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The following question refers to Section 7.3.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.\xa0\n\nThe 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\xa0Dr. Robert Mentz.\xa0\n\nDr. Mentz is associate professor of medicine and section chief for Heart Failure at Duke University, a clinical researcher at the Duke Clinical Research Institute, and editor-in-chief of the Journal of Cardiac Failure. Dr. Mentz is a mentor for the CardioNerds Clinical Trials Network as lead principal investigator for PARAGLIDE-HF and is a series mentor for this very 2022 heart failure Decipher the Guidelines Series. For these reasons and many more, he was awarded the Master CardioNerd Award during ACC22. Welcome Dr. Mentz!\xa0\n\nThe\xa0Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure\xa0series 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\xa0Dr. Amit Goyal\xa0and\xa0Dr. Dan Ambinder, with mentorship from\xa0Dr. Anu Lala,\xa0Dr. Robert Mentz, and\xa0Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.\n\nEnjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.\n\nQuestion #7\n\n\n\nMs. Valarie Sartan is a 55-year-old woman with a history of HFrEF (EF 35%) and well controlled, non-insulin dependent diabetes mellitus who presents to heart failure clinic for routine follow up. She is currently being treated with metoprolol succinate 200mg daily, lisinopril 10mg daily, empagliflozin 10mg daily, and spironolactone 50mg daily. She notes stable dyspnea with moderate exertion, making it difficult to do her yardwork. On exam she is well appearing, and blood pressure is 115/70 mmHg with normal jugular venous pulsations and trace bilateral lower extremity edema. On labs, her potassium is 4.0 mmol/L and creatinine is 0.7 mg/dL with an eGFR > 60 mL/min/1.73m2. Which of the following options would be the most appropriate next step in heart failure therapy?\xa0\n\n\nA\xa0\nIncrease lisinopril to 40mg daily\xa0\n\n\nB\xa0\nIncrease spironolactone to 100mg daily\xa0\n\n\nC\xa0\nAdd sacubitril-valsartan to her regimen\xa0\n\n\nD\xa0\nDiscontinue lisinopril and start sacubitril-valsartan in 36 hours\xa0\n\n\nE\xa0\nNo change\xa0\n\n\n\nAnswer #7\n\n\n\nExplanation\xa0\xa0\nThe correct answer is D \u2013 transitioning from an ACEi to an ARNi is the most appropriate next step in management.\xa0\xa0\n\nThe renin-angiotensin aldosterone system (RAAS) is upregulated in patients with chronic heart failure with reduced ejection fraction (HFrEF). Blockade of the RAAS system with ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), or angiotensin receptor neprilysin inhibitors (ARNi) have proven mortality benefit in these patients.\xa0\xa0\n\nThe PARADIGM-HF trial compared sacubitril-valsartan (an ARNi) with enalapril in symptomatic patients with HFrEF. Patients receiving ARNi incurred a 20% relative risk reduction in the composite primary endpoint of cardiovascular death or heart failure hospitalization. Based on these results, the 2022 heart failure guidelines recommend replacing an ACEi or ARB for an ARNi in patients with chronic symptomatic HFrEF with NYHA class II or III symptoms to further reduce morbidity and mortality (Option D). This is a class I recommendation with level of evidence of B-R and is also of high economic value. Making no changes at this time would be inappropriate (Option E).\xa0\n\nWhile it would be reasonable to increase the dose of lisinopril to 40mg (Option A), this should be pursued only if ARNi therapy is not tolerated.\xa0\xa0\n\nMineralocorticoid receptor antagonists (MRAs) have a class I (LOE A...