Review of the allocation criteria for heart transplant in Spain in 2023. SEC-Heart Failure Association/ONT/SECCE consensus document.

Heart transplant (HT) remains the best therapeutic option for patients with advanced heart failure (HF). The allocation criteria aim to guarantee equitable access to HT and prioritize patients with a worse clinical status. To review the HT allocation criteria, the Heart Failure Association of the Spanish Society of Cardiology (HFA-SEC), the Spanish Society of Cardiovascular and Endovascular Surgery (SECCE) and the National Transplant Organization (ONT), organized a consensus conference involving adult and pediatric cardiologists, adult and pediatric cardiac surgeons, transplant coordinators from all over Spain, and physicians and nurses from the ONT. The aims of the consensus conference were as follows: a) to analyze the organization and management of patients with advanced HF and cardiogenic shock in Spain; b) to critically review heart allocation and priority criteria in other transplant organizations; c) to analyze the outcomes of patients listed and transplanted before and after the modification of the heart allocation criteria in 2017; and d) to propose new heart allocation criteria in Spain after an analysis of the available evidence and multidisciplinary discussion. In this article, by the HFA-SEC, SECCE and the ONT we present the results of the analysis performed in the consensus conference and the rationale for the new heart allocation criteria in Spain.

Prognosis after heart transplant in patients with hypertrophic and restrictive cardiomyopathy. A nationwide registry analysis.

INTRODUCTION AND OBJECTIVES: Posttransplant outcomes among recipients with a diagnosis of hypertrophic cardiomyopathy (HCM) or restrictive cardiomyopathy (RCM) remain controversial. METHODS: Retrospective analysis of a nationwide registry of first-time recipients undergoing isolated heart transplant between 1984 and 2021. One-year and 5-year mortality in recipients with HCM and RCM were compared with those with dilated cardiomyopathy (DCM). RESULTS: We included 3703 patients (3112 DCM; 331 HCM; 260 RCM) with a median follow-up of 5.0 [3.1-5.0] years. Compared with DCM, the adjusted 1-year mortality risk was: HCM: HR, 1.38; 95%CI, 1.07-1.78; P=.01, RCM: HR, 1.48; 95%CI, 1.14-1.93; P=.003. The adjusted 5-year mortality risk was: HCM: HR, 1.17; 95%CI, 0.93-1.47; P=.18; RCM: HR, 1.52; 95%CI, 1.22-1.89; P<.001. Over the last 20 years, the RCM group showed significant improvement in 1-year survival (adjusted R2=0.95) and 5-year survival (R2=0.88); the HCM group showed enhanced the 5-year survival (R2=0.59), but the 1-year survival remained stable (R2=0.16). CONCLUSIONS: Both RCM and HCM were linked to a less favorable early posttransplant prognosis compared with DCM. However, at the 5-year mark, this unfavorable difference was evident only for RCM. Notably, a substantial temporal enhancement in both early and late mortality was observed for RCM, while for HCM, this improvement was mainly evident in late mortality.

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.

Incidence and Prognosis of Colorectal Cancer After Heart Transplantation: Data From the Spanish Post-Heart Transplant Tumor Registry.

In this observational and multicenter study, that included all patients who underwent a heart transplantation (HT) in Spain from 1984 to 2018, we analyzed the incidence, management, and prognosis of colorectal cancer (CRC) after HT. Of 6,244 patients with a HT and a median follow-up of 8.8 years since the procedure, 116 CRC cases (11.5% of noncutaneous solid cancers other than lymphoma registered) were diagnosed, mainly adenocarcinomas, after a mean of 9.3 years post-HT. The incidence of CRC increased with age at HT from 56.6 per 100,000 person-years among under 45 year olds to 436.4 per 100,000 person-years among over 64 year olds. The incidence rates for age-at-diagnosis groups were significantly greater than those estimated for the general Spanish population. Curative surgery, performed for 62 of 74 operable tumors, increased the probability of patient survival since a diagnosis of CRC, from 31.6% to 75.7% at 2 years, and from 15.8% to 48.6% at 5 years, compared to patients with inoperable tumors. Our results suggest that the incidence of CRC among HT patients is greater than in the general population, increasing with age at HT.

Evaluación mediante OCT del remodelado vascular pulmonar en insuficiencia cardiaca avanzada. Estudio OCTOPUS-CHF / Optical coherence tomography assessment of pulmonary vascular remodeling in advanced heart failure. The OCTOPUS-CHF study

Introducción y objetivos El remodelado vascular pulmonar es prevalente en la insuficiencia cardiaca avanzada. El cateterismo derecho es la prueba de elección, pero está limitado por la asunción de medidas indirectas, un enfoque de flujo no pulsátil, su dependencia de la carga o la variabilidad en la interpretación. Nuestro objetivo es evaluar la vasculopatía pulmonar mediante tomografía de coherencia óptica (OCT) intravascular y correlacionarla con los parámetros hemodinámicos. Métodos Estudio observacional, prospectivo y multicéntrico que incluyó a 100 pacientes en estudio previo al trasplante cardiaco. Todos se sometieron a un cateterismo derecho con OCT de la arteria pulmonar. Resultados La OCT se pudo analizar en 90 casos. La mediana de edad fue 57,50 [intervalo intercuartílico, 48,75-63,25] años y 71 eran varones (78,88%). La cardiopatía subyacente más frecuente fue la miocardiopatía dilatada no isquémica (33 pacientes [36,66%]). El grosor intimal se correlacionó con la presión arterial pulmonar media, las resistencias vasculares y el gradiente transpulmonar (coeficiente R de 0,42, 0,27 y 0,32 respectivamente). La estimación no invasiva de la presión sistólica pulmonar, el tiempo de aceleración y el acoplamiento ventriculoarterial también se correlacionaron con el grosor intimal (coeficiente R de 0,42, 0,27 y 0,49 respectivamente). Los pacientes con un grosor intimal > 0,25mm presentaron mayores presión pulmonar media (37,00 frente a 25,00mmHg; p=0,004) y resistencias vasculares (3,44 frente a 2,08 UW; p=0,017). Conclusiones La OCT pulmonar es factible y está significativamente asociada con los datos hemodinámicos. La correlación débil indica que el remodelado vascular no explica por completo la hipertensión pulmonar (AU)

Introduction and objectives Pulmonary vascular remodeling is common among patients with advanced heart failure. Right heart catheterization is the gold standard to assess pulmonary hypertension, but is limited by indirect measurement assumptions, a steady-flow view, load-dependency, and interpretation variability. We aimed to assess pulmonary vascular remodeling with intravascular optical coherence tomography (OCT) and to study its correlation with hemodynamic data. Methods This observational, prospective, multicenter study recruited 100 patients with advanced heart failure referred for heart transplant evaluation. All patients underwent right heart catheterization together with OCT evaluation of a subsegmentary pulmonary artery. Results OCT could be performed and properly analyzed in 90 patients. Median age was 57.50 [interquartile range, 48.75-63.25] years and 71 (78.88%) were men. The most frequent underlying heart condition was nonischemic dilated cardiomyopathy (33 patients [36.66%]). Vascular wall thickness significantly correlated with mean pulmonary artery pressure, pulmonary vascular resistance, and transpulmonary gradient (R coefficient=0.42, 0.27 and 0.32 respectively). Noninvasive estimation of pulmonary artery systolic pressure, acceleration time, and right ventricle-pulmonary artery coupling also correlated with wall thickness (R coefficient of 0.42, 0.27 and 0.49, respectively). Patients with a wall thickness over 0.25mm had significantly higher mean pulmonary pressures (37.00 vs 25.00mmHg; P=.004) and pulmonary vascular resistance (3.44 vs 2.08 WU; P=.017). Conclusions Direct morphological assessment of pulmonary vascular remodeling with OCT is feasible and is significantly associated with classic hemodynamic parameters. This weak association suggests that structural remodeling does not fully explain pulmonary hypertension (AU)

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.

Asistencia ventricular de larga duración en España (2007-2020). I informe del registro REGALAD / Durable ventricular assist device in Spain (2007-2020). First report of the REGALAD registry

Introducción y objetivos Se presentan las características clínicas, los resultados y las complicaciones de todos los pacientes a los que se implantó un dispositivo de asistencia circulatoria mecánica de larga duración en España entre 2007 y 2020. Métodos Análisis a partir del Registro español de asistencia ventricular de larga duración (REGALAD) en el que participaron los centros españoles con programa de asistencia ventricular mecánica. Resultado En este periodo se implantaron 263 dispositivos de asistencia ventricular de larga duración en 22 hospitales. En 182 pacientes (69%) la asistencia fue ventricular izquierda de flujo continuo; en 79 (30%), de flujo pulsátil (58 izquierdas y 21 biventriculares), y en 2 (1%) se implantó un corazón artificial total. El objetivo de la asistencia fue el puente al trasplante en 78 pacientes (30%), puente a la candidatura en 110 (42%), puente a la recuperación en 3 (1%) y la terapia de destino en 72 (27%). La supervivencia total a 6, 12 y 24 meses fue del 79, el 74 y el 69% respectivamente, y la mejor se consiguió con las asistencias izquierdas de flujo continuo (el 84, el 80 y el 75%). Las principales complicaciones asociadas fueron: infecciones (el 37% de los pacientes), hemorragias (35%), neurológicas (29%) y disfunción de la asistencia (17%). Conclusiones Las asistencias ventriculares de larga duración han irrumpido en España como un tratamiento útil en la insuficiencia cardiaca avanzada. Como en otros registros internacionales, se tiende a utilizar dispositivos izquierdos intracorpóreos de flujo continuo, que se asocian con mejores resultados. Las complicaciones relacionadas siguen siendo frecuentes y graves (AU)

Introduction and objectives This report presents the clinical characteristics, outcomes and complications of all consecutive patients implanted with a long-term mechanical circulatory support device in Spain between 2007 and 2020. Methods Analysis of the Spanish Registry of durable ventricular assist devices (REGALAD) including data form Spanish centers with a mechanical circulatory support program. Results During the study period, 263 ventricular assist devices were implanted in 22 hospitals. The implanted device was an isolated continuous-flow left ventricular assist device in 182 patients (69%), a pulsatile-flow device (58 isolated left ventricular and 21 biventricular) in 79 (30%), and a total artificial heart in 2 patients (1%). The strategy of the implant was as bridge to heart transplant in 78 patients (30%), bridge to candidacy in 110 (42%), bridge to recovery in 3 (1%) and destination therapy in 72 patients (27%). Overall survival at 6, 12 and 24 months was 79%, 74% and 69%, respectively, and was better in continuous-flow left ventricular assist devices (84%, 80%, and 75%). The main adverse events related to this therapy were infections (37% of patients), bleeding (35%), neurological (29%), and device malfunction (17%). Conclusions Durable ventricular assist devices have emerged in Spain in the last few years as a useful therapy for patients with advanced heart failure. As in other international registries, the current trend is to use continuous-flow intracorporeal left ventricular devices, which are associated with better results. Adverse events continue to be frequent and severe (AU)

Opportunistic Genetic Screening for Familial Hypercholesterolemia in Heart Transplant Patients.

Heart transplantation remains the gold standard for the treatment of advanced heart failure (HF). Identification of the etiology of HF is mandatory, as the specific pathology can determine subsequent treatment. Early identification of familial hypercholesterolemia (FH), the most common genetic disorder associated with premature cardiovascular disease, has a potential important impact on clinical management and public health. We evaluated the genetic information in the genes associated with FH in a cohort of 140 heart-transplanted patients. All patients underwent NGS genetic testing including LDLR, APOB, and PCSK9. We identified four carriers of rare pathogenic variants in LDLR and APOB. Although all four identified carriers had dyslipidemia, only the one carrying the pathogenic variant LDLR c.676T>C was transplanted due to CAD. Another patient with heart valvular disease was carrier of the controversial LDLR c.2096C>T. Two additional patients with non-ischemic dilated cardiomyopathy were carriers of variants in APOB (c.4672A>G and c.5600G>A). In our cohort, we identified the genetic cause of FH in patients that otherwise would not have been diagnosed. Opportunistic genetic testing for FH provides important information to perform personalized medicine and risk stratification not only for patients but also for relatives at concealed high cardiovascular risk. Including the LDLR gene in standard NGS cardiovascular diagnostics panels should be considered.

Durable ventricular assist device in Spain (2007-2020). First report of the REGALAD registry.

INTRODUCTION AND OBJECTIVES: This report presents the clinical characteristics, outcomes and complications of all consecutive patients implanted with a long-term mechanical circulatory support device in Spain between 2007 and 2020. METHODS: Analysis of the Spanish Registry of durable ventricular assist devices (REGALAD) including data form Spanish centers with a mechanical circulatory support program. RESULTS: During the study period, 263 ventricular assist devices were implanted in 22 hospitals. The implanted device was an isolated continuous-flow left ventricular assist device in 182 patients (69%), a pulsatile-flow device (58 isolated left ventricular and 21 biventricular) in 79 (30%), and a total artificial heart in 2 patients (1%). The strategy of the implant was as bridge to heart transplant in 78 patients (30%), bridge to candidacy in 110 (42%), bridge to recovery in 3 (1%) and destination therapy in 72 patients (27%). Overall survival at 6, 12 and 24 months was 79%, 74% and 69%, respectively, and was better in continuous-flow left ventricular assist devices (84%, 80%, and 75%). The main adverse events related to this therapy were infections (37% of patients), bleeding (35%), neurological (29%), and device malfunction (17%). CONCLUSIONS: Durable ventricular assist devices have emerged in Spain in the last few years as a useful therapy for patients with advanced heart failure. As in other international registries, the current trend is to use continuous-flow intracorporeal left ventricular devices, which are associated with better results. Adverse events continue to be frequent and severe.

Optical coherence tomography assessment of pulmonary vascular remodeling in advanced heart failure. The OCTOPUS-CHF study.

INTRODUCTION AND OBJECTIVES: Pulmonary vascular remodeling is common among patients with advanced heart failure. Right heart catheterization is the gold standard to assess pulmonary hypertension, but is limited by indirect measurement assumptions, a steady-flow view, load-dependency, and interpretation variability. We aimed to assess pulmonary vascular remodeling with intravascular optical coherence tomography (OCT) and to study its correlation with hemodynamic data. METHODS: This observational, prospective, multicenter study recruited 100 patients with advanced heart failure referred for heart transplant evaluation. All patients underwent right heart catheterization together with OCT evaluation of a subsegmentary pulmonary artery. RESULTS: OCT could be performed and properly analyzed in 90 patients. Median age was 57.50 [interquartile range, 48.75-63.25] years and 71 (78.88%) were men. The most frequent underlying heart condition was nonischemic dilated cardiomyopathy (33 patients [36.66%]). Vascular wall thickness significantly correlated with mean pulmonary artery pressure, pulmonary vascular resistance, and transpulmonary gradient (R coefficient=0.42, 0.27 and 0.32 respectively). Noninvasive estimation of pulmonary artery systolic pressure, acceleration time, and right ventricle-pulmonary artery coupling also correlated with wall thickness (R coefficient of 0.42, 0.27 and 0.49, respectively). Patients with a wall thickness over 0.25mm had significantly higher mean pulmonary pressures (37.00 vs 25.00mmHg; P=.004) and pulmonary vascular resistance (3.44 vs 2.08 WU; P=.017). CONCLUSIONS: Direct morphological assessment of pulmonary vascular remodeling with OCT is feasible and is significantly associated with classic hemodynamic parameters. This weak association suggests that structural remodeling does not fully explain pulmonary hypertension.

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.

Heart Failure with Reduced Ejection Fraction and Prognostic Scales: The Impact of Exercise Modality in Cardiopulmonary Exercise Tests.

The cardiopulmonary exercise (CPET) test is an essential tool to determine the severity, prognosis, and need for invasive treatments in heart failure with reduced ejection fraction (HFrEF) but disregards the exercise modality. The present study aimed at analyzing the differences between treadmill and cycle-ergometer exercises. This was a prospective study, involving 65 patients with HfrEF who performed treadmill exercise followed by cycle-ergometer exercise 72 h later. We enrolled 65 patients, aged 58 ± 9 years, with an ejection fraction of 29 ± 9%. Peak VO2 was 20% greater (95% CI: 18−21%; p < 0.000) on the treadmill, and the ventilatory efficiency estimated by the VE/VCO2 slope (32 ± 8 vs. 34 ± 9; p < 0.05). The ventilatory response was greater on the treadmill: maximum ventilation (55 ± 16 vs. 46 ± 11 L/min; p < 0.000) and ventilatory reserve at the maximum effort (28 ± 17 vs. 41 ± 15%; p < 0.000). These values led to a change in the functional class of 23 (51%) patients and ventilatory class of 28 (47%) patients. Differences in the main parameters, including peak VO2 and VE/VCO2, impact prognostic scales and possible advanced treatments; therefore, the results should be interpreted in accordance with the exercise modality.

Prevalence, Incidence, and Outcomes of Hyperkalaemia in Patients with Chronic Heart Failure and Reduced Ejection Fraction from a Spanish Multicentre Study: SPANIK-HF Design and Baseline Characteristics.

Hyperkalaemia is a growing concern in the treatment of patients with heart failure and reduced ejection fraction (HFrEF) as it limits the use of some prognostic-modifying drugs and has a negative impact on prognosis. The objective of the present study was to estimate the prevalence of hyperkalaemia in outpatients with HFrEF and its impact on achieving optimal medical treatment. For this purpose, a multicentre, prospective, and observational study was carried out on consecutive HFrEF patients who were monitored as outpatients in heart failure (HF) units and who, in the opinion of their doctor, received optimal medical treatment. A total of 565 HFrEF patients were included from 16 specialised HF units. The mean age was 66 ± 12 years, 78% were male, 45% had an ischemic cause, 39% had atrial fibrillation, 43% were diabetic, 42% had a glomerular filtration rate < 60 mL/min/1.7 m2, and the mean left ventricular ejection fraction was 31 ± 7%. Treatment at the study entry included: 76% on diuretics, 13% on ivabradine, 7% on digoxin, 18.9% on angiotensin-conversing enzyme inhibitors (ACEi), 11.3% on angiotensin receptors blockers (ARBs), 63.8% on angiotensin-neprilysin inhibitors (ARNi), 78.5% on mineralocorticoid receptor antagonists (MRAs), and 92.9% on beta-blockers. Potassium levels in the baseline analysis were: ≤5 mEq/L = 80.5%, 5.1−5.4 mEq/L = 13.8%, 5.5−5.9 mEq/L = 4.6%, and ≥6 mEq/L = 1.06%. Hyperkalaemia was the reason for not prescribing or reaching the target dose of an MRAs in 34.8% and 12.5% of patients, respectively. The impact of hyperkalaemia on not prescribing or dropping below the target dose in relation to ACEi, ARBs, and ARNi was significantly less. In conclusion, hyperkalaemia is a frequent problem in the management of patients with HFrEF and a limiting factor in the optimisation of medical treatment.

Remote heart failure management using the HeartLogic algorithm. RE-HEART registry.

INTRODUCTION AND OBJECTIVES: HeartLogic is a multiparametric algorithm incorporated into implantable cardioverter-defibrillators (ICD). The associated alerts predict impending heart failure (HF) decompensations. Our objective was to analyze the association between alerts and clinical events and to describe the implementation of a protocol for remote management in a multicenter registry. METHODS: We evaluated study phase 1 (the investigators were blinded to the alert state) and phases 2 and 3 (after HeartLogic activation, managed as per local practice and with a standardized protocol, respectively). RESULTS: We included 288 patients from 15 centers. In phase 1, the median observation period was 10 months and there were 73 alerts (0.72 alerts/patient-y), with 8 hospitalizations and 2 emergency room admissions for HF (0.10 events/patient-y). There were no HF hospitalizations outside the alert period. In the active phases, the median follow-up was 16 (95%CI, 15-22) months and there were 277 alerts (0.89 alerts/patient-y); 33 were associated with HF hospitalizations or HF death (n=6), 46 with minor decompensations, and 78 with other events. The unexplained alert rate was 0.39 alerts/patient-y. Outside the alert state, there was only 1 HF hospitalization and 1 minor HF decompensation. Most alerts (82% in phase 2 and 81% in phase 3; P=.861) were remotely managed. The median NT-proBNP value was higher within than outside the alert state (7378 vs 1210 pg/mL; P <.001). CONCLUSIONS: The HeartLogic index was frequently associated with HF-related events and other clinically relevant situations, with a low rate of unexplained events. A standardized protocol allowed alerts to be safely and remotely detected and appropriate action to be taken on them.

Gender differences in drug titration among heart failure patients with reduced ejection fraction in the ETIFIC trial.

INTRODUCTION AND OBJECTIVES: Optimal medical therapy decreases mortality and heart failure (HF) hospitalizations in HF patients with reduced left ventricular ejection fraction. Women have been underrepresented in clinical trials and not specifically evaluated. This study aimed to compare the safety and effectiveness of drug titration in women vs men. METHODS: This post hoc gender study of the ETIFIC multicenter randomized trial included hospitalized patients with new-onset HF with reduced ejection fraction and New York Heart Association II-III and no contraindications to beta-blockers. A structured 4-month titration process was implemented in HF clinics. The primary endpoint was the mean relative dose (% of target dose) of beta-blockers achieved by women vs men. Secondary endpoints included the mean relative doses of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists, adverse events, and other clinical outcomes at 6 months. RESULTS: A total of 320 patients were included, 83 (25.93%) women and 237 (74.06%) men (76 vs 213 analyzed). The mean±standard deviation of the relative doses achieved by women vs men were as follows: beta-blockers 62.08%±30.72% vs 64.4%±32.77%, with a difference of-2.32% (95%CI,-10.58-5.94), P = .580; and mineralocorticoid receptor antagonists 79.85%±27.72% vs 67.29%±31.43%, P =.003. No other differences in drug dosage were found. Multivariate analysis showed nonsignificant differences. CV mortality was 1 (1.20%) vs 3 (1.26%), P=1, and HF hospitalizations 0 (0.00%) vs 10 (4.22%), P=.125. CONCLUSIONS: In a post hoc analysis from the HF-titration ETIFIC trial, we found nonsignificant gender differences in drug dosage, cardiovascular mortality, and HF hospitalizations. Trial registry number: NCT02546856.

Impact of intrapatient blood level variability of calcineurin inhibitors on heart transplant outcomes.

INTRODUCTION AND OBJECTIVES: Intrapatient blood level variability (IPV) of calcineurin inhibitors has been associated with poor outcomes in solid-organ transplant, but data for heart transplant are scarce. Our purpose was to ascertain the clinical impact of IPV in a multi-institutional cohort of heart transplant recipients. METHODS: We retrospectively studied patients aged ≥18 years, with a first heart transplant performed between 2000 and 2014 and surviving≥ 1 year. IPV was assessed by the coefficient of variation of trough levels from posttransplant months 4 to 12. A composite of rejection or mortality/graft loss or rejection and all-cause mortality/graft loss between years 1 to 5 posttransplant were analyzed by Cox regression analysis. RESULTS: The study group consisted of 1581 recipients (median age, 56 years; women, 21%). Cyclosporine immediate-release tacrolimus and prolonged-release tacrolimus were used in 790, 527 and 264 patients, respectively. On multivariable analysis, coefficient of variation> 27.8% showed a nonsignificant trend to association with 5-year rejection-free survival (HR, 1.298; 95%CI, 0.993-1.695; P=.056) and with 5-year mortality (HR, 1.387; 95%CI, 0.979-1.963; P=.065). Association with rejection became significant on analysis of only those patients without rejection episodes during the first year posttransplant (HR, 1.609; 95%CI, 1.129-2.295; P=.011). The tacrolimus-based formulation had less IPV than cyclosporine and better results with less influence of IPV. CONCLUSIONS: IPV of calcineurin inhibitors is only marginally associated with mid-term outcomes after heart transplant, particularly with the tacrolimus-based immunosuppression, although it could play a role in the most stable recipients.