Abstract
Growth differentiation factor (GDF)‐15 and soluble ST2 (sST2) are established prognostic markers in acute and chronic heart failure. Assessment of these biomarkers might improve arrhythmic risk stratification of patients with non‐ischaemic, dilated cardiomyopathy (DCM) based on left ventricular ejection fraction (LVEF). We studied the prognostic value of GDF‐15 and sST2 for prediction of arrhythmic death (AD) and all‐cause mortality in patients with DCM. We prospectively enrolled 52 patients with DCM and LVEF ≤ 50%. Primary end‐points were time to AD or resuscitated cardiac arrest (RCA), and secondary end‐point was all‐cause mortality. The median follow‐up time was 7 years. A cardiac death was observed in 20 patients, where 10 patients had an AD and 2 patients had a RCA. One patient died a non‐cardiac death. GDF‐15, but not sST2, was associated with increased risk of the AD/RCA with a hazard ratio (HR) of 2.1 (95% CI = 1.1‐4.3; P = .031). GDF‐15 remained an independent predictor of AD/RCA after adjustment for LVEF with adjusted HR of 2.2 (95% CI = 1.1‐4.5; P = .028). Both GDF‐15 and sST2 were independent predictors of all‐cause mortality (adjusted HR = 2.4; 95% CI = 1.4‐4.2; P = .003 vs HR = 1.6; 95% CI = 1.05‐2.7; P = .030). In a model including GDF‐15, sST2, LVEF and NYHA functional class, only GDF‐15 was significantly associated with the secondary end‐point (adjusted HR = 2.2; 95% CI = 1.05‐5.2; P = .038). GDF‐15 is superior to sST2 in prediction of fatal arrhythmic events and all‐cause mortality in DCM. Assessment of GDF‐15 could provide additional information on top of LVEF and help identifying patients at risk of arrhythmic death.
Highlights
Non-ischaemic, dilated cardiomyopathy (DCM), characterized by left ventricular (LV) dilation and reduced systolic function without relevant coronary artery disease, represents an underlying cause for approximately one-third of heart failure patients.[1,2] Progressive heart failure and ventricular tachyarrhythmia (VT) are the most common cause of sudden death in these patients.[3]
New York Heart Association (NYHA) classification was documented for each patient at the baseline according to ESC and AHA Heart Failure Guidelines: NYHA Class I: no limitation of physical activity; NYHA Class II: slight limitation of physical activity in which ordinary physical activity leads to fatigue, palpitation, dyspnoea, or anginal pain; the person is comfortable at rest; Class III: marked limitation of physical activity in which less-than-ordinary activity results in fatigue, palpitation, dyspnoea, or anginal pain; the person is comfortable at rest; Class IV: inability to carry on any physical activity without discomfort and symptoms of heart failure or the anginal syndrome even at rest, with increased discomfort if any physical activity is undertaken.[4,26]
The area under the curve (AUC, Harrell’s C-statistic) to predict arrhythmic death (AD)/resuscitated cardiac arrest (RCA) increased from 0.68 for age, sex and left ventricular ejection fraction (LVEF) to 0.76 when Growth differentiation factor (GDF)-15 was added to a model
Summary
Non-ischaemic, dilated cardiomyopathy (DCM), characterized by left ventricular (LV) dilation and reduced systolic function without relevant coronary artery disease, represents an underlying cause for approximately one-third of heart failure patients.[1,2] Progressive heart failure and ventricular tachyarrhythmia (VT) are the most common cause of sudden death in these patients.[3]. Non-ischaemic, dilated cardiomyopathy (DCM), characterized by left ventricular (LV) dilation and reduced systolic function without relevant coronary artery disease, represents an underlying cause for approximately one-third of heart failure patients.[1,2]. Progressive heart failure and ventricular tachyarrhythmia (VT) are the most common cause of sudden death in these patients.[3]. Patients with ischaemic heart disease seem to have more benefit from prophylactic ICD implantation.[5-7]. The recently published DANISH trial has demonstrated no mortality benefit from prophylactic ICD implantation in non-ischaemic DCM.[8]. LVEF is currently the best marker for risk stratification, it lacks specificity and many DCM patients with ICDs never receive appropriate therapies.[9,10]. Noninvasive testing and LVEF could not reliably identify patients with DCM at risk of fatal VTs.[11]. The identification of additional markers for arrhythmia risk stratification of patients with DCM is essential
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