Efficacy and safety of intermittent intravenous outpatient administration of levosimendan in patients with advanced heart failure: the LION-HEART multicentre randomised trial

Aims: The LION-HEART study was a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial evaluating the efficacy and safety of intravenous administration of intermittent doses of levosimendan in outpatients with advanced chronic heart failure. Methods and results: Sixty-nine patients from 12 centres were randomly assigned at a 2: 1 ratio to levosimendan or placebo groups, receiving treatment by a 6-hour intravenous infusion (0.2 mu g/kg/min without bolus) every 2weeks for 12weeks. The primary endpoint was the effect on serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) throughout the treatment period in comparison with placebo. Secondary endpoints included evaluation of safety, clinical events and health-related quality of life (HRQoL). The area under the curve (AUC, pg.day/mL) of the levels of NT-proBNP over time for patients who received levosimendan was significantly lower than for the placebo group {344 x 10(3) [95% confidence interval (CI) 283 x 10(3)-404 x 10(3)] vs. 535 x 10(3) [443 x 10(3)-626 x 10(3)], P = 0.003}. In comparison with the placebo group, the patients on levosimendan experienced a reduction in the rate of heart failure hospitalisation (hazard ratio 0.25; 95% CI 0.11-0.56; P = 0.001). Patients on levosimendan were less likely to experience a clinically significant decline in HRQoL over time (P = 0.022). Adverse event rates were similar in the two treatment groups. Conclusions: In this small pilot study, intermittent administration of levosimendan to ambulatory patients with advanced systolic heart failure reduced plasma concentrations of NT-proBNP, worsening of HRQoL and hospitalisation for heart failure. The efficacy and safety of this intervention should be confirmed in larger trials

International Consortium for Health Outcomes Measurement (ICHOM): Standardized Patient-Centered Outcomes Measurement Set for Heart Failure Patients

Whereas multiple national, international, and trial registries for heart failure have been created, international standards for clinical assessment and outcome measurement do not currently exist. The working group's objective was to facilitate international comparison in heart failure care, using standardized parameters and meaningful patient-centered outcomes for research and quality of care assessments. The International Consortium for Health Outcomes Measurement recruited an international working group of clinical heart failure experts, researchers, and patient representatives to define a standard set of outcomes and risk-adjustment variables. This was designed to document, compare, and ultimately improve patient care outcomes in the heart failure population, with a focus on global feasibility and relevance. The working group employed a Delphi process, patient focus groups, online patient surveys, and multiple systematic publications searches. The process occurred over 10 months, employing 7 international teleconferences. A 17-item set has been established, addressing selected functional, psychosocial, burden of care, and survival outcome domains. These measures were designed to include all patients with heart failure, whether entered at first presentation or subsequent decompensation, excluding cardiogenic shock. Sources include clinician report, administrative data, and validated patient-reported outcome measurement tools: the Kansas City Cardiomyopathy Questionnaire; the Patient Health Questionnaire-2; and the Patient-Reported Outcomes Measurement Information System. Recommended data included those to support risk adjustment and benchmarking across providers and regions. The International Consortium for Health Outcomes Measurement developed a dataset designed to capture, compare, and improve care for heart failure, with feasibility and relevance for patients and clinicians worldwide

Exercise training in patients with ventricular assist devices : a review of the evidence and practical advice. A position paper from the Committee on Exercise Physiology and Training and the Committee of Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology

Exercise training (ET) and secondary prevention measures in cardiovascular disease aim to stimulate early physical activity and to facilitate recovery and improve health behaviours. ET has also been proposed for heart failure patients with a ventricular assist device (VAD), to help recovery in the patient's functional capacity. However, the existing evidence in support of ET in these patients remains limited. After a review of current knowledge on the causes of the persistence of limitation in exercise capacity in VAD recipients, and concerning the benefit of ET in VAD patients, the Heart Failure Association of the European Society of Cardiology has developed the present document to provide practical advice on implementing ET. This includes appropriate screening to avoid complications and then starting with early mobilisation, ET prescription is individualised to meet the patient's needs. Finally, gaps in our knowledge are discussed

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

Empleo del balón de contrapulsación intraaórtico como puente al trasplante cardiaco en España: resultados del estudio ASIS-TC

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. Full English text available from:www.revespcardiol.org/e

Complicaciones infecciosas relacionadas con la asistencia circulatoria mecánica de corta duración en candidatos a trasplante cardiaco urgente

Introducción y objetivos El uso de dispositivos de asistencia circulatoria mecánica de corta duración como puente a trasplante es frecuente en España. Se desconocen la epidemiología y la repercusión de las complicaciones infecciosas en estos pacientes. Métodos Descripción sistemática de la epidemiología y análisis de la repercusión pronóstica de las complicaciones infecciosas en un registro multicéntrico retrospectivo de pacientes tratados con dispositivos de asistencia circulatoria mecánica de corta duración como puente a trasplante cardiaco urgente entre 2010 y 2015 en 16 hospitales españoles. Resultados Se estudió a 249 pacientes; 87 (34, 9%) de ellos tuvieron un total de 102 infecciones. La vía respiratoria fue la localización más frecuente (n = 47; 46, 1%). En 78 casos (76, 5%) se obtuvo confirmación microbiológica; se aislaron en total 100 gérmenes causales, con predominio de bacterias gramnegativas (n = 58, 58%). Los pacientes con complicaciones infecciosas presentaron mayor mortalidad durante el periodo de asistencia circulatoria mecánica (el 25, 3 frente al 12, 3%; p = 0, 009) y menor probabilidad de recibir un trasplante (el 73, 6 frente al 85, 2%; p = 0, 025) que los pacientes sin infección. La mortalidad posoperatoria tras el trasplante fue similar en ambos grupos (con infección, el 28, 3%; sin infección, el 23, 4%; p = 0, 471). Conclusiones Los pacientes tratados con dispositivos de asistencia circulatoria mecánica de corta duración como puente al trasplante cardiaco están expuestos a un alto riesgo de complicaciones infecciosas, las cuales se asocian con una mayor mortalidad en espera del órgano. 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

2019 EACTS Expert Consensus on long-term mechanical circulatory support

Long-term mechanical circulatory support (LT-MCS) is an important treatment modality for patients with severe heart failure. Different devices are available, and many-sometimes contradictory-observations regarding patient selection, surgical techniques, perioperative management and follow-up have been published. With the growing expertise in this field, the European Association for Cardio-Thoracic Surgery (EACTS) recognized a need for a structured multidisciplinary consensus about the approach to patients with LT-MCS. However, the evidence published so far is insufficient to allow for generation of meaningful guidelines complying with EACTS requirements. Instead, the EACTS presents an expert opinion in the LT-MCS field. This expert opinion addresses patient evaluation and preoperative optimization as well as management of cardiac and non-cardiac comorbidities. Further, extensive operative implantation techniques are summarized and evaluated by leading experts, depending on both patient characteristics and device selection. The faculty recognized that postoperative management is multidisciplinary and includes aspects of intensive care unit stay, rehabilitation, ambulatory care, myocardial recovery and end-of-life care and mirrored this fact in this paper. Additionally, the opinions of experts on diagnosis and management of adverse events including bleeding, cerebrovascular accidents and device malfunction are presented. In this expert consensus, the evidence for the complete management from patient selection to end-of-life care is carefully reviewed with the aim of guiding clinicians in optimizing management of patients considered for or supported by an LT-MCS device

Guidance on the management of left ventricular assist device (LVAD) supported patients for the non-LVAD specialist healthcare provider: executive summary

The accepted use of left ventricular assist device (LVAD) technology as a good alternative for the treatment of patients with advanced heart failure together with the improved survival of patients on the device and the scarcity of donor hearts has significantly increased the population of LVAD supported patients. Device-related, and patient-device interaction complications impose a significant burden on the medical system exceeding the capacity of LVAD implanting centres. The probability of an LVAD supported patient presenting with medical emergency to a local ambulance team, emergency department medical team and internal or surgical wards in a non-LVAD implanting centre is increasing. The purpose of this paper is to supply the immediate tools needed by the non-LVAD specialized physician - ambulance clinicians, emergency ward physicians, general cardiologists, and internists - to comply with the medical needs of this fast-growing population of LVAD supported patients. The different issues discussed will follow the patient's pathway from the ambulance to the emergency department, and from the emergency department to the internal or surgical wards and eventually back to the general practitioner.Cardiolog

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III

Registro Español de Trasplante Cardiaco. XXXI Informe Oficial de la Asociación de Insuficiencia Cardiaca de la Sociedad Española de Cardiología

Introducción y objetivos Se presentan las características clínicas y los resultados de los trasplantes cardiacos realizados en España con la actualización correspondiente a 2019. Métodos Se describen las características clínicas y los resultados de los trasplantes cardiacos realizados en 2019, así como las tendencias de estos en el periodo 2010-2018. Resultados En 2019 se realizaron 300 trasplantes (8.794 desde 1984; 2.745 entre 2010 y 2019). Respecto a años previos, los cambios más llamativos son el descenso hasta el 38% de los trasplantes realizados en código urgente, y la consolidación en el cambio de asistencia circulatoria pretrasplante, con la práctica desaparición del balón de contrapulsación (0, 7%), la estabilización del uso del oxigenador extracorpóreo de membrana (9, 6%) y el aumento de los dispositivos de asistencia ventricular (29%). La supervivencia en el trienio 2016-2018 es similar a la del trienio 2013-2015 (p = 0, 34), y ambas mejores que la del trienio 2010-2012 (p = 0, 002 y p = 0, 01 respectivamente). Conclusiones Se mantienen estables tanto la actividad del trasplante cardiaco en España como los resultados en supervivencia en los últimos 2 trienios. Hay una tendencia a realizar menos trasplantes urgentes, la mayoría con dispositivos de asistencia ventricular. 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