NT-proB natriuretic peptide, risk factors and asymptomatic left ventricular dysfunction: Results of the SCReening Evaluation of the Evolution of New Heart Failure Study (SCREEN-HF)

BackgroundWe assessed left ventricular dysfunction in a population at high risk for heart failure (HF), and explored associations between ventricular function, HF risk factors and NT-proB natriuretic peptide (NT-proBNP).Methods and results3550 subjects at high risk for incident HF (≥60 years plus ≥1 HF risk factor), but without pre-existing HF or left ventricular dysfunction, were recruited. Anthropomorphic data, medical history and blood for NT-proBNP were collected. Participants at highest risk (n = 664) (NT-proBNP highest quintile; >30.0 pmol/L) and a sample (n = 51) from the lowest NT-proBNP quintile underwent echocardiography. Participants in the highest NT-proBNP quintile, compared to the lowest, were older (74 years vs. 67 years; p ConclusionA high burden of ventricular dysfunction was observed in this high risk group. Combining NT-proBNP and HF risk factors may identify those with ventricular dysfunction. This would allow resources to be focused on those at greatest risk of progression to overt HF.Michele McGrady, Christopher M. Reid, Louise Shiel, Rory Wolfe, Umberto Boffa, Danny Liew, Duncan J Campbell, David Prior, Simon Stewart, Henry Kru

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

Age-related longitudinal change in cardiac structure and function in adults at increased cardiovascular risk

Aim: Heart failure (HF) incidence increases markedly with age. We examined age-associated longitudinal change in cardiac structure and function, and their prediction by age and cardiovascular disease (CVD) risk factors, in a community-based cohort aged ≥60 years at increased CVD risk but without HF. Methods and results: CVD risk factors were recorded in 3065 participants who underwent a baseline echocardiographic examination, of whom 2358 attended a follow-up examination 3.8 [median, inter-quartile range (IQR) 3.5, 4.2] years later. Median age was 71 (IQR 67, 76) years and 55% of participants were male. Age was associated with longitudinal increase in left ventricular (LV) mass index (LVMI); decrease in LV volumes; increase in LV ejection fraction; decrease in mitral annular systolic velocity; decrease in diastolic function (decreased mitral early diastolic annular velocity (e′); and increase in left atrial volume index, mitral peak early diastolic flow velocity (E)/e′ ratio, and tricuspid regurgitant velocity (TRVmax) in men and women, except for TRVmax in men). In multivariable analysis, longitudinal increase in LVMI was explained by CVD risk factors alone, whereas age, together with CVD risk factors, independently predicted longitudinal change in all other echocardiographic parameters. CVD risk factors were differentially associated with longitudinal change in different echocardiographic parameters. Conclusions: Whereas the increase in LVMI with age was explained by CVD risk factors alone, age, together with risk factors, independently predicted longitudinal change in all other echocardiographic parameters, providing evidence for age-specific mechanisms of change in cardiac structure and function as people age. Age-associated change in LVMI, LV volumes, and diastolic function resembled what might be expected for the evolution of HF with preserved ejection fraction. Given the differential association of different CVD risk factors with longitudinal change in different echocardiographic parameters, therapies aimed at attenuation of age-associated change in cardiac structure and function, and HF evolution, will likely need to address multiple CVD risk factors

N-terminal B-type natriuretic peptide and the association with left ventricular diastolic function in a population at high risk of incident heart failure: Results of the SCReening Evaluation of the Evolution of New-Heart Failure Study (SCREEN-HF)

AimsImpaired diastolic function is associated with increased morbidity and mortality, but antecedents and predictors of progression to heart failure (HF) are not well understood. We examined associations between NT-proBNP, HF risk factors, and diastolic function in a population at high risk for incident HF.Methods and resultsA total of 3550 subjects at high risk for incident HF (=60 years plus =1 HF risk factor), but without pre-existing HF or LV dysfunction were recruited. Participants at highest risk (n = 664) (NT-proBNP in the highest quintile >254 pg/mL) underwent echocardiography. Moderate or severe diastolic dysfunction was observed in 25% [95% confidence interval (CI) 21-29%] of participants. Age (P = 0.001), male gender (P = 0.03), diabetes (P = 0.03), and NT-proBNP (P = 0.002) were associated with severity of diastolic dysfunction after adjustment for HF risk factors and LVEF. In regression analysis, log-transformed NT-proBNP was also associated with LV mass index (P = 0.05), left atrial size (P < 0.0001), and Doppler ratio of the mitral valve E/e' (P = 0.001). Multiple HF risk factors were present in the majority of participants (>70%), but no association was observed between diastolic dysfunction and the number of risk factors reported (P = 0.3). ConclusionDiastolic dysfunction was observed in one in four of these high risk subjects (= 60 years, HF risk factor, NT-proBNP >254 pg/mL). NT-proBNP, age and diabetes were strongly associated with severity of diastolic dysfunction, whereas other HF risk factors and LVEF were not. More targeted surveillance using a combination of risk factors and biomarkers may improve identification of those at great risk of incident HF. All rights reserved. © 2013 The Author

Hematopoietic Stem Cell Transplantation in People With Active Secondary Progressive Multiple Sclerosis

Background and objectives: Uncontrolled evidence suggests that autologous hematopoietic stem cell transplantation (AHSCT) can be effective in people with active secondary progressive multiple sclerosis (SPMS). In this study we compared the effect of AHSCT with that of other anti-inflammatory disease modifying therapies (DMT) on long-term disability worsening in active SPMS. Methods: We collected data from the Italian-Bone-Marrow-Transplantation-Study-Group and the Italian-Multiple-Sclerosis-Register. Patients were considered eligible if treatment had been started after the diagnosis of SPMS. Disability worsening was assessed by the cumulative proportion of patients with a 6-months confirmed-disability-progression (CDP) according to the Expanded-Disability-Status-Scale (EDSS) score. Key secondary endpoints were the EDSS time-trend after treatment start and the prevalence of disability improvement over time. Time to CDP was assessed by means of proportional hazard Cox regression models. A linear mixed model with a time*treatment group interaction was used to assess the longitudinal EDSS time-trends. Prevalence of improvement was estimated using a modified Kaplan-Meier estimator and compared between groups by bootstrapping the area under the curve. Results: 79 AHSCT-treated patients and 1975 patients treated with other DMT (beta-interferons, azathioprine, glatiramer-acetate, mitoxantrone, fingolimod, natalizumab, methotrexate, teriflunomide, cyclophosphamide, dimethyl fumarate, alemtuzumab) were matched to reduce treatment selection bias using propensity-score and overlap weighting approaches. Time to first CDP was significantly longer in transplanted patients (HR=0.50; 95%CI= 0.31-0.81; p=0.005), with 61.7% of transplanted patients free from CPD at 5 years. Accordingly, EDSS time-trend over 10 years was higher in patients treated with other DMT than in AHSCT-treated patients (+0.157 EDSS points per year compared to -0.013 EDSS points per year; interaction-p<0.001). Patients who underwent AHSCT were more likely to experience a sustained disability improvement: 34.7% of patients maintained an improvement (a lower EDSS than baseline) 3 years after transplant versus 4.6% of patients treated by other DMT (p<0.001). Discussion: The use of AHSCT in people with active SPMS is associated with a slowing of disability progression and a higher likelihood of disability improvement compared to standard immunotherapy. Classification of evidence: This study provides Class III evidence that autologous hematopoietic stem cell transplants prolonged the time to confirmed disability progression compared to other disease modifying therapies