Heart Failure with Preserved Ejection Fraction. April 4, 2018 Mike Muellerleile M.D.

Transcription

1 Heart Failure with Preserved Ejection Fraction April 4, 2018 Mike Muellerleile M.D.

2

3

4 Heart Failure with Preserved Ejection Fraction Introduction Clinical Description of HFpEF Pathophysiology of HFpEF Treatment Flavors of HFpEF

5

6

7

8

9

10 Frank starling

11 Diastolic filling is dependent on ventricular relaxation and LV diastolic distensibility

12 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

13

14 Normal Diastolic Function in a young person E wave rapid passive filling A wave atrial contraction LV recoil sucks blood: E wave Little atrial contraction needed

15 Grade I Diastolic Dysfunction Early passive filling is reduced and active filling by the atrium dominates

16 Grade II Diastolic Dysfunction pseudonormal

17 Grade III-IV Diastolic Dysfunction High filling pressures Early filling only A wave atrial contraction adds very little

18

19

20 Diastolic Heart Failure E/E < 8 GOOD E/E >15 BAD LVEDP>15 Normal I II III/IV

21

22 E/E Normal I II III/IV

23 Heart Failure with Preserved Ejection Fraction Introduction Clinical Description of HFpEF Pathophysiology Flavors of HFpEF Treatment

24 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

25 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

26

27 Heart Failure with Preserved Ejection Fraction Introduction Clinical Description of HFpEF Pathophysiology Flavors of HFpEF Treatment

28

29 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

30 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:

31 Effect of treatment on mortality (randomized controlled trials) Trial Name / Author ALLHAT - A ALLHAT - B ALLHAT - C CHARM-P DIG Hong Kong DHF Trial - A Hong Kong DHF Trial - B I-PRESERVE PEP-CHF SENIORS V-HeFT I - A V-HeFT I - B V-HEFT II Aronow et al. (1997) Relative Risk (95% CI) 1.19 (0.81, 1.75) 0.76 (0.49, 1.18) 0.90 (0.47, 1.72) 1.03 (0.87, 1.21) 1.00 (0.80, 1.25) 0.30 (0.03, 2.77) 0.16 (0.01, 2.98) 1.02 (0.91, 1.14) 1.06 (0.75, 1.51) 0.93 (0.65, 1.31) 1.31 (0.77, 2.24) 1.06 (0.59, 1.91) 0.65 (0.39, 1.09) 0.73 (0.58, 0.93) Overall (95% CI) Test for heterogeneity: I 2 =17.1%, P=0.267 Test for overall effect: P= (0.92, 1.06) Active Arm Control Arm J Am Coll Cardiol 2011;57:

32 Effect of treatment on mortality (observational studies, adjusted) Trial Name / Author OPTIMIZE-HF (Fonarow et al.) - A OPTIMIZE-HF (Fonarow et al.) - B OPTIMIZE-HF (Hernandez et al.) Shamagian et.al. - A Shamagian et.al. - B Shamagian et.al. - C Shamagian et.al. - D Dauterman et al. Dobre et al. Fukuta et al. A Fukuta et al. B Fukuta et al. C Fukuta et al. D Tribouilloy et al. Shah et al. A Shah et al. B Shah et al. C Ouzounian et al. Philbin et al. Sueta et al. - A Sueta et al. - B Sueta et al. - C Ahmed et al. Relative Risk (95% CI) 1.14 (0.81,1.60) 1.21 (0.87,1.69) 0.94 (0.83,1.06) 0.63 (0.44,0.90) 0.76 (0.43,1.34) 1.70 (1.10,2.62) 0.90 (0.59,1.38) 1.15 (0.79,1.67) 0.57 (0.37,0.88) 0.20 (0.06,0.64) 0.69 (0.24,2.02) 0.76 (0.31,1.87) 1.86 (0.71,4.90) 0.73 (0.54,0.99) 0.73 (0.68,0.79) 0.93 (0.89,0.98) 0.92 (0.87,0.97) 1.16 (0.76,1.77) 0.61 (0.30,1.25) 1.68 (1.19,2.38) 1.23 (0.80,1.89) 0.74 (0.51,1.08) 0.96 (0.62,1.42) Overall (95% CI) Test for heterogeneity: I 2 =74%, P< Test for overall effect: P= (0.84,1.02) Active Arm Control Arm J Am Coll Cardiol 2011;57:

33 Effect of treatment on exercise capacity in RCTs Trial Name / Author Aronow et al. Mottram et al. Nodari et al. Setaro et al. Kitzman et al. Hung et al. Weighted Mean Difference (95% CI) (15.98, 78.02) (-40.07, ) (-83.05, ) (-58.43, ) (-32.02, ) (0.28, ) Overall (95%CI) Test for heterogeneity: I 2 =0.0%, P=0.99 Test for overall effect: P< (27.29, 75.65) NOTE: Weights are from random effects analysis J Am Coll Cardiol 2011;57:

34 Effect of treatment on diastolic function (E/A ratio) in RCTs Trial Name / Author Hong Kong DHF Trial - A Hong Kong DHF Trial - B SENIORS Echo SWEDIC Aronow et al. (1993) Mottram et al. Nodari et al. Kitzman et al. Hung et al. Overall (95% CI) Test for heterogeneity: I 2 =50.6%, P=0.040 Test for overall effect: P=541 Weighted Mean Difference (95% CI) (-0.02, 0.00) (-0.04, -0.02) (-0.41, 0.21) 0.07 (-0.03, 0.17) 0.10 (-0.03, 0.23) (-0.22, 0.08) 0.02 (-0.08, 0.12) 0.26 (0.01, 0.51) (-0.16, 0.12) (-0.03, 0.02) NOTE: Weights are from random effects analysis J Am Coll Cardiol 2011;57:

35 Conclusion Pharmacotherapy of HFpEF demonstrates a quantifiable improvement in exercise tolerance but not mortality. J Am Coll Cardiol 2011;57:

36 Heart Failure with Preserved Ejection Fraction Introduction Clinical Description of HFpEF Pathophysiology Flavors of HFpEF Treatment

37

38 Diuretics

39

40 Blood Pressure Meds

41

42 Coronary Artery Disease

43

44 Beta Blockers, Calcium Channel Blockers

45

46 Spironolactone

47 TOPCAT 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. 50 % Spironolactone (n = 1,722) (p = 0.14) 20.4 Primary endpoint Placebo (n = 1,723) Results Primary endpoint (CV death, CHF hospitalization, or resuscitated cardiac arrest): spironolactone vs. placebo: 18.6% vs. 20.4%, HR 0.89, 95% CI , p = 0.14 CV mortality: 9.3% vs. 10.2%, p = 0.35; CHF hospitalizations: 12.0% vs. 14.2%, p = Hyperkalemia: 18.7% vs. 9.1%, p < 0.001; renal failure also was higher in the spironolactone arm Conclusions 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 Pitt B, et al. N Engl J Med 2014;370:

48

49 Sleep apnea

50 Exercise

51 Calcium Channel Blockers

52

53

54

55

56