Withdrawal of drug therapy in responders to cardiac resynchronization therapy: rationale and design of the REMOVE trial.

Introduction and objectives Cardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients. Methods The REMOVE trial (NCT05151861) is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF > 10% (provided the LVEF is < 50%); b) a reduction in LVEF > 10% accompanied by an increase > 15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted. Conclusions The results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients.

Use of a surgically implanted, nondischargeable, extracorporeal continuous flow circulatory support system as a bridge to heart transplant.

INTRODUCTION AND OBJECTIVES: We aimed to describe the clinical outcomes of the use of the CentriMag acute circulatory support system as a bridge to emergency heart transplantation (HTx). METHODS: We conducted a descriptive analysis of the clinical outcomes of consecutive HTx candidates included in a multicenter retrospective registry who were treated with the CentriMag device, configured either for left ventricular support (LVS) or biventricular support (BVS). All patients were listed for high-priority HTx. The study assessed the period 2010 to 2020 and involved 16 transplant centers around Spain. We excluded patients treated with isolated right ventricular support or venoarterial extracorporeal membrane oxygenation without LVS. The primary endpoint was 1-year post-HTx survival. RESULTS: The study population comprised 213 emergency HTx candidates bridged on CentriMag LVS and 145 on CentriMag BVS. Overall, 303 (84.6%) patients received a transplant and 53 (14.8%) died without having an organ donor during the index hospitalization. Median time on the device was 15 days, with 66 (18.6%) patients being supported for> 30 days. One-year posttransplant survival was 77.6%. Univariable and multivariable analyses showed no statistically significant differences in pre- or post-HTx survival in patients managed with BVS vs LVS. Patients managed with BVS had higher rates of bleeding, need for transfusion, hemolysis and renal failure than patients managed with LVS, while the latter group showed a higher incidence of ischemic stroke. CONCLUSIONS: In a setting of candidate prioritization with short waiting list times, bridging to HTx with the CentriMag system was feasible and resulted in acceptable on-support and posttransplant outcomes.

Mechanical circulatory support in severe primary graft dysfunction: Peripheral cannulation but not earlier implantation improves survival in heart transplantation.

BACKGROUND: Primary graft dysfunction (PGD) still affects 2% to 28% of heart transplants (HT). Severe PGD requires mechanical circulatory support (MCS) and is the main cause of death early after HT. Earlier initiation has been suggested to improve prognosis but the best cannulation strategy is unknown. METHODS: Analysis of all HT in Spain between 2010 and 2020. Early (<3 hours after HT) vs late initiation (≥3 hours after HT) of MCS was compared. Special focus was placed on peripheral vs central cannulation strategy. RESULTS: A total of 2376 HT were analyzed. 242 (10.2%) suffered severe PGD, 171 (70.7%) received early MCS and 71 (29.3%) late MCS. Baseline characteristics were similar. Patients with late MCS had higher inotropic scores and worse renal function at the moment of cannulation. Early MCS had longer cardiopulmonary bypass times and late MCS was associated with more peripheral vascular damage. No significant differences in survival were observed between early and late implant at 3 months (43.82% vs 48.26%; log-rank p = 0.59) or at 1 year (39.29% vs 45.24%, log-rank p = 0.49). Multivariate analysis did not show significant differences favoring early implant. Survival was higher in peripheral compared to central cannulation at 3 months (52.74% vs 32.42%, log-rank p = 0.001) and 1 year (48.56% vs 28.19%, log-rank p = 0.0007). In the multivariate analysis, peripheral cannulation remained a protective factor. CONCLUSIONS: Earlier MCS initiation for PGD was not superior, compared to a more conservative approach with deferred initiation. Peripheral compared to central cannulation showed superior 3-month and 1-year survival rates.

Temporal trends in the use and outcomes of temporary mechanical circulatory support as a bridge to cardiac transplantation in Spain. Final report of the ASIS-TC study.

BACKGROUND: We aimed to describe recent trends in the use and outcomes of temporary mechanical circulatory support (MCS) as a bridge to heart transplantation (HTx) in Spain. METHODS: Retrospective case-by-case analysis of 1,036 patients listed for emergency HTx while on temporary MCS in 16 Spanish institutions from January 1st, 2010 to December 31st, 2020. Patients were classified in 3 eras according to changes in donor allocation criteria (Era 1: January 2010/May 2014; Era 2: June 2014/May 2017; Era 3: June 2017/December 2020). RESULTS: Over time, the proportion of candidates listed with intra-aortic balloon pumps decreased (Era 1 = 55.9%, Era 2 = 32%, Era 3 = 0.9%; p < 0.001), while the proportion of candidates listed with surgical continuous-flow temporary VADs (Era 1 = 10.6%, Era 2 = 32%, Era 3 = 49.1%; p < 0.001) and percutaneous VADs (Era 1 = 0.3%, Era 2 = 6.3%; Era 3 = 17.2%; p < 0.001) increased. Rates of HTx increased from Era 1 (79.4%) to Era 2 (87.8%), and Era 3 (87%) (p = 0.004), while rates of death before HTx decreased (Era 1 = 17.7%; Era 2 = 11%, Era 3 = 12.4%; p = 0.037) Median time from listing to HTx increased in patients supported with intra-aortic balloon pumps (Era 1 = 8 days, Era 2 = 15 days; p < 0.001) but remained stable in other candidates (Era 1 = 6 days; Era 2 = 5 days; Era 3 = 6 days; p = 0.134). One-year post-transplant survival was 71.4% in Era 1, 79.3% in Era 2, and 76.5% in Era 3 (p = 0.112). Preoperative bridging with ECMO was associated with increased 1-year post-transplant mortality (adjusted HR=1.71; 95% CI 1.15-2.53; p = 0.008). CONCLUSIONS: During the period 2010 to 2020, successive changes in the Spanish organ allocation protocol were followed by a significant increase of the rate of HTx and a significant reduction of waiting list mortality in candidates supported with temporary MCS. One-year post-transplant survival rates remained acceptable.

Pulmonary Vascular Remodeling and Prognosis in Patients Evaluated for Heart Transplantation: Insights from the OCTOPUS-CHF Study.

OBJECTIVE: In patients with advanced heart failure, the intravascular optical coherence tomography (OCT) of subsegmental pulmonary artery measurements is correlated with right heart catheterization parameters. Our aim was to study the prognostic value of pulmonary OCT, right heart catheterization data, and the echocardiographic estimation of pulmonary pressure in patients studied for elective heart transplants. METHODS: This research is an observational, prospective, multicenter study involving 90 adults with a one-year follow-up. RESULTS: A total of 10 patients (11.1%) died due to worsening heart failure before heart transplantation, 50 underwent a heart transplant (55.6%), and 9 died in the first year after the transplant. The patients with and without events (mortality or heart failure-induced hospitalization) had similar data regarding echocardiography, right heart catheterization, and pulmonary OCT (with a median estimated pulmonary artery systolic pressure of 42.0 mmHg, interquartile range (IQR) of 30.3-50.0 vs. 47.0 mmHg, IQR 34.6-59.5 and p = 0.79, median pulmonary vascular resistance of 2.2 Wood units, IQR 1.3-3.7 vs. 2.0 Wood units, IQR 1.4-3.2 and p = 0.99, and a median pulmonary artery wall thickness of 0.2 ± 0.5 mm vs. 0.2 ± 0.6 mm and p = 0.87). CONCLUSION: Pulmonary vascular remodeling (evaluated with echocardiography, right heart catheterization, and pulmonary OCT) was not associated with prognosis in a selected sample of adults evaluated for elective heart transplants. Pulmonary OCT is safe and feasible for the evaluation of these patients.

Utility of the IMPACT score for predicting heart transplant mortality. Analysis on a contemporary cohort of the Spanish Heart Transplant Registry.

INTRODUCTION AND OBJECTIVES: The Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score was derived and validated as a predictor of mortality after heart transplantation (HT). The primary objective of this work is to externally validate the IMPACT score in a contemporary Spanish cohort. METHODS: Spanish Heart Transplant Registry data were used to identify adult (>16 years) HT patients between January 2000 and December 2015. Retransplantation, multiorgan transplantation and patients in whom at least one of the variables required to calculate the IMPACT score was missing were excluded from the analysis (N = 2810). RESULTS: Median value of the IMPACT score was five points (IQR: 3, 8). Overall, 1-year survival rate was 79.1%. Kaplan-Meier 1-year survival rates by IMPACT score categories (0-2, 3-5, 6-9, 10-14, ≥15) were 84.4%, 81.5%, 79.3%, 77.3%, and 58.5%, respectively (Log-Rank test: p < .001). Performance analysis showed a good calibration (Hosmer-Lemeshow chi-square for 1 year was 7.56; p = .47) and poor discrimination ability (AUC-ROC .59) of the IMPACT score as a predictive model. CONCLUSIONS: In a contemporary Spanish cohort, the IMPACT score failed to accurately predict the risk of death after HT.

Infectious complications associated with short-term mechanical circulatory support in urgent heart transplant candidates.

INTRODUCTION AND OBJECTIVES: Short-term mechanical circulatory support is frequently used as a bridge to heart transplant in Spain. The epidemiology and prognostic impact of infectious complications in these patients are unknown. METHODS: Systematic description of the epidemiology of infectious complications and analysis of their prognostic impact in a multicenter, retrospective registry of patients treated with short-term mechanical devices as a bridge to urgent heart transplant from 2010 to 2015 in 16 Spanish hospitals. RESULTS: We studied 249 patients, of which 87 (34.9%) had a total of 102 infections. The most frequent site was the respiratory tract (n=47; 46.1%). Microbiological confirmation was obtained in 78 (76.5%) episodes, with a total of 100 causative agents, showing a predominance of gram-negative bacteria (n=58, 58%). Compared with patients without infection, those with infectious complications showed higher mortality during the support period (25.3% vs 12.3%, P=.009) and a lower probability of receiving a transplant (73.6% vs 85.2%, P=.025). In-hospital posttransplant mortality was similar in the 2 groups (with infection: 28.3%; without infection: 23.4%; P=.471). CONCLUSIONS: Patients supported with temporary devices as a bridge to heart transplant are exposed to a high risk of infectious complications, which are associated with higher mortality during the organ waiting period.

Results of heart retransplantation: subanalysis of the Spanish Heart Transplant Registry.

INTRODUCTION AND OBJECTIVES: Heart retransplantation (ReHT) is controversial in the current era. The aim of this study was to describe and analyze the results of ReHT in Spain. METHODS: We performed a retrospective cohort analysis from the Spanish Heart Transplant Registry from 1984 to 2018. Data were collected on donors, recipients, surgical procedure characteristics, immunosuppression, and survival. The main outcome was posttransplant all-cause mortality or need for ReHT. We studied differences in survival according to indication for ReHT, the time interval between transplants and era of ReHT. RESULTS: A total of 7592 heart transplants (HT) and 173 (2.3%) ReHT were studied (median age, 52.0 and 55.0 years, respectively). Cardiac allograft vasculopathy was the most frequent indication for ReHT (42.2%) and 59 patients (80.8%) received ReHT >5 years after the initial transplant. Acute rejection and primary graft failure decreased as indications over the study period. Renal dysfunction, hypertension, need for mechanical ventilation or intra-aortic balloon pump and longer cold ischemia time were more frequent in ReHT. Median follow-up for ReHT was 5.8 years. ReHT had worse survival than HT (weighted HR, 1.43; 95%CI, 1.17-1.44; P<.001). The indication of acute rejection (HR, 2.49; 95%CI, 1.45-4.27; P<.001) was related to the worst outcome. ReHT beyond 5 years after initial HT portended similar results as primary HT (weighted HR, 1.14; 95%CI, 0.86-1.50; P<.001). CONCLUSIONS: ReHT was associated with higher mortality than HT, especially when indicated for acute rejection. ReHT beyond 5 years had a similar prognosis to primary HT.

Cold ischemia >4 hours increases heart transplantation mortality. An analysis of the Spanish heart transplantation registry.

BACKGROUND: Cold ischemia time (CIT) has been associated to heart transplantation (HT) prognosis. However, there is still uncertainty regarding the CIT cutoff value that might have relevant clinical implications. METHODS: We analyzed all adults that received a first HT during the period 2008-2018. CIT was defined as the time between the cross-clamp of the donor aorta and the reperfusion of the heart. Primary outcome was 1-month mortality. RESULTS: We included 2629 patients, mean age was 53.3 ± 12.1 years and 655 (24.9%) were female. Mean CIT was 202 ± 67 min (minimum 20 min, maximum 600 min). One-month mortality per CIT quartile was 9, 12, 13, and 19%. One-year mortality per CIT quartile was 16, 19, 21, and 28%. CIT was an independent predictor of 1-month mortality, but only in the last quartile of CIT >246 min (odds ratio 2.1, 95% confidence interval 1.49-3.08, p < .001). We found no relevant differences in CIT during the study period. However, the impact of CIT in 1-month and 1-year mortality decreased with time (p value for the distribution of ischemic time by year 0.01), particularly during the last 5 years. CONCLUSIONS: Although the impact of CIT in HT prognosis seems to be decreasing in the last years, CIT in the last quartile (>246 min) is associated with 1-month and 1-year mortality. Our findings suggest the need to limit HT with CIT > 246 min or to use different myocardial preservation systems if the expected CIT is >4 h.

Impact of pre-hospital renal function on the detection of acute kidney injury in acute decompensated heart failure.

BACKGROUND: Acute kidney injury (AKI) is a serious complication in patients hospitalized for decompensated heart failure (HF). Currently, AKI definitions consider creatinine levels at admission as reference of baseline renal function (RF). However, renal impairment may already be present at admission. We aimed to study the impact on AKI detection of considering outpatient RF as reference. METHODS: In a cohort of 458 patients hospitalized for decompensated HF, we studied the occurrence of AKI using the standardized KDIGO criteria and grading (stages: 1, 2, 3), and considering two different definitions according to the RF used as reference or baseline: the latest outpatient measurement prior to admission vs. the first measurement at admission. We compared the prevalence, timing and prognostic value for both AKI definitions. RESULTS: The definition based on outpatient RF was associated with an increase in overall AKI detection from 20.1% to 33.8% (p < 0.001), and from 3.1% to 5.0% for advanced stages (2-3) (p < 0.001); additionally, 12.5% of patients already had criteria of AKI at admission (36.8% of AKI cases). Both definitions were associated with longer hospital stay. However, only AKI already present at admission, as based on pre-hospital creatinine, was independently associated with all-cause death, in-hospital and after discharge, and death or HF readmission in the follow-up: 1 stage (HR 2.72, 95%CI 1.83-4.06, p < 0.001) and 2-3 stage (HR 7.29, 95%CI, 3.02-17.64, p < 0.001). CONCLUSIONS: Evaluation of AKI in patients admitted with HF should consider pre-hospital RF, since it improves early identification of AKI and has implications for risk assessment.

Empleo del balón de contrapulsación intraaórtico como puente al trasplante cardiaco en España: resultados del estudio ASIS-TC / Use of intra-aortic balloon pump as a bridge to heart transplant in Spain: results from the ASIS-TC study

Introducción y objetivos: En España, el balón de contrapulsación intraaórtico (BCIA) se ha usado frecuentemente como puente al trasplante cardiaco (TxC) urgente. El propósito es analizar los resultados de esta estrategia. Métodos: Se realizó una revisión retrospectiva caso por caso de los registros clínicos de 281 pacientes adultos listados para TxC urgente asistidos con BCIA en 16 hospitales españoles entre 2010 y 2015. Se analizaron la supervivencia antes y después del trasplante y la incidencia de eventos adversos. Resultados: Se trasplantó a 194 pacientes (69%; IC95%, 63,3-74,4) y 20 (7,1%; IC95%, 4,4-10,8) fallecieron durante la asistencia, cuya duración media fue de 10,9+/-9,7 días. El BCIA se explantó antes de obtener un órgano a 32 pacientes (11,4%). En 35 pacientes (12,5%; IC95%, 8,8-16,9) se implantó un dispositivo de asistencia circulatoria mecánica completa. El tiempo en la lista de espera urgente se incrementó desde 5,9+/-6,3 días en 2010 hasta 15+/-11,7 días en 2015 (p=0,001). La supervivencia a 30 días y a 1 y 5 años tras el TxC fue del 88,1% (IC95%, 85,7-90,5), 76% (IC95%, 72,9-79,1) y 67,8% (IC95%, 63,7-71,9) respectivamente. La tasa de incidencia de eventos adversos mayores -disfunción del BCIA, ictus, hemorragia o infección- durante la asistencia fue de 26 (IC95%, 20,6-32,4) eventos/1.000 pacientes-día. La tasa de incidencia de explante del BCIA por complicaciones fue de 7,2 (IC95%, 4,5-10,8) casos/1.000 pacientes-día. Conclusiones: En el contexto de listas de espera cortas, el BCIA puede utilizarse como puente al TxC urgente con resultados aceptables. Esta estrategia conlleva una incidencia significativa de eventos adversos

Introduction and objectives: In Spain, intra-aortic balloon pump (IABP) has been used frequently as a bridge to urgent heart transplant (HT). We sought to analyze the clinical outcomes of this strategy. Methods: We conducted a case-by-case, retrospective review of clinical records of 281 adult patients listed for urgent HT under IABP support in 16 Spanish institutions from 2010 to 2015. Pre- and post-transplant survival and adverse clinical events were analyzed. Results: A total of 194 (69%, 95%CI, 63.3-74.4) patients were transplanted and 20 (7.1%, 95%CI, 4.4-10.8) died during a mean period of IABP support of 10.9+/-9.7 days. IABP support was withdrawn before an organ became available in 32 (11.4%) patients. Thirty-five (12.5%, 95%CI, 8.8-16.9) patients transitioned from IABP to full-support mechanical devices. Mean urgent waiting list time increased from 5.9+/-6.3 days in 2010 to 15+/-11.7 days in 2015 (P=.001). Post-transplant survival rates at 30-days, 1-year, and 5-years were 88.1% (95%CI, 85.7-90.5), 76% (95%CI, 72.9-79.1), and 67.8% (95%CI, 63.7-71.9), respectively. The incidence rate of major adverse clinical outcomes-device dysfunction, stroke, bleeding or infection-during IABP support was 26 (95%CI, 20.6-32.4) episodes per 1000 patient-days. The incidence rate of IABP explantation due to complications was 7.2 (95%CI, 4.5-10.8) cases per 1000 patient-days. Conclusions: In a setting of short waiting list times, IABP can be used to bridge candidates to urgent HT with acceptable postoperative results, but there were significant rates of adverse clinical events during support

Venoarterial extracorporeal membrane oxygenation with or without simultaneous intra-aortic balloon pump support as a direct bridge to heart transplantation: results from a nationwide Spanish registry.

OBJECTIVES: To investigate the potential clinical benefit of an intra-aortic balloon pump (IABP) in patients supported with venoarterial extracorporeal membrane oxygenation (VA-ECMO) as a bridge to heart transplantation (HT). METHODS: We studied 169 patients who were listed for urgent HT under VA-ECMO support at 16 Spanish institutions from 2010 to 2015. The clinical outcomes of patients under simultaneous IABP support (n = 73) were compared to a control group of patients without IABP support (n = 96). RESULTS: There were no statistically significant differences between the IABP and control groups with regard to the cumulative rates of transplantation (71.2% vs 81.2%, P = 0.17), death during VA-ECMO support (20.6% vs 14.6%, P = 0.31), transition to a different mechanical circulatory support device (5.5% vs 5.2%, P = 0.94) or weaning from VA-ECMO support due to recovery (2.7% vs 0%, P = 0.10). There was a higher incidence of bleeding events in the IABP group (45.2% vs 25%, P = 0.006; adjusted odds ratio 2.18, 95% confidence interval 1.02-4.67). In-hospital postoperative mortality after HT was 34.6% in the IABP group and 32.5% in the control group (P = 0.80). One-year survival after listing for urgent HT was 53.3% in the IABP group and 52.2% in the control group (log rank P = 0.75). Multivariate adjustment for potential confounders did not change this result (adjusted hazard ratio 0.94, 95% confidence interval 0.56-1.58). CONCLUSIONS: In our study, simultaneous IABP therapy in transplant candidates under VA-ECMO support did not significantly reduce morbidity or mortality.

Valor pronóstico de la concentración sérica de lactato de los receptores de trasplante cardiaco urgente: subanálisis del estudio multicéntrico español ASIS-TC / Prognostic value of serum lactate levels in patients undergoing urgent heart transplant: A subanalysis of the ASIS-TC Spanish multicenter study

Introducción y objetivos: Analizar el impacto del lactatos sérico en receptores de trasplante cardiaco urgente en asistencia circulatoria mecánica de corta duración preoperatoria. Métodos: Se realizó un subanálisis de un registro multicéntrico español basado en pacientes incluidos en «urgencia grado 0» para trasplante cardiaco con asistencia circulatoria mecánica preoperatoria de cortaduración entre 2010 y 2015. Se seleccionó a los receptores de trasplante con cifras preoperatorias de lactato conocidas. El desenlace principal fue la supervivencia 1año tras el trasplante. Resultados: Se estudió a 177 receptores de trasplante cardiaco urgente, de los que 90 necesitaron asistencia preoperatoria con oxigenador extracorpóreo de membrana venoarterial, 51 con asistencia ventricular izquierda y 36 con asistencia biventricular. De ellos, 44 (25%) presentaban hiperlactatemia antes del trasplante( 2mmol/l). En el análisis multivariable, la cifra de lactato sérico resultó predictora independiente de mortalidad tras el trasplante (cada 0,1 mmol/l, HR ajustada = 1,02; IC95%, 1,01-1,03; p = 0,007).La supervivencia estimada al año del trasplante cardiaco fue del 53,1% (IC95%, 45,3-60,9) en los pacientes con hiperlactactemia preoperatoria y el 75,6% (IC95%, 71,8-79,4)en los pacientes sin hiperlactatemia (HR ajustada = 1,94; IC95%, 1,04-3,63; p= 0,039). El impacto pronóstico de la hiperlactatemia fue significativo en los pacientes asistidos con oxigenador extracorpóreo de membrana venoarterial, pero no en aquellos con dispositivos de asistencia ventricular. Conclusiones: Los valores preoperatorios de ácido láctico son un potente factor pronóstico independiente en receptores de trasplante cardiaco urgente

Introduction and objectives: To study the prognostic value of serum lactate in patients under temporary preoperative mechanical circulatory support who underwent urgent heart transplant. Methods: We conducted asubanalysis of a Spanish multicenter registry recording data on patients under temporary mechanical circulatory support listed for highly urgent heart transplant from 2010 to 2015. Participants selected for the present study were those who received a transplant and who had known preoperative serum lactate levels. The main study outcome was 1-year survival after transplant. Results: A total of 177 heart transplant recipients were studied; preoperatively, 90 were supported on venoarterial extracorporeal membrane oxygenation, 51 on temporary left ventricular assist devices, and 36 on temporary biventricular assist devices. Preoperative hyperlactatemia( 2mmol/L) was present in 44 (25%) patients. On multivariable analysis, pretransplant serum lactate was identified as an independent predictor of 1-year posttransplant survival (adjusted HR per 0.1mmol/L, 1.02; 95%CI, 1.01-1.03; P=.007). One-year posttransplant survival was 53.1% (95%CI, 45.3-60.9) in patients with preoperative hyperlactatemia and 75.6% (95%CI, 71.8-79.4) in those without preoperative hyperlactatemia (adjusted HR, 1.94; 95%CI, 1.04-3.63; P=.039). Preoperative hyperlactatemia correlated with adverse outcomes in patient ssupported with extracorporeal membrane oxygenation, but not in patients supported on ventricular assist devices. Conclusions: Preoperative serum lactate is a strong independent predictor of worse outcomes in patients undergoing urgent heart transplant on short-term mechanical circulatory support

Use of Intra-aortic Balloon Pump as a Bridge to Heart Transplant in Spain: Results From the ASIS-TC Study.

INTRODUCTION AND OBJECTIVES: In Spain, intra-aortic balloon pump (IABP) has been used frequently as a bridge to urgent heart transplant (HT). We sought to analyze the clinical outcomes of this strategy. METHODS: We conducted a case-by-case, retrospective review of clinical records of 281 adult patients listed for urgent HT under IABP support in 16 Spanish institutions from 2010 to 2015. Pre- and post-transplant survival and adverse clinical events were analyzed. RESULTS: A total of 194 (69%, 95%CI, 63.3-74.4) patients were transplanted and 20 (7.1%, 95%CI, 4.4-10.8) died during a mean period of IABP support of 10.9±9.7 days. IABP support was withdrawn before an organ became available in 32 (11.4%) patients. Thirty-five (12.5%, 95%CI, 8.8-16.9) patients transitioned from IABP to full-support mechanical devices. Mean urgent waiting list time increased from 5.9±6.3 days in 2010 to 15±11.7 days in 2015 (P=.001). Post-transplant survival rates at 30-days, 1-year, and 5-years were 88.1% (95%CI, 85.7-90.5), 76% (95%CI, 72.9-79.1), and 67.8% (95%CI, 63.7-71.9), respectively. The incidence rate of major adverse clinical outcomes-device dysfunction, stroke, bleeding or infection-during IABP support was 26 (95%CI, 20.6-32.4) episodes per 1000 patient-days. The incidence rate of IABP explantation due to complications was 7.2 (95%CI, 4.5-10.8) cases per 1000 patient-days. CONCLUSIONS: In a setting of short waiting list times, IABP can be used to bridge candidates to urgent HT with acceptable postoperative results, but there were significant rates of adverse clinical events during support.

Prognostic Value of Serum Lactate Levels in Patients Undergoing Urgent Heart Transplant: A Subanalysis of the ASIS-TC Spanish Multicenter Study.

INTRODUCTION AND OBJECTIVES: To study the prognostic value of serum lactate in patients under temporary preoperative mechanical circulatory support who underwent urgent heart transplant. METHODS: We conducted a subanalysis of a Spanish multicenter registry recording data on patients under temporary mechanical circulatory support listed for highly urgent heart transplant from 2010 to 2015. Participants selected for the present study were those who received a transplant and who had known preoperative serum lactate levels. The main study outcome was 1-year survival after transplant. RESULTS: A total of 177 heart transplant recipients were studied; preoperatively, 90 were supported on venoarterial extracorporeal membrane oxygenation, 51 on temporary left ventricular assist devices, and 36 on temporary biventricular assist devices. Preoperative hyperlactatemia (≥ 2 mmol/L) was present in 44 (25%) patients. On multivariable analysis, pretransplant serum lactate was identified as an independent predictor of 1-year posttransplant survival (adjusted HR per 0.1 mmol/L, 1.02; 95%CI, 1.01-1.03; P = .007). One-year posttransplant survival was 53.1% (95%CI, 45.3-60.9) in patients with preoperative hyperlactatemia and 75.6% (95%CI, 71.8-79.4) in those without preoperative hyperlactatemia (adjusted HR, 1.94; 95%CI, 1.04-3.63; P = .039). Preoperative hyperlactatemia correlated with adverse outcomes in patients supported with extracorporeal membrane oxygenation, but not in patients supported on ventricular assist devices. CONCLUSIONS: Preoperative serum lactate is a strong independent predictor of worse outcomes in patients undergoing urgent heart transplant on short-term mechanical circulatory support.

Lack of improvement in autonomic cardiac tone after sacubitril/valsartan at lower than target doses.

Autonomic regulation plays a role in the progression of heart failure with reduced ejection fraction (HrEF).Twenty-one HFrEF patients, 60.8 ±â€¯13.1 years, receiving angiotensin inhibition, were replaced by angiotensin receptor-neprilysin inhibitor (ARNI). A 24-hour Holter recording was performed before and after 3 months of the maximum tolerated dose of ARNi. We evaluated changes in autonomic tone using heart rate variability (SDNN, rMSSD, pNN50, LF, HF, LF/HF, α1, α2), and heart rate turbulence (TO and TS). ARNI was up-titrated to a maximum daily dose of 190 ±â€¯102 mg, 47.5% of the target dose. ARNI therapy was not associated with any improvement in any of the parameters related with heart rate variability or heart rate turbulence (p > 0.05 for all). ARNI use at lower than target doses did not improve autonomic cardiac tone as evaluated by 24-hour Holter monitoring.

Clinical outcomes of temporary mechanical circulatory support as a direct bridge to heart transplantation: a nationwide Spanish registry.

BACKGROUND: In Spain, listing for high-urgent heart transplantation is allowed for critically ill candidates not weanable from temporary mechanical circulatory support (T-MCS). We sought to analyse the clinical outcomes of this strategy. METHODS AND RESULTS: We conducted a case-by-case, retrospective review of clinical records of 291 adult patients listed for high-urgent heart transplantation under temporary devices from 2010 to 2015 in 16 Spanish institutions. Survival after listing and adverse clinical events were studied. At the time of listing, 169 (58%) patients were supported on veno-arterial extracorporeal membrane oxygenation (VA-ECMO), 70 (24%) on temporary left ventricular assist devices (T-LVAD) and 52 (18%) on temporary biventricular assist devices (T-BiVAD). Seven patients transitioned from VA-ECMO to temporary ventricular assist devices while on the waiting list. Mean time on T-MCS was 13.1 ± 12.6 days. Mean time from listing to transplantation was 7.6 ± 8.5 days. Overall, 230 (79%) patients were transplanted and 54 (18.6%) died during MCS. In-hospital postoperative mortality after transplantation was 33.3%, 11.9% and 26.2% for patients bridged on VA-ECMO, T-LVAD and T-BiVAD, respectively (P = 0.008). Overall survival from listing to hospital discharge was 54.4%, 78.6% and 55.8%, respectively (P = 0.002). T-LVAD support was independently associated with a lower risk of death over the first year after listing (hazard ratio 0.52, 95% confidence interval 0.30-0.92). Patients treated with VA-ECMO showed the highest incidence rate of adverse clinical events associated with T-MCS. CONCLUSION: Temporary devices may be used to bridge critically ill candidates directly to heart transplantation in a setting of short waiting list times, as is the case of Spain. In our series, bridging with T-LVAD was associated with more favourable outcomes than bridging with T-BiVAD or VA-ECMO.

Preoperative Toxoplasma gondii serostatus does not affect long-term survival of cardiac transplant recipients. Analysis of the Spanish Heart Transplantation Registry.

BACKGROUND: It's unclear whether pre-transplant T. gondii seropositivity is associated with impaired survival in heart transplant recipients. OBJECTIVES: To test the above-mentioned hypothesis in the Spanish Heart Transplantation Registry. METHODS: Post-transplant outcomes of 4048 patients aged >16years who underwent first, single-organ heart transplantation in 17 Spanish institutions from 1984 to 2014 were studied. Long-term post-transplant survival and survival free of cardiac death or retransplantation of 2434 (60%) T. gondii seropositive recipients and 1614 (40%) T. gondii seronegative recipients were compared. RESULTS: T. gondii seropositive recipients were older, had higher body mass index, and presented higher prevalence of hypertension, hypercholesterolemia, COPD and Cytomegalovirus seropositivity than T. gondii seronegative recipients. In univariable analysis, pre-transplant T. gondii seropositivity was associated with increased post-transplant all-cause mortality (non-adjusted HR 1.15; 95% CI 1.04-1.26). However, this effect was no longer statistically significant after multivariable adjustment by recipient's age and sex (adjusted HR 1.01, 95% CI 0.92-1.11). Extended multivariable adjustment by other potential confounders showed similar results (adjusted HR 0.99, 95% CI 0.89-1.11). T. gondii seropositivity had no significant effect on the composite outcome cardiac death or retransplantation (non-adjusted HR 1.08, 95% CI 0.95-1.24, p=0.235). The distribution of the causes of death was comparable in T. gondii seropositive and T. gondii seronegative recipients. No statistically significant impact of donor's T. gondii serostatus or donor-recipient T. gondii serostatus matching on post-transplant survival was observed. CONCLUSIONS: Our analysis did not show a significant independent effect of preoperative T. gondii serostatus on long-term outcomes after heart transplantation.