A canine model of chronic ischemic heart failure.

Preclinical large animal models of chronic heart failure (HF) are crucial to both understanding pathological remodeling and translating fundamental discoveries into novel therapeutics for HF. Canine models of ischemic cardiomyopathy are historically limited by either high early mortality or failure to develop chronic heart failure. Twenty-nine healthy adult dogs (30 ± 4 kg, 15/29 male) underwent thoracotomy followed by one of three types of left anterior descending (LAD) coronary artery ligation procedures: group 1 (n = 4) (simple LAD: proximal and distal LAD ligation); group 2 (n = 14) (simple LAD plus lateral wall including ligation of the distal first diagonal and proximal first obtuse marginal); and group 3 (n = 11) (total LAD devascularization or TLD: simple LAD plus ligation of proximal LAD branches to both the right and left ventricles). Dogs were followed until chronic severe HF developed defined as left ventricular ejection fraction (LVEF) < 40% and NH2-terminal-prohormone B-type natriuretic peptide (NT-proBNP) > 900 pmol/L. Overall early survival (48-h postligation) in 29 dogs was 83% and the survival rate at postligation 5 wk was 69%. Groups 1 and 2 had 100% and 71% early survival, respectively, yet only a 50% success rate of developing chronic HF. Group 3 had excellent survival at postligation 48 h (91%) and a 100% success in the development of chronic ischemic HF. The TLD approach, which limits full LAD and collateral flow to its perfusion bed, provides excellent early survival and reliable development of chronic ischemic HF in canine hearts.NEW & NOTEWORTHY The novel total left anterior descending devascularization (TLD) approach in a canine ischemic heart failure model limits collateral flow in the ischemic zone and provides excellent early survival and repeatable development of chronic ischemic heart failure in the canine heart. This work provides a consistent large animal model for investigating heart failure mechanisms and testing novel therapeutics.

Antitachycardia pacing at the His bundle is safer than conventional right ventricular antitachycardia pacing in a canine myocardial ischemic injury model.

INTRODUCTION: Antitachycardia pacing (ATP) is used to terminate ventricular tachycardia (VT) by delivering rapid, low energy pacing to the right ventricle (RV). Unfortunately, ATP is not effective against all VT episodes and can result in adverse outcomes, such as VT acceleration and degeneration into ventricular fibrillation (VF). Improving ATP is therefore desirable. Our objective was to compare the efficacy and safety of ATP delivered at the His bundle to traditional ATP. METHODS: Six dogs were anesthetized and pacing leads were implanted in the RV and His bundle. The left anterior descending artery was occluded for 2 h to create an ischemic injury. In a study 4-7 days later, a 128-electrode sock was placed snugly around the ventricles and VT was induced using rapid pacing. ATP was delivered from either the His bundle or RV lead, then attempted at the other location if unsuccessful. Success rates and instances of VT acceleration and degeneration into VF were calculated. RESULTS: We induced 83 runs of VT and attempted ATP 128 times. RV ATP was successful in 36% of attempts; His ATP was successful in 38% of attempts. RV ATP resulted in significantly more adverse outcomes. RV and His ATP induced VT acceleration in 9% and 3% of trains, respectively, and induced degeneration into VF in 5% and 1% of trains, respectively. CONCLUSION: His bundle ATP is safer, but not significantly more effective, than RV ATP.

Non-invasive epicardial and endocardial electrocardiographic imaging for scar-related ventricular tachycardia.

Aims: Contact mapping is currently used to guide catheter ablation of scar-related ventricular tachycardia (VT) but usually provides incomplete assessment of 3D re-entry circuits and their arrhythmogenic substrates. This study investigates the feasibility of non-invasive electrocardiographic imaging (ECGi) in mapping scar substrates and re-entry circuits throughout the epicardium and endocardium. Methods and results: Four patients undergoing endocardial and epicardial mapping and ablation of scar-related VT had computed tomography scans and a 120-lead electrocardiograms, which were used to compute patient-specific ventricular epicardial and endocardial unipolar electrograms (CEGMs). Native-rhythm CEGMs were used to identify sites of myocardial scar and signal fractionation. Computed electrograms of induced VT were used to localize re-entrant circuits and exit sites. Results were compared to in vivo contact mapping data and epicardium-based ECGi solutions. During native rhythm, an average of 493 ± 18 CEGMs were analysed on each patient. Identified regions of scar and fractionation comprised, respectively, 25 ± 4% and 2 ± 1% of the ventricular surface area. Using a linear mixed-effects model grouped at the level of an individual patient, CEGM voltage and duration were significantly associated with contact bipolar voltage. During induced VT, the inclusion of endocardial layer in ECGi made it possible to identify two epicardial vs. three endocardial VT exit sites among five reconstructed re-entry circuits. Conclusion: Electrocardiographic imaging may be used to reveal sites of signal fractionation and to map short-lived VT circuits. Its capacity to map throughout epicardial and endocardial layers may improve the delineation of 3D re-entry circuits and their arrhythmogenic substrates.

Noninvasive epicardial and endocardial electrocardiographic imaging of scar-related ventricular tachycardia.

BACKGROUND: The majority of life-threatening ventricular tachycardias (VTs) are sustained by heterogeneous scar substrates with narrow strands of surviving tissue. An effective treatment for scar-related VT is to modify the underlying scar substrate by catheter ablation. If activation sequence and entrainment mapping can be performed during sustained VT, the exit and isthmus of the circuit can often be identified. However, with invasive catheter mapping, only monomorphic VT that is hemodynamically stable can be mapped in this manner. For the majority of patients with poorly tolerated VTs or multiple VTs, a close inspection of the re-entry circuit is not possible. A noninvasive approach to fast mapping of unstable VTs can potentially allow an improved identification of critical ablation sites. METHODS: For patients who underwent catheter ablation of scar-related VT, CT scan was obtained prior to the ablation procedure and 120-lead body-surface electrocardiograms (ECGs) were acquired during induced VTs. These data were used for noninvasive ECG imaging to computationally reconstruct electrical potentials on the epicardium and on the endocardium of both ventricles. Activation time and phase maps of the VT circuit were extracted from the reconstructed electrograms. They were analyzed with respect to scar substrate obtained from catheter mapping, as well as VT exits confirmed through ablation sites that successfully terminated the VT. RESULTS: The reconstructed re-entry circuits correctly revealed both epicardial and endocardial origins of activation, consistent with locations of exit sites confirmed from the ablation procedure. The temporal dynamics of the re-entry circuits, particularly the slowing of conduction as indicated by the crowding and zig-zag conducting of the activation isochrones, collocated well with scar substrate obtained by catheter voltage maps. Furthermore, the results indicated that some re-entry circuits involve both the epicardial and endocardial layers, and can only be properly interpreted by mapping both layers simultaneously. CONCLUSIONS: This study investigated the potential of ECG-imaging for beat-to-beat mapping of unstable reentrant circuits. It shows that simultaneous epicardial and endocardial mapping may improve the delineation of the 3D spatial construct of a re-entry circuit and its exit. It also shows that the use of phase mapping can reveal regions of slow conduction that collocate well with suspected heterogeneous regions within and around the scar.

Understanding the Utility of Endocardial Electrocardiographic Imaging in Epi-Endocardial Mapping of 3D Reentrant Circuits.

Background: Studies of VT mechanisms are largely based on a 2D portrait of reentrant circuits on one surface of the heart. This oversimplifies the 3D circuit that involves the depth of the myocardium. Simultaneous epicardial and endocardial (epi-endo) mapping was shown to facilitate a 3D delineation of VT circuits, which is however difficult via invasive mapping. Objective: This study investigates the capability of noninvasive epicardial-endocardial electrocardiographic imaging (ECGI) to elucidate the 3D construct of VT circuits, emphasizing the differentiation of epicardial, endocardial, and intramural circuits and to determine the proximity of mid-wall exits to the epicardial or endocardial surfaces. Methods: 120-lead ECGs of VT in combination with subject-specific heart-torso geometry are used to compute unipolar electrograms (CEGM) on ventricular epicardium and endocardia. Activation isochrones are constructed, and the percentage of activation within VT cycle length is calculated on each surface. This classifies VT circuits into 2D (surface only), uniform transmural, nonuniform transmural, and mid-myocardial (focal on surfaces). Furthermore, the endocardial breakthrough time was accurately measured using Laplacian eigenmaps, and by correlating the delay time of the epi-endo breakthroughs, the relative distance of a mid-wall exit to the epicardium or the endocardium surfaces was identified. Results: We analyzed 23 simulated and in-vivo VT circuits on post-infarction porcine hearts. In simulated circuits, ECGI classified 21% as 2D and 78% as 3D: 82.6% of these were correctly classified. The relative timing between epicardial and endocardial breakthroughs was correctly captured across all cases. In in-vivo circuits, ECGI classified 25% as 2D and 75% as 3D: in all cases, circuit exits and entrances were consistent with potential critical isthmus delineated from combined LGE-MRI and catheter mapping data. Conclusions: ECGI epi-endo mapping has the potential for fast delineation of 3D VT circuits, which may augment detailed catheter mapping for VT ablation.