Heart failure : studies of prognosis and advanced therapy

Background: Heart failure (HF) is a major health problem affecting 2-3% of the Western population. The clinical syndrome of HF is associated with reduced (HFrEF) or preserved (HFpEF) ejection fraction. Around 50% of the patients have HFrEF and despite advances in treatment, prognosis remains poor and treatments are underutilized. In HFpEF the prognosis is comparable to in HFrEF, but there is no evidence-based therapy.

Aims to investigate: 1) The use of evidence-based therapy and survival over time in patients with HFrEF; 2) The use of the inotropic drug levosimendan in HF in Sweden; 3 a) Contemporary prognosis in patients with severe HFrEF; 3 b) If simple predictors of prognosis can be identifid and used as criteria for referral to a HF center; and 4) Predictors of mortality in patients hospitalized with acute decompensated HFpEF.

Evidence-based therapy and survival: We studied 5,908 HFrEF patients with New York Heart Association (NYHA) class II-IV registered in the Swedish Heart Failure registry (SwedeHF) between 2003 and 2012. The use of beta-blockers and renin angiotensin system (RAS) blockers was >85% and stable over time. There was a decrease in the use of mineralocorticoid receptor antagonists (MRA) from 53 to 42%. The use of cardiac resynchronization therapy (CRT) and implantable cardioverter defirillators (ICD) increased over time, but absolute numbers were low, less than 11% for both. In 2003 vs. 2012, the 30-day, oneyear, and 3-year survival was 92 vs. 94%, 81 vs. 77% and 58 vs. 54% respectively. The changes in survival were not statistically signifiant. Reported numbers are risk-adjusted.

The use of levosimendan in Sweden: In SwedeHF, 655 registrations were confimed with use of inotropes. Levosimendan alone was the inotropic drug of choice in 91% of the registrations. Of all levosimendan registrations, 38% were planned repetitive treatment. The proportion of planned repetitive to all levosimendan registrations ranged from 0 to 65% between hospitals.

Who should be referred to a heart failure center? We studied 10,062 HFrEF patients with NYHA class III-IV from SwedeHF. One-year survival in the age groups ≤65 years, 66-80 years, and >80 years was 90, 79, and 61% respectively. Five prespecifid risk factors were assessed as potential triggers for referral to a HF center: systolic blood pressure ≤90 mmHg; creatinine ≤160 mmol/L; hemoglobin ≤120 g/L; no use of RAS antagonist; and no use of beta-blocker. In patients <80 years of age, the presence of 1, 2, or 3-5 of these risk factors were associated with a one-year survival of 79, 60, and 39% respectively.

Risk prediction in HFpEF: HF Surveillance data from four different communities in the United States were used to study 2,304 hospitalizations of HFpEF. Mortality at 28 days and one year was 11 and 34% respectively. The most powerful predictors of mortality were higher age, hypoxia, higher blood urea nitrogen and lower hemoglobin.

Conclusions: Patients with HF face a high risk of death. In HFpEF novel interventions are urgently called for, whereas improving implementation of existing evidence-based treatments should be emphasized in HFrEF. Specifially, the poor use of ICD and CRT needs to be recognized. Levosimendan was the dominant choice of inotrope in Sweden. Effects of the frequent use of planned repetitive levosimendan treatment in a non-acute setting need to be further evaluated. Few and simple risk factors used as referral criteria to a HF center, may increase the number of patients who can benefi from further therapy. In HFpEF, risk predictors may be used for discrimination of high risk patients and contribute to further characterization of this population.

List of scientific papers

I. Thorvaldsen T, Benson L, Dahlström U, Edner M, Lund L. H. Use of evidence-based therapy and survival in heart failure in Sweden 2003-2012. Eur J Heart Fail. 2016;18(5):503-11.
https://doi.org/10.1002/ejhf.496

II. Thorvaldsen T, Benson L, Hagerman I, Dahlström U, Edner M, Lund L.H. Planned repetitive use of levosimendan for heart failure in cardiology and internal medicine in Sweden. Int J Cardiol. 2014;175(1):55-61.
https://doi.org/10.1016/j.ijcard.2014.04.243

III. Thorvaldsen T, Benson L, Ståhlberg M, Dahlström U, Edner M, Lund L.H. Triage of patients with moderate to severe heart failure Who should be referred to a heart failure center? J Am Coll Cardiol. 2014;63(7):661-71.
https://doi.org/10.1016/j.jacc.2013.10.017

IV. Thorvaldsen T, Shah A, Cheng S, Agarwal S, Claggett B, Wruck L, Chang P, Rosamond, W, Lewis E, Desai A, Lund L.H, Solomon S.D. Predicting risk in patients hospitalized for acute decompensated heart failure and preserved ejection fraction: The Atherosclerosis Risk in Communities study Heart Failure Community Surveillance. [Manuscript]