A 60-year-old man with stable ischemic heart disease, type 2 diabetes, hypertension, hyperlipidemia, and chronic kidney disease presents to the cardiology office after a recent hospitalization for a heart failure (HF) exacerbation. He has a long-standing history of coronary artery disease with 2 prior myocardial infarctions, both requiring percutaneous revascularization 15 and 10 years ago, respectively. At baseline, he has New York Heart Association (NYHA) functional Class II symptoms. He occasionally becomes lightheaded with sudden standing. He has a cardiac resynchronization therapy with defibrillator device with resultant right bundle branch block pattern and QRS duration of 125 msec on electrocardiography. He has had 3 hospitalizations in the past year for HF. His medications include metoprolol succinate 100 mg daily, sacubitril-valsartan 49-51 mg twice daily, eplerenone 25 mg daily, aspirin 81 mg daily, atorvastatin 80 mg daily, sitagliptin-metformin 50-500 mg twice daily, and insulin glargine 30 units nightly. On physical exam, his peripheral pulse is 62 bpm, blood pressure is 95/60 mmHg, there is no jugular venous distension, his lungs are clear to auscultation, and he has no peripheral edema. His laboratory evaluation includes estimated glomerular filtration rate 45 mL/min/1.73m2, low-density lipoprotein 50 mg/dL, N-terminal pro-B-type natriuretic peptide 252 pg/mL, and Hgb A1c 7.8%. Echocardiography shows a left ventricular ejection fraction of 30% and a mildly dilated left ventricle.
Which of the following is the next best step in the management of this patient to reduce his risk for future major adverse cardiovascular events (MACE) and HF hospitalizations?
Show Answer
The correct answer is: C. Start a sodium-glucose cotransporter 2 (SGLT2) inhibitor
SGLT2 inhibitors make up a relatively new class of medications that has been shown in multiple trials to reduce the risk of MACE and HF hospitalizations among patients with HF with reduced ejection fraction (HFrEF).1-5 SGLT2 inhibitors result in a 26-32% reduction in a composite of cardiovascular death, HF hospitalization, and urgent HF visits when added to optimal guideline-directed medical therapy.2,4 This benefit is seen within 28 days of initiation of the medication.4 It is hypothesized that cardiorenal benefits are derived from a combination of decrease in circulating plasma volume with lower potential for developing volume depletion, decrease in arterial stiffness, increase in hematocrit, decreased glucotoxicity, increase in weight loss, and decrease in inflammation.6 SGLT2 inhibitors are associated with a slightly increased risk of developing diarrhea, genital mycotic infections, and euglycemic diabetic ketoacidosis.3,5 Although much of the data on SGLT2 inhibitors were published after the 2019 ACC Expert Consensus Decision Pathway on patients hospitalized with HF,7 SGLT2 inhibitors should be considered in the pharmacotherapy regimen of patients with HFrEF, regardless of underlying etiology, and especially in diabetic patients.8,9 Therefore, answer C is the next best step.
This patient is clinically euvolemic and does not have elevated natriuretic peptide levels. It is unlikely that addition of a loop diuretic will reduce this patient's risk of subsequent HF hospitalizations or mortality.10,11 Therefore, answer A is not the best option. This patient has NYHA functional Class II symptoms, has Stage C HF, and is not yet fully optimized on medical therapy. Therefore, referral for left ventricular assist device implantation is premature at this point,12,13 and answer B is not the best option. Data from the recent SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) trial suggest that the cardiovascular benefits of SGLT2 inhibitors is seen in diabetic patients regardless of albuminuria status.3 Therefore, answer D is not the best option. Sacubitril-valsartan has been shown to decrease all-cause mortality, MACE, and HF hospitalizations in patients with chronic HFrEF.14 However, this patient experiences orthostasis and has relative hypotension during the office visit. He is unlikely to tolerate further dose increase; therefore, answer E is not the best option.
References:
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 2017;377:644-57.
McGuire DK, Shih WJ, Cosentino F, et al. Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: A Meta-analysis. JAMA Cardiol 2021;6:148-58.
Bhatt DL, Szarek M, Pitt B, et al. Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease. N Engl J Med 2021;384:129-39.
Zannad F, Ferreira JP, Pocock SJ, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet 2020;396:819-29.
Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. N Engl J Med 2021;384:117-28.
Zelniker TA, Braunwald EB. Mechanisms of Cardiorenal Effects of Sodium-Glucose Cotransporter 2 Inhibitors: JACC State-of-the-Art Review. J Am Coll Cardiol 2020;75:422-34.
Hollenberg SM, Stevenson LW, Ahmad T, et al. 2019 ACC Expert Consensus Decision Pathway on Risk Assessment, Management, and Clinical Trajectory of Patients Hospitalized With Heart Failure: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2019;74:1966-2011.
Das SR, Everett BM, Birtcher KK, et al. 2018 ACC Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol 2018;72:3200-23.
Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 2020;41:255-323.
Felker GM, O'Connor CM, Braunwald E, Heart Failure Clinical Research Network Investigators. Loop diuretics in acute decompensated heart failure: necessary? Evil? A necessary evil? Circ Heart Fail 2009;2:56-62.
Faris RF, Flather M, Purcell H, Poole-Wilson PA, Coats AJ. Diuretics for heart failure. Cochrane Database Syst Rev 2012;(2):CD003838.
Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013;128:1810-52.
Teuteberg JJ, Cleveland JC Jr, Cowger J, et al. The Society of Thoracic Surgeons Intermacs 2019 Annual Report: The Changing Landscape of Devices and Indications. Ann Thorac Surg 2020;109:649-60.
McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993-1004.
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