Clinical findings and prognosis of Danon’s Disease. An analysis from the Spanish multicenter Danon Registry.

Introducción y objetivos: La enfermedad de Danon (ED) es una enfermedad poco frecuente producida por mutaciones en el gen LAMP2. Se considera una enfermedad multisistémica caracterizada por: miocardiopatía hipertrófica con preexcitación y gran hipertrofia, discapacidad intelectual, miopatía, presentación infantil y peor pronóstico en varones. Existen pocas series que permitan conocer las características clínicas y el pronóstico de la ED en detalle. Métodos Estudio retrospectivo basado en el análisis de los registros clínicos de los pacientes con ED seguidos en 10 hospitales españoles. Resultados Se incluyeron 28 pacientes (3220años, 79% mujeres). Los varones demostraron una elevada prevalencia de manifestaciones extracardiacas: miopatía (80%), trastornos del aprendizaje (83%) y alteraciones visuales (60%), siendo hallazgos infrecuentes en las mujeres (5%, 0% y 24%, respectivamente). Aunque la miocardiopatía hipertrófica era la cardiopatía más habitual (67%), el grosor máximo ventricular fue 157 mm y 12 pacientes (10 mujeres) se presentaron con miocardiopatía dilatada. Sólo 11 pacientes (46%) (4 hombres y 7 mujeres) mostraron preexcitación y en 16 (67%) la enfermedad debutó por encima de los 20 años. Tras una mediana de seguimiento de 4 años (P25-752-9), 4 varones (67%) y 9 mujeres (41%) fallecieron o requirieron un trasplante. Tanto la afectación cardiaca como los eventos adversos ocurrieron más tardíamente en mujeres (37±9 vs 23±16 y 38±21 vs 20±11 años, respectivamente). Conclusiones. Las características clínicas de la ED difieren substancialmente de lo tradicionalmente considerado. La edad de presentación de la ED es más tardía, no se expresa como una patología multisistémica en mujeres y la preexcitación es poco frecuente. Aunque las mujeres presentan mal pronóstico, los eventos adversos ocurren a una edad más avanzada.Background Danon's disease (DD) is a rare disease caused by mutations in the LAMP2 gene. It is considered a multisystemic disease characterized by: hypertrophic cardiomyopathy with preexcitation and ventricular hypertrophy, intellectual disability, myopathy, childhood presentation and worse prognosis in men. Available data regarding clinical characteristics and the prognosis of the DD are scarce. Methods Retrospective study based on the analysis of the clinical records of patients with ED from 10 Spanish hospitals. Results Twenty-eight patients were included (32±20 years, 79% women). Males showed a high prevalence of extracardiac manifestations: myopathy (80%), learning disorders (837%) and visual alterations (60%), which were uncommon findings in women (5%, 0% and 24%, respectively). Although hypertrophic cardiomyopathy was the most common form of heart disease (67%), maximum wall thickness was 15±7 mm and 12 patients (10 women) presented as dilated cardiomyopathy. Only 11 patients (467%) (4 men and 7 women) showed preexcitation and in 16 (67%) the disease started above 20 years-old. After a median follow-up of 4 years (P25-75: 2-9), 4 men (67%) and 9 women (41%) died or required a heart transplant. Both cardiac involvement and adverse events occurred later in women (37 ± 9 vs 23 ± 16 and 38± 21 vs 20 ± 11 years, respectively). Conclusions Clinical characteristics of DD differ substantially from what has been traditionally considered. ED usually presents at an increased age, is not a multisystemic disease in women and preexcitation is rare. Even though, women show also a poor prognosis, adverse events occur at a later age.pre-print518 K

The Usefulness of the MEESSI Score for Risk Stratification of Patients With Acute Heart Failure at the Emergency Department.

INTRODUCTION AND OBJECTIVES: The MEESSI scale stratifies acute heart failure (AHF) patients at the emergency department (ED) according to the 30-day mortality risk. We validated the MEESSI risk score in a new cohort of Spanish patients to assess its accuracy in stratifying patients by risk and to compare its performance in different settings. METHODS: We included consecutive patients diagnosed with AHF in 30 EDs during January and February 2016. The MEESSI score was calculated for each patient. The c-statistic measured the discriminatory capacity to predict 30-day mortality of the full MEESSI model and secondary models. Further comparisons were made among subgroups of patients from university and community hospitals, EDs with high-, medium- or low-activity and EDs that recruited or not patients in the original MEESSI derivation cohort. RESULTS: We analyzed 4711 patients (university/community hospitals: 3811/900; high-/medium-/low-activity EDs: 2695/1479/537; EDs participating/not participating in the previous MEESSI derivation study: 3892/819). The distribution of patients according to the MEESSI risk categories was: 1673 (35.5%) low risk, 2023 (42.9%) intermediate risk, 530 (11.3%) high risk and 485 (10.3%) very high risk, with 30-day mortality of 2.0%, 7.8%, 17.9%, and 41.4%, respectively. The c-statistic for the full model was 0.810 (95%CI, 0.790-0.830), ranging from 0.731 to 0.785 for the subsequent secondary models. The discriminatory capacity of the MEESSI risk score was similar among subgroups of hospital type, ED activity, and original recruiter EDs. CONCLUSIONS: The MEESSI risk score successfully stratifies AHF patients at the ED according to the 30-day mortality risk, potentially helping clinicians in the decision-making process for hospitalizing patients

Short-term outcomes by chronic betablocker treatment in patients presenting to emergency departments with acute heart failure: BB-EAHFE

Aims: to evaluate the association between chronic treatment with betablockers (BB) and the severity of decompensation and short-term outcomes of patients with acute heart failure (AHF). Methods and results: we consecutively included all patients presenting with AHF to 45 Spanish emergency departments (ED) during six different time-periods between 2007 and 2018. Patients were stratified according to whether they were on chronic treatment with BB at the time of ED consultation. Those receiving BB were compared (adjusted odds ratio-OR-with 95% confidence interval-CI-) with those not receiving BB group in terms of in-hospital and 7-day all-cause mortality, need for hospitalization, and prolonged length of stay (≥7 days). Among the 17 923 recruited patients (median age: 80 years; 56% women), 7795 (43%) were on chronic treatment with BB. Based on the MEESSI-AHF risk score, those on BB were at lower risk. In-hospital mortality was observed in 1310 patients (7.4%), 7-day mortality in 765 (4.3%), need for hospitalization in 13 428 (75.0%), and prolonged length of stay (43.3%). After adjustment for confounding, those on chronic BB were at lower risk for in-hospital all-cause mortality (OR = 0.85, 95% CI = 0.79-0.92, P < 0.001); 7-day all-cause mortality (OR = 0.77, 95% CI = 0.70-0.85, P < 0.001); need for hospitalization (OR = 0.89, 95% CI = 0.85-0.94, P < 0.001); prolonged length of stay (OR = 0.90, 95% CI = 0.86-0.94, P < 0.001). A propensity matching approach yielded consistent findings. Conclusion: in patients presenting to ED with AHF, those on BB had better short-term outcomes than those not receiving BB

The FAST-FURO study: effect of very early administration of intravenous furosemide in the prehospital setting to patients with acute heart failure attending the emergency department

AIMS The effect of early administration of intravenous (IV) furosemide in the emergency department (ED) on short-term outcomes of acute heart failure (AHF) patients remains controversial, with one recent Japanese study reporting a decrease of in-hospital mortality and one Korean study reporting a lack of clinical benefit. Both studies excluded patients receiving prehospital IV furosemide and only included patients requiring hospitalization. To assess the impact on short-term outcomes of early IV furosemide administration by emergency medical services (EMS) before patient arrival to the ED. METHODS AND RESULTS In a secondary analysis of the Epidemiology of Acute Heart Failure in Emergency Departments (EAHFE) registry of consecutive AHF patients admitted to Spanish EDs, patients treated with IV furosemide at the ED were classified according to whether they received IV furosemide from the EMS (FAST-FURO group) or not (CONTROL group). In-hospital all-cause mortality, 30-day all-cause mortality, and prolonged hospitalization (>10 days) were assessed. We included 12 595 patients (FAST-FURO = 683; CONTROL = 11 912): 968 died during index hospitalization [7.7%; FAST-FURO = 10.3% vs. CONTROL = 7.5%; odds ratio (OR) = 1.403, 95% confidence interval (95% CI) = 1.085-1.813; P = 0.009], 1269 died during the first 30 days (10.2%; FAST-FURO = 13.4% vs. CONTROL = 9.9%; OR = 1.403, 95% CI = 1.146-1.764; P = 0.004), and 2844 had prolonged hospitalization (22.8%; FAST-FURO = 25.8% vs. CONTROL = 22.6%; OR = 1.189, 95% CI = 0.995-1.419; P = 0.056). FAST-FURO group patients had more diabetes mellitus, ischaemic cardiomyopathy, peripheral artery disease, left ventricular systolic dysfunction, and severe decompensations, and had a better New York Heart Association class and had less atrial fibrillation. After adjusting for these significant differences, early IV furosemide resulted in no impact on short-term outcomes: OR = 1.080 (95% CI = 0.817-1.427) for in-hospital mortality, OR = 1.086 (95% CI = 0.845-1.396) for 30-day mortality, and OR = 1.095 (95% CI = 0.915-1.312) for prolonged hospitalization. Several sensitivity analyses, including analysis of 599 pairs of patients matched by propensity score, showed consistent findings. CONCLUSION Early IV furosemide during the prehospital phase was administered to the sickest patients, was not associated with changes in short-term mortality or length of hospitalization after adjustment for several confounders

Influence of the length of hospitalisation in post-discharge outcomes in patients with acute heart failure: Results of the LOHRCA study.

To investigate the relationship between length of hospitalisation (LOH) and post-discharge outcomes in acute heart failure (AHF) patients and to ascertain whether there are different patterns according to department of initial hospitalisation. Consecutive AHF patients hospitalised in 41 Spanish centres were grouped based on the LOH (15 days). Outcomes were defined as 90-day post-discharge all-cause mortality, AHF readmissions, and the combination of both. Hazard ratios (HRs), adjusted by chronic conditions and severity of decompensation, were calculated for groups with LOH >6 days vs. LOH 6 days vs. LOH We included 8563 patients (mean age: 80 (SD = 10) years, 55.5% women), with a median LOH of 7 days (IQR 4-11): 2934 (34.3%) had a LOH 15 days. The 90-day post-discharge mortality was 11.4%, readmission 32.2%, and combined endpoint 37.4%. Mortality was increased by 36.5% (95%CI = 13.0-64.9) when LOH was 11-15 days, and by 72.0% (95%CI = 42.6-107.5) when >15 days. Conversely, no differences were found in readmission risk, and the combined endpoint only increased 21.6% (95%CI = 8.4-36.4) for LOH >15 days. Stratified analysis by hospitalisation departments rendered similar post-discharge outcomes, with all exhibiting increased mortality for LOH >15 days and no significant increments in readmission risk. Short hospitalisations are not associated with worse outcomes. While post-discharge readmissions are not affected by LOH, mortality risk increases as the LOH lengthens. These findings were similar across hospitalisation departments