Dataset Information

Arterial Properties as Determinants of Left Ventricular Mass and Fibrosis in Severe Aortic Stenosis: Findings From ACRIN PA 4008.

ABSTRACT: Background The role of arterial load in severe aortic stenosis is increasingly recognized. However, patterns of pulsatile load and their implications in this population are unknown. We aimed to assess the relationship between the arterial properties and both (1) left ventricular remodeling and fibrosis and (2) the clinical course of patients with severe aortic stenosis undergoing aortic valve replacement ( AVR ). Methods and Results We enrolled 38 participants with symptomatic severe aortic stenosis scheduled to undergo surgical AVR . Aortic root characteristic impedance, wave reflections parameters (reflection magnitude, reflected wave transit time), and myocardial extracellular mass were measured with cardiac magnetic resonance imaging and arterial tonometry Cardiac magnetic resonance imaging was repeated at 6 months in 30 participants. A reduction in cellular mass (133.6 versus 113.9 g; P=0.002) but not extracellular mass (42.3 versus 40.6 g; P=0.67) was seen after AVR . Participants with higher extracellular mass exhibited greater reflection magnitude (0.68 versus 0.54; P=0.006) and lower aortic root characteristic impedance (56.3 versus 96.9 dynes/s per cm⁵; P=0.006). Reflection magnitude was a significant predictor of smaller improvement in the quality of life (Kansas City Cardiomyopathy Questionnaire score) after AVR ( R=-0.51; P=0.0026). The 6-minute walk distance at 6 months after AVR was positively correlated with the reflected wave transit time ( R=0.52; P=0.01). Conclusions Consistent with animal studies, arterial wave reflections are associated with interstitial volume expansion in severe aortic stenosis and predict a smaller improvement in quality of life following AVR . Future trials should assess whether wave reflections represent a potential therapeutic target to mitigate myocardial interstitial remodeling and to improve the clinical status of this patient population.

SUBMITTER: Chirinos JA

PROVIDER: S-EPMC6405727 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Arterial Properties as Determinants of Left Ventricular Mass and Fibrosis in Severe Aortic Stenosis: Findings From ACRIN PA 4008.

Chirinos Julio A JA Akers Scott R SR Schelbert Erik E Snyder Bradley S BS Witschey Walter R WR Jacob Ron M RM Jamis-Dow Carlos C Ansari Bilal B Lee Jonathan J Segers Patrick P Schnall Mitchell M Cavalcante João L JL

Journal of the American Heart Association 20190101 1

Background The role of arterial load in severe aortic stenosis is increasingly recognized. However, patterns of pulsatile load and their implications in this population are unknown. We aimed to assess the relationship between the arterial properties and both (1) left ventricular remodeling and fibrosis and (2) the clinical course of patients with severe aortic stenosis undergoing aortic valve replacement ( AVR ). Methods and Results We enrolled 38 participants with symptomatic severe aortic sten ...[more]

PMID: 30590991

Similar Datasets

Project description:BackgroundAortic valve stenosis is the most common type of congenital left ventricular (LV) outflow tract obstruction. Balloon aortic valvuloplasty (BAV) has become the first-line treatment pathway in many centers. Our aim was to assess the trajectory of LV remodeling following BAV in children and its relationship to residual aortic stenosis (AS) and insufficiency (AI).MethodsChildren <18 years of age who underwent BAV for isolated aortic stenosis from 2004 to 2012 were eligible for inclusion. Those with AI before BAV, other complex congenital heart lesions, or <2 accessible follow-up echocardiograms were excluded. Baseline and serial echocardiographic data pertaining to aortic valve and LV size and function were retrospectively collected through December 2017 or the first reintervention. Longitudinal data was assessed using per-patient time profiles with superimposed trend lines using locally estimated scatterplot smoothing. Associations with reintervention or death were also evaluated.ResultsAmong the 98 enrolled children, the median (interquartile range) age at BAV was 2.8 months (0.2-75). The median (interquartile range) follow-up was 6.8 years (1.9-9.0). Children with predominantly residual AI (n=11) demonstrated progressive increases in their LV end-diastolic dimension Z score within the first 3 years after the BAV, followed by a plateau (P<0.001). Their mean LV circumferential and longitudinal strain values remained within the normal range but lower than in the non-AI group (P<0.001 and P=0.001, respectively). Children with predominantly residual aortic stenosis (n=44) had no changes in LV dimensions but had a rapid early increase in mean LV circumferential and longitudinal strain. The cumulative proportion (95% CI) of reintervention at 5 years following BAV was 33.7% (23.6%-42.4%).ConclusionsOur study demonstrates that LV remodeling occurs mainly during the first 3 years in children with predominantly residual AI after BAV, with no subsequent significant functional changes over the medium term. These data improve our understanding of expected patient trajectories and thus may inform decisions on the timing of reintervention.

Project description:Aortic valve stenosis is the most common cardiac valve disease, and with current trends in the population demographics, its prevalence is likely to rise, thus posing a major health and economic burden facing the worldwide societies. Over the past decade, it has become more than clear that our traditional genetic views do not sufficiently explain the well-known link between AS, proatherogenic risk factors, flow-induced mechanical forces, and disease-prone environmental influences. Recent breakthroughs in the field of epigenetics offer us a new perspective on gene regulation, which has broadened our perspective on etiology of aortic stenosis and other aortic valve diseases. Since all known epigenetic marks are potentially reversible this perspective is especially exciting given the potential for development of successful and non-invasive therapeutic intervention and reprogramming of cells at the epigenetic level even in the early stages of disease progression. This review will examine the known relationships between four major epigenetic mechanisms: DNA methylation, posttranslational histone modification, ATP-dependent chromatin remodeling, and non-coding regulatory RNAs, and initiation and progression of AS. Numerous profiling and functional studies indicate that they could contribute to endothelial dysfunctions, disease-prone activation of monocyte-macrophage and circulatory osteoprogenitor cells and activation and osteogenic transdifferentiation of aortic valve interstitial cells, thus leading to valvular inflammation, fibrosis, and calcification, and to pressure overload-induced maladaptive myocardial remodeling and left ventricular hypertrophy. This is especcialy the case for small non-coding microRNAs but was also, although in a smaller scale, convincingly demonstrated for other members of cellular epigenome landscape. Equally important, and clinically most relevant, the reported data indicate that epigenetic marks, particularly certain microRNA signatures, could represent useful non-invasive biomarkers that reflect the disease progression and patients prognosis for recovery after the valve replacement surgery.

Dataset Information

Arterial Properties as Determinants of Left Ventricular Mass and Fibrosis in Severe Aortic Stenosis: Findings From ACRIN PA 4008.

Publications

Arterial Properties as Determinants of Left Ventricular Mass and Fibrosis in Severe Aortic Stenosis: Findings From ACRIN PA 4008.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets