Gene Expression Signature of Non-Ischemic Cardiomyopathy Using an Inflammatory Pathway RNA Array

Introduction: The immunologic basis of non-ischemic cardiomyopathy (NICM) may be variable, particularly between genders or amongst CM types, for example peripartum CM. Understanding the immunologic mechanisms of acute NICM may provide clues to LV recovery. We present a gene expression analysis of peripheral whole blood in patients with NICM compared to normal healthy controls. Methods: In this pilot study, peripheral blood RNA was isolated from 12 patients with NICM (4 male, 4 non-peripartum female, 4 peripartum female) with EF ≤0.4 and NYHA class ≥2 symptoms and 8 healthy controls (4 male, 4 female) using the PAXgene kit. Using an inflammatory pathway array (PAHS-011, SABiosciences, Inc.), gene expression was assayed using a real-time, reverse transcriptase PCR technique (RT2 Profiler Assay, SABiosciences, Inc.). Gene expression was normalized to five housekeeping genes and compared between groups. A significant difference was defined as p-value ≤0.01. Results: Baseline mean LVEF = 0.19 ± 0.02. NYHA functional class distribution (%) was II/III/IV = 58/33/8. Six genes (CCL4, CCL13, CXCL12, IL10RA, TNF, CD40LG) were found to have statistically significant though modestly decreased expression (p-value ≤0.01), and a seventh gene (C4A) was variably up-regulated amongst NICM patients (p=0.028), Figure 1.

Conclusion: Using an inflammatory pathway array, we identified a small but significant signature gene expression pattern in patients with symptomatic NICM, confirming an immunologic basis for the disease. Additional patients and analysis can confirm this gene expression signature, and with clinical correlation, further data may help to identify patients at risk for persistent LV failure.