SGLT2 Inhibitor Use in Case of Acute Decompensated Heart Failure With Edema

Acute decompensated heart failure is associated with new or worsening symptoms such as shortness of breath, orthopnea, and volume overload.

A56-year-old man with a history of hypertension and type 2 diabetes presents to the emergency department with a chief complaint of increased bilateral pedal edema and shortness of breath with dyspnea on exertion for 6 weeks. He admits he has not been on any outpatient medical management for the last 3 years because of a variety of social and financial barriers. He denies any fevers, chills, nausea, or vomiting. He has no chest pain, pressure, tightness, or palpitations. He denies a history of claudication or history of prior diagnosis of heart failure.

On physical examination, the patient’s temperature, respiratory rate, and oxygen saturation on room air are within normal limits. He is tachycardic with a heart rate of 130 beats per minute and hypertensive with a blood pressure of 158/102 mm Hg. He is alert, conversational, and cooperative but is ill-appearing and grossly volume overloaded. His breath sounds are diminished in his lung bases bilaterally. He has a regular rhythm with no murmurs, gallops, or rubs. His jugular veins are distended to the jawline. His abdomen is distended and nontender, and he has normoactive bowel sounds in all 4 quadrants. He has 3+ bilateral lower extremity edema with edema noted up to his abdomen. Chronic venous ulcers are noted on his lateral lower extremities bilaterally. Blistering wounds are noted on his right and left index fingers and left middle finger, which the patient notes were caused by touching a hot pan at home. Cranial nerves II to XII are grossly intact and the patient demonstrates no gross focal deficits. The patient’s chemistry panel is within normal limits except for serum glucose, which is elevated to 165 mg/dL. The patient’s hemoglobin is decreased at 12.7 g/dL and the remainder of the complete blood cell count is within normal limits. Coagulation studies are also without abnormality. Point-of-care troponin level is negative at 0.03 ng/mL. Brain-type natriuretic peptide (BNP) is elevated to 221 pg/mL and hemoglobin A1c is 8.4%, confirming that the patient’s diabetes is uncontrolled over time. His D-dimer is elevated at 1.87 μg/mL, however, a chest computed tomography (CT) scan is negative for pulmonary embolism. Chest CT and chest radiography demonstrate moderate-sized bilateral pleural effusions. Electrocardiography reveals typical atrial flutter with rapid ventricular response and rates of approximately 130 to 140 beats per minute, but the patient denies any symptoms or personal history of atrial fibrillation or flutter.

Following emergency department workup, the patient is admitted to the cardiology service for acute decompensated heart failure (ADHF; NYHA class III stage C) and typical atrial flutter with rapid ventricular response.

Hospital Course

The patient is begun on rapid diuresis protocol and potassium/magnesium replacement protocol. Endocrinology is consulted on day 1 of hospitalization and the patient is initiated on a diabetic diet, supplemental insulin lispro, and dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor. The patient’s medication management includes high-dose IV furosemide, guideline-directed medical therapy including an angiotensin II receptor blocker (ARB), β-blocker, and mineralocorticoid receptor antagonist (MRA). Hydralazine 10 mg is also added for management of hypertensive urgency. He is initiated on apixaban 5 mg twice a day for oral anticoagulation for atrial flutter. Wound care is initiated for management of the patient’s venous ulcers and finger blisters.

Transthoracic echocardiogram on day 2 demonstrates left ventricular ejection fraction (LVEF) 50% to 55%, low normal left ventricular systolic function (LVSF), decreased left ventricular stroke volume (LVSV), moderate concentric left ventricular hypertrophy, normal right ventricular systolic pressure (RVSP), no valvular disease, and normal right atrium and left atrium sizes. Cardiovascular magnetic resonance imaging (cMRI) on day 5 demonstrates LVEF 69%, no vasodilator stress-induced perfusion deficits or macroscopic scar or fibrosis, and biatrial enlargement with normal LVSF/ right ventricular systolic function, likely indicating a persistent atrial flutter over time.

Diuretics are stopped on day 6 because of acute kidney injury and contraction alkalosis secondary to brisk diuresis and large volume loss. The patient’s serum creatinine level increases to 1.26 mg/dL from 0.95 mg/dL on admission, and his arterial blood gas values are as follows: pH 7.52; carbon dioxide, 53.2 mm Hg; and bicarbonate, 43.5 mEq/L. Per endocrinology, linagliptin is added to the patient’s diabetes medication regimen on day 7 with subsequent improvements in blood glucose level found.

The patient undergoes successful cavotricuspid isthmus ablation as indicated for definitive treatment of typical atrial flutter on day 9 of hospitalization. A transesophageal echocardiogram is deemed not necessary by the electrophysiology team following their review of the patient’s CT angiogram and cMRI, which show no thrombus present in the left atrial appendage.

A postprocedure review of the patient’s telemetry record on day 10 confirms sustained normal sinus rhythm. The patient has lost greater than 40 liters of fluid and his weight has decreased by more than 90 pounds since admission. The patient is discharged on day 10 with a follow-up scheduled with electrophysiology and heart failure clinic for continued outpatient management.The patient’s discharge medications include apixaban, baby aspirin, furosemide as needed, metoprolol succinate, saxagliptin, and dapagliflozin.

Discussion

Acute decompensated heart failure is characterized by new or worsening signs of heart failure such as shortness of breath, orthopnea, and volume overload that often lead to an emergency department visit and/or hospitalization for inpatient management.1-3 Major causes of ADHF include acute coronary syndrome, arrhythmias, myocarditis, acute valve syndromes, progressive valve disease, cardiomyopathic state, and poorly controlled hypertension.1 Acute decompensated heart failure affects a heterogenous patient population and is the most common discharge diagnosis among patients older than 65 years of age.4 Etiology and pathophysiologic mechanism of ADHF may be multifactorial in an individual patient, posing a challenge to long-term management and resulting in high postdischarge readmission rates.4,5

General Approach to Inpatient Management of Acute Decompensated Heart Failure

Inpatient management of ADHF should be tailored within the context of the individual patient’s presentation. General pillars of management include the following: volume management with diuresis, monitoring of electrolytes, renal function and hemodynamic status, vasodilator therapy, sodium and fluid restriction, venous thromboembolism prophylaxis, and continuation or initiation of long-term therapy.6,7 Ejection fraction is an important consideration for determining the specific therapeutic management strategy.

New guidelines from the American College of Cardiology, American Heart Association, and the Heart Failure Society of America (2022 AHA/ACC/HFSA) for the management of heart failure with preserved ejection fraction (HFpEF) recommend the use of SGLT2 inhibitors, MRAs, ARBs, angiotensin receptor/neprilysin inhibitors (ARNi), as well as treatment of hypertension and atrial fibrillation, avoidance of the routine use of nitrates or phosphodiesterase-5 inhibitors, and management of comorbidities.7 First-line management of heart failure with reduced ejection fraction (HFrEF) follows guideline-directed medical therapy (GDMT) including an ARNi,ACEI, or ARB, 1 of 3 β-blockers (bisoprolol, carvedilol, or sustained-release metoprolol succinate), MRA, SGLT2 inhibitor, and diuretics as needed.7 Robust evidence supporting the use of SGLT2 inhibitors in patients with HFrEF recently led to the inclusion of this class in the GDMT per the updated American and European guidelines in 2021 and the 2022 AHA/ACC/ HFSA guidelines.7,8

Sodium-glucose cotransporter-2 inhibitors are an established class of medications commonly used in the management of type 2 diabetes.The known mechanism of action of SGLT2 inhibitors for type 2 diabetes is the reduction of blood glucose via the promotion of urinary glucose excretion. These agents also have a protective effect on the risk for progression to diabetic kidney disease.9,10 The mechanism of action for heart failure is not currently known, but proposed mechanisms include the reduction of preload by promotion of osmotic diuresis and natriuresis, reduction of afterload by the promotion of vasodilation and improved endothelial function, improved cardiac efficiency via improved myocardial metabolism, and possible reduction of the risk for atrial arrhythmias.9,10

Several landmark trials established the evidence for inclusion of SGLT2 inhibitors in current GDMT for chronic HFrEF and recent approval for use in HFpEF (Table). The EMPEROR-Reduced trial demonstrated that among patients with symptomatic stable HFrEF (EF ≤40%), empagliflozin was superior to placebo in improving heart failure outcomes regardless of diabetes status.11,12 The DAPA-HF trial also demonstrated superior prevention of cardiovascular deaths and heart failure events among patients with HFrEF who received dapagliflozin versus placebo regardless of diabetes status.13 A meta-analysis of the EMPEROR-Reduced and

TABLE.

SGLT2 InhibitorChronic/Acute Heart FailureApproved Use

Empagliflozin Chronic: Beneficial –EMPEROR-Reduced trial –EMPEROR-Preserved trial

Acute: Beneficial –EMPULSE trial

Dapagliflozin Chronic: Beneficial –DAPA-HF trial

Acute: TBD; DICTATE-AHF trial currently in progress

Canagliflozin N/A

Ertugliflozin N/A

• Type 2 diabetes with or without CV disease

• HFrEF

• HFpEF

• Type 2 diabetes with or without CV disease or multiple CV risk factors

• HFrEF

• Chronic kidney disease at risk for progression

Type 2 diabetes with or without CV disease or diabetic nephropathy

Type 2 diabetes only

Diabetes Status

With type 2 diabetes or without11,12,15

With type 2 diabetes or without13

With type 2 diabetes only

With type 2 diabetes only

AHF, acute heart failure; CV, cardiovascular; DAPA-HF, Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure; DM, diabetes mellitus; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; TBD, to be determined