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Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in adult population and confers significant thromboembolic risk. Endothelial dysfunction has been recognized as a possible contributor to thrombogenesis in AF. The arrhythmia has been associated with thrombogenic atrial endocardial lesions and evidence of increased circulating biomarkers of endothelial dysfunction (e.g. von Willebrand factor, soluble thrombomodulin, E-selectin, asymmetric dimethylarginine, circulating endothelial cells and microparticles), and impairment of endothelium-dependent vasodilatation in the peripheral and coronary circulation has been reported in AF patients. Increased levels of biomarkers of endothelial origin (e.g. von Willebrand factor, soluble thrombomodulin, E-selectin, asymmetric dimethylarginine) have been associated with adverse outcomes in AF patients. Importantly, endothelial dysfunction has been documented in AF patients without cardio-pulmonary comorbidities or risk factors (so-called 'lone AF'), as well. In this review, we provide an overview of contemporary evidence for the alterations in endothelial function and endothelial injury in AF, with a focus on endothelial (dys)function in lone AF.

We describe a sequence of methods to produce a partial differential equation model of the electrical activation of the ventricles. In our framework, we incorporate the anatomy and cardiac microstructure obtained from magnetic resonance imaging and diffusion tensor imaging of a New Zealand White rabbit, the Purkinje structure and the Purkinje-muscle junctions, and an electrophysiologically accurate model of the ventricular myocytes and tissue, which includes transmural and apex-to-base gradients of action potential characteristics. We solve the electrophysiology governing equations using the finite element method and compute both a 6-lead precordial electrocardiogram (ECG) and the activation wavefronts over time. We are particularly concerned with the validation of the various methods used in our model and, in this regard, propose a series of validation criteria that we consider essential. These include producing a physiologically accurate ECG, a correct ventricular activation sequence, and the inducibility of ventricular fibrillation. Among other components, we conclude that a Purkinje geometry with a high density of Purkinje muscle junctions covering the right and left ventricular endocardial surfaces as well as transmural and apex-to-base gradients in action potential characteristics are necessary to produce ECGs and time activation plots that agree with physiological observations.

Introduction: The characteristics of endocardial electrograms needed to detect the overlying abnormal epicardial substrates in arrhythmogenic right ventricular cardiomyopathy with epicardial ventricular tachycardia (VT) remain unclear. This study investigated which of the endocardial electrogram characteristics could predict the overlying abnormal epicardial substrates., Methods and Results: In 20 consecutive patients (median age: 46 years, 11 men) undergoing epicardial VT ablation, detailed endocardial and epicardial mappings were obtained by using the CARTO 3 system. The endocardial electrographic characteristics (unipolar peak-to-peak voltage, unipolar peak-negative-voltage, bipolar voltage, and bipolar electrogram duration) of the opposite endocardium and epicardium in RV were retrospectively investigated (N = 1,697 paired points, 84 ± 60 pairs/patient). Endocardial predictors of the presence of epicardial dense scar (<0.5 mV), low voltage zones (LVZ; ≤1.5 mV), and ablation targets (by using activation mapping, entrainment mapping, and pace mapping) were analyzed., Results: In the multivariable analysis, (1) unipolar peak-negative voltage independently predicted the presence of epicardial LVZ, epicardial dense scar, and ablation targets; (2) bipolar voltage could not predict epicardial lesions; and (3) bipolar electrogram duration predicted epicardial LVZ, but not dense scar or ablation targets. The endocardial unipolar peak-negative voltage of <1.66 mV (89% sensitivity and 53% specificity) was the optimal cutoff point for predicting epicardial dense scar., Conclusions: In patients with RV epicardial VT, the presence of unipolar peak-negative voltage of <1.66 mV in the endocardium predicted the presence of epicardial dense scar (<0.5 mV) and potential ablation targets in the overlying epicardium., (© 2014 Wiley Periodicals, Inc.)

Background: The optimal contact force (CF) for ventricular mapping and ablation remains unvalidated. We assessed CF in different endocardial and epicardial regions during ventricular tachycardia substrate mapping using a CF-sensing catheter (Smartouch; Biosense-Webster) and compared the transseptal versus retroaortic approach., Methods and Results: In total, 8979 mapping points with CF, and force vector orientation (VO) were recorded in 21 patients, comprising 13 epicardial, 12 left ventricular (6 transseptal and 6 retroaortic approach), and 12 right ventricular endocardial maps. VO was defined as adequate when the vector was directed toward the myocardium. During epicardial mapping, 46% of the points showed an adequate VO and a median CF of 8 (4-13) g, however, with significant differences among the 8 regions. When VO was inadequate, median CF was higher at 16 (10-24) g (P<0.0001). During left ventricular and right ventricular endocardial mapping, 94% of VO were adequate. Median CF of adequate VO was higher in the left ventricular and right ventricular endocardium than in the epicardium (15 [8-25] and 13 [7-22] g versus 8 [4-13] g, respectively; both P<0.001). Global median left ventricular CF with transseptal approach was not statistically different from retroaortic approach, but CF in the apicoinferior and apicoseptal regions was higher with transseptal approach (P<0.001)., Conclusions: Ventricular mapping demonstrates important regional variations in CF, but in general, CF is higher endocardially than epicardially where poor catheter orientation is associated with higher CF. A transseptal approach may lead to improved contact particularly in the apicoseptal and inferior regions., (© 2014 American Heart Association, Inc.)

Early diastolic mitral inflow and annulus velocities ratio (E/e') is the parameter used to estimate left ventricular (LV) filling pressure, but their use for patients with reduced ejection fraction (EF) (<50 %) is controversial. LV endocardial area change rate with 3-dimensional (3-D) speckle-tracking can be used to evaluate the entire LV diastolic function, we tested the hypothesis that the early diastolic area change rate (E-ACR) represents LV relaxation, and E and E-ACR ratio (E/E-ACR) can accurately predict LV filling pressure in patients with reduced and preserved EF (≥50 %). We studied 125 patients with EF of 40 ± 17 %. E-ACR of all patients was measured using the global area change rate, and LV relaxation time constant (τ, n = 53) and pulmonary capillary wedge pressure (PCWP, n = 125) were measured by cardiac catheterization. E-ACR significantly correlated with τ (r = -0.60, p < 0.001). In the retrospective group (n = 101), E/E-ACR correlated with PCWP for patients with reduced EF as well as those with preserved EF (n = 79 and 22, r = 0.62 and 0.81, both p < 0.001). In overall patients, E/E-ACR ≥94 cm was a better predictor of elevated mean PCWP (>12 mmHg) (sensitivity: 69 %, specificity: 87 %, areas under the curves = 0.82; p < 0.001) and was a more accurate predictor than E/e' (p = 0.001) for the retrospective group. For the validation group (n = 24), E/E-ACR ≥94 cm was similarly predictive for elevated mean PCWP (sensitivity: 60 %, specificity: 100 %, positive predictive value: 100 %, negative predictive value: 78 %). In conclusions, global E-ACR by 3-D speckle-tracking proved to be dependent on LV relaxation. Moreover, E/E-ACR was found to be a powerful predictor of LV filling pressure regardless of EF.

Reduced repolarization reserve and increased transmural dispersion of repolarization (TDR) are known risk factors for Torsade de Pointes development, but less is known about the role of apex-to-base (apicobasal) repolarization in arrhythmogenesis. Three needles were inserted in rabbit left ventricle to record unipolar electrograms from endocardium to epicardium and base to apex. Total repolarization interval (TRI) and peak-to-end repolarization interval (Tp) were assessed after quinidine (n = 6) and D,L-sotalol (n = 6) perfusion in combination with the IKs inhibitor chromanol 293B. About 30 µM D,L-sotalol increased TRI and Tp more at the base (TRI + 40 ± 4 %; Tp +89 ± 11 %) relative to the apex (TRI + 28 ± 3 %, Tp + 30 ± 8 %). Similar results were obtained with quinidine: TRI and Tp increased more at the base compared to the apex. No significant differences were recorded from the endocardium to the epicardium. Our results show that combined IKr + IKs block prolonged TRI and Tp significantly more at the ventricular base than at the apex, in the absence of transmural dispersion of refractoriness. Regional changes in TRI and Tp indicate the contribution of apicobasal dispersion to arrhythmogenicity compared to TDR in a rabbit heart model.

Objectives: We compared the accuracy of NOGA endocardial mapping for delineating transmural and non-transmural infarction to the results of cardiac magnetic resonance imaging (cMRI) with late gadolinium enhancement (LE) for guiding intramyocardial reparative substance delivery using data from experimental myocardial infarction studies., Methods: Sixty domestic pigs underwent diagnostic NOGA endocardial mapping and cMRI-LE 60 days after induction of closed-chest reperfused myocardial infarction. The infarct size was determined by LE of cMRI and by delineation of the infarct core on the unipolar voltage polar map. The sizes of the transmural and non-transmural infarctions were calculated from the cMRI transmurality map using signal intensity (SI) cut-offs of>75% and>25% and from NOGA bipolar maps using bipolar voltage cut-off values of <0.8 mV and <1.9 mV. Linear regression analysis and Bland-Altman plots were used to determine correlations and systematic differences between the two images. The overlapping ratios of the transmural and non-transmural infarcted areas were calculated., Results: Infarct size as determined by 2D NOGA unipolar voltage polar mapping correlated with the 3D cMRI-LE findings (r = 0.504, p<0.001) with a mean difference of 2.82% in the left ventricular (LV) surface between the two images. Polar maps of transmural cMRI and bipolar maps of NOGA showed significant association for determining of the extent of transmural infarction (r = 0.727, p<0.001, overlap ratio of 81.6±11.1%) and non-transmural infarction (r = 0.555, p<0.001, overlap ratio of 70.6±18.5%). NOGA overestimated the transmural scar size (6.81% of the LV surface) but slightly underestimated the size of the non-transmural infarction (-3.04% of the LV surface)., Conclusions: By combining unipolar and bipolar voltage maps, NOGA endocardial mapping is useful for accurate delineation of the targeted zone for intramyocardial therapy and is comparable to cMRI-LE. This may be useful in patients with contraindications for cMRI who require targeted intramyocardial regenerative therapy.

Aims: Mapping and interpretation of wave conduction patterns recorded during simultaneous mapping of the electrical activity on both endocardial and epicardial surfaces are challenging because of the difficulty of reconstruction of reciprocal alignment of electrodes in space. Here, we suggest a method to overcome this difficulty using a concept of maximized endo-epicardial phase coherence., Methods and Results: Endo-epicardial mapping was performed in six humans during induced atrial fibrillation (AF) in right atria using two sets of 8 × 8 electrode plaques. For each electrode, mean phase coherence (MPC) with all electrodes on the opposite side of the atrial wall was calculated. Localization error was defined as a distance between the directly opposing electrode and the electrode with the maximal MPC. Overall, there was a linear correlation between MPC and distance between electrodes with R(2) = 0.34. Localization error obtained for electrodes of the plaque in six patients resulted in a mean 2.3 ± 1.9 mm for 25 s electrogram segment length. Eighty-four per cent of the measurements resulted in error smaller than 3.4 mm. The duration of the recording used to compute MPC was negatively correlated with localization error; however, the effect reached plateau for segment durations longer than 15 s., Conclusion: Application of the concept of maximized endo-epicardial phase coherence to electrograms during AF allows reconstruction of reciprocal alignment of the electrodes on the opposite side of the atrial wall. This approach may be especially useful in settings where the spatial position of endo- and epicardial electrodes for intracardiac mapping cannot otherwise be determined., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: There is a paucity of data on biophysical parameters during radiofrequency ablation of scar-mediated ventricular tachycardia (VT)., Methods and Results: Data were collected from consecutive patients undergoing VT ablation with open-irrigation. Complete data were available for 372 lesions in 21 patients. The frequency of biophysical parameter changes were: >10Ω reduction (80%), bipolar EGM reduction (69%), while loss of capture was uncommon (32%). Unipolar injury current was seen in 72% of radiofrequency applications. Both EGM reduction and impedance drop were seen in 57% and a change in all 3 parameters was seen in only 20% of lesions. Late potentials were eliminated in 33%, reduced/modified in 56%, and remained after ablation in 11%. Epicardial lesions exhibited an impedance drop (90% vs. 76%, P = 0.002) and loss of capture (46% vs. 27%, P < 0.001) more frequently than endocardial lesions. Lesions delivered manually exhibited a >10Ω impedance drop (83% vs. 71%, P = 0.02) and an EGM reduction (71% vs. 40%, P < 0.001) more frequently than lesions applied using magnetic navigation, although loss of capture, elimination of LPs, and a change in all 3 parameters were similarly observed., Conclusions: VT ablation is inefficient as the majority of radiofrequency lesions do not achieve more than one targeted biophysical parameter. Only one-third of RF applications targeted at LPs result in complete elimination. Epicardial ablation within scar may be more effective than endocardial lesions, and lesions applied manually may be more effective than lesions applied using magnetic navigation. New technologies directed at identifying and optimizing ablation effectiveness in scar are clinically warranted., (© 2014 Wiley Periodicals, Inc.)

Objective: This study demonstrated left atrial endocardial dysfunction and platelet activation in patients with atrial fibrillation and mitral stenosis., Methods: Study included 80 patients with mitral stenosis and atrial fibrillation (40 each with and without left atrial thrombosis), 15 healthy volunteers, and 10 left atrial appendage (LAA) specimens from donor hearts. Blood samples were collected through peripheral vein and left atrium, with peripheral blood samples of volunteers as controls. LAA specimens were collected during operations. LAA expressions of von Willebrand factor (vWF) and P-selectin were determined immunohistochemically; plasma concentrations were measured by enzyme-linked immunosorbent assay. LAA expressions of vWF and P-selectin genes in were quantitated with real-time fluorescent quantitative polymerase chain reaction., Results: The difference in vWF and P-selectin plasma levels between left atrial and peripheral venous blood was not significant; however, peripheral plasma levels of vWF and P-selectin were significantly higher in those with thrombosis than without thrombosis, which in turn were higher than in healthy subjects. Both vWF and P-selectin proteins were stained in both left atrial endocardium and cardiomyocytes. The normalized vWF gene expression relative to control was 3.04 in patients with thrombosis and 2.16 in those without thrombosis (P<.01). The difference in P-selectin gene expressions among the groups was not significant., Conclusions: No differences were observed in plasma levels of vWF and P-selectin between left atrial and peripheral venous blood. Over expression of vWF gene in LAA may contribute to increased plasma vWF levels. P-selectin and vWF together may play a role in thrombosis., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Augmentation index (AIx) and subendocardial viability ratio (SEVR) are widely accepted indices of wave reflection and myocardial oxygen demand relative to supply. This study aimed to validate a new tonometric device (IIM-2010A) for obtaining AIx and SEVR from radial artery. A total of 68 outpatients (32 men and 36 women) aged 20 to 76 years (44.7±16.6 years) recruited from a health screening center participated in the study. AIx was obtained from radial pressure using the HEM-9000AI and IIM-2010A devices, while SEVR was measured from carotid pressure with the tonometric method and from radial pressure by the IIM-2010A device. In a subgroup of 24 patients, the measurements of AIx and SEVR were repeated after an interval of 10 minutes. The correlation of radial AIx between the IIM-2010A and HEM-9000AI devices was highly significant (r=0.956, P<.01). Radial SEVR determined from IIM-2010A was also highly related to carotid SEVR (r=0.864, P<.01), although the value was about 13.1% lower. There was no statistically significant difference between the repeated measurements of both indices. The lower coefficient of variation (2.9% vs 4.3% for AIx, 3.3% vs 4.1% for SEVR) and higher intraclass correlation coefficient (0.96 vs 0.91 for AIx, 0.93 vs 0.86 for SEVR) of IIM-2010A confirmed better short-term reproducibility, compared with the HEM-9000AI device and carotid tonometry. The new tonometric device IIM-2010A is effective and reproducible in calculating radial AIx and SEVR and has potential use in health screening., (© 2014 Wiley Periodicals, Inc.)

Objectives: Bipolar radiofrequency (RF) devices are used epicardially by cardiac surgeons and cryoballoon endocardially by cardiac electrophysiologists for atrial fibrillation (AF) ablation, but in separate entities. The study's objective was to evaluate the feasibility and safety of combining an endocardial cryoballoon with epicardial bipolar RF ablation for the treatment of AF., Methods: A cohort of 7 patients with AF underwent a hybrid thoracoscopic surgical and endocardial ablation. To prevent bilateral sequential lung deflation in these patients with severe chronic obstructive pulmonary disease, the right pulmonary veins (PVs) were isolated using an epicardial bipolar RF clamp and the contralateral veins with an endocardial cryoballoon. A box lesion set was made epicardially using a bipolar RF pen., Results: Acutely, pacing manoeuvres proved a bidirectional block in all PVs in all patients. No complications were seen. A box lesion was made in 5 patients. During follow-up, 2 of them had AF recurrence: 1 was treated successfully with sotalol and another underwent redo RF catheter ablation with reisolation of the right inferior PV. At present, 6 of 7 patients are in sinus rhythm without any anti-arrythmic drugs during a follow-up of more than 40 ± 3 months., Conclusions: A hybrid approach to AF ablation using a cryoballoon endocardially and a bipolar RF device epicardially is feasible and safe., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: The late sodium current (INa-L) contributes importantly to rate-dependent change in action potential duration (APD) and transmural dispersion of repolarization (TDR). However, little is known about the mechanisms of increased APD rate-dependence and amplified TDR in left ventricular hypertrophy (LVH) and failure. The purpose of this study was to investigate the role of INa-L in rate-adaptation of transmural APD heterogeneity., Methods: APD, its rate-dependence and INa-L current were examined in myocytes isolated from the endocardium and epicardium of the control and LVH rabbits. AP was recorded using the standard microelectrode technique, and INa-L was recorded using the whole-cell patch clamp technique., Results: Early afterdepolarizations (EADs) were frequently recorded in the isolated myocytes of the LVH rabbits but not in those of controls. LVH prolonged APD more significantly in the endocardial myocytes than in the epicardium (31.7±3.4 vs. 21.6±1.5% n=6, p<0.05), leading to a marked increase in TDR. LVH endocardial myocytes exhibited a greater rate-dependent change in APD compared to the epicardial myocytes. INa-L densities were significantly increased in both LVH endocardium and epicardium. However, LVH increased the INa-L density preferentially in the endocardial myocytes compared to the epicardial myocytes (54.5±4.8% vs. 39.2±3.3%, n=6, p<0.05)., Conclusions: Our results demonstrate that LVH increased the INa-L preferentially in the endocardium over the epicardium, which contributes importantly to the stronger rate-dependent change in repolarization and longer APD in the endocardium. This results in an amplified TDR capable of initiating EAD and ventricular arrhythmias., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) is an arrhythmia that occurs as a result of numerous pathophysiological processes in the atria. High rate, neurohumoral activation, aging and chronic stretch activate a variety of signaling pathways leading to electrical and structural remodeling. In particular, endomysial fibrosis within the epicardial layer, which also occurs as a result of AF itself, can disrupt electrical connections between muscle bundles. This leads to electrical dissociation not only within the epicardial layer, but also between the epicardial layer and the endocardial bundle network. Although the normal, healthy atrium has a complex 3-dimensional shape, differences in activation time between the epicardial layer and the underlying trabecular network in the atrial free walls are small, and the atrial walls essentially function as a 2-dimensional surface for propagating fibrillation waves. However, progressive structural remodeling leads to increased dissociation of epicardial and endocardial activation patterns. Epi-endocardial dissociation allows fibrillation waves to propagate between epicardium and endocardium, and become visible as 'breakthrough waves' that add to the overall complexity of fibrillatory conduction and thus to AF stability. This process greatly increases the effective surface area available to fibrillation waves and causes the atrial walls to behave as a 3-dimensional substrate. Computer models support that this behavior can increase AF stability. Under these conditions, ectopic activity originating from e.g. the pulmonary veins is likely to trigger longer episodes of AF. Experiments using simultaneous endo-epicardial mapping of AF suggest that disseminated, irregular and non-repetitive ectopic focal discharges might also occur during AF. The increasingly 3-dimensional character of AF as a result of structural remodeling lowers the responsiveness to antiarrhythmic compounds and ablation therapy, thus advocating early rhythm control strategies., (Copyright © 2014. Published by Elsevier Ltd.)

Percutaneous pericardial access for epicardial mapping and ablation of ventricular arrhythmias has expanded considerably in recent years. After its description in patients with Chagas disease, the technique has provided relevant information on the arrhythmia substrate in other cardiomyopathies and has improved the results of ablation procedures in various clinical settings. Electrocardiographic criteria proposed for the recognition of the epicardial origin of ventricular tachycardias are mainly based on analysis of the first QRS components. Ventricular activation at the epicardium has a slow initial component reflecting the transmural activation and influenced by the absence of Purkinje system in the epicardium. Various parameters (pseudodelta wave, intrinsicoid deflection and shortest RS interval) of these initial intervals predict an epicardial origin in patients with scar-related ventricular tachycardias with right bundle branch block morphology. Using the same concept, the maximum deflection index was defined for the location of idiopathic epicardial tachycardias remote from the aortic root. Electrocardiogram criteria based on the morphology of the first component of the QRS (q wave in lead I) have been proposed in patients with nonischemic cardiomyopathy. All these criteria seem to be substrate-specific and have several limitations. Other information, including type of underlying heart disease, previous failed endocardial ablation, and evidence of epicardial scar on magnetic resonance imaging, can help to plan the ablation procedure and decide on an epicardial approach.

Objective: We evaluated the changes in left ventricular (LV) function and volumes after surgical anterior ventricular endocardial restoration., Methods: A total of 63 patients who had undergone surgical anterior ventricular endocardial restoration and total arterial revascularization were included. Echocardiography and myocardial single photon emission computed tomography were performed to examine LV function and volumes preoperatively, early postoperatively, and annually thereafter to 5 years after surgery. Coronary angiography was performed at 5 years postoperatively., Results: Operative mortality was 7.9% (5 of 63). Echocardiograms performed before discharge demonstrated a significantly improved LV ejection fraction that was maintained at 5 years, significantly decreased early postoperative LV end-diastolic and end-systolic volume indexes that were slightly increased at 1 year and then maintained at 5 years, and early postoperative decrement of the stroke volume index that had disappeared at 1 year and had not reappeared by 5 years. Postoperative myocardial single photon emission computed tomography showed an LV ejection fraction that had gradually improved until 2 years and was maintained at 5 years, significantly decreased LV end-diastolic and end-systolic volume indexes that were maintained at 5 years, and a stroke volume index that was unchanged until 2 years and slightly increased at 3 to 4 years. The arterial graft patency rate in the left coronary territory was 95.7% (67 of 70) at 5 years. The 10-year overall survival and adverse event-free rate were 59.2% and 61.2%, respectively., Conclusions: Improved LV ejection fraction and reduced volume indexes were maintained and the stroke volume index had not decreased at 5 years after the procedure. Preserved patency of the arterial grafts might have an important role in maintaining improved LV function., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Aims: The concealed phase of arrhythmogenic right ventricular cardiomyopathy (ARVC) may initially manifest electrophysiologically. No studies have examined dynamic conduction/repolarization kinetics to distinguish benign right ventricular outflow tract ectopy (RVOT ectopy) from ARVC's early phase. We investigated dynamic endocardial electrophysiological changes that differentiate early ARVC disease expression from RVOT ectopy., Methods: 22 ARVC (12 definite based upon family history and mutation carrier status, 10 probable) patients without right ventricular structural anomalies underwent high-density non-contact mapping of the right ventricle. These were compared to data from 14 RVOT ectopy and 12 patients with supraventricular tachycardias and normal hearts. Endocardial & surface ECG conduction and repolarization parameters were assessed during a standard S1-S2 restitution protocol., Results: Definite ARVC without RV structural disease could not be clearly distinguished from RVOT ectopy during sinus rhythm or during steady state pacing. Delay in Activation Times at coupling intervals just above the ventricular effective refractory period (VERP) increased in definite ARVC (43 ± 20 ms) more than RVOT ectopy patients (36 ± 14 ms, p = 0.03) or Normals (25 ± 16 ms, p = 0.008) and a progressive separation of the repolarisation time curves between groups existed. Repolarization time increases in the RVOT were also greatest in ARVC (definite ARVC: 18 ± 20 ms; RVOT ectopy: 5 ± 14, Normal: 1 ± 18, p<0.05). Surface ECG correlates of these intracardiac measurements demonstrated an increase of greater than 48 ms in stimulus to surface ECG J-point pre-ERP versus steady state, with an 88% specificity and 68% sensitivity in distinguishing definite ARVC from the other groups. This technique could not distinguish patients with genetic predisposition to ARVC only (probable ARVC) from controls., Conclusions: Significant changes in dynamic conduction and repolarization are apparent in early ARVC before detectable RV structural abnormalities, and were present to a lesser degree in probable ARVC patients. Investigation of dynamic electrophysiological parameters may be useful to identify concealed ARVC in patients without disease pedigrees by using endocardial electrogram or paced ECG parameters.

We report herein a rare case of endocardial blood cyst (EBC) in an adult patient. A 63-year-old asymptomatic woman underwent echocardiography, which incidentally detected a cardiac tumor in the right atrium. On echocardiography, the tumor was revealed to be a 30-mm round mass with thin, hyperechogenic walls and heterogeneously hypoechogenic contents. The lesion was attached to the septum. On computed tomography, the tumor appeared partly calcified and showed poor contrast-enhancement. On magnetic resonance imaging, the lesion appeared isointense or slightly hyperintense in T1 and T2-weighted sequences. Myxoma was strongly suspected based on these preoperative imaging findings. The tumor was successfully excised under cardiopulmonary bypass. Gross examination confirmed that the cyst was filled with blood. The cystic walls comprised thin-layered fibrous tissue lined with endocardial cells. No tumor cells were found. The diagnosis of EBC was confirmed based on histopathological examination, and the postoperative course was uneventful.

Heart failure is associated with pump dysfunction and remodeling but it is not yet known if the condition affects different transmural regions of the heart in the same way. We tested the hypotheses that the left ventricles of non-failing human hearts exhibit transmural heterogeneity of cellular level contractile properties, and that heart failure produces transmural region-specific changes in contractile function. Permeabilized samples were prepared from the sub-epicardial, mid-myocardial, and sub-endocardial regions of the left ventricular free wall of non-failing (n=6) and failing (n=10) human hearts. Power, an in vitro index of systolic function, was higher in non-failing mid-myocardial samples (0.59±0.06μWmg(-1)) than in samples from the sub-epicardium (p=0.021) and the sub-endocardium (p=0.015). Non-failing mid-myocardial samples also produced more isometric force (14.3±1.33kNm(-2)) than samples from the sub-epicardium (p=0.008) and the sub-endocardium (p=0.026). Heart failure reduced power (p=0.009) and force (p=0.042) but affected the mid-myocardium more than the other transmural regions. Fibrosis increased with heart failure (p=0.021) and mid-myocardial tissue from failing hearts contained more collagen than matched sub-epicardial (p<0.001) and sub-endocardial (p=0.043) samples. Power output was correlated with the relative content of actin and troponin I, and was also statistically linked to the relative content and phosphorylation of desmin and myosin light chain-1. Non-failing human hearts exhibit transmural heterogeneity of contractile properties. In failing organs, region-specific fibrosis produces the greatest contractile deficits in the mid-myocardium. Targeting fibrosis and sarcomeric proteins in the mid-myocardium may be particularly effective therapies for heart failure., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: Patients with atrial fibrillation (AF) with enlarged atria or previous pulmonary vein isolation (PVI) are challenging patients for catheter ablation. Thoracoscopic surgery is an effective treatment for these patients but comes at the cost of an increase in adverse events. Recently, electrophysiological (EP) guided approaches to thoracoscopic surgery have been described which consist of EP guidance by measurement of conduction block across ablation lines. In this study we describe the efficacy and safety of EP-guided thoracoscopic surgery for AF in patients with enlarged atria and/or prior failed catheter ablation., Methods & Results: A total of 72 patients were included. Two different approaches to EP-guided thoracoscopic surgery were implemented: epicardial or endocardial EP-guidance at the time of surgery. Residual intraoperative conduction requiring additional ablation was detected with epicardial or endocardial mapping techniques in 50% and 11%, respectively. Additional epicardial or endocardial ablation was performed until bidirectional block was confirmed. Follow-up consisted of an ECG and a 24h Holter at 3, 6 and 12 months after the procedure. A total of 57 patients (79%) had freedom of AF and were off anti-arrhythmic drugs at one year follow-up (30 paroxysmal (83%), 27 persistent AF (75%)). Adverse events occurred in 13 patients (6 major). None of our patients died and all events were reversible., Conclusion: EP-guidance of thoracoscopic surgery can be safely performed both epicardially and endocardially and is associated with a high rate of long-term maintenance of sinus rhythm in patients with enlarged atria and/or a previously failed ablation., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aim: To determine the role of repetitive endocardial focal activations and Purkinje fibers in the maintenance of long duration ventricular fibrillation (LDVF, VF>1 minute) in canine hearts in vivo., Methods: The study was conducted in electrophysiological laboratory of Shanghai Ruijin hospital from July 2010 to August 2012. A 64-electrode basket was introduced through a carotid artery into the left ventricle (LV) of 11 beagle dogs for global endocardial electrical mapping. In the Lugol's solution group (n=5), the subendocardium was ablated by washing with Lugol's solution. In the control group, (n=6) saline was used for ablation. Before and after saline or Lugol ablation, we determined QRS duration and QT/QTc interval in sinus rhythm (SR). We also measured the activation rates in the first 2 seconds of each minute during 7 minutes of VF for each group. If VF terminated spontaneously in less than 7 minutes, the VF segments used in activation rate analysis were reduced accordingly., Results: At the beginning of VF there was no difference between the groups in the activation rate. However, after 1 minute of LDVF the Lugol's solution group had significantly slower activation rate than the control group. In the control group, all episodes of LDVF (6/6) were successfully sustained for 7 minutes, while in the Lugol's solution group 4/5 episodes of LDVF spontaneously terminated before 7 minutes (4.8±1.4 minutes) (P=0.015). In the control group, at 5.1±1.3 minutes of LDVF, a successive, highly organized focal LV endocardial activation pattern was observed. During this period, activations partly arose in PF and spread to the working ventricular myocardium. Mapping analysis showed that these events were consistent with repetitive endocardial focal activations. No evidence of similar focal activations was observed in the Lugol's solution group., Conclusions: Repetitive endocardial focal activations in the LV endocardium may be associated with activation of subendocardial PFs. This mechanism may play an important role in the maintenance of LDVF.

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.

Background: The mechanisms that maintain long duration ventricular fibrillation (LDVF) are unclear. The difference in distribution of the Purkinje system in dogs and pigs was explored to determine if Purkinje activation propagates to stimulate working myocardium (WM) during LDVF and WM pacing., Methods and Results: In-vivo extracellular recordings were made from 1044 intramural plunge and epicardial plaque electrodes in 6 pig and 6 dog hearts. Sinus activation propagated sequentially from the endocardium to the epicardium in dogs but not pigs. During epicardial pacing, activation propagated along the endocardium and traversed the LV wall almost parallel to the epicardium in dogs, but in pigs propagated away from the pacing site approximately perpendicular to the epicardium. After 1 minute of VF, activation rate near the endocardium was significantly faster than near the epicardium in dogs (P<0.01) but not pigs (P>0.05). From 2 to 10 minutes of LDVF, recordings exhibiting Purkinje activations were near the endocardium in dogs (P<0.01) but were scattered transmurally in pigs, and the WM activation rate in recordings in which Purkinje activations were present was significantly faster than the WM activation rate in recordings in which Purkinje activations were absent (P<0.01). In 10 isolated perfused dog hearts, the LV endocardium was exposed and 2 microelectrodes were inserted into Purkinje and adjacent myocardial cells. After 5 minutes of LDVF, mean Purkinje activation rate was significantly faster than mean WM activation rate (P<0.01)., Conclusion: These extracellular and intracellular findings about activation support the hypothesis that Purkinje activation propagates to stimulate WM during sinus rhythm, pacing, and LDVF.

Introduction: This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Studying Cardiovascular and Respiratory Systems"., Background: Adaptation of the QT-interval to changes in heart rate reflects on the body-surface electrocardiogram the adaptation of action potential duration (APD) at the cellular level. The initial fast phase of APD adaptation has been shown to modulate the arrhythmia substrate. Whether the slow phase is potentially proarrhythmic remains unclear., Objectives: To analyze in-vivo human data and use computer simulations to examine effects of the slow APD adaptation phase on dispersion of repolarization and reentry in the human ventricle., Methods: Electrograms were acquired from 10 left and 10 right ventricle (LV/RV) endocardial sites in 15 patients with normal ventricles during RV pacing. Activation-recovery intervals, as a surrogate for APD, were measured during a sustained increase in heart rate. Observed dynamics were studied using computer simulations of human tissue electrophysiology., Results: Spatial heterogeneity of rate adaptation was observed in all patients. Inhomogeneity in slow APD adaptation time constants (Δτ(s)) was greater in LV than RV (Δτ(s)(LV) = 31.8 ± 13.2, Δτ(s)(RV) = 19.0 ± 12.8 s , P< 0.01). Simulations showed that altering local slow time constants of adaptation was sufficient to convert partial wavefront block to block with successful reentry., Conclusions: Using electrophysiological data acquired in-vivo in human and computer simulations, we identify heterogeneity in the slow phase of APD adaptation as an important component of arrhythmogenesis.

Background: Previous studies showed that endocardial activation during long-duration ventricular fibrillation (VF) exhibits organized activity. We identified and quantified the different types of organized activity., Methods and Results: Two 64-electrode basket catheters were inserted, respectively, into the left ventricle and right ventricle of dogs to record endocardial activation from the endocardium during 7 minutes of VF (controls, n=6). The study was repeated with the K(ATP) channel opener pinacidil (n=6) and the calcium channel blocker flunarizine (n=6). After 2 minutes of VF without drugs, 2 highly organized left ventricular endocardial activation patterns were observed: (1) ventricular electric synchrony pattern, in which endocardial activation arose focally and either had a propagation sequence similar to sinus rhythm or arose near papillary muscles, and (2) stable pattern, in which activation was regular and repeatable, sometimes forming a stable re-entrant circuit around the left ventricular apex. Between 3 and 7 minutes of VF, the percent of time ventricular electric synchrony was present was control=25%, flunarizine=24% (P=0.44), and pinacidil=0.1% (P<0.001) and the percent of time stable pattern was present was control=71%, flunarizine=48% (P<0.001), and pinacidil=56% (P<0.001). The remainder of the time, nonstable re-entrant activation with little repeatability was present., Conclusions: After 3 minutes, VF exhibits 2 highly organized endocardial activation patterns 96% of the time, one potentially arising focally in the Purkinje system that was prevented with a K(ATP) channel opener but not a calcium channel blocker and the other potentially arising from a stable re-entrant circuit near the apical left ventricular endocardium.

Background: Local abnormal ventricular activities (LAVA) in patients with scar-related ventricular tachycardia (VT) may appear at any time during or after the far-field electrogram. Although they may be separated from the far-field signal by an isoelectric line and extend beyond the end of surface QRS, they may also appear fused or buried within the QRS., Objective: The purpose of this study was to characterize LAVA in postinfarction VT patients with respect to their anatomic locations., Methods: Thirty-one patients with postinfarction VT underwent mapping/ablation during sinus rhythm with a three-dimensional electroanatomic mapping system. From a total of 18,270 electrograms reviewed in all study subjects, 1104 LAVA (endocardium 839, epicardium 265) were identified and analyzed., Results: The interval from onset of QRS complex to ventricular electrogram (EGM onset) on the endocardium was significantly shorter than the epicardium (P < .001). EGM onset was shortest in the septal endocardium and longest in the inferior and lateral epicardium. There was a significant positive correlation between EGM onset and LAVA lateness as estimated by the interval from surface QRS onset to LAVA (r = 0.52, P < .001). LAVA were more frequently detected after the QRS complex in the epicardium (241/265 [91%]) than in the endocardium (551/839 [66%], P < .001). Only 43% of endocardial septal LAVA were detected after the QRS complex., Conclusion: Lateness of LAVA is affected to a large extent by their locations. The chance of detecting late LAVA increases when electrogram onset is later. Substrate-based approach targeting delayed signals relative to the QRS complex may miss critical the arrhythmogenic substrate, particularly in the septum and other early-to-activate regions., (© 2013 Heart Rhythm Society. All rights reserved.)

Objective: The objective of this study was to evaluate the efficacy of a novel approach for endocardectomy during coronary artery bypass graft with surgical ventricular restoration in patients with postinfarction left ventricular aneurysm., Methods: One hundred sixty-eight patients underwent coronary artery bypass graft with surgical ventricular restoration from 2005 to 2011. Endocardectomy was performed as an integral part of surgical ventricular restoration for the prevention of ventricular tachycardia. The experimental group (surgical ventricular restoration-endocardectomy group; n = 74) underwent preoperative electrophysiologic study with electroanatomic left ventricular mapping. Radiofrequency ablation-induced markings were placed and were used later as guides for performing endocardectomy during coronary artery bypass graft with surgical ventricular restoration. The control group (surgical ventricular restoration group; n = 94) underwent surgical ventricular restoration without endocardectomy., Results: The 1-year mortality rates in the surgical ventricular restoration-endocardectomy and surgical ventricular restoration (control) groups were 5% and 13%, respectively. During the postoperative period, 3% of patients in the surgical ventricular restoration-endocardectomy group and 38% of patients in the surgical ventricular restoration group experienced ventricular tachycardia events (P < .05). Automatic implantable cardioverter-defibrillators were implanted in 11 patients in the surgical ventricular restoration group and in 1 patient of the surgical ventricular restoration-endocardectomy group for secondary prevention of sudden cardiac death., Conclusions: When performed as an integral part of surgical ventricular restoration, endocardectomy was crucial in preventing postoperative ventricular tachycardia. Use of radiofrequency ablation-induced markings allowed clear visualization of the reentry zones for efficient endocardectomy during coronary artery bypass graft with surgical ventricular restoration, resulting in better patient outcomes., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

The subendocardial viability ratio (SEVR), a parameter introduced by Buckberg, represents a non-invasive measure of myocardial perfusion related to left ventricular work. AIM. The aim of this study was to verify if dialysis may determine modifications of SEVR and how these modifications are modulated in the 2-day interdialytic period. METHODS.We studied 54 subjects of mean age 6314 years and receiving dialysis for 3215 months. Exclusion criteria were diabetes, resistant hypertension and peripheral vascular diseases and intradialytic hypotension evidenced during the study dialysis session. Pulse wave velocity and SEVR assessments were performed during the third dialysis session of the week, before (pre-HD) and after (post-HD) dialysis, in 2-day interdialytic period after and at the beginning of the following dialysis session. RESULTS.Dialysis reduces PWV, in particular the tertile with the lowest PWV presents the highest percentage reduction (-26%) compared with the second and the third tertiles. In the same way, dialysis leads to an increase of SEVR and patients in the tertile with the highest SEVR values maintain high SEVR values during dialysis and in the interdialytic period. Patients with severe vascular calcifications present higher PWV value and lower SEVR value. CONCLUSIONS.The results of present study demonstrate that ultrafiltration improves PWV (with a mean reduction of 16%) and SEVR (increase of 13%) and that the severity of vascular calcifications influences the effect of ultrafiltration on these two parameters. More studies are certainly necessary to verify our findings. Considered the higher mortality of patients with higher SEVR, it would be important to understand if new dialytic strategies are needed in patients with higher PVW and lower SEVR values.

Background: Analysis of unipolar voltage maps has been used to detect epicardial scar, but data to define optimal parameters to identify scar remote from the recording site is limited. This study compares the characteristics of electrograms at endocardial sites adjacent to abnormal epicardial sites., Methods and Results: Data obtained from endocardial and epicardial electroanatomical maps of 31 patients with scar-related ventricular tachycardia were reviewed. Five hundred twenty-three pairs of endo- and epicardial points were selected according to predefined criteria. The endocardial points adjacent to epicardial scar (bipolar voltage < 1.5 mV) had smaller unipolar voltage than those distant from epicardial scar (P < 0.001). In multivariable analysis, unipolar voltage was the only endocardial electrogram predictor of epicardial scar (P < 0.001, OR 0.94, 95% CI 0.93 to 0.97). An endocardial unipolar amplitude < 4.4 mV in the right ventricular (RV) (sensitivity 93%, specificity 76%) and < 5.1 mV in the left ventricular (LV) (sensitivity 91%, specificity 75%) was the optimal cutoff predicting epicardial scar. Applying these thresholds to electroanatomical maps, revealed a good match between endocardial unipolar abnormality and epicardial scar for 67% of LV and 75% of RV maps, respectively, but notably poor matches occurred in 8 (29%) maps (7 with nonischemic cardiomyopathy). Site-by-site correlations were better for ischemic than nonischemic cardiomyopathy., Conclusions: This study supports the contention that unipolar electrograms are capable of indicating overlying epicardial scar during endocardial mapping, but illustrates limitations that appear to differ with nonischemic as compared to ischemic cardiomyopathy. The presence of epicardial arrhythmia substrate cannot be excluded by analysis of unipolar endocardial maps in some patients.

Abnormal enhanced transmural dispersion of repolarization (TDR) plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes (TDP) which can be induced in long-QT (LQT) syndrome. Taking advantage of an in vitro rabbit model of LQT2, we detected the effects of KN-93, a CaM-dependent kinase (CaMK) II inhibitor on repolarization heterogeneity of ventricular myocardium. Using the monophasic action potential recording technique, the action potentials of epicardium and endocardium were recorded in rabbit cardiac wedge infused with hypokalemic, hypomagnesaemic Tyrode's solution. At a basic length (BCL) of 2000 ms, LQT2 model was successfully mimicked with the perfusion of 0.5 μmol/L E-4031, QT intervals and the interval from the peak of T wave to the end of T wave (Tp-e) were prolonged, and Tp-e/QT increased. Besides, TDR was increased and the occurrence rate of arrhythmias like EAD, R-on-T extrasystole, and TDP increased under the above condition. Pretreatment with KN-93 (0.5 μmol/L) could inhibit EAD, R-on-T extrasystole, and TDP induced by E-4031 without affecting QT interval, Tp-e, and Tp-e/QT. This study demonstrated KN-93, a CaMKII inhibitor, can inhibit EADs which are the triggers of TDP, resulting in the suppression of TDP induced by LQT2 without affecting TDR.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiomyopathy characterized by progressive fibro-fatty replacement of the right ventricular myocardium. We report a case where mapping of endocardial potentials during sinus rhythm identified the re-entry circuit of a recurrent ventricular tachycardia in a patient with ARVC. The tachycardia was subsequently ablated successfully.

As radio frequency (RF) catheter ablation becomes increasingly prevalent in the management of ventricular arrhythmia in patients, an accurate and rapid determination of the arrhythmogenic site is of important clinical interest. The aim of this study was to test the hypothesis that the inversely reconstructed ventricular endocardial current density distribution from body surface potential maps (BSPMs) can localize the regions critical for maintenance of a ventricular ectopic activity. Patients with isolated and monomorphic premature ventricular contractions (PVCs) were investigated by noninvasive BSPMs and subsequent invasive catheter mapping and ablation. Equivalent current density (CD) reconstruction (CDR) during symptomatic PVCs was obtained on the endocardial ventricular surface in six patients (four men, two women, years 23-77), and the origin of the spontaneous ectopic activity was localized at the location of the maximum CD value. Compared with the last (successful) ablation site (LAS), the mean and standard deviation of localization error of the CDR approach were 13.8 and 1.3 mm, respectively. In comparison, the distance between the LASs and the estimated locations of an equivalent single moving dipole in the heart was 25.5 ± 5.5 mm. The obtained CD distribution of activated sources extending from the catheter ablation site also showed a high consistency with the invasively recorded electroanatomical maps. The noninvasively reconstructed endocardial CD distribution is suitable to predict a region of interest containing or close to arrhythmia source, which may have the potential to guide RF catheter ablation.

Introduction: While most ventricular arrhythmias (VA) can be ablated successfully using an endocardial (endo) approach, epicardial (epi) mapping and ablation is sometimes required. There may be suggestive clues on the surface electrocardiogram; however, identification of an epi origin of VA with certainty remains problematic., Methods and Results: All patients referred for ablation of ventricular tachycardia or frequent ventricular ectopy from June 2007 to July 2011 were evaluated. Patients with completed endo and epi electroanatomical activation maps of an epi VA were included (n = 10). Bipolar electrograms (EGMs) in the area of earliest endo activation were analyzed and compared to the area of early epi activation. An EGM component was characterized as far field if it was monophasic and there was inability to capture. We identified 3 characteristics from endo mapping that consistently indicated need for epi ablation: (1) Diffusely early activation (>2 cm(2) region of sites with equally earliest activation within 10 milliseconds). (2) Sequence of a far-field EGM followed by a near-field EGM in the region of earliest endo activation. (3) Inability to capture the far-field component of the earliest EGM (stim-QRS < egm-QRS time) or reproduce morphological features of the VA complex with stimulation at the earliest endo site of activation., Conclusions: The presence of a diffusely early area of activation and inability to capture a far-field endo EGM indicates that epi ablation may be needed to eliminate a VA., (© 2013 Wiley Periodicals, Inc.)

Objectives: The goal of this study was to determine the relationship of the ventricular tachycardia (VT) isthmus to channels of preserved voltage on an electroanatomic voltage map in postinfarction cardiomyopathy., Background: Substrate mapping in patients with postinfarction cardiomyopathy and VT may involve lowering the voltage cutoff that defines the scar (<1.5 mV) to identify "channels" of relative higher voltage within the scar. However, the prevalence of channels within the scar identified by using electroanatomic mapping and the relationship to the protected VT isthmus identified by entrainment mapping is unknown., Methods: Detailed bipolar endocardial voltage maps (398 ± 152 points) from 24 patients (mean age 69 ± 9 years) with postinfarction cardiomyopathy (ejection fraction 33 ± 9%) and tolerated VT were reviewed. Endocardial scar was defined according to voltage <1.5 mV. Isolated late potentials (ILPs) were identified and tagged on the electroanatomic voltage map. The baseline voltage cutoffs were then adjusted until all channels were identified. The VT isthmus was identified using entrainment mapping., Results: Inferior and anterior/lateral infarction was present by voltage mapping in 18 and 6 patients, respectively (scar area 44 ± 24 cm(2)). By adjusting voltage cutoffs, 37 channels were identified in 21 (88%) of 24 patients. The presence of ILPs within a channel was seen in 11 (46%) of 24 patients and 17 (46%) of 37 channels. A VT isthmus site was contained within a channel in only 11 of 24 patients or 11 of 37 channels. No difference in voltage characteristics was identified between clinical and nonclinical channels. Voltage channels with ILPs harbored the clinical isthmus with a sensitivity and specificity of 78% and 85%, respectively., Conclusions: Channels were identified in 88% of patients with VT by adjusting the voltage limits of bipolar maps; however, the specificity of those channels in predicting the location of VT isthmus sites was only 30%. The presence of ILPs inside the voltage channel significantly increases the specificity for identifying the clinical VT isthmus., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Our objective was to assess whether patients with significant coronary artery disease (CAD) had reduced endocardial function assessed by layer-specific strain compared with patients without significant CAD., Background: The left ventricular (LV) wall of the heart comprises 3 myocardial layers. The endocardial layer is most susceptible to ischemic injury., Methods: Seventy-seven patients referred to coronary angiography due to suspected non-ST-segment elevation-acute coronary syndromes (NSTE-ACS) were prospectively included. Coronary occlusion was found in 28, significant stenosis in 21, and no stenosis in 28 patients. Echocardiography was performed 1 to 2 h before angiography. Layer-specific longitudinal and circumferential strains were assessed from endocardium, mid-myocardium, and epicardium by 2-dimensional (2D) speckle-tracking echocardiography (STE). Territorial longitudinal strain (TLS) was calculated based on the perfusion territories of the 3 major coronary arteries in a 16-segment LV model, whereas global circumferential strain (GCS) was averaged from 6 circumferential LV segments in all 3 layers., Results: Patients with significant CAD had worse function in all 3 myocardial layers assessed by TLS and GCS compared with patients without significant CAD. Endocardial TLS (mean -14.0 ± 3.3% vs. -19.2 ± 2.2%; p < 0.001) and GCS (mean -19.3 ± 4.0% vs. -24.3 ± 3.4%; p < 0.001) were most affected. The absolute differences between endocardial and epicardial TLS and GCS were lower in patients with significant CAD (Δ2.4 ± 3.6% and Δ6.7 ± 3.8%, respectively) than in those without significant CAD (Δ5.3 ± 2.1% and Δ10.4 ± 3.0%; p < 0.001). This reflects a pronounced decrease in endocardial function in patients with significant CAD. A receiver-operating characteristic curve analysis showed that endocardial and mid-myocardial TLS were superior to identify significant CAD compared with epicardial TLS (p < 0.05), wall motion score index (p < 0.01), and ejection fraction (EF) (p < 0.001)., Conclusions: Assessment of layer-specific strain by 2D-STE might identify NSTE-ACS patients with significant CAD. Endocardial function was more affected in patients with significant CAD compared with epicardial function and EF., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Scar presence and its characteristics play a fundamental role in several cardiac pathologies. To accurately define the extent and location of the scar is essential for a successful ventricular tachycardia ablation procedure. Nowadays, a set of widely accepted electrical voltage thresholds applied to local electrograms recorded are used intraoperatively to locate the scar. Information about cardiac mechanics could be considered to characterize tissues with different viability properties. We propose a novel method to estimate endocardial motion from data obtained with an electroanatomical mapping system together with the endocardial geometry segmented from preoperative 3-D magnetic resonance images, using a statistical atlas constructed with bilinear models. The method was validated using synthetic data generated from ultrasound images of nine volunteers and was then applied to seven ventricular tachycardia patients. Maximum bipolar voltages, commonly used to intraoperatively locate scar tissue, were compared to endocardial wall displacement and strain for all the patients. The results show that the proposed method allows endocardial motion and strain estimation and that areas with low-voltage electrograms also present low strain values.

Rationale: The spatial distribution of blood flow in the hearts of genetically modified mice is a phenotype of interest because derangements in blood flow may precede detectable changes in organ function. However, quantifying the regional distribution of blood flow within organs of mice is challenging because of the small organ volume and the high resolution required to observe spatial differences in flow. Traditional microsphere methods in which the numbers of microspheres per region are indirectly estimated from radioactive counts or extracted fluorescence have been limited to larger organs for 2 reasons; to ensure statistical confidence in the measured flow per region and to be able to physically dissect the organ to acquire spatial information., Objective: To develop methods to quantify and statistically compare the spatial distribution of blood flow within organs of mice., Methods and Results: We developed and validated statistical methods to compare blood flow between regions and with the same regions over time using 15-µm fluorescent microspheres. We then tested this approach by injecting fluorescent microspheres into isolated perfused mice hearts, determining the spatial location of every microsphere in the hearts, and then visualizing regional flow patterns. We demonstrated application of these statistical and visualizing methods in a coronary artery ligation model in mice., Conclusions: These new methods provide tools to investigate the spatial and temporal changes in blood flow within organs of mice at a much higher spatial resolution than currently available by other methods.

Background: Previous studies have reported that the left ventricular (LV) pacing site is a major determinant of the hemodynamic response to cardiac resynchronization therapy (CRT). However, lead positioning in a lateral or posterolateral cardiac vein may not be optimal for every patient. The objective of this study was to assess the relationship between the right ventricular (RV)-to-LV conduction time and the systolic function during CRT on the basis of changes to LV pressure-volume loops., Methods: Left ventricular pressure and volume data were determined using a conductance catheter during CRT device implantation in 10 patients. Four endocardial LV sites were systematically assessed at four atrioventricular delays. The RV-to-LV conduction time was measured as the time interval between spontaneous peak R waves, recorded through the RV lead and the LV catheter., Results: The optimal pacing site varied among patients. However, the pacing site associated with the maximum RV-to-LV conduction time resulted in a stroke volume improvement comparable to the pacing site identified through individual hemodynamic optimization (41 ± 17 mL vs 44 ± 18 mL, P = 0.266). Moreover, the RV-to-LV conduction time recorded at each endocardial pacing site correlated positively with the increase in stroke volume (r = 0.537; P < 0.001), stroke work (r = 0.642; P < 0.001), and the pressure-derivative maximum (r = 0.646; P < 0.001) obtained with CRT., Conclusions: An optimal acute response to CRT can be obtained by positioning the LV lead at the site associated with the maximum RV-to-LV conduction time. A significant correlation appears to exist between RV-to-LV conduction time and the improvement in systolic function with CRT., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

Background: Endo-epicardial dissociation (EED) of electric activations resulting in transmural conduction of fibrillation waves (breakthroughs) has been postulated to contribute to the complexity of the substrate of atrial fibrillation (AF). The aim of this study was to elucidate the correlation between EED and incidence of breakthrough and to test the plausibility of transmural conduction versus ectopic focal discharges as sources of breakthrough., Methods and Results: We analyzed high-resolution simultaneous endo-epicardial in vivo mapping data recorded in left atrial free walls of goats with acute AF, 3 weeks and 6 months of AF (all n=7). Waves were analyzed for number, size, and width and categorized according to their origin outside (peripheral wave) or within the mapping area (breakthrough). Breakthrough incidence was lowest (2.1±1.0%) in acute AF, higher (11.4±6.1%) after 3 weeks (P<0.01 versus acute AF) and highest (14.2±3.8%) after 6 months AF (P<0.001 versus acute AF) and similar in the epicardium and endocardium. Most of the breakthroughs (86%; n=564) could be explained by transmural conduction, whereas only 13% (n=85) could be explained by ectopic focal discharges. Transmural microreentry did not play a role as source of breakthrough., Conclusions: This is the first study to present simultaneous endo-epicardial in vivo mapping data at sites of breakthrough events. Breakthrough incidence and degree of EED increased with increasing AF substrate complexity. In goat left atrial free walls, most of the breakthroughs can be explained by transmural conduction, whereas ectopic focal discharges play a limited role as source of breakthrough.

Aims: It remains difficult to detect subtle left ventricular (LV) myocardial dysfunction in chronic aortic regurgitation (AR) patients with the preserved ejection fraction (EF)., Methods and Results: We studied 36 chronic severe AR patients undergoing surgical correction with the EF of 58 ± 6% (all ≥ 50%). Echocardiography was performed before and 12 ± 8 months after surgical correction. We used two-dimensional speckle-tracking strain imaging to evaluate global radial strain in the inner-half (GRSinner), outer-half (GRSouter), and total (GRStotal) layer from the mid-LV short-axis view. We also evaluated the transmural strain profile in the LV posterior wall by using myocardial tissue Doppler radial strain, and the location of peak strain was determined as the percentage of the distance from the endocardium to the epicardium accounted for by the wall thickness. Fifteen EF-matched normal volunteers were studied for comparison. GRSinner for AR patients was significantly smaller than that for controls (28.9 ± 12.9 vs. 37.1 ± 9.1%, P = 0.032), and the location of peak strain had significantly shifted to the epicardial side compared with that in controls (27.1 ± 14.0-13.2 ± 4.8%, P = 0.001). In contrast, GRStotal and GRSouter were similar for the two groups. After surgical correction, EF increased from 58 ± 6 to 62 ± 7% (P = 0.018), GRSinner from 27.8 ± 12.5 to 37.7 ± 14.6% (P < 0.0001), and the location of peak strain significantly shifted to the endocardial side (26.9 ± 13.9-19.1 ± 11.9%, P = 0.028). However, GRStotal and GRSouter did not change., Conclusion: The LV endocardium side, impaired in chronic AR patients with the preserved EF, improved after surgical correction. Our observations may prove useful for evaluating subtle early changes in such patients.

The objective of this study was to assess the impact of right ventricular (RV) trabeculae and papillary muscles on measured volumes and function assessed by cardiovascular magnetic resonance imaging in patients with repaired tetralogy of Fallot. Sixty-five patients with repaired tetralogy of Fallot underwent routine cardiovascular magnetic resonance imaging. Endocardial and epicardial contours were drawn manually and included trabeculae and papillary muscles in the blood volume. Semi-automatic threshold-based segmentation software excluded these structures. Both methods were compared in terms of end-diastolic, end-systolic and stroke volume, ejection fraction and mass. Observer agreement was determined for all measures. Exclusion of trabeculae and papillary muscle in the RV blood volume decreased measured RV end-diastolic volume by 15 % (from 140 ± 35 to 120 ± 32 ml/m(2)) compared to inclusion, end-systolic volume by 21 % (from 74 ± 23 to 59 ± 20 ml/m(2)), stroke volume by 9 % (from 66 ± 16 to 60 ± 16 ml/m(2)) and relatively increased ejection fraction by 7 % (from 48 ± 7 to 51 ± 8 %) and end-diastolic mass by 79 % (from 28 ± 7 to 51 ± 10 g/m(2)), p < .01. Excluding trabeculae and papillary muscle resulted in an improved interobserver agreement of RV mass compared to including these structures (coefficient of agreement of 87 versus 78 %, p < .01). Trabeculae and papillary muscle significantly affect measured RV volumes, function and mass. Semi-automatic threshold-based segmentation software can reliably exclude trabeculae and papillary muscles from the RV blood volume.

Conduction channels and electrograms with isolated component/late potentials are sensitive markers of the substrate of post-myocardial infarction sustained monomorphic ventricular tachycardia (VT). Ablation of all conduction channels and isolated component/late potentials (complete endocardial VT substrate ablation [CEVTSA]) during sinus rhythm could simplify and facilitate the ablation procedure, mainly in patients without references for clinical VT substrate identification. The aim of this study was to assess the safety, efficacy, and predictors of VT recurrence after CEVTSA. Electroanatomic mapping and CEVTSA were performed in 59 post-myocardial infarction patients (mean age 67 ± 9 years, mean left ventricular ejection fraction 30 ± 11%), 24 of whom did not have clinical VT substrate references. The mean areas of scar (≤1.5 mV) and dense scar (≤0.5 mV) were 76 ± 42 and 34 ± 24 cm(2), respectively; isolated component/late potentials and conduction channels were identified and ablated in 97% and 83% of patients (mean ablation area 14 ± 10 cm(2)). No life-threatening complications occurred during the procedure. After 1 year and at the end of follow-up (mean 39 ± 21 months), 81% and 58% of patients were free of VT. No differences were observed between patients with and without specific clinical VT substrate identification. Univariate analysis identified the left ventricular ejection fraction, VT cycle length (VTCL), infarct location (inferior vs anterior), and dense scar area as predictors of VT recurrence, and Cox analysis identified VTCL (hazard ratio 0.42, p <0.001) and dense scar area (hazard ratio 2.65, p <0.0006) as independent predictors. No patients with dense scar area ≤25 cm(2) and VTCL >350 ms had recurrences. In conclusion, CEVTSA is safe and effective, even in patients without clinical VT substrate identification. Scar area and VTCL are valuable predictors of VT recurrence., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Recent studies have shown that short duration ventricular fibrillation (SDVF) and long duration ventricular fibrillation (LDVF) are maintained by different mechanisms. The objective of this study is to evaluate how the defibrillation threshold (DFT) varies over the duration of fibrillation since the mechanism of VF maintenance changes as VF progresses., Methods: Twelve canines were randomly divided into two groups (Group A and B, n=6 each). DFTs were measured three times in each group: SDVF (20s), LDVF (3min in Group A and 7min in Group B) and the first episode of refibrillation after successful defibrillation for LDVF. Two 64-electrode baskets used to globally map the endocardium were deployed into the left ventricle and right ventricle, respectively., Results: LDVF-DFT in Group A was significantly higher than that of Group B (628±98V vs 313±81V, P<0.001). In Group B, the DFT of refibrillation was significantly increased compared with the LDVF-DFT (570±199V vs 313±81V, P=0.035) but did not differ from the DFT of refibrillation in Group A (570±199V vs 638±116V, P=0.39). Highly synchronised activation patterns on the left ventricular endocardium were observed between 3 and 7min of LDVF in Group B but not within 3min-LDVF in Group A or during refibrillation in each group., Conclusions: DFT varied during different stages of VF. The highly synchronised activation patterns exhibiting after 3min VF might contribute to the decreased LDVF-DFT., (Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Endocardial voltage mapping (EVM) identifies low-voltage right ventricular (RV) areas, which may represent the electroanatomic scar substrate of life-threatening tachyarrhythmias. We prospectively assessed the prognostic value of EVM in a consecutive series of patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D)., Methods and Results: We studied 69 consecutive ARVC/D patients (47 males; median age 35 years [28-45]) who underwent electrophysiological study and both bipolar and unipolar EVM. The extent of confluent bipolar (<1.5 mV) and unipolar (<6.0 mV) low-voltage electrograms was estimated using the CARTO-incorporated area calculation software. Fifty-three patients (77%) showed ≥1 RV electroanatomic scars with an estimated burden of bipolar versus unipolar low-voltage areas of 24.8% (7.2-31.5) and 64.8% (39.8-95.3), respectively (P=0.009). In the remaining patients with normal bipolar EVM (n=16; 23%), the use of unipolar EVM unmasked ≥1 region of low-voltage electrogram affecting 26.2% (11.6-38.2) of RV wall. During a median follow-up of 41 (28-56) months, 19 (27.5%) patients experienced arrhythmic events, such as sudden death (n=1), appropriate implantable cardioverter defibrillator interventions (n=7), or sustained ventricular tachycardia (n=11). Univariate predictors of arrhythmic outcome included previous cardiac arrest or syncope (hazard ratio=3.4; 95% confidence interval, 1.4-8.8; P=0.03) and extent of bipolar low-voltage areas (hazard ratio=1.7 per 5%; 95% confidence interval, 1.5-2; P<0.001), whereas the only independent predictor was the bipolar low-voltage electrogram burden (hazard ratio=1.6 per 5%; 95% confidence interval, 1.2-1.9; P<0.001). Patients with normal bipolar EVM had an uneventful clinical course., Conclusions: The extent of bipolar RV endocardial low-voltage area was a powerful predictor of arrhythmic outcome in ARVC/D, independently of history and RV dilatation/dysfunction. A normal bipolar EVM characterized a low-risk subgroup of ARVC/D patients.

Assessment of transmural extent (TME) of necrosis after acute myocardial infarction (MI) remains a major problem in clinical practice. The study sought to determine whether speckle tracking imaging (STI) could differentiate transmural from nontransmural acute MI by assessment of endocardial and epicardial torsion. TME of infarct was measured by contrast-enhanced magnetic resonance imaging. Patients were divided into two groups according to TME (transmural MI group [TME ≥ 50%, n = 36] and nontransmural MI group [TME < 50%, n = 35]). As a control group, 30 subjects without evidence of structural heart disease were included. Conventional echocardiography and STI were done in controls and patients before and 1 month after percutaneous coronary intervention. Compared with control subjects, endocardial and epicardial torsion in patients with transmural and nontransmural MI were all extremely decreased (all P < 0.01). One month after percutaneous coronary intervention, there was no significant increase in endocardial and epicardial torsion in transmural MI patients. However, apical rotation and left ventricular torsion resumed slightly but significantly in the epicardium (but not endocardium) in patient with nontransmural MI (3.11 ± 0.81 vs. 4.37 ± 1.15°, P < 0.01; 3.69 ± 1.07 vs. 5.52 ± 1.89°, P < 0.01, respectively). The combined evaluation of endocardial and epicardial torsion by STI may be used to differentiate transmural from nontransmural MI after revascularization.

Introduction: Evidence indicates that rheumatoid arthritis (RA) patients have increased susceptibility to myocardial ischaemia that contributes to myocardial infarction. The subendocardial viability ratio (SEVR) can be measured using pulse wave analysis and reflects myocardial oxygen supply and demand. The objective of the present study was to examine specific predictors of SEVR in RA patients, with a specific focus on inflammation and classical cardiovascular disease (CVD) risk factors., Methods: Two patient cohorts were included in the study; a primary cohort consisting of 220 RA patients and a validation cohort of 127 RA patients. All patients underwent assessment of SEVR using pulse wave analysis. Thirty-one patients from the primary cohort who were about to start anti-inflammatory treatment were prospectively examined for SEVR at pretreatment baseline and 2 weeks, 3 months and 1 year following treatment. Systemic markers of disease activity and classical CVD risk factors were assessed in all patients., Results: The SEVR (mean ± standard deviation) for RA in the primary cohort was 148 ± 27 and in the validation cohort was 142 ± 25. Regression analyses revealed that all parameters of RA disease activity were associated with SEVR, along with gender, blood pressure and heart rate. These findings were the same in the validation cohort. Analysis of longitudinal data showed that C-reactive protein (P < 0.001), erythrocyte sedimentation rate (P < 0.005), Disease Activity Score in 28 joints (P < 0.001), mean blood pressure (P < 0.005) and augmentation index (P < 0.001) were significantly reduced after commencing anti-TNFα treatment. Increasing C-reactive protein was found to be associated with a reduction in SEVR (P = 0.02) and an increase in augmentation index (P = 0.001)., Conclusion: The present findings reveal that the SEVR is associated with markers of disease activity as well as highly prevalent classical CVD risk factors in RA, such as high blood pressure and diabetes. Further prospective studies are required to determine whether the SEVR predicts future cardiac events in RA.