Heart Failure Guillaume Jondeau Hôpital Bichat, Paris, France
Epidemiology Importance of PEF Europe
I-PREFER study. Abstract: 2835 Prevalence of HF Preserved LV systolic Function older (65 vs 62 y, p<0.001), female (50% vs 28%, p<0.001) 80 70 obese (39% vs 27%, p<0.001) 60 50 40 HTN (78% vs 53%, p<0.001), 30 20 AF (29% vs 24%, p=0.03) less AMI (21% vs 44%, 10 0 Middle east Latin America Africa p<0.001)
Diagnosis of the disease Unusual use of echography
Ultrasonographic detection of pleural effusion (US-PE) P1654 83 ambulatory HF patients (39% men, aged 77±12 years) mean follow-up of 652±456 days, 1826 visits 77 visits : high possibility of worsening HF 1749 : low possibility of worsening HF US-PE sensitivity 76.6% [95%CI 65.6-85.5%] specificity 98.6% [95%CI 98.0-99.1%] positive predictive value 71.1% [95%CI 60.1-80.5%] negative predictive value 99.0% [95%CI 98.4-99.4%]
Comet tail
Ultrasound lung comets as prognostic determinant in heart disease N 5088 1,102 consecutive in-patients (aged 69±12 years, 751 males) ULC score : n of ULC from 28 scanning sites on anterior and lateral right and left hemithoraxes, from the 2d to the 5th intercostal. Diagnosis at admission stable angina (n = 219, 20%), acute coronary syndrome (n = 216, 19%), primary (n = 74, 6%) or ischaemic CMP (n = 132, 12%), valvular heart disease (n = 134, 12%), arrhythmias (n = 154, 14%), other (n = 173, 17%). On multivariate analysis, ULC > 30 ( [HR] 2.17; 95% [CI] 1.78-2.64) provided additional prognostic information on age (HR 1.02; CI 1.01-1.03), diabetes mellitus (HR 1.47; CI 1.08-2.06), NYHA class (HR 1.28; CI 1.13-1.43).
Pathophysiology Importance of the RA pressure
Liver function tests and hemodynamics in end-stage heart failure patients P1652 186 end-stage HF 57±10 years, 77% male, at time of listing for heart transplantation between 1997 and 2009. Predominantly cholestatic enzyme pattern 60 50 RAP the only independent predictor of T-Bil (r=0.37; p=0.028) and GGT (r=0.44; p=0.006) in a stepwise multiple regression analysis CI not correlated with cholestatic enzymes nor transaminases 40 30 20 10 0 T Bil GGT A LP A ST % patients w ith increase value
renal failure = filtration rate 1) Altered kidney Comorbidity diabetes, age, Cardiogenic shock 2) perfusion gradient 2a) perfusion pressure systemic arterial pressure pressure in renal artery Selective vasoconstriction Arterial stenosis 2b) venous pressure 2b 2a 1
Domman JACC 2009 53 582
Pronostication of the patients
Tubular damage and outcome in chronic heart failure N 5090 2131 pts from the GISSI-HF trial Pronostic value of egfr (chronic kidney disease) albuminuria Tubular damage (3 increased): Kidney Injury Molecule 1 (KIM-1), N-acetyl-beta-D-glucosaminidase (NAG) Neutrophil Gelatinase Associated Lipocalin (NGAL)
patients referred for heart transplantation in the era of device therapy P2461 715 CHF patients referred for heart transplantation 54±12 years; ICD: 244; CRT: 30; CRT-D: 108; none: 333 follow-up of 962±912 days, 354 patients died or received urgent heart transplant or LVAD HFSS effective in discriminating patients into low, medium and highrisk groups in all device groups peak VO2 did not discriminated between low (> 14) and medium (10.1 to 14 ml/min/kg) risk in device patients The recommendation to transplant patients with HFSS medium to high risk HFSS (unchanged) with ICD and/or CRT, a peak VO2 10 but not 14 ml/min/kg may now identify the high risk group which should be considered for transplantation
therapy
Randomised Placebo Controlled, Parrallel Group, Multidose, to evaluate the effect of RLY5016 in Heart Failure Patients (PEARL HF) Polymer binds K+ in colon, no Na load, better tolerated that Kayexalate 25 meq/d extra K excretion: K plasma level 6.5 5.5; 4 3.8 100 patients (2 groups of 50 patients): 68 years, 60% males, BMI 28, CHF 4.5 years, LVEF 40%, egfr 80 ml/min 73% ACE + BB, 75% diuretic
PEARL HF 30g RLY5016 Placebo K baseline 4.69 4.65 K 4 weeks 4.48 4.93* aldo 50 mg 90% 74%* GI side effect 21% 6%*
Systolic Heart failure treatment with the If inhibitor ivabradine Trial M. Komajda on behalf of the Investigators
Primary objective To evaluate whether the I f inhibitor ivabradine improves cardiovascular outcomes in patients with : 1. moderate to severe chronic heart failure 2. left ventricular ejection fraction 35% 3. heart rate 70 bpm and in sinus rhythm 4. the best possible recommended therapy
Study endpoints Primary composite endpoint Cardiovascular death Hospitalization for worsening heart failure Other endpoints All-cause / CV / HF death All-cause / CV / HF hospitalization Composite of CV death, hospitalization for HF or non-fatal MI NYHA class / Patient & Physician Global Assessment Swedberg K, et al. Eur J Heart Fail. 2010;12:75-81.
Patients and follow-up 7411 screened 6558 randomized 3268 to ivabradine 3290 to placebo Excluded: 27 Excluded: 26 3241 analysed 2 lost to follow-up 3264 analysed 1 lost to follow-up Median study duration: 22.9 months; maximum: 41.7 months Lancet. Online 29-08-2010
Baseline characteristics Ivabradine 3241 Placebo 3264 Mean age, y 60.7 60.1 Male, % 76 77 Ischaemic aetiology, % 68 67 NYHA II, % 49 49 NYHA III/IV, % 51 51 Previous MI, % 56 56 Diabetes, % 30 31 Hypertension, % 67 66 Lancet. Online 29-08-2010
Mean heart rate reduction Heart rate (bpm) 90 Mean ivabradine dose: 6.4 mg bid at 1 month Ivabradine Placebo 6.5 mg bid at 1 year 80 80 75 75 70 67 60 64 50 0 2 weeks 1 4 8 12 16 20 24 28 32 Months Lancet. Online 29-08-2010
Primary composite endpoint Cumulative frequency (%) 40 30 Ivabradine n=793 (14.5%PY) Placebo n=937 (17.7%PY) HR = 0.82 p<0.0001 Ivabradine Placebo - 18% 20 10 0 0 6 12 18 24 30 Months Lancet. Online 29-08-2010
Hospitalization for heart failure Cumulative frequency (%) 30 20 Ivabradine n=514 (9.4%PY) Placebo n=672 (12.7%PY) HR = 0.74 p<0.0001 Ivabradine Placebo - 26% 10 0 0 6 12 18 24 30 Months Lancet. Online 29-08-2010
Cardiovascular death Cumulative frequency (%) 30 Ivabradine n=449 (7.5%PY) Placebo n=491 (8.3%PY) HR = 0.91 p=0.128 Ivabradine Placebo 20 10 0 0 6 12 18 24 30 Months Lancet. Online 29-08-2010
Effect of ivabradine on outcomes Endpoints Hazard ratio 95% CI p value Primary composite endpoint 0.82 [0.75;0.90] p<0.0001 CV death 0.91 [0.80;1.03] p=0.128 Hospitalization for HF 0.74 [0.66;0.83] p<0.0001 All-cause death 0.90 [0.80;1.02] p=0.092 Death from HF 0.74 [0.58;0.94] p=0.014 Hospitalization for any cause 0.89 [0.82;0.96] p=0.003 Hospitalization for CV reason 0.85 [0.78;0.92] p=0.0002 Lancet. Online 29-08-2010
Effect of ivabradine in prespecified subgroups Age <65 years 65 years Sex Male Female Beta-blockers No Yes Aetiology of heart failure Non-ischaemic Ischaemic NYHA class NYHA class II NYHA class III or IV Diabetes No Yes Hypertension No Yes Baseline heart rate <77 bpm 77 bpm Test for interaction p=0.029 0.5 1.0 Hazard ratio Favours ivabradine Favours placebo 1.5 Lancet. Online 29-08-2010
Take home messages Importance of LVSPEF Echo: look at the lungs Importance of RA pressure: liver, kidney Prognosis: renal function Transplantation VO2 < 10 ml/kg/min Therapy Ivabradine (EF<35%, HR>>70, BB...) Update guidelines resynchro