Επιλογή ασθενών για θεραπεία καρδιακού επανασυγχρονισμού με εκτίμηση δυσυγχρονισμού και τη χρήση δυναμικής ηχωκαρδιογραφίας με δοβουταμίνη. Ε. Πουλιδάκης1, Κ. Αγγέλη2, Σ. Σιδερής2, Ι. Φελέκος2, Ε. Σφενδουράκη2, Ι. Κουτάγιαρ2, Κ. Πολυτάρχου1, Ε. Γιαννούλης1, M. Κούκος1, Ε. Μαργιούλα1, Ν. Ντόκας1, Σ. Λιάπης1, Κ. Λιόντου1, Κ. Τριανταφύλλου1, Π. Διλαβέρης2, Κ. Γκαντζούλης2, Κ. Κάππος1, Α.Σ. Μανώλης2, Χ. Στεφανάδης2, Δ. Τούσουλης2  1Γενικό Νοσοκομείο Αθηνών «Ο Ευαγγελισμός» 2Γενικό Νοσοκομείο Αθηνών «Ο Ιπποκράτειο»

Survival after CRT

Reverse remodeling after CRT Auricchio A, Prinzen FW. Circulation Journal Vol.75, March 2011

Response rate

Echo for CRT candidate selection

New echo approaches Speckle tracking echocardiography (STE) Septal flash (SF) Apical rocking (ApR) Low dose Dobutamine Stress Echocardigraphy (LD-DSE) (Real time 3 Dimensional Echocardiography)

Speckle tracking Echo Gray-scale based technique Angle-independent comprehensive assessment of myocardial deformation Identifies speckles and then tracks them frame-by-frame Bansal M, Kasliwal RR. Indian heart journal 2013

Septal Flash – Apical Rocking Stankovic I et al. European Heart Journal – Cardiovascular Imaging (2016) 17, 262–269

Predictive value of SF and ApR Stankovic I et al. European Heart Journal – Cardiovascular Imaging (2016) 17, 262–269

Kloosterman M. et al

Auricchio A, Prinzen FW. Circulation Journal Vol.75, March 2011

Late responders

Purpose of the study Investigate the role of for the identification of LD-DSE (for ICR and viability) along with simple and easy to use dyssynchrony parameters for the identification of responders or late responders to CRT. 

Inclusion Criteria Adult patients referred for CRT Heart failure NYHA II-IV Fulfilling CRT indications at the time of the enrolment: EF<35% QRS>120ms (130) OMT Exclusion criteria Recent revascularisation Reversible cause of HF Enrollment 1/2011 – 12/2013

Protocol Before CRT Right after CRT 6 months 2-4 years Clinical assessment √ - NYHA class ECG EF / LV volumes Dyssynchrony ICR – Viability 6MWT MLHFQ

Dysynchrony Assessment & LD-DSE Septal to posterior wall motion delay (SPWMD) Opposing wall delay by TDI Intraventricular dyssynchrony Time to peak circumferential strain by STE Septal flash and Apical Rocking Inotropic contractile reserve Viability of the posterolateral wall

Septal to posterior wall motion delay Parasternal long-axis M-mode cursor at the midventricular level TDI enabled Identify the time delay from peak inward septal motion to peak inward posterior wall. Reported cut-off value of ≥130ms (252ms)

Opposing wall delay by TDI Optimized 2D imaging – A4C Position the LV cavity in the center of the sector and aligned as vertically as possible Set the depth to include the level of the mitral annulus Activate color TD Place regions of interest in the basal of opposing LV walls Determine time from onset of the QRS complex to the peak systolic velocity for each region Reported cut-off value of >65-100ms

Interventricular dyssynchrony Assessed as the interventricular mechanical delay (IVMD) time from QRS onset to the onset of LV ejection versus RV ejection measured as the onset of pulsed Doppler flow velocities in the LV and RV outflow tracts A5C and PSAX (aortic valve level) views Reported cut-off value of >40-50ms

Time to peak circumferential strain by STE PSAX – papillary muscles level Region of interest by tracking the endocardial and epicardial border 6 standard segments Time to peak circumferential strain Dyssynchrony defined as difference in earliest and latest segment (TmaxCS) Reported cut-off value of ≥130ms for radial strain

Septal flash and Apical Rocking The presence of ApRock and SF was visually assessed pre-implantation. A4C view and PLAX m-mode respectively All readings were initially performed by two readers. Stankovic I et al. European Heart Journal – Cardiovascular Imaging (2016) 17, 262–269

Patient Chart 123 screened 5-> withdrew consent 4-> received ICD only 1-> died before implantation 5->unsuccessful LV lead implantation 1->died during hospitalization 1-> CRT suspended due to proarrhythmia 106 patients

Study Population Demographics Age (y) 66.7 ± 9.8 Male/Female 84 / 22 Ischemic /Non-ischemic 62 / 44 NYHA (class) II-IV LVEF (%) 28± 7.8 ECG & Treatment LBBB 64 (60.4%) B-blockers 99 (94.3%) ACEIs/ARBs 100 (93.3%) MRA 89 (83.9%) Diuretic 101 (95.3%) Risk factors HTN 32 (30.2%) DM 19 (17.9%) Smoking 13 (12.2%) Dyslipidemia 31 (29.2%) FH 22 (20.7%) Comorbidities CKD 24 (22.6%) COPD 10 (9.4%) STROKE/TIA PAD 6 (5.6%)

Outcomes 74 (69.8%) had clinical improvement (in NYHA) 54 (50.9%) classified as responders (-15%LVESV) 12 (11.3%) additional late responders 2 patients died within 6 months 10 non-responders died after the initial follow up Parameter Baseline 6month FU NYHA 2.5 ± 0.7 1.8 ± 0.9 QRS 152 ± 33.8 136.5 ± 22.6 EF 28 ± 7.8 35 ± 9.8 LVESV 133.6 ± 49.7 115.6 ± 50.3 6MWT 318.5±116.4 367.7±142.6 MLHFQ 33 ± 14.3 26.1 ± 14.4

Predictive ability Test AUC Cutoff Sens% Spec% QRS 145 81.5 50 LBBB 0.597 145 81.5 50 LBBB 0.658 75.9 55.8 Intra 0.543 37.5 42.3 Inter 0.655 26.5 64.8 67.3 SPWMD 0.775 158 57.4 98.1 Strain 0.835 53.5 87 71.2 ApR 0.709 63 78,8 SF 0.736 82.7 ApR/SF 0.772 83.3 ICR 0.768 19.7 96.3 69.2 Viability 0.587 19.2 ICR+Viab 0.799 94 65.4

Predictive ability Late Responders Clinical Improvement Test AUC QRS 0,514 LBBB 0,603 Intra 0,482 Inter 0,634 SPWMD 0,761 Strain (TmaxCS) 0,83 ApR 0,72 SF 0,652 ApR/SF 0,754 ICR 0,791 Viability 0,617 ICR+Viability 0,802 Test AUC QRS 0,433 LBBB 0,619 Intra 0,466 Inter 0,612 SPWMD 0,645 Strain (TmaxCS) 0,754 ApR 0,715 SF 0,614 ApR/SF 0,726 ICR 0,788 Viability 0,649 ICR+Viability 0,81

Predictive ability of dyssynchrony in those with both ICR & Viability Absence of either ICR and IL wall viability had a negative predictive value of 94,4% If these patients are excluded from the analysis, the performance of dyssynchrony parameters is enhanced Test AUC QRS 0,669 LBBB 0,645 Intra 0,454 Inter 0,664 SPWMD 0,855 Strain (TmaxCS) 0,916 AR/SF 0,874

Discussion Results, in general, consistent with the literature Selected indices are widely used and easily implemented We compared the predictive value of LD-DSE in identifying CRT responders with that of multiple commonly used echo modalities and indices Our study also addresses the issue of late response to CRT

Limitations Number of patients Rather low percentage of responders Strain in one axis

Conclusion LD-DSE and dyssynchrony parameters outperformed ECG criteria for CRT patient selection. A stepwise approach with an initial assessment of ICR and viability in CRT candidates and further dyssynchrony analysis, in those with both ICR>20% and viable IL wall, could help decision making for possible CRT in equivocal cases. TmaxCS, SPWMD, ApR and SF, are simple and reliable predictors of CRT response.

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