334. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #28 with Dr. Gregg Fonarow

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 Academy Fellow Dr. Maryam Barkhordarian, answered first by Hopkins Bayview medicine resident & CardioNerds Academy Faculty Dr. Ty Sweeny, 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.

Mr. Gene D’aMeTi, 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.

Sacubitril-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.


Throughout 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?


Resume Losartan only


Start Amlodipine


Increase current Hydralazine dose


Start Isosorbide dinitrate therapy


Both C & D


The correct answer is E – both increasing the current hydralazine dose (C) and starting isosorbide dinitrate therapy (D).


Although 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.


In 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. In patients with current or previously symptomatic HFrEF who cannot be given first-line agents (like ARNi, ACEi, ARB) due to intolerance or renal insufficiency, combination therapy of hydralazine & isosorbide dinitrate might be considered to reduce morbidity and mortality (Class 2b, LOE C-LD).


Dihydropyridine calcium channel blockers such as Amlodipine (choice B) are not recommended for treatment of HFrEF (COR 3, LOE A), though may be considered for treating elevated blood pressure despite optimization of GDMT.

Main Takeaway

In self-identified African Americans, the addition of hydralazine & isosorbide dinitrate to GDMT has additional mortality & morbidity benefits.


Should a patient have drug intolerances or renal dysfunction that precludes the use of ACEi/ARB/ARNi, hydralazine & isosorbide dinitrate is a reasonable alternative.

Guideline Loc.

·       Section 7.3.5-8

·       Table 14, Table 15

334. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #28 with Dr. Gregg Fonarow
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