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Aims Radiofrequency catheter ablation of atrial flutter and fibrillation may be favoured by large, elongated lesions. We compared bipolar ablation with unipolar ablation from one or two electrodes in the porcine heart. Methods and Results In vitro, confluent lesions were reliably created by a ‘dielectrode’ catheter (energy delivered simultaneously (in parallel) from two 4mm electrodes spaced 1mm apart, towards an indifferent electrode), and a ‘bipolar’ catheter (energy delivered (in series) between two 4mm electrodes spaced 5mm apart). Sixteen anaesthetized pigs were randomized to standard unipolar (4), dielectrode (6) or bipolar (6) ablation. Two radiofrequency current deliveries of 30s duration (70°C) were administered to the inferior vena cava–tricuspid valve isthmus and two to the right atrial free wall in all animals. After 4h, the lesions were examined macroscopically and histologically. Mean (SD) endocardial lesion length×width×depth measured 7·4 (2·4)×5·4 (2·2)×2·8 (0·8)mm in the standard unipolar mode, 10·2 (1·4)×6·3 (0·7)×3·3 (1·1)mm in the dielectrode mode and 14·0 (3·6)×6·0 (1·7)×3·8 (1·2)mm in the bipolar mode. Thus lesion length increased significantly through the three groups (P<0·001), while width and depth did not. Conclusion Both dielectrode and bipolar ablation were feasible in porcine right atrial ablation, and created longer lesions than the standard unipolar mode. By allowing a larger interelectrode distance, bipolar ablation created the longest lesions and may be favourable when linear lesions are necessary. [ABSTRACT FROM PUBLISHER]

Background : The response to cardiac resynchronization therapy (CRT) depends on septal viability and correction of abnormal septal motion. This study investigates if cardiac magnetic resonance (CMR) as a single modality can identify CRT responders with combined imaging of pathological septal motion (septal flash) and septal scar. Methods : In a prospective, multicenter, observational study of 136 CRT recipients, septal scar was assessed using late gadolinium enhancement (LGE) ( n = 127) and septal flash visually from cine CMR sequences. The primary endpoint was CRT response, defined as ≥15% reduction in LV end-systolic volume with echocardiography after 6 months. The secondary endpoint was heart transplantation or death of any cause assessed after 39 ± 13 months. Results : Septal scar and septal flash were independent predictors of CRT response in multivariable analysis (both p < 0.001), while QRS duration and morphology were not. The combined approach of septal scar and septal flash predicted CRT response with an area under the curve of 0.86 (95% confidence interval (CI): 0.78-0.94) and was a strong predictor of long-term survival without heart transplantation (hazard ratio 0.27, 95% CI: 0.10-0.79). The accuracy of the approach was similar in the subgroup with intermediate (130-150 ms) QRS duration. The combined approach was superior to septal scar and septal flash alone ( p < 0.01). Conclusions: The combined assessment of septal scar and septal flash using CMR as a single-image modality identifies CRT responders with high accuracy and predicts long-term survival.

Purpose: Response to cardiac resynchronization therapy (CRT) is reduced in patients with high left ventricular (LV) scar burden, in particular when scar is located in the LV lateral wall or septum. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) can identity scar, but is not feasible in all patients. This study investigates if myocardial metabolism by 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contractile function by echocardiographic strain are alternatives to LGE-CMR., Methods: In a prospective multicenter study, 132 CRT candidates (91% with left bundle branch block) were studied by speckle tracking strain echocardiography, and 53 of these by FDG-PET. Regional myocardial FDG metabolism and peak systolic strain were compared to LGE-CMR as reference method., Results: Reduced FDG metabolism (<70% relative) precisely identified transmural scars (≥50% of myocardial volume) in the LV lateral wall, with area under the curve (AUC) 0.96 (95% confidence interval (CI) 0.90-1.00). Reduced contractile function by strain identified transmural scars in the LV lateral wall with only moderate accuracy (AUC = 0.77, CI 0.71-0.84). However, absolute peak systolic strain >10% could rule out transmural scar with high sensitivity (80%) and high negative predictive value (96%). Neither FDG-PET nor strain identified septal scars (for both, AUC < 0.80)., Conclusions: In CRT candidates, FDG-PET is an excellent alternative to LGE-CMR to identify scar in the LV lateral wall. Furthermore, preserved strain in the LV lateral wall has good accuracy to rule out transmural scar. None of the modalities can identify septal scar., Clinical Trial Registration: The present study is part of the clinical study "Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy (CRID-CRT)", which was registered at clinicaltrials.gov (identifier NCT02525185)., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: We designed this study to assess the acute effects of different fusion strategies and left ventricular (LV) pre-excitation/post-excitation on LV dP/dt max and QRS duration (QRSd)., Methods: We measured LV dP/dt max and QRSd in 19 patients having cardiac resynchronisation therapy (CRT). Two groups of biventricular pacing were compared: pacing the left ventricle (LV) with FUSION with intrinsic right ventricle (RV) activation (FUSION), and pacing the LV and RV with NO FUSION with intrinsic RV activation. In the NO FUSION group, the RV was paced before the expected QRS onset. A quadripolar LV lead enabled distal, proximal and multipoint pacing (MPP). The LV was stimulated relative in time to either RV pace or QRS-onset in four pre-excitation/post-excitation classes (PCs). We analysed the interactions of two groups (FUSION/NO FUSION) with three different electrode configurations, each paced with four different degrees of LV pre-excitation (PC1-4) in a statistical model., Results: LV dP/dt max was higher with NO FUSION than with FUSION (769±46 mm Hg/s vs 746±46 mm Hg/s, p<0.01), while there was no difference in QRSd (NO FUSION 156±2 ms and FUSION 155±2 ms). LV dP/dt max and QRSd increased with LV pre-excitation compared with pacing timed to QRS/RV pace-onset regardless of electrode configuration. Overall, pacing LV close to QRS-onset (FUSION) with MPP shortened QRSd the most, while LV dP/dt max increased the most with LV pre-excitation., Conclusion: We show how a beneficial change in QRSd dissociates from the haemodynamic change in LV dP/dt max with different biventricular pacing strategies. In this study, LV pre-excitation was the main determinant of LV dP/dt max , while QRSd shortens with optimal resynchronisation., Competing Interests: Competing interests: LOG and RC are full-time employees in Medtronic. HHO has received honorary from Abbott Medical, Stockholder Pacertool; patent applications within the field of cardiac resynchronisation therapy., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Three distinct septal contraction patterns typical for left bundle branch block may be assessed using echocardiography in heart failure patients scheduled for cardiac resynchronization therapy (CRT). The aim of this study was to explore the association between these septal contraction patterns and the acute haemodynamic and electrical response to biventricular pacing (BIVP) in patients undergoing CRT implantation., Methods and Results: Thirty-eight CRT candidates underwent speckle tracking echocardiography prior to device implantation. The patients were divided into two groups based on whether their septal contraction pattern was indicative of dyssynchrony (premature septal contraction followed by various amount of stretch) or not (normally timed septal contraction with minimal stretch). CRT implantation was performed under invasive left ventricular (LV) pressure monitoring and we defined acute CRT response as ≥10% increase in LV dP/dtmax. End-diastolic pressure (EDP) and QRS width served as a diastolic and electrical parameter, respectively. LV dP/dtmax improved under BIVP (737 ± 177 mmHg/s vs. 838 ± 199 mmHg/s, P < 0.001) and 26 patients (68%) were defined as acute CRT responders. Patients with premature septal contraction (n = 27) experienced acute improvement in systolic (ΔdP/dtmax: 18.3 ± 8.9%, P < 0.001), diastolic (ΔEDP: -30.6 ± 29.9%, P < 0.001) and electrical (ΔQRS width: -23.3 ± 13.2%, P < 0.001) parameters. No improvement under BIVP was observed in patients (n = 11) with normally timed septal contraction (ΔdP/dtmax: 4.0 ± 7.8%, P = 0.12; ΔEDP: -8.8 ± 38.4%, P = 0.47 and ΔQRS width: -0.9 ± 11.4%, P = 0.79)., Conclusion: Septal contraction patterns are an excellent predictor of acute CRT response. Only patients with premature septal contraction experienced acute systolic, diastolic, and electrical improvement under BIVP., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Objectives: The purpose of this study was to investigate how LBBB and CRT modify RV free wall function by direct ventricular interaction., Background: Right ventricular (RV) function influences prognosis in patients with left bundle branch block (LBBB) and cardiac resynchronization therapy (CRT). There is, however, limited insight into how LBBB and CRT affect RV function., Methods: In 24 patients with LBBB with nonischemic cardiomyopathy, RV and left ventricular (LV) strain by speckle-tracking echocardiography was measured before and after CRT. Underlying mechanisms were studied in 16 anesthetized dogs with ultrasonic dimension crystals and micromanometers., Results: Patients with LBBB demonstrated distinct early systolic shortening in the RV free wall, which coincided with the typical abnormal early systolic septal shortening. In animals, this RV free wall contraction pattern resulted in reduced myocardial work as a large portion of the shortening occurred against low pressure during early systole, coinciding with abnormal leftward septal motion. RV systolic function was maintained by vigorous contraction in the late-activated LV lateral wall, which pushed the septum toward the RV. CRT reduced abnormal septal motion and increased RV free wall work because there was less inefficient shortening against low pressure., Conclusions: LBBB reduces workload on the RV free wall because of abnormal septal motion and delayed activation of the LV lateral wall. Restoring septal and LV function by CRT increases workload in RV free wall and may explain why patients with RV failure respond poorly to CRT. (Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy [CRID-CRT]; NCT02525185)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Regional myocardial work may be assessed by pressure-strain analysis using a non-invasive estimate of left ventricular pressure (LVP). Strain by speckle tracking echocardiography (STE) is not always accessible due to poor image quality. This study investigated the estimation of regional myocardial work from strain by feature tracking (FT) cardiac magnetic resonance (CMR) and non-invasive LVP., Methods and Results: Thirty-seven heart failure patients with reduced ejection fraction, left bundle branch block (LBBB), and no myocardial scar were compared to nine controls without LBBB. Circumferential strain was measured by FT-CMR in a mid-ventricular short-axis cine view, and longitudinal strain by STE. Segmental work was calculated by pressure-strain analysis. Twenty-five patients underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography. Segmental values were reported as percentages of the segment with maximum myocardial FDG uptake. In LBBB patients, net CMR-derived work was 51 ± 537 (mean ± standard deviation) in septum vs. 1978 ± 1084 mmHg·% in the left ventricular (LV) lateral wall (P < 0.001). In controls, however, there was homogeneous work distribution with similar values in septum and the LV lateral wall (non-significant). Reproducibility was good. Segmental CMR-derived work correlated with segmental STE-derived work and with segmental FDG uptake (average r = 0.71 and 0.80, respectively)., Conclusion: FT-CMR in combination with non-invasive LVP demonstrated markedly reduced work in septum compared to the LV lateral wall in patients with LBBB. Work distribution correlated with STE-derived work and energy demand as reflected in FDG uptake. These results suggest that FT-CMR in combination with non-invasive LVP is a relevant clinical tool to measure regional myocardial work., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: This study sought to investigate how regional left ventricular (LV) function modifies septal motion in left bundle branch block (LBBB)., Background: In LBBB, the interventricular septum often has marked pre-ejection shortening, followed by immediate relengthening (rebound stretch). This motion, often referred to as septal flash, is associated with positive response to cardiac resynchronization therapy (CRT)., Methods: In 10 anesthetized dogs, we induced LBBB by radiofrequency ablation and occluded the circumflex (CX) (n = 10) and left anterior descending (LAD) (n = 6) coronary arteries, respectively. Myocardial dimensions were measured by sonomicrometry and myocardial work by pressure-segment length analysis. In 40 heart failure patients with LBBB, including 20 with post-infarct scar and 20 with nonischemic cardiomyopathy, myocardial strain was measured by speckle-tracking echocardiography and myocardial work by pressure-strain analysis. Scar was assessed by cardiac magnetic resonance imaging with late gadolinium enhancement., Results: During LBBB, each animal showed typical septal flash with pre-ejection shortening and rebound stretch, followed by reduced septal systolic shortening (p < 0.01). CX occlusion caused LV lateral wall dysfunction and abolished septal flash due to loss of rebound stretch (p < 0.0001). Furthermore, CX occlusion restored septal systolic shortening to a similar level as before induction of LBBB and substantially improved septal work (p < 0.001). LAD occlusion, however, accentuated septal flash by increasing rebound stretch (p < 0.05). Consistent with the experimental findings, septal flash was absent in patients with LV lateral wall scar due to lack of rebound stretch (p < 0.001), and septal systolic shortening and septal work far exceeded values in nonischemic cardiomyopathy (p < 0.0001). Septal flash was present in most patients with anteroseptal scar., Conclusions: LV lateral wall dysfunction and scar abolished septal flash and markedly improved septal function in LBBB. Therefore, function and scar in the LV lateral wall should be taken into account when septal motion is used to evaluate dyssynchrony., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to investigate the hypothesis that patients with left bundle branch block (LBBB) are hypersensitive to elevated afterload., Background: Epidemiological data suggest that LBBB can provoke heart failure in patients with hypertension., Methods: In 11 asymptomatic patients with isolated LBBB and 11 age-matched control subjects, left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were measured by echocardiography. Systolic arterial pressure was increased by combining pneumatic extremity constrictors and handgrip exercise. To obtain more insight into mechanisms of afterload response, 8 anesthetized dogs with left ventricular (LV) micromanometer and dimension crystals were studied during acutely induced LBBB and aortic constriction. Regional myocardial work was assessed by LV pressure-dimension analysis., Results: Consistent with normal afterload dependency, elevation of systolic arterial pressure by 38 ± 12 mm Hg moderately reduced LVEF from 60 ± 4% to 54 ± 6% (p < 0.01) in control subjects. In LBBB patients, however, a similar blood pressure increase caused substantially larger reduction in LVEF (p < 0.01), from 56 ± 6% to 42 ± 7% (p < 0.01). There were similar findings for GLS. In the dog model, aortic constriction abolished septal shortening (p < 0.02), and septal work decreased to negative values (p < 0.01). Therefore, during elevated systolic pressure, the septum made no contribution to global LV work, as indicated by net negative work, and instead absorbed energy from work done by the LV lateral wall., Conclusions: Moderate elevation of arterial pressure caused marked reductions in LVEF and GLS in patients with LBBB. This reflects a cardiodepressive effect of elevated afterload in the dyssynchronous ventricle and was attributed to loss of septal function., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: There are conflicting data and no consensus on how to measure acute response to cardiac resynchronization therapy (CRT). This study investigates, which contractility indices are best markers of acute CRT response., Methods and Results: In eight anaesthetized dogs with left bundle branch block, we measured left ventricular (LV) pressure by micromanometer and end-diastolic volume (EDV) and end-systolic volume (ESV) by sonomicrometry. Systolic function was measured as LV ejection fraction (EF), peak rate of LV pressure rise (LV dP/dtmax) and as a gold standard of contractility, LV end-systolic elastance (Ees), and volume axis intercept (V0) calculated from end-systolic pressure-volume relations (ESPVR). Responses to CRT were compared with inotropic stimulation by dobutamine. Both CRT and dobutamine caused reduction in ESV (P < 0.01) and increase in LV dP/dtmax (P < 0.05). Both interventions shifted the ESPVR upwards indicating increased contractility, but CRT which reduced V0 (P < 0.01), caused no change in Ees. Dobutamine markedly increased Ees, which is the typical response to inotropic stimulation. Preload (EDV) was decreased (P < 0.01) by CRT, and there was no change in EF. When adjusting for the reduction in preload, CRT increased EF (P = 0.02) and caused a more marked increase in LV dP/dtmax (P < 0.01)., Conclusion: Increased contractility by CRT could not be identified by Ees, which is a widely used reference method for contractility. Furthermore, reduction in preload by CRT attenuated improvement in contractility indices such as EF and LV dP/dtmax. These results suggest that changes in LV volume may be more sensitive markers of acute CRT response than conventional contractility indices.

Background: Patient-specific left ventricular (LV) lead optimisation strategies with immediate feedback on cardiac resynchronisation therapy (CRT) effectiveness are needed. The purpose of this study was to compare contractility surrogates derived from biventricular lead motion analysis to the peak positive time derivative of LV pressure (dP/dt max) in patients undergoing CRT implantation., Methods: Twenty-seven patients underwent CRT implantation with continuous haemodynamic monitoring. The right ventricular (RV) lead was placed in apex and a quadripolar LV lead was placed laterally. Biplane fluoroscopy cine films facilitated construction of three-dimensional RV-LV interlead distance waveforms at baseline and under biventricular pacing (BIVP) from which the following contractility surrogates were derived; fractional shortening (FS), time to peak systolic contraction and peak shortening of the interlead distance (negative slope). Acute haemodynamic CRT response was defined as LV ∆dP/dt max ≥ 10 %., Results: We observed a mean increase in dP/dt max under BIVP (899±205 mm Hg/s vs 777±180 mm Hg/s, p<0.001). Based on ΔdP/dt max , 18 patients were classified as acute CRT responders and nine as non-responders (23.3%±10.6% vs 1.9±5.3%, p<0.001). The baseline RV-LV interlead distance was associated with echocardiographic LV dimensions (end diastole: R=0.61, p=0.001 and end systole: R=0.54, p=0.004). However, none of the contractility surrogates could discriminate between the acute CRT responders and non-responders (ΔFS: -2.5±2.6% vs - 2.0±3.1%, p=0.50; Δtime to peak systolic contraction: -9.7±18.1% vs -10.8±15.1%, p=0.43 and Δpeak negative slope: -8.7±45.9% vs 12.5±54.8 %, p=0.09)., Conclusion: The baseline RV-LV interlead distance was associated with echocardiographic LV dimensions. In CRT recipients, contractility surrogates derived from the RV-LV interlead distance waveform could not discriminate between acute haemodynamic responders and non-responders., Competing Interests: Competing interests: Trent Fischer, Lars Ove Gammelsrud and Richard Cornelussen are full time Medtronic employees.

Aims: A difficult cardiac resynchronization therapy (CRT) implantation scenario emerges when no lateral pacing option exists. The aim of this study was to explore the effect of biventricular pacing (BIVP) on vectorcardiographic parameters in patients with a non-lateral left ventricular (LV) lead position. We hypothesized that perimeter and area reduction for both the QRS complex and T-wave would predict acute CRT response., Methods and Results: Twenty-six patients (14 ischaemic) with a mean age of 63 ± 10 years and standard CRT indication underwent device implantation with continuous LV pressure registration. The LV lead was placed in either an anterior or apical position. Biventricular pacing was performed at a rate 10% above intrinsic rhythm with acute CRT response defined as LV ΔdP/dtmax >10%. Using this criterion 12 patients were identified as acute CRT responders (responders: 16.7 ± 4.8% vs. non-responders: 1.9 ± 5.3%, P < 0.001). Vectorcardiographic assessment of the QRS complex and T-wave were performed at baseline and under BIVP. Based on the observed changes in three-dimensional area and perimeter, ΔQRS-area (responders: -46.7 ± 39.6% vs. non-responders: 1.1 ± 50.9%, P = 0.006) was considered as the preferred parameter. Receiver operating characteristic curve analysis identified -40% as the optimal cut-off value (sensitivity 67% and specificity 93%) for prediction of acute CRT response (AUC = 0.81, P < 0.01). A significant correlation was observed between LV ΔdP/dtmax and ΔQRS-area (R2 = 0.37, P = 0.001)., Conclusion: ΔQRS-area is correlated to LV ΔdP/dtmax and predicts acute CRT response in patients with a non-lateral LV lead position. Assessment of ΔQRS-area might be a useful tool for patient specific LV lead placement when no lateral pacing option exists.

Aims: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in heart failure. However, prediction of the outcome remains difficult. We aimed to investigate for echocardiographic predictors of ventricular arrhythmias and fatal outcome and to explore how myocardial function is changed by biventricular pacing in heart failure., Methods and Results: We prospectively included 170 heart failure patients (66 ± 10 years, New York Heart Association class 2.8 ± 0.5, 48% ischaemic cardiomyopathy) and recorded ventricular arrhythmias and fatal end point defined as death, heart transplantation, or left ventricular assist device implantation during 2 years. Two-dimensional echocardiography was performed before and 6 months after CRT implantation. CRT response was defined as ≥15% reduction in end-systolic volume at 6 months. Speckle-tracking technique was performed to assess longitudinal and circumferential left ventricular function, defined as global longitudinal (GLS) and circumferential strain (GCS), and to assess mechanical dyssynchrony, defined as mechanical dispersion. GLS before CRT was a predictor of fatal end point independently of CRT response [hazard ratio, HR 1.14 (1.02-1.27), P = 0.02]. Patients with GLS better than -8.3% showed event-free survival benefit (log rank, P < 0.001). Mechanical dispersion at 6 months was an independent predictor of ventricular arrhythmias [HR 1.20 (1.06-1.35), P = 0.005]. CRT responders (59%) had improvement of both GLS and GCS., Conclusion: In heart failure patients with CRT, worse longitudinal function before CRT was an important predictor of fatal outcome during 2 years, independently of CRT response. Mechanical dispersion at 6 months was a strong predictor of ventricular arrhythmias. CRT response by reverse remodelling was dependent on improvement of both longitudinal and circumferential function., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Risk prediction of ventricular arrhythmias after myocardial infarction (MI) is still insufficient. Prolonged QTc is a known risk marker of mortality and ventricular arrhythmias. QTc has not achieved clinical importance in predicting arrhythmic events in patients after MI. Recent studies have displayed that the terminal part of the QT-interval, Tpeak to Tend (TpTe), may be a more promising predictor of adverse outcome. Herein, we assessed whether TpTe may serve as a predictor of ventricular arrhythmias in patients with previous MI fulfilling current implantable cardioverter-defibrillator (ICD) indications., Methods: Seventy-six patients with previous MI eligible for ICD therapy were prospectively enrolled. ECG measurements at baseline were recorded using a 12-lead ECG with 50 mm/s paper speed. TpTe was measured from peak of the T wave to end of T wave. Events during follow up were defined as ventricular arrhythmias requiring appropriate ICD therapy, including antitachycardia pacing and shock., Results: During 23 ± 19 months, arrhythmic events occurred in 36 (47%) patients. TpTe was longer in ICD patients with recorded ventricular arrhythmias compared with those without (116 ± 26 ms vs. 102 ± 20 ms; P = 0.01), whereas ejection fraction (EF) at baseline did not differ (35 ± 9% vs. 35 ± 11%; P = 0.87). TpTe was an independent predictor of ventricular arrhythmias when adjusted for age, EF and QRS duration (HR 1.16; 95% CI 1.03-1.31; P = 0.02)., Conclusions: TpTe predicted malignant arrhythmias in patients after MI independently of EF. TpTe may contribute in the risk stratification of patients to identify post-MI patients disposed to malignant arrhythmias and their need of ICD therapy., (© 2014 Wiley Periodicals, Inc.)