Dataset Information

Abnormalities in 3-Dimensional Left Ventricular Mechanics With Anthracycline Chemotherapy Are Associated With Systolic and Diastolic Dysfunction.

ABSTRACT: OBJECTIVES:The objective of this study was to evaluate the changes in three-dimensional (3D) speckle-tracking echocardiography-derived measures of mechanics and their associations with systolic and diastolic dysfunction after anthracyclines. BACKGROUND:An improved understanding of the changes in 3D cardiac mechanics with anthracyclines may provide important mechanistic insight and identify new metrics to detect cardiac dysfunction. METHODS:A total of 142 women with breast cancer receiving doxorubicin (240 mg/m2) with or without trastuzumab underwent 3D speckle-tracking echocardiography at standardized intervals prior to, during, and annually after chemotherapy. Left ventricular ejection fraction (LVEF), global circumferential strain (GCS), global longitudinal strain (GLS), principal strain, twist, and torsion were quantified. Linear regression analyses defined the associations between clinical factors and 3D parameters. Linear regression models with cluster robust variance estimators determined the associations between 3D measures and 2-dimensional (2D) LVEF and Doppler-derived E/e' over time. RESULTS:There were significant abnormalities in 3D LVEF, GCS, GLS, and principal strain post-doxorubicin compared with control subjects (p < 0.001). The 3D parameters worsened post-anthracyclines, and only partially recovered to baseline over a median of 2.1 years (interquartile range: 1 to 4 years). Higher blood pressure and body mass index were associated with worse post-anthracycline 3D GCS and GLS, respectively. All 3D measures were associated with 2D LVEF at the same visit; only 3D LVEF, GCS, GLS, and principal strain were associated with 2D LVEF at subsequent visits (p < 0.05). In exploratory analyses, 3D LVEF and GCS were associated with subsequent systolic function independent of their corresponding 2D measures. The 3D LVEF, GCS, principal strain, and twist were significantly associated with concurrent, but not subsequent, E/e'. CONCLUSIONS:Anthracyclines result in early and persistent abnormalities in 3D mechanics. The 3D LVEF and strain measures are associated with concurrent and subsequent systolic dysfunction, and concurrent diastolic dysfunction. Future research is needed to define the mechanisms and clinical relevance of abnormal 3D mechanics.

SUBMITTER: Zhang KW

PROVIDER: S-EPMC6417916 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Abnormalities in 3-Dimensional Left Ventricular Mechanics With Anthracycline Chemotherapy Are Associated With Systolic and Diastolic Dysfunction.

Zhang Kathleen W KW Finkelman Brian S BS Gulati Gaurav G Narayan Hari K HK Upshaw Jenica J Narayan Vivek V Plappert Ted T Englefield Virginia V Smith Amanda M AM Zhang Carina C Hundley W Gregory WG Ky Bonnie B

JACC. Cardiovascular imaging 20180314 8

OBJECTIVES:The objective of this study was to evaluate the changes in three-dimensional (3D) speckle-tracking echocardiography-derived measures of mechanics and their associations with systolic and diastolic dysfunction after anthracyclines. BACKGROUND:An improved understanding of the changes in 3D cardiac mechanics with anthracyclines may provide important mechanistic insight and identify new metrics to detect cardiac dysfunction. METHODS:A total of 142 women with breast cancer receiving doxoru ...[more]

PMID: 29550306

Similar Datasets

Project description:PurposeTo assess the impact of left ventricular (LV) diastolic dysfunction on left atrial (LA) phasic volume and function using dual-source CT (DSCT) and to find a viable alternative prognostic parameter of CT for LV diastolic dysfunction through quantitative evaluation of LA phasic volume and function in patients with LV diastolic dysfunction.Materials and methodsSeventy-seven patients were examined using DSCT and Doppler echocardiography on the same day. Reservoir, conduit, and contractile function of LA were evaluated by measuring LA volume (LAV) during different cardiac phases and all parameters were normalized to body surface area (BSA). Patients were divided into four groups (normal, impaired relaxation, pseudonormal, and restrictive LV diastolic filling) according to echocardiographic findings. The LA phasic volume and function in different stages of LV diastolic function was compared using one-way ANOVA analysis. The correlations between indexed volume of LA (LAVi) and diastolic function in different stages of LV were evaluated using Spearman correlation analysis.ResultsLA ejection fraction (LAEF), LA contraction, reservoir, and conduit function in patients in impaired relaxation group were not different from those in the normal group, but they were lower in patients in the pseudonormal and restrictive LV diastolic dysfunction groups (P < 0.05). For LA conduit function, there were no significant differences between the patients in the pseudonormal group and restrictive filling group (P = 0.195). There was a strong correlation between the indexed maximal left atrial volume (LAVmax, r = 0.85, P < 0.001), minimal left atrial volume (LAVmin, r = 0.91, P < 0.001), left atrial volume at the onset of P wave (LAVp, r = 0.84, P < 0.001), and different stages of LV diastolic function. The LAVi increased as the severity of LV diastolic dysfunction increased.ConclusionsLA remodeling takes place in patients with LV diastolic dysfunction. At the same time, LA phasic volume and function parameters evaluated by DSCT indicated the severity of the LV diastolic dysfunction. Quantitative analysis of LA phasic volume and function parameters using DSCT could be a viable alternative prognostic parameter of LV diastolic function.

Project description:BackgroundPatients with chronic kidney disease (CKD) and coincident heart failure with preserved ejection fraction (HFpEF) may constitute a distinct HFpEF phenotype. Osteopontin (OPN) is a biomarker of HFpEF and predictive of disease outcome. We recently reported that OPN blockade reversed hypertension, mitochondrial dysfunction, and kidney failure in Col4a3-/- mice, a model of human Alport syndrome.ObjectivesThe purpose of this study was to identify potential OPN targets in biopsies of HF patients, healthy control subjects, and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), and to characterize the cardiac phenotype of Col4a3-/- mice, relate this to HFpEF, and investigate possible causative roles for OPN in driving the cardiomyopathy.MethodsOGDHL mRNA and protein were quantified in myocardial samples from patients with HFpEF, heart failure with reduced ejection fraction, and donor control subjects. OGDHL expression was quantified in hiPS-CMs treated with or without anti-OPN antibody. Cardiac parameters were evaluated in Col4a3-/- mice with and without global OPN knockout or AAV9-mediated delivery of 2-oxoglutarate dehydrogenase-like (Ogdhl) to the heart.ResultsOGDHL mRNA and protein displayed abnormal abundances in cardiac biopsies of HFpEF (n = 17) compared with donor control subjects (n = 12; p < 0.01) or heart failure with reduced ejection fraction patients (n = 12; p < 0.05). Blockade of OPN in hiPS-CMs conferred increased OGDHL expression. Col4a3-/- mice demonstrated cardiomyopathy with similarities to HFpEF, including diastolic dysfunction, cardiac hypertrophy and fibrosis, pulmonary edema, and impaired mitochondrial function. The cardiomyopathy was ameliorated by Opn-/- coincident with improved renal function and increased expression of Ogdhl. Heart-specific overexpression of Ogdhl in Col4a3-/- mice also improved cardiac function and cardiomyocyte energy state.ConclusionsCol4a3-/- mice present a model of HFpEF secondary to CKD wherein OPN and OGDHL are intermediates, and possibly therapeutic targets.

Dataset Information

Abnormalities in 3-Dimensional Left Ventricular Mechanics With Anthracycline Chemotherapy Are Associated With Systolic and Diastolic Dysfunction.

Publications

Abnormalities in 3-Dimensional Left Ventricular Mechanics With Anthracycline Chemotherapy Are Associated With Systolic and Diastolic Dysfunction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets