Abstract
Purpose Inflammation appears to play a central role in promoting myocardial demise among advanced heart failure (HF) patients (pts). Caspase 1 (C1), a key element of the inflammasome, triggers inflammation, cell death, and progressive remodeling of the heart. Thus, we analyzed C1 expression in normals, end-stage HF pts awaiting ventricular assist device or heart transplant (VAD/TX), and acutely decompensated (AD) HF pts not requiring VAD/TX. We hypothesize a surge of C1 correlates with HF severity and unloading the heart will result in clinical improvement and C1 mitigation. Methods and Materials C1 was measured in the heart muscle and blood of pts pre and post treatment with ELISA: cardiogenic shock (n=45), decompensated HF (n=45), and normal controls (n=5). Additional variables collected include NYHA class, serum brain natriuretic peptide (BNP), and weight. Results In 45 HF pts who underwent VAD/TX, C1 concentrations were four times elevated in the heart compared to normal (p=.02). After VAD therapy (n=21) serum levels of C1 decreased significantly (174±22.7 to 120±14.1 pg/ml, p=.003) while clinical parameters notably improved (BNP 1773±254 to 636±125 pg/ml, p=.003, NYHA class IV to II). Pre-VAD C1 expression in serum highly correlated with C1 expression in heart muscle (R=.54, p=.01). Among 45 ADHF pts treated medically, C1 levels were 27% lower than cardiogenic shock pts (174±22.7 vs 137±9.2 pg/ml, p=.10) and significantly decreased during treatment (137±9.2 to 115±7.8 pg/ml, p=.0006). This was associated with a significant decline in weight and BNP levels (207±11.1 to 205±11 lbs, p=.0003; 1401±200 to 1251±184 pg/ml, p=.004). Conclusions C1 levels assessed in blood or heart muscle appear to mirror the clinical and cellular demise of advanced HF. Unloading of the heart via VAD or medical therapy leads to clinical improvement and marked C1 receding suggesting C1 demarcates reverse remodeling of the myocardium. C1 levels ≤115 pg/ml might be indicative of stable HF.
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