Damien Logeart. Disclosure: none

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1 Damien Logeart Disclosure: none 13/1/211

2 HEART FAILURE AND MYOCARDIOPATHIES Best of 21 Damien Logeart Hôpital Lariboisière, Paris Service Cardiologie INSERM U942 Cliquez pour modifier le style des sous-titres du masque 13/1/211

3 ESC guidelines 28 HF + LVEF.4 Detect major Co-morbidities Diuretic + ACE-I (or ARB) Titrate to clinical stability Anemia Renal dysfunction Diabetes Betablocker. Persisting signs and symptoms Aldost. antagonist OR ARB Persisting signs and symptoms LVEF.35 QRS 12 msec Consider CRT or CRT-D 13/1/211 Consider digoxin, LVAD, transplantation Consider ICD

4 Benefits of betablockers in HF role of heart rate Tertile avec plus fort delta de réduction de la FC 15 bpm en moyenne Tertile avec plus faible delta de réduction de la FC 8 bpm en moyenne 13/1/211 McAlister et al. Ann Intern Med 29

5 13/1/211 SHIFT effects of pure HR lowering in HF (ivabradine) 6558 patients, NYHA 2-3, LVEF 35% (mean 29%), hospit during previous 12 months and heart rate 7bpm (mean 8bpm) under optimal treatment: 9% ACE-I, 9% BB (5% with target dose), 6% antialdosterone ivabradine 5 à 7.5mgx2/j vs placebo Mean HR (bpm) weeks Placebo Ivabradine Mont hs Swedberg K, Komajda M et al. Lancet 21; 376:

6 SHIFT : benefit of ivabradine in HF with HR 7bpm CV death or HF hospitalisation (%) CV mortality ou HF hospitalisation RRR= 18% p<,1 Placebo Ivabr adine NNT: 26 patients during 1 year M 8 Events 4 HR 95% CI p value o i All cause mortality,9,8;1,2 P=,92 s CV mortality,91,8;1,3 p=,128 HF mortality,74,58;,94 p=,14 HF hospitalisation,74,66;,83 p<,1 All cause hospitalisation,89,82;,96 p=,3 CV cause hospitalisation,85,78;,92 p=,2 13/1/211 Swedberg K, Komajda M et al. Lancet 21; 376:

7 5 87 bpm P<. 1 8 to <87 bpm 75 to <8 bpm 72 to <75 bpm 7 to <72 bpm HR at inclusion and outcome Mo n t h s HR with ivabradine (day 28) and outcome <75 bpm bpm 6-<65 bpm 65-<7 bpm <6 bpm 1 Böhm 13/1/211 M et al. Lancet 21; 376 J M o i s

8 ESC guidelines 28 HF + LVEF.4 Detect major Co-morbidities Diuretic + ACE-I (or ARB) Titrate to clinical stability Anemia Renal dysfunction Diabetes Betablocker. Persisting signs and symptoms Aldost. antagonist OR ARB Persisting signs and symptoms LVEF.35 QRS 12 msec Consider CRT or CRT-D 13/1/211 Consider digoxin, LVAD, transplantation Consider ICD

9 EMPHASIS eplerenone in mild HF 2737 heart failure, 55 years, NYHA 2, LVEF 3%, under optimal treatment with CV related-hospitalisation in previous 6 months or BNP > 25 or NTproBNP > 5pg/ml Exclusion : K+ > 5.mM, egfr < 3ml/min/1.73m² 1ary end-point: CV death or hospitalisation for HF è eplerenone 25-5mg/j vs placebo with planned follow-up of 48 months 13/1/211 Zannad F et al. N Engl J Med 211;364:11-21

10 EMPHASIS strong benefits of eplerenone in mild HF 2737 heart failure, 55 years, NYHA 2, LVEF 3%, 1ary end-point: CV death or hospitalisation for HF è eplerenone 25-5mg/j vs placebo 13/1/211 Zannad F et al. N Engl J Med 211;364:11-21

11 EMPHASIS 13/1/211 Zannad F et al. N Engl J Med 211;364:11-21

12 ESC guidelines 28 HF + LVEF.4 Diuretic + ACE-I (or ARB) Titrate to clinical stability Betablocker + Ivabradine if HR 7 Persisting signs and symptoms Aldost. antagonist Persisting signs and symptoms LVEF.35 QRS 12 msec Consider CRT or CRT-D 13/1/211 Consider digoxin, LVAD, transplantation Consider ICD

13 ESC guidelines 28 HF + LVEF.4 Diuretic + ACE-I (or ARB) Titrate to clinical stability Betablocker Persisting signs and symptoms Aldost. antagonist OR ARB Persisting signs and symptoms LVEF.35 QRS 12 msec Consider CRT or CRT-D 13/1/211 Consider digoxin, LVAD, transplantation Consider ICD

14 RAFT: benefit of CRT (on top of ICD) in mild to moderate HF CRT and "hard" end-points (death / hospitalisation): - COMPANION: ICD-CRT and CRT better than medical ttt in NYHA CARE-HF: CRT alone better than medical ttt in NYHA MADIT-CRT: ICD-CRT better than alone ICD on HF events in NYHA 2 - REVERSE: CRT better than medical ttt on remodelling and symptoms RAFT 1798 patients, NYHA 2 (or 3), LVEF 3% (mean 23%), QRS 12msec or 2msec if paced (mean 158 and 28msec respectively) 1ary end-point: death from any cause or hospitalisation for HF è ICD alone or ICD-CRT 13/1/211 Tang AS et al. N Engl J Med 21;363:

15 RAFT: benefit of CRT (on top of ICD) in mild to moderate HF Benefit of CRT increased with increase in QRS (QRS 15msec: HR.59 QRS < 15msec: HR.99) More complications in CRT group 13/1/211 Tang AS et al. N Engl J Med 21;363:

16 21 Focused Update of ESC guidelines on device therapy in heart failure LVEF 35% (and optimal medical ttt) CRT-D/CRT-P Patients Class/level of evidence NYHA 3 or 4* (*ambulatory) Sinus rhythm NYHA 2 Sinus rhythm QRS 12msec QRS 15msec I / A I / A NYHA 3 or 4 Atrial fibrillation QRS 13msec PM dependency/frequent pacing Concomitant PM indication NYHA 3-4, QRS 12msec or < 12msec NYHA 2, QRS<12msec IIa / B or C I / B IIa / C IIb / C REVERSE and MADIT-CRT (published in 29) 13/1/211

17 ESC guidelines 28 HF + LVEF.4 Diuretic + ACE-I (or ARB) Titrate to clinical stability Betablocker Persisting signs and symptoms Aldost. antagonist OR ARB Persisting signs and symptoms LVEF <.35 QRS > 12 msec Consider CRT or CRT-D 13/1/211 Consider ICD Consider others treatments, LVAD, transplantation

18 LV assist devices: have we reached a new era? Improved QOL, longer duration, short and long term survival Improvement in safety +++ Destination therapy? ESC guidelines 21 update LVAD Patients Class/level of evidence Destination therapy 13/1/211 NYHA 3b or 4, LVEF 25% Peak VO2 < 14 IIb / B Heartware (n = 14) compared to Intermacs registry 2) ADVANCE study Aaranson K et al. AHA 211 (n=499, mainly HeartMate End-point: survival at 6 months and non-inferiority

19 Cell therapy: almost ready for practice?? STAR-heart 391 chronic HF (with previous MI 8y), LVEF 35% è BMC group (n = 191): 6.6x17 BMCs and control group (n = 2) Follow-up after 3, 12, 6 months 13/1/211 Strauer BE et al. Eur J Heart Fail 21;12:721

20 Monitoring and follow-up of HF patients Structured telephone support RR 95 CI n Mortality HF hospitalisation Telemonitoring RR 95 CI n Mortality HF hospitalisation /1/211 Inglis SC et al. Cochrane Database of Systematic Reviews 21

21 Monitoring and follow-up of HF patients 1653 patients with recent hospitalisation for HF è telemonitoring or usual care 1ary end-point: readmission or death within 18 days 13/1/211 Chaudhry SI et al. NEJM 21; 363:231-9

22 Cardiomyopathy LV non compaction 15 LVNC/154 suspected cases (26 centers, 2 years) CMH and Fabry disease 392 CMH (29 centers, 2 years) 9 avec test "papier" positif 4 patients avec Fabry (1.8% des CMH chez > 4 ans) + 8 autres patients par dépistage familial Habib 13/1/211 G et al. Eur J Heart Fail 21 online Hagege A et al. Heart 211;97:131e136

23 Genetic counselling and testing in cardiomyopathies: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases 13/1/211 Charron P et al. Eur Heart J 21

24 Important positive results 13/1/211 CONCLUSIONS New validated concept/new beneficial drug: heart rate lowering by ivabradine Aldosterone inhibitors : major benefits also in moderate HF Benefits of CRT, new guidelines/indication for moderate HF Reinforced hopes LV assist devices in advanced HF Cell therapy and gene therapy Disease-managements strategies: further evaluation are mandatory before final adoption Preserved EF HF: always no EBM Acute HF: poor EBM

25 13/1/211

26 Safety : K+ > 5.mM in 11.8% vs 7.2% (p<.1) Blood pressure: reduced by 2.5 mmhg with eplerenone (vs.3 with placebo, p.1) 13/1/211

27 Gene therapy: emerging promises CUPID trial phase 2 Recombinant AAV with SERCA2a cdna: MYDICAR 39 patients with chronic HF, LVEF 35%, NYHA 3-4 è 3 active groups with 3 different injected doses and 1 control group (n = 14) Serial assessment: NYHA, MLWHFQ, VO2, NTproBNP, LVEF, LVEDV 12,5 1,5 8,5 6,5 4,5 2,5,5-1,5-3,5 9,5 8 6,5 5 3,5 2 VO2 peak NTproBNP,5 LVE LVESV -1-1 F 13/1/211-2 Greenberg BH et al. Heart Failure 21-2,

28 Peripartum cardiomyopathy 1 / 2-4 births and no recovery in 5% cases Mechanisms? oxydative stress-mediated cleavage of prolactin 16-kDa form 2 women with PPCM, mean LVEF 27%, NYHA 3-4 in 5% diagnosed during 1st month after delivery, randomized, open-label Bromocriptine 8 weeks or not 58 vs 36% 13/1/211 Sliwa K et al. Circulation. 21;121:

29 Monitoring and follow-up: usefulness of NTproBNP 278 patients for HF 3 groups: - Usual care - Multidisciplinary care (4 visits at home by nurse and 2 consults with cardio) - NTproBNP-guided: consult with cardio every 15days if BNP > 22pg/ml 1ary end-point: survival without HF-readmission But no effect on mortality 13/1/211 Berger R et al. J Am Coll Cardiol 21;55:645-53