In addition to today’s resource please review CORE IM‘s Behinds the Scenes Videos: Heart Failure with Preserved Ejection Fraction.
Posted: June 23, 2024
By: Dr. Alice Kennedy, Dr. Shreya P. Trivedi, Dr. Jennifer Ho, Dr. Rati Vani and Dr. Waleed Rehman
Audio: Dr. Alice Kennedy
Today, I review, link to, and excerpt from CORE IM‘s HFpEF: 5 Pearls Segment.
Posted: June 5, 2024
By: Dr. Rati Vani, Dr. Jennifer Ho, Dr. Ravi Patel, Dr. Emily Lau and Dr. Shreya P. Trivedi
Graphic: Dr. Jesse Powell, Dr. Michelle Lo
Peer Review: Dr. Greg Katz, Dr. Randy Goldberg, Dr. Snehal Bhatt
All that follows is from the above resource.
TIME STAMPS CME-MOC SHOW NOTES TRANSCRIPT REFERENCES
Time Stamps
- 01:59 Pearl 1 – What is HFpEF?
- 11:22 Pearl 2 – Echo findings and diastolic dysfunction
- 19:21 Pearl 3 – BNP
- 25:06 Pearl 4 – Advanced Testing
- 32:03 Pearl 5 – Treatments for HFpEF
Show Notes
Pearl 1: What is Heart Failure with Preserved Ejection Fraction (HFpEF)?
- Definition
- Clinical syndrome of volume overload and elevated left filling pressures at rest OR exercise in a patient EF of 50% or higher
- Poorly understood systemic syndrome that is likely an umbrella term for multiple conditions
- Symptoms: dyspnea on exertion, PND, orthopnea, fatigue, exercise intolerance
- Physical exam findings: JVD, pulmonary rales, LE edema
- Pathogenesis for “Garden Variety” HFpEF or Cardiometabolic HFpEF
- Originally thought of as a result of long-standing hypertension leading to LV remodeling and stiffness
- Now, thought to be a result of obesity and cardiometabolic disease leading to systemic low grade inflammation, but still with evolving understanding
- Coronary microvascular dysfunction, endothelial dysfunction, and altered myocardial energetics are thought to be central to pathogenesis
- Risk Factors
- Age
- Cardiometabolic risk factors: obesity, hypertension, diabetes, CAD, sedentary lifestyle
- Over 80% of HFpEF patients are overweight or obese
- Female specific risk factors include hypertensive disorders of pregnancy, specifically preeclampsia
- Increased risk factors lead to increased prevalence of “garden variety” HFpEF
- HFpEF makes up about 50% of HF cases, though the proportion is increasing due to an increase in cardiometabolic risk factors
- HFpEF masqueraders
- Based on history and physical examination, “masqueraders” of HFpEF must be ruled out
- Clues towards possible HFpEF masqueraders
- Suspected HFpEF but with low H2FPEF score*
*A Simple, Evidence-Based Approach to Help Guide Diagnosis of Heart Failure With Preserved Ejection Fraction [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Circulation. 2018 Aug 28;138(9):861-870. doi: 10.1161/CIRCULATIONAHA.118.034646.
*H2FPEF Score: At Last, a Properly Validated Diagnostic Algorithm for Heart Failure With Preserved Ejection Fraction [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Originally Published 27 August 2018. Circulation Volume 138, Number 9. https://doi.org/10.1161/CIRCULATIONAHA.118.035711
- Kussmaul’s sign (increased JVP with inspiration)
- Low voltage ECG relative to increased wall thickness
- Intolerance of standard GDMT/neurohormonal blockade
- Risk factors present for infiltrative/restrictive HFpEF in a young patient
- Non-cardiac masqueraders: Pulmonary disease, kidney disease or nephrotic syndrome, cirrhosis, anemia, chronic venous insufficiency
- Cardiac masqueraders: Hypertrophic cardiomyopathy, restrictive cardiomyopathy, cardiac amyloidosis, cardiac sarcoidosis, hemochromatosis, valvular disease (severe stenosis, regurgitation, or mixed), myocarditis, pericardial disease
Pearl 2: Echo Findings and Diastolic Dysfunction
- Echo findings alone cannot make or exclude a diagnosis of HFpEF
- Diastolic dysfunction = inability to fill ventricle with adequate preload volume (end diastolic volume) at acceptably low pressures
- Diastolic dysfunction and HFpEF* are NOT synonymous terms
- Diastolic dysfunction is an abnormality in relaxation/filling, separate from LVEF or symptoms
- Diastolic dysfunction can be a part of human aging
- Diastolic dysfunction is a risk factor for development of HFpEF
- Diastolic dysfunction cannot be observed on resting echocardiograms of ⅓ of HFpEF patients
- Diagnosed by echo with the following parameters, where 2 parameters is indeterminate and 3 or more is diastolic dysfunction
- LA volume index > 34 mL/m2
- E/e’ > 12-14
- e’ velocity
- Septal e’ velocity < 7 cm/s
- Lateral e’ velocity < 10 cm/s
- TR velocity > 2.8 m/s
- Other echo findings
- Elevated LV filling pressure, either at rest or with exertion
- Usually assessed with E/e’ (early diastolic transmitral inflow velocity to mitral annular tissue velocity)
- LA pressure increases -> progressive LA dilation
- Increased LV mass index
- Pulmonary hypertension in 70-80% of HFpEF patients
- PA pressure estimated using TR jet velocity and RA pressure
- RV dysfunction in 20-35% of HFpEF patients (marker of increased morbidity and mortality)
*A Simple, Evidence-Based Approach to Help Guide Diagnosis of Heart Failure With Preserved Ejection Fraction [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Circulation. 2018 Aug 28;138(9):861-870. doi: 10.1161/CIRCULATIONAHA.118.034646.
*H2FPEF Score: At Last, a Properly Validated Diagnostic Algorithm for Heart Failure With Preserved Ejection Fraction [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Originally Published 27 August 2018. Circulation Volume 138, Number 9. https://doi.org/10.1161/CIRCULATIONAHA.118.035711
*Heart failure with preserved ejection fraction: an update on pathophysiology, diagnosis, treatment, and prognosis [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Braz J Med Biol Res. 2020 Jun 5;53(7):e9646. doi: 10.1590/1414-431X20209646. eCollection 2020.
*Echo for diastology [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Ann Card Anaesth. 2016 Oct;19(Supplement):S12-S18. doi: 10.4103/0971-9784.192585.
The Role of Echocardiography in Heart Failure with Preserved Ejection Fraction: What Do We Want from Imaging? [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Heart Fail Clin. 2019 Apr;15(2):241-256. doi: 10.1016/j.hfc.2018.12.004. Epub 2019 Feb 2.
Pearl 3: BNP
- Natriuretic peptides are produced/released due to increased myocardial wall stress and cardiac stretch
- May be normal in HFpEF
- HFpEF does not necessarily elevate end diastolic wall stress (when concentric remodeling with LV hypertrophy occurs)
- BNP is just one clue in diagnosing HFpEF, but must be combined with the entire clinical picture and echocardiogram
- NT-pro-BNP is influenced by key features of HFpEF (AF, obesity, renal impairment, age)
- Obesity is associated with lower BNP levels
- AF and chronic kidney disease are associated with higher BNP levels
- Natriuretic peptide deficiency, which is strongly correlated with obesity, may leave individuals more susceptible to pressure/volume overload
- “Natriuretic” means sodium in the urine
- Since BNP makes an individual urinate out sodium, one can understand why BNP might be elevated in volume overload and why lower than expected levels might be problematic.
Pearl 4: Advanced Testing
- HFpEF probability scores
- H2FPEF score
- Use only with clinical suspicion of HFpEF
- More useful in outpatient setting
- Estimates probability of HFpEF vs non-cardiac causes of dyspnea
- Heavy, Hypertensive, Atrial fibrillation, Pulmonary Hypertension, Elder, Filling Pressures
- HFA-PEFF Score *
- Calculated using functional/morphological criteria (based on echo) and biomarker criteria (BNP) levels to estimate probability of HFpEF
- If diagnosis remains uncertain, consider RHC, including provocative maneuvers
- Exercise RHC/stress echo to eval for elevated filling pressures that develop during exercise
- Cardiac MRI and other advanced testing (e.g. cardiac PET) not required for a diagnosis of HFpEF, but can be used to investigate HFpEF masqueraders (e.g., hypertrophic cardiomyopathies, cardiac amyloidosis, or cardiac sarcoidosis)
*HFA-PEFF Score: How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Eur Heart J. 2019 Oct 21;40(40):3297-3317. doi: 10.1093/eurheartj/ehz641.
Pearl 5: Treatments for HFpEF
- Control risk factors
- Manage hypertension, coronary artery disease, diabetes, and obesity
- Medications
- SGTL2i is the first line choice for HFpEF (class IIa in AHA/ACC guidelines, class I in ESC guidelines)
- MRA (class IIb in AHA/ACC guidelines)
- ACE/ARB/ARNI (class IIb in AHA/ACC guidelines)
- Add on loop diuretics to decrease congestion
- Outcomes and trial data:
- EMPEROR-Preserved: Empagliflozin in HFmrEF and HFpEF
- Empagliflozin decreased risk of HF hospitalization and CV mortality in patients with HFmrEF or HFpEF (EF > 40%)
- 13.8% event rate in the empagliflozin group vs. 17.1% in placebo group (HR 0.79, 95% CI 0.69-0.90)
- DELIVER: Dapagliflozin in HFmrEF and HFpEF
- Dapagliflozin reduced HF hospitalizations and CV mortality in patients with HFmrEF or HFpEF (EF > 40%)
- 16.4% event rate in dapaglifozin group vs. 19.5% in placebo group (HR 0.82, 95% CI 0.73-0.92)
- TOPCAT: Spironolactone for HFpEF
- Spironolactone is associated with a small reduction in HF hospitalization, but does not reduce CV mortality in HFpEF
- Heterogeneous results across regions of enrollment in the trial have raised controversy about the trial results
- Post-hoc analysis showed statistically significant benefit in the Americas for the primary composite outcome of CV death, aborted cardiac arrest, or heart failure hospitalization (HR 0.82, 95% CI 0.69-0.98)
- CHARM-Preserved: ARBs in HFpEF
- Candesartan had no effect on CV mortality but prevented admissions for HF hospitalization for those with EF > 40%
- PARAGON-HF: ARNI in symptomatic HFpEF
- Compared to valsartan alone, sacubitril-valsartan did not lower HF hospitalizations or CV mortality, however, there was improvement in NYHA class and less decline in renal function in the sacubitril-valsartan group
- Possible benefit in those with EF in lower range of eligibility
- Sacubitril/valsartan was associated with reduction in HF hospitalization/CV mortality in women, but not men
- Future of GLP-1 agonists
- The STEP-HFpEF trial showed treatment with semaglutide 2.4 mg weekly led to greater reductions in weight loss, symptoms, and physical limitations compared to placebo
- Ongoing trials are assessing effects on CV events and mortality
