1. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 Ruolo dell'imaging cardiaco per una corretta selezione dei pazienti candidati alla CRT Donato Mele

2. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 LV dilatation no longer required compared to the 2007 ESC Guidelines.

3. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011

4. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 The number of non-responders is high (about 30-50% depending on response definition and HF etiology). CRT is not without complications (11% periprocedural, 4% device-related according to the 2009 European CRT Survey). Economic resources are limited and a wise use of them is expected. Therefore, today identification of CRT non-responders is a needed health care strategy. CRT FOR NYHA CLASS II-IV PATIENTS

5. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 Can mechanical dyssynchrony help to identify CRT non-responders? CRT FOR NYHA CLASS II-IV PATIENTS

6. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 After initial enthusiasm… CRT FOR NYHA CLASS II-IV PATIENTS

7. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 Intra-LVInter-ventricular Relative time Atrio-ventricular Global Segmental Δ time Δ time RV vs. LV pre-ejection; Doppler flow Δ time velocity onset, RV vs. LV; Pulsed TD Δ time hit the highest point velocity, RV vs. LV; Color TD LV filling time ÷ total cycle time; Doppler flow Global Segmental Time variability Global QRS to aortic valve opening; Doppler flow 2 segments 3 segments 4 segments 6 segments 8 segments: Peak velocity; Color TD 12 segments: Peak velocity; Color TD - Max deflection; M-mode - Peak velocity; Color TD - Velocity onset; Pulsed TD - Peak velocity; Color TD - Peak strain/strain rate; Color TD - Peak velocity; Color TD - Displacement peak; Color TD 16 segments: Ejection; 3D % basal segments with negative strain rate post aortic valve closure; Color TD Lateral wall contraction post aortic valve closure; Pulsed TD 12 segment std. dev. of time to peak velocity; Color TD Abbreviations: LV = left ventricular RV = right ventricular TD = tissue Doppler 6 segment std dev of strain ÷ mean strain; Color TD Time to peak strain coefficient of variation; custom application QRS to peak lateral wall deflection; M-mode QRS to peak velocity; Color coded, Color TD Absolute time Averaged peak displacement normalized to cardiac cycle length; custom application QRS to end of lateral wall contraction; Pulsed TD Qualitative 5 basal segment; Pulsed TD - Radial strain; Color TD The Babel (Dyssynchrony) Tower

8. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 Results of the Predictors of Response to CRT (PROSPECT) Trial Chung ES et al; Circulation 2008. Given the modest sensitivity and specificity in this multicenter setting despite training and central analysis, no single echocardiographic measure of dyssynchrony may be recommended to improve patient selection for CRT beyond current guidelines. Conv echo DTI

9. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 Does mechanical dyssynchrony evaluation still have a sense after the PROSPECT study? CRT FOR NYHA CLASS II-IV PATIENTS

10. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 BACK TO BASIC: LBBB DYSSYNCHRONY

11. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 SPECKLE-TRACKING ECHOCARDIOGRAPHY: Comprehensive assessment of myocardial deformation Longitudinal deformation Radial deformation Torsion Radial deformation Circumferential deformation Torsional deformation Apex Base LONGITUDINAL CIRCUMFERENTIAL RADIAL TORSION

12. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 RADIAL STRAIN DYSSYNCHRONY

13. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 normal dyssynchrony Novel Speckle-Tracking Radial Strain From Routine Black-and-White Echo Images to Quantify Dyssynchrony and Predict Response to CRT Suffoletto et al, Circulation 2006;113:960-968 6 mid-ventricle myocardial segments PREDICTIVE VALUE OF RADIAL STRAIN DYSSYNCHRONY

14. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 PREDICTIVE VALUE OF RADIAL STRAIN DYSSYNCHRONY Assessment of Left Ventricular Dyssynchrony by Speckle Tracking Strain Imaging Comparison Between Longitudinal, Circumferential, and Radial Strain in CRT Delgado V, JACC 2008 Radial Longitudinal Radial

15. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 Multicenter prospective study on 132 patients

16. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011

17. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 Usefulness of Echo Dyssynchrony in Pts with Borderline QRS duration to Assist With Selection for CRT Oyenuga et al, JACC Imaging 2010; 2:132-140 Borderline QRS=100-130 ms Cut-off130 ms strain

18. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 SPECKLE TRACKING ECHO FOR CARDIAC DYSSYNCHRONY ADVANTAGES OF THE SPECKLE TRACKING TECHNIQUE: Pathophysiologic sound (it assesses myocardial deformation, not motion or displacement) Correlates with MRI More accessible than MRI ADVANTAGES OF THE RADIAL DYSSYNCHRONY INDEX: Easy to apply Rapid Highly reproducible More predictive data compared with MRI

19. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 NORMALE ECOCARDIOGRAFIA 3D systolic dyssynchrony index 11,22% DISSINCRONO systolic dyssynchrony index 0,62%

20. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 Real-Time 3D Echo in Patient Selection for Cardiac Resynchronization Therapy Kapetanakis et al, JACC imaging 2011

21. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 The issue of LV scar burden CRT FOR NYHA CLASS III-IV PATIENTS

22. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 Effect of Posterolateral Scar Tissue on Clinical and Echocardiographic Improvement After CRT Bleeker et al - Circulation 2006;113:969-976 40 ischemic HF pts, NYHA class III-IV, LV-EF 35%, QRS>120 msec, LBBB Transmural scar: hyperenhancement 51-100% of LV wall thickness Contrast-enhanced MRI of a patient with transmural scar tissue in the posterolateral wall. Percentages of responders to CRT for 4 different patient categories based on the presence or absence of transmural posterolateral scar tissue (Scar+/Scar-) in combination with the presence or absence of baseline LV dyssynchrony 65 ms (Dys+/Dys-). Combined assessment of scar tissue and LV dyssynchrony is needed for best prediction of CRT response.

23. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 Leyva et al – Heart 2009;95:1619-1625 148 HF pts, NYHA class III-IV, LV-EF<35%, QRS120 msec Development and validation of a clinical index to predict survival after CRT DSC Index: Dyssynchrony, Scar (posterolateral location), Creatinine

24. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 Effects of global longitudinal strain and total scar burden on response to CRT in patients with ischaemic dilated cardiomyopathy DAndrea A et al. Eur J Heart F 2009; 11: 58-67 Average Global longitudinal strain (GLS) correlates closely with MRI total scar burden (r=0.64, P<0.001). GLS and radial intraventricular dyssynchrony were powerful independent determinants of response to CRT.

25. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011

26. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 The issue of LV pacing site CRT FOR NYHA CLASS III-IV PATIENTS

27. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011

28. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 Pacing a segment with peak radial strain amplitude <10% is associated with poor outcomes of CRT

29. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 LV PACING SITE RELATIVE TO SCAR LOCATION BY ECHOCARDIOGRAPHY Mele D et al, submitted Non responders Responders

30. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 The issue of LV contractile reserve CRT FOR NYHA CLASS III-IV PATIENTS

31. Azienda Ospedaliera Universitaria - Ferrara Roma 2010 Cut-offAutoreParametroEnd-point VALUTAZIONE DELLA RISERVA CONTRATTILE DEL VENTRICOLO SINISTRO Eco-stress con dobutamina a bassa dose Ciampi Q et al, Eur J Heart Fail 2009 Da Costa A et al, Heart Rhythm 2006 Ypenburg C et al, Am Heart J 2007 Tuccillo B et al, J Interv Card Electrophysiol 2008 LV-EF>7.5% ESV 15% a 6 mesi >25%LV-EF Riduzione eventi di scompenso cardiaco a 12,1 8,7 mesi ESV 15% a dopo 11 mesi (mediana) WMSI0.20 >25%LV-EF ESV 15% a 6 mesi Viareggio 2011

32. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 CONCLUSIONS

33. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 The response of the average patient to a therapy is not necessarily the response of the individual patient standing before the clinician (C Bernard, 1865). Identification of patients with highest probability of CRT response could allow allocate resources to those patients who can really benefit from the treatment. Cause of nonresponse to CRT is probably multifactorial: beyond dyssynchrony, factors related to the myocardial substrate play an important role (global scar burden, scar at pacing site and contractile reserve).

34. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 STEP I - VALUTARE LE INDICAZIONI ALL IMPIANTO (Classe IA) STEP II - VALUTARE LA PROBABILITA DI RISPOSTA A LUNGO TERMINE Eziologia non ischemica QRS>150 ms Blocco di branca sinistra Scarso scar burden totale (soprattutto nelle forme ischemiche) Conservata riserva contrattile globale (soprattutto nelle forme non ischemiche) Normale funzione renale Utile aggiungere la quantificazione della dissincronia meccanica se: QRS intermedio (120-150 msec) Blocco di branca destra Blocco di branca sinistra senza evidenza di bounce settale Indicazioni off-label (QRS stretto 35%) ALTA PROBABILITA DI RISPOSTA POSITIVA IN CLASSE NYHA III-IV Classe NYHA II-IV Terapia medica ottimizzata FE ventricolare sinistra 35% QRS>120 ms (classe NYHA III-IV) o >150 msec (classe NYHA II) Ritmo sinusale STEP III - IDENTIFICARE IL SITO DI PACING OTTIMALE Zona più ritardata e vitale (senza cicatrice transmurale) APPROCCIO A STEP PER LO STUDIO DEI CANDIDATI ALLA CRT

35. Azienda Ospedaliera Universitaria - Ferrara Napoli 2011 3D Speckle Tracking Echo: ONE STOP-SHOP APPROACH LV function Dyssynchrony (with torsion) Global scar burden Target zone characterization Contractile reserve