Volume 12, Issue 7, Pages (July 2015)

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Volume 12, Issue 7, Pages 1548-1557 (July 2015) His-bundle pacing versus biventricular pacing in cardiac resynchronization therapy patients: A crossover design comparison Daniel L. Lustgarten, MD, PhD, FHRS, Eric M. Crespo, MD, MPH, FHRS, Irina Arkhipova-Jenkins, MD, Robert Lobel, MD, Joseph Winget, MD, Jodi Koehler, MS, Evan Liberman, BS, Todd Sheldon, MS Heart Rhythm Volume 12, Issue 7, Pages 1548-1557 (July 2015) DOI: 10.1016/j.hrthm.2015.03.048 Copyright © 2015 Heart Rhythm Society Terms and Conditions

Figure 1 Protocol design summary including a description of the fate of the 29 enrolled patients. Full follow-up was obtained for 12 patients. Two patients normalized their QRS with His-bundle pacing (HBP), but their thresholds to achieve effect were >4.5 mV/1 ms and they were exited. †One of the 8 judged not to narrow at implant did, in fact, show evidence of QRS narrowing on subsequent offline analysis. BiV = biventricular pacing; LV = left ventricle. Heart Rhythm 2015 12, 1548-1557DOI: (10.1016/j.hrthm.2015.03.048) Copyright © 2015 Heart Rhythm Society Terms and Conditions

Figure 2 Six-month outcomes comparing His-bundle pacing (His) and biventricular pacing (BiV) responses. A: Ejection fraction was measured using the Simpson biplane method. B: New York Heart Association (NYHA) classification. C: Quality-of-life comparisons measured using the Minnesota Living with Heart Failure Questionnaire. D: Six-minute hall walk test. Differences between biventricular and His-bundle pacing were statistically not significant (P >.05). Error bars are the standard deviation. Heart Rhythm 2015 12, 1548-1557DOI: (10.1016/j.hrthm.2015.03.048) Copyright © 2015 Heart Rhythm Society Terms and Conditions

Figure 3 Six-month echocardiographic outcomes data. A, B: Biplane view was used to measure left ventricular (LV) volumes. C: Apical 4-chamber color Doppler measurements of mitral regurgitation (MR) jet area. D: Flow–velocity integral of the left ventricular outflow tract (LVOT) was measured using pulse wave. P values compare His-bundle pacing (His) and biventricular pacing (BiV) with baseline conduction. Differences between biventricular and His-bundle pacing were >.05 in each case. Error bars are the standard deviation. Heart Rhythm 2015 12, 1548-1557DOI: (10.1016/j.hrthm.2015.03.048) Copyright © 2015 Heart Rhythm Society Terms and Conditions

Figure 4 Pacing threshold summary. A: Capture thresholds and pulse widths at implant (Imp) and at 12 months for the His-bundle pacing (HBP), and right ventricular (RV) and left ventricular (LV) leads. B: Output required on the HBP lead to elicit maximal normalization of the QRS. Standard deviation bars are notably high in panel A for both the HBP and LV leads, in each case due to a single outlier (2 different patients) for which maximal output was required for capture. Error bars are the standard deviation. Heart Rhythm 2015 12, 1548-1557DOI: (10.1016/j.hrthm.2015.03.048) Copyright © 2015 Heart Rhythm Society Terms and Conditions

Figure 5 Electrophysiologic resynchronization. Standard surface precordial leads (25 mm/s sweep speed; top) and 12-lead surface leads and intracardiac electrograms (bottom) for each respective condition (200 mm/s). A: Native conduction with left bundle branch block, QRS duration 166 ms. Conduction time from His to lateral left ventricular (LV) wall is 225 ms. B: Pacing from the His-bundle pacing (HBP) lead at high output (8 V/1.5 ms). The change in morphology—more rapid dV/dt, axis normalization—are consistent with nonselective HBP with anteroseptal preexcitation pattern. The local ventricular electrogram on the octapolar catheter is coincident with and saturated by the stimulus artifact. LV timing is advanced by 100 ms. Note that because of local ventricular capture, the total QRS duration is similar to native conduction (160 ms) C: HBP output has been decreased to 4.25 V/1.5 ms. The surface ECG is now isoelectric from stimulus artifact to QRS onset, and QRS measures 125 ms. Septal ventricular activation now occurs well after the local stimulus artifact from the HBP lead, indicating selective HBP. Timing from His to LV activation remains advanced by 100 ms, proving re-engagement of the left fascicles dormant during native conduction. D: Further decrease in output (4 V/1.5 ms) results in native QRS morphology, coincident with return of His–LV timing to baseline (225 ms: selective HBP without QRS normalization). DHBL = actively fixed HBP lead from which pacing is being performed in panels B–D; His d to His 4 = bipolar leads on the octapolar His catheter in the His position (anteroseptal); LV = left ventricular lead in a lateral coronary sinus branch. Heart Rhythm 2015 12, 1548-1557DOI: (10.1016/j.hrthm.2015.03.048) Copyright © 2015 Heart Rhythm Society Terms and Conditions

Figure 6 Acute hemodynamic effect of His-bundle pacing (HBP) with QRS normalization: The top 6 tracings are precordial leads (25 mm/s) with femoral arterial pressure tracing at the bottom. A: First 3 QRSs are from AAI pacing, rate 80. Highlighted portion and arrow show the switch to DDD-HBP, 80 bpm. With slight offset the femoral arterial tracing increases, on average about 10 mm Hg (red arrow on left). B: Opposite switch (DDD-HBP to AAI, 80 bpm) results in an equivalent decrease in femoral arterial pressure (red arrow on right). These changes were sustained and reproducible. Heart Rhythm 2015 12, 1548-1557DOI: (10.1016/j.hrthm.2015.03.048) Copyright © 2015 Heart Rhythm Society Terms and Conditions

Figure 7 Vector-dependent fascicular capture. Each panel shows the precordial surface leads for 3 conditions. Left: Patient’s native conduction with left bundle branch block (LBBB), QRS duration 160 ms. Middle: High-output His-bundle pacing with nonselective capture (NS-HBP) and overall morphology nearly identical to native conduction. Right: Bipolar pacing with His lead tip cathodal and left ventricular (LV) tip anodal (device programmed in “bipolar” mode hence “bipolar HBP”). QRS narrows markedly with precordial R-wave progression, consistent with early left fascicular activation. The absence of R wave in V1 indicates the absence of LV free-wall anodal capture. The patient’s ejection fraction improved from 20% to 35% after 6 months of bipolar HBP. Heart Rhythm 2015 12, 1548-1557DOI: (10.1016/j.hrthm.2015.03.048) Copyright © 2015 Heart Rhythm Society Terms and Conditions