Left Ventricular Stimulation Research Articles

Adaptive versus conventional cardiac resynchronisation therapy in patients with heart failure (AdaptResponse): a global, prospective, randomised controlled trial

Continuous automatic optimisation of cardiac resynchronisation therapy (CRT), stimulating only the left ventricle to fuse with intrinsic right bundle conduction (synchronised left ventricular stimulation), might offer better outcomes than conventional CRT in patients with heart failure, left bundle branch block, and normal atrioventricular conduction. This study aimed to compare clinical outcomes of adaptive CRT versus conventional CRT in patients with heart failure with intact atrioventricular conduction and left bundle branch block. This global, prospective, randomised controlled trial was done in 227 hospitals in 27 countries across Asia, Australia, Europe, and North America. Eligible patients were aged 18 years or older with class 2-4 heart failure, an ejection fraction of 35% or less, left bundle branch block with QRS duration of 140 ms or more (male patients) or 130 ms or more (female patients), and a baseline PR interval 200 ms or less. Patients were randomly assigned (1:1) via block permutation to adaptive CRT (an algorithm providing synchronised left ventricular stimulation) or conventional biventricular CRT using a device programmer. All patients received device programming but were masked until procedures were completed. Site staff were not masked to group assignment. The primary outcome was a composite of all-cause death or intervention for heart failure decompensation and was assessed in the intention-to-treat population. Safety events were collected and reported in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02205359, and is closed to accrual. Between Aug 5, 2014, and Jan 31, 2019, of 3797 patients enrolled, 3617 (95·3%) were randomly assigned (1810 to adaptive CRT and 1807 to conventional CRT). The futility boundary was crossed at the third interim analysis on June 23, 2022, when the decision was made to stop the trial early. 1568 (43·4%) of 3617 patients were female and 2049 (56·6%) were male. Median follow-up was 59·0 months (IQR 45-72). A primary outcome event occurred in 430 of 1810 patients (Kaplan-Meier occurrence rate 23·5% [95% CI 21·3-25·5] at 60 months) in the adaptive CRT group and in 470 of 1807 patients (25·7% [23·5-27·8] at 60 months) in the conventional CRT group (hazard ratio 0·89, 95% CI 0·78-1·01; p=0·077). System-related adverse events were reported in 452 (25·0%) of 1810 patients in the adaptive CRT group and 440 (24·3%) of 1807 patients in the conventional CRT group. Compared with conventional CRT, adaptive CRT did not significantly reduce the incidence of all-cause death or intervention for heart failure decompensation in the included population of patients with heart failure, left bundle branch block, and intact AV conduction. Death and heart failure decompensation rates were low with both CRT therapies, suggesting a greater response to CRT occurred in this population than in patients in previous trials. Medtronic.

The last shall be the first: the role of combined QLV- and CMR-determined electromechanical concordance in predicting optimal left ventricular stimulation site in cardiac resynchronisation therapy

Abstract Funding Acknowledgements Type of funding sources: None. Background/introduction Optimisation of cardiac resynchronisation therapy (CRT) response still represents a significant challenge to cardiac electrophysiology. In this regard, perhaps the area of greatest uncertainty revolves around optimal left ventricular lead (LVL) position and in particular whether this should be directed at areas of latest electrical or mechanical activation given the equivocal evidence on their precise relationship in heart failure (HF) patients. Furthermore, while echocardiography has demonstrated that LVL aimed at regions of greatest mechanical delay maximises CRT response, cardiac magnetic resonance (CMR) with its greater spatial resolution and tissue definition is yet to demonstrate a role in doing so. Purpose To retrospectively evaluate concordance between latest electrical and CMR-determined mechanical activation in a CRT population and its relationship with reverse remodeling. Methods This is a retrospective single center analysis of 104 CRT patients. All patients had CMR and echocardiography performed before implantation. During implantation, coronary sinus angiogram was performed and electrical delay (QLV time with RV-LV time greater than 80 ms) was mapped on all veins suitable for lead implantation and LVL was positioned in the region of latest electrical activation programming LVL cathode accordingly. LVL cathode position was thus assumed to represent the region of latest electrical delay. A post-hoc analysis was then conducted by means of CART-Tech® software providing radial strain and scar maps on a 36-segment anatomical model. Patients were then stratified based on concordance between LVL cathode position (using 3D heart models superimposed on 2D angiography images) and most mechanically delayed segments (either the three most delayed segments or adjacent ones) or non concordance (one or more segments between LVL cathode and three most mechanically delayed segments). Data from patient follow-up was collected with echocardiography at least 3 months after implant date. CRT response was expressed as reduction in end-systolic volume (ESV) greater than 15%. Results A preliminary analysis of the first 30 patients of our cohort was conducted. Electromechanical concordance and non-concordance were present in 24 and 6 patients, respectively. Baseline patient characteristics including demographics, comorbidities, HF aetiology, ECG and echocardiography features were comparable between groups except for scar burden, which was higher in the non-concordance group. Response to CRT was 80% in the concordant vs. 20% in the non-concordant group. Conclusions While a confounding effect of scar burden cannot be excluded, these preliminary data suggest that electromechanical concordance in LVL cathode placement may represent a predictor of optimal CRT response. The full scope of this study will be fully appreciated in the coming month on completion of analysis of the entire patient cohort.

PO-04-194 PROGNOSTIC SIGNIFICANCE OF ELECTROPHYSIOLOGIC TESTING FOR VENTRICULAR ARRHYTHMIAS IN PATIENTS WITH MITRAL ANNULAR DISJUNCTION

Mitral annular disjunction (MAD), with or without mitral valve prolapse (MVP), is associated with a higher risk of ventricular arrhythmias (VA) and sudden cardiac death. The prognostic significance of VA inducibility during electrophysiological studies (EPS) in patients with MAD is unclear. To assess the prognostic significance of VA inducibility in patients with MAD undergoing EPS. We included 21 patients with MAD and no history of sustained VAs who underwent EPS for risk stratification. Patients who underwent ablation of any VA during the same procedure were excluded. EPS protocol included programmed ventricular stimulation with up to triple extrastimuli and with burst pacing from 2 ventricular sites. Post-EPS events including sustained VAs, appropriate implantable-cardioverter defibrillator (ICD) shocks, and sudden death, were assessed according to the EPS results. Mean age at the time of EPS was 46±16 years, and 15 (71.4%) patients were female. Mean MAD length was 10±4 mm. 18 (85.7%) patients had MVP (bileaflet MVP in 15 patients and posterior MVP in 3 patients). Non-sustained ventricular tachycardia (NSVT) was induced in 2 (9.5%) patients, sustained monomorphic ventricular tachycardia (VT) in 4 (19%) patients, and ventricular fibrillation (VF) in 9 (42.9%) patients, while six (28.6%) patients had no inducible VAs. 10 (47.6%) patients underwent ICD implantation due to inducible sustained VT (n=4) or VF (n=6), while 5 (23.8%) patients received an implantable loop recorder (ILR). After a median follow-up of 18.9 months, 4 (19%) patients had incident sustained VT or VF, all among patients with an ICD. These events occurred in 2 of the 4 patients with inducible VT and 2 of the 9 with inducible VF, while no events occurred in those with inducible NSVT or no inducible VAs. Inducible sustained VT or VF at EPS did not demonstrate a statistically significant association with incident sustained VAs (p=0.13). No deaths occurred in any patients in this series. More than half of patients with MAD referred for risk stratification EPS had inducible sustained VT or VF. Inducibility of VT/VF was not statistically associated with incident sustained VAs though this analysis is limited by the small sample size. Larger prospective studies are needed to clarify the role of EPS with standardized protocols in the risk stratification of patients with MAD, including investigation of the value of right and left ventricular stimulation.

A rapid wide complex tachycardia

A rapid wide complex tachycardia

Proarrhythmic effect of bipolar epicardial left ventricular stimulation in CRT resolved maintaining biventricular pacing with unipolar-cathodical configuration: A peculiar case report.

The effect of cardiac resynchronization therapy (CRT) on the risk of ventricular arrhythmias is controversial. Several studies reported a decreased risk, but some studies reported a potential proarrhythmic effect of epicardial left ventricular pacing resolved upon discontinuation of biventricular pacing (BiVp). A 67-year-old woman with a history of heart failure due to nonischemic cardiomyopathy and left bundle branch block was hospitalized for CRT device implantation. Unpredictably, as soon as the leads have been connected to the generator, an electrical storm (ES) occurred with relapsing self-resolving polymorphic ventricular tachycardia (PVT) triggered by ventricular extra beats with short-long-short sequences. The ES was resolved without interrupting BiVp switching to unipolar left ventricular (LV) pacing. This allowed to keep CRT active with extreme clinical benefit for the patient and to demonstrate that the cause of the PVT was the anodic capture of bipolar LV stimulation. Reverse electrical remodeling was also demonstrated after 3 months of effective BiVp. Proarrhythmic effect of CRT is a rare but significant complication of CRT, and it may compel to discontinuation of the BiVp. The reversal of the physiological transmural activation sequence of epicardial LV pacing and subsequent prolonging of corrected QT interval have been speculated as the most probable explanation, but our case highlights the possibility that the anodic capture may play a relevant role in PVT genesis.

539 GOING BEYOND CRT NON-RESPONSE: ECHO-GUIDED LEFT BUNDLE-BRANCH PACING

Abstract We present the case of a 56-year-old man affected by heart failure (HF) with reduced ejection fraction (HFrEF) and permanent atrial fibrillation, who previously underwent a CRT-D implant with left ventricular stimulation delivered by an epicardial pacing lead due to an unfavourable CS anatomy. We upgraded this system to left bundle branch pacing. The LBB lead was connected to the atrial plug in of the device in order to deliver multisite left ventricular pacing. The device was programmed in DDDR mode and the delay between the two LV pacing sites was chosen (modifying atrioventricular delay) after multimodality assessment (both electrocardiographic and echocardiographic) to obtain the best resynchronization and systolic performance.

Abstract 12821: Progressive Improvement in Left Ventricular Performance Associated With Progressive Regional Dyssynchrony

Background : We have shown that non-excitatory epicardial stimulation (NES) increases measures of cardiac function mediated by local release of norepinephrine. In this further investigation we determined whether NES is accompanied by improved indices of left ventricular (LV) performance, reflected in PV loops and timing of aortic valve opening and closing. Methods : Anesthetized pigs (n=6) were instrumented with a LV high-fidelity pressure/volume conductance transducer, thoracic aortic pressure transducer, left atrial (LA)/ LV epicardial electrodes, and sonomicrometer segment length (SL) gauges placed proximal (lateral base) and distal (posterior mid LV) to the LV stimulation site. During constant LA pacing, LV pulses (0.8ms, 2-3x threshold volts) were applied during the absolute refractory period for 3 minutes (3x), before and after β-receptor blockade (BB, metoprolol). Data were analyzed at baseline, and at an estimated 30%, 60% and 100% of developed ventricular dyssynchrony (DVD) contraction pattern. Results: Consistent with earlier findings, NES resulted in an early shortening and relaxation pattern of the proximal SL manifest as an 80% decrease in the LVP vs. SL loop area in the absence of change in the remote segment. This was accompanied by an increase in peak systolic pressure and LV dP/dt max. Although NES did not change the area of the LVP vs. LV volume loop (stroke work) or alter the interval from LV electrical activation (R wave) to the onset of LV pressure increase, aortic valve opening occurred up to 14.1 ± 2.8 ms earlier (p <0.01) compared to baseline. The duration of an open aortic valve slightly increased (6.0 ± 3.9 ms) whereas ejection duration from valve opening to peak Pao decreased 18.2 ± 3.0 ms (p < 0.01). Conclusion : These findings demonstrate that NES elicits a local contractile dysynchrony resulting in an enhanced cardiac inotropic state characterized by more rapid global LV contraction with earlier aortic valve opening with no change in stroke work.

Endocardial pacing is not haemodynamically superior to trans-coronary sinus epicardial pacing in cardiac resynchronization therapy: the Endo-Epi CRT study

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Medtronic Background Cardiac resynchronization therapy (CRT) conventionally involves trans-coronary sinus, epicardial left ventricular (LV) pacing. Some studies have suggested that endocardial LV pacing may be superior to epicardial LV pacing. Objectives To compare the acute haemodynamic effects of CRT when delivered from endocardial (Endo-CRT) and epicardial LV stimulation sites (Epi-CRT). Methods and results Sixteen CRT recipients (aged 70.4 ± 10.1 years [mean ± SD], 62.5% male, QRS: 156.5 ± 16.1 ms, LBBB in 13 [81.3%]) in sinus rhythm underwent intra-procedural measurements of the rate of rise of LV pressure (dP/dtmax) during Endo- and Epi-CRT (RADI pressure wire). Epi-CRT was delivered in basal, mid and apical positions. The Endo-CRT pacing site was chosen using iterative, biplane fluoroscopic views, to target the same position as the Epi-CRT site on the endocardium (see Figure A). Compared to AAI pacing (10 beats per minute above intrinsic rate), both Endo-CRT and Epi-CRT led to an increase in LV dP/dtmax (6.52 ± 8.90% and 6.15 ± 7.97% respectively, both p < 0.001). There were no significant differences in the change in LV dP/dtmax (ΔLV dP/dtmax) between Endo-CRT and Epi-CRT at basal (p = 0.54), mid (p = 0.78) or apical LV stimulation sites (p = 0.12) [Figure B]. Conclusions Endo-CRT is not haemodynamically superior to Epi-CRT. Abstract Figure.

Feasibility of intraprocedural integration of cardiac CT to guide left ventricular lead implantation for CRT upgrades.

BackgroundOptimal positioning of the left ventricular (LV) lead is an important determinant of cardiac resynchronization therapy (CRT) response.ObjectiveEvaluate the feasibility of intraprocedural integration of cardiac computed tomography (CT) to guide LV lead implantation for CRT upgrades.MethodsPatients undergoing LV lead upgrade underwent ECG‐gated cardiac CT dyssynchrony and LV scar assessment. Target American Heart Association segment selection was determined using latest non‐scarred mechanically activating segments overlaid onto real‐time fluoroscopy with image co‐registration to guide optimal LV lead implantation. Hemodynamic validation was performed using a pressure wire in the LV cavity (dP/dtmax)).Results18 patients (male 94%, 55.6% ischemic cardiomyopathy) with RV pacing burden 60.0 ± 43.7% and mean QRS duration 154 ± 30 ms underwent cardiac CT. 10/10 ischemic patients had CT evidence of scar and these segments were excluded as targets. Seventeen out of 18 (94%) patients underwent successful LV lead implantation with delivery to the CT target segment in 15 out of 18 (83%) of patients. Acute hemodynamic response (dP/dtmax ≥ 10%) was superior with LV stimulation in CT target versus nontarget segments (83.3% vs. 25.0%; p = .012). Reverse remodeling at 6 months (LV end‐systolic volume improvement ≥15%) occurred in 60% of subjects (4/8 [50.0%] ischemic cardiomyopathy vs. 5/7 [71.4%] nonischemic cardiomyopathy, p = .608).ConclusionIntraprocedural integration of cardiac CT to guide optimal LV lead placement is feasible with superior hemodynamics when pacing in CT target segments and favorable volumetric response rates, despite a high proportion of patients with ischemic cardiomyopathy. Multicentre, randomized controlled studies are needed to evaluate whether intraprocedural integration of cardiac CT is superior to standard care.

Left Ventricular Stimulation With Electrical Latency Predicts Mortality in Patients Undergoing Cardiac Resynchronization Therapy.

This study sought to evaluate the prognostic value of the time interval from left ventricular (LV) pacing to the earliest onset of QRS complex (S-QRS) for long-term clinical outcomes in patients who underwent cardiac resynchronization therapy (CRT). The electrical latency during LV pacing evaluated by S-QRS is associated with local tissue property, and the S-QRS ≥37ms has been previously proposed as an independent predictor of mechanical response to CRT. This study included 82 consecutive patients with heart failure with reduced LV ejection fraction (≤35%) and a wide QRS complex (≥120ms) who underwent CRT. Patients were divided into a short S-QRS group (SS-QRS;<37ms) and a long S-QRS group (LS-QRS;≥37ms). The primary endpoint was total mortality, including LV assist device implantation or heart transplantation, whereas the secondary endpoint was total mortality or HF hospitalization. S-QRS was 25.9 ± 5.3ms in SS-QRS and 51.5 ± 13.7ms in LS-QRS (p<0.01), and baseline QRS duration and electrical activation at the LV pacing site (i.e., Q-LV) were similar. During mean follow-up of 44.5 ± 21.1months, 24patients (29%) reached the primary endpoint, whereas the secondary endpoints were observed in 47 patients (57%). LS-QRS had significantly worse event-free survival for both endpoints. LS-QRS was an independent predictor of total mortality (hazard ratio: 2.6; 95% confidence interval: 1.11 to 6.12; p=0.03) and the secondary composite events (hazard ratio: 2.4; 95% confidence interval: 1.31 to 4.33; p<0.01). The S-QRS ≥37ms at the LV pacing site was a significant predictor of total mortality and HF hospitalization. S-QRS-guided optimal LV lead placement is critical in patients who receive CRT.

Time interval from left ventricular stimulation to QRS onset is a predictor of mortality in patients with cardiac resynchronization therapy

Abstract Introduction In our previous report, the time interval from left ventricular (LV) pacing to the earliest onset of QRS (S-QRS interval) has been found to be an independent predictor of mechanical response to cardiac resynchronization therapy (CRT). The S-QRS interval may indicate the conduction disturbance relevant to the localized tissue property such as scar or fibrotic lesion. Therefore, S-QRS interval longer than 37ms was associated with poor response to CRT, and proposed as suboptimal LV lead position. Then, we hypothesized that the longer S-QRS interval at the LV pacing site could be related to long term mortality and heart failure events in patients with CRT. Methods This retrospective study included 82 consecutive heart failure patients with sinus rhythm, reduced LV ejection fraction (≤35%), and a wide QRS complex (≥120ms), who undergone CRT implantation between 2012 January and 2017 December. Patients were divided into Short S-QRS group (&amp;lt;37ms, SS-QRS) and Long S-QRS group (≥37ms, LS-QRS) according to the previously reported optimal cut off value. A responder was defined as one with ≥15% reduction in LV end-systolic volume assessed by echocardiography at 6 months after CRT. The primary endpoint was total mortality, which included LV assist device implantation or heart transplantation. The secondary endpoints included the composite endpoint of total mortality or heart failure hospitalization. Results The study patients were divided into SS-QRS (N=43, age 65.9±13.2 years, 77% male) and LS-QRS (N=39, age 63.0±13.4, 85% male). In the electrocardiographic measurements, there were no significant differences in baseline QRS duration (162.4±30.3ms in SS-QRS vs. 154.5±31.6ms in LS-QRS, P=0.19) and LV local activation time assessed as Q-LV interval (118.3±34.3ms in SS-QRS vs. 115.3±32.0ms in LS-QRS, P=0.71). S-QRS interval was 25.9±5.3ms in SS-QRS and 51.5±13.7ms in LS-QRS (P&amp;lt;0.01), and the responder rate was significantly higher in SS-QRS compared with LS-QRS (79% vs. 29%, P&amp;lt;0.01). During mean follow up of 47.7±22.4 months, 24 patients (29%) reached to the primary endpoint, while the secondary endpoints were observed in 47 patients (57%). LS-QRS patients had significantly worse event-free survival for both primary and secondary endpoints (Figure). After the multivariate Cox regression analysis, LS-QRS (≥37ms) was an independent predictor of total mortality (HR=2.6, 95% CI: 1.11 to 6.12, P=0.03) and the secondary composite events (HR=2.4, 95% CI: 1.31 to 4.33, P&amp;lt;0.01). Conclusion The S-QRS interval longer than 37ms, which may reflect the conduction disturbance relevant to the scar or fibrotic lesion at the LV pacing site, was a significant predictor of the total mortality and heart failure hospitalization. These findings have implications for the optimal LV lead placement in patients with CRT device. Clinical outcomes according to S-QRS Funding Acknowledgement Type of funding source: None

Cathodic-anodal left ventricular stimulation during cardiac resynchronization therapy: haemodynamic evaluation and electrocardiographic analysis

Abstract Background Cardiac resynchronization therapy (CRT) is an established treatment for heart failure with reduced ejection fraction (HFrEF). However, one third of patients are “non responders”. Cathodic-anodal (CA) left ventricle (LV) capture is a multisite pacing occurring during CRT using both bipolar and quadripolar LV lead. It allows depolarization to arise simultaneously from the cathode and the anode of the bipole located on the LV epicardium, activating a larger volume of myocardium than cathodal pacing alone, thus potentially improving electromechanical synchrony (figure 1). We have previously proven that CA-LV stimulation is feasible and similar to bicathodic multipoint pacing (MPP) in terms of QRS wavefront activation. Purpose We aimed to evaluate both the acute intraprocedural haemodynamic and electrical effects of CA biventricular stimulation (CA-BS), comparing it with right-ventricle only pacing (Right Ventricle-Stimulation: RV-S), single-point CRT (Single Point-Biventricular Stimulation: SP-BS) and multipoint bicathodic biventricular stimulation (Multi Point-Biventricular Stimulation:MP-BS) in de novo CRT implants. Methods Ten patients candidates to CRT (LV ejection fraction ≤35% and left bundle branch block) received a quadripolar LV lead. Four pacing configurations were tested: RV-S, SP-BS, MP-BS and CA-BS, where cathode and the anode were the same electrodes used as cathodes in MP-BS. QRS duration by 12-lead ECG was defined as the time from the earliest ventricular deflection until the return to the isoelectric line. Haemodynamic assessment by radial artery catheterization using Pressure Recording Analytical Method processed the following parameters: dP/dT max (mmHg/msec), systolic arterial pressure (aPsys, mmHg), diastolic arterial pressure (aPdia, mmHg), mean arterial pressure (aPmean, mmHg), Cardiac Index (CI, l/min/m2), Stroke Volume Index (SVI, ml/min/m2). Results dP/dT max and aPmean increased significantly from RV-S to SP-BS (mean dP/dT max 0,82±0,28 versus 0,87±0,29 mmHg/msec, p=0,02; mean aPmean 89±19 versus 93±20 mmHg, p=0,01), but not from RV-S to MP-BS. Comparing RV-S to CA-BS, only aPmean exhibited a significant increase (mean aPmean 89±19 versus 92±20 mmHg, p=0,01). There were no haemodynamic differences between SP-BS, MP-BS and CA-BS. QRS duration reduced significantly from RV-S (167±10 msec) to each biventricular stimulation (135±14 msec, p=0,0002 for SP-BS; 130±17 msec, p=0,0001 for MP-BS; 129±18 msec, p=0,0002 for CA-BS) and from SP-BS to MP-BS and CA-BS (p=0,03 for both), whereas there were no difference comparing MP-BS and CA-BS. Conclusions CA-LV stimulation is not superior to single-point CRT in terms of acute haemodynamic performance, whereas it reduces the duration of ventricular electrical activation, showing an electrohaemodynamic mismatch. Long-term studies are needed to evaluate if acute electrical benefits of CA stimulation can predict chronic benefits, in terms of reverse cardiac remodelling. Cathodic-anodal left ventricular capture Funding Acknowledgement Type of funding source: None

Left Ventricular Enlargement, Cardiac Resynchronization Therapy Efficacy, and Impact of MultiPoint Pacing.

Left ventricular (LV) epicardial pacing results in slowly propagating paced wavefronts. We postulated that this effect might limit cardiac resynchronization therapy efficacy in patients with LV enlargement using conventional biventricular pacing with single-site LV pacing, but be mitigated by LV stimulation from 2 widely spaced sites using MultiPoint pacing with wide anatomic separation (MPP-AS: ≥30 mm). We tested this hypothesis in the multicenter randomized MPP investigational device exemption trial. Following implant, quadripolar biventricular single-site pacing was activated in all patients (n=506). From 3 to 9 months postimplant, among patients with available baseline LV end-diastolic volume (LVEDV) measures, 188 received biventricular single-site pacing and 43 received MPP-AS. Patients were dichotomized by median baseline LVEDV indexed to height (LVEDVIMedian). Outcomes were measured by the clinical composite score (primary efficacy end point), quality of life, LV structural remodeling (↑EF >5% and ↓ESV 10%) and heart failure event/cardiovascular death. LVEDVIMedian was 1.1 mL/cm. Baseline characteristics differed in patients with LVEDVI>Median versus LVEDVI≤Median. Among patients with LVEDVI>Median, biventricular single-site pacing was less efficacious compared to patients with LVEDVI≤Median (clinical composite score, 65% versus 79%). In contrast, MPP-AS programming generated greater clinical composite score response (92% versus 65%, P=0.023) and improved quality of life (-31.0±29.7 versus -15.7±22.1, P=0.038) versus biventricular single-site pacing in patients with LVEDVI>Median. Reverse remodeling trended better with MPP-AS programming. In patients with LVEDVI>Median, heart failure event rate increased following the 3-month randomization point with biventricular single-site pacing (0.0150±0.1725 in LVEDVI>Median versus -0.0190±0.0808 in LVEDVI ≤Median, P=0.012), but no heart failure event occurred in patients with MPP-AS programming between 3 and 9 months in LVEDVI>Median. All measured outcomes did not differ in patients receiving MPP-AS and biventricular single-site pacing with LVEDVI≤Median. Conventional biventricular single-site pacing, even with a quadripolar lead, has reduced efficacy in patients with LV enlargement. However, the greatest response rate in patients with larger hearts was observed when programmed to MPP-AS pacing.

Left ventricular paced activation in cardiac resynchronization therapy patients with left bundle branch block and relationship to its electrical substrate.

BackgroundCardiac resynchronization therapy (CRT) uses left ventricular (LV) pacing to restore rapid synchronized LV activation when it is delayed in patients with myocardial disease.ObjectiveAlthough intrinsic LV activation delays are understood, little is known about reactions to LV stimulation and whether they are affected by QRS duration (QRSd), morphology, LV substrate, or choice of electrode pair. The purpose of this study was to test these interactions.MethodsIn 120 heart failure patients with left bundle branch block (LBBB) and QRS >120 ms receiving CRT with quadripolar LV leads, device-based measurements of intrinsic activation delay (qLV) and paced inter- (and intra-) LV conduction times were evaluated at the proximal and distal LV bipoles.ResultsDuring intrinsic conduction, qLV varied little between the proximal and distal pairs in patients with LBBB (n = 120; age 68 ± 11 years; 63% male; ejection fraction 25% ± 7%; 33% ischemic cardiomyopathy; QRSd 162 ± 19 ms). A minority (30%) had conduction barriers (ie, gradients) (ΔqLV 29 ± 8 ms vs 9 ± 5 ms in patients without gradients; P <.01), which occurred equally in ischemic and nonischemic patients. A majority were functional (and not scar-mediated), as they resolved with pacing in most patients (75%). Importantly, LV-paced conduction times were unrelated to baseline QRS morphology (LBBB 166 ± 30 ms vs RBBB control 172 ± 30 ms; P = NS), longer than intrinsic conduction (166 ± 30 ms vs 129 ± 28 ms; P <.01), and varied significantly by electrode pair (ie, small distances) and etiology. Correlation between intrinsic activation delay (qLV) and LV-paced conduction time was poor (R2 = 0.278; P <.05).ConclusionLV-paced effect, which is core to CRT, is unpredictable based on conventionally used measures and should be considered during CRT optimization.

Ablation of Reentry-Vulnerable Zones Determined by Left Ventricular Activation From Multiple Directions: A Novel Approach for Ventricular Tachycardia Ablation: A Multicenter Study (PHYSIO-VT).

The optimal method to identify the arrhythmogenic substrate of scar-related ventricular tachycardia (VT) is unknown. Sites of activation slowing during sinus rhythm (SR) often colocalize with the VT circuit. However, the utility and limitations of such approach for guiding ablation are unknown. We conducted a multicenter study in patients with infarct-related VT. The left ventricular (LV) was mapped during activation from 3 directions: SR (or atrial pacing), right ventricular, and LV pacing at 600 ms. Ablation was applied selectively to the cumulative area of slow activation, defined as the sum of all regions with activation times of ≥40 ms per 10 mm. Hemodynamically tolerated VTs were mapped with activation or entrainment. The primary outcome was a composite of appropriate implanted cardioverter-defibrillator therapies and cardiovascular death. In 85 patients, the LV was mapped during activation from 2.4±0.6 directions. The direction of LV activation influenced the location and magnitude of activation slowing. The spatial overlap of activation slowing between SR and right ventricular pacing was 84.2±7.1%, between SR and LV pacing was 61.4±8.8%, and between right ventricular and LV pacing was 71.3±9.6% (P<0.05 between all comparisons). Mapping during SR identified only 66.2±8.2% of the entire area of activation slowing and 58% critical isthmus sites. Activation from other directions by right ventricular and LV stimulation unmasked an additional 33% of slowly conducting zones and 25% critical isthmus sites. The area of maximal activation slowing often corresponded to the site where the wavefront first interacted with the infarct. During a follow-up period of 3.6 years, the primary end point occurred in 14 out of 85 (16.5%) patients. The spatial distribution of activation slowing is dependent on the direction of LV activation with the area of maximal slowing corresponding to the site where the wavefront first interacts with the infarct. This data may have implications for VT substrate mapping strategies.

Left Ventricular Rapid Pacing Via the Valve Delivery Guidewire in Transcatheter Aortic Valve Replacement

ObjectivesThis study investigated whether left ventricular (LV) stimulation via a guidewire-reduced procedure duration while maintaining efficacy and safety compared with standard right ventricular (RV) stimulation. BackgroundRapid ventricular pacing is necessary to ensure cardiac standstill during transcatheter aortic valve replacement (TAVR). MethodsThis is a prospective, multicenter, single-blinded, superiority, randomized controlled trial. Patients undergoing transfemoral TAVR with a SAPIEN valve (Edwards Lifesciences, Irvine, California) were allocated to LV or RV stimulation. The primary endpoint was procedure duration. Secondary endpoints included efficacy, safety, and cost at 30 days. ResultsBetween May 2017 and May 2018, 307 patients were randomized, but 4 were excluded because they did not receive the intended treatment: 303 patients were analyzed in the LV (n = 151) or RV (n = 152) stimulation groups. Mean procedure duration was significantly shorter in the LV stimulation group (48.4 ± 16.9 min vs. 55.6 ± 26.9 min; p = 0.0013), with a difference of –0.12 (95% confidence interval: –0.20 to –0.05) in the log-transformed procedure duration (p = 0.0012). Effective stimulation was similar in the LV and RV stimulation groups: 124 (84.9%) versus 128 (87.1%) (p = 0.60). Safety of stimulation was also similar in the LV and RV stimulation groups: procedural success occurred in 151 (100%) versus 151 (99.3%) patients (p = 0.99); 30-day MACE-TAVR (major adverse cardiovascular event-transcatheter aortic valve replacement) occurred in 21 (13.9%) versus 26 (17.1%) patients (p = 0.44); fluoroscopy time (min) was lower in the LV stimulation group (13.48 ± 5.98 vs. 14.60 ± 5.59; p = 0.02), as was cost (€18,807 ± 1,318 vs. €19,437 ± 2,318; p = 0.001). ConclusionsCompared with RV stimulation, LV stimulation during TAVR was associated with significantly reduced procedure duration, fluoroscopy time, and cost, with similar efficacy and safety. (Direct Left Ventricular Rapid Pacing Via the Valve Delivery Guide-wire in TAVR [EASY TAVI]; NCT02781896)

Lead choice in cardiac implantable electronic devices: an Italian survey promoted by AIAC (Italian Association of Arrhythmias and Cardiac Pacing)

ABSTRACTBackground: Few data are available regarding lead preferences of electrophysiologists during cardiac implantable electronic devices (CIEDs) implantation. Aim of this survey is to evaluate the leads used, and the reasons behind these choices, in a large population of implanters.Methods: A questionnaire was sent to all 314 Italian centers with experience in CIED implantation.Results: 103 operators from 100 centers (32% of centers) responded. For atrium, passive leads represented first choice for pacemakers and defibrillators (71% and 64% of physicians, respectively), mainly for safety. For right ventricle, active fixation was preferred (61% and 93% operators in pacemaker and defibrillator patients), for higher versatility in positioning and lower dislodgement risk. For left ventricular stimulation, quadripolar leads were preferred by more than 80% of respondents, for better phrenic nerve and myocardial threshold management; active-fixation leads represent a second choice, in order to prevent or manage dislodgement (78% and 17% of respondents, respectively), but 44% of operators considered them dangerous.Conclusions: The choice of leads is heterogeneous. Trends are toward active-fixation right ventricular leads and passive-fixation atrial leads (particularly in pacemaker patients, considered frailer). For left ventricular stimulation, operators’ majority want to disposition all kind of leads, although quadripolar leads are the favorites.

Multicenter prospective observational long-term follow-up study of endocardial cardiac resynchronization therapy using the Jurdham procedure

Endocardial cardiac resynchronization therapy (eCRT) avoids the limitations and failures of coronary sinus (CS) resynchronization. However, data regarding long-term outcomes are lacking. The purpose of this study was to report the long-term outcome of eCRT performed using the Jurdham procedure in a real-world setting. eCRT was performed in patients who failed a CS implant or failed to respond to cardiac resynchronization therapy (CRT), or in selected patients requiring lifelong oral anticoagulation (OAC). Left ventricular ejection fraction (LVEF), New York Heart Association functional class (NYHA FC), and left ventricular stimulation parameters were assessed during long-term follow-up (FU). From August 2009 to March 2018, the Jurdham procedure was performed in 88 patients at 15 centers in 8 countries, with FU of 32.88 ± 61.52 months (range 0-88 months; 196 patient-years). NYHA FC improved from 2.9 preimplant to 1.3 during FU. LVEF increased <10 percentage points from baseline in 7% of patients, between 10 and 20 percentage points in 11% of patients, and >20 percentage points in 82% of patients. All-cause mortality at 60 months was 30.5%. Three transient ischemic attacks (1.53 per 100 patient-years) and 6 strokes (3.06 per 100 patient-years) occurred. Of the 6 patients with stroke, 4 (66%) had almost complete recovery. eCRT using the Jurdham procedure is an effective and safe technique in anticoagulated patients. This approach may be an attractive option for patients with failed CS implants or nonresponders to CS CRT. In addition, it might be a reasonable approach as a first option for treatment of patients requiring lifelong OAC.

Bipolar active fixation left ventricular lead or quadripolar passive fixation lead? An Italian multicenter experience.

About one-third of patients receiving cardiac resynchronization therapy (CRT) are not responders, due to either patient selection or technical issues. Left ventricular quadripolar passive fixation leads (QPL) and bipolar active fixation (BAF) leads have been designed to ensure a targeted left ventricular stimulation area, minimizing lead dislodgments and phrenic nerve stimulation (PNS). The aim was to compare real-world safety and efficacy of BAF (Attain Stability, Medtronic Plc.) and QPL (Attain Performa, Medtronic Plc.). We performed a retrospective analysis examining procedural and follow-up data of 261 BAF and 124 QPL (programmed to single-site left ventricular pacing), included in the ClinicalService project from 16 Italian hospitals. At median follow-up of 12 months, no difference in left ventricular pacing threshold was recorded between BAF and QPL (1.3 ± 0.9 V @0.4 ms vs. 1.3 ± 1.0 V @0.4 ms; P = 0.749). Total left ventricular lead dislodgement rate was 1.43/100 patient-years in BAF vs. 2.9/100 patient-years in QPL (P = 0.583). However, no dislodgements occurred among BAF after hospital discharge. Events requiring repeated surgery or permanently turning CRT off occurred in 0.8% of BAF, as compared with 4.0% of QPL (P = 0.025). There was no difference between groups in the echo CRT responders' rate (70% of BAF and 66% of QPL; P = 0.589) or in the annual rate of heart failure hospitalization (P = 0.513). BAF resulted in noninferior clinical outcome and CRT responders' rate in comparison to QPL. Moreover, BAF ensured more precise and stable placement in cardiac veins, with comparable electrical performance and less than 1% patients with unsolved PNS.

Alternative left ventricular pacing approaches for optimal cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) improves mortality, morbidity, and quality of life in selected heart failure patients with severe left ventricular (LV) ejection fraction impairment. However, between 20% and 40% of device recipients do not benefit clinically from CRT. Indeed, some anatomic and technical difficulties are related to the coronary venous implantation site via the coronary sinus (CS). Additionally, electrical constraints have been described, and CS does not always correspond to the optimal LV lead position. In the last decade, engineers and physicians have worked together to overcome the challenging LV lead implantation, and various biventricular pacing alternatives have been developed to improve CRT response. Inthis review, we discuss the evolution from CS pacing to wireless LV stimulation and His-bundle pacing.