Noon conference

1. +
Heart Failure:
In 30 min or less!
Sara O. Weiss, MD
January 15, 2019

2. +
Objectives
 Know the most common causes of HF
 Understand how to diagnose HF
 Understand the management of HF

3. +
Magnitude of the Problem
 HF is common:
 Only CV dz increasing in prevalence
 HF is expensive:
 $30 billion dollars (2010)
 HF is deadly:
 20% mortality at 1 yr
Heart Disease and Stroke Statistics--2010 Update: A Report From the
American Heart Association; Circulation 2010

4. +
Diagnotic Pearls
 CLINICAL diagnosis
 Syndrome
 Signs and Sxs
 CXR
 EKG
 TTE
 EF normal
 EF not normal

5. +
Lab Pearls
 BNP Pearls
 One time measurement
 Should not be used to adjust
diuretics
 Lower in obese pts
 Increased with age
 Increased in women
 Increased in CKD
 Hyponatremia
 End organ dysfx
 Liver
 Kidney
 Brain

6. +
Frame Work for Management
 New CM or HF diagnosis
1. Etiology?
2. Stage and Class?
3. Treat hemodynamics
4. Treat hormonal disarray
5. Device Therapy
6. Advanced Therapies (LVAD, transplant)

7. +
Frame Work for Management
 New CM or HF diagnosis
1. Etiology?
2. Stage and Class?
3. Treat hemodynamics
4. Treat hormonal disarray
5. Device Therapy
6. Advanced Therapies (LVAD, transplant)

8. Etiology
Coronary Artery Dz
Non-Ischemic Causes
 Valvular disease
 Myocardial toxins (EtOH,
cocaine)
 Myocarditis
 Hypertension
 Post-partum
 Hypertrophic CM
Gheorghiade M, Bonow RO. Circulation 1998;97:282-289.
Coronary
artery
disease
68%
Non-
Ischemic
32%

9. + Stage v. NYHA Class
1Hunt SA et al. J Am Coll Cardiol. 2001;38:2101–2113.
2New York Heart Association/Little Brown and Company, 1964. Adapted from: Farrell MH et al.JAMA.2002;287:890–897.
Stage NYHA Class
AAt high risk for heart failure but without
structural heart disease or symptoms
of heart failure (eg, patients with
HTN or coronary artery disease)
BStructural heart disease but without
symptoms of heart failure
CStructural heart disease with prior or
current symptoms of heart failure
DRefractory heart failure requiring
specialized interventions
I Asymptomatic
II Symptomatic with moderate exertion
IV Symptomatic at rest
III Symptomatic with minimal exertion
None

10. +
Frame Work for Management
 New CM or HF diagnosis
1. Etiology?
2. Stage and Class?
3. Treat hemodynamics
1. Increase cardiac output
2. Make them euvolemic
4. Treat hormonal disarray
5. Device Therapy
6. Advanced Therapies (LVAD, transplant)

11. +
Pathophysiology
 Hemodynamic Model
 Inadequate pump fx
 Poor “forward flow”
 Unable to explain the progressive nature
 Negative Remodeling
 Neurohormonal Dysregulation
 Architectural distortion

12. +Neurohormonal Disarry
Organ Failure
Cell Death
Increased Load and Increased Wall Stress
Reduced System Performance
Altered Gene
Expression
Cytokine
Expression
Growth
Remodeling
Ischemia
Energy Depletion
Myocardial Insult
Activation of RAAS and SNS
Fetal Gene Program
ANP, BNP
LVH
Fibrosis
ApoptosisVentricular
Dyssynchrony
Abnormal Ca2+
Handling
Necrosis

13. +
Management
 Hemodynamic Therapy
 IABP
 Inotropes
 Diuresis
 Afterload reduction
 ~Digoxin
 Neurohormonal Therapy
 Renin/Angiotensin Axis Blockade
 Adrenergic Axis Blockade
 Aldosterone Blockade
 Nitric Oxide Axis

14. +
Cardiogenic Shock
IABP and Inotropes
 Mechanical support:
 IABP
 Impella
 Inotropes
 Dobutamine
 Millrinone
 Epinephrine

15. Diuretic Pearls
Furosemide
 6 hr half-life
 Variable oral
bioavailability
Torsemide &
bumetinide
 Almost 100% oral
bioavailability
Furosemide
IV
20 mg
Furosemide
PO
40 mg
Torsemide
PO/IV
20 mg
Bumetinide
PO/IV
1 mg

16. Ace Inhibitors/ARBs
Antagonize RAAS
Delay ventricular
remodeling
Reduce
hospitalizations
Improve survival

17. +
AceI Pearls
 AceI first line
 Cough
 more common in women
 Fear not:
 Hypotension
 Hyperkalemia
 Renal insufficiency

18. +
ARNIs: Angiotesin Receptor-
Neprilysin Inhibitors
 Neprilysin
 Endopeptidase that degrades natriuretic peptides, bradykinin and
adrenomedullin
 Neprilysin inhibitor increases these favorable hormones
 Entresto
 Neprilysin+ARB inhibitor
 Succubitril + valsartan

19. +
 PARADIGM-HF trial 2014
 ~8000 patients
 Randomized to entresto 97/103mg BID v enalapril 10mg BID
 Reduced hospitalizations and CV mortality
McMurray et al. NEJM 2014; 371: 993

20. McMurray JJV et al. N Engl J Med 2014;371:993-1004

21. +

22. Hydralazine/Nitrates
Potent vasodilator
afterload reduction
Increased NO
formation
VHeFT 1991
 Hydralazine/ISDN v.
enalapril
 Subgroup analysis of AA
pts
AHeft 2004

23. +
Hydralazine/Nitrate Pearls
 Must be used in combination
 TID dosing is difficult
 Rebound tachycardia
 Use with beta blockers

24. Aldosterone Antagonists
Spironolactone
Eplerenone
Weak diuretics
Pitt B et al. N Engl J Med. 1999;341:709–717.
1.00
Placebo
Months
ProbabilityofSurvival
Spironolactone
0.95
0.90
0.85
0.80
0.75
0.70
0.65
0.60
0.55
0.50
0.45
0.00
0 3 6 9 12 15 18 21 24 27 30 33 36
↓27% mortality
P<.001
RALES

25. +
Aldosterone Antagonist Pearls
 Beware of hyperkalemia!
 Decrease potassium supplementation
 Check levels frequently
 Contraindicated in renal insufficiency
 Women: Cr > 2.0
 Men: Cr > 2.5

26. +
Digitalis Investigators. N Engl J Med 1997;336:525-533.
0
10
20
30
40
Mortality HF
hospitalization
Eventrateat37months(%)
Digoxin
Placebo
P= 0.06
P= 0.001
Digoxin

27. Digoxin Pearls
Narrow therapeutic window!
 Renal clearance decreased in elderly and in women
Target level: 0.5-1.0 Figure 2
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 >=2.0
Serum Digoxin Concentration
MortalityRate DIG Trial Mortality Rates in Men by Trough
Level Measured 1 Month After Randomization
Placebo Crude Rate
Crude Rate, digoxin
Risk Adjusted Rate, digoxin
n = 1171 digoxin
2639 placebo

28. +
Survival Benefits of Beta Blockers
COPERNICUS2MERIT-HF1
Time (years)
Mortality
1.0
0.6
0.8
P<0.00013
0 1 2
1.0
0.6
0.8
Risk  34%
0 1 2
b-blocker
Placebo
b-blocker
Placebo
P=0.0062
Risk  35 %
Carvedilol: n=1156
Placebo: n=1133
Metop Succ: n=1990
Placebo: n=2001
1. MERIT-HF Study Group. Lancet 1999;353:2001-2007.
2. Packer M, et al. N Engl J Med 2001;344:1651-1658.

29. +
Number at risk
Carvedilol 1511 1367 1259 1155 1002 383
Metop tart 1518 1359 1234 1105 933 352
Time (years)
Mortality(%)
0
10
20
30
40
0 1 2 3 4 5
hazard ratio 0.83,
95% CI 0.74-0.93, p=0.0017
Metoprolol tartate
Carvedilol
COMET
Lancet 2003; 362:7-13

30. +
Beta Blocker Pearls
 Benefits in 3-6 months
 Euvolemic patients only
 Not all beta blockers are created equally
 Carvedilol
 Metoprolol Succinate (not metop tartate)
 Bisoprolol
 Fear not the bradycardia
 High dose is better than low dose

31. +
Ivabradine
 Elevated HR is poor prognostic indicator
 Ivabradine is a negative chronotrope
 SHIFT trial
 ~6500 patients
 LVEF <35%
 HR > 70 on “maximally tolerated doses” of βb
 Reduced composite end-point of CV mortality and HF
hospitalizations
Swedberg et al. Lancet 2010; 376: 875

32. +
Supplements
 Omega-3-FAs
 Class IIa, LOE B
 GISSI-HF study
 ~7000 patients
 Randomized to omega-3-FA 1
gram v placebo
 Reduced hospitalizations and
death
 Co-enzyme Q10
 Not in guidelines yet
 Q-SYMBIO study 2014
 ~420 patients
 Randomized to CoQ10 100mg
TID v placebo
 Decreased hospitalizations
and death
Tavarri et al. Lancet 2008; 372: 1223
Mortensen et al. JACC:HF 2014; 2: 641

33. +
What NOT to use in HF
 NSAIDs
 CCBs
 Non-dihydropyridine (diltiazem, verapamil)
 Dihydropyridines (felodipine)
 Amlodipine ok
 Glitazones
 Cilostazol
 Alcohol

34. +
Take home points
 Etiology?
 Always think CAD!!
 Treat hemodynamics
 Inotropes
 Afterload reduction
 Treat hormonal disarray
 Renin/angiotensin/aldo axis
 Adrenergic axis