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Background Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long‐term follow‐up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre–transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort and up to 2 validation cohorts (N=543 for overall validation). In the derivation cohort (519 individuals; median age, 84 years, 45% women, 95% White individuals), we identified 3 axes of left ventricular remodeling, broadly specifying systolic function, diastolic function, and chamber volumes. Metabolite signatures of each axis specified both known and novel pathways in hypertrophy and cardiac dysfunction. Over a median of 3.1 years (205 deaths), a metabolite score for diastolic function was independently associated with post–transcatheter aortic valve implantation death (adjusted hazard ratio per 1 SD increase in score, 1.54 [95% CI, 1.25–1.90]; P

Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT‐proBNP at baseline in 499 patients. Left ventricular ejection fraction 2; P≤0.002 for each) when the other biomarker was elevated, but not when the other biomarker was normal (interaction P=0.015). Conclusions Among patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve implantation, elevations in circulating cardiac troponin and NT‐proBNP are more common as GLS worsens. Biomarkers of cardiac damage and stress are independently associated with mortality after transcatheter aortic valve implantation, whereas GLS is not. These findings may have implications for risk stratification of asymptomatic patients to determine optimal timing of valve replacement.

Abstract Aims We sought to clarify the role of ventriculo–arterial (V–A) coupling in the treatment of nonischemic dilated cardiomyopathy (NIDCM) by adding a mineralocorticoid receptor antagonist (MRA) to conventional anti‐failure therapy. Methods and results We employed cardiac magnetic resonance imaging to quantify left ventricular (LV) contractility and V–A coupling in normal subjects at rest (n = 11) and in patients with NIDCM (n = 12) before and after long term anti‐failure therapy, in which MRA was added to conventional anti‐failure therapy. After ≥6 months' treatment in NIDCM patients, LV volumes and mass decreased, and the LV ejection fraction increased from a median of 24% (17, 27) (interquartile range IQR) to 47 (42, 52) (P 0.05). The V–A coupling ratio, Ea/end‐systolic elastance (single‐beat method), decreased by −1.08 (−1.96, −0.55), (P = 0.003), as did Ea/end‐systolic pressure/end‐systolic pressure ratio, −0.54 (0.35, 0.87), (P = 0.002). The preload recruitable stroke work (PRSW) increased as did PRSW indexed for Ea (both P = 0.002), which reflected ‘total circulatory performance’. Conclusions In NIDCM, adding MRA to conventional anti‐failure therapy markedly improved LV ejection fraction and reduced peripheral vascular resistance, due to both improved LV contractility and especially to enhanced V–A coupling, as Ea decreased to normal. Total circulatory performance was a sensitive indicator of both LV pump performance and the arterial loading conditions.

Background Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown. Methods and Results In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core‐laboratory‐measured LV mass index, cTnT, and NT‐proBNP. LVH was defined by sex‐specific guideline cut‐offs and elevated biomarker levels were based on age and sex cut‐offs. Adjusted Cox proportional hazards models evaluated associations between LVH and biomarkers and all‐cause death out to 5 years. Elevated cTnT and NT‐proBNP were present in 82% and 86% of patients with moderate/severe LVH, respectively, as compared with 66% and 69% of patients with no/mild LVH, respectively (P

Background: Greater left ventricular (LV) wall stress is associated with adverse outcomes among patients with prevalent heart failure (HF). Less is known about the association between LV wall stress and incident HF., Objectives: The purpose of the study was to identify clinical factors associated with wall stress and test the association between wall stress and incident HF., Methods: We studied 4,601 ARIC (Atherosclerosis Risk In Communities) study participants without prevalent HF who underwent echocardiography between 2011 and 2013. LV end systolic and diastolic wall stress (LVESWS, LVEDWS) were calculated from chamber and wall thickness, systemic blood pressure, and transmitral Doppler E/e' as a surrogate for LV end diastolic pressure. Incident HF was ascertained by International Classification of Diseases (ICD)-9/10 claims for hospitalized HF through December 31, 2016. We used Cox regression to test the association between wall stress and incident HF, adjusted for demographics, traditional cardiovascular risk factors, prevalent coronary artery disease and atrial fibrillation, creatinine, N-terminal pro-B-type natriuretic peptide, troponin, triglycerides, C-reactive protein, LV ejection fraction, and LV mass., Results: The cohort had a median age of 75 years and 58% women, with 18% identifying as Black. Median LVESWS and LVEDWS were 48.8 (25th-75th percentile: 39.3-60.1) and 18.9 (25th-75th percentile: 15.8-22.5) kdynes/cm 2 , respectively. LVESWS and LVEDWS were modestly related (rho = 0.30, P  < 0.001). Over 4.6 years of median follow-up (156 HF events), each 1 kdyne/cm 2 greater LVEDWS was significantly associated with higher risk of incident HF (HR: 1.03; 95% CI: 1.01-1.06), while LVESWS was not (HR: 1.00; 95% CI: 0.99-1.01)., Conclusions: Among community-dwelling elderly individuals, greater LVEDWS is associated with a higher risk for incident HF., Competing Interests: This study was funded by the 10.13039/100000002National Institutes of Health (Drs White, Brittain, Lindman, Mosley, Shah, Wells, Kuipers, Gupta [R01HL153607, R01HL148661, R01HL154153, R38HL167237]); 10.13039/100005485American College of Cardiology/Association of Black Cardiologists Bristol Myers Squibb (Dr Dixon), Department of Veteran’s Affairs (VA), 10.13039/100000968American Heart Association (Drs Perry and Shah), 10.13039/100006520Edwards Lifesciences (Dr Lindman), and Cytokinetics (Dr Shah). Dr Shah is a co-inventor on a patent for ex-RNAs’ signatures of cardiac remodeling and in the past 12 months has served as a consultant for Cytokinetics. Dr Lindman has in the past 12 months served as a consultant for Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Supervised exercise training improves outcomes in patients with pulmonary arterial hypertension (PAH). The effect of an unsupervised activity intervention has not been tested., Research Question: Can a text-based mobile health intervention increase step counts in patients with PAH?, Study Design and Methods: We performed a randomized, parallel arm, single-blind clinical trial. We randomized patients to usual care or a text message-based intervention for 12 weeks. The intervention arm received three automated text messages per day with real-time step count updates and encouraging messages rooted in behavioral change theory. Individual step targets increased by 20% every 4 weeks. The primary end point was mean week 12 step counts. Secondary end points included the 6-min walk test, quality of life, right ventricular function, and body composition., Results: Among 42 randomized participants, the change in raw steps between baseline and week 12 was higher in the intervention group (1,409 steps [interquartile range, -32 to 2,220] vs -149 steps [interquartile range, -1,010 to 735]; P = .02), which persisted after adjustment for age, sex, baseline step counts, and functional class (model estimated difference, 1,250 steps; P = .03). The intervention arm took a higher average number of steps on all days between days 9 and 84 (P < .05, all days). There was no difference in week 12 six-minute walk distance. Analysis of secondary end points suggested improvements in the emPHasis-10 score (adjusted change, -4.2; P = .046), a reduction in visceral fat volume (adjusted change, -170 mL; P = .023), and nearly significant improvement in tricuspid annular plane systolic excursion (model estimated difference, 1.2 mm; P = .051)., Interpretation: This study demonstrated the feasibility of an automated text message-based intervention to increase physical activity in patients with PAH. Additional studies are warranted to examine the effect of the intervention on clinical outcomes., Clinical Trial Registration: ClinicalTrials.gov; No. NCT03069716; URL: www.clinicaltrials.gov., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)