Expert insights into overcoming diagnostic hurdles and advancing management of HFpEF

As heart failure with preserved ejection fraction (HFpEF) increasingly impacts global health, clinicians face distinct challenges in its identification and therapeutic approaches. At an expert meeting chaired by Professor Hung-Fat Tse of the School of Clinical Medicine, the University of Hong Kong, a panel of local cardiologists shared insights into effective and accurate HFpEF diagnosis in clinical practice, alongside strategies for its prevention and treatment.

Outcomes in HFpEF comparable to HFrEF
Heart failure (HF) is a heteroge­neous syndrome characterized by dynamic functional and structur­al changes, covering a spectrum of phenotypes with distinct and over­lapping characteristics. While current guidelines classify HF patients based on left ventricular ejection fraction (LVEF), the understanding of patient outcomes on the basis of the over­all phenotype is still evolving. [ESC Heart Fail 2021;8:2741-2754]

“The incidence of HFpEF is rising, and patient outcomes are as poor as for HF with reduced ejection fraction [HFrEF], including similar 5-year over­all survival and readmission rates, as shown by data from various registries, such as those in the US and the Hong Kong HF Registry. A study of 1,693 hos­pitalized patients with HF found no sta­tistically significant difference in 6-month risk of death or rehospitalization be­tween patients with HFpEF and HFrEF [58 vs 56 percent; p=0.687], challeng­ing the perception that HFpEF carries a better prognosis. While comorbidities such as hypertension, atrial fibrillation [AF], chronic kidney disease [CKD], di­abetes, stroke and chronic obstructive pulmonary disease [COPD] are preva­lent across all HF groups, they are gen­erally higher in HFpEF, with overlapping conditions exacerbating mortality risk. Critically, LVEF alone poorly predicts adverse outcomes,” said Dr Catherine Shea of Queen Mary Hospital. [JACC Cardiovasc Imaging 2018;11:1-11; J Am Coll Cardiol 2017;70:2476-2486; J Card Fail 2016;22:600-608; ESC Heart Fail 2021;8:2741-2754; Eur J Heart Fail 2024;26:854-868]

Predominant HFpEF phenotypes in the region
According to findings of the PARAGON-HF trial, Asia-Pacific HF­pEF patients are on average young­er (mean age, 72 years), have a high prevalence of diabetes despite low obesity rates, and face greater risks of cardiovascular (CV) death and HF hospitalization (HFH) than those from Central Europe, Latin America and Western Europe. [Circ Heart Fail 2021;14:e007901]

Most panellists noted that local HFpEF patients are typically elderly and present with AF, hypertension, diabetes, and CKD. They may also present with nonspecific symptoms, such as shortness of breath (SoB). Additionally, some obese patients may have undiagnosed obstructive sleep apnoea (OSA). [Tse HF, et al, HF Ex­pert Meeting, 2025]

Clinical challenges of diagnosing HFpEF
Diagnosing HFpEF is challeng­ing in clinical practice, often lead­ing to delayed identification and underdiagnosis.

Nonspecific symptoms and patient’ perception
The panellists pointed out that the primary issue is the nonspecific nature of HFpEF symptoms, such as SoB on exertion, fatigue and oedema. Patients, particularly older adults and those with multiple comorbidities, of­ten attribute these to ageing or other conditions, making them unaware of the serious implications. This diagnos­tic complexity is further compounded by the absence of overt volume over­load. [Tse HF, et al, HF Expert Meeting, 2025] “It is estimated that >15 percent of older adults with unexplained exer­tional dyspnoea have undiagnosed HF, predominantly HFpEF,” Shea noted. [Eur J Heart Fail 2014;16:772-777]

“Diagnostic accuracy is further complicated by sex-specific differenc­es. Women with HFpEF often present with higher ejection fraction and more concentric LV remodelling, meaning that sex-neutral ‘normal’ thresholds may lead to underestimation of under­lying dysfunction,” Shea added. [J Am Coll Cardiol 2023;81:1835-1878]

Nuances of NT-proBNP interpretation
“Interpreting N-terminal pro-B-type natriuretic peptide [NT-proBNP] results is nuanced, as various clini­cal and physiological variables may impact its level, including common HFpEF comorbidities. For example, NT-proBNP levels are markedly low­er in patients with obesity-related [ie, BMI ≥35 kg/m²] HFpEF; conversely, AF independently raises NT-proBNP – and therefore specific adjusted cutoffs may be required,” highlighted Shea. [J Am Coll Cardiol 2025;86:1823-1839; PLoS Med 2025;22:e1004550]

“Moreover, normal NT-proBNP does not rule out HFpEF in outpatient settings, with up to one-third of such patients ultimately diagnosed with the condition,” remarked Professor Alex Lee of the Department of Medi­cine and Therapeutics, Chinese Uni­versity of Hong Kong (CUHK). This was demonstrated in a study of pa­tients with unexplained SoB, where 37 percent of those referred for inva­sive cardiopulmonary exercise testing were found to have HFpEF despite normal NT-proBNP levels. [Eur Heart J 2022;43:1941-1951]

Availability of diagnostic tests
Current European Society of Car­diology (ESC) guidelines recommend objective evidence of cardiac structur­al and/or functional abnormalities, with an LVEF of ≥50 percent, confirmed by echocardiography and elevated NT-proBNP levels. However, outpatient NT-proBNP is currently not routinely available in Hong Kong’s public setting. While echocardiography remains the gold standard for diagnosis, most pan­ellists pointed out that extended waiting times can present challenges to timely diagnosis. [Eur Heart J 2021;42:3599-3726; Tse HF, et al, HF Expert Meeting, 2025]

The panellists noted that porta­ble point-of-care ultrasound could enable more readily available initial cardiac assessment before formal echocardiography, though effective implementation necessitates appro­priate training. Ultimately, in settings where specific diagnostic tests for HFpEF are less readily available, clin­ical judgment is of high importance. Clinical suspicion driven by patients’ comorbidities remains key, emphasiz­ing the need for continued diagnostic support in the primary care setting. [Tse HF, et al, HF expert meeting, 2025]

Cases presented by Dr Michael Wong of the Grantham Hospital (case 1) and Lee (cases 2 and 3) illustrate how HFpEF is identified in clinical practice despite these challenges. “Whilst LVEF is not an essential element for HF initial diagnosis, an accurate measurement of LVEF by echocardiography should be documented preferably within 6 weeks after HF is diagnosed by history, phys­ical exam and markers of congestion, such as NT-proBNP elevation or chest X-ray,” Lee emphasized.

Comorbidity management: Preventing HFpEF and optimizing outcomes
Patients with HFpEF often present with a higher burden of comorbidities vs those with HFrEF or HF with mild­ly reduced ejection fraction (HFmrEF). Based on local data, major comorbidi­ties in HF patients include hypertension, AF, diabetes, CAD, previous ischaemic stroke, and CKD. These comorbidities are inter-related, worsen overall prog­nosis and outcomes, and impact out­comes of CV and non-CV events. [Eur J Heart Fail 2024;26:854-868; J Card Fail 2016;22:600-608; J Am Coll Cardi­ol 2023;81:1835-1878]

The panellists agreed that aggressive­ly treating these comorbidities is crucial to preventing and managing HFpEF, particu­larly in patients with both T2D and CKD, in whom hospitalization and mortality risks are significantly elevated. Since un­derlying metabolic disease, mineralocor­ticoid receptor (MR) overactivation, and renin-angiotensin-aldosterone system (RAAS) activation are key pathophysio­logical pathways common to both HF and CKD, drugs targeting these pathways of­fer dual benefits. For instance, finerenone, a nonsteroidal MRA, reduces the risk of CV and kidney outcomes in patients with concurrent T2D and CKD, with benefits independent of SGLT2i and glucagon-like peptide-1 receptor agonist use. The pan­ellists also highlighted the importance of public education for HFpEF prevention, emphasizing risk factors such as obesity. [J Am Coll Cardiol 2023;81:1835-1878; Diabetologia 2024;67:246-262; Hyper­tension 2018;72:537-548; Eur Heart J 2022;43:474-484; Tse HF, et al, HF Ex­pert Meeting, 2025]

Treating HFpEF early improves outcomes
“HF progression is typically punc­tuated by repeated worsening events, with real-world data indicating that one in six patients develop worsening HF within 18 months of diagnosis,” noted Professor Chu-Pak Lau of the Depart­ment of Medicine, University of Hong Kong (HKU). “Given the high 2-year mortality [22.5 percent] and that over half of patients [56 percent] are rehos­pitalized within 30 days of the worsen­ing HF event, early initiation of optimally dosed guideline-directed medical thera­py [GDMT] is imperative for reducing HF symptoms and improving outcomes.” [J Am Coll Cardiol 2019;73:935-944; Drugs 2023;83:747-759]

Pivotal SGLT2i trials, including EMPEROR-Reduced, EMPEROR-Preserved and DELIVER, demonstrat­ed significant and early reduction in the composite endpoint of CV death or HFH across the entire LVEF spectrum (HFrEF, HFmrEF and HFpEF populations). Furthermore, finerenone significantly reduced the composite endpoint of worsening HF events and CV death in HFmrEF and HFpEF patients in the FINEARTS-HF study. Notably, finerenone was associ­ated with early clinical benefits, with the first nominal statistical significance ob­served as early as day 28 and sustained through final follow-up. The efficacy and rapid onset of benefit observed for both SGLT2is across the LVEF spectrum, alongside finerenone’s early benefit in those with LVEF ≥40 percent, provide a strong rationale for their early initiation. Importantly, finerenone’s benefits were observed irrespective of concomitant SGLT2i use, suggesting that combined use may offer additive protection against CV events, with complementary roles in treating patients with HFmrEF and HFpEF. [N Engl J Med 2020;383:1413-1424; N Engl J Med 2021;385:1451-1461; N Engl J Med 2024;391:1475-1485; J Am Coll Cardiol 2025;85:199-202; Circula­tion 2025;151:149-158; N Engl J Med 2022;387:1089-1098]

“ESC’s guidelines recommend ini­tiating SGLT2i and diuretics, alongside treating comorbidities, once HFpEF is diagnosed, with additional finerenone to be considered for patients with both T2D and CKD,” noted Lau. “Finerenone use in HFpEF is endorsed by the Inter­national Cardio Alliance to Improve Dis­ease Outcomes [iCARDIO] and Japan Heart Failure Society [JHFS] guidelines.” [Eur Heart J 2023;44:3627-3639; Heart Lung Circ 2025;34:651-653; Circ J 2025;89:1278-1444]

The panellists underscored that HFpEF treatment needs to be individ­ualized based on comorbidities and specific phenotypes. They advocat­ed for early initiation of SGLT2i and nonsteroidal MRA, whether simulta­neously or in rapid sequence during hospitalization, due to their efficacy and good safety profiles. This compre­hensive and personalized approach re­flects the evolving landscape of HFpEF treatment and aims to optimize patient outcomes. [Tse HF, et al, HF Expert Meeting, 2025]