant Tumour Registry.

BACKGROUND: Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma. METHODS: This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti-interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003. RESULTS: Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used. CONCLUSIONS: Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively.