Dataset Information

Plasma biomarkers that reflect determinants of matrix composition identify the presence of left ventricular hypertrophy and diastolic heart failure.

ABSTRACT:

Background

Chronic pressure overload (such as arterial hypertension) may cause left ventricular (LV) remodeling, alterations in cardiac function, and the development of diastolic heart failure. Changes in the composition of the myocardial extracellular matrix may contribute to the development of pressure-overload-induced LV remodeling. We hypothesized that a specific pattern of plasma biomarker expression that reflected changes in these pathophysiological mechanisms would have diagnostic application to identify (1) patients who have development of LV hypertrophy (LVH) and (2) patients with LVH who have development of diastolic heart failure.

Methods and results

Plasma concentration of 17 biomarkers (matrix metalloproteinase [MMP]-1, -2, -3, -7, -8, and -9; tissue inhibitors -1, -2, -3, and -4; N-terminal propeptide of brain natriuretic peptide (NT-proBNP); cardiotrophin; osteopontin; soluble receptor for advanced glycation end products; collagen I teleopeptide; collagen I NT-proBNP; and collagen III N-terminal propetide [PIIINP]), an echocardiogram, and 6-minute hall walk were performed on 241 referent control subjects, 144 patients with LVH but no evidence of heart failure, and 61 patients with LVH and diastolic heart failure (DHF). A plasma multibiomarker panel consisting of increased MMP-7, MMP-9, TIMP-1, PIIINP, and NT-proBNP predicted the presence of LVH with an area under the curve of 0.80. A plasma multibiomarker panel consisting of increased MMP-2, TIMP-4, PIIINP, and decreased MMP-8 predicted the presence of DHF with an area under the curve of 0.79. These multibiomarker panels performed better than any single biomarker including NT-proBNP and better than using clinical covariates alone (area under the curve, 0.73 for LVH and 0.68 for DHF).

Conclusions

Plasma biomarkers reflecting changes in extracellular matrix fibrillar collagen homeostasis, combined into a multibiomarker panel, have discriminative value in identifying the presence of structural remodeling (LVH) and clinical disease (DHF).

SUBMITTER: Zile MR

PROVIDER: S-EPMC4071931 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Publications

Plasma biomarkers that reflect determinants of matrix composition identify the presence of left ventricular hypertrophy and diastolic heart failure.

Zile Michael R MR Desantis Stacia M SM Baicu Catalin F CF Stroud Robert E RE Thompson Sheila B SB McClure Catherine D CD Mehurg Shannon M SM Spinale Francis G FG

Circulation. Heart failure 20110224 3

<h4>Background</h4>Chronic pressure overload (such as arterial hypertension) may cause left ventricular (LV) remodeling, alterations in cardiac function, and the development of diastolic heart failure. Changes in the composition of the myocardial extracellular matrix may contribute to the development of pressure-overload-induced LV remodeling. We hypothesized that a specific pattern of plasma biomarker expression that reflected changes in these pathophysiological mechanisms would have diagnostic ...[more]

PMID: 21350055

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Project description:AimsConcentric hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of active diastolic Ca2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the concentrically hypertrophied heart following pressure-overload.Methods and resultsRats were subjected to aortic banding (AB), and experiments were performed 6 weeks after surgery using sham-operated rats as controls. In vivo ejection fraction and fractional shortening were normal, confirming preservation of systolic function. Left ventricular concentric hypertrophy and diastolic dysfunction following AB were indicated by thickening of the ventricular wall, reduced peak early diastolic tissue velocity, and higher E/e' values. Slowed relaxation was also observed in left ventricular muscle strips isolated from AB hearts, during both isometric and isotonic stimulation, and accompanied by increases in passive tension, viscosity, and extracellular collagen. An altered titin phosphorylation profile was observed with hypophosphorylation of the phosphosites S4080 and S3991 sites within the N2Bus, and S12884 within the PEVK region. Increased titin-based stiffness was confirmed by salt-extraction experiments. In contrast, isolated, unloaded cardiomyocytes exhibited accelerated relaxation in AB compared to sham, and less contracture at high pacing frequencies. Parallel enhancement of diastolic Ca2+ handling was observed, with augmented NCX and SERCA2 activity and lowered resting cytosolic [Ca2+].ConclusionIn the hypertrophied heart with preserved systolic function, in vivo diastolic dysfunction develops as cardiac fibrosis and alterations in titin phosphorylation compromise left ventricular compliance, and despite compensatory changes in cardiomyocyte Ca2+ homeostasis.

Project description:BackgroundLeft ventricular (LV) long-axis shortening at the cardiac base is a determinant of left atrial (LA) reservoir function. Cardiac amyloidosis (CA) is characteristic of amyloid deposition predominantly in the LV basal wall. We investigated the relationship between LV basal strain and LA reservoir strain among patients with pathological LV hypertrophy and subsequently evaluated the diagnostic ability of LA reservoir strain to identify CA etiology and its predictive value for heart failure hospitalization.MethodsWe retrospectively analyzed 341 patients with LV hypertrophy. Cardiac etiologies were diagnosed by tissue biopsy, cardiac magnetic resonance imaging or 99mTc-PYP scintigraphy. LV basal strain and LA reservoir strain were analyzed.ResultsPatients were diagnosed with CA (n = 75) and other etiologies (n = 266). LV basal strain was correlated with LA reservoir strain in the CA group (r = 0.58, p < 0.01) and the non-CA group (r = 0.44, p < 0.01). A binary logistic regression analysis showed that relative apical sparing of longitudinal strain, septal E/e' and LA reservoir strain had the ability to discriminate between the CA and non-CA groups (p < 0.01 for all). The area under the curve for relative apical sparing of longitudinal strain had a stronger ability than LA reservoir strain to discriminate CA from non-CA etiologies (0.90 versus 0.81, respectively; p < 0.01). During the follow-up period (median 2.7 years), the incidence of heart failure hospitalization was higher in the CA group than the non-CA group (35% versus 14%, respectively; p < 0.01). According to univariate Cox regression analysis, three LA factors (LA reservoir strain, E/e' and LA volume index) were associated with heart failure hospitalization in the non-CA group (p < 0.05 for all).ConclusionsLA reservoir strain was associated with LV basal strain among patients with pathological LV hypertrophy. Echocardiographic assessment of LA reservoir strain might add diagnostic value to identify CA etiology in these patients.

Dataset Information

Plasma biomarkers that reflect determinants of matrix composition identify the presence of left ventricular hypertrophy and diastolic heart failure.

Background

Methods and results

Conclusions

Publications

Plasma biomarkers that reflect determinants of matrix composition identify the presence of left ventricular hypertrophy and diastolic heart failure.

Similar Datasets

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