Erwan DONAL Cardiologie CHU RENNES

Transcription

1 Nancy, Vendredi 18 septembre 2015 "Insuffisance cardiaque à fraction d'éjection ventriculaire gauche préservée : on avance!" Erwan DONAL Cardiologie CHU RENNES erwan.donal@chu-rennes.fr 1

2 Diagnosis of Heart Failure Poor specificity and poor sensitivity ESC HF guideliens

3 By 2030, >8 million people in the United States (1 in every 33) will have HF Circ Heart Fail. 2013;6:

4 HFREF Heart Failure: 2-3% of population, HFPEF 10-20% of elderly AHA Statistics, Go Circ 2014 Bimodal distribution of EF OPTIMIZE-HF, Fonarow JACC

5 Supine pulmonary arterial wedge pressure (PAWP) by average E/e ratio groups using the recommended cut off of 13. Mário Santos et al. Circ Heart Fail. 2015;8:

6 KaRen. Patients Characteristics Main baseline clinical characteristics At admission for acute HF N /% 539 Age 77±9 Gender (females) 303 (56%) Hypertension 419 (78%) Prior Heart failure 216 (40%) Prior Stroke 56 (10%) Coronary artery disease 158 (29%) Prior AMI 77 (15%) Valvular heart disease 74 (14%) Diabetes 161 (30%) Renal dysfunction 146 (27%) Anemia 202 (37%) COPD 73 (14%) Donal et al ACVD

7 HFPEF characteristics: Big differences by study design Approximate Baseline and Outcome data from Different HFPEF settings OPTIMIZE -HF HFPEF Fonarow JACC 2007, Patel JACC HF 2013 OPTIMIZE -HF HFREF Fonarow JACC 2007 Owan / Bhatia NEJM 2006 KaRen HFPEF Lund EJHF 2014 Swedish Heart Failure Registry HFPEF Lund JAMA 2012, 2014 BASELINE risk factors and severity and? Presence of HF Swedish Heart Failure Registry HFREF Lund JAMA 2012, 2014 HFPEF trials Age Women, % Hypertension % CAD % DM % AF % Lung disease % Obesity % SBP Creatinine GFR 61 GFR 63 GFR NT-proBNP Hb Diuretic use % OUTCOMES 1-yr mortality % 1-yr mort or HF hosp % 7

8 Event in OPTIMIZE-HF Preserved LVEF Depressed LVEF P-value In-hospital mortality 2.9% 3.9% < Post-discharge mortality (60-90 days) 9.5% 9.8% Rehospitalization at days 29.2% 29.9% Post-discharge mortality or rehospitalization at days Heart Failure Preserved EF: prognosis 35.3% 36.1% year survival : 35% after a HF hospitalization QoL poor ~end-stage renal disease Care of patients with HFpEF can be frustrating Diagnosis is not straightforward Comorbidities are common Treatment still an Enigma 8 Fonarow et al. JACC 2007

9 KaRen Data Time to 1-st hospitalization or allcause of death MAGGIC-Meta-analyis: Mortality for patients with HF-PEF and HF- REF, adjusted for age, gender, aetiology of heart failure, hypertension, diabetes, atrial fibrillation. Mean follow-up time = 28 months Primary outcome event : 177 patients (42.9%) - 61 death (14.8%) HF-hospit (28.1%) Donal et al. EJHF Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) Eur Heart J 2012;33:

10 The incidence of hospitalizations for HF and deaths in KaRen was high and E/e predicted adverse clinical outcomes E/e with a cut-off = Donal et al EJHF 2015

11 the primary outcome: time to all-cause mortality or first heart failure hospitalization Lund, Donal et al EJHF

12 the secondary outcome: time to all-cause mortality Lund, Donal et al EJHF

13 Readmission rate Mortality rate very elderly veterans with a first HF hospitalization during the study period. Thirty-day mortality decreased from 14% to 7% (both P<0.001) and 1-year mortality decreased from 49% to 27% (P<0.001). 13 Circ Heart Fail. 2011;4:

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16 HFPEF Treatment - failed CHARM-Preserved: CV death or HF hospitalization Yusuf, Lancet 2003 PEP-CHF: Death or HF hospitalization Cleland, EHJ 2006 Why? Difficult definition Difficult diagnosis Heterogeneous (some patients did not have HF) I-PRESERVE: Death or CV hospitalization Massie, NEJM 2008 Solution: Phenotyping = Characterize HFPEF patients Match treatment to phenotype Match endpoint to phenotype and treatment TOPCAT: Death or HF Hospitalization Pitt NEJM 2014, Pfeffer Circ 2014

17 HFpEF: Treatment? No treatment has yet been shown, convincingly, to reduce morbidity and mortality in patients with HFpEF. Diuretics Best BP control ESC HF Guidelines; EJHF 2008 ESC HF Guidelines EHJ

18 Meta-analysis No negative trends in any outcome There is no significant effect on mortality (relative risk: 0.99; 95% confidence interval [CI]: 0.92 to 1.06) in randomized controlled trials, and the results appear homogeneous... Effects of Treatment on Exercise Tolerance, Cardiac Function, and Mortality in Heart Failure With Preserved Ejection Fraction : A Meta-Analysis Holland DL et al. JACC (16):

19 Effect of treatment on mortality in observational studies There appears to be a favorable effect on mortality but with a great heterogeneity and a much greater heterogeneity than among the RCTs Effects of Treatment on Exercise Tolerance, Cardiac Function, and Mortality in Heart Failure With Preserved Ejection Fraction : A Meta-Analysis Holland DL et al. JACC (16):

20 Only 183 patients drawn from 6 trials There appears to be a significant effect on exercise capacity (weighted difference 51.47; 95% CI: to 75.65) in RCTs, and the results appear homogeneous. Effects of Treatment on Exercise Tolerance, Cardiac Function, and Mortality in Heart Failure With Preserved Ejection Fraction : A Meta-Analysis 20 Holland DL et al. JACC (16):

21 Lack of Improvement in resting diastolic function despite significant improvements in exercise capacity Treatment Effect on Diastolic Function in RCTs There is no significant effect on diastolic function (E/A ratio [weighted difference 0.01; 95% CI: 0.03 to 0.02]) in RCTs Effects of Treatment on Exercise Tolerance, Cardiac Function, and Mortality in Heart Failure With Preserved Ejection Fraction : A Meta-Analysis 21 Holland DL et al. JACC (16):

22 Why have prior clinical trials of HFpEF failed? Heterogeneity (syndrome, not a specific disease process) Exercise induced diastolic dysfunction Chronic volume overload Associated RF failure of pulmonary hypertension What s the objective? Shah. JACC 2013;62:1339 Kitzman. JACC 2011; 57:

23 Conclusions A principle for futur studies in HFpEF: Add Life to the remaining years than to add years to the remaining life Diastolic dysfunction is probably not the main or the only abnormality to which HFpEF treatment should be targeted Need for objective criteria for HFpEF Need for homogeneous samples >> great expectations in the upcoming treatments 23

24 Based on a comparison of 2 key trials, LIFE and I-PRESERVE, the poor outcomes in patients with HF-PEF may not be explained by LVH or other comorbidities. (Campbell et al JAm Coll Cardiol 2012;60: ) 2 things that most clearly differentiate patients with HF-PEF from those with hypertension : the clinical syndrome of heart failure (and often previous hospital admission with heart failure) and elevated natriuretic peptide levels. Phenotyping by phenomapping Shah Heart Failure Clinics 2014, Circulation