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BACKGROUND: Long-term outcomes are poorly understood, and data in patients undergoing transvenous lead extraction (TLE) are lacking. OBJECTIVE: The purpose of this study was to evaluate factors influencing survival in patients undergoing TLE depending on extraction indication. METHODS: Clinical data from consecutive patients undergoing TLE in the reference center between 2000 and 2019 were prospectively collected. The total cohort was divided into groups depending on whether there was an infective or noninfective indication for TLE. We evaluated the association of demographic, clinical, and device-related and procedure-related factors on mortality. RESULTS: A total of 1151 patients were included. Mean follow-up was 66 months, and mortality was 34.2% (n = 392). Of these patients, 632 (54.9%) and 519 (45.1%) were for infective and noninfective indications, respectively. A higher proportion in the infection group died (38.6% vs 28.5%; P <.001). In the total cohort, multivariable analysis demonstrated increased mortality risk with age >75 years (hazard ratio [HR] 2.98; 95% confidence interval [CI] 2.35-3.78; P <.001), estimated glomerular filtration rate <60 mL/min/1.73 m2 (HR 1.67; 95% CI 1.31-2.13; P <.001), higher cumulative comorbidity (HR 1.17; 95% CI 1.09-1.26; P <.001), reduced risk per percentage increase in left ventricular ejection fraction (HR 0.98; 95% CI 0.97-0.99; P <.001), and near unity per year of additional lead dwell time (HR 0.98; 95% CI 0.96-1.00; P = .037). Kaplan-Meier survival curves demonstrated worse prognosis, with a higher number of leads extracted and increasing comorbidities. CONCLUSION: Long-term mortality for patients undergoing TLE remains high. Consensus guidelines recommend evaluating risk for major complications when determining whether to proceed with TLE. This study suggests also assessing longer-term outcomes when considering TLE in those with a high risk of medium- and long-term mortality, particularly for noninfective indications.

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The ARTO device is a percutaneous device for functional mitral regurgitation composed of a transseptal anchor and a T-bar sitting in the coronary sinus which reduce the minor axis of the mitral valve. We present a case showing the technical feasibility of an LV lead implant in patients with an ARTO device in situ.

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BACKGROUND: Longer-term outcomes of patients post transvenous lead extraction (TLE) are poorly understood in patients with cardiac resynchronization therapy (CRT) devices. OBJECTIVES: A propensity score (PS)-matched analysis evaluating outcomes post TLE in CRT and non-CRT populations was performed. METHODS: Data from consecutive patients undergoing TLE between 2000 and 2019 were prospectively collected. Patients surviving to discharge and reimplanted with the same device were included. The cohort was split depending on presence of CRT device. Associations with all-cause mortality and hospitalization were assessed by Kaplan-Meier estimates. An exploratory endpoint was evaluated whether early (<7 days) or late (>7 days) reimplantation was associated with poorer outcomes. RESULTS: Of 1005 patients included, 285 (25%) had a CRT device. Median follow-up was 57.00 [27.00-93.00] months, age at explant was 67.7 ± 12.1 years, 83.3% were male, and 54.4% had an infective indication for TLE. PS was calculated using 43 baseline characteristics. After matching, 192 CRT patients were compared with 192 non-CRT patients. In the matched cohort, no significant difference with respect to mortality (hazard ratio [HR] = 1.01, 95% confidence interval [CI] [0.74-1.39], P = .093) or hospitalization risk (HR = 1.2, 95% CI [0.87-1.66], P = .265) was observed. In the matched CRT group, late reimplantation was associated with increased mortality (HR = 1.64, [1.04-2.57], P = .032) and hospitalization risk (HR = 1.57, 95% CI [1.00-2.46], P = .049]. CONCLUSION: Outcomes of CRT patients post TLE are similarly as poor as those of non-CRT patients in matched populations. Reimplantation within 7 days was associated with better outcomes in a CRT population but was not observed in a non-CRT population, suggesting prolonged periods without biventricular pacing should be avoided.

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BACKGROUND: Transvenous lead extraction (TLE) may be performed by superior approach using the original implant vein or via a femoral approach; however, limited comparative data exists. We compare outcomes between femoral versus nonfemoral TLE approaches and determine predictors of bailout transfemoral lead extraction in patients undergoing initial TLE via the original implant vein by a superior approach. METHODS: All consecutive TLEs between October 2000 and March 2018 were prospectively collected (n = 1052). Patients were dichotomized into femoral (n = 118) and nonfemoral (n = 934) groups. RESULTS: Demographics were balanced between femoral vs nonfemoral groups. Patients in the femoral group had significantly higher mean lead dwell times (11.6 ± 9.7 vs 6.6 ± 6.6 years, P < .001), mean number of leads extracted (2.7 ± 1.3 vs 2.0 ± 1.0, P < .001), 30-day procedure related major complications (including deaths) (8.5% vs 1.1%, P < .001) and emergency thoracotomy rates (4.2% vs 0.7%, P = .007). All-cause 30-day mortality rates were similar between groups (3.4% vs 2.0%, P = .315). Prolonged lead dwell time and increased number of leads extracted were predictive of a bailout transfemoral approach at multivariable analysis. CONCLUSION: Femoral approach TLE is associated with increased risk of 30-day procedure related major complications but not 30-day all-cause mortality. Prolonged lead dwell time and increased number of leads extracted are independent predictors for bailout transfemoral lead extraction. Such patients should be considered high risk of major complications and performed by high-volume lead extraction centers with experience in multiple approaches and techniques including experience with transfemoral lead extraction.

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AIMS: Transvenous lead extraction (TLE) may be necessary due to system infection/erosion or lead malfunction. Cardiac resynchronization therapy (CRT) patients undergoing TLE may be at greater risk due to increased comorbidities. We examined whether patients with CRT systems undergoing TLE had more comorbidities and higher 30-day mortality than those with non-CRT devices. METHODS AND RESULTS: All TLEs between October 2000 and December 2016 were prospectively collected. During this period 925 TLEs occurred (CRT group 231, non-CRT group 694). Cardiac resynchronization therapy patients were older (68.1 ± 10.8 years vs. 64.3 ± 16.1 years, P = 0.024); more likely male (85.7% vs. 69%, P < 0.001); had lower mean left ventricular ejection fraction (34.1 ± 12.7% vs. 48.3 ± 12.9%, P < 0.001); had higher prevalence of renal impairment (33.8% vs. 13.7%, P < 0.001) and were more likely to have ≥2 comorbidities (84% vs. 40.1%, P < 0.001). Mean lead dwell time was lower in the CRT group (5.6 ± 5.5 years vs. 7.6 ± 7.1 years, P = 0.002). There was no significant difference in all-cause 30-day mortality rates between CRT (3.0%, n = 7) and non-CRT patients (2.0%, n = 14) (P = 0.443). The majority of deaths in both groups were due to sepsis. Univariate and multivariate analysis showed age, renal impairment and sepsis were associated with increased risk of 30-day mortality. Transvenous lead extraction of a CRT system did not predict 30-day mortality. CONCLUSION: Transvenous lead extraction in CRT patients was not associated with increased 30-day mortality when compared with non-CRT patients. Age, renal impairment and sepsis were independent predictors of 30-day mortality. Sepsis was the main cause of 30-day mortality.

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BACKGROUND: Transvenous lead extraction (TLE) may be necessary due to infective and noninfective indications. We aim to identify predictors of 30-day mortality and risk factors between infective versus noninfective groups and systemic versus local infection subgroups. METHODS: A total of 925 TLEs between October 2000 and December 2016 were prospectively collected and dichotomized (infective group n = 505 vs noninfective group n = 420 and systemic infection n = 164 vs local infection n = 341). RESULTS: All-cause major complication including deaths was significantly higher (5.1%, n = 26 vs 1.2%, n = 5, P = 0.001) as well as 30-day mortality (4.0%, n = 20 vs 0.2%, n = 1, P < 0.001) in the infective group compared to the noninfective group. Both subgroups (systemic vs local infection) were balanced for demographics. All-cause major complication including deaths was significantly higher (9.1%, n = 15 vs 3.2%, n = 11, P = 0.008) as well as all-cause 30-day mortality (7.9%, n  = 13 vs 2.1%, n = 7, P = 0.003) in the systemic infection subgroup compared to the local infection subgroup. CONCLUSION: Patients undergoing TLE for infective indications are at greater risk of 30-day all-cause mortality compared to noninfective patients. Patients undergoing TLE for systemic infective indications are at greater risk of 30-day all-cause mortality compared to patients with local infection. Renal impairment, systemic infection, and elevated preprocedure C-reactive protein are independent predictors of 30-day all-cause mortality in patients undergoing TLE for an infective indication.

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Myocardial stiffness is a valuable clinical biomarker for the monitoring and stratification of heart failure (HF). Cardiac finite element models provide a biomechanical framework for the assessment of stiffness through the determination of the myocardial constitutive model parameters. The reported parameter intercorrelations in popular constitutive relations, however, obstruct the unique estimation of material parameters and limit the reliable translation of this stiffness metric to clinical practice. Focusing on the role of the cost function (CF) in parameter identifiability, we investigate the performance of a set of geometric indices (based on displacements, strains, cavity volume, wall thickness and apicobasal dimension of the ventricle) and a novel CF derived from energy conservation. Our results, with a commonly used transversely isotropic material model (proposed by Guccione et al.), demonstrate that a single geometry-based CF is unable to uniquely constrain the parameter space. The energy-based CF, conversely, isolates one of the parameters and in conjunction with one of the geometric metrics provides a unique estimation of the parameter set. This gives rise to a new methodology for estimating myocardial material parameters based on the combination of deformation and energetics analysis. The accuracy of the pipeline is demonstrated in silico, and its robustness in vivo, in a total of 8 clinical data sets (7 HF and one control). The mean identified parameters of the Guccione material law were [Formula: see text] and [Formula: see text] ([Formula: see text], [Formula: see text], [Formula: see text]) for the HF cases and [Formula: see text] and [Formula: see text] ([Formula: see text], [Formula: see text], [Formula: see text]) for the healthy case.

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ECG imaging is an emerging technology for the reconstruction of cardiac electric activity from non-invasively measured body surface potential maps. In this case report, we present the first evaluation of transmurally imaged activation times against endocardially reconstructed isochrones for a case of sustained monomorphic ventricular tachycardia (VT). Computer models of the thorax and whole heart were produced from MR images. A recently published approach was applied to facilitate electrode localization in the catheter laboratory, which allows for the acquisition of body surface potential maps while performing non-contact mapping for the reconstruction of local activation times. ECG imaging was then realized using Tikhonov regularization with spatio-temporal smoothing as proposed by Huiskamp and Greensite and further with the spline-based approach by Erem et al. Activation times were computed from transmurally reconstructed transmembrane voltages. The results showed good qualitative agreement between the non-invasively and invasively reconstructed activation times. Also, low amplitudes in the imaged transmembrane voltages were found to correlate with volumes of scar and grey zone in delayed gadolinium enhancement cardiac MR. The study underlines the ability of ECG imaging to produce activation times of ventricular electric activity-and to represent effects of scar tissue in the imaged transmembrane voltages.

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BACKGROUND: Cardiac anatomy and function adapt in response to chronic cardiac resynchronization therapy (CRT). The effects of these changes on the optimal left ventricle (LV) lead location and timing delay settings have yet to be fully explored. OBJECTIVE: To predict the effects of chronic CRT on the optimal LV lead location and device timing settings over time. METHODS: Biophysical computational cardiac models were generated for 3 patients, immediately post-implant (ACUTE) and after at least 6 months of CRT (CHRONIC). Optimal LV pacing area and device settings were predicted by pacing the ACUTE and CHRONIC models across the LV epicardium (49 sites each) with a range of 9 pacing settings and simulating the acute hemodynamic response (AHR) of the heart. RESULTS: There were statistically significant differences between the distribution of the AHR in the ACUTE and CHRONIC models (P < 0.0005 in all cases). The site delivering the maximal AHR shifted location between the ACUTE and CHRONIC models but provided a negligible improvement (<2%). The majority of the acute optimal LV pacing regions (76-100%) and device settings (76-91%) remained optimal chronically. CONCLUSION: Optimization of the LV pacing location and device settings were important at the time of implant, with a reduced benefit over time, where the majority of the acute optimal LV pacing region and device settings remained optimal with chronic CRT.

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AIMS: The efficacy of cardiac resynchronization therapy (CRT) is known to vary considerably with pacing location, however the most effective set of metrics by which to select the optimal pacing site is not yet well understood. Computational modelling offers a powerful methodology to comprehensively test the effect of pacing location in silico and investigate how to best optimize therapy using clinically available metrics for the individual patient. METHODS AND RESULTS: Personalized computational models of cardiac electromechanics were used to perform an in silico left ventricle (LV) pacing site optimization study as part of biventricular CRT in three patient cases. Maps of response to therapy according to changes in total activation time (ΔTAT) and acute haemodynamic response (AHR) were generated and compared with preclinical metrics of electrical function, strain, stress, and mechanical work to assess their suitability for selecting the optimal pacing site. In all three patients, response to therapy was highly sensitive to pacing location, with laterobasal locations being optimal. ΔTAT and AHR were found to be correlated (ρ < -0.80), as were AHR and the preclinical activation time at the pacing site (ρ ≥ 0.73), however pacing in the last activated site did not result in the optimal response to therapy in all cases. CONCLUSION: This computational modelling study supports pacing in laterobasal locations, optimizing pacing site by minimizing paced QRS duration and pacing in regions activated late at sinus rhythm. Results demonstrate information content is redundant using multiple preclinical metrics. Of significance, the correlation of AHR with ΔTAT indicates that minimization of QRSd is a promising metric for optimization of lead placement.

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INTRODUCTION: Computational modeling of cardiac arrhythmogenesis and arrhythmia maintenance has made a significant contribution to the understanding of the underlying mechanisms of arrhythmia. We hypothesized that a cardiac model using personalized electro-anatomical parameters could define the underlying ventricular tachycardia (VT) substrate and predict reentrant VT circuits. We used a combined modeling and clinical approach in order to validate the concept. METHODS AND RESULTS: Non-contact electroanatomic mapping studies were performed in 7 patients (5 ischemics, 2 non-ischemics). Three ischemic cardiomyopathy patients underwent a clinical VT stimulation study. Anatomical information was obtained from cardiac magnetic resonance imaging (CMR) including high-resolution scar imaging. A simplified biophysical mono-domain action potential model personalized with the patients' anatomical and electrical information was used to perform in silico VT stimulation studies for comparison. The personalized in silico VT stimulations were able to predict VT inducibility as well as the macroscopic characteristics of the VT circuits in patients who had clinical VT stimulation studies. The patients with positive clinical VT stimulation studies had wider distribution of action potential duration restitution curve (APD-RC) slopes and APDs than the patient with a negative VT stimulation study. The exit points of reentrant VT circuits encompassed a higher percentage of the maximum APD-RC slope compared to the scar and non-scar areas, 32%, 4%, and 0.2%, respectively. CONCLUSIONS: VT stimulation studies can be simulated in silico using a personalized biophysical cardiac model. Myocardial spatial heterogeneity of APD restitution properties and conductivity may help predict the location of crucial entry/exit points of reentrant VT circuits.

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Cardiac resynchronisation therapy (CRT) is an established treatment for heart failure, however the effective selection of patients and optimisation of therapy remain controversial. While extensive research is ongoing, it remains unclear whether improvements in patient selection or therapy planning offers a greater opportunity for the improvement of clinical outcomes. This computational study investigates the impact of both physiological conditions that guide patient selection and the optimisation of pacing lead placement on CRT outcomes. A multi-scale biophysical model of cardiac electromechanics was developed and personalised to patient data in three patients. These models were separated into components representing cardiac anatomy, pacing lead location, myocardial conductivity and stiffness, afterload, active contraction and conduction block for each individual, and recombined to generate a cohort of 648 virtual patients. The effect of these components on the change in total activation time of the ventricles (ΔTAT) and acute haemodynamic response (AHR) was analysed. The pacing site location was found to have the largest effect on ΔTAT and AHR. Secondary effects on ΔTAT and AHR were found for functional conduction block and cardiac anatomy. The simulation results highlight a need for a greater emphasis on therapy optimisation in order to achieve the best outcomes for patients.

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BACKGROUND: Multisite pacing (MSP) of the left ventricle is proposed as an alternative to conventional single-site LV pacing in cardiac resynchronization therapy (CRT). Reports on the benefits of MSP have been conflicting. A paradigm whereby not all patients derive benefit from MSP is emerging. OBJECTIVE: We sought to compare the hemodynamic and electrical effects of MSP with the aim of identifying a subgroup of patients more likely to derive benefit from MSP. METHODS: Sixteen patients with implanted CRT systems incorporating a quadripolar LV pacing lead were studied. Invasive hemodynamic and electroanatomic assessment was performed during the following rhythms: baseline (non-CRT); biventricular (BIV) pacing delivered via the implanted CRT system (BIV(implanted)); BIV pacing delivered via an alternative temporary LV lead (BIV(alternative)); dual-vein MSP delivered via 2 LV leads; MultiPoint Pacing delivered via 2 vectors of the quadripolar LV lead. RESULTS: Seven patients had an acute hemodynamic response (AHR) of <10% over baseline rhythm with BIV(implanted) and were deemed nonresponders. AHR in responders vs nonresponders was 21.4% ± 10.4% vs 2.0% ± 5.2% (P < .001). In responders, neither form of MSP provided incremental hemodynamic benefit over BIV(implanted). Dual-vein MSP (8.8% ± 5.7%; P = .036 vs BIV(implanted)) and MultiPoint Pacing (10.0% ± 12.2%; P = .064 vs BIV(implanted)) both improved AHR in nonresponders. Seven of 9 responders to BIV(implanted) had LV endocardial activation characterized by a functional line of block during intrinsic rhythm that was abolished with BIV pacing. All these patients met strict criteria for left bundle branch block (LBBB). No nonresponders exhibited this line of block or met strict criteria for LBBB. CONCLUSION: Patients not meeting strict criteria for LBBB appear most likely to derive benefit from MSP.

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BACKGROUND: Acute indicators of response to cardiac resynchronisation therapy (CRT) are critical for developing lead optimisation algorithms and evaluating novel multi-polar, multi-lead and endocardial pacing protocols. Accounting for beat-to-beat variability in measures of acute haemodynamic response (AHR) may help clinicians understand the link between acute measurements of cardiac function and long term clinical outcome. METHODS AND RESULTS: A retrospective study of invasive pressure tracings from 38 patients receiving an acute pacing and electrophysiological study was performed. 602 pacing protocols for left ventricle (LV) (n = 38), atria-ventricle (AV) (n = 9), ventricle-ventricle (VV) (n = 12) and endocardial (ENDO) (n = 8) optimisation were performed. AHR was measured as the maximal rate of LV pressure development (dP/dtMx) for each beat. The range of the 95% confidence interval (CI) of mean AHR was ~ 7% across all optimisation protocols compared with the reported CRT response cut off value of 10%. A single clear optimal protocol was identifiable in 61%, 22%, 25% and 50% for LV, AV, VV and ENDO optimisation cases, respectively. A level of service (LOS) optimisation that aimed to maximise the expected AHR 5th percentile, minimising variability and maximising AHR, led to distinct optimal protocols from conventional mean AHR optimisation in 34%, 78%, 67% and 12.5% of LV, AV, VV and ENDO optimisation cases, respectively. CONCLUSION: The beat-to-beat variation in AHR is significant in the context of CRT cut off values. A LOS optimisation offers a novel index to identify the optimal pacing site that accounts for both the mean and variation of the baseline measurement and pacing protocol.

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BACKGROUND: Diffuse myocardial fibrosis may provide a substrate for the initiation and maintenance of ventricular arrhythmia. T1 mapping overcomes the limitations of the conventional delayed contrast-enhanced cardiac magnetic resonance (CE-CMR) imaging technique by allowing quantification of diffuse fibrosis. OBJECTIVE: The purpose of this study was to assess whether myocardial tissue characterization using T1 mapping would predict ventricular arrhythmia in ischemic and non-ischemic cardiomyopathies. METHODS: This was a prospective longitudinal study of consecutive patients receiving implantable cardioverter-defibrillators in a tertiary cardiac center. Participants underwent CMR myocardial tissue characterization using T1 mapping and conventional CE-CMR scar assessment before device implantation. The primary end point was an appropriate implantable cardioverter-defibrillator therapy or documented sustained ventricular arrhythmia. RESULTS: One hundred thirty patients (71 ischemic and 59 non-ischemic) were included with a mean follow-up period of 430 ± 185 days (median 425 days; interquartile range 293 days). At follow-up, 23 patients (18%) experienced the primary end point. In multivariable-adjusted analyses, the following factors showed a significant association with the primary end point: secondary prevention (hazard ratio [HR] 1.70; 95% confidence interval [95% CI] 1.01-1.91), noncontrast T1(_native) for every 10-ms increment in value (HR 1.10; CI 1.04-1.16; 90-ms difference between the end point-positive and end point-negative groups), and Grayzone(_2sd-3sd) for every 1% left ventricular increment in value (HR 1.36; CI 1.15-1.61; 4% difference between the end point-positive and end point-negative groups). Other CE-CMR indices including Scar(_2sd), Scar(_FWHM), and Grayzone(_2sd-FWHM) were also significantly, even though less strongly, associated with the primary end point as compared with Grayzone(_2sd-3sd). CONCLUSION: Quantitative myocardial tissue assessment using T1 mapping is an independent predictor of ventricular arrhythmia in both ischemic and non-ischemic cardiomyopathies.

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BACKGROUND: Many patients with electrical dyssynchrony who undergo cardiac resynchronization therapy (CRT) do not obtain substantial benefit. Assessing mechanical dyssynchrony may improve patient selection. Results from studies using echocardiographic imaging to measure dyssynchrony have ultimately proved disappointing. We sought to evaluate cardiac motion in patients with heart failure and electrical dyssynchrony using cardiovascular magnetic resonance (CMR). We developed a framework for comparing measures of myocardial mechanics and evaluated how well they predicted response to CRT. METHODS: CMR was performed at 1.5 Tesla prior to CRT. Steady-state free precession (SSFP) cine images and complementary modulation of magnetization (CSPAMM) tagged cine images were acquired. Images were processed using a novel framework to extract regional ventricular volume-change, thickening and deformation fields (strain). A systolic dyssynchrony index (SDI) for all parameters within a 16-segment model of the ventricle was computed with high SDI denoting more dyssynchrony. Once identified, the optimal measure was applied to a second patient population to determine its utility as a predictor of CRT response compared to current accepted predictors (QRS duration, LBBB morphology and scar burden). RESULTS: Forty-four patients were recruited in the first phase (91% male, 63.3 ± 14.1 years; 80% NYHA class III) with mean QRSd 154 ± 24 ms. Twenty-one out of 44 (48%) patients showed reverse remodelling (RR) with a decrease in end systolic volume (ESV) ≥ 15% at 6 months. Volume-change SDI was the strongest predictor of RR (PR 5.67; 95% CI 1.95-16.5; P = 0.003). SDI derived from myocardial strain was least predictive. Volume-change SDI was applied as a predictor of RR to a second population of 50 patients (70% male, mean age 68.6 ± 12.2 years, 76% NYHA class III) with mean QRSd 146 ± 21 ms. When compared to QRSd, LBBB morphology and scar burden, volume-change SDI was the only statistically significant predictor of RR in this group. CONCLUSION: A systolic dyssynchrony index derived from volume-change is a highly reproducible measurement that can be derived from routinely acquired SSFP cine images and predicts RR following CRT whilst an SDI of regional strain does not.

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BACKGROUND: We sought to compare left ventricular (LVepi) and biventricular epicardial pacing (BIVepi) with LV (LVendo) and BIV endocardial pacing (BIVendo) in patients with chronic heart failure with an emphasis on the underlying electrophysiological mechanisms and hemodynamic effects. METHODS AND RESULTS: Ten patients with chronically implanted cardiac resynchronization devices underwent temporary LVendo and BIVendo pacing with an LV endocardial roving catheter. A pressure wire and noncontact mapping array were placed to the LV cavity to measure LVdP/dtmax and perform electroanatomical mapping. At the optimal endocardial position, the acute hemodynamic response (AHR) was superior to epicardial stimulation, the AHR to BIVendo pacing and LVendo pacing being comparable (21±15% versus 22±17%; P=NS). During intrinsic conduction, QRS duration was 185±30 ms, endocardial LV total activation time 92±27 ms, and trans-septal activation time 60±21 ms. With LVendo pacing, QRS duration (187±29 ms; P=NS) and endocardial LV total activation time (91±23 ms; P=NS) were comparable with intrinsic conduction. There was no significant difference in endocardial LV total activation time between LVendo and BIVendo pacing (91±23 versus 85±15 ms; P=NS). Assessment of isochronal maps identified slow trans-septal conduction with both LVendo and BIVendo pacing resulting in activation of almost the entire LV endocardium prior to septal breakout, thereby limiting any possible fusion with either pacing mode. CONCLUSIONS: The equivalent AHR to LVendo and BIVendo pacing may be explained by prolonged trans-septal conduction limiting fusion of electrical wavefronts. The optimal AHR was associated with predominantly LV pre-excitation and depolarization. Our results suggest that LV pacing alone may offer a viable endocardial stimulation strategy to achieve cardiac resynchronization.

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INTRODUCTION: A quadripolar left ventricular (LV) pacing can deliver multipoint pacing (MPP). It is unknown if this confers improved cardiac function compared to conventional cardiac resynchronization therapy (CRT). METHODS AND RESULTS: We aimed to characterize changes in acute cardiac contractility and hemodynamics with multisite left ventricular "multipoint" pacing (MPP) in a prospective multicenter study in patients implanted with a CRT-defibrillator incorporating a quadripolar LV lead. The device was programmed to deliver MPP acutely pacing with eight configurations of varying timing delays. Global peak LV radial strain and LV outflow velocity time integral (LVOT VTI) were measured for conventional CRT and each MPP configuration. Out of the eight tested MPP configurations, the one that yielded the best echocardiographic measurement for each patient was defined as "optimal MPP". Forty CRT recipients had complete radial strain datasets suitable for analysis. Compared to conventional CRT, the mean peak radial strain was significantly higher for the optimal MPP configuration (18.3 ± 7.4 vs. 9.3 ± 5.3%, p < 0.001), and at least one MPP configuration was significantly superior (>20%) in 63% of patients. LVOT VTI data were collected in a subset of 13 patients. In these patients, mean VTI was significantly higher for optimal MPP compared to conventional CRT (13.5 ± 2.7 vs. 10.9 ± 3.3 cm, p < 0.01). CONCLUSION: MPP delivered via a quadripolar LV lead resulted in a significant improvement in acute cardiac contractility and hemodynamics compared to conventional CRT in the majority of patients studied. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01044784.

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AIMS: Alternative forms of cardiac resynchronization therapy (CRT), including biventricular endocardial (BV-Endo) and multisite epicardial pacing (MSP), have been developed to improve response. It is unclear which form of stimulation is optimal. We aimed to compare the acute haemodynamic response (AHR) and electrophysiological effects of BV-Endo with MSP via two separate coronary sinus (CS) leads or a single-quadripolar CS lead. METHODS AND RESULTS: Fifteen patients with a previously implanted CRT system received a second temporary CS lead and left ventricular (LV) endocardial catheter. A pressure wire and non-contact mapping array were placed into the LV cavity to measure LVdP/dtmax and perform electroanatomical mapping. Conventional CRT, BV-Endo, and MSP were then performed (MSP-1 via two epicardial leads and MSP-2 via a single-quadripolar lead). The best overall AHR was found using BV-Endo pacing with a 19.6 ± 13.6% increase in AHR at the optimal endocardial site over baseline (P < 0.001). There was an increase in LVdP/dtmax with MSP-1 and MSP-2 compared with conventional CRT, but this was not statistically significant. Biventricular endocardial pacing from the optimal site was significantly superior to conventional CRT (P = 0.039). The AHR achieved when BV-Endo pacing was highly site specific. Within individuals, the best pacing modality varied and was affected by the underlying substrate. Left ventricular activation times did not predict the optimal haemodynamic configuration. CONCLUSION: Biventricular endocardial pacing and not MSP was superior to conventional CRT, but was highly site specific. Within individuals, however, different methods of stimulation are optimal and may need to be tailored to the underlying substrate.

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