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The following question refers to Section 7.3 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.\nThe question is asked by Palisades Medical Center medicine resident & CardioNerds Academy Fellow\xa0Dr. Maryam Barkhordarian, answered first by Hopkins Bayview medicine resident & CardioNerds Academy Faculty\xa0Dr. Ty Sweeny, and then by expert faculty Dr. Gregg Fonarow.\nDr. 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.\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.\nEnjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\tQuestion #28\n\t\t\t\t\t\n\n\n\nMr. Gene D\u2019aMeTi, a 53-year-old African American man with ischemic cardiomyopathy and heart failure with reduced ejection fraction (LVEF 30-35%), is recently admitted with acutely decompensated heart failure and acute kidney injury on chronic kidney disease stage III. His outpatient regiment includes sacubitril-valsartan 97-103mg BID, carvedilol 25mg BID, and hydralazine 50mg TID.\nSacubitril-valsartan was held because of worsening renal function. Despite symptomatic improvement with diuresis, his renal function continues to decline. He is otherwise well perfused & with preservation of other end organ function.\n\xa0\nThroughout this hospitalization, he has steadily become more hypertensive with blood pressures persisting in the 170s/90s mmHg. What would be an appropriate adjustment to his medication regimen at this time?\n\n\n\n\nA\n\n\nResume Losartan only\n\n\n\n\nB\n\n\nStart Amlodipine\n\n\n\n\nC\n\n\nIncrease current Hydralazine dose\n\n\n\n\nD\n\n\nStart Isosorbide dinitrate therapy\n\n\n\n\nE\n\n\nBoth C & D\n\n\n\n\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\tAnswer #28\n\t\t\t\t\tExplanationThe correct answer is E \u2013 both increasing the current hydralazine dose (C) and starting isosorbide dinitrate therapy (D).\xa0Although ACEI/ARB therapy (choice A) has shown a mortality and morbidity benefit in HFrEF, caution should be used in patients with renal insufficiency. In this patient with ongoing decline in renal function, RAAS-inhibiting therapies (ACEi, ARB, ARNI, MRA) should be avoided. In this case, as his RAAS-I has been stopped, it would be reasonable to increase current therapies to target doses (or nearest dose tolerated), as these demonstrated both safety and efficacy in trials (Class 1, LOE A). Considering that his high dose ARNI was stopped, it is unlikely that either hydralazine or isosorbide dinitrate alone, even at maximal doses, would be sufficient to control his blood pressure (Options C and D, respectively). Interestingly, in the original study by Massie et. Al (1977), the decision was made to combine these therapies as the result was thought to be superior to either medication alone. ISDN would provide preload reduction, while Hydralazine would decrease afterload. Consequently, we do not have data looking at the individual benefit of either medication in isolation.\xa0In self-identified African Americans with NYHA class III or IV HFrEF already on optimal GDMT, the addition of hydralazine & isosorbide dinitrate is recommended to improve symptoms and reduce mortality and morbidity (Class 1, LOE A). In this case, as the patient has evidence of progressive renal disfunction, we are limited in using traditional RAAS-I, such as ACEI, ARB, or ARNI.