Use of an SGLT2i in a patient with heart failure with preserved ejection fraction

History and presentation
A 70-year-old male with a history of atrial fibrillation (AF), who was seen regularly at our Cardiology clinic, noted progressively worsening shortness of breath (SoB) and reduced exercise tolerance (New York Heart Association [NYHA] functional class II) over the past 6 months.

He underwent an ablation procedure at the age of 60 years in 2014, and remained asymptomatic without AF recurrence until 2022, when he was admitted for AF and diagnosed with hypertension. Coronary angiography showed minor coronary artery disease, and echocardiography revealed a left ventricular ejection fraction (LVEF) of 55 percent with mild left atrial enlargement. He was started on metoprolol tartrate 50 mg BID and rivaroxaban 20 mg QD for AF management, along with atorvastatin 20 mg QD for hyperlipidaemia. His arrhythmia remained controlled for the next 2 years.

In early 2024, the patient presented to follow-up with progressively worsening SoB and reduced exercise tolerance. He used to cycle 30 km but could barely cycle in the past few months. Physical examination at the clinic showed a satisfactory blood pressure of 104/54 mmHg, a pulse of 56/min and no lower limb oedema. ECG showed sinus rhythm. Echocardiography was ordered, but the expected waiting time was >2 years. N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing, performed to assist with diagnosis, revealed an elevated level of 1,507 pg/mL. The patient subsequently underwent echocardiography in a private clinic, which showed an LVEF of 65 percent, grade 1 diastolic dysfunction, moderate left atrial enlargement, mild mitral regurgitation, and trivial tricuspid regurgitation. Based on these results, the patient was diagnosed with heart failure with preserved ejection fraction (HFpEF).

Treatment and response
In September 2024, the patient started taking a sodium-glucose cotransporter-2 inhibitor (SGLT2i), empagliflozin 10 mg QD, due to its benefits in HFpEF. After 4 months of treatment, he reported improved symptoms, including reduced SoB and increased exercise capacity. He was able to resume cycling, though not yet at his previous 30 km distance. His NYHA functional class improved from II to I, and his NT-proBNP level decreased by 20.5 percent to 1,198 pg/mL. There were no significant changes in volume status, as the patient was not oedematous at baseline. Follow-up in May 2025 (around 8 months after treatment) showed further reduction in NT-proBNP level to 887pg/mL. Overall, the patient also tolerated empagliflozin well with no adverse events observed.

Discussion
HF affects 1–3 percent of the population, with HFpEF accounting for approximately half of all HF cases. The prevalence of HFpEF increases with age, making it the most common form of HF in the elderly. Despite its global prevalence, HFpEF remains underrecognized with unique challenges in diagnosis and management.^1-3

Diagnosing HF in ambulatory or outpatient settings can be difficult, particularly in HFpEF patients without evident volume overload, such as our patient above. HFpEF patients typically present with normal ejection fraction and nonspecific symptoms including dyspnoea, exercise intolerance and oedema, which are common in the older population and can be caused by both cardiac and noncardiac conditions.⁴  In Hong Kong, long waiting times for echocardiography in public healthcare settings may further delay HF diagnosis and treatment. Additionally, accurate interpretation of echocardiography findings usually require specialized expertise, which may be limited in general practice.

NT-proBNP testing is a valuable adjunct in confirming or ruling out HF, particularly in cases of unexplained dyspnoea. Using NT-proBNP as an initial screening tool can help streamline the diagnostic process, prioritize patients for earlier echocardiographic assessment in resource-limited setting, and enable earlier treatment. In our patient, the elevated NT-proBNP level aided in diagnosis despite the delay in echocardiographic assessment and the absence of overt congestion, offering critical insight alongside other clinical findings to guide early treatment planning. NT-proBNP also serves as a monitoring tool, with studies showing that a ≥30 percent reduction in NT-proBNP level between admission and discharge is associated with improved outcomes, including a reduced risk of the composite outcome of mortality and readmission.^5,6

Despite its usefulness, NT-proBNP levels should be interpreted carefully in certain populations. For example, NT-proBNP levels are often lower in obese individuals, which is particularly relevant in HFpEF, where obesity is a common comorbidity.⁷ Additionally, elevated NT-proBNP level may be seen in other non–heart failure conditions such as valvular heart disease, arrhythmias, and pulmonary embolism, non–cardiac conditions such as acute stroke, and in patients with renal insufficiency.⁸ Therefore, NT-proBNP should not be used in isolation; instead, it should be interpreted with other findings to provide incremental value to clinical judgement.

In addition to the challenges of underdiagnosis, therapeutic options for HFpEF used to be limited, with diuretics being the mainstay treatment for volume overload. Availability of newer therapeutic options, including SGLT2is such as empagliflozin, has changed the treatment landscape for patients with HFpEF.⁹

As the only drug class to consistently achieve primary endpoints in HF trials across the spectrum of LVEF, SGLT2is are recommended as a foundational class of guideline-directed medical therapy (GDMT) for HF by international guidelines, including those of the European Society of Cardiology (ESC) and American Heart Association. The ESC 2023 focused update of its 2021 HF guidelines provides a Class 1A recommendation for SGLT2is in patients with HFpEF to reduce the risk of HF hospitalization or cardiovascular (CV) death, indicating its importance in first-line treatment of HFpEF.^10,11

In the EMPEROR-Preserved trial involving 5,988 patients with NYHA functional class II–IV HF and LVEF ≥40 percent, empagliflozin significantly reduced the composite primary endpoint of CV death or hospitalization for HF vs placebo (hazard ratio, 0.79; 95 percent confidence interval, 0.69–0.90; p<0.001) after a median follow-up of 26.2 months. (Figure) A prespecified analysis of the trial showed significant improvement in health-related quality of life in patients on empagliflozin as early as in week 12, with benefits sustained for ≥1 year.^12,13

NT-proBNP testing is valuable for both diagnosis and monitoring of HF, but it is not yet available in all public hospitals in Hong Kong. Ensuring broader access to NT-proBNP testing, alongside professional education and public awareness campaigns, is essential for timely diagnosis and management of HFpEF. GDMT, particularly SGLT2is, should be initiated as early as possible to improve patient outcomes. 

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