A functional variant of the neuropeptide S receptor‐1 gene modulates clinical outcomes and healthcare utilization in patients with systolic heart failure: results from the Interdisciplinary Network Heart Failure ( INH ) Study

Aims Psychopathologies may occur in heart failure ( HF ) and can be associated with adverse outcomes. Amongst neuropeptide S receptor gene functional sequence variants, the T‐allele [asparagine(107)isoleucine, NPSR1 rs324981] has been identified as a risk factor for increased anxiety/overinterpretation of bodily symptoms. We investigated all‐cause death and re‐hospitalization (composite primary endpoint, CPEP ) and healthcare utilization in patients hospitalized for decompensated systolic HF with the TT vs. the AT / AA genotype. Methods and results Participants in the Interdisciplinary Network Heart Failure programme were eligible if consenting to genetic testing ( n = 924) and randomization to usual care ( UC , n = 464) or nurse‐co‐ordinated disease management ( DM , n = 460). Follow‐up was 180 days (100% complete). Compared with AT / AA carriers ( n = 726), TT genotype carriers ( n = 198) had more CPEP events [47% vs. 39%, hazard ratio ( HR ) 1.27, 95% confidence interval ( CI ) 1.01–1.61, P = 0.044] and were more frequently re‐hospitalized (43% vs. 35%, HR 1.31, 95% CI 1.02–1.67, P = 0.033); mortality rate was similar in both groups ( HR 1.11, 95% CI 0.68–1.81, P = 0.664). In subjects undergoing DM , CPEP and re‐hospitalization occurred more often in TT (51% and 47%) than in AT / AA carriers (36% and 33%; HR 2.14, 95% CI 1.44–3.19, and HR 2.29, 95% CI 1.52–3.44, genotype/treatment interaction both P = 0.007). Furthermore, TT genotype carriers undergoing DM visited cardiologists and other specialists more often than AT / AA carriers ( P = 0.009 and P = 0.005). With UC , event rates did not differ between genotype subgroups. Conclusion We identified a psychogenetic determinant of clinical outcomes and healthcare utilization after acute HF , which was modulated by the type of care. Future investigations need to clarify whether NPSR1 genotyping might further enhance the concept of ‘personalized’ medicine in HF . Trial registration: ISRCTN23325295 .