The following question refers to Section 7.3 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. 

The question is asked by Palisades Medical Center medicine resident & CardioNerds Intern Dr. Maryam Barkhordarian, answered first by MedStar Washington Hospital Center cardiology hospitalist & CardioNerds Academy Graduate Dr. Luis Calderon, and then by expert faculty Dr. Gregg Fonarow.

Dr. Fonarow is the Professor of Medicine and Interim Chief of UCLA’s Division of Cardiology, Director of the Ahmanson-UCLA Cardiomyopathy Center, and Co-director of UCLA’s Preventative Cardiology Program.

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Question #8

Ms. Flo Zinn is a 60-year-old woman seen in cardiology clinic for follow up of her chronic HFrEF management. She has a history of stable coronary artery disease, hypertension, hypothyroidism, and recurrent urinary tract infections. She does not have a history of diabetes and recent hemoglobin A1c is 5.0%. Her current medications include carvedilol, sacubitril-valsartan, eplerenone, and atorvastatin. Her friend was recently placed on an SGLT2 inhibitor and asks if she should be considered for one as well. Which of the following is the most important consideration when deciding to start this patient on an SGLT2 inhibitor?

A

The patient does not have a history of type 2 diabetes and so does not qualify for SGLT2 inhibitor therapy

B

While SGLT2 inhibitors improve hospitalization rates for HFrEF, there is no evidence that they improve cardiovascular mortality

C

Patients taking SGLT2 inhibitors tend to suffer a more rapid decline in renal function than patients not taking SGLT2 inhibitor therapy

D

Patients may be at a higher risk for genitourinary infections if an SGLT2 inhibitor is started

Answer #8

Explanation

The correct answer is D – SGLT2 inhibitors have been associated with increased risk of genitourinary infections.

Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors have gathered a lot of press recently as the new kid on the block with respect to heart failure management. While they were initially developed as antihyperglycemic medications for treating diabetes, early cardiovascular outcomes trials showed reduced rates of heart failure hospitalization amongst study participants independent of glucose-lowering effects and irrespective of baseline heart failure status – only 10-14% of patients carried a heart failure diagnosis at baseline. This prompted trials to study the effects of SGLT2 inhibitors in patients with symptomatic chronic HFrEF who were already on guideline directed medical therapy irrespective of the presence of type 2 diabetes mellitus. The DAPA-HF and EMPEROR-Reduced trials showed that dapagliflozin and empagliflozin, respectively, both conferred statistically significant improvements in a composite of heart failure hospitalizations and cardiovascular death (Option B). Most interestingly, these effects were seen irrespective of diabetes history. In light of these findings, the 2022 HF guidelines recommend SGLT2 inhibitors in patients with chronic, symptomatic HFrEF with or without diabetes to reduce hospitalization for HF and cardiovascular mortality (Class I, LOE A).

The benefits of SGLT2 inhibitors extend beyond cardiovascular health. Analyses of the DAPA-HF and EMPEROR-Reduced trials showed that patients receiving SGLT2 inhibitor therapy had fewer serious renal outcomes and slower rates of decline in eGFR than patients in the control groups.

As with all medications, though, SGLT2 inhibitors must be used with an awareness of some potentially serious side effects. SGLT2 inhibitors have been associated with higher rates of genitourinary infections, potentially related to the increased glycosuria associated with sodium-glucose co-transporter 2 inhibition. Trials have shown a 2 to 4-fold increased risk of vulvovaginal candidiasis for patients on SGLT2is compared to placebo. SGLT2 inhibitor use has also been associated with bacterial urinary tract infections, Fournier’s gangrene, and euglycemic ketoacidosis.

Main Takeaway

SGLT2 inhibitors are now a class I recommendation for patients with chronic symptomatic HFrEF regardless of whether or not they have diabetes. Although SGLT2i increased risk for genital infections, they were otherwise well tolerated in the trials.

Guideline Loc.

Section 7.3.4

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