Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.

Introduction and objectives: Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies. Methods: Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA. Results: Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group. Conclusion: Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.

Soluble HLA-G levels in heart transplant recipients: Dynamics and correlation with clinical outcomes.

PURPOSE: To describe the evolution of the serum levels of soluble HLA-G (s-HLA-G) during the first 12 months after heart transplantation (HT) and to correlate it with clinical outcomes. METHODS: Observational study based in a single-center cohort of 59 patients who underwent HT between December-2003 and March-2010. Soluble HLA-G levels were measured from serum samples extracted before HT, and 1, 3, 6 and 12 months after HT. The cumulative burden of s-HLA-G expression during the first post-transplant year was assessed by means of the area under the curve (AUC) of s-HLA-G levels over time and correlated with the acute rejection burden -as assessed by a rejection score-, the presence of coronary allograft vasculopathy (CAV) grade ≥ 1 and infections during the first post-transplant year; as well as with long-term patient and graft survival. Mean follow-up was 12.4 years. RESULTS: Soluble HLA-G levels decreased over the first post-transplant year (p = 0.020). The AUC of s-HLA-G levels during the first post-transplant year was higher among patients with infections vs. those without infections (p = 0.006). No association was found between the AUC of s-HLA-G levels and the burden of acute rejection or the development of CAV. Overall long-term survival, long-term survival free of late graft failure and cancer-free survival were not significantly different in patients with an AUC of s-HLA-G levels higher or lower than the median of the study population. CONCLUSIONS: Soluble HLA-G levels decreased over the first year after HT. Higher HLA-G expression was associated with a higher frequency of infections, but not with the burden of acute rejection or the development of CAV, neither with long-term patient or graft survival.

Cancer in patients with heart failure: Incidence, risk factors and prognostic impact.

AIMS: To assess the incidence of cancer diagnosis and cancer-related mortality in patients with heart failure (HF). METHODS: Observational study based in a prospective cohort of patients with HF referred to a specialized Spanish clinic between 2010 and 2019. The observed incidence of malignancies (excluding non-melanoma skin cancer) was compared to that expected for the general Spanish population according to the Global Cancer Observatory. RESULTS: We studied 1909 consecutive patients with HF. Over a median follow-up of 4.07 years, 165 new cases of malignancy were diagnosed. Observed age-standardized incidence rates of cancer were 861 (95% CI 618.4-2159.4) cases per 100,000 patients-years in men and 728.5 (95% CI 451.1-4308.7) cases per 100,000 patients-years in women; while age-standardized incidence rates of cancer expected for the general Spanish population were 479.4 cases per 100,000 patients-years in men (risk ratio = 1.80) and 295.5 cases per 100,000 patients-years in women (risk ratio = 2.46). Both a history of pre-existing malignancy at baseline and the development of new malignancies during follow-up were associated with reduced survival. Observed age-standardized cancer-related mortality was 344.1 (95% CI 202.1-1675) deaths per 100,000 patient-years in men and 217.0 (95% CI 32.8-3949.3) deaths per 100,000 patient-years in women; while age-standardized cancer-related mortality expected for the general Spanish population was 201.4 deaths per 100,000 patients-years in men (risk ratio = 1.71) and 96.2 deaths per 100,000 patients-years in women (risk ratio = 2.26). CONCLUSION: Patients with HF showed higher incidence rates of cancer diagnosis and cancer-related mortality than those expected for the general population.

Determinants of maximal oxygen uptake in patients with heart failure.

AIMS: Maximum oxygen uptake (VO2max ) is an essential parameter to assess functional capacity of patients with heart failure (HF). We aimed to identify clinical factors that determine its value, as they have not been well characterized yet. METHODS: We conducted a retrospective, observational, single-centre study of 362 consecutive patients with HF who underwent cardiopulmonary exercise testing (CPET) as part of standard clinical assessment since 2009-2019. CPET was performed on treadmill, according to Bruce's protocol (n = 360) or Naughton's protocol (n = 2). We performed multivariable linear regression analyses in order to identify independent clinical predictors associated with peak VO2max . RESULTS: Mean age of study patients was 57.3 ± 10.9 years, mean left ventricular ejection fraction was 32.8 ± 14.2%, and mean VO2max was 19.8 ± 5.2 mL/kg/min. Eighty-nine (24.6%) patients were women, and 114 (31.5%) had ischaemic heart disease. Multivariable linear regression analysis identified six independent clinical predictors of VO2max , including NYHA class (B coefficient = -2.585; P < 0.001), age (B coefficient per 1 year = -0.104; P < 0.001), tricuspid annulus plane systolic excursion (B coefficient per 1 mm = +0.209; P < 0.001), body mass index (B coefficient per 1 kg/m2  = -0.172; P = 0.002), haemoglobin (B coefficient per 1 g/dL = +0.418; P = 0.007) and NT-proBNP (B coefficient per 1000 pg/mL = -0.142; P = 0.019). CONCLUSIONS: The severity of HF (NYHA class, NT-proBNP) as well as age, body composition and haemoglobin levels influence significantly exercise capacity. In patients with HF, the right ventricular systolic function is of greater importance for the physical capacity than the left ventricular systolic function.

Comparación de mortalidad pronosticada y mortalidad observada en pacientes con insuficiencia cardiaca tratados en una unidad clínica especializada / Comparison of predicted and observed mortality in patients with heart failure treated at a specialized unit

INTRODUCCIÓN Y OBJETIVOS: Analizar la supervivencia de los pacientes con insuficiencia cardiaca (IC) tratados en una unidad especializada. MÉTODOS: Estudio prospectivo de una cohorte de pacientes con IC tratados en una unidad especializada entre 2011 y 2017. Se comparó la mortalidad observada a 1 y 3 años con la mortalidad pronosticada por la puntuación de riesgo del Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC). RESULTADOS: Se estudió a 1.280 pacientes, con una mediana de la puntuación MAGGIC de 19 [intervalo intercuartílico, 13-24]. Las tasas de prescripción de bloqueadores beta, inhibidores de la enzima de conversión de la angiotensina, antagonistas del receptor de la angiotensina II, antagonistas del receptor de mineralcorticoides y sacubitrilo-valsartán fueron del 93, el 67, el 22, el 73 y el 16% respectivamente. La puntuación MAGGIC mostró una discriminación adecuada de la mortalidad a 1 año (estadístico c=0,71) y a 3 años (estadístico c=0,76). La mortalidad observada fue significativamente menor que la pronosticada, tanto a 1 año (el 6,2 frente al 10,9%; cociente observada/pronosticada=0,57; p < 0,001) como a 3 años (el 16,7 frente al 27,7%; cociente observada/pronosticada=0,60; p < 0,001). Esta discrepancia se observó en diversos subgrupos, excepto en los pacientes mayores de 70 años (el 29,9 frente al 34,7%; cociente observada/pronosticada=0,86; p = 0,126) y en pacientes con fracción de eyección> 40% (el 19,6 frente al 20,7%; cociente observada/pronosticada=0,95; p = 0,640). CONCLUSIONES: Los pacientes con IC tratados en una unidad especializada presentaron una mortalidad inferior a la pronosticada por la puntuación MAGGIC

INTRODUCTION AND OBJECTIVES: To analyze survival in heart failure (HF) patients treated at a specialized unit. METHODS: Prospective cohort-based study of HF patients treated at a specialized unit from 2011 to 2017. Observed 1- and 3-year mortality rates were compared with those predicted by the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score. RESULTS: We studied 1280 patients, whose median MAGGIC risk score was 19 [interquartile range, 13-24]. Prescription rates of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, and sacubitril-valsartan were 93%, 67%, 22%, 73%, and 16%, respectively. The MAGGIC risk score showed good discrimination for mortality at 1 year (c-statistic=0.71) and 3 years (c-statistic=0.76). Observed mortality was significantly lower than predicted mortality, both at 1 year (6.2% vs 10.9%; observed/predicted ratio=0.57; P<.001) and at 3 years (16.7% vs 27.7%; observed/predicted ratio=0.60; P<.001). This discrepancy was found in several subgroups, except in patients aged> 70 years (29.9% vs 34.7%; observed/predicted ratio=0.86; P=.126) and in patients with ejection fraction> 40% (19.6% vs 20.7%; observed/predicted ratio=0.95; P=.640). CONCLUSIONS: Mortality in HF patients treated at a specialized clinic was significantly lower than that predicted by the MAGGIC risk score

Incidencia, factores de riesgo e impacto pronóstico de la infección por citomegalovirus tras el trasplante cardiaco / Incidence, risk factors and prognostic impact of cytomegalovirus infection after heart transplantation

INTRODUCCIÓN Y OBJETIVOS: Analizar el impacto pronóstico de la infección por citomegalovirus (CMV) durante el primer año tras el trasplante cardiaco (TC) y describir factores de riesgo. MÉTODOS: Se realizó un estudio retrospectivo unicéntrico que incluyó 222 receptores de TC. La identificación de factores de riesgo de infección por CMV se llevó a cabo mediante la regresión multivariable de Cox. A través de los métodos de Kaplan-Meier y Cox se analizó la influencia de la infección por CMV durante el primer año sobre la supervivencia e incidencia de eventos clínicos adversos en el seguimiento a largo plazo. RESULTADOS: En el análisis multivariante, el estado serológico donante/receptor frente a CMV (hazard ratio [HR] 1,92, intervalo de confianza 95% [IC 95%] 1,2-3,09; p = 0,007), la edad del receptor (HR 1,02, IC 95%: 1,00-1,1; p = 0,02), la diabetes (HR 1,86, IC 95%: 1,4-3,05; p = 0,01), el soporte circulatorio mecánico (HR 1,59, IC 95%: 1,06-2,38; p = 0,03) y el uso de tacrolimus (HR 1,64, IC 95%: 1,13-2,36; p = 0,009) resultaron predictores independientes de infección por CMV postrasplante. No se detectó una influencia significativa de la infección por CMV durante el primer año postrasplante sobre la mortalidad, la incidencia de insuficiencia cardiaca, enfermedad vascular del injerto o rechazo agudo. CONCLUSIONES: La infección por CMV durante el primer año postrasplante no se asoció a un peor pronóstico a largo plazo

INTRODUCTION AND OBJECTIVES: To assess the risk factors of cytomegalovirus (CMV) infection after heart transplant (HT) and its influence on long-term prognosis. METHODS: We conducted a retrospective single-centre study of 222 HT recipients. Risk factors for CMV infection were identified by means of multivariable Cox́s regression. Kaplan-Meier analysis and Cox́s regression were used to assess the long-term prognostic impact of CMV infection during the first post-transplant year. RESULTS: Donor-recipient CMV serologic matching (hazard ratio [HR] 1.92, 95% confidence interval [95% CI] 1.2-3.09, p=.007), recipient age (HR 1.02, 95% CI: 1.00-1.1, p=.02), diabetes mellitus (HR 1.86, 95% CI: 1.4-3.05, p=.01), pre-transplant circulatory support (HR 1.59, 95% CI: 1.06-2.38, p=.03) and the use of tacrolimus (HR 1.64, 95% CI: 1.13-2.36, p=.009) were independently associated with increased risk of CMV infection. CMV infection during the first year post-HT was not associated with worse transplant outcomes in terms of mortality, incidence of heart failure, cardiac allograft vasculopathy or acute rejection. CONCLUSIONS: CMV infection was not associated with impaired long-term prognosis after HT

Comparison of predicted and observed mortality in patients with heart failure treated at a specialized unit.

INTRODUCTION AND OBJECTIVES: To analyze survival in heart failure (HF) patients treated at a specialized unit. METHODS: Prospective cohort-based study of HF patients treated at a specialized unit from 2011 to 2017. Observed 1- and 3-year mortality rates were compared with those predicted by the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score. RESULTS: We studied 1280 patients, whose median MAGGIC risk score was 19 [interquartile range, 13-24]. Prescription rates of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, and sacubitril-valsartan were 93%, 67%, 22%, 73%, and 16%, respectively. The MAGGIC risk score showed good discrimination for mortality at 1 year (c-statistic=0.71) and 3 years (c-statistic=0.76). Observed mortality was significantly lower than predicted mortality, both at 1 year (6.2% vs 10.9%; observed/predicted ratio=0.57; P<.001) and at 3 years (16.7% vs 27.7%; observed/predicted ratio=0.60; P<.001). This discrepancy was found in several subgroups, except in patients aged> 70 years (29.9% vs 34.7%; observed/predicted ratio=0.86; P=.126) and in patients with ejection fraction> 40% (19.6% vs 20.7%; observed/predicted ratio=0.95; P=.640). CONCLUSIONS: Mortality in HF patients treated at a specialized clinic was significantly lower than that predicted by the MAGGIC risk score.

Incidence, risk factors and prognostic impact of cytomegalovirus infection after heart transplantation. / Incidencia, factores de riesgo e impacto pronóstico de la infección por citomegalovirus tras el trasplante cardiaco.

INTRODUCTION AND OBJECTIVES: To assess the risk factors of cytomegalovirus (CMV) infection after heart transplant (HT) and its influence on long-term prognosis. METHODS: We conducted a retrospective single-centre study of 222 HT recipients. Risk factors for CMV infection were identified by means of multivariable Cox́s regression. Kaplan-Meier analysis and Cox́s regression were used to assess the long-term prognostic impact of CMV infection during the first post-transplant year. RESULTS: Donor-recipient CMV serologic matching (hazard ratio [HR] 1.92, 95% confidence interval [95% CI] 1.2-3.09, p=.007), recipient age (HR 1.02, 95% CI: 1.00-1.1, p=.02), diabetes mellitus (HR 1.86, 95% CI: 1.4-3.05, p=.01), pre-transplant circulatory support (HR 1.59, 95% CI: 1.06-2.38, p=.03) and the use of tacrolimus (HR 1.64, 95% CI: 1.13-2.36, p=.009) were independently associated with increased risk of CMV infection. CMV infection during the first year post-HT was not associated with worse transplant outcomes in terms of mortality, incidence of heart failure, cardiac allograft vasculopathy or acute rejection. CONCLUSIONS: CMV infection was not associated with impaired long-term prognosis after HT.

Galectina-3 circulante tras el trasplante cardiaco: dinámica a largo plazo y valor pronóstico / Circulating galectin-3 following heart transplant: long-term dynamics and prognostic value

Introducción y objetivos Los valores plasmáticos de galectina-3 (Gal-3) están elevados y se correlacionan con la mortalidad total y cardiovascular en pacientes con insuficiencia cardiaca, pero su correlación con el pronóstico tras el trasplante cardiaco (TxC) es desconocida. El objetivo fue describir la tendencia evolutiva y el valor pronóstico de este biomarcador tras el TxC. Métodos Mediante enzimoinmunoensayo, se midieron las concentraciones plasmáticas de Gal-3 en muestras de suero de 122 receptores de TxC, antes y 1, 3, 6 y 12 meses después de este. Mediante regresión de Cox se analizó el valor pronóstico del valor plasmático de Gal-3 a los 12 meses del TxC. El objetivo primario del estudio fue la variable combinada muerte o disfunción del injerto. Resultados: Las concentraciones de Gal-3 disminuyeron progresivamente durante el primer año tras el TxC (medianas: pretrasplante, 19,1 ng/ml; 1 año postrasplante, 14,6 ng/ml; p<0,001). Los valores de Gal-3 1 año tras el TxC se asociaron con mayor riesgo de muerte o disfunción del injerto (HR por 1 ng/ml: 1.04; IC95%: 1,01-1,08; p=0,008). La capacidad predictiva del biomarcardor fue moderada: área bajo la curva ROC, 0,72 (IC95%: 0,60-0,82; p<0,001). Conclusiones Las concentraciones plasmáticas de Gal-3 disminuyeron progresivamente durante el primer año tras el TxC. Un valor plasmático elevado de Gal-3 1 año tras el TxC se correlacionó con un pronóstico adverso

Introduction and Objectives: Circulating galectin-3 (Gal-3) is elevated and significantly correlates with all-cause and cardiovascular mortality in patients with heart failure. However, the relationship between serum Gal-3 and heart transplant (HT) outcomes is unclear. The aim of this study was to describe the longitudinal trend and prognostic value of Gal-3 levels after HT. Methods: Banked serum samples were available from 122 HT recipients, collected before transplant and at 1, 3, 6, and 12 months posttransplant. Gal-3 levels in these serum samples were measured by enzyme immune assay. Multivariable Cox regression was performed to determine the prognostic value of 12-month posttransplant Gal-3 serum levels. The primary endpoint was the composite variable all-cause death or graft failure over long-term posttransplant follow-up. Results: Circulating Gal-3 concentration steadily decreased during the first year after HT (median values: pretransplant, 19.1 ng/mL; 1-year posttransplant, 14.6 ng/mL; P<.001). Circulating Gal-3 levels 1-year posttransplant were associated with an increased risk of all-cause death or graft failure (adjusted HR per 1 ng/mL, 1.04; 95%CI, 1.01-1.08; P=.008). The predictive accuracy of this biomarker was moderate: (area under the ROC curve, 0.72 (95%CI, 0.60-0.82; P<.001). Conclusions: Circulating Gal-3 steadily decreased during the first year after HT. However, 1-year posttransplant Gal-3 serum levels that remained elevated were associated with increased long-term risk of death and graft failure

Circulating Galectin-3 Following Heart Transplant: Long-term Dynamics and Prognostic Value.

INTRODUCTION AND OBJECTIVES: Circulating galectin-3 (Gal-3) is elevated and significantly correlates with all-cause and cardiovascular mortality in patients with heart failure. However, the relationship between serum Gal-3 and heart transplant (HT) outcomes is unclear. The aim of this study was to describe the longitudinal trend and prognostic value of Gal-3 levels after HT. METHODS: Banked serum samples were available from 122 HT recipients, collected before transplant and at 1, 3, 6, and 12 months posttransplant. Gal-3 levels in these serum samples were measured by enzyme immune assay. Multivariable Cox regression was performed to determine the prognostic value of 12-month posttransplant Gal-3 serum levels. The primary endpoint was the composite variable all-cause death or graft failure over long-term posttransplant follow-up. RESULTS: Circulating Gal-3 concentration steadily decreased during the first year after HT (median values: pretransplant, 19.1 ng/mL; 1-year posttransplant, 14.6 ng/mL; P<.001). Circulating Gal-3 levels 1-year posttransplant were associated with an increased risk of all-cause death or graft failure (adjusted HR per 1 ng/mL, 1.04; 95%CI, 1.01-1.08; P=.008). The predictive accuracy of this biomarker was moderate: area under the ROC curve, 0.72 (95%CI, 0.60-0.82; P<.001). CONCLUSIONS: Circulating Gal-3 steadily decreased during the first year after HT. However, 1-year posttransplant Gal-3 serum levels that remained elevated were associated with increased long-term risk of death and graft failure.

Polymorphisms in genes related to the complement system and antibody-mediated cardiac allograft rejection.

BACKGROUND: Heart transplantation (HT) is a life-saving treatment for patients with end-stage heart failure. One of the main problems after HT is the humoral response termed antibody-mediated rejection (AMR). Complement activation plays a key role in AMR contributing to graft damage. The aim of this study was to analyze genetic variants in genes related to the complement pathways that could be associated with the development of AMR. METHODS: Analysis of 51 genes related to the complement pathway was performed by next-generation sequencing in 46 HT recipients, 23 with and 23 without AMR. Statistical analysis was performed with SNPstats and R. RESULTS: We identified 2 single nucleotide polymorphisms, 1 in the mannose-binding lectin 2 gene (p.Gly54Asp-MBL2) and 1 in the complement factor properdin gene (p.Asn428(p=)-CFP), that showed significant association with the absence and development of AMR, respectively. Moreover, the presence of the rare allele in p.Gly54Asp-MBL2 control patients correlated with an immunodeficiency of mannose-binding lectin (6.24 ng/ml vs 207.50 ng/ml, p < 0.01), whereas the presence of the rare allele p.Asn428(p=)-CFP in patients with AMR correlated with higher levels of properdin protein (14.65 µg/ml vs 10.77 µg/ml, p < 0.05). CONCLUSIONS: AMR is a complex phenotype affected by many recipient factors. Variants in p.Gly54Asp-MBL2 and p.Asn428(p=)-CFP genes, encoding mannose-binding lectin 2 and properdin, may influence the risk of AMR.

Analysis of variants in the HCN4 gene and in three single nucleotide polymorphisms of the CYP3A4 gene for association with ivabradine reduction in heart rate: A preliminary report.

BACKGROUND: Ivabradine, a selective bradycardic drug, inhibits the If. In patients with heart failure (HF), ivabradine reduces the risk of rehospitalization and mortality. The average heart rate (HR) reduction is 8-10 beats, although clinical trials reveal interindividual variability. The aim of the study is to identify variants associated with HR reduction produced by ivabradine in genes involved in the drug metabolism (CYP3A4) or related to the drug target (HCN4). METHODS: In an exploratory cohort (n = 11), patients started on ivabradine were genotyped and the HR reduction was studied. RESULTS: The mean HR reduction after the treatment was 18.10 ± 12.26 bpm. The HR reduction was ≥ 15 bpm in 3 patients and > 5 and < 15 bpm in 7 patients. Four synonymous variants, L12L, L520L, P852P, and P1200P, were detected in the HCN4 gene (frequency = 0.045, 0.045, and 0.681, respectively). Moreover, the CYP3A4*1F and CYP3A4*1B were found in one patient each and CYP3A4*1G was presented in 3 patients. CONCLUSIONS: This is the first study using an exploratory pharmacogenetic approach that attempts to explain interindividual variability in ivabradine HR reduction. However, more research must be undertaken in order to determine the role of variants in HCN4 and CYP3A4 genes in response to ivabradine.

Significado pronóstico y evolución a largo plazo de la frecuencia cardiaca en los pacientes con trasplante cardiaco / Prognostic significance of heart rate and its long-term trend in cardiac transplant patients

Introducción y objetivos. Estudiar la evolución y el significado pronóstico de la frecuencia cardiaca tras el trasplante cardiaco. Métodos. Estudio observacional de 170 pacientes que recibieron un trasplante cardiaco bicavo entre 1995 y 2005; todos estaban en ritmo sinusal. La frecuencia cardiaca en reposo se determinó a partir de electrocardiogramas al final del primer año tras el trasplante y anualmente hasta el décimo año. Mediante análisis de Cox, se evaluó la incidencia de eventos adversos en un seguimiento medio de 8,9 ± 3,1 años. El evento principal del estudio fue la variable combinada muerte o disfunción del injerto. Resultados. La frecuencia cardiaca en reposo, medida al final del primer año tras el trasplante, fue un predictor independiente del evento combinado principal (hazard ratio = 1,054; intervalo de confianza del 95%, 1,028-1,080; p < 0,001). Se observó una asociación estadísticamente significativa con la mortalidad total (hazard ratio = 1,058; intervalo de confianza del 95%, 1,030-1,087; p < 0,001) y con la mortalidad por causas cardiacas (hazard ratio = 1,069; intervalo de confianza del 95%, 1,026-1,113; p = 0,001), pero no con la disfunción del injerto (hazard ratio = 1,028; intervalo de confianza del 95%, 0,989-1,069; p = 0,161). Para los pacientes con frecuencia cardiaca ≥ 105 y < 90 lpm frente a aquellos con 90-104 lpm, las hazard ratio del evento principal fueron, respectivamente, 2,233 (intervalo de confianza del 95%, 1,250-3,989, p = 0,007) y 0,380 (intervalo de confianza del 95%, 0,161-0,895; p = 0,027). Este parámetro presentó una tendencia decreciente en los primeros 10 años del trasplante (p = 0,001). Los pacientes con incremento neto de frecuencia cardiaca en el seguimiento mostraron mayor incidencia de eventos adversos. Conclusiones. La frecuencia cardiaca elevada es un marcador pronóstico adverso tras el trasplante cardiaco (AU)

Introduction and objectives. The aim of the present study was to examine the prognostic significance of heart rate and its trend in heart transplantation. Methods. This observational study enrolled 170 patients who received a bicaval heart transplant between 1995 and 2005; all were in sinus rhythm. The resting heart rate was determined via electrocardiography at the end of the first posttransplant year and annually until the tenth year. Cox analysis was used to evaluate the incidence of adverse events with a mean (standard deviation) follow-up of 8.9 (3.1) years. The primary study end point was the composite outcome of death or graft dysfunction. Results. The resting heart rate at the end of the first posttransplant year was an independent predictor of the primary composite end point (hazard ratio = 1.054; 95% confidence interval, 1.028-1.080; P < .001) and was significantly associated with total mortality (hazard ratio = 1.058; 95% confidence interval, 1.030-1.087; P < .001) and mortality from cardiac causes (hazard ratio = 1.069; 95% confidence interval, 1.026-1.113; P = .001), but not with graft dysfunction (hazard ratio = 1.028; 95% confidence interval, 0.989-1.069; P = .161). For patients with a heart rate ≥ 105 or < 90 bpm vs those with 90-104 bpm, the hazard ratios of the primary end point were 2.233 (95% confidence interval, 1.250-3.989; P = .007) and 0.380 (95% confidence interval, 0.161-0.895; P = .027), respectively. Heart rate tended to decrease in the first 10 years after transplantation (P = .001). Patients with a net increase in heart rate during follow-up showed a higher incidence of adverse events. Conclusions. An elevated heart rate is an adverse prognostic marker after heart transplantation (AU)

Clinical evaluation of rosuvastatin in heart transplant patients with hypercholesterolemia and therapeutic failure of other statin regimens: short-term and long-term efficacy and safety results.

We conducted an observational study of 30 heart transplant recipients with serum low-density lipoprotein cholesterol (LDL-c) >100 mg/dl despite previous statin therapy, who were treated with rosuvastatin 10 mg daily (5 mg in case of renal dysfunction). Serum lipids, creatine phosphokinase (CPK), bilirubin, and hepatic enzymes were prospectively measured 2, 4, and 12 weeks after the initiation of the drug. Clinical outcomes of patients who continued on long-term rosuvastatin therapy beyond this 12-week period were reviewed in February 2015. Over the 12-week period following rosuvastatin initiation, serum levels of total cholesterol (TC) and LDL-c and the ratio TC/high-density lipoprotein cholesterol (HDL-c) decreased steadily (P < 0.001). Average absolute reductions of these three parameters were -48.7 mg/dl, -46.6 mg/dl, and -0.9, respectively. Seventeen (57%) achieved a serum LDL-c < 100 mg/dl. No significant changes from baseline were observed in serum levels of triglycerides, HDL-c, hepatic enzymes, bilirubin, or CPK. Twenty-seven (90%) patients continued on long-term therapy with rosuvastatin over a median period of 3.6 years, with no further significant variation in lipid profile. The drug was suspended due to liver toxicity in 1 (3.3%) patient and due to muscle toxicity in 2 (6.7%) patients. All adverse reactions resolved rapidly after rosuvastatin withdrawal. Our study supports rosuvastatin as a reasonable alternative for heart transplant recipients with hypercholesterolemia and therapeutic failure of other statin regimens.

Prognostic Significance of Heart Rate and its Long-term Trend in Cardiac Transplant Patients.

INTRODUCTION AND OBJECTIVES: The aim of the present study was to examine the prognostic significance of heart rate and its trend in heart transplantation. METHODS: This observational study enrolled 170 patients who received a bicaval heart transplant between 1995 and 2005; all were in sinus rhythm. The resting heart rate was determined via electrocardiography at the end of the first posttransplant year and annually until the tenth year. Cox analysis was used to evaluate the incidence of adverse events with a mean (standard deviation) follow-up of 8.9 (3.1) years. The primary study end point was the composite outcome of death or graft dysfunction. RESULTS: The resting heart rate at the end of the first posttransplant year was an independent predictor of the primary composite end point (hazard ratio=1.054; 95% confidence interval, 1.028-1.080; P<.001) and was significantly associated with total mortality (hazard ratio=1.058; 95% confidence interval, 1.030-1.087; P<.001) and mortality from cardiac causes (hazard ratio=1.069; 95% confidence interval, 1.026-1.113; P=.001), but not with graft dysfunction (hazard ratio=1.028; 95% confidence interval, 0.989-1.069; P=.161). For patients with a heart rate ≥ 105 or<90 bpm vs those with 90-104 bpm, the hazard ratios of the primary end point were 2.233 (95% confidence interval, 1.250-3.989; P=.007) and 0.380 (95% confidence interval, 0.161-0.895; P=.027), respectively. Heart rate tended to decrease in the first 10 years after transplantation (P=.001). Patients with a net increase in heart rate during follow-up showed a higher incidence of adverse events. CONCLUSIONS: An elevated heart rate is an adverse prognostic marker after heart transplantation.

Venous thromboembolism in heart transplant recipients: incidence, recurrence and predisposing factors.

BACKGROUND: A high frequency of venous thromboembolism (VTE) has been observed after lung, kidney, and liver transplantation. However, data about the incidence of this complication among heart transplant (HT) recipients are lacking. METHODS: We analyzed the incidence, recurrence, and predisposing factors of VTE in a single-center cohort of 635 patients who underwent HT from April 1991 to April 2013. Deep venous thrombosis (DVT) and pulmonary embolism (PE) were considered as VTE episodes. RESULTS: During a median post-transplant follow-up of 8.4 years, 62 VTE episodes occurred in 54 patients (8.5%). Incidence rates of VTE, DVT, and PE were, respectively, 12.7 (95% confidence interval [CI], 9.7-16.3), 8.4 (95% CI, 6.0-11.4), and 7.0 (95% CI 4.8-9.7) episodes per 1,000 patient-years. Incidence rates of VTE during the first post-transplant year and beyond were, respectively, 45.1 (95% CI, 28.9-67.1) and 8.7 (95% CI 6.2-11.2) episodes per 1,000 patient-years. The incidence rate of VTE recurrence after a first VTE episode was 30.5 (95% CI, 13.2-60.2) episodes per 1,000 patient-years. By means of multivariable Cox regression, chronic renal dysfunction, older age, obesity, and the use of mammalian target of rapamycin inhibitors were identified as independent risk factors for VTE among HT recipients. CONCLUSIONS: VTE is a frequent complication after HT, mainly during the first post-operative year. In view of a high recurrence rate, long-term anti-coagulation should be considered in HT recipients who experience a first VTE episode.

Utilidad de la escala INTERMACS para estratificar el pronóstico tras el trasplante cardiaco urgente / Usefulness of the INTERMACS scale for predicting outcomes after urgent heart transplantation

Introducción y objetivos. Analizar el valor pronóstico de la escala INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) en pacientes tratados con trasplante cardiaco urgente. Métodos. Análisis retrospectivo de 111 pacientes tratados con trasplante cardiaco urgente en nuestro centro entre abril de 1991 y octubre de 2009. Se asignó retrospectivamente a los pacientes a tres niveles de la escala INTERMACS en función de su situación clínica previa al trasplante cardiaco. Resultados. Los pacientes del grupo INTERMACS 1 (n=31) presentaban mayor frecuencia de cardiopatía isquémica (p=0,03) y shock tras cardiotomía (p=0,02) que los pacientes del grupo INTERMACS 2 (n=55) y los pacientes del grupo INTERMACS 3–4 (n=25), así como mayores dosis de catecolaminas (p=0,001), mayor empleo de ventilación mecánica (p<0,001), balón de contrapulsación (p=0,002) y dispositivos de asistencia ventricular (p=0,002) y mayores tasas de infección preoperatoria (p=0,015). El grupo INTERMACS 1 también mostraba mayores cifras de presión venosa central (p=0,02), GOT (p=0,002), GPT (p=0,006) y creatinina (p<0,001) y menores cifras de hemoglobina (p=0,008) y aclaramiento de creatinina (p=0,001). Tras el trasplante cardiaco, los pacientes del grupo INTERMACS 1 presentaron mayores incidencias de fracaso primario del injerto (p=0,03) y necesidad de terapia de sustitución renal (p=0,004), y su supervivencia a largo plazo fue menor que la de los pacientes de los grupos INTERMACS 2 (log rank=5,1; p=0,023; razón de riesgos [HR]=3,1; intervalo de confianza [IC] del 95%, 1,4-6,8) e INTERMACS 3-4 (log rank=6,1; p=0,013; HR=4; IC del 95%, 1,3-12,3). Conclusiones. Nuestros resultados indican que la escala INTERMACS resulta útil para estratificar el pronóstico postoperatorio tras el trasplante cardiaco urgente(AU)

Introduction and objectives: Our aim was to assess the prognostic value of the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) scale in patients undergoing urgent heart transplantation (HT). Methods: Retrospective analysis of 111 patients treated with urgent HT at our institution from April, 1991 to October, 2009. Patients were retrospectively assigned to three levels of the INTERMACS scale according to their clinical status before HT. Results: Patients at the INTERMACS 1 level (n = 31) more frequently had ischemic heart disease (P = .03) and post-cardiothomy shock (P = .02) than patients at the INTERMACS 2 (n = 55) and INTERMACS 3-4 (n = 25) levels. Patients at the INTERMACS 1 level showed higher preoperative catecolamin doses (P = .001), a higher frequency of use of mechanical ventilation (P < .001), intraaortic balloon (P = .002) and ventricular assist devices (P = .002), and a higher frequency of preoperative infection (P = .015). The INTERMACS 1 group also presented higher central venous pressure (P = .02), AST (P = .002), ALT (P = .006) and serum creatinine (P < .001), and lower hemoglobin (P = .008) and creatinine clearance (P = .001). After HT, patients at the INTERMACS 1 level had a higher incidence of primary graft failure (P = .03) and postoperative need for renal replacement therapy (P = .004), and their long-term survival was lower than patients at the INTERMACS 2 (log rank 5.1, P = .023; HR 3.1, IC 95% 1.1-8.8) and INTERMACS 3-4 level (log rank 6.1, p = 0.013; HR 6.8, IC 95% 1.2-39.1). Conclusions: Our results suggest that the INTERMACS scalemay be a useful tool to stratify postoperative prognosis after urgent HT(AU)