Circulating and myocardial cytokines predict cardiac structural and functional improvement in patients with heart failure undergoing mechanical circulatory support

Abstract

BACKGROUND: Recent prospective multicenter data from patients with advanced heart failure demonstrated that left ventricular assist device (LVAD) support combined with standard heart failure medications, induced significant cardiac structural and functional improvement, leading to high rates of LVAD weaning in selected patients. We investigated whether preintervention myocardial and systemic inflammatory burden could help identify the subset of patients with advanced heart failure prone to LVAD-mediated cardiac improvement to guide patient selection, treatment, and monitoring. METHODS AND RESULTS: Ninety-three patients requiring durable LVAD were prospectively enrolled. Myocardial tissue and blood were acquired during LVAD implantation, for measurement of inflammatory markers. Cardiac structural and functional improvement was prospectively assessed via serial echocardiography. Eleven percent of the patients showed significant reverse remodeling following LVAD support (ie, responders). Circulating tumor necrosis factor alpha, interleukin (IL)-4, IL-5, IL-6, IL-7, IL-13, and interferon gamma were lower in responders, compared with nonresponders (P<0.05, all comparisons). The myo-cardial tissue signal transducer and activator of transcription-3, an inflammatory response regulator, was less activated in re-sponders (P=0.037). Guided by our tissue studies and a multivariable dichotomous regression analysis, we identified that low levels of circulating interferon gamma (odds ratio [OR], 0.06; 95% CI, 0.01– 0.35) and tumor necrosis factor alpha (OR, 0.05; 95% CI, 0.00– 0.43), independently predict cardiac improvement, creating a 2-cytokine model effectively predicting respond-ers (area under the curve, 0.903; P<0.0001). CONCLUSIONS: Baseline myocardial and systemic inflammatory burden inversely correlates with cardiac improvement following LVAD support. A circulating 2-cytokine model predicting significant reverse remodeling was identified, warranting further in-vestigation as a practical preintervention tool in identifying patients prone to LVAD-mediated cardiac improvement and device weaning.