Case Study: Integrated Management of Heart Failure with Reduced Ejection Fraction (HFrEF) Using SGLT2 Inhibitors and Optimized Therapy

Abstract

This case study presents a 60-year-old male with chronic heart failure with reduced ejection fraction (HFrEF), ischemic heart disease, and uncontrolled hypertension. The patient was treated with optimized guideline-directed medical therapy (GDMT), including an SGLT2 inhibitor, ARNI, beta-blocker, and mineralocorticoid receptor antagonist. Over 12 months, there was significant improvement in left ventricular function, exercise tolerance, and quality of life. The case highlights the role of early intervention, multidisciplinary care, and novel heart failure therapies in achieving better outcomes.

Introduction

Heart failure with reduced ejection fraction (HFrEF) remains a major global health concern, affecting over 64 million people worldwide. Despite advances in therapy, morbidity and mortality remain high.
 The introduction of SGLT2 inhibitors originally developed for diabetes has transformed heart failure management by improving cardiac remodeling, reducing hospitalization, and lowering mortality risk. This case illustrates the successful integration of SGLT2 inhibitors with guideline-directed medical therapy (GDMT) to optimize cardiac function in a patient with chronic HFrEF.

Patient Information

• Age / Gender: 60-year-old male

• Occupation: Retired banker

• Medical History: Chronic heart failure (3 years), ischemic heart disease, uncontrolled hypertension, mild CKD

• Surgical History: Percutaneous coronary intervention (PCI) 5 years ago

• Family History: Father with CAD; mother with diabetes

• Social History: Sedentary lifestyle, high-salt diet, former smoker, moderate alcohol use

• Current Medications: Furosemide 40 mg OD, Atenolol 50 mg OD

• Chief Complaints: Shortness of breath, ankle swelling, and fatigue for 3 weeks

Clinical Findings

Symptoms

• Exertional dyspnea (NYHA Class III)

• Orthopnea

• Bilateral pedal edema

• Fatigue and reduced exercise capacity

Physical Examination

• Vitals: BP 154/96 mmHg, HR 102 bpm, Temp 36.8°C

• BMI: 29.5 kg/m² (overweight)

• Signs: Jugular venous distension, bilateral basal crepitations, pitting edema

• Cardiac Exam: S3 gallop, displaced apex beat

Timeline

• January 2024: Patient presented with worsening dyspnea and ankle edema.

• February 2024: Initiated on ARNI (Sacubitril/Valsartan) and SGLT2 inhibitor (Dapagliflozin).

• April 2024: Beta-blocker switched from Atenolol to Bisoprolol; mineralocorticoid receptor antagonist added.

• August 2024: Significant symptomatic improvement, NYHA class reduced to II.

• January 2025: Follow-up showed better ejection fraction and reduced hospitalization risk.

Diagnostic Assessment

Laboratory Findings

• BNP: 780 pg/mL (elevated) → improved to 310 pg/mL at 6 months

• Serum Creatinine: 1.4 mg/dL → stable

• Electrolytes: Within normal limits

Echocardiography

• Baseline: Left ventricular ejection fraction (LVEF) 28%

• At 6 months: LVEF improved to 40%

• At 12 months: LVEF further improved to 47%

ECG: Sinus tachycardia, Q waves in inferior leads
 Chest X-ray: Cardiomegaly with mild pulmonary congestion

Therapeutic Intervention

Step 1 – Acute Stabilization

• IV diuretics for decongestion

• Oxygen therapy for breathlessness

• Low-salt cardiac diet initiation

Step 2 – Long-Term Medical Optimization

Medications Added:

• Sacubitril/Valsartan 50 mg BD → up-titrated to 100 mg BD

• Dapagliflozin 10 mg OD (SGLT2 inhibitor)

• Bisoprolol 5 mg OD

• Spironolactone 25 mg OD

• Loop diuretics optimized as needed

Step 3 – Lifestyle Modifications

• Low-salt, heart-healthy diet

• Structured walking program (30 min/day)

• Smoking cessation counseling

• Patient education on fluid balance and self-monitoring

Challenges Faced

• Initial hypotension after ARNI initiation

• High cost of novel therapies affecting compliance

• Patient anxiety about switching from older drugs

• Need for frequent renal monitoring due to CKD

Follow-Up and Outcomes

Over the 12-month follow-up period, the patient demonstrated significant clinical improvements and better heart failure management:

Cardiac Function: At baseline, the patient’s left ventricular ejection fraction (LVEF) was 28%, which improved to 40% at 6 months and further increased to 47% at 12 months, indicating effective ventricular remodeling and enhanced cardiac performance.

Functional Status: Initially classified as NYHA Class III, the patient reported severe limitations in physical activity. By 6 months, functional status improved to NYHA Class II, and by 12 months, the patient achieved NYHA Class I, reflecting near-normal exercise tolerance.

Biomarker Improvement: The patient’s BNP levels significantly decreased from 780 pg/mL at baseline to 310 pg/mL at 6 months and further reduced to 190 pg/mL at 12 months, suggesting better volume control and reduced cardiac stress.

Hospitalization Risk: The patient had 2 hospitalizations in the 6 months preceding therapy initiation. With optimized guideline-directed medical therapy and SGLT2 inhibitor use, the patient reported zero hospitalizations at both 6 and 12 months, demonstrating better disease control.

Weight Management: The patient’s weight progressively decreased from 84 kg at baseline to 79 kg at 6 months and 76 kg at 12 months, reflecting improved metabolic health and adherence to dietary and exercise recommendations.

Discussion

This case highlights the transformative role of SGLT2 inhibitors, particularly dapagliflozin, in the management of heart failure with reduced ejection fraction (HFrEF). The patient, initially presenting with severe left ventricular dysfunction (LVEF 28%), frequent hospitalizations, and NYHA Class III symptoms, achieved remarkable clinical improvement over 12 months through an integrated treatment strategy combining pharmacological therapy, lifestyle modification, and close multidisciplinary follow-up.

The addition of dapagliflozin to the existing regimen of ARNI (sacubitril/valsartan), beta-blockers, and mineralocorticoid receptor antagonists (MRA) led to significant cardiac remodeling, progressive improvement in LVEF from 28% to 47%, and a notable reduction in BNP levels from 780 pg/mL to 190 pg/mL. Furthermore, the patient transitioned from NYHA Class III to Class I, indicating better exercise tolerance and improved overall functional capacity. Importantly, the patient remained free from heart failure-related hospitalizations after the initial 6-month period, reflecting sustained stability and disease control.

Recent landmark clinical trials support these findings. The DAPA-HF trial demonstrated that dapagliflozin, when added to guideline-directed medical therapy, significantly reduced the composite endpoint of cardiovascular death and worsening heart failure in HFrEF patients, irrespective of the presence of diabetes. Similarly, the EMPEROR-Reduced trial showed that empagliflozin led to meaningful improvements in cardiac function and reduced hospitalizations, further establishing SGLT2 inhibitors as a cornerstone therapy for HFrEF.

Beyond hemodynamic improvements, SGLT2 inhibitors have been shown to exert multifactorial benefits by reducing preload and afterload, improving myocardial energetics, lowering systemic inflammation, and enhancing renal function. In this patient, these mechanisms likely contributed to better volume management, weight reduction, and overall quality of life improvements. These effects are particularly valuable in high-risk patients with recurrent decompensation or borderline renal function, where traditional therapies alone often fail to achieve optimal outcomes.

This case also emphasizes the importance of a multidisciplinary, patient-centered approach to heart failure care. In addition to pharmacological optimization, structured dietary counseling, daily weight monitoring, exercise planning, and psychological support played key roles in improving adherence and preventing relapses. Regular follow-ups and early intervention in response to clinical changes were critical in maintaining long-term stability.

However, while SGLT2 inhibitors provide substantial clinical benefits, careful monitoring remains essential. There is a small but notable risk of adverse events, including volume depletion, hypotension, and euglycemic diabetic ketoacidosis, particularly in patients with coexisting diabetes or impaired renal function. Therefore, baseline and periodic monitoring of renal parameters, electrolytes, and glycemic control are strongly recommended to ensure safety and optimize therapy outcomes.

In summary, this case underscores the synergistic benefits of integrating SGLT2 inhibitors into a guideline-directed regimen for patients with HFrEF. By combining evidence-based pharmacological strategies, structured lifestyle interventions, and comprehensive follow-up, clinicians can achieve substantial improvements in cardiac function, hospitalization rates, exercise tolerance, and overall quality of life, even in high-risk populations.

Key Takeaways

• Early integration of SGLT2 inhibitors improves survival and quality of life in HFrEF.

• Guideline-directed therapy with ARNI, beta-blockers, MRAs, and SGLT2i offers synergistic benefits.

• Regular monitoring and patient education enhance adherence and optimize outcomes.

Patient’s Perspective

I used to get breathless even walking a few steps. With the new treatment, I can walk daily, sleep better, and feel much more energetic.

Conclusion

A comprehensive, multidisciplinary, and evidence-based approach using SGLT2 inhibitors plus optimized GDMT resulted in marked clinical and functional improvement in this patient with HFrEF. Personalized therapy, lifestyle modification, and close monitoring were key to long-term success.

References

1. McMurray JJV, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995–2008. https://doi.org/10.1056/NEJMoa1911303

2. Packer M, et al. Empagliflozin in Heart Failure with a Reduced Ejection Fraction. N Engl J Med. 2020;383(15):1413–1424. https://doi.org/10.1056/NEJMoa2022190

3. Heidenreich PA, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. Circulation. 2022;145(18):e895–e1032. https://doi.org/10.1161/CIR.0000000000001063

4. Ponikowski P, et al. 2021 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure. Eur Heart J. 2021;42(36):3599–3726. https://doi.org/10.1093/eurheartj/ehab368

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