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Association between left ventricular diastolic function and right ventricular function and morphology in asymptomatic aortic stenosis.

ABSTRACT: BACKGROUND:Aortic stenosis (AS) is a progressive disease in which left ventricular (LV) diastolic dysfunction is common. However, the association between diastolic dysfunction and right ventricular (RV) loading conditions and function has not been investigated in asymptomatic AS patients. METHODS AND FINDINGS:A total of 41 patients underwent right heart catheterization and simultaneous echocardiography at rest and during maximal supine exercise, stratified according to resting diastolic function. Cardiac chamber size and morphology was assessed using cardiac magnetic resonance imaging (cMRI). RV stroke work index, pulmonary artery (PA) compliance, PA elastance, PA pulsatility index, and right atrial pressure (RAP) were calculated at rest and maximal exercise. Ten patients (24%) had normal LV filling pattern, 20 patients (49%) had grade 1, and 11 patients (27%) had grade 2 diastolic dysfunction. Compared to patients with normal diastolic filling pattern, patients with diastolic dysfunction had lower RV end-diastolic volume (66 ± 11 ml/m2 vs. 79 ± 15 ml/m2, p = 0.02) and end-systolic volume (25 ± 7 ml/m2 vs. 32 ± 9 ml/m2, p = 0.04). An increase in mean RAP to ?15 mmHg following exercise was not seen in patients with normal LV filling, compared to 4 patients (20%) with mild and 7 patients (63%) with moderate diastolic dysfunction (p = 0.003). PA pressure and PA elastance was increased in grade 2 diastolic dysfunction and correlated with RV volume and maximal oxygen consumption (r = -0.71, p < 0.001). CONCLUSIONS:Moderate diastolic dysfunction is associated with increased RV afterload (elastance), which is compensated at rest, but is associated with increased RAP and inversely related to maximal oxygen consumption during maximal exercise.

SUBMITTER: Christensen NL

PROVIDER: S-EPMC6667115 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Association between left ventricular diastolic function and right ventricular function and morphology in asymptomatic aortic stenosis.

Christensen Nicolaj Lyhne NL Dahl Jordi Sanchez JS Carter-Storch Rasmus R Jensen Kurt K Pecini Redi R Steffensen Flemming Hald FH Søndergaard Eva Vad EV Videbæk Lars Melgaard LM Møller Jacob Eifer JE

PloS one 20190730 7

<h4>Background</h4>Aortic stenosis (AS) is a progressive disease in which left ventricular (LV) diastolic dysfunction is common. However, the association between diastolic dysfunction and right ventricular (RV) loading conditions and function has not been investigated in asymptomatic AS patients.<h4>Methods and findings</h4>A total of 41 patients underwent right heart catheterization and simultaneous echocardiography at rest and during maximal supine exercise, stratified according to resting dia ...[more]

PMID: 31361748

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Project description:Importance:The optimal timing to operate in patients with asymptomatic severe aortic stenosis (AS) remains controversial. Left ventricular global longitudinal strain (LV GLS) may help to identify patients who might benefit from undergoing earlier aortic valve replacement. Objective:To investigate the prevalence of impaired LV GLS, the natural course of LV GLS, and its prognostic implications in patients with asymptomatic severe AS with preserved left ventricular ejection fraction (LVEF). Design, Setting, and Participants:This registry-based study included the institutional registries of 3 large tertiary referral centers and 220 patients with asymptomatic severe AS and preserved LVEF (>50%) who were matched for age and sex with 220 controls without structural heart disease. The echocardiograms of patients and controls were performed between 1998 and 2017. Exposures:Both clinical and echocardiographic data were assessed retrospectively. Severe AS was defined by an indexed aortic valve area less than 0.6 cm2/m2. Left ventricular global longitudinal strain was evaluated on transthoracic echocardiography using speckle tracking imaging. Main Outcomes and Measures:The prevalence of impaired LV GLS, the natural course of LV GLS, and the association of impaired LV GLS with symptom onset and the need for aortic valve intervention. Results:Two hundred twenty patients (mean [SD] age, 68 [13] years; 126 men [57%]) were included. Despite comparable LVEF, LV GLS was significantly impaired in patients with asymptomatic severe AS compared with age- and sex-matched controls without AS (mean [SD] LV GLS, -17.9% [2.5%] vs -19.6% [2.1%]; P < .001). After a median follow-up of 12 (interquartile range, 7-23) months, mean (SD) LV GLS significantly deteriorated (-18.0% [2.6%] to -16.3% [2.8%]; P < .001) while LVEF remained unchanged. Patients with impaired LV GLS at baseline (>-18.2%) showed a higher risk for developing symptoms (P = .02) and needing aortic valve intervention (P = .03) at follow-up compared with patients with more preserved LV GLS (≤-18.2%). Conclusions and Relevance:Subclinical myocardial dysfunction that is characterized by impaired LV GLS is often present in patients with asymptomatic severe AS with preserved LVEF. Left ventricular global longitudinal strain further deteriorates over time and impaired LV GLS at baseline is associated with an increased risk for progression to the symptomatic stage and the need for aortic valve intervention.

Project description:Importance:Clinical practice guidelines currently endorse a reliance on clinical symptoms of overt left ventricular (LV) failure to time aortic valve replacement for severe aortic stenosis; however, delayed aortic valve replacement can result in irreversible LV injury and adverse outcomes. Blood metabolomic signatures possess prognostic value in heart failure; this study assesses whether they are informative in aortic stenosis. Objective:To evaluate the value of metabolomic signatures in reflecting the extent of maladaptive LV remodeling in patients with end-stage aortic stenosis undergoing transcatheter aortic valve replacement, and to assess whether this procedure reverses metabolomic aberrations. Design, Setting, and Participants:This study of 44 patients with symptomatic severe aortic stenosis who underwent transfemoral transcatheter aortic valve replacement at a single-center tertiary care hospital. Liquid chromatography-mass spectrometry-based metabolomic profiling was performed on blood samples collected before and 24 hours after the procedure, and analyses were conducted to identify metabolites related to the measures of LV remodeling. Main Outcomes and Measures:We evaluated LV ejection fraction, LV mass index, and relative wall thickness, as well as levels of the acylcarnitines C16, C18:1, C18:2, C18, C26, choline, and kynurenine. Results:We enrolled 44 patients with severe aortic stenosis with a mean (SD) age of 81.9 (8.5) years, of whom 23 (52%) were women. The mean (SD) LV ejection fraction was 56.7% (18.2%), mean (SD) LV mass index was 117.3 (41.4) g/m2, and relative wall thickness was 0.53 (0.14). The mean β values of acylcarnitines C16, C18:1, C18:2, C18, and C26 were independently associated with LV mass index (C16: mean, 19.24; 95% CI, 5.48-33.01; P = .008; C18:1: mean, 26.18; 95% CI, 14.04-38.32; P < 1.0 × 10-4; C18:2: mean, 17.42; 95% CI, 3.40-31.43; P = .02; C18: mean, 25.25; 95% CI, 10.91-39.58; P = .001; C26: mean, 19.93; 95% CI, 4.41-35.45; P = .01), even after adjustments for age, sex, diabetes status, renal function, and B-type natriuretic peptide (BNP). Circulating levels of C18:2 acylcarnitine were associated with LV ejection fraction before and after multivariable adjustment (mean, -6.11; 95% CI, -10.88 to 1.34; P = .01). Blood metabolite levels did not independently relate to relative wall thickness. Within 24 hours of transcatheter aortic valve replacement, circulating levels of C16 decreased by 30.2% (P = 7.3 × 10-6), C18:1 by 42.7% (P = 3.7 × 10-8), C18:2 by 37.3% (P = 5.1 × 10-6), and C18 by 38.3% (P = 3.4 × 10-5). Conclusions and Relevance:In symptomatic patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, circulating levels of long-chain acylcarnitines were independently associated with measures of maladaptive LV remodeling, and metabolic perturbations lessened after procedure completion. Further efforts are needed to determine the clinical applicability of these novel biomarkers.

Dataset Information

Association between left ventricular diastolic function and right ventricular function and morphology in asymptomatic aortic stenosis.

Publications

Association between left ventricular diastolic function and right ventricular function and morphology in asymptomatic aortic stenosis.

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