Coronary Sinus Neuropeptide Y Levels and Adverse Outcomes in Patients With Stable Chronic Heart Failure

1. In patients with stable heart failure, adrenergic co-transmitter neuropeptide Y (NPY) levels can identify patients at risk of adverse outcomes related to hyperadrenergic activation

Evidence Rating Level: 2 (Good)

The adrenergic co-transmitter neuropeptide Y (NPY) is one of the neurotransmitters released by cardiac sympathetic nerve terminals, and may represent an important biomarker in the prognostication of patients with chronic heart failure (CHF). This prospective cohort study investigated coronary sinus (CS) NPY levels in 105 patients with stable CHF at the time elective cardiac resynchronization therapy (CRT) device implantation to determine the role of NPY levels in predicting adverse outcomes, including chronic heart failure hospitalization, death, orthotopic heart transplantation and ventricular assist device placement. The mean left ventricular ejection fraction (LVEF) of the sample was 26% (SD 7%). Patients were optimized with beta-blockers (90%), angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or nitrate/hydralazine combination (95%), and/or aldosterone antagonist (25%) prior to treatment. Researchers found that for patients with CS NPY levels greater than 130 pg/mL, the hazard ratio for event-free survival was increased (HR 9.5, 95% CI 2.92 to 30.5, p<0.001). Eight deaths and 28 heart failure hospitalizations were reported. Following CRT device implantation and follow-up, 59 patients were considered CRT responders at six-months post-treatment. Baseline NPY levels were not significantly different between responders and non-responders (difference = – 2.2 pg/mL, p = 0.76). Following molecular analyses of CHF patients and organ donor controls, NPY levels were associated with eGFR (rs = -0.36, p<0.001), N-terminal-pro hormone brain natriuretic peptide (rs = 0.33, p = 0.004), and left ventricular diastolic dimension (rs = -0.35, p<0.001), but not LVEF, functional status, age, or CRT response. Adjusting for LVEF, eGFR, and age to determine event-free (left ventricular assist device, cardiac transplant, death) survival for CS NPY levels greater than 130 pg/mL suggested similar findings to the previous analyses. Significantly reduced mean (SD) NPY protein was noted in cardiomyopathy (13.7 [7.6]) compared to controls (31.4 [3.7]; p<0.001) in stellate ganglia neurons and, with similar mRNA levels between these groups, suggests that CHF patients experience increased release from stellate ganglia neurons. This study therefore suggests that CS NPY levels may be associated with outcomes in stable CHF patients undergoing CRT, where elevated neuronal activity may serve as a mediating mechanism in these patients.