Heart failure with preserved ejection fraction in primary care

Background: Heart failure with preserved ejection fraction (HFpEF) is a condition associated with low quality of life, high morbidity and mortality. It constitutes a diagnostic challenge and there is little evidence of effective treatments. In spite of its high prevalence and the fact that many (17-36%) of these patients are managed in Primary Care (PC) most of the studies on the condition were performed in Hospital Care (HC).

Aims: The aim of this thesis was to describe HFpEF in PC, its characteristics, comorbidities and mortality as well as further prognostic and diagnostic difficulties and potential underdiagnosis.

Methods: The initial three studies were based on the Swedish quality registry for Heart Failure (HF) patients (SwedeHF). Patients without echocardiographic results (16%) were excluded. A total of 1802 patients from PC and 7852 from HC, all with an Ejection Fraction (EF) ≥ 40% were studied to identify comorbidities, risk factors and outcomes, and to compare PC- with HC-patients in the first study. The second study analyzed the prognostic value of N-terminal Brain Natriuretic Peptide (NT-proBNP) in HFpEF-patients managed in PC. 924 patients; 360 patients with EF 40-49%, Heart Failure with Midrange Ejection Fraction, (HFmrEF) and 564 patients with EF≥50% (HFpEF). The third study identified gender differences and was based on the 1802 patients from Study 1, divided into HFmrEF and HFpEF. The fourth study was performed in Gustavsbergs PC centre. Ninetysix patients that had contacted the General Practitioner (GP) unit for one of the three common HF- symptoms breathlessness, tiredness or ankle swelling were included to find potential underdiagnosis and to evaluate an internet-based self-test for HF.

Results: HFpEF patients managed in PC were older and the majority were women, compared with patients managed in HC. Only 2.8% had no comorbidity and all-cause mortality after 1 year was 7.8%. Smoking, Chronic Obstructive Pulmonary Disease (COPD) Diabetes mellitus (DM), age and heart rate were shown to be independent risk factors for mortality in PC. Echocardiographc examinations are often missing. In matched controls there were more RAS-antagonists and betablockers prescribed in HC. Study I. There was a clear association between levels of NT-proBNP and mortality, but only on a group level. Numerous variables were associated with increased NT-proBNP and further independently with mortality. Study II. Men had higher age-adjusted mortality than women. In women with HFpEF more than half of the cases had another cause of death than cardiovascular diseases. The dominating causes of death were malignant diseases and respiratory diseases but altogether 13 different causes were identified. Study III. There was an underdiagnosis of HFpEF of 21%, all in women. We also found an acceptable accuracy of an internet-based self-test for HF. Study IV.

Conclusion: Patients with HFpEF in PC constitutes a heterogenous group with high age and many comorbidities that may interfere with the pathophysiology of HF and irrespectively affect both morbidity and mortality. The patients are older (mean 78 y.), the proportion of women is higher (46.7% vs 36.3 %) and they have other independent risk factors than those managed in HC. A single evidence-based treatment of HFpEF-patients is not available. The results of this thesis suggest that HFpEF-patients in PC have an age-related multi-organ damage with great need of careful diagnostic and individualized magement. There is a substantial risk for underdiagnosis.

List of scientific papers

I. B. Eriksson, P. Wändell, U. Dahlström, P. Näsman, L. H. Lund & M. Edner. Comorbidities, risk factors and outcomes in patients with heart failure and an ejection fraction of more than or equal to 40 % in primary care- and hospital care-based outpatient clinics. A report from the Swedish heart failure registry. Scandinavian Journal of Primary Health Care. 2018; 36:2: 207-215.
https://doi.org/10.1080/02813432.2018.1459654

II. B. Eriksson, P. Wändell, U. Dahlström, P. Näsman, L. H. Lund & M. Edner. Limited value of NT-proBNP as a prognostic marker of all-cause mortality in patients with heart failure with preserved and mid-range ejection fraction in primary care: A report from the Swedish heart failure registry. Scandinavian Journal of Primary Health Care. 2019; 37(1):1-10.
https://doi.org/10.1080/02813432.2019.1684029

III. B. Eriksson, P. Wändell, U. Dahlström, P. Näsman, L. H. Lund & M. Edner. Gender associated differences concerning characteristics and mortality in heart failure patients with ejection fraction equal to or above 40% managed in primary care: A report from the Swedish heart failure registry. [Submitted]

IV. B. Eriksson, M. Edner, C. Linde, K. Knudsen-Malmqvist & H. Persson. Validation of an internet-based self-test for Heart Failure diagnosis and assessment of underdiagnosis of Heart Failure in Primary Care. [Submitted]