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Heart Failure with Preserved Ejection Fraction April 4, 2018 Mike Muellerleile M.D.
Heart Failure with Preserved Ejection
Fraction
April 4, 2018
Mike Muellerleile M.D.
Heart Failure with Preserved Ejection
Fraction
Introduction
Clinical Description of HFpEF
Pathophysiology of HFpEF
Treatment
Flavors of HFpEF
Frank starling
Diastolic filling is dependent on ventricular
relaxation and LV diastolic distensibility
Diastolic Dysfunction by Echo
We measure the inflow thru
the mitral valve from the
LA to the LV
Early passive filling is the
ventricle springing open
to sucks blood into the LV
Late filing is the atria
contraction
Normal Diastolic Functionin a young person
E wave rapid passive
filling
A wave atrial
contraction
LV recoil sucks blood:
E wave
Little atrial contraction
needed
Grade I Diastolic Dysfunction
Early passive filling is
reduced and active filling
by the atrium dominates
Grade II Diastolic Dysfunction
“pseudonormal”
Grade III-IV Diastolic
Dysfunction
High filling pressures
Early filling only
A wave atrial
contraction adds very
little
Diastolic Heart Failure
E/E’ < 8
GOOD
E/E’>15
BAD
LVEDP>15
Normal I II III/IV
E/E’
Normal I II III/IV
Heart Failure with Preserved Ejection
Fraction
Introduction
Clinical Description of HFpEF
Pathophysiology
Flavors of HFpEF
Treatment
Diastolic Heart Failure
Must have normal LV function (>40-
50%)
No valve disease or arrhythmia
Must present with heart failure
Evidence for abnormal LV filling is
helpful
Diastolic Heart Failure
Prevalence is highest over 75 years,
Women >Men
Mortality rate is half that of CHF: 5-8%
a year
Related to HTN, A. Fib., anemia, CRI,
Presentation is identical to CHF
Heart Failure with Preserved Ejection
Fraction
Introduction
Clinical Description of HFpEF
Pathophysiology
Flavors of HFpEF
Treatment
Relative Impairments in Hemodynamic Exercise Reserve Parameters in Heart Failure With Preserved Ejection
Fraction
A Study-Level Pooled Analysis
Ambarish Pandey, Rohan Khera, Bryan Park, Mark Haykowsky, Barry A. Borlaug, Gregory D. Lewis, Dalane
W. Kitzman, Javed Butler and Jarett D. Berry
Effects of Treatment on Exercise
Tolerance, Cardiac Function and
Mortality in Heart Failure with
Preserved Ejection Fraction; A Meta-
Analysis
David J. Holland BScApp, Dharam J. Kumbhani MD, SM,
Salim H. Ahmed MD, Thomas H. Marwick MBBS, PhD, FACC
J Am Coll Cardiol 2011;57:1676-86
Effect of treatment on mortality
(randomized controlled trials)
Hong Kong DHF Trial - A
Hong Kong DHF Trial - B
Overall (95% CI)
Test for heterogeneity: I2=17.1%, P=0.267
Test for overall effect: P=0.699
I-PRESERVE
V-HEFT II
V-HeFT I - A
ALLHAT - B
SENIORS
V-HeFT I - B
ALLHAT - C
ALLHAT - A
CHARM-P
DIG
PEP-CHF
Aronow et al. (1997)
0.99 (0.92, 1.06)
1.02 (0.91, 1.14)
0.65 (0.39, 1.09)
1.31 (0.77, 2.24)
0.76 (0.49, 1.18)
0.93 (0.65, 1.31)
1.06 (0.59, 1.91)
0.90 (0.47, 1.72)
1.19 (0.81, 1.75)
1.03 (0.87, 1.21)
1.00 (0.80, 1.25)
0.30 (0.03, 2.77)
1.06 (0.75, 1.51)
0.73 (0.58, 0.93)
0.16 (0.01, 2.98)
10.1 1 10
Active Arm Control Arm
Trial Name / Author Relative Risk (95% CI)
J Am Coll Cardiol 2011;57:1676-86
0.1 1 10
Overall (95% CI)
Test for heterogeneity: I2=74%, P<0.0001
Test for overall effect: P=0.103
Ahmed et al.Sueta et al. - CSueta et al. - BSueta et al. - A
Philbin et al.
Ouzounian et al.Shah et al. CShah et al. BShah et al. A
Tribouilloy et al.Fukuta et al. DFukuta et al. C
Fukuta et al. BFukuta et al. A
Dobre et al.
Dauterman et al.
Shamagian et.al. - DShamagian et.al. - CShamagian et.al. - BShamagian et.al. - A
OPTIMIZE-HF (Hernandez et al.)
OPTIMIZE-HF (Fonarow et al.) - B
OPTIMIZE-HF (Fonarow et al.) - A
Active Arm Control Arm
0.93 (0.84,1.02)
0.96 (0.62,1.42)0.74 (0.51,1.08)1.23 (0.80,1.89)1.68 (1.19,2.38)
0.61 (0.30,1.25)
1.16 (0.76,1.77)0.92 (0.87,0.97)0.93 (0.89,0.98)0.73 (0.68,0.79)
0.73 (0.54,0.99)1.86 (0.71,4.90)0.76 (0.31,1.87)
0.69 (0.24,2.02)0.20 (0.06,0.64)
0.57 (0.37,0.88)
1.15 (0.79,1.67)
0.90 (0.59,1.38)1.70 (1.10,2.62)0.76 (0.43,1.34)0.63 (0.44,0.90)
0.94 (0.83,1.06)1.21 (0.87,1.69)1.14 (0.81,1.60)
Trial Name / Author Relative Risk (95% CI)
Effect of treatment on mortality
(observational studies, adjusted)
J Am Coll Cardiol 2011;57:1676-86
NOTE: Weights are from random effects analysis
Overall (95%CI)Test for heterogeneity: I2=0.0%, P=0.99
Test for overall effect: P<0.0001
Nodari et al.
Kitzman et al.
Mottram et al.
Aronow et al.
Setaro et al.
Hung et al.
51.47 (27.29, 75.65)
90.00 (-83.05, 263.05)
48.00 (-32.02, 128.02)
64.00 (-40.07, 168.07)
47.00 (15.98, 78.02)
96.00 (-58.43, 250.43)
54.00 (0.28, 107.72)
0 50 100 150 200150 100 50200
Trial Name / Author Weighted Mean Difference (95% CI)
Effect of treatment on exercise capacity
in RCTs
J Am Coll Cardiol 2011;57:1676-86
NOTE: Weights are from random effects analysis
Overall (95% CI)
Test for heterogeneity: I2=50.6%, P=0.040
Test for overall effect: P=541
Aronow et al. (1993)
Hong Kong DHF Trial - A
SENIORS Echo
Nodari et al.
Hong Kong DHF Trial - B
Hung et al.
SWEDIC
Kitzman et al.
Mottram et al.
-0.01 (-0.03, 0.02)
0.10 (-0.03, 0.23)
-0.01 (-0.02, 0.00)
-0.10 (-0.41, 0.21)
0.02 (-0.08, 0.12)
-0.03 (-0.04, -0.02)
-0.02 (-0.16, 0.12)
0.07 (-0.03, 0.17)
0.26 (0.01, 0.51)
-0.07 (-0.22, 0.08)
0-2 -1 0 1 2
Trial Name / Author Weighted Mean Difference (95% CI)
Effect of treatment on diastolic function (E/A ratio) in RCTs
J Am Coll Cardiol 2011;57:1676-86
Conclusion
Pharmacotherapy of HFpEF demonstrates a
quantifiable improvement in exercise
tolerance but not mortality.
J Am Coll Cardiol 2011;57:1676-86
Heart Failure with Preserved Ejection
Fraction
Introduction
Clinical Description of HFpEF
Pathophysiology
Flavors of HFpEF
Treatment
Diuretics
Blood Pressure Meds
Coronary Artery Disease
Beta Blockers, Calcium Channel Blockers
Spironolactone
TOPCAT
• Primary endpoint (CV death, CHF hospitalization, or resuscitated cardiac arrest): spironolactone vs. placebo: 18.6% vs. 20.4%, HR 0.89, 95% CI 0.77-1.04, p = 0.14
• CV mortality: 9.3% vs. 10.2%, p = 0.35; CHF hospitalizations: 12.0% vs. 14.2%, p = 0.042
• Hyperkalemia: 18.7% vs. 9.1%, p < 0.001; renal failure also was higher in the spironolactone arm
Trial design: Patients with heart failure with preserved ejection fraction (HFpEF) were
randomized to spironolactone (initiated at 15 mg/day; median dose 25 mg/day) or placebo.
Patients were followed for 6 years.
Results
Conclusions
Pitt B, et al. N Engl J Med 2014;370:1383-92
(p = 0.14)
Spironolactone
(n = 1,722)
Primary endpoint
• Spironolactone was not superior to placebo for CV
outcomes in HFpEF patients (majority on ACEI/ARB)
• Significantly higher rate of hyperkalemia and renal
failure in patients treated with spironolactone
• Reduction in CHF hospitalizations with
spironolactone is hypothesis generating and
deserves further study
0
25
50
18.620.4
Placebo
(n = 1,723)
%
Sleep apnea
Exercise
Calcium Channel Blockers
