Plasma Biomarkers That Reflect Determinants of Matrix Composition Identify the Presence of Left Ventricular Hypertrophy and Diastolic Heart Failure

Study Questions:

Is there a specific pattern of plasma biomarker expression that 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 (DHF)?

Methods:

The study cohort was comprised of 241 control subjects, 144 patients with LVH but no evidence of HF, and 61 patients with LVH and DHF. Plasma concentration of 17 biomarkers, reflecting changes in pathophysiological mechanisms accompanying pressure-overload–induced LV remodeling, including 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), as well as an echocardiogram and 6-minute hall walk were performed on the study cohort.

Results:

The study investigators found that 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:

The study investigators concluded that 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).

Perspective:

This is an important study because its findings suggest that biomarkers allow early prediction of LV remodeling and development of DHF. The next step would be to validate these findings in a large prospective cohort, and to determine whether this early detection could be utilized to start therapy that would reverse LV remodeling and prevent clinical HF.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Chronic Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Hypertrophy, Left Ventricular, Extracellular Matrix, Heart Failure, Diastolic, Biological Markers, Fibrillar Collagens, Homeostasis, Collagen, Procollagen, Natriuretic Peptide, Brain


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