Left Atrial Pacing Research Articles

Atrial voltage analysis following vein of marshall alcohol infusion predicts mitral line block

Abstract Background The vein of Marshall (VOM) is a promising therapeutic target for the atrial fibrillation (AF) treatment, fitting perfectly with the "Coumel triangle" as it contains triggers of focal activities and stable reentries, autonomic parasympathetic and sympathetic connection and it represents substrate for perimitral flutters. Lateral mitral line (ML) represents a fundamental part of the anatomical ablation setup for the treatment of AF but its bidirectional block is very difficult to achieve by endocardial ablations. Ethanol infusion into the VoM (VOM-EI) has demonstrated high effectiveness in facilitating ML block. Newly-formed bipolar lesion after VOM-EI is considered an index of effectiveness of the alcoholization procedure. Voltage analysis assessment after VOM-EI in predicting ML block is poorly investigated. Purpose To compare unipolar and bipolar low-voltage areas (LVAs) along VOM trajectory after VOM-EI, and their role in predicting ML block. Methods We enrolled 59 patients undergoing catheter ablation for persistent AF or mitral isthmus dependent atrial flutter. We performed first a high-density voltage map of the left atrium. After VOM-EI, a LA remap was performed. The area width difference was obtained and defined as ∆LVA (see Figure 1). Normal Bipolar voltage cutoffs were 0.50 mV in case of sinus rhythm or 0.29 mV in case of AF. Unipolar cutoffs were respectively 2.7 mV in sinus rhythm and 1.1 mV in AF. The anatomical lesions set, after VOM-EI, included wide antral PVI, linear lesion for dome and ML isthmus following the newly-formed lesion after the VOM-EI. Systematic lines block validation was performed. ML block was defined after coronary sinus electrograms sequence inversion (septal-to-lateral) during left atrial appendage pacing. In case of residual conduction gaps, RF applications into the coronary sinus-great cardiac vein were done to target residual epicardial gaps. Ablation time to obtain ML block (AblTime) was obtained. Results In our group, 56/59 patients (94.5%) achieved mitral isthmus block. Bipolar and unipolar low voltage areas after VOM-EI were 9.9 ± 6.9 cm2 and 12.2 ± 5.9 cm2 respectively. Bipolar ∆LVAs were significantly lower compared with unipolar ∆LVA (8.2 ± 6.5 cm2 vs 9.4 ± 6.0 cm2; p= 0.03). A strong linear correlation between AblTime and bipolar ∆LVA (R: 0.76) and a significant correlation between AblTime and unipolar ∆LVA (R: 0.6) were found (Figure 2). Patients that required coronary sinus applications to reach ML block (13/59, 22%), presented lower ∆LVAs at logistic regression both at bipolar (p<0.01) and unipolar (p=0.03) analysis. Conclusions Unipolar and bipolar voltage analysis along the mitral isthmus trajectory predicts ML block achievement, with VOM-EI inducing wider unipolar LVAs than bipolar LVAs. Furthermore, wider unipolar and bipolar LVAs post VOM-EI are linked to a shorter AblTime and an increased probability of avoiding the need to target epicardial gaps via the CS musculature.LVA along VOM territory after VOM EI∆LVAs linear correlation with AblTime

ATRIAL VOLTAGE ANALYSIS FOLLOWING VEIN OF MARSHALL ETHANOL INFUSION PREDICTS MITRAL LINE BLOCK

Abstract Background The vein of Marshall (VoM) is a promising target for atrial fibrillation (AF) treatment, matching with the ‘Coumel triangle‘ by housing triggers, autonomic connections, and serving as a substrate for perimitral flutters. Lateral mitral line (ML) represents a fundamental part for AF treatment, but achieving bidirectional block through endocardial ablations is challenging. VoM ethanol infusion (VOM–EI) facilitates ML block, with the newly–formed bipolar lesion serving as an effectiveness index. Voltage analysis assessment after VOM–EI in predicting ML block is poorly investigated. Purpose To compare unipolar and bipolar low–voltage areas (LVAs) along VOM trajectory after VOM–EI, and their role in predicting ML block. Methods We enrolled 59 patients undergoing catheter ablation of persistent AF or ML–dependent atrial flutter. High–density voltage mapping of left atrium was followed by VOM–EI and LA remapping. The area width difference was obtained and defined as ΔLVA. Normal bipolar voltage cutoffs were 0.50 mV in sinus rhythm or 0.29 mV in AF. Unipolar cutoffs were 2.7 mV and 1.1 mV, respectively. After VOM–EI, anatomical lesions included PVI, linear lesion for dome and ML isthmus. Systematic lines block validation was performed, defining ML block after coronary sinus (CS) electrograms sequence inversion (septal–to–lateral) during left atrial appendage pacing. Radiofrequency (RF) applications into the CS–great cardiac vein targeted epicardial gaps if present. Ablation time for ML block (AblTime) was obtained. Results In our cohort, 94.5% achieved ML block. Bipolar and unipolar low voltage areas after VOM–EI were 9,9 ± 6,9 cm2 and 12,2 ± 5,9 cm2 respectively. Bipolar ΔLVAs were significantly lower than unipolar ΔLVA (8.2 ± 6.5 cm2 vs. 9.4 ± 6.0 cm2; p=0.03) (Fig 1). A strong linear correlation between AblTime and bipolar ΔLVA (R: 0.76), and a significant correlation between AblTime and unipolar ΔLVA (R: 0.6) were found (Fig 2). Patients requiring RF applications into the CS for ML block (13/59, 22%) showed lower ΔLVAs in logistic regression for both bipolar (p<0.01) and unipolar (p=0.03) analyses. Conclusions VOM–EI induces unipolar LVAs wider than bipolar along the mitral isthmus trajectory. Unipolar and bipolar voltage analysis predicts a short time ML block achievement. Moreover, wider unipolar and bipolar LVAs following VOM–EI correlates with higher likelihood to avoid the targeting of epicardial gaps via the CS musculature.

Advances in device-based treatment of heart failure with preserved ejection fraction: evidence from clinical trials.

Heart failure with preserved ejection fraction (HFpEF) is a group of clinical syndromes that exhibit a remarkably heterogeneous phenotype, characterized by symptoms and signs of heart failure, left ventricular diastolic dysfunction, elevated levels of natriuretic peptides, and an ejection fraction greater than or equal to 50%. With the aging of the population and the escalating prevalence of hypertension, obesity, and diabetes, the incidence of HFpEF is progressively rising. Drug therapy options for HFpEF are currently limited, and the associated high risk of cardiovascular mortality and heart failure rehospitalization significantly impact patients' quality of life and longevity while imposing a substantial economic burden on society. Recent research indicates that certain device-based therapies may serve as valuable adjuncts to drug therapy in patients with specific phenotypes of HFpEF, effectively improving symptoms and quality of life while reducing the risk of readmission for heart failure. These include inter-atrial shunt and greater splanchnic nerve ablation to reduce left ventricular filling pressure, implantable heart failure monitor to guide diuresis, left atrial pacing to correct interatrial dyssynchrony, cardiac contractility modulation to enhance cardiac calcium handling, as well as renal denervation, baroreflex activation therapy, and vagus nerve stimulation to restore the autonomic imbalance. In this review, we provide a comprehensive overview of the mechanisms and clinical evidence pertaining to these devices, with the aim of enhancing therapeutic strategies for HFpEF.

PO-02-206 A MECHANISM FOR PACING-INDUCED REGIONAL CONTRACTILE DYSFUNCTION MEDIATED BY RELEASED CATECHOLAMINES

We have previously shown that non-excitatory epicardial stimulation (NES) increases measures of cardiac function mediated by local release of norepinephrine. In this further investigation we focused on the effects of NES on the local myocardial contractile pattern. Farm pigs were anesthetized and instrumented with a LV high-fidelity pressure/volume conductance transducer, thoracic aortic pressure transducer, left atrial (LA)/ LV epicardial electrodes, and sonomicrometer segment length (SL) gauges placed proximal (lateral base) and distal (posterior mid LV) to the LV stimulation site. During constant LA pacing, LV pulses (0.8ms, 2-3x threshold volts) were applied during the absolute refractory period before and after β-receptor blockade (BB, metoprolol). Regional contractile function was analyzed by constructing LVP vs. SL loops in a beat-by-beat fashion thus allowing characterization of local cardiac function in relation to LV pressure over the entire cardiac cycle. NES resulted in a local contractile dysfunction characterized by an early shortening, subsequent lengthening, and re-shortening pattern during the cardiac cycle in the SL gauge proximal (middle tracing), but not remote to the stimulation site (bottom tracing). The onset of early lengthening in the proximal SL coincided with peak pressure generation, followed by re-shortening as LV pressure fell. The LVP vs. SL loop was markedly altered. This contractile effect rapidly waned within 10-15 seconds after cessation of electrical stimulation and was abolished by BB. The NES induced dysfunction developed within an average of 5-10 seconds of stimulation onset and was accompanied by increases in several global indices of cardiac function (dP/dt, peak LVP, early aortic valve opening) which were also abrogated by B-blockade. These findings demonstrate that pacing elicits local catecholamine release that may cause dyssynergy and mimic the regional pacing-induced contractile dysfunction seen at pacing sites in man.

Abstract 12821: Progressive Improvement in Left Ventricular Performance Associated With Progressive Regional Dyssynchrony

Background : We have shown that non-excitatory epicardial stimulation (NES) increases measures of cardiac function mediated by local release of norepinephrine. In this further investigation we determined whether NES is accompanied by improved indices of left ventricular (LV) performance, reflected in PV loops and timing of aortic valve opening and closing. Methods : Anesthetized pigs (n=6) were instrumented with a LV high-fidelity pressure/volume conductance transducer, thoracic aortic pressure transducer, left atrial (LA)/ LV epicardial electrodes, and sonomicrometer segment length (SL) gauges placed proximal (lateral base) and distal (posterior mid LV) to the LV stimulation site. During constant LA pacing, LV pulses (0.8ms, 2-3x threshold volts) were applied during the absolute refractory period for 3 minutes (3x), before and after β-receptor blockade (BB, metoprolol). Data were analyzed at baseline, and at an estimated 30%, 60% and 100% of developed ventricular dyssynchrony (DVD) contraction pattern. Results: Consistent with earlier findings, NES resulted in an early shortening and relaxation pattern of the proximal SL manifest as an 80% decrease in the LVP vs. SL loop area in the absence of change in the remote segment. This was accompanied by an increase in peak systolic pressure and LV dP/dt max. Although NES did not change the area of the LVP vs. LV volume loop (stroke work) or alter the interval from LV electrical activation (R wave) to the onset of LV pressure increase, aortic valve opening occurred up to 14.1 ± 2.8 ms earlier (p <0.01) compared to baseline. The duration of an open aortic valve slightly increased (6.0 ± 3.9 ms) whereas ejection duration from valve opening to peak Pao decreased 18.2 ± 3.0 ms (p < 0.01). Conclusion : These findings demonstrate that NES elicits a local contractile dysynchrony resulting in an enhanced cardiac inotropic state characterized by more rapid global LV contraction with earlier aortic valve opening with no change in stroke work.

DefiPaceTM System, A New Device for Cardioversion of Atrial Fibrillation After Cardiac Surgery - Preliminary Results.

Postoperative atrial fibrillation (POAF) is a frequent complication following cardiac surgery. This study examined the safety and efficacy of the new system consisting of two bi-atrial temporary pacing and cardioversion electrodes, a ventricular electrode and the device (combined external pacemaker and cardioverter) for low-energy atrial cardioversion. The temporary electrodes were placed on the left and right atrium during open heart surgery. Pacing thresholds and sensing were measured up to the 6th postoperative day. The satisfactory handling of the electrodes was measured with a visual analog scale (VAS) 1-10, with 10 being the best and 1 being the lowest. In case of POAF, R-wave synchronous low-energy shocks (0.5-10 J) were applied for cardioversion. Temporary electrodes were implanted in 29 patients (age 65.6 10.4 years; 21 males, 14 OPCAB, 15 on-pump cardiac operations). Left or right atrial pacing thresholds ranged from 1.9 1.3 V/ms to 5.0 3.3 V/ms and P-wave sensing from 0.9 0.6 mV to 1.5 0.7 mV. VAS for handling of electrodes: implantation 7.1 0.8 and removal 8.4 1.0. POAF was observed in four patients. Two patients had successful atrial cardioversion with 3.5 J and 4.5 J. One patient converted spontaneously, and one patient remained in PAOF. There were no device-related adverse events. The system can be used safely in patients undergoing cardiac surgery.

B-PO04-216 BI-ATRIAL PACING VIA Y-ADAPTOR USING THE VEIN OF MARSHALL

We present a rare case of a patient with sick sinus syndrome (SSS) due to stab wound, who inadvertently had right atrial appendage (RAA) isolation during ablation. To report a unique technique of a bi-atrial pacing via Y-adaptor with left atrial (LA) lead in the Vein of Marshall (VOM). N/A A 64-year-old male with a stab to the heart underwent two tricuspid valve repairs complicated by RA enlargement and SSS which required permanent pacemaker (PPM). He developed recurrent atypical atrial flutter despite dofetilide use. During mapping his flutter noted to originate from the RAA. While ablating his flutter, it terminated and inadvertently led to RAA isolation. This resulted in lack of RAA pacing signal conducting to rest of atria (including LA and AV node), increasing risk of thrombosis in LA due to atria standstill and chronic RV pacing. Decision was made to restore conduction without compromising RAA pacing. Attempts to deploy to pace the interatrial septum failed due to a very large and scarred RA. The coronary sinus (CS) was cannulated and venogram demonstrated VOM to be too small for a passive lead. A 59 cm active fixation lead was then screwed into the ostium of VOM with good LA pacing threshold (0.7 V at 0.4 ms, 599 ohms). Both atrial leads (RAA and LA/VOM) were then connected via Y-adapter to the RA port of the pacemaker (Figure 1). Bi-atrial pacing threshold was good (1 V at 0.4 ms, 450 ohms). EKG demonstrated successful bi-atrial pacing with RV conduction. RAA isolation in pacer-dependent patients can lead to chronic RV pacing and LA standstill. Y-adapter bi-atrial leads can restore bi-atrial pacing and conduction.

Chronic HDAC6 Activation Induces Atrial Fibrillation Through Atrial Electrical and Structural Remodeling in Transgenic Mice.

Atrial fibrillation (AF) is a relatively common complication of hypertension. Chronic hypertension induces cardiac HDAC6 catalytic activity. However, whether HDAC6 activation contributes to hypertension-induced AF is still uncertain. We examined whether chronic cardiac HDAC6 activation-induced atrial remodeling, leading to AF induction.The HDAC6 constitutively active transgenic (TG) (HDAC6 active TG) mouse overexpressing the active HDAC6 protein, specifically in cardiomyocytes, was created to examine the effects of chronic HDAC6 activation on atrial electrical and structural remodeling and AF induction in HDAC6 active TG and non-transgenic (NTG) mice. Left atrial burst pacing (S1S1 = 30 msec) for 15-30 sec significantly increased the frequency of sustained AF in HDAC6 active-TG mice compared with NTG mice. Left steady-state atrial pacing (S1S1 = 80 msec) decreased the atrial conduction velocity in isolated HDAC6 active TG compared with NTG mouse atria. The atrial size was similar between HDAC6 active TG and NTG mice. In contrast, atrial interstitial fibrosis increased in HDAC6 active TG compared with that of NTG mouse atria. While protein expression levels of both CX40 and CX43 were similar between HDAC6 active TG and NTG mouse atria, a heterogeneous distribution of CX40 and CX43 occurred in HDAC6 active-TG mouse atria but not in NTG mouse atria. Gene expression of interleukin 6 increased in HDAC6 active TG compared with NTG mouse atria.Chronic cardiac HDAC6 activation induced atrial electrical and structural remodeling, and sustained AF. Hypertension-induced cardiac HDAC6 catalytic activity may play important roles in the development of AF.

Dynamic comparisons of epicardial electrograms between the left atrium and pulmonary veins in atrial fibrillation in goat model

Objective: To compare epicardial electrograms between the left atrium (LA) and pulmonary veins (PVs) dynamically at development of persistent atrial fibrillation(AF) in goats PVs. Methods: Ten female goats were instrumented with electrodes at the LA and left side PV. Sustained AF (＞24 h) was induced in the goat by rapid intermittent left atrial pacing for(9.5±2.3)days at a pacing interval of 20 ms for 1 s with a maximum output of 6.0 V, followed by a 2-s period without pacing. Characteristics of PVs and LA epicardial electrograms were analyzed in the development of AF. Results: With prolonged stimulation, the duration of AF was prolonged, complex fractionated atrial electrograms(CFAEs) in LA and was increased gradually, PVs had more CFAEs than LA all the time. When induced AF lasted for more than 24 h, CFAEs in PVs became sustained approximately (2.7%±3.6% vs 92.6%±6.4%, at onset of AF vs AF lasted for more than 24 h, P＜0.05), and the ratio of CFAEs in PVs was more than that in LA (92.6%±6.4% vs 72.8%±5.3%, P＜0.05). Conclusion: The epicardial CFAEs are in specific area, which increase along with electrical remodeling. The epicardial CFAEs may play an important role in the maintenance of AF in this model.

Epiphenomenal Re-Entry and Spurious Focal Activation Detection by Atrial Fibrillation Mapping Algorithms.

The purpose of this study was to validate the ability of mapping algorithms to detect rotational activations (RoA) and focal activations (FoA) during fibrillatory conduction (FC) and atrial fibrillation (AF) and understand their mechanistic relevance. Mapping algorithms have been proposed to detect RoA and FoA to guide AF ablation. Rapid left atrial pacing created FC-fibrillatory electrograms-with and without AF induction in dogs (n=17). Activation maps were constructed using Topera (Abbott, St. Paul, Minnesota) or CARTOFINDER (Biosense Webster, Irvine,California) algorithms. Mapping strategies included: panoramic noncontact mapping with a basket catheter (CARTOFINDER n=6, Topera n=5); and sequential contact mapping using 8-spline OctaRay catheter (Biosense Webster) (n=6). Offline frequency and spectral analysis were also performed. Algorithm-detected RoA was manually verified. The right atrium (RA) consistently exhibited fibrillatory signals during FC. FC with and without AF hadsimilar left-to-right frequency gradients. Basket maps were either uninterpretable (847 of 990 Topera, 132 of 148 Cartofinder) or had unverifiable RoA. OctaRay contact mapping showed 4% RoA (n=30 of 679) and63% FoA (n=429 of 679). Verified RoA clustered at consistent sites, was more common in the RA than leftatrium (odds ratio: 3.5), and colocalized with sites of frequency breakdown in the crista terminalis and RA appendage. During pacing, spurious FoA sites were identified around the atria, but not at the actual pacing sites. RoA and FoA site distribution was similar during pacing with and without induction, and during induced AF. Mapping algorithms were unable to detect pacing sites as true drivers of FC, and detected epiphenomenal RoA and FoA sites unrelated to AF induction or maintenance. Algorithm-detected RoA and FoAdidnot identify true AF drivers.

Effects and Mechanisms of Cutting Upper Thoracic Sympathetic Trunk on Ventricular Rate in Ambulatory Canines with Persistent Atrial Fibrillation.

Objective The purpose is to observe the effects and neural mechanism of cutting upper thoracic sympathetic trunk (TST) on the ventricular rate (VR) during persistent atrial fibrillation (AF). Methods Twelve beagle dogs were halving to the control group and experimental group, 6 dogs for each group. Both groups were performed with left atrial rapid pacing (600 beats/min) to induce sustained AF. The experimental group underwent cutting upper TST after a sustained AF model was established, while the control group received thoracotomy without cutting TST. Bilateral stellate ganglion (SG) and left atrial myocardium were harvested for tyrosine-hydroxylase (TH) immunohistochemical staining. Results After cutting upper TST for 30 minutes, the average VR was 121.5 ± 8.7 bpm (95% CI, 114.8 to 128.0) in the experimental group, which was significantly slower than that of the control group (144.5 ± 4.2 bpm (95% CI, 141.5 to 148.0)) (P < 0.001). After cutting upper TST for 1 month, the average VR of the experimental group (106.5 ± 4.9 bpm (95% CI, 102.0 to 110.0)) was also significantly slower versus that of the control group (139.2 ± 5.6 bpm (95% CI, 135.0 to 143.8)) (P < 0.001). Compared with the control group, both left stellate ganglion (LSG) and right stellate ganglion (RSG) of the experimental group caused neural remodeling characterized by decreased ganglionic cell density and reduced TH staining. TH-positive component was significantly decreased in the left atrium of the experimental group compared with the control group. Conclusions Cutting upper TST could reduce fast VR during persistent AF. Cutting upper TST induced bilateral SG neural remodeling and reduced sympathetic nerve density in the left atrium, which could contribute to the underlying mechanism of VR control during AF.

Systematic Evaluation of High-Resolution Activation Mapping to Identify Residual Endocardial and Epicardial Conduction Across the Mitral Isthmus.

This study sought to systematically evaluate the ability of a high-resolution mapping system (Rhythmia, Boston Scientific, Marlborough, Massachusetts) to rapidly and accurately localize residual endocardial and epicardial conduction after mitral isthmus (MI) ablation, facilitating MI block. Achieving conduction block across the mitral isthmus (MI) is challenging. Fifty consecutive patients undergoing MI ablation after pulmonary vein isolation were enrolled. After initial endocardial radiofrequency (RF) ablation across the lateral MI, high-resolution activation mapping of the MI with simultaneous coronary sinus (CS) mapping was performed to verify block or localize residual conduction across the MI during left atrial (LA) appendage and CS pacing. Propagation maps were used to identify residual conduction across the MI as endocardial, via the CS or Marshall tract. In all 50 patients, after the initial endocardial ablation across the MI, repeat high-resolution mapping of the LA and CS was obtained (median: 3,329 mapped points; 4.0min of mapping time). The initial endocardial MI ablation resulted in block in 9 of 50 patients (18%). In the remaining 41 patients, the propagation map identified residual conduction in 4 patterns: 1) only endocardial gap in 12 patients (29%); 2) only CS connection in 10 patients (24%); 3) both endocardial and CS connections in 14 patients (34%); and 4) Marshall tract connection in 5 patients (12%). In 8 patients, the propagation map revealed residual conduction, despite differential atrial pacing suggesting bidirectional block. Focal ablation at the identified residual conduction site (median: 0.7min of RF) resulted in block in 49 of 50 (98%) patients. High-resolution propagation maps of the LA/CS rapidly and accurately localize residual endocardial and epicardial conduction across the MI. Focal ablation with short RF time at the identified gap(s) achieved complete block across MI in 98% of cases.

Left Atrial Enhancement Correlates With Myocardial Conduction Velocity in Patients With Persistent Atrial Fibrillation.

BackgroundConduction velocity (CV) heterogeneity and myocardial fibrosis both promote re-entry, but the relationship between fibrosis as determined by left atrial (LA) late-gadolinium enhanced cardiac magnetic resonance imaging (LGE-CMRI) and CV remains uncertain.ObjectiveAlthough average CV has been shown to correlate with regional LGE-CMRI in patients with persistent AF, we test the hypothesis that a localized relationship exists to underpin LGE-CMRI as a minimally invasive tool to map myocardial conduction properties for risk stratification and treatment guidance.Method3D LA electroanatomic maps during LA pacing were acquired from eight patients with persistent AF following electrical cardioversion. Local CVs were computed using triads of concurrently acquired electrograms and were co-registered to allow correlation with LA wall intensities obtained from LGE-CMRI, quantified using normalized intensity (NI) and image intensity ratio (IIR). Association was evaluated using multilevel linear regression.ResultsAn association between CV and LGE-CMRI intensity was observed at scales comparable to the size of a mapping electrode: −0.11 m/s per unit increase in NI (P < 0.001) and −0.96 m/s per unit increase in IIR (P < 0.001). The magnitude of this change decreased with larger measurement area. Reproducibility of the association was observed with NI, but not with IIR.ConclusionAt clinically relevant spatial scales, comparable to area of a mapping catheter electrode, LGE-CMRI correlates with CV. Measurement scale is important in accurately quantifying the association of CV and LGE-CMRI intensity. Importantly, NI, but not IIR, accounts for changes in the dynamic range of CMRI and enables quantitative reproducibility of the association.

No effects of cardiac resynchronization therapy and right ventricular pacing on the right ventricle in patients with heart failure and atrial fibrillation

Background The right ventricle (RV) function is crucial in heart failure with reduced ejection fraction (HFrEF), especially in patients with atrial fibrillation (AF). Aims. To assess the RV structure and function in patients with HFrEF, permanent atrial fibrillation (AF), cardiac resynchronization therapy (CRT) and RV pacing (RVp) with two- and three-dimensional echocardiography. Methods. Patients with ischemic HFrEF (NYHA II-III; LVEF ≤40%) were enrolled. The studied groups were: sinus rhythm (SR, control); AF and no implanted devices - AF/0; AF and CRT - AF/CRT; AF and RVp - AF/RVp. Two- and three-dimensional echocardiographic parameters of RV structure and function were analyzed in study groups. Results. The study included a group of 126 patients: n = 32 with SR, n = 28 with AF/0, n = 25 with AF/CRT and n = 41 with AF/RVp. Results were worse in AF groups than in SR: right ventricular ejection fraction, %, mean (SD): SR − 48.2 (7.5), AF/0 − 36.5 (6.5), AF/CRT − 38.3 (7.6), AF/RVp − 37.1 (7.7), p < .001. Other parameters lower in AF groups than in SR were: RV end-systolic volume, longitudinal strain of the free wall and tricuspid lateral annular systolic velocity. There were no differences between groups with AF and CRT and RV pacing in other analyzed parameters between AF groups and SR. Conclusions. In heart failure with reduced left ventricular ejection fraction and atrial fibrillation right ventricular pacing and cardiac resynchronization therapy were not associated with modified right ventricular function. Further prospective studies are needed to evaluate prognostic significance of these results.

Association of Left Atrial High-Resolution Late Gadolinium Enhancement on Cardiac Magnetic Resonance With Electrogram Abnormalities Beyond Voltage in Patients With Atrial Fibrillation.

Conflicting data have been reported on the association of left atrial (LA) late gadolinium enhancement (LGE) with atrial voltage in patients with atrial fibrillation. The association of LGE with electrogram fractionation and delay remains to be examined. We sought to examine the association between LA LGE on cardiac magnetic resonance and electrogram abnormalities in patients with atrial fibrillation. High-resolution LGE cardiac magnetic resonance was performed before electrogram mapping and ablation in atrial fibrillation patients. Cardiac magnetic resonance features were quantified using LA myocardial signal intensity Z score (SI-Z), a continuous normalized variable, as well as a dichotomous LGE variable based on previously validated methodology. Electrogram mapping was performed pre-ablation during sinus rhythm or LA pacing, and electrogram locations were coregistered with cardiac magnetic resonance images. Analyses were performed using multilevel patient-clustered mixed-effects regression models. In the 40 patients with atrial fibrillation (age, 63.2±9.2 years; 1312.3±767.3 electrogram points per patient), lower bipolar voltage was associated with higher SI-Z in patients who had undergone previous ablation (coefficient, -0.049; P<0.001) but not in ablation-naive patients (coefficient, -0.004; P=0.7). LA electrogram activation delay was associated with SI-Z in patients with previous ablation (SI-Z: coefficient, 0.004; P<0.001 and LGE: coefficient, 0.04; P<0.001) but not in ablation-naive patients. In contrast, increased LA electrogram fractionation was associated with SI-Z (coefficient, 0.012; P=0.03) and LGE (coefficient, 0.035; P<0.001) only in ablation-naive patients. The association of LA LGE with voltage is modified by ablation. Importantly, in ablation-naive patients, atrial LGE is associated with electrogram fractionation even in the absence of voltage abnormalities.

Characterization of Residual Conduction Gaps After HotBalloon-Based Antral Ablation of Atrial Fibrillation - Evidence From Ultra-High-Resolution 3-Dimensional Mapping.

The electrophysiological characteristics of residual conduction gaps between the left atrium (LA) and pulmonary veins (PVs) after HotBalloon-based wide antral ablation (HBWA) of atrial fibrillation (AF) remain incompletely understood. This study aimed to characterize the residual gaps by means of ultra-high-resolution mapping.Methods and Results:A total of 55 AF patients underwent HBWA by a predetermined protocol (6-shot total-based antral approach). LA-PV maps were created using 64-electrode minibasket catheters. In total, 55 residual gaps were identified among 26 (47%) patients. Residual gaps included 33 left superior (LS: 60%), 10 left inferior (18%), 6 right superior (11%), and 6 right inferior (11%) PVs. Those gaps demonstrated both extremely lower bipolar amplitudes (0.11 [interquartile range: 0.06-0.27] mV) and conduction velocities (0.75±0.27 m/s); however, the length was confined (10.3±4.1 mm) except for the LSPV anterior carina (12.2±2.4 mm) region. Among the carina regions, all gaps had far-field potentials consistently added to the PV potentials. Left atrial appendage pacing to split the far-field activity identified confined gap regions (6.7±1.9 mm). Touch-up ablation eliminated the residual PV potentials in all cases. HBWA resulted in a certain degree of residual gap conduction in particular antral regions. These gaps exhibited narrow lengths with lower amplitudes, and often had far-field recordings from the left atrial appendage. Combined with pacing maneuvers, ultra-high-resolution activation maps could both visualize all confined gaps and ensure a bare minimum of touch-up ablations in all patients with gap conduction.

IL-1β Plays an Important Role in Pressure Overload-Induced Atrial Fibrillation in Mice.

Hypertension is one risk for atrial fibrillation (AF) and induces cardiac inflammation. Recent evidence indicates that pressure overload-induced ventricular structural remodeling is associated with the activation of nucleotide binding-oligomerization domain (NOD)-like receptor P3 (NLRP3) inflammasomes, including an apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC). We hypothesized that NLRP3 inflammasomes are an initial sensor for danger signals in pressure overload-induced atrial remodeling, leading to AF. Transverse aortic constriction (TAC) or a sham procedure was performed in mice deficient for ASC-/- and interleukin-1β (IL-1β-/-). One week after the procedure, electrical left atrial burst pacing from the esophagus was performed for 30 s to induce AF. IL-1β, monocyte chemotactic protein 1 (MCP-1), connective tissue growth factor (CTGF), and collagen 1 gene expression were also examined. The electrical burst pacing induced AF in TAC-operated wild-type (WT) (p < 0.001) and ASC-/- (p < 0.05) mice, compared to no AF in the sham-operated WT and ASC-/- mice, respectively. In contrast, the number of mice in which sustained AF was induced was similar between TAC-operated IL-1β-/- and sham-operated IL-1β-/- mice (p > 0.05). The expression of all genes tested was increased in TAC-operated WT and ASC-/- mice compared with sham-operated WT and ASC-/- mouse atria, respectively. CTGF and collagen 1, but not MCP-1, gene expressions were increased in TAC-operated IL-1β-/- mouse atria compared with sham-operated WT and IL-1β-/- mouse atria. In contrast, the IL-1β gene was not detected in either TAC-operated or sham-operated IL-1β-/- mouse atria. These results suggest that an IL-1β activation pathway, different from NLRP3 inflammasomes, plays an important role in pressure overload-induced sustained AF.

Clinical impact of ethanol infusion into the vein of Marshall on the mitral isthmus area evaluated by atrial electrograms recorded inside the coronary sinus

The left atrial myocardium (LAM) and coronary sinus (CS) musculature (CSM) generate atrial electrograms recorded inside the CS (AECSs). The vein of Marshall (VOM) courses the mitral isthmus (MI), and ethanol infusion into the VOM (EI-VOM) is useful to ablate it. However, its detailed effect on the MI, which contains the LAM, CSM, and those connections, is unknown. The purpose of this study was to investigate the impact of EI-VOM on the MI by assessing the AECS. Eighty-four consecutive patients with atrial fibrillation undergoing MI ablation with successful EI-VOM were included. After EI-VOM, radiofrequency (RF) catheter touchup ablation was performed at MI gap sites or inside the CS (RFCS), as needed, to achieve bidirectional conduction block. Ablation effects on AECSs were evaluated during the MI ablation procedure. AECSs demonstrated double potentials consisting of low-amplitude LAM components and high-amplitude CSM components in 31 patients (37%). Of those patients, 21 had a distal-to-proximal activation sequence of the LAM along with a proximal-to-distal activation sequence of the CSM during left atrial appendage pacing, suggesting CSM isolation from the LAM due to electrical LAM-CSM disconnection. Only 2 of the 21 patients required RFCS. The remaining 10 patients with distal-to-proximal activation in both CSM and LAM, suggesting incomplete CSM isolation and persistent LAM-CSM conduction, required RFCS. Overall, combined EI-VOM with RF created bidirectional conduction block at the MI in 78 patients (93%). EI-VOM can ablate the LAM and myocardial connections between the LAM and CSM. Careful assessment of AECSs can predict a requirement for RFCS.

Heart rhythm model for the simulation of electric fields in transesophageal atrial pacing and cardiac resynchronization therapy

Abstract Electric field of biventricular (BV) pacing, left ventricular (LV) electrode position and electrical interventricular desynchronization are important parameters for successful cardiac resynchronization therapy (CRT) in patients with heart failure, sinus rhythm and reduced LV ejection fraction. The aim of the study was to evaluate electric pacing field of transesophageal left atrial (LA) pacing and BV pacing with 3D heart rhythm simulation. Bipolar right atrial (RA), right ventricular (RV), LV electrodes and multipolar hemispherical esophageal LA electrodes were modeled with CST (Computer Simulation Technology, Darmstadt). Electric pacing field were simulated with bipolar RA and RV pacing with Solid S (Biotronik) electrode, bipolar LV pacing with Attain 4194 (Medtronic) electrode and bipolar LA pacing with TO8 (Osypka) esophageal electrode. 3D heart rhythm model with esophagus allowed electric pacing field simulation of 4-chamber pacing with bipolar intracardiac RA, RV, LV pacing and bipolar transesophageal LA pacing. The pacing amplitudes were 3V RA pacing amplitude, 50V LA pacing amplitude, 1.5V RV pacing amplitude and 3V LV pacing amplitude with 0.5ms pacing pulse duration. The atrioventricular delay between RA pacing and BV pacing was 140ms atrioventricular pacing delay and simultaneous RV and LV pacing. Electric pacing fields were simulated during the different pacing modes AAI, VVI, DDD and DDD0V. The intracardiac far-field pacing potentials were evaluated with intracardiac electrodes and a distance of 1mm from the electrodes with RA electrode 1.104V, RV electrode 0.703V and LV electrode 1.32V. The transesophageal far-field pacing potential was evaluated with transesophageal electrode and a distance of 10mm from the elelctrode with LA electrode 6.076V. Heart rhythm model simulation with esophagus allows evaluation of electric pacing fields in AAI, VVI, DDD, DDD0V and DDD0D pacing modes. Electric pacing field of RA, RV and LV pacing in combination with LA pacing may additional useful pacing mode in CRT non-responders.

Percutaneousepicardial pacing using a novel transverse sinus device.

Transvenous lead implantation has multiple drawbacks and complications that can be overcome by epicardial lead placement. We aimed to design percutaneously implanted epicardial leads that are anchored through the transverse sinus (TS). We designed a novel multielectrode pacing device with four bipole electrode pairs. The device is advanced through the TS, with both ends externalized out of the pericardium. We tested the prototype in one proof-of-concept and 5 additional acute canine experiments. The TS device recorded ventricular and atrial electrograms. The median amplitude of near-field ventricular electrograms was 3.3mA (IQR 2.0-4.3) and of near-field atrial electrograms was 2.1mA (IQR 1.3-2.2). The median ventricular threshold (N=30) was 1.1mA (IQR 0.7-3.1) at a median pulse width of 0.5ms (IQR 0.5-0.5). The median atrial threshold (N=10) was 2.4mA (IQR 1.1-7.8) at a median pulse width of 0.5ms (IQR 0.5-0.9). Right and left ventricular and atrial pacing morphologies were noted while pacing electrodes adjacent to these chambers. Simultaneous left (LV) and right ventricular (RV) pacing showed reduction in QRS duration from 116ms (RV) and 105ms (LV) to 91ms. On necropsy, the device was located in the TS in all animals. There were TS abrasions in one animal, and no other acute complications. This study highlights a novel approach to epicardial pacing harnessing the unique anatomy of the transverse sinus as an anchoring point. Placement of this novel transverse sinus device was safe and feasible, with acceptable atrial and ventricular thresholds.