Standard Biventricular Pacing Research Articles

Association Between use of an Adaptive Cardiac Resynchronization Therapy Algorithm and Healthcare Utilization and Cost

To assess the association between use of adaptive pacing on clinical and economic outcomes of CRT recipients in a real-world analysis. The AdaptivCRTTM algorithm was shown in prior subgroup analyses of prospective trials to achieve clinical benefits, but a large prospective trial showed nonsignificant changes in the endpoint of mortality or heart failure hospitalizations. CRT-implanted patients from the Optum Clinformatics® database with ≥90 days of follow-up were included. Remote monitoring data was used to classify patients based on CRT setting - adaptive biventricular and left ventricular pacing (aCRT) vs. standard biventricular pacing (Standard CRT). Inverse probability of treatment weighting was used to adjust for baseline differences between groups. Mortality, 30-day readmissions, healthcare utilization, and payer and patient costs were evaluated post-implantation. This study included 2,412 aCRT and 1,638 Standard CRT patients (mean follow-up: 2.4 ± 1.4 years), with balanced baseline characteristics after adjustment. The aCRT group was associated with lower all-cause mortality (adjusted hazard ratio = 0.88 [95% confidence interval (CI):0.80, 0.96]), fewer all-cause 30-day readmissions (adjusted incidence rate ratio = 0.87 [CI:0.81, 0.94]), and fewer all-cause and HF-related inpatient, outpatient, and emergency department (ED) visits. The aCRT cohort was also associated with lower all-cause outpatient payer-paid amounts and lower all-cause and HF-related inpatient and ED patient-paid amounts. In this retrospective analysis of a large real-world cohort, use of an adaptive CRT algorithm was associated with lower mortality, reduced healthcare resource utilization, and lower payer and patient costs. While cardiac resynchronization therapy (CRT) improves quality of life and clinical outcomes for certain heart failure patients, some patients do not respond to this therapy. Adaptive CRT algorithms (aCRT), such as AdaptivCRTTM, have been developed with the goal of improving effectiveness of CRT, and consequently, clinical and economic outcomes. This research study used a large database of administrative claims data - which contains information on patient demographics, diagnoses, healthcare services received, mortality, and cost data - to compare clinical and economic outcomes between CRT patients with the aCRT algorithm turned on (aCRT group) and CRT patients with the aCRT algorithm turned off (standard CRT group). Statistical methods were used to adjust for baseline differences between the aCRT group and standard CRT groups. Ultimately, the aCRT group was found to have a lower risk of all-cause mortality, fewer all-cause 30-day readmissions, fewer hospital visits (including inpatient, outpatient, and emergency department visits), and lower costs to payers and patients for specific types of costs.

Effectiveness of dynamic atrioventricular optimization during patient exercise in cardiac resynchronization therapy

Abstract Background Cardiac resynchronization therapy (CRT) is considered the standard treatment for patients with heart failure and prolonged QRS duration. Recent studies suggest that atrioventricular delay (AVD) optimization can play a key role in QRS narrowing, thus improving CRT outcomes. For this purpose, device-based algorithms have been developed. In particular, the SyncAV algorithm continuously monitors the patient’s intrinsic AVD and dynamically adjusts the pacing AVD to allow fusion of the left ventricle pacing with intrinsic right ventricle depolarization. SyncAV optimization is usually performed in a single patient condition, i.e. at rest, and in a single operating scenario of the device, i.e. during atrial sensing. Purpose This study aims to compare QRS narrowing after AVD optimization using SyncAV in CRT-treated patients at rest, during moderate exertion, and during an increase in the atrial pacing rate. Methods This is a prospective, non-randomized, non-blinded, multicenter study. The study population consisted of patients in sinus rhythm, PR interval < 350 ms, and rest ventricular rate < 100 bpm. Within one month from the implant, patients were assessed for AVD optimization with SyncAV, selecting the offset (i.e. 10 to 40% AVD) that resulted in the shortest QRS duration (QRSd). Subsequently, patients performed moderate physical activity using a bicycle ergo-meter while a surface ECG was collected. QRSd was assessed once patients achieved a heart rate over 20 bpm to baseline heart rate, up to 100 bpm. Finally, QRSd narrowing was evaluated during a programmed increase in atrial pacing (i.e. >20 bpm of baseline atrial rate). Results Nine patients were treated with CRT and enrolled (age 67,3 ± 13,2 years; 66% male; LV ejection fraction 33,7±2,9 %; intrinsic QRSd 155,6 ± 12,7 ms) with intact atrioventricular conduction (PR interval 170,6±25,8 ms). The median SyncAV offset that provided the best QRSd reduction was 20 % (10 - 35%). Intrinsic QRSd was reduced to 132,7 ± 10,0 ms (-14,2±9,4%) with standard biventricular pacing and to 122,0 ± 11,2 ms (-21,2±8,5%) with SyncAV optimization. During exercise the mean heart rate was 88,1 bpm, the QRSd was reduced to 132,7 ± 10,0 ms (-14,2±9,4%) with standard biventricular pacing and to 124,9 ± 14,9 ms (-19,3±10,8 %) with SyncAV optimization. The mean heart rate during atrial pacing was 90 bpm with paced QRSd of 126,0 ±13,9 ms (-18,9±7,3% from baseline) with SyncAV optimization and paced PR interval of 198,2±22,7ms. Conclusion We evaluated the effectiveness of SyncAV for AVD optimization in out-of-clinic. This study demonstrates the possibility of narrowing the QRSd using SyncAV at several activity levels. Nevertheless, a deeper evaluation is needed to confirm our findings, investigating the SyncAV role in a larger population of patients.

Left Bundle Branch Optimized Implantable Cardioverter Defibrillator (LOT-ICD) implantation in a Patient with Myotonic Dystrophy

Left bundle branch (LBB) optimized implantable cardioverter defibrillator (LOT-ICD) is a recently emerged alternative to the standard biventricular pacing - ICD (BiVp-ICD). The IS-1 connector pin of the ICD lead was closed with a protective cap and the LBB pacing (LBBP) lead was inserted into the ICD generator at the ventricular P/S hole. Herein, we presented a myotonic dystrophy patient who underwent LOT-ICD device implantation because of a high degree of atrioventricular block and heart failure with mid-range ejection fraction. A DDD-ICD (DF-1) was implanted in our patient which has been attached to the atrial lead (RA hole), the LBBP lead (ventricular IS-1 hole), and the ICD lead (ventricular DF-1 hole). The IS-1 pin of the ICD lead was closed accordingly. The LOT-ICD should be considered an option to standard BiVp-ICD associated with lower cost, lower procedure time, and no phrenic nerve capture.

Feasibility study on cardiac resynchronization in the treatment of heart failure by single left bundle branch pacing

To examine the feasibility of single left bundle branch pacing for cardiac resynchronization therapy (CRT) by carrying out a frequency adaptive atrioventricular delay (RAAVD) algorithm and automatic optimization of the single left bundle branch pacing atrioventricular interval (AVI) based on the right atrioventricular interval (RAS–RVS). Thirty-six patients with CRT class Ia indications according to the European Society of Cardiology 2016 guidelines and implanted with RAAVD functional three-chamber pacemakers were prospectively enrolled in this study. Patients were divided into a single left bundle branch pacing group (n = 21) and a standard biventricular pacing group (n = 15). The optimization of the two groups was performed under standard cardiac colour Doppler ultrasound, followed by the comparison of the QRS width, cardiac function improvement, and echocardiography indicators. The ratio of AVI to the right atrial-right ventricular interval (RAS–RVS) after single LV pacing optimization was defined as the single left bundle branch pacing coefficient (LUBBPε). In comparison to the BVP, the QRS was significantly narrowed (P = 0.017), accompanied by a significantly increased proportion of patients with NYHA class I and II, as well as the 6MWT. Compared with standard biventricular pacing, LVEDD was significantly shortened (P = 0.045), accompanied by significantly improved LAD, AVVTI, EA distance/RR, IVMD, and TS-SD after the operation. RAS–RVS was 156 ± 33 ms, the optimized AVI was 102 ± 10 ms, and LUBBPε was calculated to be 0.66 ± 0.06. Depending on the LUBBPε, a three-chamber pacemaker with a single left bundle branch pacing system was developed based on RAS–RVS-optimized AVI automatically. A three-chamber pacemaker with single left bundle branch pacing can achieve CRT based on RAS–RVS, reaching the optimal AVI of 66% of RAS–RVS.

Comparative study of the effects of left ventricular and biventricular pacing on indices of cardiac function and clinical status of heart failure patients: preliminary results of READAPT study

Abstract Nonresponse to cardiac resynchronization therapy (CRT) has been related with right ventricular dysfunction. Preferential left ventricular pacing (pLVP) can overcome iatrogenic right ventricular dysfunction by achieving left ventricle resynchronization and by allowing for intrinsic activation of the right side, with ramifications extending beyond cardiac output and atrial fibrillation occurrence. Moreover, the AdaptivCRT® algorithm also automatically adjusts interventricular (V-V) delay every minute, optimizing it by means of comparing relative activation delay between right and left ventricles (electrically – driven optimization). In the present study we evaluated the effects of a pLVP algorithm on 50 heart failure patients (all Caucasians, 49% male; 66 +/- 8 years old; 46% ischemic cardiomyopathy; 41% diabetics; NYHA II-III) following randomization to standard biventricular pacing and pLVP, on echocardiographic and cardiopulmonary exercise test indices of functional status, as well as a self-reported quality of life questionnaire. Device programming was based on echocardiography-evaluated maximization of stroke volume and subsequent interventricular and atrioventricular delay adjustments delegated to the device. The follow-up consisted of 6 and 12-months visits; after the 1rst month of optimizing maximum CRT response. Results Significant comparative effects of LVP over optimized CRT were noted regarding RV systolic velocity in TDI even from 6-months from baseline (6% increase, p=0.01); while end-systolic diameter of left ventricle was increased by 4% in 6-months in CRT group (p=0.01), while no significant difference was observed in LVP group. At 12 months endsystolic volume was significantly decreased (16%, p=0.01) and left ventricular systolic longitudinal strain was improved in 12 months in LVP group compared to CRT group (p- for interaction =0.001). Additionally, in cardiorespiratory exercise test LVP group showed improved inotropic reserve compared to CRT group according to maximum SBP achieved (20% increase, p<0.01 for interaction); while all other cardiorespiratory indices shoed borderline significant changes at 12 -months. Minnesota score was significantly reduced in LV-P group by 70% at 6-months; whereas no significant change was observed in CRT group (p for interaction <0.01). Conclusions In the preliminary findings of READAPT study, it seems that LV pacing optimized by a standardized echocardiographic protocol in patients with preserved AV conduction, LBBB, can achieve a higher percentage of synchronized LV pacing associated with improved patient quality of life; right ventricular function and endsystolic volume at 6 and 12-months of follow-up, over echo-optimized CRT pacing.

CRT non-responder to responder conversion rate in the MORE-CRT MPP Trial.

To assess the impact of MultiPoint™ Pacing (MPP) in cardiac resynchronization therapy (CRT) non-responders after six months of standard biventricular pacing (BiVP). The trial enrolled 5,850 patients who planned to receive a CRT device. The echocardiography core laboratory assessed CRT response before implant and after six months of BiVP; non-response to BiVP was defined as < 15% relative reduction in left ventricular end-systolic volume (LVESV). Echocardiographic non-responders were randomized in a 1:1 ratio to receive MPP (541 patients) or continued BiVP (570 patients) for an additional six months and evaluated the conversion rate to the echocardiographic response. The characteristics of both groups at randomization were comparable. The percentage of non-responder patients who became responders to CRT therapy was 29.4% in the MPP arm and 30.4% in the BIVP arm (p=0.743). In patients with > 30 mm spacing between the two left ventricular pacing sites (MPP-AS), identified during the first phase as a potential beneficial subgroup, no significant difference in the conversion rate was observed. Our trial shows that approximately 30% of patients, who do not respond to CRT in the first six months, experience significant reverse remodeling in the following six months. This finding suggests that CRT benefit may be delayed or slowly incremental in a relevant proportion of patients and that the percentage of CRT responders may be higher than what has been described in short/middle-term studies. MPP does not improve CRT response in non-responders to BiVP, even with MPP-AS.

Implant failures in conduction system pacing: single centre experience

Abstract Funding Acknowledgements Type of funding sources: None. Background Conduction system pacing (CSP) ensures physiological ventricular activation and avoids the dyssynchrony associated with traditional myocardial pacing. New dedicated tools makes it possible to increase procedural success but not yet comparable to myocardial pacing. Objective Retrospective analysis of 3-years CSP implants, focusing on implant failures. Methods From January 2019 to June 2022, 639 CSP implant were performed (91% PMs and 9% ICDs). Single-chamber ICDs implants and devices replacements were excluded from the analysis because the conduction system pacing could not be an option in those cases. Pacing indications were standard with prevalence of AV block (51%); AF with slow ventricular rate 14.5%; sick sinus syndrome 14.5%; ablate&amp;pace 4%; heart failure or cardiomyopathy 14.5%, re-interventions after malfunction of a previous implant 1.5%. Mean age was 78±9 years; 62% were males. Results CSP was successfully achieved in 605 cases (94.6%). In 34 cases lead implant failed. Reasons for failure were "anatomical" in 15 cases (5 due to excessive right atrial enlargement, 5 due to severe pulmonary hypertension; 3 due to scar in the septum and 2 due to stenosis of the venous axis in upgrading procedure) and "technical" in 19 cases (5 due to unacceptable high thresholds, 10 due to uncorrected bundle branch block, 4 due to dislodgment during cutting without reposition). In 52% of the CSP implant failures, an underlying cardiomyopathy or heart failure were documented. Considering CSP failure, the implant was concluded with standard biventricular pacing in 18 cases (in 4 cases the coronary sinus implantation also failed) while 16 implants were concluded with the lead implanted in the septum or apex. Conclusions conduction system pacing is feasible in daily clinical practice; available tools allow to achieve high procedural success rate (94.8% implant success rate in our experience). Procedural failures were 5.2% and were caused by anatomical (44%) or technical reason (56%).

Comparison of myocardial depolarization spreading after resynchronization with left bundle branch area pacing versus biventricular pacing

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Left bundle branch area pacing (LBBAP) is an emerging new method of cardiac resynchronization therapy (CRT) in patients with left bundle branch block (LBBB). Studies comparing LBBAP with standard biventricular pacing (BiV) have shown similar post-operative shortening of QRS duration and left ventricular activation times. Calculation of equivalent dipole (ED) trajectories from 12-lead high-resolution ECG (hrECG) provides additional insight into myocardial depolarization and may be used for further assessment of left ventricular activation. Purpose The aim of this study was to determine myocardial depolarization patterns with assessment of ED trajectories in patients undergoing CRT with LBBAP or BiV and to compare them to myocardial depolarization patterns of healthy controls. Methods Twenty-five heart failure patients in sinus rhythm and LBBB with indication for CRT were randomized in LBBAP or BiV pacing group. Five-minute supine 12-lead hrECG recordings before and one month after implantation were assessed. LBBAP group was compared to BiV group and both groups were compared to the control of healthy subjects with normal surface ECG. The QRS duration was measured manually by two independent electrophysiologists and averaged. ED trajectories were constructed with the use of inverse algorithm method. The length of ED trajectory was defined as a line between the start and the end of the ED trajectory and its orientation with azimuth and elevation angles. (Figure 1). Results Eleven patients received LBBAP and 14 BiV. There were no differences in baseline characteristics (72% male, 64% non-ischemic cardiomyopathy) between groups. The average baseline QRS duration was 174±20 ms in LBBAP and 180±17 ms in BiV group (p=0.42). QRS duration decreased to 134±14 ms after LBBAP (p&amp;lt;0.01) and 137±11 ms after BiV pacing (p&amp;lt;0.01) and was comparable in both groups (p=0.59). There was also no difference in absolute (p=0.72) or relative (p=0.72) QRS shortening. The absolute and relative ED shortening did not differ (p=0.43 and p=0.38, respectively). At follow-up, analysis of ED trajectories showed a significant difference in elevation angle in both groups (p&amp;lt;0.01). The elevation angle in LBBAP group (6±30°) was significantly different from the angle in BiV group (-44±33°) (p &amp;lt; 0.01), pointing more toward apex of the heart (Figure 2). Furthermore, elevation angle in LBBAP was more similar (absolute difference 49°) to healthy subjects than the elevation angle in BiV group (absolute difference 103°) (p&amp;lt;0.01). There was no intergroup difference in azimuth angle (p=0.07). Conclusion Compared to BiV pacing, resynchronization with LBBAP produces significantly different ED trajectory orientation, which was more comparable to orientation in healthy controls. While both resynchronization methods result in similar QRS narrowing, LBBAP may provide more physiological depolarization of the left ventricle in comparison to BiV.

LB-456088-3 LEFT BUNDLE BRANCH AREA VERSUS CORONARY VENOUS LEAD PLACEMENT AS THE INITIAL IMPLANT STRATEGY FOR CARDIAC RESYNCHRONIZATION THERAPY - RESULTS FROM THE SYNCHRONY COLLABORATIVE GROUP

Left bundle branch area pacing (LBBAP) is a feasible alternative to standard biventricular pacing (BiVp) for cardiac resynchronization therapy (CRT). However, LBBAP has not been well studied as an initial implant CRT strategy.

B-PO03-190 COMPARISON OF ADAPTIVE AND NON-ADAPTIVE PACING MODES WITH BIVENTRICULAR STIMULATION ON TIME-TO-PEAK DERIVATIVE OF LEFT VENTRICULAR PRESSURE

Time-to-peak dP/dt (Td) is marker of mechanical 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 Td. Td shortens with resynchronization. In this study we investigated the acute changes in Td with standard BIVP and fusion with intrinsic conduction, single or multiple LV electrodes and different VV-intervals. 19 patients with sinus rhythm and LBBB undergoing CRT implantation were studied. We measured pressures with an indwelling LV pressure sensor 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 (A) and Non-Adaptive (NA) BIVP 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. Average Td (data pooled) with RVP was 173±2ms, MPP 144±0.4ms and BIVP 150±0.4ms. Analyzing pacingmode (A,NA), VV-timing (LVonly,Pre,Post) and electrode (LVdist,LVprox,MPP) we found that Td was shorter (p<0.01) with A(Post) for all electrode combinations [LVdist] 143±4ms, [LVprox] 140±4ms and [MPP] 134±4ms, while Td with A(Pre) was shorter with [MPP] 139±4ms only. NA(Post)[MPP] at 145±4ms and NA(Post)[LVdist] at 146±4ms provided the shortest Td (p<0.01) of the NA pacing modes, and Td with NA(Post)[MPP] was shorter (p<0.01) than all NA pacing modes. A(post)[MPP] provided the shortest Td of all (134±4ms, p<0.01). 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 modes.

Comparison of adaptive and non-adaptive pacing modes on time-to-peak dP/dt in multipoint pacing or standard biventricular pacing with different degrees of intraventricular fusion

Abstract 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 &amp;lt; 0.05 changes are reported. 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 &amp;lt; 0.01) with A(Post) for all electrode combinations [LVdist] 143 ± 4ms, [LVprox] 140 ± 4ms and [MPP] 134 ± 4ms, while Td with A(Pre) was shorter with [MPP] 139 ± 4ms only. A(post)[MPP] provided shorter Td than the other adaptive modes (p &amp;lt; 0.01). NA(Post)[MPP] at 145 ± 4ms and NA(Post)[LVdist] at 146 ± 4ms provided the shortest Td (p &amp;lt; 0.01) of the NA pacing modes, and Td with NA(Post)[MPP] was shorter (p &amp;lt; 0.01) than all NA pacing modes. 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.

P4529Atrioventricular optimization in cardiac resynchronization therapy with quadripolarleads, improves energy handling and quality of life in heart failure patients: HUMVEE Trial

Abstract Background Cardiac resynchronization therapy (CRT) is a well-established technique for symptomatic heart failure (HF) patients, producing significant clinical benefits. Recent studies have revealed the potential role of multipoint pacing (MPP) in improving response and clinical outcomes. The aim of Heart failUre study of Multisite pacing effects on VEntriculoartErial coupling (HUMVEE) trial was to evaluate the association between MPP of the left ventricle vs those of standard biventricular pacing (BVP) on: a) ventriculoarterial coupling (VAC) and energy efficiency of the failing heart, b) diastolic function, c) quality of life, and d) NT-proBNP levels. Methods HUMVEE is a single-center, prospective (13 months) trial (clinicaltrials.gov identifier NCT03189368), of 54 NYHA III patients (69±9 years; 79% men; 50% dilated cardiomyopathy), under optimal tolerated medical therapy, with standard BVP indication, having being implanted with a CRT system able to deliver both modes of pacing. Creatinine and NT-proBNP levels and echocardiographic measurements (VAC calculation, strain rate, diastolic function assessment), as well as 6-min-walking-test and quality of life (MLHF questionnaire) were measured at baseline, 6 months post BVP optimization (right before MPP activation) and at the end of follow-up (6 months post MPP optimization). Cardiac power (CP) was calculated according the equation: CP=Cardiac Output x Mean Aortic Pressure/451. Results Both CRT and MPP improved 6-min-walk (differences at baseline/6 mo/end of FU: 277±27 vs. 345±27 vs 363±27 m, p=0.07); left ventricular ejection fraction (24,2% vs 30,6%vs, 32%, p=0.05); end -diastolic diameters of left ventricle (65±1,4 vs. 63±1.7 vs. 61±1.1, p=0.03); end-systolic volume (150±15 vs. 140±10 vs. 131±13, p=0.08); stroke volume (41.6±9 vs. 53.6±14 vs. 62±9, p=0.0001 for MPP); left atrial volume (76±5 vs. 74±10 vs 61±6, p=0.001 for MPP), E/Emv (14±5 vs. 12±4 vs. 11±3, p=0.05 for MPP); NtproBNP (2782±1000 vs. 2080±2500 vs. 2000±1000, p=0.05 for MPP). VAC was reduced from 1.14±0.27 to 1.1±0.17 (p=0.1) while CP increased from 564.2±142 to 768±103 (p=0.009). Quality of life score (the lower the better) improved from 23.75±17 at baseline to 17.25±10 at end of FU (p=0.05). Conclusions MPP is a new, promising pacing modality with the potential to improve HF patients' outcome, offering additive effects on myocardial energy balance, cardiac power, systolic and diastolic ventricular function and aortoventricular coupling, especially in ischemic patients. HUMVEE trial illustrates those clinical, imaging and biochemical divergences of MPP from standard BVP that reflect significant improvement in quality of life in patients with advanced HF and cardiac dysychronization.

Adaptive cardiac resynchronization therapy is associated with decreased risk of incident atrial fibrillation compared to standard biventricular pacing: A real-world analysis of 37,450 patients followed by remote monitoring

The AdaptivCRT algorithm (aCRT) automatically adjusts atrioventricular delays each minute to achieve ventricular fusion through left ventricular (LV) or biventricular (BiV) pacing. aCRT is associated with superior clinical outcomes compared to standard BiV pacing, but the association of aCRT and subsequent atrial fibrillation (AF) in a real-world population has not been fully evaluated. The purpose of this study was to investigate the incidence of AF ≥48 hours with aCRT vs standard BiV pacing after implant. Patients implanted with a cardiac resynchronization therapy (CRT) device between 2013 and 2016 were studied via the de-identified Medtronic CareLink database. For univariate and multivariate survival analyses, Kaplan-Meier and Cox proportional hazards were used, respectively. Of 37,450 patients (mean age 69.1 ± 11.0 years; 67.9% male) followed for a mean 15.5 ± 9.1 months, 9.7% (n = 3647) developed ≥48 hours of AF. In univariate analysis, compared with standard BiV pacing, the aCRT BiV and LV mode was associated with a 54% lower risk of ≥48 hours of AF (P <.001) at 2 years, which persisted after multivariate adjustment (hazard ratio 0.53; 95% confidence interval 0.49-0.57; P <.001), even when stratified by sensed PR interval ≤200 ms and >200 ms. Higher percentages of LV-only pacing with aCRT were associated with lower incidence of AF (comparing >92% LV-only pacing vs 0%-5% LV-only pacing: HR 0.05; 95% CI 0.04-0.06; P <.001). In a large, real-world population of CRT recipients, aCRT pacing compared to standard BiV pacing was associated with a lower incidence of AF in patients with both long and short PR intervals. A higher percentage of LV-only pacing during aCRT was also associated with lower incidence of AF.

Eligibility of cardiac resynchronization therapy patients for subcutaneous implantable cardioverter defibrillators.

Before subcutaneous implantable cardioverter defibrillator (S-ICD) implantation, the adequacy of sensing is required to be verified through surface ECG screening. Our objective was to determine whether S-ICD can be considered as a supplementary therapy in patients who are receiving biventricular (BIV) pacing. We evaluated 48 patients with BIV devices to determine S-ICD candidacy during BIV, left ventricular (LV), right ventricular (RV) pacing, and intrinsic conduction (left bundle branch block-LBBB) by using an automated screening tool. Eligibility was defined by the presence of at least one appropriate vector in the supine and standing positions. Eligibility was verified during BIV pacing in 34 (71%) patients. In patients screened-out, QRS duration was longer (p= 0.035) and ischemic cardiomyopathy was more frequent (p= 0.027). LV-only pacing was associated with a lower passing rate (46%) (p< 0.001 versus BIV). The LBBB QRS morphology during inhibited ventricular pacing was acceptable in 51% of patients. The QRS generated by RV pacing was acceptable in 25% of patients. In patients who passed the screening test during BIV, the QRS was not acceptable in 76% during RV pacing (i.e., accidental loss of LV capture). The concomitant adequacy during inhibited ventricular pacing (i.e., possible intrinsic conduction) was not assessed in 40% of patients. S-ICD may be a supplemental therapy in the majority of CRT patients. Standard BIV pacing should be preferred to the LV-only pacing mode, as it is more frequently associated with adequacy of S-ICD sensing. Spontaneous LBBB and RV-paced QRS morphologies are frequently inadequate. Therefore, in patients selected for concomitant S-ICD and CRT implantation, accidental loss of LV capture or possible intrinsic conduction must be prevented.

Hemodynamic comparison of different multisites and multipoint pacing strategies in cardiac resynchronization therapies

PurposeIn order to increase the responder rate to CRT, stimulation of the left ventricular (LV) from multiple sites has been suggested as a promising alternative to standard biventricular pacing (BIV). The aim of the study was to compare, in a group of candidates for CRT, the effects of different pacing configurations—BIV, triple ventricular (TRIV) by means of two LV leads, multipoint (MPP), and multipoint plus a second LV lead (MPP + TRIV) pacing—on both hemodynamics and QRS duration.MethodsFifteen patients (13 male) with permanent AF (mean age 76 ± 7 years; left ventricular ejection fraction 33 ± 7%; 7 with ischemic cardiomyopathy; mean QRS duration 178 ± 25 ms) were selected as candidates for CRT. Two LV leads were positioned in two different branches of the coronary sinus. Acute hemodynamic response was evaluated by means of a RADI pressure wire as the variation in LVdp/dtmax.ResultsPer patient, 2.7 ± 0.7 veins and 5.2 ± 1.9 pacing sites were evaluated. From baseline values of 998 ± 186 mmHg/s, BIV, TRIV, MPP, and MPP-TRIV pacing increased LVdp/dtmax to 1200 ± 281 mmHg/s, 1226 ± 284 mmHg/s, 1274 ± 303 mmHg, and 1289 ± 298 mmHg, respectively (p < 0.001). Bonferroni post-hoc analysis showed significantly higher values during all pacing configurations in comparison with the baseline; moreover, higher values were recorded during MPP and MPP + TRIV than at the baseline or during BIV and also during MPP + TRIV than during TRIV. Mean QRS width decreased from 178 ± 25 ms at the baseline to 171 ± 21, 167 ± 20, 168 ± 20, and 164 ± 15 ms, during BIV, TRIV, MPP, and MPP-TRIV, respectively (p < 0.001).ConclusionsIn patients with AF, the acute response to CRT improves as the size of the early activated LV region increases.

Heart failure study of multipoint pacing effects on ventriculoarterial coupling: Rationale and design of the HUMVEE trial.

Cardiac resynchronization therapy (CRT) is an established therapy for symptomatic heart failure (HF). Unfortunately, many recipients remain nonresponders. Studies have revealed the potential role of multipoint pacing (MPP) in improving response and outcomes. The aim of this study is to compare the effects of MPP against those of standard biventricular pacing (BVP) on (i) ventriculoarterial coupling (VAC) and energy efficiency of the failing heart, (ii) diastolic function, (iii) quality of life, and (iv) NT-proBNP levels and glomerular filtration rate (GFR) during a follow-up of 13months. HUMVEE is a single-center, prospective, observational, crossover cohort study. Seventy-six patients with BVP indication will be implanted with a system able to deliver both pacing modes. BVP will be activated at implantation and optimized 1month after. At 6months postoptimization MPP will be activated and optimized. Optimization will be performed based on stroke volume maximization, as assessed by ultrasound. Laboratory measurements (GFR and NT-proBNP) and echocardiographic studies (VAC calculation, strain rate, diastolic function) will be performed at implantation, 6months post-BVP optimization and at the end of 13months of follow-up (6months post-MPP optimization). Potential reduction in arrhythmogenesis by MPP will also be assessed. MPP is a pacing modality with the potential to improve HF patients' outcomes. The HUMVEE trial will attempt to associate any potential added beneficial effects of MPP over standard BVP with alterations in VAC and energy efficiency of the heart, thus uncovering a novel mechanistic link between MPP and improved outcomes in HF.

Left Univentricular Pacing by Rate-Adaptive Atrioventricular Delay in Treatment of Chronic Heart Failure.

BackgroundCardiac resynchronization therapy (CRT) is efficacious in the treatment of chronic heart failure (CHF); however, because it is non-physiological, some patients are unresponsive. The present study used rate-adaptive atrioventricular delay (RAAVD) to track the physiological atrioventricular delay and investigated the effects of left univentricular pacing on CRT.Material/MethodsPatients with CHF fulfilling the indication of CRT Class I were categorized into a left univentricular pacing by RAAVD group and a standard biventricular pacing group. Preoperative and postoperative electrocardiography QRS duration, echocardiographic indicators, quality of life, cardiac function, and annual treatment cost were estimated. The standard deviation (RS/R-SD5) of the S/R ratio in lead V1 at 5 heart rate segments in the left univentricular pacing by RAAVD was calculated, and the accuracy of RAAVD in tracking the physiological AV delay was evaluated.ResultsThe comparison between the left univentricular pacing by RAAVD group and the standard biventricular pacing group after operation showed a significantly reduced QRS duration (137±11 vs. 144±11 ms, P<0.05), increased AVVTI (21.84±2.25 vs. 20.45±2.12 cm, P<0.05), reduced IVMD (64.27±12.29 vs. 71.39±13.64 ms, P<0.05), decreased MRA (3.09±1.12 vs. 3.73±1.19 cm2, P<0.05), and reduced average annual treatment cost (1.30±0.1 vs. 2.20±0.2 million Yuan, P<0.05). The RS/R-SD5 in the left univentricular pacing by RAAVD group was negatively correlated with improvements in cardiac function (r=−0.394, P=0.031).ConclusionsLeft univentricular pacing by RAAVD has treatment effects similar to those of standard biventricular pacing, and is an economically and physiologically effective method for biventricular systolic resynchronization in the treatment of CHF.

Rationale and design of a randomized trial to assess the safety and efficacy of MultiPoint Pacing (MPP) in cardiac resynchronization therapy: The MPP Trial.

Although the majority of Class III congestive heart failure (HF) patients treated with cardiac resynchronization therapy (CRT) show a clinical benefit, up to 40% of patients do not respond to CRT. This paper reports the design of the MultiPoint Pacing (MPP) trial, a prospective, randomized, double-blind, controlled study to evaluate the safety and efficacy of CRT using MPP compared to standard biventricular (Bi-V) pacing. A maximum of 506 patients with a standard CRT-D indication will be enrolled at up to 50 US centers. All patients will be implanted with a CRT-D system (Quartet LV lead Model 1458Q with a Quadra CRT-D, Abbott) that can deliver both MPP and Bi-V pacing. Standard Bi-V pacing will be activated at implant. At 3months postimplant, patients in whom the echocardiographic parameters during MPP are equal or better than during Bi-V pacing are randomized (1:1) to either an MPP or Bi-V arm. The primary safety endpoint is freedom from system-related complications at 9months. Each patient's response to CRT will be evaluated using a heart-failure clinical composite score, consisting of a change in NYHA functional class, patient global assessment score, HF events, and cardiovascular death. The primary efficacy endpoint is the proportion of responders in the MPP arm compared with the Bi-V arm between 3 and 9months. This trial seeks to evaluate whether MPP via a single quadripolar LV lead improves hemodynamic and clinical responses to CRT, both in clinical responders and nonresponders.

Left univentricular pacing for cardiac resynchronization therapy using rate-adaptive atrioventricular delay.

ObjectiveTo evaluate left univentricular (LUV) pacing for cardiac resynchronization therapy (CRT) using a rate-adaptive atrioventricular delay (RAAVD) algorithm to track physiological atrioventricular delay (AVD).MethodsA total of 72 patients with congestive heart failure (CHF) were randomized to RAAVD LUV pacing versus standard biventricular (BiV) pacing in a 1: 1 ratio. Echocardiography was used to optimize AVD for both groups. The effects of sequential BiV pacing and LUV pacing with optimized A-V (right atrio-LV) delay using an RAAVD algorithm were compared. The standard deviation (SD) of the S/R ratio in lead V1 at five heart rate (HR) segments (RS/R-SD5), defined as the “tracking index,” was used to evaluate the accuracy of the RAAVD algorithm for tracking physiological AVD.ResultsThe QRS complex duration (132 ± 9.8 vs. 138 ± 10 ms, P < 0.05), the time required for optimization (21 ± 5 vs. 50 ± 8 min, P < 0.001), the mitral regurgitant area (1.9 ± 1.1 vs. 2.5 ± 1.3 cm2, P < 0.05), the interventricular mechanical delay time (60.7 ± 13.3 ms vs. 68.3 ± 14.2 ms, P < 0.05), and the average annual cost (13,200 ± 1000 vs. 21,600 ± 2000 RMB, P < 0.001) in the RAAVD LUV pacing group were significantly less than those in the standard BiV pacing group. The aortic valve velocity-time integral in the RAAVD LUV pacing group was greater than that in the standard BiV pacing group (22.7 ± 2.2 vs. 21.4 ± 2.1 cm, P < 0.05). The RS/R-SD5 was 4.08 ± 1.91 in the RAAVD LUV pacing group, and was significantly negatively correlated with improved left ventricular ejection fraction (LVEF) (ΔLVEF, Pearson's r = −0.427, P = 0.009), and positively correlated with New York Heart Association class (Spearman's r = 0.348, P = 0.037).ConclusionsRAAVD LUV pacing is as effective as standard BiV pacing, can be more physiological than standard BiV pacing, and can decrease the average annual cost of CRT.

96-38: Intermediate and long term outcomes of permanent LV coronary sinus pacing without an RV lead- two LV leads may be better than one!

Purpose: Chronic LV pacing may be superior to RV pacing and the placement of an RV lead may result in damage to the tricuspid valve, particularly in the case of a prosthetic or repaired valve. The purpose of this study is to evaluate the safety and feasibility of permanent pacing the LV via the coronary sinus with one or two LV leads without the use of an RV pacing lead. Methods: Consecutive patients referred for permanent pacemaker placement following tricuspid replacement or repair and selected patients referred for complete heart block who did not fit the criteria for standard biventricular pacing at the time of implant were included in this series. Patients in the latter group were implanted in the pre-Block HF era. Patients who received a standard single or dual chamber pacemaker had a single bipolar left ventricular lead placed in a lateral branch of the coronary sinus. Patients receiving a biventricular pacemaker had a quadripolar left ventricular lead placed in a standard lateral branch of the coronary sinus and a second bipolar left ventricular lead placed in an anterior branch of the coronary sinus. All patients in sinus rhythm received an atrial lead positioned in the right atrial appendage. Patients were followed in the pacemaker clinic at 4 weeks post implant, three months and then every six months thereafter. We evaluated LV pacing thresholds at implant and on going success of pacing therapy. Results: Eleven patients, mean age 65.9 ± 3.8 SEM, were included in this study. Two patients were pacemaker dependent at the time of pacemaker implant. Four patients had a bioprosthetic tricuspid valve and one had undergone a tricuspid valve repair. One patient had severe tricuspid regurgitation following a previously implanted pacemaker and was status post extraction of the RV lead. Two patients had cardiomyopathies felt to be rate related and planned AV node ablations. One patient had severe left ventricular dysfunction immediately post aortic valve replacement. One patient had a dilated cardiomyopathy but an ejection fraction >35%. One patient had permanent atrial fibrillation and cardiomyopathy thought to be due to a rapid ventricular response whose LV function had normalized post implanted biventricular ICD and AV node ablation. This patient presented with an RV lead fracture and a chronic bipolar LV lead. Eight patients received a dual chamber pacemaker pulse generator (PG), 2 a biventricular PG and 1 a single chamber pacemaker. All patients underwent successful device implant and there were no peri-operative complications. LV pacing thresholds at implant were 1.8 ± 0.3 SEM Volts @ 0.5 msec in patients with a single LV lead and 0.7 ± 0.2 SEM Volts @ 0.5 msec in patients with two LV coronary sinus leads. One patient with a single LV lead required the addition of an RV lead at 10 months post implant due to diaphragmatic stimulation. One patient with a single LV lead experienced diaphragmatic pacing if pacing outputs were increased more than 1 volt above threshold. No other patients experienced any pacing related issues during a mean follow up of 22.6 ± 6.7 SEM months. Two patients met the criteria for a biventricular ICD a mean of 8 months post pacemaker implant and were upgraded. Conclusions: Intermediate to long term permanent pacing with only LV coronary sinus lead(s) and no RV lead is promising in terms of safety and feasibility. The use of a biventricular pulse generator with two LV leads including one quadripolar lead may result in lower pacing thresholds and more pacing vector options to avoid diaphragmatic pacing and requires further evaluation.