Intermittent inotropic support with levosimendan in advanced heart failure as destination therapy: The LEVO-D registry.

AIM: Patients with advanced heart failure (AHF) who are not candidates to advanced therapies have poor prognosis. Some trials have shown that intermittent levosimendan can reduce HF hospitalizations in AHF in the short term. In this real-life registry, we describe the patterns of use, safety and factors related to the response to intermittent levosimendan infusions in AHF patients not candidates to advanced therapies. METHODS AND RESULTS: Multicentre retrospective study of patients diagnosed with advanced heart failure, not HT or LVAD candidates. Patients needed to be on the optimal medical therapy according to their treating physician. Patients with de novo heart failure or who underwent any procedure that could improve prognosis were not included in the registry. Four hundred three patients were included; 77.9% needed at least one admission the year before levosimendan was first administered because of heart failure. Death rate at 1 year was 26.8% and median survival was 24.7 [95% CI: 20.4-26.9] months, and 43.7% of patients fulfilled the criteria for being considered a responder lo levosimendan (no death, heart failure admission or unplanned HF visit at 1 year after first levosimendan administration). Compared with the year before there was a significant reduction in HF admissions (38.7% vs. 77.9%; P < 0.0001), unplanned HF visits (22.7% vs. 43.7%; P < 0.0001) or the combined event including deaths (56.3% vs. 81.4%; P < 0.0001) during the year after. We created a score that helps predicting the responder status at 1 year after levosimendan, resulting in a score summatory of five variables: TEER (+2), treatment with beta-blockers (+1.5), Haemoglobin >12 g/dL (+1.5), amiodarone use (-1.5) HF visit 1 year before levosimendan (-1.5) and heart rate >70 b.p.m. (-2). Patients with a score less than -1 had a very low probability of response (21.5% free of death or HF event at 1 year) meanwhile those with a score over 1.5 had the better chance of response (68.4% free of death or HF event at 1 year). LEVO-D score performed well in the ROC analysis. CONCLUSION: In this large real-life series of AHF patients treated with levosimendan as destination therapy, we show a significant decrease of heart failure events during the year after the first administration. The simple LEVO-D Score could be of help when deciding about futile therapy in this population.

Association of Genetic Variants With Outcomes in Patients With Nonischemic Dilated Cardiomyopathy.

BACKGROUND: The clinical relevance of genetic variants in nonischemic dilated cardiomyopathy (DCM) is unsettled. OBJECTIVES: The study sought to assess the prognostic impact of disease-causing genetic variants in DCM. METHODS: Baseline and longitudinal clinical data from 1,005 genotyped DCM probands were retrospectively collected at 20 centers. A total of 372 (37%) patients had pathogenic or likely pathogenic variants (genotype positive) and 633 (63%) were genotype negative. The primary endpoint was a composite of major adverse cardiovascular events. Secondary endpoints were end-stage heart failure (ESHF), malignant ventricular arrhythmia (MVA), and left ventricular reverse remodeling (LVRR). RESULTS: After a median follow-up of 4.04 years (interquartile range: 1.70-7.50 years), the primary endpoint had occurred in 118 (31.7%) patients in the genotype-positive group and in 125 (19.8%) patients in the genotype-negative group (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.17-1.94; P = 0.001). ESHF occurred in 60 (16.1%) genotype-positive patients and in 55 (8.7%) genotype-negative patients (HR: 1.67; 95% CI: 1.16-2.41; P = 0.006). MVA occurred in 73 (19.6%) genotype-positive patients and in 77 (12.2%) genotype-negative patients (HR: 1.50; 95% CI: 1.09-2.07; P = 0.013). LVRR occurred in 39.6% in the genotype-positive group and in 46.2% in the genotype-negative group (P = 0.047). Among individuals with baseline left ventricular ejection fraction ≤35%, genotype-positive patients exhibited more major adverse cardiovascular events, ESHF, and MVA than their genotype-negative peers (all P < 0.02). LVRR and clinical outcomes varied depending on the underlying affected gene. CONCLUSIONS: In this study, DCM patients with pathogenic or likely pathogenic variants had worse prognosis than genotype-negative individuals. Clinical course differed depending on the underlying affected gene.

How to Find Lessons from the Public Health Literature: Example of a Scoping Study Protocol on the Neighborhood Environment.

BACKGROUND: As key determinants of many favorable health and quality of life outcomes, it is important to identify factors associated with mobility and social participation. Although several investigations have been carried out on mobility, social participation and neighborhood environment, there is no clear integration of these results. This paper presents a scoping study protocol that aims to provide a comprehensive understanding of how the physical and social neighborhood environment is associated with or influences mobility and social participation in older adults. METHODS: The rigorous methodological framework for scoping studies is used to synthesize and disseminate current knowledge on the associations or influence of the neighborhood environment on mobility and social participation in aging. Nine databases from public health and other fields are searched with 51 predetermined keywords. Using content analysis, all data are exhaustively analyzed, organized, and synthesized independently by two research assistants. DISCUSSION: A comprehensive synthesis of empirical studies provides decision-makers, clinicians and researchers with current knowledge and best practices regarding neighborhood environments with a view to enhancing mobility and social participation. Such a synthesis represents an original contribution and can ultimately support decisions and development of innovative interventions and clear guidelines for the creation of age-supportive environments. Improvements in public health and clinical interventions might be the new innovation needed to foster health and quality of life for aging population. Finally, the aspects of the associations or influence of the neighborhood environment on mobility and social participation not covered by previous research are identified. CONCLUSIONS: Among factors that impact mobility and social participation, the neighborhood environment is important since interventions targeting it may have a greater impact on an individual's mobility and social participation than those targeting individual factors. Although investigations from various domains have been carried out on this topic, no clear integration of these results is available yet.