Ruolo dell'imaging cardiaco per una corretta selezione dei pazienti candidati alla CRT Donato Mele

1. Ruolo dell'imaging cardiaco per una corretta selezione dei pazienti candidati alla CRT Donato Mele

2. LV dilatation no longer required compared to the 2007 ESC Guidelines.

4. CRT FOR NYHA CLASS II-IV PATIENTS • 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.

5. CRT FOR NYHA CLASS II-IV PATIENTS Can mechanical dyssynchrony help to identify CRT non-responders?

6. CRT FOR NYHA CLASS II-IV PATIENTS After initial enthusiasm…

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

8. 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. CRT FOR NYHA CLASS II-IV PATIENTS Does mechanical dyssynchrony evaluation still have a sense after the PROSPECT study?

10. BACK TO BASIC: LBBB DYSSYNCHRONY

11. SPECKLE-TRACKING ECHOCARDIOGRAPHY: Comprehensive assessment of myocardial deformation Longitudinal deformation Base LONGITUDINAL Circumferential deformation Radial deformation Radial deformation CIRCUMFERENTIAL • Torsion Apex Torsional deformation TORSION RADIAL

12. RADIAL STRAIN DYSSYNCHRONY

13. 6mid-ventricle myocardial segments PREDICTIVE VALUE OF RADIAL STRAIN 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 normal dyssynchrony

14. 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 Radial Longitudinal

15. Multicenter prospective study on 132 patients

17. 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 Cut-off≥130 ms strain Borderline QRS=100-130 ms

18. 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. ECOCARDIOGRAFIA 3D NORMALE DISSINCRONO systolic dyssynchrony index 11,22% systolic dyssynchrony index 0,62%

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

21. CRT FOR NYHA CLASS III-IV PATIENTS The issue of LV scar burden

22. Combined assessment of scar tissue and LV dyssynchrony is needed for best prediction of CRT response. 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 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-). Contrast-enhanced MRI of a patient with transmural scar tissue in the posterolateral wall.

23. Development and validation of a clinical index to predict survival after CRT Leyva et al – Heart 2009;95:1619-1625 148 HF pts, NYHA class III-IV, LV-EF<35%, QRS≥120 msec DSC Index: Dyssynchrony, Scar (posterolateral location), Creatinine

24. Effects of global longitudinal strain and total scar burden on response to CRT in patients with ischaemic dilated cardiomyopathy D’Andrea 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.

26. CRT FOR NYHA CLASS III-IV PATIENTS The issue of LV pacing site

28. Pacing a segment with peak radial strain amplitude <10% is associated with poor outcomes of CRT

29. LV PACING SITE RELATIVE TO SCAR LOCATION BY ECHOCARDIOGRAPHY Mele D et al, submitted Non responders Responders

30. CRT FOR NYHA CLASS III-IV PATIENTS The issue of LV contractile reserve

31. VALUTAZIONE DELLA RISERVA CONTRATTILE DEL VENTRICOLO SINISTRO Eco-stress con dobutamina a bassa dose Autore Parametro Cut-off End-point Riduzione eventi di scompenso cardiaco a 12,18,7 mesi Da Costa A et al, Heart Rhythm 2006 LV-EF >25% ESV ≥15% a 6 mesi Ypenburg C et al, Am Heart J 2007 LV-EF >7.5% ESV ≥15% a 6 mesi Tuccillo B et al , J Interv Card Electrophysiol 2008 LV-EF >25% ESV ≥15% a dopo 11 mesi (mediana) Ciampi Q et al, Eur J Heart Fail 2009 WMSI ≥0.20 Viareggio 2011

32. CONCLUSIONS

33. 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. APPROCCIO A STEP PER LO STUDIO DEI CANDIDATI ALLA CRT STEP I - VALUTARE LE INDICAZIONI ALL’ IMPIANTO (Classe IA) • 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 II - VALUTARE LA PROBABILITA’ DI RISPOSTA A LUNGO TERMINE ALTA PROBABILITA’ DI RISPOSTA POSITIVA IN CLASSE NYHA III-IV • 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” <120 msec, FE>35%) STEP III - IDENTIFICARE IL SITO DI PACING OTTIMALE • Zona più ritardata e vitale (senza cicatrice transmurale)

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