Levosimendán ambulatorio repetitivo como puente al trasplante cardiaco / Repetitive ambulatory levosimendan as a bridge to heart transplantation

Introducción y objetivos:El levosimendán ambulatorio repetitivo es una opción como puente al trasplante cardiaco (TxC), aunque la evidencia sobre su eficacia y su seguridad es escasa. El objetivo del registro LEVO-T es describir a los pacientes en lista de TxC que reciben levosimendán, sus pautas y los eventos clínicos durante el seguimiento, en comparación con los que no lo reciben. Métodos: Se revisó en retrospectiva a los pacientes en lista de espera para TxC electivo de 14 centros españoles desde 2015 hasta 2020. Resultados: Se incluyó a 1.015 pacientes consecutivos; los 238 (23,4%) que recibieron levosimendán mostraron más ingresos por insuficiencia cardiaca (IC) el año anterior y peor perfil clínico. Las dosis fijas por necesidades clínicas fueron la pauta más frecuente. Dos pacientes (0,8%) presentaron arritmias ventriculares no mortales. No hubo diferencias en hospitalizaciones por IC entre los que comenzaron levosimendán en los primeros 30 días después de inclusión y los que no (el 33,6 frente al 34,5%; p=0,848). De estos últimos, 102 (32,9%) pasaron a levosimendán después de un ingreso por IC, y la tasa de ingresos por IC/mes varió de 0,57 antes del levosimendán a 0,21 después. El análisis mediante emparejamiento por puntuación de propensión no mostró diferencias entre los pacientes con y sin levosimendán en la supervivencia a 1 año tras la inclusión en lista (HR=1,03; IC95%, 0,36-2,97; p=0,958) ni en la supervivencia tras el TxC (HR=0,97; IC95%, 0,60-1,56; p=0,958). Conclusiones: El levosimendán ambulatorio repetitivo como puente al trasplante cardiaco es un tratamiento frecuente y seguro que podría reducir ingresos por IC. (AU)

Introduction and objectives: Repetitive ambulatory doses of levosimendan are an option as a bridge to heart transplantation (HT), but evidence regarding the safety and efficacy of this treatment is scarce. The objective of the LEVO-T Registry is to describe the profile of patients on the HT list receiving levosimendan, prescription patterns, and clinical outcomes compared with patients not on levosimendan. Methods: We retrospectively reviewed all patients listed for elective HT from 2015 to 2020 from 14 centers in Spain. Results: A total of 1015 consecutive patients were included, of whom 238 patients (23.4%) received levosimendan. Patients treated with levosimendan had more heart failure (HF) admissions in the previous year and a worse clinical profile. The most frequent prescription pattern were fixed doses triggered by the patients’ clinical needs. Nonfatal ventricular arrhythmias occurred in 2 patients (0.8%). No differences in HF hospitalizations were found between patients who started levosimendan in the first 30 days after listing and those who did not (33.6% vs 34.5%; P=.848). Among those who did not, 102 patients (32.9%) crossed over to levosimendan after an HF admission. These patients had a rate of 0.57 HF admissions per month before starting levosimendan and 0.21 afterwards. Propensity score matching analysis showed no differences in survival at 1 year after listing between patients receiving levosimendan and those who did not (HR, 1.03; 95%CI, 0.36-2.97; P=.958) or in survival after HT (HR, 0.97; 95%CI, 0.60-1.56; P=.958). Conclusions: Repetitive levosimendan in an ambulatory setting as a bridge to heart transplantation is commonly used, is safe, and may reduce HF hospitalizations. (AU)

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.

Prevalence, Characteristics, and Prognostic Relevance of Donor-Transmitted Coronary Artery Disease in Heart Transplant Recipients.

BACKGROUND: The reported prevalence of donor-transmitted coronary artery disease (TCAD) in heart transplantation (HT) is variable, and its prognostic impact remains unclear. OBJECTIVES: The goal of this study was to characterize TCAD in a contemporary multicentric cohort and to study its prognostic relevance. METHODS: This was a retrospective study of consecutive patients >18 years old who underwent HT in 11 Spanish centers from 2008 to 2018. Only patients with a coronary angiography (c-angio) within the first 3 months after HT were studied. Significant TCAD (s-TCAD) was defined as any stenosis ≥50% in epicardial coronary arteries, and nonsignificant TCAD (ns-TCAD) as stenosis <50%. Clinical outcomes were assessed by means of Cox regression and competing risks regression. Patients were followed-up for a median period of 6.3 years after c-angio. RESULTS: From a cohort of 1,918 patients, 937 underwent c-angio. TCAD was found in 172 patients (18.3%): s-TCAD in 65 (6.9%) and ns-TCAD in 107 (11.4%). Multivariable Cox regression analysis did not show a statistically significant association between s-TCAD and all-cause mortality (adjusted HR: 1.44; 95% CI: 0.89-2.35; P = 0.141); however, it was an independent predictor of cardiovascular mortality (adjusted HR: 2.25; 95% CI: 1.20-4.19; P = 0.011) and the combined event cardiovascular death or nonfatal MACE (adjusted HR: 2.42; 95% CI: 1.52-3.85; P < 0.001). No statistically significant impact of ns-TCAD on clinical outcomes was detected. The results were similar when reassessed by means of competing risks regression. CONCLUSIONS: TCAD was not associated with reduced survival in patients alive and well enough to undergo post-HT angiography within the first 3 months; however, s-TCAD patients showed increased risk of cardiovascular death and MACE.

Repetitive ambulatory levosimendan as a bridge to heart transplantation.

INTRODUCTION AND OBJECTIVES: Repetitive ambulatory doses of levosimendan are an option as a bridge to heart transplantation (HT), but evidence regarding the safety and efficacy of this treatment is scarce. The objective of the LEVO-T Registry is to describe the profile of patients on the HT list receiving levosimendan, prescription patterns, and clinical outcomes compared with patients not on levosimendan. METHODS: We retrospectively reviewed all patients listed for elective HT from 2015 to 2020 from 14 centers in Spain. RESULTS: A total of 1015 consecutive patients were included, of whom 238 patients (23.4%) received levosimendan. Patients treated with levosimendan had more heart failure (HF) admissions in the previous year and a worse clinical profile. The most frequent prescription pattern were fixed doses triggered by the patients' clinical needs. Nonfatal ventricular arrhythmias occurred in 2 patients (0.8%). No differences in HF hospitalizations were found between patients who started levosimendan in the first 30 days after listing and those who did not (33.6% vs 34.5%; P=.848). Among those who did not, 102 patients (32.9%) crossed over to levosimendan after an HF admission. These patients had a rate of 0.57 HF admissions per month before starting levosimendan and 0.21 afterwards. Propensity score matching analysis showed no differences in survival at 1 year after listing between patients receiving levosimendan and those who did not (HR, 1.03; 95%CI, 0.36-2.97; P=.958) or in survival after HT (HR, 0.97; 95%CI, 0.60-1.56; P=.958). CONCLUSIONS: Repetitive levosimendan in an ambulatory setting as a bridge to heart transplantation is commonly used, is safe, and may reduce HF hospitalizations.

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.

Real world comparison of spironolactone and eplerenone in patients with heart failure.

AIMS: In the absence of previous direct comparative studies, we aimed to evaluate the effectiveness of spironolactone and eplerenone in patients with heart failure and reduced ejection fraction (HFrEF) in a real-world clinical setting. METHODS: Using Fine-Gray´s competing risk regression, we compared the clinical outcomes of 293 patients with chronic HF and left ventricular ejection fraction <40% treated with eplerenone and 293 propensity-score matched individuals treated with spironolactone. Study subjects were selected from a prospective cohort of 1404 ambulatory patients with HFrEF seen since 2010 to 2019 in a single specialized HF clinic, among which 992 received a mineralocorticoid receptor antagonist at baseline. Median follow-up was 3.95 years. RESULTS: No statistically significant differences between patients treated with eplerenone versus spironolactone were observed with regard to the risk of the primary composite end-point cardiovascular death or HF hospitalization (HR 0.95; 95% CI 0.73-1.23; p= 0.677). However, eplerenone use was associated to lower cardiovascular mortality (HR 0.55; 95% CI 0.35-0.85; p= 0.008) and lower all-cause mortality (HR 0.67; 95% CI 0.47-0.95; p= 0.027). The incidence of drug suspension due to side effects (HR 0.58, 95% CI 0.40-0.85; p= 0.005) and drug suspension due to any reason (HR 0.70, 95% CI 0.51-0.97; p= 0.033) were lower among patients treated with eplerenone. CONCLUSIONS: In this observational, real-world, propensity-score matched study of patients with HFrEF, eplerenone was associated to lower cardiovascular mortality and lower all-cause mortality than spironolactone.

Amiloidosis cardíaca por cadenas ligeras y por transtirretina: características clínicas, historia natural y predictores pronósticos / Light chain and transthyretin cardiac amyloidosis: Clinical characteristics, natural history and prognostic factors

Antecedentes y objetivos: La amiloidosis cardíaca (AC) por cadenas ligeras (AC-AL) y por transtirretina (AC-ATTR) son los dos subtipos más frecuentes de la enfermedad. Nos propusimos caracterizar clínicamente estas entidades y analizar su pronóstico.Material y métodosRealizamos una revisión retrospectiva de todos los pacientes diagnosticados con AC entre 1998 y 2018 en un centro español. Además de recoger las características clínicas y los resultados de las pruebas complementarias al diagnóstico, analizamos la supervivencia y la incidencia de desenlaces clínicos adversos.ResultadosIdentificamos 105 pacientes con AC, 65 con AC-ATTR y 40 con AC-AL. La edad media era de 74,4 años; el 24,8% eran mujeres. En ambos grupos la insuficiencia cardíaca (IC) fue la forma de presentación clínica más frecuente (55,2%). Los hallazgos electrocardiográficos más prevalentes fueron el patrón de pseudoinfarto (68,5%) y un índice de Sokolow-Lyon < 1,5 mV (67,7%), sin diferencias entre los dos subtipos. La supervivencia a 1, 3 y 5 años fue del 43,3%, 40,4% y 35,4%, respectivamente, en pacientes con AC-AL y del 85,1%, 57,3% y 31,4% en pacientes con AC-ATTR (p = 0,004). El subtipo AC-AL (HR 3,41; IC 95% 1,45-8,06; p = 0,005), el ingreso previo por IC (HR 4,25; IC 95% 1,63-11,09; p = 0,003) y una clase NYHA III-IV (HR 2,76; IC 95% 1,09-7,03; p = 0,033) fueron predictores independientes de mortalidad, mientras que el tratamiento betabloqueante se asoció con una mayor supervivencia (HR 0,23; IC 95% 0,09-0,59; p = 0,002).ConclusionesExisten ciertas diferencias en la presentación clínica de los pacientes con AC-AL y AC-ATTR. Ambas entidades, y muy especialmente la AC-AL, presentan un pobre pronóstico vital. (AU)

Introduction and objectives: Light-chain amyloidosis (AL-CA) and transthyretin amyloidosis (ATTR-CA) are the most common types of cardiac amyloidosis (CA). We sought to study the clinical characteristics and prognosis of both diseases.MethodsWe conducted a single-centre, retrospective review of all patients diagnosed with CA between 1998 and 2018. Clinical characteristics, complementary tests, survival and other adverse clinical events were studied.ResultsWe identified 105 patients with CA, 65 ATTR-CA and 40 AL-CA. Mean age was 74.4 years; 24.8% were women. In both groups, heart failure was the most frequent clinical presentation (55.2%). The most prevalent electrocardiographic findings were the pseudoinfarct pattern (68.5%) and a Sokolow-Lyon index < 1.5 mV (67.7%), with no differences between the two subtypes of CA. One-year, 3-year, and 5-year survival was 43.3%, 40.4% and 35.4%, respectively, in AC-AL patients, and 85.1%, 57.3% and 31.4% in AC-ATTR patients (p = 0.004). AL-CA subtype (HR 3.41; 95% CI 1.45-8.06; p = 0.005), previous admission for heart failure (HR 4.25; 95% CI 1.63-11.09; p = 0.003) and a NYHA class III-IV (HR 2.76; 95% CI; 1.09-7.03; p = 0.033) were independent predictors of mortality, while beta-blocker therapy was associated with longer survival (HR 0.23; 95% CI 0.09-0.59; p = 0.002).ConclusionsDifferences exist between the clinical presentation of AL-CA and ATTR-CA patients. Both diseases, particularly AL-CA, are associated with poor life prognosis. (AU)

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.

Light chain and transthyretin cardiac amyloidosis: Clinical characteristics, natural history and prognostic factors. / Amiloidosis cardíaca por cadenas ligeras y por transtirretina: características clínicas, historia natural y predictores pronósticos.

INTRODUCTION AND OBJECTIVES: Light-chain amyloidosis (AL-CA) and transthyretin amyloidosis (ATTR-CA) are the most common types of cardiac amyloidosis (CA). We sought to study the clinical characteristics and prognosis of both diseases. METHODS: We conducted a single-centre, retrospective review of all patients diagnosed with CA between 1998 and 2018. Clinical characteristics, complementary tests, survival and other adverse clinical events were studied. RESULTS: We identified 105 patients with CA, 65 ATTR-CA and 40 AL-CA. Mean age was 74.4 years; 24.8% were women. In both groups, heart failure was the most frequent clinical presentation (55.2%). The most prevalent electrocardiographic findings were the pseudoinfarct pattern (68.5%) and a Sokolow-Lyon index < 1.5 mV (67.7%), with no differences between the two subtypes of CA. One-year, 3-year, and 5-year survival was 43.3%, 40.4% and 35.4%, respectively, in AC-AL patients, and 85.1%, 57.3% and 31.4% in AC-ATTR patients (p = 0.004). AL-CA subtype (HR 3.41; 95% CI 1.45-8.06; p = 0.005), previous admission for heart failure (HR 4.25; 95% CI 1.63-11.09; p = 0.003) and a NYHA class III-IV (HR 2.76; 95% CI; 1.09-7.03; p = 0.033) were independent predictors of mortality, while beta-blocker therapy was associated with longer survival (HR 0.23; 95% CI 0.09-0.59; p = 0.002). CONCLUSIONS: Differences exist between the clinical presentation of AL-CA and ATTR-CA patients. Both diseases, particularly AL-CA, are associated with poor life prognosis.

Spanish Heart Transplant Registry. 31th Official Report of the Heart Failure Association of the Spanish Society of Cardiology.

INTRODUCTION AND OBJECTIVES: The present report describes the clinical characteristics and outcomes of heart transplants in Spain and updates the data to 2019. METHODS: We describe the clinical characteristics and outcomes of heart transplants performed in Spain in 2019, as well as trends in this procedure from 2010 to 2018. RESULTS: In 2019, 300 transplants were performed (8794 since 1984; 2745 between 2010 and 2019). Compared with previous years, the most notable findings were the decreasing rate of urgent transplants (38%), and the consolidation of the type of circulatory support prior to transplant, with an almost complete disappearance of counterpulsation balloon (0.7%), stabilization in the use of extracorporeal membrane oxygenation (9.6%), and an increase in the use of ventricular assist devices (29.0%). Survival from 2016 to 2018 was similar to that from 2013 to 2015 (P=.34). Survival in both these periods was better than that from 2010 to 2012 (P=.002 and P=.01, respectively). CONCLUSIONS: Heart transplant activity has remained stable during the last few years, as have outcomes (in terms of survival). There has been a trend to a lower rate of urgent transplants and to a higher use of ventricular assist devices prior to transplant.

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

Circulating miR-181a-5p as a new biomarker for acute cellular rejection in heart transplantation.

BACKGROUND: Acute cellular rejection (ACR) is a major complication in heart transplantation (HTx). Endomyocardial biopsy is the reference method for early detection of ACR, but a new non-invasive approach is needed. Tentative candidates could be circulating microRNAs. This study aimed to discover and validate microRNAs in serum for ACR detection after HTx. METHODS: This prospective, observational, single-center study included 121 HTx patients. ACR was graded according to International Society of Heart and Lung Transplantation classification (0R-3R). First, in the discovery phase, microRNA expression profile was carried out in serum samples from patients at pre-rejection, during, and post-rejection time (0RS1 → 2RS2` → 0RS3). Relative expression (2-∆Cq) of 179 microRNAs per sample was analyzed by reverse transcription quantitative polymerase chain reaction. Second, a microRNA with a significant rise and fall pattern during ACR was selected for the next validation phase, where it was analyzed (reverse transcription quantitative polymerase chain reaction) in serum samples from 2 groups of patients: the no-ACR group (0R grade) and the ACR group (≥2R grade). Finally, a sensitivity analysis (receiver operating characteristic curve) was done to assess microRNA accuracy for ACR detection in HTx. RESULTS: A total of 21 ACR episodes (0RS1 → 2RS2 → 0RS3) with their respective serum samples (n = 63) were included in the discovery phase. Among the 179 microRNAs analyzed, only miR-181a-5p met the rise and fall criteria. In the validation phase, miR-181a-5p relative expression (2-∆Cq) in the ACR group (n = 45) was significantly overexpressed (p < 0.0001) vs the no-ACR group (n = 45). miR-181a-5p showed an area under the curve of 0.804 (95% confidence interval: 0.707-0.880); sensitivity and specificity of 78% and 76%, respectively; and a negative predicted value of 98%. CONCLUSIONS: miR-185a-5p in serum is a candidate as a non-invasive ACR biomarker (area under the curve = 0.80 and negative predicted value = 98%). Thus, this biomarker could reduce the need for endomyocardial biopsies and the associated risks and costs of this invasive procedure.

Diagnóstico y tratamiento de la obstrucción al flujo en dispositivos de asistencia ventricular de flujo continuo. Un problema infrecuente / Flow obstruction of continuous-flow ventricular assist devices. Diagnosis and treatment of an uncommon problem

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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.