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Abstract   Aims  Diabetes mellitus, chronic obstructive pulmonary disease, and chronic kidney disease are prevalent in patients with heart failure with reduced ejection fraction (HFrEF). We have analysed the impact of co‐morbidities on quality of life (QoL) and outcome.    Methods and results  A total of 397 patients (58.8 ± 11.0 years, 73.6% with New York Heart Association functional class ≥3) with stable advanced HFrEF were followed for a median of 1106 (inter‐quartile range 379–2606) days, and 68% of patients (270 patients) experienced an adverse outcome (death, urgent heart transplantation, and implantation of mechanical circulatory support). Chronic obstructive pulmonary disease was present in 16.4%, diabetes mellitus in 44.3%, and chronic kidney disease in 34.5% of patients; 33.5% of patients had none, 40.0% had one, 21.9% had two, and 3.8% of patient had three co‐morbidities. Patients with more co‐morbidities reported similar QoL (assessed by Minnesota Living with Heart Failure Questionnaire, 45.46 ± 22.21/49.07 ± 21.69/47.52 ± 23.54/46.77 ± 23.60 in patients with zero to three co‐morbidities,  P  for trend = 0.51). Multivariable regression analysis revealed that furosemide daily dose, systolic blood pressure, New York Heart Association functional class, and body mass index, but not the number of co‐morbidities, were significantly ( P  &lt; 0.05) associated with QoL. Increasing co‐morbidity burden was associated with worse survival ( P  &lt; 0.0001), lower degree of angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker treatment ( P  = 0.001), and increasing levels of BNP (mean of 685, 912, 1053, and 985 ng/L for patients with zero to three co‐morbidities,  P  for trend = 0.008) and cardiac troponin (sm‐cTnI,  P  for trend = 0.0496), which remained significant ( P  &lt; 0.05) after the adjustment for left ventricular ejection fraction, left ventricular end‐diastolic diameter, right ventricular dysfunction grade, body mass index, and estimated glomerular filtration rate.    Conclusions  In stable advanced HFrEF patients, co‐morbidities are not associated with impaired QoL, but negatively affect the prognosis both directly and indirectly through lower level of HF pharmacotherapy and increased myocardial stress and injury.

The effect of three major co‐morbidities on quality of life and outcome of patients with heart failure with reduced ejection fraction