Cardiac Resynchronization Therapy in Non-Ischemic Cardiomyopathy: Role of Multimodality Imaging

Non-ischemic cardiomyopathy encompasses a heterogeneous group of diseases, with a generally unfavorable long-term prognosis. Cardiac resynchronization therapy (CRT) is a useful therapeutic option for patients with symptomatic heart failure, currently recommended by all available guidelines, with outstanding benefits, especially in non-ischemic dilated cardiomyopathy. Still, in spite of clear indications based on identifying a dyssynchronous pattern on the electrocardiogram (ECG,) a great proportion of patients are non-responders. The idea that multimodality cardiac imaging can play a role in refining the selection criteria and the implant technique and help with subsequent system optimization is promising. In this regard, predictors of CRT response, such as apical rocking and septal flash have been identified. Promising new data come from studies using cardiac magnetic resonance and nuclear imaging for showcasing myocardial dyssynchrony. Still, to date, no single imaging predictor has been included in the guidelines, probably due to lack of validation in large, multicenter cohorts. This review provides an up-to-date synthesis of the latest evidence of CRT use in non-ischemic cardiomyopathy and highlights the potential additional value of multimodality imaging for improving CRT response in this population. By incorporating all these findings into our clinical practice, we can aim toward obtaining a higher proportion of responders and improve the success rate of CRT.

Πρόβλεψη ανταπόκρισης στη θεραπεία καρδιακού επανασυγχρονισμού με υπερηχογραφικά κριτήρια σε ασθενείς με καρδιακή ανεπάρκεια

Ιστορικό: Η μη ανταπόκριση στη θεραπεία καρδιακού επανασυγχρονισμού (ΘΚΕ) παραμένει ένα ζήτημα, παρά τη βελτίωση των κριτηρίων επιλογής. Σκοπός της παρούσας μελέτης ήταν η διερεύνηση του ρόλου της ηχωκαρδιογραφίας για την επιλογή ασθενών που θα έχουν ανταπόκριση ή καθυστερημένη ανταπόκριση σε ΘΚΕ, χρησιμοποιώντας παραμέτρους δυσυγχρονισμού και εφαρμογές δυναμικής ηχωκαρδιογραφίας. Μέθοδοι: 106 ασθενείς με συμπτωματική καρδιακή ανεπάρκεια εξετάστηκαν πριν, 6 μήνες μετά και 2 έως 4 χρόνια μετά την εφαρμογή του ΘΚΕ. Η ινότροπη συστολική εφεδρεία (ΙΣΕ) και η βιωσιμότητα του οπισθίου τοιχώματος της αριστερής κοιλίας (ΟΤΑΚ) μελετήθηκαν με δυναμική ηχωκαρδιογραφία. Ο δυσυγχρονισμός εκτιμήθηκε με: 1) Καθυστέρηση κίνησης μεταξύ διαφραγματικού και οπισθίου τοιχώματος (Septal-to-posterior wall motion delay - SPWMD με m-mode 2) Καθυστέρηση μεταξύ διαφραγματικού και πλαγίου τοιχώματος (Septal to lateral wall delay -SLD) από το TDI 3) Διακοιλιακή μηχανική καθυστέρηση (Interventricular mechanical delay -IVMD) 4) Διαφορά στο χρόνο μέχρι τη μέγιστη κυκλοτερή παραμόρφωση (Difference in time to peak circumferential strain -TmaxCS) με ηχωκαρδιογραφία ιχνηλάτησης σημείων 5) «Ταλάντωση κορυφής» (Apical rocking - ApR) και «αναλαμπή μεσοκοιλιακού διαφράγματος» (septal flash - SF) με οπτική εκτίμηση. Αποτελέσματα: Σε έξι μήνες υπήρχαν 54 άτομα που ανταποκρίθηκαν, και δώδεκα επιπλέον άτομα είχαν καθυστερημένη ανταπόκριση. Το TmaxCS είχε τη μεγαλύτερη προγνωστική αξία, με μια περιοχή κάτω από την καμπύλη (AUC) 0,835, ακολουθούμενο από την συνδυασμένη παρουσία ΙΣΕ και βιωσιμότητας του ΟΤΑΚ (AUC 0,799), το m-mode (AUC = 0,775) και την παρουσία ApR ή/και SF (AUC = 0.772). Η προγνωστική ικανότητα του ApR και του ICR αυξάνεται εάν συμπεριληφθούν και τα άτομα με καθυστερημένη ανταπόκριση. Η απόδοση των παραμέτρων δυσυγχρονισμού ενισχύεται, σε ασθενείς με ΙΣΕ και βιωσιμότητα του ΟΤΑΚ. Συμπέρασμα: Η δυναμική ηχωκαρδιογραφία και οι παράμετροι δυσυγχρονισμού είναι απλοί και αξιόπιστοι δείκτες πρόβλεψης της απόκρισης στη ΘΚΕ, εντός 6μήνου ή καθυστερημένα. Μια σταδιακή προσέγγιση με μια αρχική εκτίμηση ΙΣΕ και βιωσιμότητας και, εάν αυτή είναι θετική, μια περαιτέρω ανάλυση δυσυγχρονισμού, θα μπορούσε να βοηθήσει στην λήψη αποφάσεων σε αμφιλεγόμενες κλινικά περιπτώσεις.

Low septal to lateral wall 18F-FDG ratio is highly associated with mechanical dyssynchrony in non-ischemic CRT candidates

Background In order to better understand the concept of mechanical dyssynchrony, a promising hallmark of cardiac resynchronization therapy (CRT) response, we investigated its effect on regional myocardial metabolism and myocardial blood flow (MBF) in non-ischemic CRT candidates. Results Thirty consecutive non-ischemic CRT eligible patients underwent static 18F-FDG and resting dynamic 13N-NH3 PET/CT. 18F-FDG uptake and MBF for septal and lateral wall were analysed and septal-to-lateral wall ratios (SLR) were calculated. Based on the presence of mechanical dyssynchrony (septal flash and/or apical rocking) on echocardiography, patients were divided into 2 groups, with (n = 23) and without (n = 7) mechanical dyssynchrony. Patients with mechanical dyssynchrony had significantly lower 18F-FDG SUVmean in the septum compared with the lateral wall (5.58 ± 2.65 vs 11.19 ± 4.10, p < 0.0001), while patients without mechanical dyssynchrony had a more homogeneous 18F-FDG distribution (7.33 ± 2.88 vs 8.31 ± 2.50, respectively, p = 0.30). Similarly, MBF was significantly different between the septal and lateral wall in the dyssynchrony group (0.57 ± 0.11 ml/g/min vs 0.92 ± 0.23 ml/g/min, respectively, p < 0.0001), whereas no difference was observed in the non-dyssynchrony group (0.61 ± 0.23 ml/g/min vs 0.77 ± 0.21 ml/g/min, respectively, p = 0.16). 18F-FDG SLR, but not MBF SLR, was associated with the presence of mechanical dyssynchrony and showed a significant inverse correlation with volumetric reverse remodeling after CRT (r = − 0.62, p = 0.001). Conclusions Non-ischemic heart failure patients with mechanical dyssynchrony demonstrate heterogeneous regional metabolism and MBF compared with patients without dyssynchrony. However, only 18F-FDG SLR appeared to be highly associated with the presence of mechanical dyssynchrony. Trial registration Clinicaltrials, NCT02537782. Registered 2 September 2015.

P5429Mechanical dyssynchrony has a higher predictive value for CRT response than different ECG-based definitions of LBBB

Background/Aim To investigate the value of baseline assessment of mechanical dyssynchrony (Dyss) in predicting response to cardiac resynchronization therapy (CRT) in comparison to the classic ECG definition of left bundle branch block (LBBB) (Classic-def) as well as the recently proposed Sex- based definition (Sex-def.). Methods The baseline ECGs of 194 patients (31% females, 39% with ischemic cardiomyopathy, mean QRS width 159±25 ms and mean LVEF 29±8%) were investigated for identifying the criteria of LBBB before CRT implantation. Classic-def., defined as notched or slurred QRS complex in at least two of the leads I, aVL, V1, V2, V5 and V6 with a total width of at least 120 ms in addition to the absence of Q wave in lead I, V5 and V6 was identified in 74% of the study population. Sex-def. was identified in 69%, which is a QRS duration of at least 140 and 130 ms for men and women respectively with otherwise the same criteria of the Classic definition. Dyss was defined as the presence of either apical rocking and/or septal flash in 2D echocardiography prior to implantation. Volumetric response to CRT was defined as a reduction of at least 15% of the LV-end systolic volume (ESV) at follow up echocardiography (12±6 months after device implantation). Results Patient with baseline Dyss showed the highest response rates (76%) with a sensitivity of 88%, a specificity of 63% and an area under the curve (AUC) of 0.76 (P<0.001) compared to 70% (sensitivity 82%, specificity 47%, AUC 0.65, P<0.01) in patients with Sex-def. and 65% (sensitivity 84%, specificity 40%, AUC 0.62, P=0.01) in patients with Classic-def. (Figure A). Pairwise comparisons showed that the accuracy of the Sex-def. did not differ significantly from the Classic-def. in response prediction (AUC=0.65 vs. 0.62 for Sex-def. vs. Classic-def. respectively, P=0.27). Alternatively, Dyss showed a significantly higher accuracy in predicting response to therapy (AUC=0.76) as compared to Sex-def. and Classic-def. (P=0.02 and <0.01 respectively, Figure B). Mech. dyssynchrony vs. ECG-based LBBB Conclusion The presence of Apical rocking and/or septal flash before CRT is associated with better response to CRT as compared to various ECG definitions of LBBB. Although a Sex-based definition of LBBB showed a trend of better response to CRT as compared to the Classic definition, it was not statistically significant.