Editors' ChoiceHeart Failure

Hunting for Those with Heavy Hearts

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Science Translational Medicine  13 Apr 2011:
Vol. 3, Issue 78, pp. 78ec50
DOI: 10.1126/scitranslmed.3002481

People who consistently carry excessive workloads might try meditation or exercise as responses to the pressure, but signs of the constant stress eventually surface. Similarly, individuals who have longstanding high blood pressure can ultimately suffer diastolic heart failure (DHF); but before that happens, their hearts respond to the pressure overload by undergoing left ventricular hypertrophy (LVH), a myocardial remodeling process that can go undetected for years. Symptoms of impending DHF—breathlessness, poor exercise tolerance, and swollen ankles—often are chalked up to old age. Sorely needed are better ways to predict this common and dire consequence of constant pressure. Now, Zile et al. have devised a panel of biomarkers that reflect the underlying pathophysiological changes that occur as a person progresses from LVH to DHF.

Excess pressure in the heart can cause changes in the makeup of the myocardial extracellular matrix (ECM). In this study, the authors set out to identify plasma biomarkers of this transformation. To profile the transition from LVH to DHF, clinical parameters and serum concentrations of 17 proteins were assessed in three groups of patients: healthy controls, those with LVH, and those with DHF. Zile et al. identified differences in the serum concentrations of some of these proteins that discriminated between LVF and DHF patients; among these biomarkers were specific matrix metalloproteinases (MMPs) (ones that degrade collagen, a structural protein in the ECM), their tissue inhibitors (TIMPs), and collagen III N-terminal propeptides (which participate in collagen synthesis). These changes indicated a local shift in cell-type activation and an enhancement in ECM proteolytic events, which are signs of a heart under pressure. Discrimination among patients who lie along the continuum of LVH to DHF is clinically challenging. This panel of biomarkers may be used to develop a method that would fill an important diagnostic niche. The next step will be the validation of these biomarkers in an independent prospective cohort of patients.

M. R. Zile et al., Plasma biomarkers that reflect determinants of matrix composition identify the presence of left ventricular hypertrophy and diastolic heart failure. Circ. Heart Fail. 10.1161/CIRCHEARTFAILURE.110.958199 (24 February 2011). [Abstract]

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