Discordant HFpEF scores in atrial fibrillation — case discussion

Presentation

Practice case (not a real patient). A 73-year-old man has a year of exertional breathlessness. He has permanent atrial fibrillation, a BMI of 31 kg/m² and takes two antihypertensive drugs. Coronary CT angiography last year showed no significant coronary disease, and he has no features of pericardial constriction.^[6][4] Echocardiography shows an LVEF of 58% (never previously below 50%) and no significant valve disease. Mitral E velocity is 99 cm/s, septal e′ 9 cm/s and lateral e′ 10.8 cm/s, so septal E/e′ is 11 and average E/e′ 10; TR peak velocity is 2.7 m/s with an estimated PA systolic pressure of 32 mmHg.^[1][6][4] LA volume index is 39 mL/m², LV mass index 118 g/m² with a relative wall thickness of 0.44, and GLS 17% (absolute value). His NT-proBNP is 420 pg/mL.^[4]

Step 1 — Does he meet the guideline criteria?

• ESC 2026: he has symptoms, and his LVEF is ≥50% and has not previously been <50%, so the first two criteria are met.^[1]
• ESC 2026 Table 10 objective evidence: LV mass index ≥115 g/m² (male) and RWT >0.42 meet the LV hypertrophy row, and E/e′ >9 at rest meets the filling-pressure row; his LA volume index of 39 mL/m² is below the >40 mL/m² AF threshold, and neither PA systolic pressure >35 mmHg nor TR velocity at rest >2.8 m/s is present.^[1]
• His NT-proBNP of 420 pg/mL is above the suggested age-adjusted level for 50–75 years that ESC 2026 reports from the HFA-ESC consensus (≥250 pg/mL, above which HF is ‘likely’ in the outpatient setting), although AF is among the ESC 2026 Table 9 causes of increased natriuretic peptide levels.^[1]
• HFA-PEFF says masqueraders such as heart valve disease, arrhythmias and pericardial constriction need to be excluded, and that a patient with a normal LVEF and HF-like symptoms caused by significant CAD is not considered to have HFpEF; valve disease and significant coronary disease have been excluded and constriction is not suspected, but his permanent AF is an arrhythmia.^[4]
• HFA-PEFF Table 2 lists atrial/ventricular arrhythmias among the potential specific aetiologies underlying HFpEF-like syndromes in step 4, and the same paper also lists atrial fibrillation among the typical clinical demographics of step 1 and says the most important indication for the ECG is to detect AF, which is highly predictive of underlying HFpEF.^[4]
• The HFA-PEFF paper describes overlap in symptoms, signs, echocardiographic findings and natriuretic peptide levels between HFpEF and AF; its authors say they did not adopt the alternative view that AF per se could be used as a stand-alone indicator of HFpEF, while emphasising the close association between AF and HFpEF.^[4]
• The held HFA-PEFF article text gives no rule for deciding whether his AF is the masquerader or part of HFpEF, so the masquerader check stays open, at least for his AF, rather than complete.^[4]

Step 2 — The two scores disagree

• H2FPEF = 8: AF 3, obesity (BMI >30 kg/m²) 2, age >60 years 1, two antihypertensives 1, septal E/e′ >9 1; PA systolic pressure is not >35 mmHg. AHA/ACC/HFSA 2022 reads ≥6 as high likelihood.^[6][2]
• HFA-PEFF step 2 in AF, functional domain: average E/e′ 10 is a minor criterion (9–14), 1 point, and TR velocity 2.7 m/s and GLS 17% meet no criterion. Other step 2 criteria: none met (septal e′ 9 cm/s and lateral e′ 10.8 cm/s at age <75 years; PA systolic pressure 32 mmHg).^[4]
• Morphological domain: LA volume index 39 mL/m² is minor in AF (34–40 mL/m²) and LV mass index ≥115 g/m² in men or RWT >0.42 is also minor, so that domain scores 1. Biomarker domain: NT-proBNP 420 pg/mL is minor in AF (375–660 pg/mL), 1 point.^[4]
• HFA-PEFF says its distinct natriuretic peptide and LAVI thresholds for sinus rhythm and AF are based on existing literature and consensus and need more prospective research for their validation, and that other functional measures are also likely to be affected by concomitant AF.^[4]
• His HFA-PEFF total is 3, intermediate (2–4), so HFA-PEFF sends him to step 3 functional testing.^[4]
• In a community study of 4,892 ARIC participants aged 67 to 90 years at visit 5 (2011 to 2013) without other common cardiopulmonary causes of dyspnoea, the authors reported that a significant fraction of patients are classified discordantly by using both algorithms: among those with unexplained dyspnoea, 28% were high risk by only one algorithm.^[8]
• ESC 2026 says diagnostic scoring systems, if employed, should be interpreted with caution and used primarily to raise clinical suspicion rather than to establish a definitive diagnosis, and that in cases of diagnostic uncertainty further investigations such as CPET, exercise stress echocardiography or invasive haemodynamic assessment may be considered.^[1]

Step 3 — Exercise echocardiography

At peak supine bicycle exercise, his average E/e′ is 13 and his peak TR velocity rises to 3.5 m/s.^[4]

• HFA-PEFF says exercise echocardiography should be considered abnormal if average E/e′ at peak stress increases to ≥15, with or without a peak TR velocity >3.4 m/s; it adds 2 points for an average exercise E/e′ ≥15, or 3 with a peak TR velocity >3.4 m/s, and his E/e′ of 13 does not reach that, so his test adds no points.^[4]
• HFA-PEFF says an increase only in TR velocity should not be used to diagnose HFpEF, because it might be caused simply by a normal hyperdynamic response to exercise (with increased pulmonary blood flow) in the absence of LV diastolic dysfunction.^[4]
• With his score still <5, HFA-PEFF recommends an invasive haemodynamic stress test in any case of doubt, especially if a therapeutic decision depends on it.^[4]
• ESC 2026: right heart catheterization may be considered in selected patients with suspected HFpEF or structural heart disease to confirm the diagnosis, or when clinical examination and non-invasive testing are insufficient to understand the haemodynamic state (Class IIb, Level C); its footnote adds that this potentially includes exercise right heart catheterization.^[1]

Step 4 — Invasive haemodynamics

Right heart catheterization: resting PCWP 11 mmHg; at peak supine exercise PCWP 27 mmHg.^[1][4]

• ESC 2026 says a PCWP ≥25 mmHg with exercise is generally considered diagnostic of HFpEF, and HFA-PEFF classifies a peak exercise PCWP ≥25 mmHg as HFpEF.^[1][4]
• His resting PCWP of 11 mmHg was in the range HFA-PEFF calls a normal mPCWP at rest (<12 mmHg), and that did not exclude HFpEF: HFA-PEFF says normal resting LVEDP or mean PCWP does not exclude HFpEF, and that in compensated HFpEF haemodynamic alterations may be detected only during exercise or when the patient deteriorates.^[4]

Step 5 — Final aetiology

His cardiologist suspects cardiac amyloidosis and wants to know whether a specific cause is present.^[1][4]

• HFA-PEFF step 4: most cases of HFpEF are related to common risk factors and comorbidities, but the possibility of a specific underlying aetiology should always be considered; specific aetiologies that may be treatable include inherited or acquired infiltrative, restrictive, inflammatory or genetic cardiomyopathies.^[4]
• ESC 2026: initial diagnostic testing with serum and urine immunofixation, serum free light chains assay, and DPD/PYP/HMDP bone scintigraphy is recommended in patients with HF and a suspicion of cardiac amyloidosis (Class I, Level B).^[1]
• ESC 2026: contrast-enhanced CMR is recommended in suspected cardiomyopathy, or where the underlying aetiology of HF is uncertain if further characterization is likely to add value to patient care (Class I, Level C).^[1]