Introduction

The landscape of heart failure (HF) has changed dramatically over the last few decades. HF with preserved ejection fraction (HFpEF) has now become a major health care challenge, as despite its high prevalence and growing incidence in the older population, there is a distinct lack of evidence-based prognostic therapies.1, 2

In the last two decades, evidence-based disease-modifying drugs and multidisciplinary HF outpatient programmes have greatly improved the care of patients with HF, which is particularly true for those with reduced ejection fraction (HFrEF).3-6 By transition of key elements of such programmes, near home management of stable HFrEF patients by general practitioners, preferably supported by HF nurses, and/or by eHealth, seems feasible and can lead to reduction of use of resources and achieve ‘best care on the right place’.4, 5, 7-9

Most patients with HF are diagnosed in primary care.6, 10 In general practice, the diagnosis of HF is typically based on symptoms and signs, followed by electrocardiography (ECG), and preferably by the addition of natriuretic peptide measurements. If abnormal, referral should follow for echocardiography to confirm the diagnosis and differentiate between the three main HF types, that is, HFpEF, HF with mid-range ejection fraction (HFmrEF), and HFrEF, and to identify correctable abnormalities. These cases are nearly always of slow onset; acute onset HF is generally diagnosed in the hospital, sometimes preceded by an initial period with complaints unrecognized as HF symptoms.

Previous studies reported that HFpEF mainly affects older women, whereas HFrEF affects younger men.1, 2, 11 Despite these observations, there is a lack of comparison on the distribution of sex and different types of HF over different health care settings: community, general practice, and cardiology hospital-based setting. This information may contribute to early diagnosis of HF and tailored management of HF patients in the specific health care setting.

We therefore assessed the distribution of sex and HF types (HFrEF, HFmrEF, and HFpEF) in an older population (65 to 79 years) among community-dwelling high-risk men and women with screening-detected HF, in HF patients from primary care, and in HF patients in the cardiology outpatient setting.

Methods Study design, study population, and outcome definition

In this descriptive study, we included six studies: four cross-sectional screening studies among older high-risk community people (463 HF patients), one study from general practice (434 HF patients), and a large registry study of outpatient cardiology departments containing data from 10 910 HF patients (Table 1). The studies were conducted between 2001 and 2016 in the Netherlands and are described in detail elsewhere.12-17

Table 1. Study characteristics and diagnostic criteria to define heart failure Domain High-risk community General practice Cardiology OPC van Riet van Mourik Boonman-de Winter Rutten Valk Brugts Design Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Time window 2010–2012 2010–2012 2009–2010 2001–2003 2011 2013–2016 Study population ≥65 years old. No previous diagnosis of heart failure. Presented in primary care with shortness of breath on exertion. ≥65 years old. No previous diagnosis of heart failure. Classified as frail (≥ chronic or vitality threatening diseases and/or using ≥5 prescribed drugs daily during the last year) and exercise intolerance and/or dyspnoea. ≥60 years old. No previous diagnosis of heart failure. Diagnosis of diabetes mellitus type 2. ≥65 years old. No previous diagnosis of heart failure. General practitioner's diagnosis of COPD based on the ICPC codes R91 or R95. Community-dwelling individuals registered in primary care with a heart failure diagnosis (International Classification of Primary Care code K77) during at least two encounters. ≥18 years old. Diagnosed with chronic heart failure and treated at Dutch outpatient heart failure clinics. Heart failure diagnosis and definition Expert panel decision. Signs and symptoms of heart failure and structural or functional echocardiographic evidence of cardiac dysfunction at rest. Expert panel decision. Signs and symptoms of heart failure and structural or functional echocardiographic evidence of cardiac dysfunction at rest. Expert panel decision. Signs and symptoms of heart failure and structural or functional echocardiographic evidence of cardiac dysfunction at rest. Expert panel decision. Signs and symptoms of heart failure and structural or functional echocardiographic evidence of cardiac dysfunction at rest. Expert panel decision. Signs and symptoms of heart failure and structural or functional echocardiographic evidence of cardiac dysfunction at rest. Cardiologists at individual centres. Signs and symptoms of heart failure and structural or functional echocardiographic evidence of cardiac dysfunction at rest. Participants without a previous heart failure diagnosis (n) 585 370 581 405 Participants (n) 683 10 910 Prevalence of newly detected heart failure (%) 16% 35% 28% 21% Prevalence of confirmed heart failure (%) 64% 100% COPD, chronic obstructive pulmonary disease; OPC, outpatient clinic. Screening studies in high-risk community patients

Between 2010 and 2012, van Riet and co-workers screened for HF in 585 patients aged ≥65 years presenting to general practice with shortness of breath (SOB) on exertion in the previous 12 months and unknown with a history of established HF.12 All participants underwent history taking, physical examination, ECG, and a blood test for measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP). Only those with an abnormal electrocardiogram or NT-proBNP level exceeding the exclusionary cut-point for non-acute onset HF of >125 pg/mL underwent echocardiography. An expert panel established presence or absence of HF according to the criteria of the 2012 European Society of Cardiology (ESC) HF guidelines.18

Also between 2010 and 2012, van Mourik and co-workers screened for HF in 570 community-dwelling frail persons aged ≥65 years, unknown with a history of HF with a two-step screening strategy.13 First, they received a questionnaire about SOB and exercise tolerance. Those with exercise intolerance and/or SOB were invited to visit the general practice for a local screening programme, similarly as in the study of van Riet et al. Again, the final diagnosis was determined by a panel of experts based on all available diagnostic data, and presence or absence of HF established according to the criteria of the 2008 ESC HF guidelines, which are similar to the 2012 guidelines on HF.19

Boonman-de Winter and co-workers screened 581 patients aged 60 years or over with type 2 diabetes (T2D) and without a history of HF.14 Between February 2009 and March 2010, these patients underwent a similar standardized diagnostic work-up, and an expert panel decided on presence or absence of HF according to the criteria of the 2008 ESC HF guidelines.19

Between 2001 and 2003, Rutten and co-workers screened 405 participants aged 65 years of over with a general practitioner's diagnosis of chronic obstructive pulmonary disease (COPD) and unknown with a history of HF.15 Also in this study, a similar diagnostic work-up including echocardiography and an expert panel was used to establish presence or absence of HF according to the diagnostic criteria of the 2001 ESC HF guidelines, which are similar to the 2012 guidelines on HF.20

Routine general practice care

Valk and co-workers conducted a cross-sectional study among 683 patients from 30 general practices (70 000 individuals enlisted) with a general practitioner's diagnosis of HF between June and November 2011.16 Information on the diagnosis, medical history, medication use, and laboratory tests were collected from electronic medical record. An expert panel consisting of two cardiologists and an experienced general practitioner used all available diagnostic information and adjudicated the presence or absence of HF according to the criteria of the 2012 ESC HF guidelines.18 In 434 patients (63.5%), HF was established by the panel and these patients were included in the current study.

Outpatient cardiology clinics

Brugts and co-workers studied 10 910 patients with established HF receiving routine care at 34 Dutch cardiology outpatient centres in the period 2013–2016 and who were enrolled in the CHECK-HF registry.17 HF was diagnosed, similarly as in the screening studies and primary care study, that is, signs and symptoms suggestive of HF plus structural and/or functional cardiac abnormalities with echocardiography, and in accordance with the 2012 ESC guidelines.18

Outcome definition

The objective of this study is to assess the distribution of HF type (i) in those with screening-detected HF in the high-risk community, (ii) in patients with confirmed HF from primary care, and (iii) in those with confirmed HF in the outpatient cardiology clinics. For the current study, we reclassified the types of HF in the six studies according to the 2016 ESC guidelines on HF into the following: HFrEF if left ventricular ejection fraction (LVEF) < 40%, HFmrEF if LVEF 40–49%, and HFpEF if LVEF ≥ 50%.6 An overview of the studies with patient characteristics and the diagnostic criteria used to define HF is given in Table 1.

Ethical approval

The studies conformed to the principles outlined in the Declaration of Helsinki.21 The studies of van Riet, van Mourik, and Rutten were approved by the Medical Ethics Committee of the University Medical Center Utrecht, the Netherlands; all participants gave written informed consent. The study of Boonman-de Winter was approved by the institutional review board of the University Medical Center Utrecht and the Admiraal de Ruyter Hospital in Goes, the Netherlands; all participants gave written informed consent. The study of Valk was approved by the Regional Medical Ethics Committee (Verenigde Commissies Mensgebonden Onderzoek—VCMO) of four hospitals in the Utrecht region, including the Meander Medical Center in Amersfoort, the Netherlands. The CHECK-HF registry study was approved by the ethics committee of Maastricht University Medical Center 2017, Maastricht, the Netherlands.

Statistical analysis

For men and women, we extracted age-specific data regarding HFrEF, HFmrEF, and HFpEF diagnosis in strata of 5 years (65–69; 70–74; 75–79) from the three health care settings and for each outpatient cardiology centre separately. As age categories such as <65 and >80 years hamper comparability of prevalence estimates between studies due to the unknown age range and distribution, we restricted ourselves to the 5 year strata between 65 and 79 years because all studies provided these age-specific categories. Results are presented in absolute numbers and percentages.

Patient characteristics are presented as counts and percentages per health care setting for the following comorbidities: ischaemic heart disease, atrial fibrillation, diabetes, renal dysfunction, COPD, hypertension, hyperlipidaemia, peripheral artery disease, stroke, or transient ischaemic attack. If (i) studies used different definitions and (ii) if more than 10% of values were missing, the information was not presented.

All visualizations were performed in R statistical software Version 4.3, Foundation for Statistical Computing, Vienna, Austria.22

Results

In the high-risk community, among 1407 screened patients between 65 and 79 years old (703 women and 704 men), 288 (20.5%) had screen-detected HF. In the routine general practice, there were 160 confirmed cases of HF in patients between 65 and 79 years old. In the outpatient cardiology clinics, there were 4742 HF patients between 65 and 79 years old with numerically known LVEF.

Sex and heart failure type distribution

In the high-risk community, 146 of the 288 screening-detected HF patients were women (51%). Of the 288 patients, 15% had HFrEF, 12% HFmrEF, and 74% HFpEF. HFpEF was the most prevalent screening-detected type of HF for both men and women, being present in 82% of women and in 65% of men with HF (Figure 1, Table 2).

Distribution of sex and HFrEF, HFmrEF, and HFpEF in the high-risk community, general practice, and cardiology outpatient clinics. HF, heart failure; HFmrEF, heart failure with mid-range ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; OPC, outpatient clinic.

Table 2. Age-specific and sex-specific number of patients with heart failure with reduced, mid-range, and preserved ejection fraction in the high-risk community, general practice, and outpatient cardiology clinics High-risk community Age (years) Men (n = 142) Women (n = 146) HFrEF HFmrEF HFpEF HFrEF HFmrEF HFpEF Total 65–69 9 11 26 3 1 16 66 (23%) 70–74 12 7 28 6 3 53 109 (38%) 75–79 7 4 38 5 8 51 113 (39%) Total 28 (10%) 22 (8%) 92 (32%) 14 (5%) 12 (4%) 120 (42%) 288 (100%) General practice Age (years) Men (n = 91) Women (n = 69) HFrEF HFmrEF HFpEF HFrEF HFmrEF HFpEF Total 65–69 7 3 3 4 2 5 24 (15%) 70–74 9 9 11 6 8 8 51 (32%) 75–79 21 10 18 9 4 23 85 (53%) Total 37 (23%) 22 (14%) 32 (20%) 19 (12%) 14 (9%) 36 (23%) 160 (100%) Cardiology OPC Age (years) Men (n = 3050) Women (n = 1692) HFrEF HFmrEF HFpEF HFrEF HFmrEF HFpEF Total 65–69 652 116 144 243 73 103 1331 (28%) 70–74 738 142 149 311 78 163 1581 (33%) 75–79 771 167 171 402 117 202 1830 (39%) Total 2161 (46%) 425 (9%) 464 (10%) 956 (20%) 268 (6%) 468 (10%) 4742 (100%) HFmrEF, heart failure with mid-range ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; OPC, outpatient clinic.

In the routine general practice, 69 of the 160 confirmed HF patients were women (43%). Of the 160 patients, 35% had HFrEF, 23% HFmrEF, and 43% HFpEF. In women, HFpEF was the most prevalent HF type (52%), while in men, this was HFrEF (41%).

In the outpatient cardiology clinics, 1692 of the 4742 HF patients were women (36%). Of the 4742 patients, 66% had HFrEF, 15% HFmrEF, and 20% HFpEF. HFrEF was the most prevalent HF type in both women (56%) and men (71%). The distribution of HFrEF, HFmrEF, and HFpEF varied considerably between the 34 outpatient cardiology centres, ranging from 32% to 91% for HFrEF, 0% to 29% for HFmrEF, and 1% to 40% for HFpEF.

Comorbidities

In all three domains, patients with HFrEF and HFmrEF more often had a history of ischaemic heart disease than patients with HFpEF. In addition, in the general practice and the outpatient cardiology centres, patients with HFpEF more often had a history of atrial fibrillation and hypertension (Table 3). Although renal dysfunction is important in HF, unfortunately information on that topic was insufficient for presentation due to differences between studies in definition, and missing data (20%) from routine care.

Table 3. Baseline characteristics of included patient populations: patients with heart failure between 65 and 79 years old High-risk community Men Women HFrEF (n = 28) HFmrEF (n = 22) HFpEF (n = 92) HFrEF (n = 14) HFmrEF (n = 12) HFpEF (n = 120) Ischaemic heart disease, n (%) 9 (32) 12 (55) 38 (41) 6 (43) 5 (42) 28 (23) Atrial fibrillation, n (%) 3 (11) 2 (9) 13 (14) 2 (14) 4 (33) 14 (12) Diabetes, n (%)a 1 (5) 5 (24) 24 (38) 3 (27) 0 (0) 24 (34) COPD, n (%)b 4 (36) 5 (63) 16 (20) 3 (33) 1 (13) 15 (14) Hypertension, n (%) 13 (46) 10 (46) 66 (72) 10 (71) 8 (67) 94 (78) Hypercholesterolaemia, n (%)c 10 (36) 8 (36) 51 (55) 8 (57) 8 (67) 68 (57) Peripheral artery disease, n (%) 3 (11) 4 (18) 11 (12) 1 (7) 1 (8) 10 (8) Stroke or TIA, n (%) 5 (18) 2 (9) 13 (14) 0 (0) 2 (17) 17 (14) General practice Men Women HFrEF (n = 37) HFmrEF (n = 22) HFpEF (n = 32) HFrEF (n = 19) HFmrEF (n = 14) HFpEF (n = 36) Ischaemic heart disease, n (%) 25 (68) 10 (46) 10 (31) 11 (58) 5 (36) 9 (25) Atrial fibrillation, n (%) 14 (38) 12 (54) 22 (69) 3 (16) 7 (50) 22 (61) Diabetes, n (%) 13 (35) 7 (32) 17 (53) 8 (42) 6 (43) 8 (22) COPD, n (%) 4 (11) 7 (32) 4 (13) 1 (5) 6 (43) 11 (31) Hypertension, n (%) 17 (46) 8 (36) 24 (75) 9 (47) 7 (50) 23 (64) Hypercholesterolaemia, n (%)c 23 (62) 14 (64) 19 (59) 11 (58) 8 (57) 20 (56) Peripheral artery disease, n (%) NA NA NA NA NA NA Stroke or TIA, n (%) 2 (5) 1 (5) 8 (25) 2 (11) 3 (21) 5 (14) Cardiology OPC Men Women HFrEF (n = 2161) HFmrEF (n = 425) HFpEF (n = 464) HFrEF (n = 956) HFmrEF (n = 268) HFpEF (n = 468) Ischaemic heart disease, n (%) 1323 (63) 237 (58) 203 (45) 405 (44) 101 (39) 102 (23) Atrial fibrillation, n (%) 553 (26) 137 (33) 175 (38) 184 (20) 92 (35) 164 (35) Diabetes, n (%) 615 (32) 130 (34) 162 (37) 281 (32) 69 (28) 184 (42) COPD, n (%) 396 (20) 90 (24) 104 (24) 176 (20) 47 (19) 87 (20) Hypertension, n (%) 763 (40) 173 (45) 217 (50) 371 (43) 113 (47) 250 (57) Hypercholesterolaemia, n (%) 302 (16) 44 (12) 49 (11) 117 (14) 35 (14) 67 (15) Peripheral artery disease, n (%) 158 (8) 19 (5) 16 (4) 45 (5) 13 (5) 20 (5) Stroke or TIA, n (%) NA NA