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Eur Heart J Imaging Methods Pract
Eur Heart J Imaging Methods Pract
ehjimp
European Heart Journal. Imaging Methods and Practice
2755-9637
Oxford University Press UK

10.1093/ehjimp/qyae059
qyae059
Original Article
AcademicSubjects/MED00010
AcademicSubjects/MED00160
AcademicSubjects/MED00200
AcademicSubjects/MED00870
Eurheartj/27
Eurheartj/29
Variability in approach to exercise stress echocardiography for diagnosis of heart failure with preserved ejection fraction: an international survey on real-world practice
Tani Yuta Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan

Reddy Yogesh N V Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA

Verbrugge Frederik H Centre for Cardiovascular Diseases, University Hospital Brussels, Jette 1090, Belgium
Faculty of Medicine and Pharmacy, Vrije Universiteit Brussels, Jette 1090, Belgium

https://orcid.org/0000-0001-9067-4129
Yang Jeong Hoon Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
Department of Cardiology, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea

Negishi Kazuaki Nepean Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales 2747, Australia

Harada Tomonari Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan

Kagami Kazuki Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan
Division of Cardiovascular Medicine, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan

Saito Yuki Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan
Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan

Yuasa Naoki Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan

Sorimachi Hidemi Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan

Murakami Fumitaka Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan

https://orcid.org/0000-0002-0011-7589
Kato Toshimitsu Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan

Wada Naoki Department of Rehabilitation Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan

Ishii Hideki Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan

https://orcid.org/0000-0002-5473-0688
Obokata Masaru Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan

Corresponding author. E-mail: obokata.masaru@gunma-u.ac.jp
1 2024
12 6 2024
12 6 2024
2 1 qyae05906 3 2024
24 5 2024
04 7 2024
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.
2024
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Abstract

Aims

The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging based on resting assessments. Exercise echocardiography is often used to unmask abnormalities that develop during exercise, but the diagnostic criteria have not been standardized. This study aimed to elucidate how cardiologists utilize exercise echocardiography to diagnose HFpEF in real-world practice.

Methods and results

An international web-based survey involving 87 cardiologists was performed. We also performed a retrospective cross-sectional study to investigate the impact of different exercise echocardiographic diagnostic criteria in 652 dyspnoeic patients who underwent exercise echocardiography. The HFA-PEFF algorithm was the most commonly used exercise echocardiography criterion for HFpEF diagnoses (48%), followed by the ASE/EACVI criteria (24%) and other combinations of multiple parameters (22%). Among 652 patients, the proportion of HFpEF diagnosis varied substantially according to the criteria used ranging from 20.1% (ASE/EACVI criteria) to 44.3% (HFA-PEFF algorithm). Many cases (49.4–70.5%) remained indeterminate after exercise echocardiography, but only 41% of surveyed cardiologists would utilize exercise right heart catheterization to resolve an indeterminate result. Despite these diagnostic uncertainties, 54% of surveyed cardiologists would utilize exercise echocardiography results to initiate sodium–glucose co-transporter 2 inhibitors.

Conclusion

In real-world practice, exercise echocardiographic criteria utilized across cardiologists vary, which meaningfully impacts the frequency of HFpEF diagnoses, with indeterminate results being common. Despite these diagnostic uncertainties, many cardiologists initiate pharmacotherapy based on exercise echocardiography. The lack of consensus on universal diagnostic criteria for exercise echocardiography and approaches to indeterminate results may limit the delivery of evidence-based treatment for HFpEF.

Graphical Abstract

Graphical Abstract

diagnosis
exercise stress echocardiography
heart failure with preserved ejection fraction
questionnaire
survey
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pmcIntroduction

Recent clinical trials have shown convincing beneficial effects of pharmacotherapy in heart failure with preserved ejection fraction (HFpEF), such as sodium–glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1-) agonists.1–3 This makes its correct and early identification more important.4 Nevertheless, the diagnosis of HFpEF among people with chronic dyspnoea but without overt congestion remains challenging and relies on the demonstration of objective evidence of elevated left ventricular (LV) filling pressures by diagnostic tests such as natriuretic peptide or standard echocardiography.5–8 Importantly, LV filling pressures are often normal in patients with HFpEF at rest but increase abnormally during physiological stress, such as exercise.7,9–11 Recent guidelines recommend using exercise stress testing to detect such haemodynamic abnormalities during exercise in cases of diagnostic uncertainty based on resting assessments,12–14 and exercise stress echocardiography (i.e. diastolic stress echocardiography) being non-invasive is often used for the identification of occult HFpEF.7,10,15–19 However, universal exercise protocols and diagnostic criteria have not been established. As a result, their application in clinical practice may vary widely, affecting the diagnosis (or prevalence) and ultimately the management of HFpEF.

Accordingly, our main objective was to investigate the current practice of exercise stress echocardiography by collecting opinions from various cardiologists via a web-based international survey. We also performed a cross-sectional study to determine the impact of different diagnostic criteria on the proportion of HFpEF diagnoses using a large cohort of individuals undergoing exercise echocardiography.

Methods

An international survey for exercise stress echocardiography

This international web-based survey was designed to determine current practices regarding exercise stress echocardiography for the evaluation of HFpEF or dyspnoea. A group of HF or echocardiography specialists (Y.N.V.R., F.H.V., J.H.Y., K.N., T.H., and M.O.) developed and edited the survey, which included 16 individual questions (see Supplementary data online, Supplementary Materials). The survey was distributed to cardiologists through social networking services (SNS) [X (former Twitter) and Facebook] of the Echocardiography Laboratory, Gunma University Hospital, the Japanese Association of Young Echocardiography Fellow (JAYEF), and individual investigators. The questionnaire was also emailed to investigators’ colleagues. This survey was approved by the Ethics Board of the Gunma University Hospital (HS2023-057). The data underlying this article cannot be shared publicly due to the privacy of individuals who participated in the study.

A cross-sectional study

To investigate the impact of different criteria on HFpEF diagnosis, we performed a retrospective cross-sectional study. Consecutive series of 865 patients who were referred to the Gunma University echocardiographic laboratory for exercise stress echocardiography for the evaluation of unexplained dyspnoea between September 2019 and November 2023 were identified. We excluded patients without symptoms, current or previously documented reduced ejection fraction (EF < 50%), significant left-sided valvular heart disease (>moderate regurgitation, >mild stenosis); infiltrative, restrictive, or hypertrophic cardiomyopathy, non-group II pulmonary hypertension (PH), those younger than 20 years old, those who did not perform ergometer exercise echocardiography, and duplicate cases. This study was also approved by our Institutional Review Board with a waiver of informed consent (HS2023-118).

Details of the exercise stress echocardiographic examination in our laboratory are described previously.10,17,18 Briefly, all patients underwent semi-supine ergometer exercise, starting with a 20 watts (W) load for 5 min, with 20 W-increments in 3 min to participants’ exhaustion (Angio imaging, Lode B.V., Groningen, Netherlands). Echocardiographic images were recorded at baseline and at all stages of exercise to obtain trans-mitral inflow, mitral annular tissue velocities, tricuspid regurgitation (TR) velocity, and LV outflow pulse Doppler time–velocity integral.

The diagnosis of HFpEF was coded using different schemes: the recommendations from the American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) for the assessment of LV diastolic dysfunction;14 and the HFA-PEFF diagnostic algorithm from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).13 The diagnosis of HFpEF was first coded from resting echocardiographic data using the ASE/EACVI recommendations for the assessment of elevated LV filling pressure (see Supplementary data online, Figure S1A). Then, exercise stress echocardiography was considered abnormal (i.e. HFpEF) when all of the following criteria were met: septal E/e′ > 15 during exercise, exercise TR velocity >2.8 m/sec, and septal e′ velocity at baseline is <7 cm/sec (see Supplementary data online, Figure S1B).14 The results were normal (non-cardiac dyspnoea) when septal E/e’ ratio was <10 with exercise and peak TR velocity was <2.8 m/sec with exercise. If either the resting or exercise result was positive, the diagnosis of HFpEF was coded.

The HFA-PEFF algorithm calculates a score based on resting echocardiography and natriuretic peptide levels (0–6 points, Step 2). A score ≥5 points was defined as HFpEF while a score of <2 was considered as non-cardiac dyspnoea. Among patients with intermediate scores (2–4 points), two or three points were added depending on the E/e’ ratio and TR velocity during exercise stress echocardiography (Step 3). A diagnosis of HFpEF was coded if the combined score from Step 2 to Step 3 was ≥5 points (see Supplementary data online, Figure S2).13

The reproducibility of E/e’ and TR velocity during peak exercise was assessed in 30 randomly selected patients. Intra- and inter-observer agreement was evaluated after the same observer and another experienced reader repeated the analysis using intraclass correlation coefficients (ICCs).

Statistical analysis

Data are reported as mean (standard deviation), median (interquartile range: IQR), or number (%) unless otherwise noted. Between-group differences were compared using the χ2 test. Within-group differences were compared by paired t-test or Wilcoxon signed rank test. All tests were two-sided, with statistical significance set at P < 0.05. All statistical analyses were performed using JMP 17.1.0 (SAS Institute, Cary, NC, USA).

Results

The international survey

Characteristics of participants

A total of 87 cardiologists from 71 hospitals in 13 countries participated in this survey during ∼5 weeks from 10 August to 19 September 2023. The characteristics of the participants are shown in Table 1. The largest number of participants was from Japan (64%), followed by Belgium, Italy, and South Korea (Table 1). Nearly half of the participants (44%) were practicing at hospitals with more than 100 exercise stress echocardiography cases per year. Sixty-three participants (72%) were echocardiography specialists and 59 (68%) were heart failure specialists (Table 1). More than half of the participants (59%) had ≥6 years of experience with exercise stress echocardiography.

Table 1 Characteristics of the participants

	n = 87	
Region, n (%)		
 East Asia (Japan, South Korea)	65 (75%)	
 Europe (Belgium, France, Germany, Italy, Portugal, Spain)	18 (21%)	
 North America (USA)	3 (3%)	
 Others	1 (1%)	
Specialty and subspecialty,a n (%)		
 General cardiologist	43 (49%)	
 Echocardiography specialist	63 (72%)	
 Heart failure specialist	59 (68%)	
 Other cardiovascular imaging specialist	2 (2%)	
 EP specialist	1 (1%)	
 Interventional cardiologist	10 (11%)	
 Others	2 (2%)	
Experience of ESE, n (%)　(n = 86)		
 0–1 years	8 (9%)	
 2–5 years	27 (32%)	
 6–10 years	26 (30%)	
 >10 years	25 (29%)	
Number of ESE performed at practicing hospital per year, n (%)		
 1–50 cases	32 (37%)	
 51–100 cases	17 (19%)	
 101–300 cases	24 (28%)	
 301–500 cases	6 (7%)	
 >500 cases	8 (9%)	
Percentage of ESE for HFpEF or dyspnoea		
 0%	4 (5%)	
 1–25%	41 (47%)	
 26–50%	12 (14%)	
 51–75%	22 (25%)	
 76–100%	8 (9%)	
RA pressure estimation method during ESE a , n (%) (n = 81)		
 Use resting RAP value	33 (41%)	
 Measure IVC-based RAP during exercise	27 (33%)	
 Use fixed value (e.g. 10 mmHg)	22 (27%)	
 Measure IVC-based RAP in the recovery	10 (12%)	
 Measure peripheral venous pressure	2 (2%)	
 Others	1 (1%)	
EP, Electrophysiology; ESE, exercise stress echocardiography; HFpEF, heart failure with preserved ejection fraction; IVC, inferior vena cava; RAP, right atrial pressure; RVSP, right ventricular systolic pressure; TR, tricuspid regurgitation; and USA, United States of America.

aMultiple answers allowed.

Echocardiographic variables measured during exercise

Figure 1 demonstrates echocardiographic variables routinely measured during exercise echocardiography at the surveyed cardiologists’ medical centre. TR velocity, trans-mitral inflow velocity, E/e’ ratio, and mitral e’ velocity were assessed in more than 85% of the participants. Several cutoff values of TR velocity during exercise are proposed for an HFpEF diagnosis.12–14 Of the participants who answered with a single cutoff value (n = 78), the most commonly proposed cutoff for exercise TR velocity was 3.3 m/sec (49%), followed by 2.8 m/sec (17%) and 3.4 m/sec (10%; Figure 2). Similarly, an estimated right ventricular systolic pressure (eRVSP) during the exercise of 60 mmHg was the most frequently used cutoff value for an HFpEF diagnosis (28%), followed by 50 mmHg (17%) and 35 mmHg (15%; Figure 2). Thirty-three (41%) participants responded that they would use resting right atrial (RA) pressure value when estimating exercise RVSP (Table 1). The severity of mitral regurgitation was also assessed in most of the participants (75%). One-third of the participants reported that they would obtain mPAP/CO slope or ultrasound B-lines during exercise.

Figure 1 Frequency of echocardiographic variables measured during exercise stress echocardiography. *Multiple answers allowed. Values are expressed as percentages. E/e’, the ratio of early diastolic mitral inflow to mitral annular tissue velocities; HFpEF, heart failure with preserved ejection fraction; IVC, inferior vena cava; LVEF, left ventricular ejection fraction; LVOT-PW, left ventricular outflow tract pulse wave Doppler; mPAP/CO slope, the slope of estimated pulmonary artery mean pressure to cardiac output; MR, mitral regurgitation; TAPSE, tricuspid annular plane systolic excursion; TMF, trans-mitral inflow velocity pattern; TR, tricuspid regurgitation; and TV s’, systolic tissue velocity at the lateral tricuspid valve.

Figure 2 Cutoff values of TR velocity and estimated right ventricular pressure during exercise for HFpEF diagnoses. Values are expressed as percentages. eRVSP, estimated right ventricular systolic pressure; and other abbreviations as in Figure 1.

Diagnostic criteria of HFpEF by exercise stress echocardiography

Of 81 participants who responded, nearly half of the participants (48%) reported that they use the HFA-PEFF algorithm (i.e. exercise avg. E/e’ ≥ 15 and exercise TR velocity >3.4 m/sec) for the diagnosis of HFpEF, followed by the ASE/EACVI criteria (23%; i.e. exercise avg. E/e’ > 14, exercise TR velocity >2.8 m/sec, and septal e’ velocity at baseline <7.0 cm/sec) or other combinations of multiple parameters (22%; Figure 3). In participants who reported using multiple echocardiographic parameters, two would use the combination of trans-mitral inflow velocity pattern and TR velocity and other two would use the combination of trans-mitral inflow velocity pattern, E/e’ ratio, and TR velocity, while the remaining would use other combinations (e.g. E/e’ ratio, TR velocity, mPAP/CO slope, ultrasound B-lines, inferior vena cava, etc.). Some cardiologists answered that they diagnose HFpEF based on a single echocardiographic parameter (exercise E/e’ ratio, n = 2; and exercise TR velocity, n = 2). A comparison of responses from Asia and Europe reveals that the HFA-PEFF algorithm was used more frequently in Asia than in Europe (54.8% in Asia vs. 23.5% in Europe) while the use of the ASE/EACVI criteria was similar (24.2% in Asia vs. 23.5% in Europe). The use of other combinations of multiple parameters was more commonly used in Europe than in Asia (16.1% in Asia vs. 47.1% in Europe).

Figure 3 Proportions of most frequently used diagnostic criteria for HFpEF by exercise stress echocardiography. Values are expressed as percentages. ASE/EACVI, the American Society of Echocardiography/European Association of Cardiovascular Imaging; CPET-ESE, cardiopulmonary exercise test and exercise stress echocardiography; HFA-PEFF, the Heart Failure Association Pre-test assessment, echocardiography and natriuretic peptide, functional testing, final aetiology; and other abbreviations as in Figure 1.

Questionnaires for therapeutic implication of exercise echocardiography and invasive cardiopulmonary exercise test

Of 84 participants who answered, the majority (n = 45, 54%) would initiate SGLT2 inhibitors based on the results of exercise stress echocardiography. Approximately half of all participants (n = 52%) reported that invasive cardiopulmonary exercise tests are available in their hospitals. Two-thirds of the participants (64%) responded that they would consider an invasive exercise haemodynamic test if concern for PAH was present, followed by negative exercise echocardiographic results but high suspicion for HFpEF (55%), low diagnostic quality examination (e.g. poor image quality; 45%), and intermediate exercise echocardiographic results (41%; Figure 4).

Figure 4 Indications for exercise right heart catheterization for the diagnosis of HFpEF. *Multiple answers allowed. Values are expressed as percentages. ESE, exercise stress echocardiography; PAH, pulmonary artery hypertension; and other abbreviations as in Figure 1.

Results of the retrospective cross-sectional study

The final cohort of the retrospective cross-sectional study included 652 subjects. Overall, patients were elderly and predominantly women (59.4%), with multiple cardiac and metabolic comorbidities, but only modestly elevated natriuretic peptide levels (Table 2). On average, LV end-diastolic volume and mass index, LA volume, and eRVSP were normal, with a borderline elevation of E/e’ ratio at rest. During exercise, E/e’ ratio and eRVSP were significantly increased, with a modest increase in mitral e’ velocity (all P < 0.0001).

Table 2 Baseline characteristics

	n = 652	
Age (years)	70.4 ± 12.3	
Female, n (%)	387 (59.4%)	
Body mass index (kg/m2)	23.9 ± 5.1	
Comorbidities		
Coronary artery disease, n (%)	58 (9%)	
Diabetes mellitus, n (%)	136 (21%)	
Hypertension, n (%)	479 (73%)	
Atrial fibrillation, n (%)	148 (23%)	
COPD, n (%)	52 (8%)	
H2FPEF score (points)	2 (2, 4)	
Medications (n = 647)		
ACEI, ARB, or ARNI, n (%)	236 (36%)	
Beta-blockers, n (%)	137 (21%)	
Loop diuretics, n (%)	140 (22%)	
MRA, n (%)	65 (10%)	
SGLT2 inhibitors, n (%)	47 (7%)	
Laboratories		
BNP (pg/mL), n = 272	51 (20, 120)	
NT-proBNP (pg/mL), n = 434	157 (78, 492)	
Creatinine (mg/dL), n = 617	0.78 (0.66, 0.98)	
Vital signs		
Heart rate (bpm)	72 ± 14	
Systolic BP (mmHg), n = 643	128 ± 19	
Resting echocardiography		
LV end-diastolic volume (mL), n = 625	72 ± 26	
LV mass index (g/m2), n = 641	83 ± 23	
LV ejection fraction (%)	63 ± 7	
LA volume index (mL/m2), n = 645	29 (22, 39)	
E-wave (cm/sec), n = 651	70 ± 22	
Mitral e’ (cm/sec), n = 650	6.4 ± 1.9	
E/e’ ratio (septal), n = 649	11.7 ± 4.7	
eRVSP (mmHg), n = 615	22 ± 8	
Exercise echocardiography		
Peak (W)	55 ± 24	
Peak mitral e’ (cm/sec), n = 650	8.7 ± 2.5	
Peak E/e’ ratio (septal), n = 649	13.8 ± 5.3	
Peak eRVSP (mmHg), n = 607	42 ± 13	
Data are mean ± SD, median (interquartile range), or n (%).

ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin-receptor blockers; ARNI, angiotensin-receptor–neprilysin inhibitors; BNP, B-type natriuretic peptide; BP, blood pressure; COPD, chronic obstructive pulmonary disease; E/e’ ratio, the ratio of early diastolic mitral inflow to mitral annular tissue velocities; eRVSP, estimated right ventricular systolic pressure; LA, left atrial; LV, left ventricular; MRA, mineralocorticoid-receptor antagonists; NT-pro BNP, N-terminal pro B-type natriuretic peptide; and SGLT2, sodium–glucose co-transporter-2.

Figure 5 shows the frequency of HFpEF diagnosis according to different diagnostic criteria. The rate of HFpEF diagnosis was the lowest (n = 55, 8.4%) when the ASE/EACVI resting criteria were applied. The addition of the ASE/EACVI-based exercise echocardiography criteria to the resting ASE/EACVI assessments resulted in a modest increase in HFpEF diagnosis (n = 131, 20.1%), with a large number of indeterminate cases (n = 460, 70.5%). When the resting HFA-PEFF algorithm (Step 2) was applied, the rate of HFpEF diagnosis was increased to 31.7% (n = 207), but a large number of cases remained inconclusive (2–4 points; n = 404, 62.0%). The frequency of HFpEF diagnosis was increased to 44.3% (n = 289), with a decreased rate of indeterminate cases (n = 322, 49.4%).

Figure 5 Proportion of HFpEF diagnosis according to the different diagnostic criteria. Values are expressed as percentages. Ex, exercise; and other abbreviations as in Figures 1 and 3.

The intra-observer ICCs for exercise E/e’ ratio and TR velocity were 0.87 and 0.87, respectively. The corresponding inter-observer ICCs were 0.83 and 0.93, respectively.

Discussion

The diagnosis of HFpEF remains challenging. Current guidelines recommend exercise stress echocardiography for the evaluation of HFpEF, but it remains unclear how it is performed in real-world clinical practice and how the results are interpreted to guide treatment. This study is the first investigation to determine the current practice of exercise stress echocardiography by collecting worldwide opinions from cardiologists via a web-based international survey. The main findings are as follows: (i) the exercise echo diagnostic criteria utilized for HFpEF diagnosis differed among individual cardiologists, with the HFA-PEFF algorithm and the ASE/EACVI criteria being the two most frequently used criteria; (ii) the prevalence of HFpEF diagnoses in patients with dyspnoea differed substantially depending on the criteria that were used; (iii) more than half of the participating cardiologists indicated that they would start SGLT2 inhibitors based on the results of exercise stress echocardiography; and (iv) indeterminate results were common in our retrospective cohort, and less than half of cardiologists would refer for confirmatory exercise right heart catheterization in the presence of indeterminate results. These data provide important clinical implications: they point out inconsistencies in the worldwide evaluation of HFpEF with exercise stress echocardiography, and they emphasize the need for universal protocol and diagnostic criteria to maximize its utility in clinical practice.

Variety of echocardiographic parameters measured during exercise

The diagnosis of HFpEF is challenging among patients with euvolemia because cardiac congestion is difficult to evaluate non-invasively and many patients develop abnormal haemodynamics only during physiological stress, such as exercise.4–11 Recent guidelines emphasize the importance of exercise stress testing to detect such abnormalities,12–14 and exercise stress echocardiography has been increasingly advocated as an initial test to enhance the diagnosis of HFpEF.7,10,15–19 However, there are no universal protocols, measurements, or diagnostic criteria for exercise stress echocardiography for the evaluation of HFpEF. This may affect the quality of the test and ultimately clinical management.

In this international survey, we obtained opinions from cardiologists, the majority of whom had ≥6 years of experience with exercise echocardiography. We found that trans-mitral inflow velocity, mitral e’ velocity, E/e’ ratio, and TR velocity were the four most frequently obtained parameters during exercise echocardiography. This may be related to the current consensus statements,12–14 but data to support the accuracy and optimal combination of imaging parameters to estimate LV filling pressures during exercise remain limited.20 Some studies have demonstrated robust correlations of exercise echocardiographic parameters (e.g. E/e’ ratio, TR velocity) with invasively measured data,7,21–23 but others have not reproduced these favourable correlations.20,24 There is no agreement concerning cutoff values of diagnostic variables and they are based on expert consensus opinion.12–14 In fact, our survey found that cutoff values of TR velocity or estimated RVSP varied widely among physicians (Figure 2). The current study reveals the important, previously unrecognized limitations of exercise stress echocardiography. Other important limitations also exist: an isolated increase in TR velocity is not sufficient to diagnose HFpEF because it may be caused by precapillary pulmonary arterial hypertension or a normal hyperdynamic response to exercise in the absence of LV diastolic dysfunction.12 In addition, TR velocity alone cannot account for increased RA pressure during exercise. In our survey, many cardiologists reported using resting or fixed RA pressure to estimate RA pressure during exercise. This may lead to serious underestimation of RA and RVSP, and thus HFpEF diagnosis.21,23 Recent studies have demonstrated the potential utility of emerging parameters such as ultrasound B-lines and mPAP/CO slope,18,25–27 and further investigations are required on the combined accuracy of these multiple parameters.

The diversity of diagnostic criteria and its adverse effects

The primary limitation of exercise stress echocardiography for the evaluation of HFpEF is the lack of validated diagnostic criteria.18 To address the impact of different diagnostic criteria in real-world practice, we combined the international survey and cross-sectional study. Our survey demonstrated that the diagnostic criteria used varied significantly among individual cardiologists (Figure 3). Overall, the HFA-PEFF algorithm and the ASE/EACVI criteria were the two most frequently used criteria. Differences in the frequency were observed between Asia and Europe, but most importantly, the proportion of HFpEF diagnoses in patients with dyspnoea differed substantially according to the diagnostic criteria used (Figure 5). Although the accuracy of these two diagnostic criteria is beyond the scope of the current study due to the lack of the gold standard of invasive exercise haemodynamic test, the large difference in the proportion of HFpEF or indeterminate diagnosis caused by the different diagnostic criteria used suggests that appropriate treatment may not be delivered to patients in clinical practice. Indeed, our survey revealed that the majority of cardiologists would initiate SGLT2 inhibitors based on the results of exercise stress echocardiography. Further studies are warranted to establish an evidence-based criterion for exercise stress echocardiography to diagnose HFpEF with definitive ascertainment of HFpEF or non-cardiac dyspnoea status by the gold standard of invasive exercise haemodynamic testing.

Future perspectives

In this cross-sectional study, a large proportion of patients were classified as intermediate/indeterminate, especially by current exercise criteria, an issue that contributes to the diagnostic challenges for HFpEF by exercise stress echocardiography. Invasive exercise haemodynamic test is the gold standard test to diagnose or rule out HFpEF.6,13 Notably, less than half of cardiologists surveyed would consider an exercise right heart catheterization with an inconclusive exercise echocardiogram result, suggesting further clarification of this category and optimal approach is needed. In addition, invasive haemodynamic exercise testing is not available in many hospitals worldwide and the optimal approach to diagnosis in these settings from an indeterminate exercise echocardiogram is uncertain. As such, further studies are needed to develop and validate the optimal exercise echocardiography criteria for the diagnosis of HFpEF.

Limitations

The current investigation has certain limitations. Although this survey was open access, distribution of the survey through SNS might be limited to reach a wide range of cardiologists worldwide. For example, physicians who were not on SNS would have been excluded from the study. Because the survey was targeted to cardiologists who perform exercise echocardiography, the number of participants was relatively small, with a limited number of countries. Half of the participating cardiologists were practicing in Japan, which might limit the generalizability of the results. Many surveyed cardiologists might practice at specialized centres, which also introduced bias. The retrospective nature of the cross-sectional study might introduce selection bias. The cross-sectional study did not address the diagnostic accuracy of the two diagnostic schemes. We did not assess advanced echocardiographic parameters, such as LV and RV longitudinal strain. The percentage of cardiologist responses regarding the prescription of SGLT2 inhibitors should be interpreted in light of the fact that exercise echocardiography was not an inclusion criterion in the two large clinical trials of SGLT2 inhibitors.1,2 Nevertheless, this is the first investigation to determine the current real-world practice of exercise stress echocardiography for the diagnosis of HFpEF.

Conclusion

In real-world practice, exercise echocardiography criteria used for HFpEF diagnosis vary among cardiologists, even among those with years of experience with exercise echocardiography. While many cardiologists consider initiating SGLT2 inhibitors based on the results of exercise stress echocardiography, the frequency of HFpEF diagnoses varies substantially depending on the diagnostic criteria used. The lack of universal diagnostic criteria may limit the delivery of appropriate treatment to patients with HFpEF. Further studies are needed to establish the optimal protocol and diagnostic criteria for the diagnosis of HFpEF.

Consent

This study was approved by our Institutional Review Board (HS2023-057 and HS2023-118) with a waiver of informed consent.

Supplementary data

Supplementary data are available at European Heart Journal - Imaging Methods and Practice online.

Supplementary Material

qyae059_Supplementary_Data

Acknowledgements

Dr Obokata received research grants from the Fukuda Foundation for Medical Technology, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Nippon Shinyaku, Takeda Science Foundation, Japanese Circulation Society, Japanese College of Cardiology, AMI Inc., Nippon Boehringer-Ingelheim, JSPS KAKENHI (21K16078), and AMED (23jm0210104h0002). Dr Harada received research grants from the Bayer Academic Support.

Funding

None declared.

Conflict of interest: Dr Obokata received speaker honoraria from Novartis, Otsuka Pharmaceutical, AstraZeneca, and Nippon Boehringer-Ingelheim. Dr Ishii received lecture fees from AstraZeneca Inc., Bayer Pharmaceutical Co., Ltd, Boehringer-Ingelheim Japan, Bristol-Myers Squibb Inc., Daiichi-Sankyo Pharma Inc., MSD K.K., Mitsubishi Tanabe Pharma Co., Ltd, Mochida Pharmaceutical Co., Ltd, Novartis Japan, and Pfizer Japan Inc.

Data availability

Due to ethical restrictions imposed by the Ethics Committee and to protect the privacy of individuals, raw data cannot be publicly shared.

Lead author biography

Yuta Tani is a physical therapist and is currently enrolled in a doctoral programme at the Gunma University Graduate School of Medicine. He has been active in clinical research and his research interests include heart failure, especially heart failure with preserved ejection fraction (HFpEF). From the viewpoint of a physical therapist, Yuta Tani focuses on the evaluation and management of HFpEF.
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