Mutual Arrangements of Coronary Blood Vessels within the Right Atrial Appendage Vestibule

Background: The aim of our study was to investigate the presence and mutual relationships of coronary vessels within the right atrial appendage (RAA) vestibule. Methods: We examined 200 autopsied hearts. The RAA vestibule was cross-sectioned along its isthmuses (superior, middle, and inferior). Results: The right coronary artery (RCA) was present in 100% of the superior RAA isthmuses but absent in 2.0% of hearts within the middle isthmus and in 6.5% of hearts within the inferior RAA isthmus. Its diameter was quite uniform along the superior (2.6 ± 0.8 mm), middle (2.9 ± 1.1 mm), and inferior (2.7 ± 0.9 mm) isthmuses (p = 0.12). The location of the RCA varied significantly, and it was sometimes accompanied by other accessory coronary vessels. In all the isthmuses, the RCA ran significantly closer to the endocardial surface than to the epicardial surface (p < 0.001). At the superior RAA isthmus, the artery was furthest from the right atrial endocardial surface and this distance gradually decreased between the middle RAA isthmus and the inferior RAA. Conclusions: This study was the most complex analysis of the mutual arrangements and morphometric characteristics of coronary blood vessels within the RAA vestibule. Awareness of additional blood vessels within the vestibule can help clinicians plan and perform safe and efficacious procedures in this region.

In-vivo endocardial and epicardial quantitative comparison of multi-wave based non-invasive inverse electrocardiography

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the Dutch Heart Foundation Introduction Non-invasive mapping of ventricular activation using inverse electrocardiography (iECG) in patients with cardiomyopathy during sinus rhythm, may improve risk stratification for sudden cardiac death. However, iECG is complicated by multiple simultaneous endocardial activation waves (multi-wave) mediated by the His-Purkinje system, especially when the QRS complex is narrow. The activation estimation should be based on a realistic physiological model of the His-Purkinje system combining multiple waves initiated at His-Purkinje associated endocardial locations. Equivalent double layer based iECG provides an estimation of both the endocardial and epicardial surface. To improve accuracy, equivalent double layer based iECG was supplemented with electro-anatomical structures associated with the His-Purkinje system to test initial ventricular activation (Figure, Panel C). Multi-wave iECG local activation timing (LAT) maps and invasive LAT maps during sinus rhythm were quantitatively compared. Purpose Quantitative comparison of multi-wave iECG in His-Purkinje mediated cardiac activation using invasive activation maps in patients. Methods Thirteen patients referred for invasive electro-anatomical mapping (EAM) of the endocardial and epicardial surface were included. Prior to EAM, each subject underwent 64 electrode body surface potential mapping, cardiac computed tomography (CT) imaging, and 3D imaging of electrode positions. Anatomical models of the ventricles, lungs and thorax were created using CT images and supplemented with electrode positions (Figure, Panel A-B). Electro-anatomical structures associated with the His-Purkinje system were incorporated in ventricular anatomical models (Figure, Panel C) and multiple simultaneous activation waves were simulated. Invasive endocardial and epicardial LAT maps were quantitatively compared to iECG LAT maps. Invasive EAM LAT maps were quantitatively compared to estimated iECG LAT maps (Figure, Panel D) using inter-map correlation coefficients (CC, Pearson’s) and absolute differences (AD). Results Mean inter-map CC and AD were 0.54 ± 0.19 and 18 ± 7 ms respectively for the epicardial surface (n = 13). Similar to the RV endocardial surface (n = 10, CC = 0.50 ± 0.29, AD = 20 ± 8 ms) and the LV endocardial surface (n = 4, CC = 0.44 ± 0.26, AD = 25 ± 7 ms). Conclusion(s): Quantitative comparison of the multi-wave iECG method showed overall moderate performance. This novel iECG method provides a physiologically more realistic and more robust estimation of sinus rhythm and may serve as a tool for detection of electro-anatomical substrates and risk stratification. Compared to other available non-invasive ECG methods, multi-wave iECG captures His-Purkinje mediated ventricular activation better. This method might also be useful for the accurate detection and localization of structural conduction disorders. Abstract Figure. Multi-Wave inverse electrocardiography

The incidence and clinical ramifications for leadless pacemaker fixation mechanism exposure on the epicardial surface

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Boston Scientific and Abbott Background Leadless pacemaker (LP) fixation mechanism exposure (FE) by penetration of the epicardial surface has been described. Previously reported animal model studies showed FE for 7/10 Micra LPs, versus 4/10 CapSureFix Novus RV pacing leads (both Medtronic). However, it is unknown whether FE causes pericardial effusion or pericarditis or does not have clinical significance. Purpose To determine the incidence of FE of a novel LP in a chronic animal model and its association with acute or chronic pericardial effusion. Methods Canine subjects were implanted with novel LPs (Boston Scientific) in an ongoing study. Acute pericardial effusion was assessed by post-procedural transthoracic echocardiography (TTE). Chronic pericardial effusion was assessed by TTE 90 days after implantation and post-mortem assessed pericardial fluid colour (PFC) and volume (PFV). FE was assessed visually at necropsy. Mann-Whitney U tests and chi-squared tests were used to determine whether greater PFV, more haemorrhagic PFC or LP implantation location differed significantly between subjects with and without FE. Results Results to date are reported. Canine subjects (n = 71) were chronically implanted with LPs. Due to 14 in-vivo retrievals, data is shown of 57 subjects with LPs in situ at necropsy. Pre-deployment radiocontrast injection confirmed LP position (RV apex n = 41; RV apicoseptal n = 16), and mechanical stability and electrical testing confirmed adequate talon fixation after deployment. Necropsy after median 94 days (IQR 91-540) demonstrated FE in 11 cases (19%) (figure). No acute nor chronic pericardial effusion was seen on TTE. Mean PFV for animals with and without FE was 1.8 and 1.6 cc, respectively. FE did not show an association with PFV or colour (p= 0.53 and p = 0.83, respectively). For two animals, PFV and PFC are not available; FE was not observed in either of these cases. LP implantation location was not associated with incidence of FE (p = 1.00). Conclusion Fixation mechanism exposure by the talons of a novel leadless pacemaker was observed in 19% of animals implanted and was not associated with acute or chronic pericardial effusion. Abstract Figure 1

Mutual arrangements of coronary blood vessels within the right atrial appendage vestibule.

Introduction: The aim of our study was to investigate the presence and mutual relationships of coronary vessels within the right atrial appendage RAA vestibule. Methods and Results: We examined 200 autopsied hearts. The RAA vestibule was cross sectioned along its isthmuses (superior, middle, and inferior). We assessed the presence and mutual relationships between coronary blood vessels. The right coronary artery (RCA) was present in 100% of the superior RAA isthmuses but absent in 2.0% of hearts within the middle isthmus and in 6.5% of hearts within the inferior RAA isthmus. Its diameter was quite uniform along the superior (2.6±0.8mm), middle (2.9±1.1mm) and inferior (2.7±0.9mm) isthmuses (p=0.12). The location of the RCA varied significantly, and it was sometimes accompanied by other accessory coronary vessels. In all the isthmuses, the RCA ran significantly closer to the endocardial surface than to the epicardial surface (p<0.001). At the superior RAA isthmus, the artery was furthest from the right atrial endocardial surface and this distance gradually decreased between the middle RAA isthmus and the inferior RAA isthmus (9.0±4.0 vs. 6.2±3.0 vs. 4.8±2.3mm, respectively; p<0.001). The interposed RCA was found in 7.0% of cases within the superior isthmus, in 2.5% within the middle isthmus and in 1.5% within the inferior isthmus. Conclusions: This study was the most complex analysis of the mutual arrangements and morphometric characteristics of coronary blood vessels within the RAA vestibule. Awareness of additional blood vessels within the vestibule can help clinicians plan and perform safe and efficacious procedures in this region.

Epicardial Surface Area of Infarction

Background: Microvascular obstruction (MO) is a pathophysiologic complication of acute myocardial infarction that portends poor prognosis; however, it is transient and disappears with infarct healing. Much remains unknown regarding its pathophysiology and whether there are predictors of MO that could function as stable surrogates. We tested for clinical and cardiovascular magnetic resonance predictors of MO to gain insight into its pathophysiology and to find a stable surrogate. Methods: Three hundred two consecutive patients from 2 centers underwent cardiovascular magnetic resonance within 2 weeks of first acute myocardial infarction. Three measures of infarct morphology: infarct size, transmurality, and a new index—the epicardial surface area (EpiSA) of full-thickness infarction—were quantified on delayed-enhancement cardiovascular magnetic resonance. Results: Considering all clinical characteristics, only measures of infarct morphology were independent predictors of MO. EpiSA was the strongest predictor of MO and provided incremental predictive value beyond that of infarct size and transmurality ( P <0.0001). In patients with 3-month follow-up cardiovascular magnetic resonance (n=81), EpiSA extent remained stable while MO disappeared, and EpiSA was a predictor of adverse ventricular remodeling. After 20 months of follow-up, 11 died and 1 had heart transplantation. Patients with an EpiSA larger than the median value (≥6%) had worse outcome than those with less than the median value (adverse events: 6.4% versus 1.9%, P =0.045). Conclusions: The EpiSA of infarction is a novel index of infarct morphology which accurately predicts MO during the first 2 weeks of MI, but unlike MO, does not disappear with infarct healing. This index has potential as a stable surrogate of the presence of acute MO and may be useful as a predictor of adverse remodeling and outcome which is less dependent on the time window of patient assessment.

Noninvasive assessment of dynamic cardiac electrophysiology in normal human subjects

Introduction Electrocardiographic imaging (ECGI) has been used to investigate arrhythmia mechanisms in various conditions. Data on normal human subjects, especially in Europe, are scarce. Dynamic characteristics of ventricular activation and recovery during sinus rhythm have not been assessed before. Purpose To examine cardiac electrophysiology and its dynamic aspects in normal subjects using ECGI, in order to provide a range of normal patterns and values for activation (AT) and recovery times (RT), activation-recovery intervals (ARI, a surrogate for action potential duration) and their dynamicity. Methods 11 Subjects (age 57±7 years, 27% male, all normal LVEF) with atypical chest pain who underwent a cardiac CT-scan as part of clinical care but who were negative for any pathology on full examination were included. A validated non-commercial potential-based formulation of ECGI was used to reconstruct unipolar electrograms (EGMs) on the epicardial surface for three sinus beats within minutes from each other, per individual. ATs and RTs were determined as the maximum negative upslope during QRS, and maximum positive upslope during T wave of the local EGMs. Additionally, we determined locations of first and last activation and recovery. Inter- and intra-individual differences were computed. Results Subjects had normal 12-lead characteristics without ST-deviations, and an average QTc interval of 415±18ms. Figure 1, panel A shows ECGI during sinus rhythm for 3 representative subjects, and panel B summarizes all findings on the entire epicardium. The first epicardial activation breakthrough typically occurred on the right ventricle (RV), consistent with the concept that the thinner RV wall accounts for a faster transmural activation. Last activation was mostly on the base of the left ventricle (LV), on the inferior to lateral wall. Earliest recovery occurred predominantly on the anterior surface, while latest recovery occurred on the inferior surface. Complete activation of the epicardial surface (from earliest to latest AT) took 41±8ms, while recovery (earliest AT to latest RT) took 317±24ms and average ARI (local AT to local RT) took 232±23ms. Thus, inter-individual variation of recovery duration was higher than of activation. Intra-individual differences between beats in ATs, RTs and ARIs of distinct sinus beats were small (2.3±3.1ms, 9.7±8.8ms and 9.8±9.1ms, respectively) suggesting that ECGI enables stable reconstruction quality (Figure 1, panel C). Conclusion In this cohort, noninvasive ECGI provides novel insights in ventricular electrophysiology. Electrical recovery is more variable than activation, both intra-individually and inter-individually. Overall, AT, RT and ARI differences between sinus beats were low. ECGI appears suitable to assess dynamic electrical patterns during cardiac pathology. Figure 1 Funding Acknowledgement Type of funding source: None

Evaluation of noninvasive electrophysiological imaging accuracy for focal atrial arrhythmias

Background High accuracy of noninvasive electrocardiographic imaging (ECGI) has recently been shown for topical diagnostics of ventricular arrhythmias. However, the precision of diagnostics of atrial focal arrhythmias requires clarification. To estimate the accuracy of ECGI for premature atrial contraction (PAC) we performed atrial pacing in patients with CRT system and compared early activation zone (EAZ) with pacemaker's tip location. Purpose To determine the accuracy of ECGI for focal atrial arrhythmias using atrial pacing. Methods Twenty-six patients (m/f – 18/9), age (min–max) 52 (26–78) with CRT system and pacemaker's tip location in the right atrium (RA) appendage underwent ECGI (“Amycard 01C”) in combination with CT or MR imaging. Thirty-four atrial pacing (mono- and bipolar) was performed in all patients using standard amplitude 1.5–3.8 mV. Epi-/endocardial polygonal heart models were created and isopotential maps were calculated. The distance between EAZ and the pacemaker's tip were measured for ECG recordings without using the isoline filter on endocardial surface (Fig. 1) as well as for epicardial surface. The time between epicardial and endocardial EAZ breakthrough was calculated also. Results On endocardial surface the EAZ was located in RA appendage, the base of superior cava vena or superior lateral RA wall. The distance (mm) (Me (min; max)) between EAZ and the pacemacer's tip was 28 (6; 68). For epicardial surface in most cases the EAZ was also located in RA appendage, the base of superior cava vena or superior lateral RA wall. In two cases the EAZ was located in inferior septal RA wall, in one case - in superior septal RA wall and in five cases the EAZ was undetectable. The distance between EAZ and the pacemacer's tip was 22 (6; 48). The time (ms) (Mean; Me (min; max)) between EAZ of the endocardial and epicardial surfaces was 16; 7 (0; 68). Conclusion ECGI allows to assess the location of focal atrial arrhythmias on endocardial surface and sometimes on epicardial surface also within the three segments. The results of this study revealed that accuracy of ECGI for atrial arrhythmias is worse than for ventricular arrhythmias. However, it is better on epicardial surface of atrium when EAZ can be determined. Funding Acknowledgement Type of funding source: None

P357Epicardial abnormal electrical activity in unselected patients with ischemic ventricular tachycardia: a pilot mapping study

Background radiofrequency catheter ablation (RFA) on the endocardial ventricular surface is widely used for post-myocardial infarction (post-MI) ventricular tachycardia (VT) treatment. It has been described that about 10% of patients with post-MI require additional epicardial ablation for successful VT termination. However, there is still lack of data regarding the extent of scarring and the presence of local abnormal ventricular electrical activity (LAVA, low-voltage and/or fractionated signals) on the epicardial surface in patients with ischemic VT. Purpose to assess the extent of epicardial electrophysiological substrate in patients with remote myocardial infarction and indications for VT ablation. Methods thirteen out of 59 patients with sustained ischemic VT (12 men; mean age 59,9 ± 9,5) and without previous cardiac surgery signed an informed consent to undergo epicardial mapping and comprized the study population. Endocardial access was used previously as primary method in 4 patients ICD/ CRT-D had been previously implanted in 11 patients: mean left ventricle ejection fraction was 38,8 ± 10,6 %: hemodynamically unstable VT was present in 10 patients; the most frequent scar localization by ECG and transthoracic echocardiography – left ventricle (LV) inferior wall (10 patients), LV lateral wall – (7 patients). All patients underwent full clinical evaluation. Electrophysiological procedure and catheter ablation was performed under general anesthesia. Epicardial access was obtained through percutaneous subxyphoid puncture. Voltage mapping of endocardial and epicardial surfaces was performed. Maps were evaluated for the presence of LAVA. Ablation was performed at sites of LAVA on either side of the ventricular wall. Results epicardial access was successful in 12 patients. Bi- and unipolar mapping was successfully performed and analyzed in 11 subjects. LAVA was present in all but one patient on endocardial surface and in 9 (82%) out of 12 patients on epicardial surface. Localization of endocardial and epicardial LAVA coincided in 8 (67%) patients suggesting transmural ischemic scar. One patient had only epicardial scar, 1 patient had septal endocardial scar without LAVA on the epicardial surface. In one patient LAVA sites were localized on different left ventricle walls. More extensive unipolar than bipolar endocardial scar area was found (11,8 (IQR:2,0;31,6) vs 45,8 (IQR:17,1;86,5) сm2; р=0,03). Epicardial unipolar scar area prevailed over bipolar scar area: median 46.0 cm2 (IQR: 15.9;55.5) vs 107.7 cm2 (IQR: 84.3;168.9) р=0,04. LAVA epicardial area was wider than endocardial: 19.7 cm2 (IQR: 2.3; 29.7) vs 4.1 cm2 (IQR: 0.4; 23.8) р=0.03. Conclusion according to the results of our pilot study in unselected patients with ischemic VT, epicardial arrhythmogenic substrate was detected in 82% of cases. Epicardial LAVA area significantly prevailed over endocardial LAVA area.

Bovine cardiac mesothelial hyperplasia: a common incidental finding in adult cattle

Cardiac mesothelial hyperplasia forming pale plaque lesions on the epicardial surface is a common incidental finding in the hearts of aged humans. A similar phenomenon with a more papillary appearance has also been reported as an incidental finding in dogs and mice. These lesions are believed to occur in response to friction between the epicardium and overlying pericardium. We investigated this lesion in adult cattle, a phenomenon that has been associated with bovine leukemia virus infection and epicardial lymphoma. We examined 73 hearts from adult cattle, predominantly of dairy breeds: 53 from a rendering facility and 20 from a state diagnostic laboratory. Cardiac mesothelial hyperplasia was much more prevalent in cattle than in other reported species (97% of examined hearts). The most common distribution was overlying the great vessels in a dark red papillary pattern. Cardiac mesothelial hyperplasia was also variably observed on all 4 cardiac chambers and the pericardium. Occasionally these lesions took on a smooth plaque-like appearance resembling those observed in humans. The lesions varied from 0.25 cm2 to covering 90% of the epicardial surface. No association was observed between cardiac mesothelial hyperplasia and bovine leukemia virus infection or cardiac lymphoma. Cardiac mesothelial hyperplasia was a common incidental finding in bovine hearts that must be distinguished from neoplasia and acute or chronic inflammation.