Marat Fudim, MD Duke University

1. Acute Heart Failure Management-
Old and New Ways
Marat Fudim, MD, MHS
Division of Cardiology,
Duke University
@FudimMarat

2. Disclosures
 Research Support:
– Translating Duke Health, Mario Award, Duke Heart Center Leadership Council
Award, Duke Chair’s Award, American Heart Association, Bodyport, BTG
Pharma, Daxor, NIH – K23, Bayer
 Consultant to:
– Axon Therapies, Bodyport, Boston Scientific, CVRx, Daxor, Edwards
Lifesciences, Inovise, PreHealth, Respicardia, Viscardia, Zoll

3. Decongestion in Clinical Practice
Diuretics, Vasodilators, Ultrafiltration
Strategy: Bolus diuretics vs IV Cont.
Felker et al. NEJM, 2011
Fudim et al. AHJ 2021
Mullens et al. EJHF 2019

4. Neutral Phase III trials, 2001-2020
Neutral Phase III HF trials 2001-2020
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020
BEST-HF
CHARM-Preserved
DIG-PEF
PEP-CHF
VERITAS
EVEREST
I-PRESERVE
PROTECT
ASCEND-HF
RELAX-AHF
RELAX-AHF 2
TRUE-AHF
ATHENA-HF
ASTRONAUT
ALDO-DHF
TOPCAT
PARAGON-HF
RED-HF
HFrEF neutral
HFpEF
AHF
Val-HeFT
COMET
CHARM-Alt
CHARM-Add SENIORS
EMPHASIS-HF
HEAAL
SHIFT
PARADIGM-HF
A-HeFT
HFrEF positive
EMPEROR-REDUCED
DAPA-HF
VICTORIA
Fudim, Apostolou Fudim, Apostolou

5. Innovation in Decongestion
• Few advances in
decongestive therapies
• Innovation will require
unconventional thinking

6. 1. Challenging the Heart Failure Paradigm
Chaudhry et al. Circulation. 2007
Zile et al. Circulation. 2008
4 weeks
Weight gain of ≥ 2 lb in 46% (N=268)

7. With Heart Failure Variability of Plasma and RBC Volume is the Norm
7
∏Miller WL. Fluid Volume Overload and
Congestion in Heart Failure: Time to
Reconsider Pathophysiology and How Volume
Is Assessed. Circ Heart Fail. (2016),
9:e002922.

8. (J Am Coll Cardiol HF 2018;6:940–8) © 2018 by the American College of Cardiology Foundation.
Plasma and Red Cell Volume Phenotypes in Hospitalized HF Patients N=245

9. Argaiz, Twitter 2020
Stressed Blood Volume in Heart Failure

10. Volume Redistribution Concept: Splanchnic Nerve Modulation
Heart Failure
Volume redistribution
into thoracic
compartment
↑ Sympathetic tone
↑ Splanchnic vascular tone
↓ Vascular compliance
Congestion
Hypothesis:
Splanchnic Nerve Block as
Treatment in Acute Heart Failure
Volume redistribution
into abdominal
compartment
↓ Sympathetic tone
↓ Splanchnic vascular tone
↑ Vascular compliance
Decongestion
Fallick et al. Circ HF 2011
Fudim et al. JAHA 2017
Fudim et al. Circulation 2018

11. Splanchnic Nerve Modulation
Fudim et al. J. Appl Phys 2017
Bapna et al. Under Review
Stimulation Stimulation Stimulation
Epidural block
1 ✓

12. Splanchnic HF-1 (Acute Heart Failure)
Baseline
1
5
m
i
n
30min
45min
60min
7
5
m
i
n
90min
25
30
35
40
45
50
55
Pulmonary Arterial Mean Pressure
mmHg
B
a
s
e
l
i
n
e
1
5
m
i
n
3
0
m
i
n
45min
6
0
m
i
n
7
5
m
i
n
90min
0
10
20
30
40
mmHg
Wedge Pressure
80
90
100
110
mmHg
Mean Arterial Pressure
SNB SNB
SNB SNB
2
3
4
L/min/m2
Cardiac Index
* * * * *
*
* * * * *
*
* * * * * *
* * *
Fudim et al. Circulation 2018
Fudim et al. EHJ 2018
1
2
✓
✓
N=13
* Pre as reference p <0.05

13. Droogan CJ, et al., HFSA Sep 2016, Poster 297.
2. Optimizing the Volume Status (Red Blood Cells and Plasma)

14. (J Am Coll Cardiol HF 2018;6:940–8) © 2018 by the American College of Cardiology Foundation.

15. - Intravascular and extravascular decongestion is the central goal
- Patients get discharged with persistent congestion and volume overload
- Overdiuresis is a concern
- ”Low and Slow” to protect from overdiuresis/allow capillary refill
Optimization of Diuresis
Target-1 and Target-2 studies
(Total N=19):
- Increase UOP (tripling)
- Allowed for higher diuretic use
- No evidence of AKI
Biegus et al. EJHF 2019

16. 3. Targeting the Cardiorenal Syndrome
 In AHF, RA and Wedge
pressure have the strongest
association with worse
outcomes
 RA has the strongest
association with cardiorenal
syndrome
 The ability to lower filling
pressures appears to be
prognostically more important
than improving CI.
Copper et al. JCF 2016
Brinkley et al. AHJ 2018
Ronco et al. JACC 2008

17. Congestive Kidney Disease
CHF
RA Pressure 5mmHg RA Pressure 30mmHg
Kidneys are encapsulated
High venous pressure  high interstitial kidney pressure pressure
Burnett et al. Am J Physiol 1980

18. Transcatheter Renal Venous Decongestion (TRVD)
Flow

19. Mechanical Unloading of Heart: Aortix
• Mean flow rate through the
device: 3.5 L/min
• Improved EF and Stroke
Volume by echo
• Mean rate of urine output
increased 10-fold (range
2.5–25.0x)
C
outflow
inflow
Vora et al. CCI 2019

20. Kapur NK et al. CCI 2019
N=8
30% of Blood Flow
70% of Blood Flow
4. Restricting Cardiac Preload

21. 5. Interstitial Decongestion
Fudim, JACC, 2021

22. Enhancing Lymph Drainage into the Venous System
Abraham, CSI Device-HF Webinar 2021

23. Jonas, TCT 2019

24. 6. Direct Renal Decongestion
The JuxtaFlow System®
induces negative pressure in
the kidney
JuxtaFlow Catheters
connect to an external
diaphragm pump
Increases urine production

25. Results from FIM Study
0
200
400
600
800
1000
1200
1400
1600
1800
2000
0
10
20
30
40
50
60
70
Control
(24 hr)
Treatment
(24 hr)
Post-Tx
(24 hr)
0
50
100
150
200
250
300
350
400
Control
(24 hr)
Treatment
(24 hr)
Post-Tx
(24 hr)
▲51% ▲56% ▲145%
▲34%
• Preliminary results from human feasibility study (VOID-HF): data from the first three patients; may not represent the full data set
• Patients were admitted for ADHF and persistently volume overloaded despite receiving 240 mg IV furosemide daily. Diuretic dose was held constant for the duration of the study.
Restoring Normal
Fluid Volume Improving Filtration
Maintaining
Fluid Volume
Net Fluid Loss (mL) Measured GFR
(mL/min)
Sodium Excretion
(mmol)
▲796%
▲436%

26. Conclusions
Acute HF and congestion is complex
Important to understand the underlying mechanism of
congestion – in order to match with appropriate treatment
Need to be open to new and innovative approaches to
decongestion