In these vulnerable subjects with advanced NYHA class III-IV, elevation of CA125 levels was strongly associated with higher risk of all-cause mortality, cardiovascular mortality, composite of death or HF readmission and MACE during follow-up, independently of NTproBNP, LVEF, age, recent admission, evidence of pleural effusion, serum sodium, and treatment with digoxin. The gene discussed is NPPB; the disease is Pleural effusion.