#458 Heart Failure with Reduced Ejection Fraction

October 21, 2024 | By Deb Gorth

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Transcript available via YouTube

Kittleson Rules Outpatient Heart Failure Volume 1

Provide superb outpatient care for your patients with HFrEF. Identify underlying causes of heart failure and titrate medications with ease. Dr Michelle Kittleson @MKittlesonMD (Cedars Sinai) breaks down the nuances of treating this common cardiac condition. 

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Show Segments

• 00:00 Introduction 
• 03:22 Case Presentation: Newly Diagnosed Heart Failure
• 07:26 Using Physical Exam Findings to Guide Diuresis
• 11:58 The Four Pillars of Guideline-Directed Medical Therapy for Heart Failure
• 15:07 Optimizing Therapy and Follow-Up in Heart Failure Patients
• 22:10 The Benefits of High-Intensity Initiation and Titration of Guideline-Directed Medical Therapy
• 28:02 Consideration of Other Medications
• 40:02 Referral to Advanced Heart Failure Specialist
• 49:11 Optimizing Therapy and Follow-Up
• 55:33 Conclusion and Book Recommendation

Heart Failure with Reduced Ejection Fraction Pearls

1. The first question you should ask yourself when someone presents with a newly diagnosed cardiomyopathy is, what is the cause?
2. All four pillars of heart failure treatment should be at target doses within six weeks of hospital discharge; this results in an absolute risk reduction for death or HF readmission of 8 percent in just six months (STRONG-HF). 
3. Have a reason why a patient is not on one medication from each of the four pillars. It can be useful to search the EMR to see if a medication was previously discontinued and why it was discontinued. 
4. Optimizing heart failure medication is a patient-centered process that should consider the amount of blood pressure room and money that each patient has to “spend.” 
5. Dr. Kittleson recommends slipping once a day medications in at bedtime; a side effect of metoprolol is fatigue, so patients might as well take it at night and be tired before going to bed. 
6. If the ARNI and SGLT2i are too expensive, Dr. Kittleson recommends reaching for a generic ACEi which is incrementally worse than the ARNI and then spending the savings on a SGLT2i.
7. While treating hypertension, reach for the ARB over the ACEi, but for HFrEF ACEi are preferred to ARBs (ELITE II TRIAL and CONSENSUS TRIAL). Only reach for an ARB if the patient has a history of angioedema. 
8. Beware of indication creep, hydralazine/isosorbide is an inferior treatment than ACEis and should only be used in specific scenarios once the patient is maxed out on GDMT (V-HeFT II). 
9. It’s ‘HF with improved ejection fraction’ NOT ‘HF with recovered EF’; withdrawing GDMT on patients with HFimpEF leads to worse outcomes (TRED-HF).

Heart Failure with Reduced Ejection Fraction

Identify Etiology

So your patient has an ejection fraction < 40%? The first question you should ask yourself when someone presents with a newly diagnosed cardiomyopathy is, what is the cause? Start with common causes and let your history and physical guide you to less common causes. In the developed world, the most likely cause of heart failure with reduced ejection fraction (HFrEF) is ischemic heart disease (Yuseuf et al 2023), and this etiology should be evaluated using risk stratification (lipids and HbA1C) and an appropriate ischemic study (stress test, coronary CT, or left heart catheterization) based on pretest probability and institutional availability. Additional investigation should include a thorough history evaluating the possibility of rheumatologic disease (Prasad et al 2015), substance use (think cocaine, alcohol, methamphetamines), and family history suggesting a genetic component. Your work up can be rounded out with an assessment for tachycardia/arrhythmia (ECG/loop recorder), TSH, serum ferritin, and HIV serologies. Just to be complete, don’t forget zebras like acromegaly can also cause heart failure (Colao et al 2019).

Kittleson Rule: Don’t check a test that won’t change your management. 

A B-type natriuretic peptide (BNP) has limited utility outside of the initial diagnosis of heart failure. A physical exam showing elevated JVP and edema combined with a patient history of orthopnea and dyspnea on exertion is going to tell you if the patient is congested. Diuresis should be titrated to symptoms and physical exam not BNP. However, extremely high BNP (> 5000 ng/L) has prognostic value; a BNP this high carries with it a ~50% 3 month mortality (Zhang et al 2015). 

Treatment of HFrEF

The Four Pillars Treatment 

1. Angiotensin pathway inhibition: Angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan is superior to angiotensin-converting enzyme inhibitors (ACEi) (PARADIGM-HF), which are in turn superior to angiotensin receptor blockers (ARBs) (CONSENSUS TRIAL). 
2. Evidence-based beta blockers: Metoprolol succinate (MERIT-HF), carvedilol twice daily (Packer et al 1996), bisoprolol (CIBIS) 
3. Mineralocorticoid antagonists (MRA): eplerenone (EMPHASIS-HF) or spironolactone (Pitt et al 1999) 
4. Sodium-glucose cotransportor-2 (SGLT2) inhibitors: empagliflozin (EMPEROR-Reduced) or dapagliflozin (DAPA-HF) 

Initiating Core HF Treatment

There are no hard and fast rules for the order to initiate these medications. However, all four medications should be at target doses within six weeks of hospital discharge; this results in an absolute risk reduction for heart failure readmission or death of 8 percent in just six months (STRONG-HF).  Dr. Kittleson favors rapid sequence initiation, and she reminds us that it’s important to remember which medicines make patients feel better.  She typically starts with the ANRI, followed by MRA, then the SGLT2i, and then once a patient is optimized and decongested she adds the beta blocker. Dr. Kittleson starts with metoprolol succinate 12.5 mg and spironolactone 25 mg, checking labs every week when titrating. After a patient has achieved a stable dose, check labs every 3 months. Have a reason why if a patient is not on one medication from each of the four pillars. It can be useful to search the EMR to see if a medication was previously discontinued and why it was discontinued. Intolerance of guideline-directed medical therapy (GDMT) is a poor prognostic indicator, but many patients simply are not started on or reach target doses of appropriate therapy (Kocabase et al 2023). 

Optimizing heart failure medication is a patient-centered process that should consider the amount of blood pressure room and money that each patient has to “spend.” Due to its survival benefit, Dr. Kittleson recommends reaching for the ARNI as the first medication when budgeting blood pressure. Metoprolol succinate can be chosen over carvedilol, because it is once a day and does not have alpha blocking properties, sparing a majority of the blood pressure effect. Dr. Kittleson recommends slipping once a day medications in at bedtime; a side effect of metoprolol is fatigue, so they might as well take it at night and be tired before going to bed. Furthermore, she discourages patients from checking their blood pressure if they feel well; if they can go about their day without almost fainting when they stand up, the number doesn’t matter. 

Cost is often an issue with getting patients on sacubitril-valsartan and an SGLT2i. Dr. Kittleson recommends having a frank conversation with your patients to be sure that they can comfortably afford their medication. If the ARNI and SGLT2i are too expensive, she recommends using a generic ACEi which is incrementally worse than the ARNI and then spend the savings on a SGLT2i. While treating hypertension,  you can use the better-tolerated ARB over the ACEi, but for HFrEF ACEi are preferred to ARBs (ELITE II TRIAL and CONSENSUS TRIAL). Only reach for an ARB if the patient has a history of angioedema. 

Adjunctive HF Medications

In addition to the four pillars of HRrEF treatments, there are a few additional medications that can be used in rare circumstances. Hydralazine/isosorbide (A-HeFT), ivabradine (SHIFT), and vericiguat (VICTORIA) all have narrow indications in specific patient populations.  

Beware of indication creep, hydralazine/isosorbide is an inferior treatment than ACEis and should only be used in specific scenarios (V-HeFT II). The A-HeFT trial studied self-described Black Americans who had HFrEF. At the time of the trial (2004), the patients were already on optimal meds per their physician–90% of trial participants were on ACEi and 70% were on beta blocker therapy–and the starting blood pressure of the trial was 120 mmHg systolic. Hydralazine/isosorbide should be reserved for patients who have additional blood pressure room after already being maxed out on GDMT. 

Ivabradine inhibits the “funny” current and reduces HR without reducing cardiac contractility. Ivabradine is indicated in patients with an EF <35%, who are consistently in sinus rhythm, and have a HR > 70 beats/min despite maximum tolerated beta blocker (SHIFT).

Vericiguat, an oral guanylyl cyclase stimulator, is used for high risk patients with worsening symptoms already on GDMT (VICTORIA). These patients are very sick. If a patient is being considered for vericiguat, this medication should be a piece of a conversation that includes discussion of advanced therapies and palliative care. 

Follow Up Care After GDMT Optimization

Check an echo 3-6 months after optimization on GDMT. In observational cohorts, many patients can achieve HF with improved ejection fraction (HFimpEF) (from ≤35% to > 50%) after treatment with GDMT (Veltmann et al 2024). N.B., it’s HF with improved ejection fraction NOT HF with recovered EF; withdrawing GDMT on patients with HFimpEF results in worse outcomes (TRED-HF).

Kittleson Pet Peeve (a direct application of the Kittleson Rule noted above): checking an echo on a patient with known HF who is decompensated.

Only consider ICD, CRT, or mitral valve repair after GDMT is optimized. ICD implantation is indicated for primary prevention in patients with NYHA class II-III symptoms and LVEF <35% or NYHA class I with LVEF <30% (Butler et al 2022). CRT-D is indicated in patients with LVEF < 30%, and an intrinsic QRS duration > 120 msec (or paced QRS > 200 msec) (RAFT 14 year f/u and RAFT). Mitral regurgitation can either be primary, the valve’s fault, or secondary, the ventricle’s fault. MITRA-FR and COAPT are two studies with seemingly conflicting results looking at mitral valve repair in HFrEF. MITRA-FR studied patients with severe MR without attention to LV size and current medical therapy; this study did not show benefit. However, COAPT looked at a much more curated cohort of patients that considered LV shape and existing optimization of GDMT; with careful patient selection, COAPT showed benefits of lower HF hospitalization, lower mortality, and higher quality of life. 

Patients should see a cardiologist if their clinical status changes. A useful mnemonic for when to refer for advanced therapies is I NEED HELP; I = IV inotropes, N = NYHA IIIB/IV or persistently elevated natriuretic peptides, E = End organ dysfunction, E = Ejection fraction < 20%, D = Defibrillator shocks, H = Hospitalizations > 1, E = Edema despite escalating diuretic agents, L = Low blood pressure and high heart rate, P = Progressive intolerance of GDMT (Baumwol 2017)

Links

Mastering the Art of Patient Care

Goal

Listeners will learn the ins-and-outs of outpatient HFrEF management. 

Learning objectives

After listening to this episode listeners will…

1. Develop an approach to the outpatient management of HFrEF
2. Recognize the importance of guideline directed medical therapy for HFrEF
3. Learn strategies to initiate and monitor titration of the four pillars of therapy
4. Recognize when to refer patients with HFrEF to specialists

Disclosures

Dr. Kittleson reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Gorth DJ, Kittleson MM, Williams PN, Watto MF. “#458 Heart Failure with Reduced Ejection Fraction”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast October 21, 2024.