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Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Norwegian South East Health Authorities Introduction Identification of disease modification prior to implantation of Cardiac Resynchronization Therapy may help select the right patients, increase responder-rates and promote the utilization of CRT. We tested the hypothesis that shortening of time-to-peak left ventricular pressure rise (Td) with CRT is useful to predict long-term volumetric response (End-systolic volume (ESV) decrease >15%) to CRT. Methods Forty-five heart failure patients admitted for CRT implantation with a class I/IIa indication according to current ESC/AHA guidelines were included in the study. Td was measured from onset QRS at baseline and from onset of pacing with CRT. Results Baseline characteristics were mean age 63 ± 10 years , 71% males, NYHA class 2.5, 87% LBBB, QRS duration 173 ± 15ms, EF biplane 31 ± 1%, ESV 144 ± 12mL and end-diastolic volume 2044 ± 14mL. At 6-months follow-up six patients increased ESV by 5 ± 8%, while 37 responders (85%) had a mean ESV decrease of 40 ± 2%. Responders presented with a higher Td at baseline compared to non-responders (163 ± 4ms vs 119 ± 9ms, p Conclusions Td at baseline and the shortening of Td with CRT accurately identifies responders to CRT, with incremental value on top of current guidelines, in a population with already high response rates. Td carries the potential to become the marker for prediction of long-term volumetric response in CRT candidates. Abstract Figure.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Norwegian South East Health Authorities Introduction Resynchronization therapy effectively restores myocardial function. No measures exist that specifically quantifies resynchronization. A parameter that quantifies resynchronization should be able to detect effective resynchronization and should not respond to changes in contractility caused by heterometric regulation. Left ventricular pacing (LVP) is associated with dyssynchronous contraction patterns, while biventricular pacing (BIVP) promotes resynchronization dependent on the pacing position of the LV electrode. Purpose We compared the acute differences between BIVP and LVP with regards to the preload dependent maximum rate of the LV pressure rise (dP/dtmax), and time to peak dP/dt (Td) to determine which better reflect dyssynchrony and resynchronization. Methods Twenty nine patients in heart failure with LBBB underwent CRT implantation with continuous LV pressure registration. The LV lead was first placed in either apical or anterior position followed by a permanent placement in a lateral position. Sequential LVP and BIVP pacing were performed for one minute, at a rate 10% above intrinsic heart rate, before dP/dtmax measurements were recorded. For LVP, BIVP and RVP a patient specific AV delay was used to avoid fusion with intrinsic conduction. Td was defined as the time from pacemaker stimuli to peak dP/dt. Mixed linear models were used for statistics, numbers are estimated marginal means ± SEM and are only reported when with significance set at p Results We found no differences in dP/dtmax between BIVP (899 ± 37mmHg/s) and LVP (910 ± 37mmHg/s), while RVP (799 ± 37mmHg/s) was lower. Td was lower with BIVP (165 ± 4ms) than LVP (178 ± 4ms) and RVP (184 ± 4ms). We found no differences in dP/dtmax between lateral (890 ± 35mmHg/s) and anterior (874 ± 38mmHg/s) while apical (824 ± 38mmHg/s) was lower. Td was lower in lateral (171 ± 4ms) than in anterior (179 ± 4ms) and apical (182 ± 4ms) positions. BIVP in lateral position (158 ± 4ms) was lower than any other pacingmode*position, with BIVP*anterior at 173 ± 4ms) and LVP*lateral at 170 ± 2ms. No difference was seen in dP/dtmax between (BIVP + LVP)*(lateral + anterior) that was higher than all other pacingmode*positions. Conclusion Td shortens with BIVP and lateral position, and even more so with BIVP in lateral position and thus reflects resynchronization compared to all other combinations tested. DP/dtmax did not reflect resynchronization as BIVP/LVP and lateral/anterior performs equally good. There are no differences between dP/dtmax with any combination of pacing mode (BIVP + LVP) with position (anterior + lateral). This suggests that Td reflects resynchronization while dP/dtmax does not. Resynchronization with biventricular pacing in lateral position translates into a shorter Td and hence links electrical and mechanical events. Td could be the missing link between electrical and mechanical dyssynchrony and may serve as a biomarker for cardiac resynchronization therapy.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Norwegian South East heath Authorities Background We investigated the homeometric autoregulation utilizing a stepwise change in heart rate on dP/dtmax and time to peak dP/dt (Td) with biventricular pacing (BIVP) and the LV lead positioned in the apical, anterior and lateral positions. Pacing at low HR (LHR) and high heart rates (HHR) changes contractility through homeometric autoregulation (Bowditch effect) without changing the resynchronization itself. Purpose To determine the effect of a change in contractility through homeometric autoregulation on two different effect measures of resynchronization therapy. Methods Twenty-nine patients in heart failure with LBBB underwent CRT implantation with continuous LV pressure registration. The LV lead was first placed in either apical or anterior position followed by a permanent placement in a lateral position. Sequential BIVP pacing was performed for one minute, at a rate 10% above intrinsic heart rate (LHR = 75 ± 9bpm), before dP/dtmax measurements were recorded, and the sequence was repeated with pacing rate increased by 30% (HHR = 98 ± 11bpm). Td was defined as the time from pacemaker stimuli to peak dP/dt. Mixed linear models were used for statistics, numbers are estimated marginal means ± SEM. Significance was set at p Results DP/dtmax was higher with HHR in lateral position (1036 ± 41mmHg/s) than with LHR (933mmHg/s). The same was observed for all other lead positions. However, there was no difference between lateral position with LHR and apical position with HHR (930 ± 44mmHg/s). There were no differences in Td between LHR and HHR, but Td was shorter with BIVP in lateral position at pacing LHR (158 ± 4ms) and HHR (155 ± 4ms) than in all other positions. Overall dP/dtmax increased by 10% from LHR to HHR (888 ± 41mmHg/s vs. 980 ± 41 mmHg/s), while overall Td decreased by 2.4% from 168 ± 4ms to 164 ± 4ms. We found a linear relationship between Td and dP/dtmax (R = 0.7) with β=-0.07 that would indicate a 6ms reduction in Td going from LHR to HHR. The overall change in Td from LHR to HHR could therefore be attributed to the change in dP/dtmax. Conclusion Homeometric regulation does not influence Td, but Td is sensitive to changes in resynchronization and pacing lead position. Td is shorter with BIVP in lateral position at both high and low HR as would be expected from a biomarker of resynchronization. HR influences dP/dtmax so distinction between optimal and non-optimal positions using dP/dtmax may be difficult without knowledge of homeometric state.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Norwegian South-East Health Authorities Background We have investigated the timing of the peak left ventricular pressure rise, time to peak dP/dt (Td) as marker of resynchronization to be measured during implantation for detection of effective resynchronization. Td links the time domain (dyssynchrony) to the mechanical domain (pressure) as the dyssynergic muscular contractions resulting from electrical dyssynchrony delays pressure development and hence the timing of peak dP/dt, Td. Td shortens with resynchronization. Purpose In this study we investigated the acute changes in Td by comparing pacing the left ventricle (LV) with fusion of intrinsic right ventricular (RV) conduction (Adaptive, A) with pacing RV and LV (Non-Adaptive, NA), with and without multipoint pacing (MPP) and with different degrees of intraventricular pacing delays (RV-LV). Methods 19 patients with sinus rhythm and LBBB undergoing CRT implantation were studied. We measured pressures with an indwelling LV pressure catheter. Td was calculated as the time from onset of pacing to peak dP/dt, and averaged in 10 subsequent beats at each stage of pacing. We used quadripolar LV pacing leads positioned in what was considered an optimal mid/basal posterolateral/ lateral branch of the coronary sinus and sequential pacing (DDD) was performed; Adaptive and Non-Adaptive pacing was performed at LV distal [LVdist], proximal electrode [LVprox] and at both electrodes as multipoint pacing [MPP]. VV-timing: LV pacing was performed relative to QRS onset (either as a result of intrinsic activation or RV pace, mean ± SD): 1. LV only -76 ± 21ms before QRS activation with minimal fusion with RV activation (LVonly); 2. -28 ± 14ms before QRS activation (Pre); 3. 12 ± 15ms after (Post) QRS activation. Linear mixed models were used for statistics of the pooled data. Results are estimated marginal means ±SEM, and only significant P Results Average Td (data pooled) with RVP was 173 ± 2ms, MPP 144 ± 0.4ms and BIVP 150 ± 0.4ms. When analyzing the interaction between pacingmode (A,NA), VV-timing (LVonly,Pre,Post) and electrode(LVdist,LVprox,MPP) in all interventions we found that Td was shorter (p Conclusion Td shortens the most with LV MPP timed to near simultaneous intrinsic RV activation, indicating a beneficial mechanical effect from Adaptive MPP compared to standard biventricular pacing.

Aims A difficult cardiac resynchronization therapy (CRT) implantation scenario emerges when no lateral pacing option exists. The aim of this study was to explore the effect of biventricular pacing (BIVP) on vectorcardiographic parameters in patients with a non-lateral left ventricular (LV) lead position. We hypothesized that perimeter and area reduction for both the QRS complex and T-wave would predict acute CRT response. Methods and results Twenty-six patients (14 ischaemic) with a mean age of 63 ± 10 years and standard CRT indication underwent device implantation with continuous LV pressure registration. The LV lead was placed in either an anterior or apical position. Biventricular pacing was performed at a rate 10% above intrinsic rhythm with acute CRT response defined as LV ΔdP/dtmax >10%. Using this criterion 12 patients were identified as acute CRT responders (responders: 16.7 ± 4.8% vs. non-responders: 1.9 ± 5.3%, P