Comprehensive assessment of device-based therapy for heart failure with reduced ejection fraction

Background: Despite a recommendation by the European guidelines, the use of implantable cardioverter defibrillators (ICD) for the primary prevention of sudden cardiac death (SCD) in patients with heart failure with reduced ejection fraction (HFrEF) is scarce. This might be explained by a lower risk of SCD in contemporary patients with HFrEF, so that the need for primary prevention ICD use in these patients has been questioned. Aims: The overall aim of this thesis was to further evaluate the controversies regarding the use of device-based therapy and particularly regarding the primary prevention use of ICDs in contemporary treated patients with HFrEF. The specific aims were to: - Evaluate the association between primary prevention ICD use and mortality in contemporary treated patients with HFrEF (Study I). - Investigate the association between primary prevention ICD use and mortality in contemporary treated patients with HFrEF eligible for cardiac resynchronization therapy (CRT, Study II). - Explore the association between socioeconomic status and use of device-based therapies and outcomes in patients with heart failure (Study III). - Describe the impact of the predicted risk of SCD and all-cause mortality on primary prevention ICD use, as well as on its association with mortality in patients with HFrEF (Study IV). Methods and Results: For all studies, the Swedish Heart Failure Registry (SwedeHF) was used, and patients eligible for primary prevention ICD use (Study I and IV), patients also treated with CRT (Study II) and patients with available information on socioeconomic status (Study III) were further selected. - Study I: Only 10% of the patients eligible for ICD use were actually treated with the device. In a propensity score matched cohort, ICD use was associated with a 27% lower 1-year and a 12% lower 5-year risk of all-cause mortality. The findings were consistent across several prespecified sub-groups, including older vs. younger patients and those with vs. without ischemic heart diasease. - Study II: Among patients with CRT, ICD use was less likely in older patients, females and those not referred to heart failure nurse-led outpatient clinics. In a propensity score matched cohort, combinde use of CRT and ICD was associated with a 24% lower 1-year and a 18% lower 3-year risk of all-cause mortality. - Study III: Lower socioeconomic status, defined as the prevalence of lower income and/or lower education and/or living alone, was associated with a lower likelihood of referral to specialized follow-up care and a lower likelihood of ICD use; and also with a higher risk of heart failure hospitalization and all-cause mortality, even after adjustments for heart failure severity and treatments. - Study IV: Patients elgible for primary prevention ICD use were categorized by two readily available clinical scores (Seattle Heart Failure Model and Seattle Proportional Risk Model) into four groups based on their predicted SCD/mortality risk being high/low. Even in patients with a high SCD and a low mortality risk, ICDs were only used in 18.2%. Relevant predictors of ICD non-use were follow-up in primary care (vs. specialized care) and lower socioeconomic status. Primary prevention ICD use was only associated with a lower all-cause/cardiovascular mortality risk in patients with a high predicted SCD but a low predicted mortality risk. Conclusions: In contemporary HFrEF patients, even in those treated with CRT, primary prevention ICD use was associated with a lower mortality risk (Study I and II). Nevertheless, ICDs were still underused for the primary prevention of SCD in patients with HFrEF, even if they had a high predicted SCD risk (Study I and IV). Lower quality of HF care and lower socioeconomic status were relevant barriers to the implementation of primary prevention ICD use (Study III and IV), which highlights the need to improve both HF care and the access to it (Study III). Furthermore, the relatively low magnitude of the mortality risk reduction with primary prevention ICD use in contemporary patients with HFrEF calls for better patient selection, which can be achieved by applying easily applicable clinical scores (Study IV)

Transcriptional Active Parvovirus B19 Infection Predicts Adverse Long-Term Outcome in Patients with Non-Ischemic Cardiomyopathy

Parvovirus B19 (B19V) is the predominant cardiotropic virus currently found in endomyocardial biopsies (EMBs). However, direct evidence showing a causal relationship between B19V and progression of inflammatory cardiomyopathy are still missing. The aim of this study was to analyze the impact of transcriptionally active cardiotropic B19V infection determined by viral RNA expression upon long-term outcomes in a large cohort of adult patients with non-ischemic cardiomyopathy in a retrospective analysis from a prospective observational cohort. In total, the analyzed study group comprised 871 consecutive B19V-positive patients (mean age 50.0 ± 15.0 years) with non-ischemic cardiomyopathy who underwent EMB. B19V-positivity was ascertained by routine diagnosis of viral genomes in EMBs. Molecular analysis of EMB revealed positive B19V transcriptional activity in n = 165 patients (18.9%). Primary endpoint was all-cause mortality in the overall cohort. The patients were followed up to 60 months. On the Cox regression analysis, B19V transcriptional activity was predictive of a worse prognosis compared to those without actively replicating B19V (p = 0.01). Moreover, multivariable analysis revealed transcriptional active B19V combined with inflammation [hazard ratio 4.013, 95% confidence interval 1.515–10.629 (p = 0.005)] as the strongest predictor of impaired survival even after adjustment for age and baseline LVEF (p = 0.005) and independently of viral load. The study demonstrates for the first time the pathogenic clinical importance of B19V with transcriptional activity in a large cohort of patients. Transcriptionally active B19V infection is an unfavourable prognostic trigger of adverse outcome. Our findings are of high clinical relevance, indicating that advanced diagnostic differentiation of B19V positive patients is of high prognostic importance

Iron deficiency is a common disorder in general population and independently predicts all-cause mortality: results from the Gutenberg Health Study

Background!#!Iron deficiency is now accepted as an independent entity beyond anemia. Recently, a new functional definition of iron deficiency was proposed and proved strong efficacy in randomized cardiovascular clinical trials of intravenous iron supplementation. Here, we characterize the impact of iron deficiency on all-cause mortality in the non-anemic general population based on two distinct definitions.!##!Methods!#!The Gutenberg Health Study is a population-based, prospective, single-center cohort study. The 5000 individuals between 35 and 74 years underwent baseline and a planned follow-up visit at year 5. Tested definitions of iron deficiency were (1) functional iron deficiency-ferritin levels below 100 µg/l, or ferritin levels between 100 and 299 µg/l and transferrin saturation below 20%, and (2) absolute iron deficiency-ferritin below 30 µg/l.!##!Results!#!At baseline, a total of 54.5% of participants showed functional iron deficiency at a mean hemoglobin of 14.3 g/dl; while, the rate of absolute iron deficiency was 11.8%, at a mean hemoglobin level of 13.4 g/dl. At year 5, proportion of newly diagnosed subjects was 18.5% and 4.8%, respectively. Rate of all-cause mortality was 7.2% (n = 361); while, median follow-up was 10.1 years. After adjustment for hemoglobin and major cardiovascular risk factors, the hazard ratio with 95% confidence interval of the association of iron deficiency with mortality was 1.3 (1.0-1.6; p = 0.023) for the functional definition, and 1.9 (1.3-2.8; p = 0.002) for absolute iron deficiency.!##!Conclusions!#!Iron deficiency is very common in the apparently healthy general population and independently associated with all-cause mortality in the mid to long term

Left Ventricular Unloading Is Associated With Lower Mortality in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation

International audienceBackground: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to treat cardiogenic shock. However, VA-ECMO might hamper myocardial recovery. The Impella unloads the left ventricle. This study aimed to evaluate whether left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO was associated with lower mortality. Methods: Data from 686 consecutive patients with cardiogenic shock treated with VA-ECMO with or without left ventricular unloading using an Impella at 16 tertiary care centers in 4 countries were collected. The association between left ventricular unloading and 30-day mortality was assessed by Cox regression models in a 1:1 propensity score–matched cohort. Results: Left ventricular unloading was used in 337 of the 686 patients (49%). After matching, 255 patients with left ventricular unloading were compared with 255 patients without left ventricular unloading. In the matched cohort, left ventricular unloading was associated with lower 30-day mortality (hazard ratio, 0.79 [95% CI, 0.63–0.98]; P =0.03) without differences in various subgroups. Complications occurred more frequently in patients with left ventricular unloading: severe bleeding in 98 (38.4%) versus 45 (17.9%), access site–related ischemia in 55 (21.6%) versus 31 (12.3%), abdominal compartment in 23 (9.4%) versus 9 (3.7%), and renal replacement therapy in 148 (58.5%) versus 99 (39.1%). Conclusions: In this international, multicenter cohort study, left ventricular unloading was associated with lower mortality in patients with cardiogenic shock treated with VA-ECMO, despite higher complication rates. These findings support use of left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO and call for further validation, ideally in a randomized, controlled trial