Long‐term safety of intravenous cardiovascular agents in acute heart failure: results from the European Society of Cardiology Heart Failure Long‐Term Registry

[Abstract] Aims. The aim of this study was to assess long‐term safety of intravenous cardiovascular agents—vasodilators, inotropes and/or vasopressors—in acute heart failure (AHF). Methods and results. The European Society of Cardiology Heart Failure Long‐Term (ESC‐HF‐LT) registry was a prospective, observational registry conducted in 21 countries. Patients with unscheduled hospitalizations for AHF (n = 6926) were included: 1304 (18.8%) patients received a combination of intravenous (i.v.) vasodilators and diuretics, 833 (12%) patients received i.v. inotropes and/or vasopressors. Primary endpoint was long‐term all‐cause mortality. Main secondary endpoints were in‐hospital and post‐discharge mortality. Adjusted hazard ratio (HR) showed no association between the use of i.v. vasodilator and diuretic and long‐term mortality [HR 0.784, 95% confidence interval (CI) 0.596–1.032] nor in‐hospital mortality (HR 1.049, 95% CI 0.592–1.857) in the matched cohort (n = 976 paired patients). By contrast, adjusted HR demonstrated a detrimental association between the use of i.v. inotrope and/or vasopressor and long‐term all‐cause mortality (HR 1.434, 95% CI 1.128–1.823), as well as in‐hospital mortality (HR 1.873, 95% CI 1.151–3.048) in the matched cohort (n = 606 paired patients). No association was found between the use of i.v. inotropes and/or vasopressors and long‐term mortality in patients discharged alive (HR 1.078, 95% CI 0.769–1.512). A detrimental association with inotropes and/or vasopressors was seen in all geographic regions and, among catecholamines, dopamine was associated with the highest risk of death (HR 1.628, 95% CI 1.031–2.572 vs. no inotropes). Conclusions. Vasodilators did not demonstrate any association with long‐term clinical outcomes, while inotropes and/or vasopressors were associated with increased risk of all‐cause death, mostly related to excess of in‐hospital mortality in AHF

Conversion from immediate-release tacrolimus to prolonged-release tacrolimus in stable heart transplant patients: a retrospective study

[Abstract] Background Lifelong adherence with post-transplant immunosuppression is challenging, with nonadherence associated with greater acute rejection (AR) risk. Methods This retrospective study evaluated conversion from immediate-release tacrolimus (IRT) to prolonged-release tacrolimus (PRT), between January 2008 and December 2012 in stable adult heart transplant recipients. Cumulative incidence rate (IR) of AR and infection pre- and postconversion, safety, tacrolimus dose and trough levels, concomitant immunosuppression, and PRT discontinuation were analyzed (intention-to-treat population). Results Overall, 467 patients (mean age, 59.3 [SD, 13.3] years) converted to PRT at 5.1 (SD, 4.9) years post transplant and were followed for 3.4 (SD, 1.5) years. During the 6 months post conversion, 5 patients (1.1%; 95% CI, 0.35%–2.48%) had an AR episode and IR was 2.2/100 patient-years (95% CI, 0.91–5.26). Incidence of rejection preconversion varied by time from transplant to conversion. Infection IR was similar post- and preconversion (9.2/100 patient-years [95% CI, 7.4–11.3] vs 10.6/100 patient-years [95% CI, 8.8–12.3], respectively; P = .20). Safety variables remained similar post conversion. The IR of mortality/graft loss was 2.3/100 patient-years (95% CI, 1.7–3.1). Conclusions Conversion from IRT to PRT in heart transplant recipients in Spain was associated with no new safety concerns and appropriate immunosuppressive effectiveness

Health‐related quality of life, social support, and caregiver burden between six and 120 months after heart transplantation: a Spanish multicenter cross‐sectional study

[Abstract] A multicenter cross-sectional study was conducted to determine the current heart transplant (HTx) outcomes in Spain. Clinical and functional status, health-related quality of life (HRQoL), social support, and caregiver burden were analyzed in 303 adult transplant recipients (77.9% males) living with one functioning graft. Mean age at time of HTx (SD) was 56.4 (11.4) years, and the reason for transplantation in all patients was congestive heart failure. All patients had received a first heart transplant 6 (± 1), 12 (± 2), 36 (± 6), 60 (± 10), or 120 (± 20) months previously. Participants completed the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ-5D, the Duke-UNC Functional Social Support Questionnaire, and the Zarit Caregiver Burden Scale. Reasonable HRQoL, social support, and caregiver burden levels were found at all time points, although a slight decrease in HRQoL was recorded at 120 months (p ≤ 0.033). Multivariate regression analyses showed that complications, comorbidities, and hospitalizations were associated with HRQoL (EQ-5D: 48.4% of explained variance, F4,164 = 38.46, p < 0.001; KCCQ overall summary score: 45.0%, F3,198 = 54.073, p < 0.001). Patient functional capabilities and complications affected caregiver burden (p < 0.05). In conclusion, HTx patients reported reasonable levels of HRQoL with low caregiver burden. Clinical variables related to these outcomes included functional status, complications, and number of admissions

Adecuación en España a las recomendaciones terapéuticas de la guía de la ESC sobre insuficiencia cardiaca: ESC Heart Failure Long-term Registry

[Abstract] Introduction and objectives. To estimate the percentage of heart failure patients in Spain that received the European Society of Cardiology recommended treatments, and in those that did not, to determine the reasons why. Methods. The study included 2834 consecutive ambulatory patients with heart failure from 27 Spanish hospitals. We recorded general information, the treatment indicated, and the reasons why it was not prescribed in some cases. In patients who met the criteria to receive a certain drug, true undertreatment was defined as the percentage of patients who, without justification, did not receive the drug. Results. In total, 92.6% of ambulatory patients with low ejection fraction received angiotensin converting enzyme inhibitors or angiotensin receptor blockers, 93.3% beta-blockers, and 74.5% mineralocorticoid receptor antagonists. The true undertreatment rates were 3.4%, 1.8%, and 19.0%, respectively. Target doses were reached in 16.2% of patients receiving angiotensin converting enzyme inhibitors, 23.3% of those with angiotensin receptor blockers, 13.2% of those prescribed beta-blockers, and 23.5% of those with mineralocorticoid receptor antagonists. Among patients who could benefit from ivabradine, 29.1% received this drug. In total, 36% of patients met the criteria for defibrillator implantation and 90% of them had received the device or were scheduled for implantation, whereas 19.6% fulfilled the criteria for resynchronization therapy and 88.0% already had or would soon have the device. In patients who met the criteria, but did not undergo device implantation, the reasons were not cost-related. Conclusions. When justified reasons for not administering heart failure drugs were taken into account, adherence to the guideline recommendations was excellent. Exclusive use of the percentage of treated patients is a poor indicator of the quality of healthcare in heart failure. Measures should be taken to improve the attainment of optimal dosing in each patient.[Resumen] Introducción y objetivos. Estimar la proporción de pacientes con insuficiencia cardiaca atendidos en España que reciben los tratamientos recomendados por la Sociedad Europea de Cardiología y razones de que no los reciban, en su caso. Métodos. Se incluyó a 2.834 pacientes ambulatorios consecutivos con insuficiencia cardiaca de 27 hospitales españoles. Se recogió información general, tratamiento indicado y causas de que no lo recibiera, en su caso. De los pacientes que cumplen criterios para recibir tratamiento, infratratamiento real es la proporción que, sin justificación, no lo recibe. Resultados. El 92,6% de los pacientes ambulatorios con fracción de eyección reducida recibieron inhibidores de la enzima de conversión de la angiotensina o antagonistas del receptor de la angiotensina II; el 93,3%, bloqueadores beta y el 74,5%, antagonistas del receptor mineralocorticoideo. El infratratamiento real es del 3,4, el 1,8 y el 19,0% respectivamente. Alcanzan dosis objetivo de inhibidores de la enzima de conversión de la angiotensina el 16,2% de los pacientes; de antagonistas de los receptores de la angiotensina II, el 23,3%; de bloqueadores beta, el 13,2% y de antagonistas del receptor mineralocorticoideo, el 23,5%. El 29,1% de los pacientes que podrían beneficiarse de ivabradina la reciben; el 36% cumple criterios para implantar desfibrilador; de ellos, el 90% lo tienen ya implantado o programado; las cifras correspondientes en resincronización son el 19,6 y el 88,0%; el porcentaje restante no se debe a causas económicas. Conclusiones. Considerando razones justificadas para no administrar fármacos a estos pacientes, el cumplimiento de las guías es excelente. Utilizar solo la proporción de pacientes tratados es un mal indicador de calidad de la asistencia en insuficiencia cardiaca. Es necesario introducir medidas que mejoren el logro de la dosis óptima para cada paciente

Prevalence and severity of renal dysfunction among 1062 heart transplant patients according to criteria based on serum creatinine and estimated glomerular filtration rate: results from the CAPRI study

[Abstract] Chronic kidney disease (CKD) is staged on the basis of glomerular filtration rate; generally, the MDRD study estimate, eGFR, is used. Renal dysfunction (RD) in heart transplant (HT) patients is often evaluated solely in terms of serum creatinine (SCr). In a cross-sectional, 14-center study of 1062 stable adult HT patients aged 59.1 ± 12.5 yr (82.3% men), RD was graded as absent-or-mild (AoM), moderate, or severe (this last including dialysis and kidney graft) by two classifications: SCr-RD (SCr cutoffs 1.6 and 2.5 mg/dL) and eGFR-RD (eGFR cutoffs 60 and 30 mL/min/1.73 m2). SCr-RD was AoM in 68.5% of patients, moderate in 24.9%, and severe in 6.7%; eGFR-RD, AoM in 38.6%, moderate in 52.2%, severe in 9.2%. Among patients evaluated 9.5 yr post-HT (the periods defined by time-since-transplant quartiles), AoM/moderate/severe RD prevalences were 9.5, SCr-RD 58/32/10%, eGFR-RD 32/52/16%. The prevalence of severe RD increases with time since transplant. If the usual CKD stages are appropriate for HT patients, the need for less nephrotoxic immunosuppressants and other renoprotective measures is greater than is suggested by direct SCr-based grading, which should be abandoned as excessively insensitive

Impact of short-term mechanical circulatory support with extracorporeal devices on postoperative outcomes after emergency heart transplantation: data from a multi-institutional Spanish cohort

[Abstract] Objectives. We sought to investigate the potential impact of preoperative short-term mechanical circulatory support (MCS) with extracorporeal devices on postoperative outcomes after emergency heart transplantation (HT). Methods. We conducted an observational study of 669 patients who underwent emergency HT in 15 Spanish hospitals between 2000 and 2009. Postoperative outcomes of patients bridged to HT on short-term MCS (n = 101) were compared with those of the rest of the cohort (n = 568). Short-term MCS included veno-arterial extracorporeal membrane oxygenators (VA-ECMOs, n = 23), and both pulsatile-flow (n = 53) and continuous-flow (n = 25) extracorporeal ventricular assist devices (VADs). No patient underwent HT on intracorporeal VADs. Results. Preoperative short-term MCS was independently associated with increased in-hospital postoperative mortality (adjusted odds-ratio 1.75, 95% CI 1.05–2.91) and overall post-transplant mortality (adjusted hazard-ratio 1.60, 95% CI 1.15–2.23). Rates of major surgical bleeding, cardiac reoperation, postoperative infection and primary graft failure were also significantly higher among MCS patients. Causes of death and survival after hospital discharge were similar in MCS and non-MCS candidates. Increased risk of post-transplant mortality affected patients bridged on pulsatile-flow extracorporeal VADs (adjusted hazard-ratio 2.21, 95% CI 1.48–3.30) and continuous-flow extracorporeal VADs (adjusted hazard-ratio 2.24, 95% CI 1.20–4.19), but not those bridged on VA-ECMO (adjusted hazard-ratio 0.51, 95% CI 0.21–1.25). Conclusions. Patients bridged to emergency HT on short-term MCS are exposed to an increased risk of postoperative complications and mortality. In our series, preoperative bridging with VA-ECMO resulted in comparable post-transplant outcomes to those of patients transplanted on conventional support

Preoperative INTERMACS profiles determine postoperative outcomes in critically ill patients undergoing emergency heart transplantation: analysis of the Spanish National Heart Transplant Registry

[Abstract] Background. Postoperative outcomes of patients with advanced heart failure undergoing ventricular assist device implantation are strongly influenced by their preoperative Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles. We sought to investigate whether a similar association exists in patients undergoing emergency heart transplantation. Methods and Results. By means of the Spanish National Heart Transplant Registry database, we identified 704 adult patients treated with emergency heart transplantation in 15 Spanish centers between 2000 and 2009. Post-transplant outcomes were analyzed pertaining to patient preoperative INTERMACS profiles, which were retrospectively assigned by 2 blinded cardiologists. Before transplantation, INTERMACS profile 1 (critical cardiogenic shock) was present in 207 patients, INTERMACS profile 2 (progressive decline) in 291, INTERMACS profile 3 (inotropic dependence) in 176, and INTERMACS profile 4 (resting symptoms) was present in 30 patients. In-hospital postoperative mortality rates were, respectively, 43%, 26.8%, and 18% in patients with profiles 1, 2, and 3 to 4 (P<0.001). INTERMACS 1 patients also presented the highest incidence of primary graft failure (1: 31.3%, 2: 22.3%, 3–4: 21.8%; P=0.03) and postoperative need for dialysis (1: 33.2%, 2: 18.9%, 3–4: 21.5%; P<0.001). Adjusted odds-ratios for in-hospital postoperative mortality were 4.38 (95% confidence interval, 2.51–7.66) for profile 1 versus 3 to 4, 2.49 (95% confidence interval, 1.56–3.97) for profile 1 versus 2, and 1.76 (95% confidence interval, 1.02–3.03) for profile 2 versus 3 to 4. Long-term survival after hospital discharge was not influenced by preoperative INTERMACS profiles. Conclusions. Preoperative INTERMACS profiles determine outcomes after emergency heart transplantation. Results call for a change in policies related to the management of heart transplant candidates presenting with INTERMACS profiles 1 and 2

Hyperkalemia in Heart Failure Patients in Spain and Its Impact on Guidelines and Recommendations: ESC-EORP-HFA Heart Failure Long-Term Registry

[Abstract] Introduction and objectives: Hyperkalemia is a growing concern in the treatment of patients with heart failure and reduced ejection fraction because it limits the use of effective drugs. We report estimates of the magnitude of this problem in routine clinical practice in Spain, as well as changes in potassium levels during follow-up and associated factors. Methods: This study included patients with acute (n=881) or chronic (n=3587) heart failure recruited in 28 Spanish hospitals of the European heart failure registry of the European Society of Cardiology and followed up for 1 year. Various outcomes were analyzed, including changes in serum potassium levels and their impact on treatment. Results: Hyperkalemia (K+> 5.4 mEq/L) was identified in 4.3% (95%CI, 3.7%-5.0%) and 8.2% (6.5%-10.2%) of patients with chronic and acute heart failure, respectively, and was responsible for 28.9% of all cases of contraindication to mineralocorticoid receptor antagonist use and for 10.8% of all cases of failure to reach the target dose. Serum potassium levels were not recorded in 291 (10.8%) of the 2693 chronic heart failure patients with reduced ejection fraction. During follow-up, potassium levels increased in 179 of 1431 patients (12.5%, 95%CI, 10.8%-14.3%). This increase was directly related to age, diabetes, and history of stroke and was inversely related to history of hyperkalemia. Conclusions: This study highlights the magnitude of the problem of hyperkalemia in patients with heart failure in everyday clinical practice and the need to improve monitoring of this factor in these patients due to its interference with the possibility of receiving optimal treatment.[Resumen] Introducción y objetivos. La hiperpotasemia es una preocupación creciente en el tratamiento de los pacientes con insuficiencia cardiaca y fracción de eyección reducida, pues limita el uso de fármacos eficaces. Este trabajo ofrece estimaciones de la magnitud de este problema en la práctica clínica habitual en España, los cambios en las concentraciones de potasio en el seguimiento y los factores asociados. Métodos. Pacientes con insuficiencia cardiaca aguda (n = 881) y crónica (n = 3.587) seleccionados en 28 hospitales españoles del registro europeo de insuficiencia cardiaca de la European Society of Cardiology y seguidos 1 año para diferentes desenlaces, incluidos cambios en las cifras de potasio y su impacto en el tratamiento. Resultados. La hiperpotasemia (K+ > 5,4 mEq/l) está presente en el 4,3% (IC95%, 3,7-5,0%) y el 8,2% (6,5-10,2%) de los pacientes con insuficiencia cardiaca crónica y aguda; causa el 28,9% de todos los casos en que se contraindica el uso de antagonistas del receptor de mineralocorticoides y el 10,8% de los que no alcanzan la dosis objetivo. Del total de 2.693 pacientes ambulatorios con fracción de eyección reducida, 291 (10,8%) no tenían registrada medición de potasio. Durante el seguimiento, 179 de 1.431 (12,5%, IC95%, 10,8-14,3%) aumentaron su concentración de potasio, aumento relacionado directamente con la edad, la diabetes mellitus y los antecedentes de ictus e inversamente con los antecedentes de hiperpotasemia. Conclusiones. Este trabajo destaca el problema de la hiperpotasemia en pacientes con insuficiencia cardiaca de la práctica clínica habitual y la necesidad de continuar y mejorar la vigilancia de este factor en estos pacientes por su interferencia en el tratamiento óptimo

Long-term safety of intravenous cardiovascular agents in acute heart failure: results from the European Society of Cardiology Heart Failure Long-Term Registry

AIMS: The aim of this study was to assess long-term safety of intravenous cardiovascular agents-vasodilators, inotropes and/or vasopressors-in acute heart failure (AHF). METHODS AND RESULTS: The European Society of Cardiology Heart Failure Long-Term (ESC-HF-LT) registry was a prospective, observational registry conducted in 21 countries. Patients with unscheduled hospitalizations for AHF (n = 6926) were included: 1304 (18.8%) patients received a combination of intravenous (i.v.) vasodilators and diuretics, 833 (12%) patients received i.v. inotropes and/or vasopressors. Primary endpoint was long-term all-cause mortality. Main secondary endpoints were in-hospital and post-discharge mortality. Adjusted hazard ratio (HR) showed no association between the use of i.v. vasodilator and diuretic and long-term mortality [HR 0.784, 95% confidence interval (CI) 0.596-1.032] nor in-hospital mortality (HR 1.049, 95% CI 0.592-1.857) in the matched cohort (n = 976 paired patients). By contrast, adjusted HR demonstrated a detrimental association between the use of i.v. inotrope and/or vasopressor and long-term all-cause mortality (HR 1.434, 95% CI 1.128-1.823), as well as in-hospital mortality (HR 1.873, 95% CI 1.151-3.048) in the matched cohort (n = 606 paired patients). No association was found between the use of i.v. inotropes and/or vasopressors and long-term mortality in patients discharged alive (HR 1.078, 95% CI 0.769-1.512). A detrimental association with inotropes and/or vasopressors was seen in all geographic regions and, among catecholamines, dopamine was associated with the highest risk of death (HR 1.628, 95% CI 1.031-2.572 vs. no inotropes). CONCLUSIONS: Vasodilators did not demonstrate any association with long-term clinical outcomes, while inotropes and/or vasopressors were associated with increased risk of all-cause death, mostly related to excess of in-hospital mortality in AHF