#460 Heart Failure with Preserved Ejection Fraction

November 4, 2024 | By Deb Gorth

Audio

Video

Transcript available via YouTube

Kittleson Rules Outpatient Heart Failure Volume 2

Preserve your sanity while treating heart failure with preserved ejection fraction.  Dr Michelle Kittleson @MKittlesonMD (Cedars Sinai) illuminates this confounding cardiac condition.

Claim CME for this episode at curbsiders.vcuhealth.org!

Patreon | Episodes | Subscribe | Spotify | YouTube | Newsletter | Contact | Swag! | CME

Show Segments

• 00:00 Introduction and Advice for Physicians
• 02:24 Case Presentation
• 04:16 Understanding HFpEF
• 08:11 Differential Diagnosis of Dyspnea and Edema
• 11:30 Diagnosing HFPEF: H2F-PEF Score and Testing
• 17:07 Managing Comorbidities in HFpEF
• 20:54 Non-Pharmacological Interventions: Weight Loss and Exercise
• 23:16 Understanding the Challenges of HFpEF
• 25:08 Medications
• 30:13 Promising Results of GLP-1 Receptor Agonists
• 36:38 Managing Salt and Water Intake

HFpEF Pearls

1. It’s important to think about the differential diagnosis for both dyspnea and edema when considering a HFpEF diagnosis; don’t automatically blame the heart. 
2. H₂FPEF score is a clinical tool that uses accessible data to suggest the probability that the patient you are treating has HFpEF, but like anything in medicine you need to interpret the H₂FPEF score through the lens of your pretest probability and not forget about other causes of the observed symptoms (Reddy et al 2018, MDCalc). 
3. Don’t miss amyloidosis! Amyloidosis is an under-recognized cause of HFpEF; a little more than 1 in 8 cases of HFpEF may be attributed to amyloidosis (González-Lopéz et al 2015). Missing this diagnosis means inadvertently withholding life saving medication. (Check out Episode #427 Kittleson Rules Amyloidosis for a deep dive on this condition)
4. HFpEF is often characterized by periods of quiescence punctuated by discrete exacerbations triggered by clear inciting factors (Ex: NSAID use, excessive fluid intake) with a return to baseline one fluid status is improved. A slow progressive decline is less likely due to HFpEF.
5. Checking a BNP is useful in diagnosing HFpEF, but not much else. Dr. Kittleson rarely checks a BNP and encourages you to trust your history and use other tools like the JVP to evaluate cardiac congestion. 
6. SGLT2 inhibitors are the first medication to meet their primary endpoint in a HFpEF clinical trial (dapagliflozin (DELIVER) or empagliflozin (EMPEROR-PRESERVED)).
7. In HFpEF patients, finerenone reduced death from cardiovascular causes and led to a significantly lower rate of a composite of total worsening heart failure events and cardiovascular death when compared to placebo (FINEARTS-HF).
8. Patients should see a cardiologist if the diagnosis is unclear (potentially valvular disease, pericardial disease, or amyloidosis) or if the patient is on medications but not responding to treatment. 

Heart failure with preserved ejection fraction

Unlike heart failure with reduced ejection fraction (HFrEF), there is not a single definitive test to diagnose heart failure with preserved ejection fraction (HFpEF). It’s important to think about the differential diagnosis for both dyspnea and edema when considering a HFpEF diagnosis; don’t automatically blame the heart. 

The universal definition of heart failure: 

The patient should have both symptoms of heart failure with an ejection fraction >50% (orthopnea, dyspnea, edema, elevated jugular venous pressure, S3, hepatojugular reflux) and objective evidence of a problem with the heart (elevated BNP [ambulatory > 35 pg/mL / pro-BNP > 125 mg/mL or hospitalized BNP > 100 pg/mL / pro-BNP > 300 pg/mL] or evidence of cardiogenic pulmonary or systemic congestion) (Bozkurt et al 2021).

Dyspnea Differential Diagnosis

A dyspneic patient does not automatically have HFpEF. HFpEF is just one of a myriad of possible diagnoses leading to shortness of breath. Dyspnea can be caused by cardiac conditions, pulmonary conditions, anemia, neuromuscular conditions, and even anxiety. Cardiac causes include cardiomyopathy, coronary artery disease, valvular disease, arrhythmia, and pericardial disease. 

The history can help guide your clinical assessment: if there is a family history of sudden death, think hypertrophic cardiomyopathy; if they have prior surgeries and calcification of their pericardium on chest x-ray, think pericardial disease. 

Edema Differential Diagnosis

Edema comes from either increased hydrostatic pressure or decreased oncotic pressure. Increased hydrostatic pressure could be due to cirrhosis with portal hypertension, kidney failure, venous insufficiency, heart problems, cardiomyopathy, valvular disease, or medications like calcium channel blockers and steroids. Decreased oncotic pressure is caused by there not being enough protein creating oncotic pressure to hold fluid in the vessels. Reduced oncotic pressure can either be a production issue (cirrhosis, gut malabsorption, malnutrition) or a loss issue (nephrotic syndrome). Lymphedema looks distinctly different from volume overload edema. The Stemmer sign (thickening of the skin at the base of the second finger or toe) is a physical exam finding to help guide your diagnosis of lymphedema (Gross and Greene 2019). See our episode on lower extremity edema (#316) for a deeper dive. 

H₂FPEF score is a clinical tool that uses accessible data to suggest the probability that the patient you are treating has HFpEF. It can help guide your thought process when making a diagnosis of HFpEF, but like anything in medicine you need to interpret the H₂FPEF score through the lens of your pretest probability.  A score of  ≥ 6 points is highly suggestive of HFpEF whereas a score of 2-5 could be investigated further (Reddy et al 2018, MDCalc): 

1. Heavy: BMI > 30 kg/m² (+2)
2. Hypertensive: 2 or more antihypertensives (+1)
3. Atrial Fibrillation (+3)
4. Pulmonary hypertension; echo estimated PASP >35 mmHg (+1)
5. Elder: > 60 years (+1)
6. Filling pressure : doppler E/e’ > 9 (+1)

Don’t miss amyloidosis! Amyloidosis is an under-recognized cause of HFpEF; a little more than 1 in 8 cases of HFpEF may be attributed to amyloidosis (González-Lopéz et al 2015). Missing this diagnosis means inadvertently withholding life saving medication from patients, and we would not want to do that. See Episode #427 Kittleson Rules Amyloidosis for a deep dive into this condition. 

Every disease has a trajectory and the progression of disease can suggest etiology. Dr. Kittleson notest that HFpEF is often characterized by periods of quiescence punctuated by discrete exacerbations triggered by clear inciting factors (Ex: NSAID use, fluid overload) with a return to baseline once fluid status is improved. A slow progressive decline is less likely HFpEF; this is more characteristic of amyloidosis or constrictive pericarditis. 

Tests to evaluate a patient with suspected HFpEF

Patients presenting with dyspnea and edema should be evaluated with standard lab tests including CMP to look at kidney function and liver function, urinalysis to assess for proteinuria, CBC/iron studies to assess the presence of anemia and to screen for hemochromatosis. An echocardiogram can differentiate between many of the cardiac causes of dyspnea, and a cardiac MRI could be useful in patients that do not fit the classic HFpEF demographic of an older individual with comorbidities. An abdominal ultrasound may be useful if cirrhosis is suspected. 

Checking a BNP is useful in diagnosing HFpEF, but not much else. Patients with HFpEF tend to have a lower BNP than similarly congested patients with HFrEF. The BNP can be normal even in patients hospitalized with volume overload due to HFpEF when they are obese (Khalid et al 2017). Dr. Kittleson rarely checks a BNP and encourages you to trust your history and use other tools like the JVP to evaluate congestion. However, extremely high BNP (> 5000 ng/L) can provide useful information in the form of patient prognosis; a value this high carries with it a ~50% 3 month mortality (Zhang et al 2015). 

Medications for HFpEF

Diuretics like furosemide are a necessary evil to keep patients decongested and have a Class 1 indication if fluid retention or NYHA Class III-IV (Kittleson 2023).

SGLT2 inhibitors are the first medication to meet their primary endpoint in a HFpEF clinical trial (dapagliflozin (DELIVER) or empagliflozin (EMPEROR-PRESERVED)). SGLT2 inhibitors currently carry a 2a indication; however, this rating may be outdated and undersell the data supporting these medications, because it was established when only one of the two SGLT2i trials was published (Kittleson 2023).

***HOT OFF THE PRESSES***

The nonsteroidal mineralocorticoid receptor antagonist finerenone reduced death from cardiovascular causes and led to a significantly lower rate of a composite of total worsening heart failure events and cardiovascular death when compared to placebo (FINEARTS-HF).

***HOT OFF THE PRESSES***

Spironolactone has a 2b indicated for HFpEF based on a subgroup analysis of the North and South American population of the international TOPCAT trial.  The trial included patients from North and South America, and Russia and Georgia. These two patient groups had vastly different event rates. Additionally, the Russian/Georgian patients did not have an increase in either their potassium or creatinine when started on spironolactone. While the whole patient population did not show a benefit, spironolactone was beneficial when examined in the American populations alone. 

Sacubitril/valsartan has a 2b indication for all women with HFpEF, and men with EF <55-60% (PARAGON-HF).

Candesartan has a 2b indication for patients who are ARNI eligible who cannot take this medication (CHARM-PRESERVED).

Treatment approaches for HFpEF and its comorbidities

Hypertension: Dr. Kittleson suggests using thiazide diuretics because they do double duty, and consider ARNI/MRAs because there is some data indicating efficacy in HFpEF. 

Atrial Fibrillation: Anticoagulation for thromboembolic prophylaxis is indicated in nearly all HFpEF patients due to their elevated CHA2DS2-VASc score. The benefit of rhythm control versus rate control is still not 100% established in patients with HFpEF (Reddy et al 2022 and Kelly et al 2019), so Dr. Kittleson likes to treat patients according to their symptoms.  

Chronic Kidney Disease: These patients should already be on an SGLT2i, and you can consider an ARNI/ARB to slow the progression of kidney disease. 

Sleep apnea: Many patients with HFpEF suffer from sleep apnea. This condition should be screened for and treated in the HFpEF population (Javaheri et al 2017).

Weight Loss: Exercise and dieting have been shown to help patients with HFpEF feel better. Brisk walking for >150 minutes/week (≥30 minutes a day) (Arnett et al 2019) or caloric restriction (Kitzman et al 2016) both have positive outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are known to help with weight loss (STEP-1), and they are actively being studied in the HFpEF population (HFpEF SUMMIT (NCT04847557)). The recent results from STEP-HFpEF indicate that semaglutide leads to better symptom management in patients with HFpEF.  

Salt and Water Intake: HFpEF patients tend to be more salt sensitive than patients with HFrEF. Patients will likely feel better if they reduce salt intake and they should be prompted to note how they feel after increased salt or water intake. 

When to Refer to a Specialist: While HFpEF usually can be managed by a primary care provider, patients should see cardiologists if the diagnosis is unclear (potentially valvular disease, pericardial disease, or amyloidosis) or if the patient is on medications but not responding to treatment. The pneumonic CHECK-IN can be used if you are considering whether referral is appropriate: Collaboration (need for specialist), High-risk features (multiple hospitalizations, PH, RV dysfunction), Extensive evaluation needed (exercise testing/RHC/CMR), Cardio renal syndrome, Knowledge of HFpEF mimics (valvular disease, amyloid, pericardial disease), Increased need for diuretic agents, NYHA Class III or IV symptoms (less than ordinary activity cases fatigue).

Links

Mastering the Art of Patient Care

Goal

Listeners will learn to recognize and manage heart failure with preserved ejection fraction in the ambulatory setting. 

Learning objectives

After listening to this episode listeners will…

1. Feel confident with their differential diagnosis for dyspnea and edema 
2. Have a targeted framework to identify HFpEF
3. Develop an approach to initiate guideline directed medical therapy for HFpEF
4. Know when to refer to a cardiologist or heart failure specialist 

Disclosures

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

Citation

Gorth DJ, Kittleson MM, Williams PN, Watto MF. “#460 Heart Failure with Preserved Ejection Fraction”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast November 4, 2024.