Heart Failure with Preserved Ejection Fraction: Diagnostic Updates
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Kavita Sharma, MD Johns Hopkins University
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Heart Failure with Preserved Ejection Fraction: Diagnostic Updates
- 1. Heart Failure with Preserved Ejection Fraction: Diagnostic Updates Kavita Sharma, MD Associate Professor of Medicine Director, Heart Failure/Cardiac Transplantation Director, JHU Heart Failure with Preserved Ejection Fraction Program Johns Hopkins Univ. School of Medicine Duke Heart Failure Symposium May 4, 2024
- 2. Disclosures Research Funding Support: • AHA SFRN (16SFRN27870000), Amgen, FNIH- HeartShare AMP Advisory Board/Consultant: • AstraZeneca, Alleviant, Bayer, Boehringer-Ingelheim, Bristol Myers Squib, Cytokinetics, Edwards LifeSciences, Janssen, Novartis, NovoNordisk, Regeneron, RIVUS 2
- 3. Objectives • Case presentation • Diagnostic algorithms for HFpEF • Hemodynamic testing • Advances in Phenotyping in HFpEF
- 4. Patient F.S. • 61 yo F referred to JHU HFpEF Clinic • PMH: HTN, obesity, OSA, pre-DM • HPI: 2 years of progressive dyspnea with walking, 2 pillow orthopnea, bendopnea, occasional PND • Exam: BMI 40, BP 140/70, HR 75 Obese AA female, labored getting onto exam table, JVP 12, + HJR, S1/S2 without gallop, clear lungs, mild non-pitting edema.
- 5. Patient Case: Studies • Na 143, K 4.4 • Creat 1.4 • Hgb 12.6 • TSH 1.50 • HgbA1c 6.2 • Trop-I negative • Kappa/lambda: 0.9 • NT-proBNP 52 • EKG: NSR, HR 70 • Echocardiogram: – EF 60-65% – LVDD 4.21 – IVSd 1.3 cm – LA diam 3.7 cm – E/e’ 9.3 – “normal diastolic filling pattern for age” – normal RV size
- 6. Next Steps? • Is this HFpEF? • Empirically treat? • Is more testing needed…?
- 7. 2022 AHA/ACC/HFSA Guidelines - Classifications of HF Type of HF According to LVEF Criteria HFrEF (HF with reduced EF) LVEF ≤40% HFimpEF (HF with improved EF) Previous LVEF ≤40% and a follow-up measurement of LVEF >40% HFmrEF (HF with mildly reduced EF) LVEF 41%–49% Evidence of spontaneous or provokable increased LV filling pressures (eg, elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement) HFpEF (HF with preserved EF) LVEF ≥50% Evidence of spontaneous or provokable increased LV filling pressures (eg, elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement) May 7, 2024 Heidenreich PA et al. Circulation. 2022;145:e895–e1032
- 8. HFpEF Diagnostic Evaluation Borlaug, Sharma, Shah, Ho. JACC. 2023 (18) 1810–1834
- 9. H2FPEF Score Reddy Y. et al. Circulation 2018;138:861–870. Our patient: Score 4
- 10. HFA-PEFF Scoring Algorithm Pieske et al. Eur J Heart Fail. 2020 Mar;22(3):391-412. Our patient: Score 2
- 11. In the real world… JHU HFpEF Clinic • LVEF ≥ 50% and • Signs and symptoms of CHF and • Objective evidence of a cardiac problem – Elevated NTproBNP or – Structural heart disease (LAE, LVH, DD) or – Resting elevated PCWP (≥ 15 mmHg) or elevated LV end-diastolic pressure (≥ 15 mmHg) or – Rise in PCWP with exercise to ≥ 25 mmHg
- 12. Patient Case: Exercise RHC • Baseline: – RA 8 – PA 23/13 (16) – PAWP 11 – PA sat 66.7% – CO 4.63 / CI 1.97 – PVR 1.08 • Peak exercise, 25W – RA 20 – PA 45/28 (34) – PAWP 28 – PA sat 54%, – CO 10.3 / CI 4.38 – PVR 0.58 Supine bicycle exercise test Diagnosis: Exercise-induced HFpEF
- 13. Epidemiology of HFpEF • > 6 million with heart failure in the U.S; HFpEF currently accounts for ~50% of all HF cases. HFpEF Incidence HFpEF Prevalence HFpEF Clinical Outcomes • 27 cases per 10,000 person-years • Lifetime risk: 1 in 10 at age 45 years • 1-1.5% of population • Highly age-dependent • 5-year mortality: 75.3% (GWTG registry) • 30-day all-cause readmission rate: 21% Secular trends incidence over time prevalence over time ? Sex differences HFpEF vs HFrEF HFpEF incidence rising relative to HFrEF HFpEF prevalence rising relative to HFrEF Similarly poor survival CV death in HFpEF vs HFrEF Borlaug, Sharma, Shah, Ho. JACC. 2023 (18) 1810–1834
- 14. Why is HFpEF hard to diagnose? • Multiple co-morbidities, heterogeneous • Overlapping symptoms (dyspnea, fatigue, exercise intolerance) • Challenging physical exam • Lack of adequate non-invasive tools (biomarkers, imaging) • Limited access to specialized testing
- 15. Evolving Phenotype of HFpEF Shah S. J CV Transl Res. 2017;10(3): 233–244 .
- 16. Phenotypes of HFpEF Borlaug, Sharma, Shah, Ho. JACC. 2023 (18) 1810–1834
- 17. Hemodynamic Phenotyping 0 10 20 30 40 0 2 4 6 PCWP (mmHg) CI (L/min/m 2 ) CONGESTION -- + ADEQUATE PERFUSION -- + A: Dry-Warm N=65, 29% B: Wet-Warm N=84, 37% D: Dry-Cold N=37, 16% C: Wet-Cold N=41, 18% Jani V, Sharma K et al. 2024 Under review. “Cold HFpEF” • Older • Afib • Smaller hearts • RV dysfunction
- 18. Hemodynamic Phenotyping – Clinical Outcomes Jani V, Sharma K et al. 2024 Submitted.
- 19. Hahn V, Sharma K et al. JACC-HF 2020;8:712-24.
- 20. Correlates of HFpEF-CA Hahn V, Sharma K. JACC-HF 2020;8:712-24. *Suspect cardiac amyloidosis in older patients, normal BMI, normal BP, LVH, elevated NTproBNP + troponin
- 21. Deep Phenotyping in HFpEF
- 22. JHU HFpEF Precision Medicine Center of Excellence • Director: Kavita Sharma MD • Over 900 patients seen; >400 in Redcap registry • Clinical Team: Tiara Askew RN, Sarah Riley CRNP • Research Coordinators: Erin Ricketts, MJ Lee, Antra Kumari • Baseline assessments in Clinic: – 6 minute walk test, Frailty , QOL assessment, Echocardiogram, CAD assessment, labs • Right heart catheterization with exercise and IRB protocol for Endomyocardial biopsies (194 patients) • Blood banked in over 250 patients • Referral center for patient care, clinical trials, translational research – Referral base: HF Bridge Clinic, Inpatient services, Pulmonary Clinics, JHU Community Physicians, Regional and National referral center
- 23. Summary • HFpEF incidence and prevalence is rising, yet the diagnosis is often missed. • Diagnostic algorithms for HFpEF are improving, however limited in obese patients; non-invasive or invasive hemodynamic testing may be needed. • HFpEF mimickers should be considered and ruled out. • Deep phenotyping (clinical, hemodynamic, blood, tissue) is ongoing to help identify subgroups and better target therapies.
Editor's Notes
- It is important to note that the H2FPEF score was derived and validated in patients with unexplained dyspnea. In patients with overt signs and symptoms of HF (Figure 6) and elevated NPs, a low H2FPEF score does not exclude HFpEF, but may point to atypical causes of the HFpEF syndrome such as infiltrative cardiomyopathies.
- An increase in pulmonary capillary wedge pressure (PCWP) at rest (≥15 mmHg) or exercise (≥25 mmHg) made at end expiration confirms the diagnosis during supine exercise.119 An increase in PCWP relative to the increase in cardiac output during exercise >2 mmHg/l/min has also been used to establish the diagnosis of HFpEF,121 but this metric may only apply to upright exercise as pressures are much higher in the supine position, and application to supine exercise may reclassify a significant minority of patients into the wrong diagnostic category.122 While invasive exercise testing provides definitive diagnosis, it is not universally available and carries greater cost and requirement for expertise compared to non-invasive imaging modalities. Alternative provocative maneuvers have been tested, including saline infusion and passive leg raise. An increase in PCWP ≥18 mmHg with saline or ≥19 mmHg with leg raise may also help to identify patients with HFpEF.123,124 Exercise stress echocardiography is also used as an alternative to invasive hemodynamic exercise testing and offers incremental value to resting echocardiography in isolation, but is often limited by the ability to acquire diagnostic quality imaging during stress, and false negative results as a number of patients with HFpEF may not display elevation in E/e’ or other surrogate markers with exertion.117,126
- While the overall incidence of HF in the United States appears to be stable or even declining, the incidence of HFpEF specifically continues to rise (Figure 1).10,11 Across 4 community-based cohorts, the incidence rate of HFpEF is estimated at ~27 cases per 10,000 person-years.12 Over the span of two decades, secular trends in the Framingham Heart Study suggest a more than 50% higher incidence rate in 2000-2009 versus 1990-1999. Similarly, the prevalence of HFpEF is increasing and is expected to exceed that of HFrEF in the near future.13 Specifically, data from the national inpatient sample demonstrate that the number of HFpEF hospitalizations more than doubled from 189,260 in 2008 to 495,095 in 2018.14 Using pooled data from the Cardiovascular Health Study and Multi-Ethnic Study of Atherosclerosis, the estimated lifetime risk of HFpEF at age 45 years is more than 10% in both men and women.15 Taken together, these data suggest that the total burden of HFpEF is projected to become the dominant HF subtype in the future, affecting approximately 1 in 10 adults over their lifetime.
- This paradigm shift in HFpEF has really nicely been depicted by Sanjiv Shah showing that HFpEF is increasingly being recognized to be far more complex, with multiple pathophysiologies, including hypertensive remodeling, obesity/metabolic stress, aging, and sedentary lifestyle, all leading to global loss of cardiac, vascular, and peripheral reserve, which are the hallmarks of HFpEF. In particular, efforts to understand peripheral, skeletal muscle and microvasculature mechanisms really have been led at Penn through the work of Payman Zamani, Julio Chirinos and others in their group pursuing clinical and translational research in this area.
- Figure 1. Assessment of Clinical Hemodynamic Profiles in HFpEF. We stratified our JHU HFpEF cohort that had undergone hemodynamic testing by congestion and perfusion status. We defined wet as PCWP > 15, and warm as CI > 2.2. To our surprise, over 34% of patients had a CI < 2.2, suggestion impaired perfusion in spite of the nomenclature “Preserved EF”
- Figure 2. Kaplan-Meier Survival Curves According to Clinical Hemodynamic Profiles. When we evaluated for clinical outcomes by hemodynamic phenotype group, we found that those Congested (“wet) patients had worse outcomes, and within that group, cold profile with low CI fared worse. Combined endpoint of all-cause mortality and heart failure hospitalization within 36 months of enrollment. The median follow-up time for all-cause mortality was 47 months. +P< 0.02; Wet-Warm vs. Dry-Cold. ‡P < 0.02, Dry-Warm vs. Dry-Cold; ∗P<0.01, Dry-Warm vs. Wet-Warm.
- Largest myocardial tissue report in HFpEF to date. N=108 patients referred to JHU HFpEF Clinic from 2014-2018 underwent RHC and EM Bx (IRB protocol), for assessment of histology, compared to HFrEF (n=20) and Controls (n=13) Tissue assessed for fibrosis, inflammation (CD68+ cells), hypertrophy, and presence of amyloidosis