Déclaration de Relations Professionnelles -Disclosure Statement of Financial Interest SPEAKER NAME. Nothing to disclose

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1 Déclaration de Relations Professionnelles -Disclosure Statement of Financial Interest SPEAKER NAME Nothing to disclose

2 Resynchronisation en pédiatrie Paediatric resynchronisation J. Janoušek Kardiocentrum Klepnutím and lze upravit Cardiovascular styl předlohy Research podnadpisů. Centre University Hospital Motol Prague, Czech Republic Kardiocentrum

3 Why? Dyssynchrony generates marked regional heterogeneity of both function and loading with subsequent structural and cellular remodeling

4 Different types of mechanical intra-ventricular dyssynchrony Kass DA, JACC 2008

5 Geographic distribution of regions of early and delayed activation Clustered Dispersed Amenable to CRT Helm RH et al.,circulation Not amenable to CRT

6 Dispersed segmental dyssynchrony 120 ms

7 Clustered segmental dyssynchrony 300 ms

8 Be sure to differentiate between dyssynchrony amenable and not amenable to CRT Klepnutím lze upravit styl předlohy podnadpisů.

9 How? by electrical preexcitation of the late contracting segments Klepnutím lze upravit styl předlohy podnadpisů.

10 CRT case l l l l Boy, 8 years of age Uneventful history Diminished exercise tolerance since 6 months Severe dilated CMP Etiology unknown l Negative: l» EMB» Serology» Metabolic screening» Coronary angiography QRS = 120 ms I II III av R avl avf V1 V2 V3 V4 V5 V6

11 Clustered segmental dyssynchrony 300 ms

12 Resynchronization by LV free wall pacing normal activation paced activation late activation pacing site SA N AV N V1 R V L V

13 40 ms Before CRT, after 3 weeks of optimal HF therapy, EF=14% After 3 weeks of CRT, EF = 28 %

14 CRT: Improved cardiac function at diminished energy cost Nelson GS et al., Circulation 2000

15 Cellular remodeling in CRT Animal model of dyssynchronous heart failure P38 MAPK, CaMKI, TNF-α: fibrosis and apoptosis Chakir et al.,circulation 2009

16 Cellular remodeling in CRT Excitation-contraction coupling Sarcoplasmatic reticulum calcium ATPase 2α Response to adrenergic stimulation β αδρενορεχεπτορ γενε εξπρεσσιον ϖσ Πηοσπηολαµβαν Improved Ca cycling with Ca uptake into SR P =0.03 Vanderheyden M et al., JACC 2008 Mullens W et al., Heart Rhythm 2008

17 Reverse cellular remodeling in CRT l Restoration of» intracellular Ca cycling» normal balance between catecholamine stimulation and myocyte adrenergic responsiveness» normal connexine distribution and conduction velocity in late contracting segments l Regression of mediators of apoptosis and fibrosis

18 CR T ACE inhibitors β βλοχκερσ ACE inhibitors Courtesy F. Prinzen

19 When and for whom? Klepnutím lze upravit styl předlohy podnadpisů.

20 Available larger CRT studies in pediatric/congenital heart disease CRT definition: resynchronization pacing of the systemic ventricle Design: Retrospective, non-randomized l Dubin AM et al. J Am Coll Cardiol 2005;46: » multi-center» N = 103» Response definition: in EF l Cecchin F et al. JCE 2009;20:58-65» single-center» N = 60» Response definition: 10 % proportional in EF and/or in NYHA class l Janousek J et al. Heart 2009,95: » multi-center» N = 109» Response definition: in EF and/or NYHA class

21 Diagnoses Dubin AM et al. J Am Coll Cardiol 2005;46: Cecchin F et al. JCE 2009;20:58-65 Janousek J et al. Heart 2009, 95:

22 Types of electrical dyssynchrony Dubin AM et al. J Am Coll Cardiol 2005;46: Cecchin F et al. JCE 2009;20:58-65 Janousek J et al. Heart 2009, 95:

23 Systemic ventricular ejection fraction P <0.05 mean P <0.001 median P <0.001 mean Dubin AM et al. J Am Coll Cardiol 2005;46: Cecchin F et al. JCE 2009;20:58-65 Janousek J et al. Heart 2009, 95:

24 RV pacing-associated LV failure Change after CRT EF/FAC units mean (SD) SVEDD z-score median NYHA median Upgrade from RV pacing, systemic LV (N=44) All other pts (N=54) (16.5) -2.1 Grade (10.9) -0.8 Grade 2 2 P =0.101 =0.036 =0.030 Janousek J et al. Heart 2009;95:

25 Systemic ventricular morphology Dubin AM et al. J Am Coll Cardiol 2005;46: Cecchin F et al. JCE 2009;20:58-65 Janousek J et al. Heart 2009, 95:

26 Systemic RV median2 8.8 Age [yrs] median1 2.7 median2 7.0 Dubin AM et al. J Am Coll Cardiol 2005;46: Cecchin F et al. JCE 2009;20:58-65 Jannousek J et al. Heart 2009, 95: Janousek J et al. Heart 2009, 95:

27 Functional classification NYHA 1/2 62 % of responders Dubin AM et al. J Am Coll Cardiol 2005;46: Cecchin F et al. JCE 2009;20:58-65 Janousek J et al. Heart 2009, 95:

28 CRT in mildly symptomatic heart failure (REVERSE trial) CRT off CRT on Linde C et.al. JACC 2008

29 Non-responders Dubin AM et al. J Am Coll Cardiol 2005;46: Cecchin F et al. JCE 2009;20:58-65 Janousek J et al. Heart 2009, 95:

30 Predictors of non-response to CRT Janousek J et al. Heart 2009, Epub ahead of print

31 Potential response to CRT The edge situations Primary dyssynchrony, secondary heart failure 100 % pump efficiency Klepnutím lze upravit styl předlohy podnadpisů. 50 % dyssynchrony CR T time

32 Potential response to CRT The edge situations Primary myocardial failure, secondary dyssynchrony 100 % pump efficiency 50 % CRT time

33 CRT in children l Heterogenous anatomic and functional substrates l High efficacy in specific situations» RV pacing-associated LV failure l Non-uniform effects in others» Systemic RV, SV l Beneficial also in mildly symptomatic HF» NYHA II l Therapy failures predominantly confined to» Highly symptomatic pts» Severely dilated systemic ventricles

34 Major limitations of paediatric CRT studies l No pre-specified indication criteria l No data on mechanical dyssynchrony» Lead placement at late sites? l Difficulties with assessment of systemic RV/SV function l Follow-up to short to evaluate true role of CRT in long-term patient management» HF Morbidity» Survival benefits» Long-term remodeling

35 Clustered Dispersed

36 Klepnutím lze upravit styl předlohy podnadpisů.

37 CRT in CHD patients: how, when and why? l How?» By electrical preexcitation of the late contracting segments l When?» Early enough» One of the few causal treatments of heart failure! l Why?» To correct clustered systemic ventricular mechanical dyssynchrony» To induce reverse structural and cellular remodelling» To improve functional status, morbidity and survival