Marat Fudim, MD Duke University

1. Treatment for HFpEF– Current
State of the Art and Ongoing Trials
@FudimMarat
Marat Fudim, MD, MHS
Associate Professor
Division of Cardiology,
Duke University

2. Disclosures
 Research Support:
– NIH, Doris Duke, Reprieve, Sardocor
 Consultant/Ownership Interest:
– Abbott, Alio Health, Alleviant, Artha, Audicor, AxonTherapies, Bodyguide,
Bodyport, Boston Scientific, Broadview, Cadence, Cardioflow, Coridea, CVRx,
Daxor, Deerfield Catalyst, Edwards LifeSciences, Echosens, EKO, Feldschuh
Foundation, Fire1, FutureCardia, Galvani, Gradient, Hatteras, HemodynamiQ,
Impulse Dynamics, Intershunt, Medtronic, Merck, NIMedical, NovoNordisk,
NucleusRx, NXT Biomedical, Orchestra, Pharmacosmos, PreHealth, Presidio,
Procyreon, ReCor, SCPharma, Shifamed, Splendo, Summacor, SyMap, Verily,
Vironix, Viscardia, Zoll.

3. 3
Reversals in the Decline of Heart Failure Mortality in the US, 1999 to 2021
Sayed, Fudim JAMA Card 2024

4. Unmet Need in HFpEF
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021
CHARM-Preserved
DIG-PEF
PEP-CHF
I-PRESERVE
PROTECT
ASCEND-HF
RELAX-AHF
RELAX-AHF 2
TRUE-AHF
ATHENA-HF
ASTRONAUT
ALDO-DHF
TOPCAT
PARAGON-HF
POSITIVE
NEUTRAL
2022
EMPEROR
PRESERVED
2023
DELIVER HF
REDUCE LAP
STEP HFpEF
NEAT HFPEF
INDIE HFPEF

5. Common HFpEF phenotypes
Cardiorena
l
Autoimmune /
inflammatory
Cardiometaboli
c

6. 6
HF With Preserved Ejection Fraction
Recommendations for HF With Preserved Ejection Fraction*
Referenced studies that support the recommendations are summarized in the Online Data Supplements.
COR LOE Recommendations
1 C-LD
1. Patients with HFpEF and hypertension should have medication titrated to
attain blood pressure targets in accordance with published clinical practice
guidelines to prevent morbidity.
2a C-EO
3. In patients with HFpEF, management of AF can be useful to improve
symptoms.

7. 7
Colors correspond to COR in Table
2.
Medication recommendations for HFpEF are
displayed.
*Greater benefit in patients with LVEF closer to
50%.
ARB indicates angiotensin receptor blocker;
ARNi, angiotensin receptor-neprilysin inhibitor;
HF, heart failure; HFpEF, heart failure with
preserved ejection fraction; LVEF, left
ventricular ejection fraction; MRA,
mineralocorticoid receptor antagonist; and
SGLT2i, sodium-glucose cotransporter 2
inhibitor.

8. The current gold standard
SGLT2
26%
Relative
Risk CV
death
12%
Relative
Risk HF
Hosp
MRA
18% 26%
ARNI
22%
SGLT2 MRA ARNI
The Pillars of Medical Therapy in HFrEF
Vaduganathan Lancet 2022
Pfeffer Circulation 2014
Solomon NEJM 2019
In the Americas
In LVEF LVEF 45-57%

9. What Doesn’t Work
Beta Blockers (Induces chronotropic insufficiency)
3: No-
Benefit
B-R
7. In patients with HFpEF, routine use of nitrates or phosphodiesterase-5 inhibitors
to increase activity or QOL is ineffective.

10. Additional Therapies Beyond Drugs?

11. Don’t Forget the Comorbidities
Obesity
Hypertension
Diabetes
Chronic Kidney Disease
Sleep Apnea
Atrial Fibrillation

12. HFpEF: Beyond the Heart
HFpEF: Inflammation induced Aging of the CV System
Borlaug, JACC, 2023; Mesquita, Aging Cell, 2021

13. Clinical trials of anti-inflammatory therapies for HF
Trials that included patients with HFpEF are highlighted in light blue
Figure adapted from Pugliese NR et al. Cardiovasc Res 2022
TNFR
Cardiomyocyte
IL-1βR
MPO
Syst emic inflammat ion
MPO inhibit ors
SATELLITE*
ENDEAVOR(ongoing)
Atherosclerosis
Vascular injury
↑ Permeability
NLRP3 inflammasome
↑ IL-18 ↑ IL-1β
↑IL-6
Colchicine
COLpEF (ongoing)
Canakinum ab
CANTOS* -HF
Anakinra
REDHART*
D-HART*
D-HART2
Et anercept
RECOVER
RENAISSANCE
RENEWAL
Inflixim ab
ATTACH
Zilt ivekim ab
HERMES
(ongoing)
TNF-α
Myocardial hypertrophy
Myocardial stiffness
Fibrogenic mediators

14. HERMES – IL-6 Inhibition

15. Improve
Outcomes?
Data processing and
analysis. Protocol
based decision making/
optimization of HF-
Therapy
Further
decisions
taken by
physician as
necessary

16. • Interatrial shunting has demonstrated promise as a treatment for
symptomatic patients via left to right atrial unloading
EXERCISE
8mm diameter
shunt
Therapeutic Rationale:
Interatrial Shunt Size and Left Atrial Decompression
SHUNT
NO SHUNT
Kaye et al. J CardFail. 2014

17. Atrial Shunt Devices
Corvia IASD V-Wave Ventura Shunt Occlutech AFR Alleviant System
No-implant Shunt
Implantable Shunts
8mm ID; 19mm OD 5.1mm ID; 14.3mm OD 8-10mm ID; 21-23mm OD 7mm; RF-excision

18. Decongestion Trials

19. Pulmonary Hypertension Focus

20. Myocardium - Gene Transfer Study
1st World-wide cases of gene transfer in HFpEF

21. Take Home Messages
 HFpEF is a National Emergency
 Comorbidity management is essential
 Few existing therapeutic options
 Devices are up and coming
21