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Patients with atrial fibrillation (AF) have risk factors that predispose to thoracic aneurysmal disease (TAD) and atherosclerosis. In this study in patients with AF, we assessed the occurrence of incidental TAD and assessed if a validated predictive score used to predict AF, the CHARGE-AF score, was associated with greater aortic dimensions. We also assessed the prevalence of coronary calcification. We conducted a cross-sectional study of 1,000 consecutive patients with AF undergoing chest multidetector CT during evaluation for pulmonary vein isolation. A dilated aortic root or ascending aorta (AA, dimension/ body surface area >2.05 cm/m 2 ) were found in 195 (20%). A total of 12 (1%) had significant aortic aneurysmal enlargement of > 5.0 cm. Advancing age, a bicuspid aortic valve, hypertension, and male gender were associated with increased aortic dimensions. Aortic root dimensions increased linearly (p < 0.001) and ascending aortic dimensions increased nonlinearly across CHARGE-AF deciles (p < 0.001). Nearly two-thirds (63%) had coronary calcification, 38% of whom were not on lipid-lowering therapy. In conclusion, in patients with AF undergoing gated chest CT, 1 in 5 had previously undetected TAD, with a small proportion having significantly aneurysmal dimensions approaching surgical thresholds. Risk factors previously established to increase the propensity to develop AF are also associated with increased TAD. These findings raise the need to consider a surveillance strategy for TAD in patients with AF, particularly in those with other risk factors for aortic disease. A high prevalence of coronary calcium was also detected, representing an opportunity to optimize statin therapy in patients with AF., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Our aim was to assess how atrial fibrillation (AF) induction, chronicity, and RR interval irregularity affect left atrial (LA) function and size in the setting of underlying heart failure (HF), and to determine whether AF effects can be mitigated by vagal nerve stimulation (VNS)., Methods: HF was induced by 4-weeks of rapid ventricular pacing in 24 dogs. Subsequently, AF was induced and maintained by atrial pacing at 600 bpm. Dogs were randomized into control (n = 9) and VNS (n = 15) groups. In the VNS group, atrioventricular node fat pad stimulation (310 μs, 20 Hz, 3-7 mA) was delivered continuously for 6 months. LA volume and LA strain data were calculated from bi-weekly echocardiograms., Results: RR intervals decreased with HF in both groups (p = 0.001), and decreased further during AF in control group (p = 0.014), with a non-significant increase in the VNS group during AF. LA size increased with HF (p<0.0001), with no additional increase during AF. LA strain decreased with HF (p = 0.025) and further decreased after induction of AF (p = 0.0001). LA strain decreased less (p = 0.001) in the VNS than in the control group. Beat-by-beat analysis showed a curvilinear increase of LA strain with longer preceding RR interval, (r = 0.45, p <0.0001) with LA strain 1.1% higher (p = 0.02) in the VNS-treated animals, independent of preceding RR interval duration. The curvilinear relationship between ratio of preceding and pre-preceding RR intervals, and subsequent LA strain was weaker, (r = 0.28, p = 0.001). However, VNS-treated animals again had higher LA strain (by 2.2%, p = 0.002) independently of the ratio of preceding and pre-preceding RR intervals., Conclusions: In the underlying presence of pacing-induced HF, AF decreased LA strain, with little impact on LA size. LA strain depends on the preceding RR interval duration.

Background: Left atrial (LA) strain is a sensitive measure of LA mechanics. However, its relationship with rhythm outcomes after catheter ablation in patients with atrial fibrillation (AF) is not well established. The aim of this study was to evaluate whether baseline LA global longitudinal strain (LAε) predicts rhythm outcomes in patients who undergo catheter ablation for AF., Methods: In 256 patients with AF (paroxysmal, 204; persistent, 52), comprehensive echocardiography was performed with assessment of LAε by using Velocity Vector Imaging to calculate average strain values from apical four- and two-chamber views before ablation (median, 41 days; interquartile range, 1-95 days)., Results: After a median of 8.0 months (interquartile range, 4.0-23.3 months) of follow-up, 149 patients (58%) had maintained sinus rhythm and 107 patients (42%) had recurrence of AF. In our study cohort (mean age 59 ± 11 years; mean left ventricular ejection fraction, 58 ± 10%), impaired total LAε (LAεtotal) was associated with greater left ventricular mass index (r = -0.245, P < .001) and worsening left ventricular diastolic function (ratio of transmitral flow peak early diastolic velocity to peak early diastolic velocity of the mitral annulus: r = -0.357, P < .001; maximal LA volume index: r = -0.393, P < .001). Patients with LAεtotal < 23.2% showed a higher incidence of AF recurrence compared with patients with LAεtotal ≥ 23.2% (log-rank P < .001). In multivariate Cox proportional-hazards analysis, LAεtotal was independently related to rhythm outcomes (hazard ratio, 0.944; 95% confidence interval, 0.915-0.975; P < .001) after AF ablation. Moreover, LAεtotal provided incremental predictive value for rhythm outcomes over clinical features (increment in global χ(2) = 14.63, P < .001)., Conclusions: In patients with AF, baseline LAεtotal was associated with rhythm outcome after catheter ablation., (Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Introduction: Atrial fibrillation (AF) and heart failure (HF) frequently coexist. We have previously demonstrated that selective atrioventricular node (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during AF. Due to withdrawal of vagal activity in HF, the therapeutic effects of AVN-VS may be compromised in the combined condition of AF and HF. Accordingly, this study was designed to evaluate the therapeutic effects of AVN-VS to control ventricular rate in AF and HF., Methods and Results: A combined model of AF and HF was created by implanting a dual chamber pacemaker in 24 dogs. A newly designed bipolar electrode was inserted into the ganglionic AVN fat pad and connected to a nerve stimulator for delivering AVN-VS. In all dogs, HF was induced by high rate ventricular pacing at 220 bpm for 4 weeks. AF was then induced and maintained by rapid atrial pacing at 600 bpm after discontinuation of ventricular pacing. These HF + AF dogs were randomized into control (n = 9) and AVN-VS (n = 15) groups. In the latter group, vagal stimulation (310 μs, 20 Hz, 3-7 mA) was delivered continuously for 6 months. Compared with the control, AVN-VS had a consistent effect on ventricular rate slowing (by >50 bpm, all P < 0.001) during the entire 6-month observation period that was associated with left ventricular functional improvement. Moreover, AVN-VS was well tolerated by the treated animals., Conclusions: AVN-VS achieved consistent rate slowing, which was associated with improved ventricular function in a canine AF and HF model. Thus, AVN-VS may be a novel, effective therapeutic option in the combined condition of AF and HF., (© 2012 Wiley Periodicals, Inc.)

Objective: Occlusion of the left atrial appendage is proposed to reduce the risk of stroke in patients with atrial fibrillation. The third-generation atrial exclusion device, modified to provide uniform distribution of pressure at appendage exclusion, was assessed for safety and effectiveness in a canine model and compared with a surgical stapler., Methods: The atrial exclusion device consists of 2 parallel, straight, rigid titanium tubes and 2 nitinol springs with a knit-braided polyester fabric. Fourteen mongrel dogs were implanted with the device at the base of the left atrial appendage via a median sternotomy. In each dog, the right atrial appendage was stapled with a commercial apparatus for comparison. The animals were evaluated at 7 days (n = 3), 30 days (n = 5), and 90 days (n = 6) after implantation by epicardial echocardiography, left atrial and coronary angiography, gross pathology, and histology., Results: Left atrial appendage exclusion was complete and achieved without hemodynamic instability, and coronary angiography revealed that the left circumflex artery was patent in all cases. A new endothelial tissue layer developed on the occluded orifice of the left atrium 90 days after implantation. This endothelial layer was not evident on the stapled right atrial appendage., Conclusion: In dogs, the third-generation atrial exclusion device achieved easy, reliable, and safe exclusion of the left atrial appendage with favorable histologic results. Clinical application could provide a new therapeutic option for reducing the risk of stroke in patients with atrial fibrillation.

Purpose: Recent studies have demonstrated that ventricular rate control is a viable treatment strategy for patients in atrial fibrillation (AF). The purpose of this study was to determine whether or not the benefits of coupled pacing (ie, a proposed rate control therapy) could be used during persistent AF., Description: Six mongrel dogs were chronically implanted with endocardial atrial and ventricular pacemaker leads and two standard dual-chamber pacemakers. With the use of two custom "Y"-lead adapters, the pacemakers were used to induce AF and to apply coupled pacing. Left ventricular end-diastolic and systolic volumes were measured by echocardiography to determine ejection fractions., Evaluation: Persistent AF significantly increased both ventricular rate and left ventricular dimensions. After sustained coupled pacing had been applied for 3 to 4 weeks, left ventricular volumes and contractile rate were significantly reduced and returned toward the values measured prior to the induction of persistent AF. Coupled pacing increased the ejection fraction that had been reduced by persistent AF., Conclusions: Coupled pacing reversed the left ventricular remodeling caused by the tachycardia resulting from AF.

Background: Coupled pacing (CP), which consists of delivering a premature electrical stimulation to the heart after the effective refractory period of ventricular activation, is a novel method for controlling ventricular rate during atrial fibrillation (AF). It also has been established that CP improves pump function by enhancing external cardiac work and myocardial efficiency., Objective: The purpose of the present study was to determine if two time delays for CP (short and long) would result in similar improvements in ventricular function., Methods: In a canine model, we applied CP at two time delays (CP-S and CP-L) during two stages: sinus rhythm (SR) and acute AF. The cardiac responses to CP during SR served as the nontachycardic and nondepressed control. During both rhythms, we shortened the coupling interval until we obtained maximal contractility, designated CP-S. Next, we increased the delay until we started to see a measurable secondary contraction (left ventricular pressure development of approximately 20 mmHg). These longer delays were designated CP-L., Results: Our results showed that the ventricular rate of intrinsic activation (VRIA) remained decreased despite prolongation of the time delay of CP during both AF and SR. Also, both delays of CP increased left ventricular systolic pressure (LVSP) and dLVP/dt, which are indices of myocardial contractility. In contrast, CP increased external cardiac work only during AF. Prolonging this time delay did not markedly decrease the improvement in external cardiac work. Myocardial O(2) consumption (MVO(2)) did not significantly change as the result of CP during either SR or AF. Finally, myocardial efficiency improved during AF as the result of CP at both time delays., Conclusions: In conclusion, shorter time delays for CP increased contractile strength during both SR and AF. However, extending the time delay of CP had minimal effects on diminishing the improved ventricular pump function and energetics that resulted from CP during AF. Thus, the maximal enhancement of myocardial contractility via CP-S was not needed to maintain the improved ventricular function during acute AF when CP is applied.

Objectives: The aim of this study was to assess whether Frank-Starling mechanism has an independent effect on left ventricular (LV) performance in atrial fibrillation (AF)., Background: Ventricular performance in AF depends on variable contractility through the interval-force mechanism based on the ratio of preceding and pre-preceding RR intervals (RR(p)/RR(pp)). The impact of end-diastolic volume (EDV) variability, through the Frank-Starling mechanism, is not well understood., Methods: We induced AF in 16 open chest dogs. RR intervals, LV pressure, LV volume, and aortic flow were collected for >400 beats during rapid AF (ventricular cycle length 292 +/- 66 ms). In six of the dogs, additional data were collected while average ventricular cycle length was prolonged from 258 +/- 34 ms to 445 +/- 80 ms by selective vagal nerve stimulation of the AV node., Results: The relations of maximal LV power (LVPower) and peak LV pressure derivative (dP/dt) versus RR(p)/RR(pp) were fitted to the equation y = A * (1 - EXP (RR(p)/RR(pp)min - RR(p)/RR(pp))/C) and the residuals (RES) of these relations were analyzed. LVPower and dP/dt strongly correlated with RR(p)/RR(pp) (r(2) = 0.67 +/- 0.12 and 0.66 +/- 0.12, P < .0001 for all correlations). Importantly, RES-LVPower and RES-dP/dt showed linear correlation with EDV (r(2) = 0.20 +/- 0.14 and r(2) = 0.24 +/- 0.17, P < .01 for all correlations). In the six dogs with slowed average ventricular rate, the slope of both residual relationships (RES-LVPower vs EDV and RES- dP/dt vs EDV) decreased (P < .03 for both)., Conclusions: The Frank-Starling mechanism contributes to ventricular performance in AF independently of the interval-force effects of the beat-to-beat variability in cardiac contractility. The Frank-Starling mechanism is sensitive to the average ventricular rate.

Atrial fibrillation (AF) is characterized by short and irregular ventricular cycle lengths (VCL). While the beneficial effects of heart rate slowing (i.e., the prolongation of VCL) in AF are well recognized, little is known about the impact of irregularity. In 10 anesthetized dogs, R-R intervals, left ventricular (LV) pressure, and aortic flow were collected for >500 beats during fast AF and when the average VCL was prolonged to 75%, 100%, and 125% of the intrinsic sinus cycle length by selective atrioventricular (AV) nodal vagal stimulation. We used the ratio of the preceding and prepreceding R-R intervals (RR(p)/RR(pp)) as an index of cycle length irregularity and assessed its effects on the maximum LV power, the minimum of the first derivative of LV pressure, and the time constant of relaxation by using nonlinear fitting with monoexponential functions. During prolongation of VCL, there was a pronounced decrease in curvature with the formation of a plateau, indicating a lesser dependence on RR(p)/RR(pp). We conclude that prolongation of the VCL during AF reduces the sensitivity of the LV performance parameters to irregularity.

Background: Selective atrioventricular nodal (AVN) vagal stimulation (AVN-VS) has emerged as a novel strategy for ventricular rate (VR) control in atrial fibrillation (AF). Although AVN-VS preserves the physiological ventricular activation sequence, the resulting rate is slow but irregular. In contrast, AVN ablation with pacemaker implantation produces retrograde activation (starting at the apex), with regular ventricular rhythm. We tested the hypothesis that, at comparable levels of VR slowing, AVN-VS provides hemodynamic benefits similar to those of ablation with pacemaker implantation., Methods and Results: AVN-VS was delivered to the epicardial fat pad that projects parasympathetic nerve fibers to the AVN in 12 dogs during AF. A computer-controlled algorithm adjusted AVN-VS beat by beat to achieve a mean ventricular RR interval of 75%, 100%, 125%, or 150% of spontaneous sinus cycle length. The AVN was then ablated, and the right ventricular (RV) apex was paced either irregularly (i-RVP) using the RR intervals collected during AVN-VS or regularly (r-RVP) at the corresponding mean RR. The results indicated that all 3 strategies improved hemodynamics compared with AF. However, AVN-VS resulted in significantly better responses than either r-RVP or i-RVP. i-RVP resulted in worse hemodynamic responses than r-RVP. The differences among these modes became less significant when mean VR was slowed to 150% of sinus cycle length., Conclusions: AVN-VS can produce graded slowing of the VR during AF without destroying the AVN. It was hemodynamically superior to AVN ablation with either r-RVP or i-RVP, indicating that the benefits of preserving the physiological antegrade ventricular activation sequence outweigh the detrimental effect of irregularity.

Although the beneficial effects of ventricular rate (VR) slowing during atrial fibrillation (AF) are axiomatic, the precise relationship between VR and hemodynamics has not been determined. We hypothesized that selective atrioventricular node (AVN) vagal stimulation (AVN-VS) by varying the nerve stimulation intensity could achieve precise graded slowing and permit evaluation of an optimal VR during AF. The aims of the present study were the following: 1) to develop a method for computerized vagally controlled VR slowing during AF, 2) to determine the hemodynamic changes at each level of VR slowing, and 3) to establish the optimal anterograde VR during AF. AVN-VS was delivered to the epicardial fat pad that projects parasympathetic nerve fibers to the AVN in 14 dogs. Four target average VR levels, corresponding to 75%, 100%, 125%, and 150% of the sinus cycle length (SCL), were achieved by computer feedback algorithm. VR slowing resulted in improved hemodynamics and polynomial fit analysis found an optimum for the cardiac output at VR slowing of 87% SCL. We conclude that this novel method can be used to maintain slow anterograde conduction with best hemodynamics during AF.

In year 2016, the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI) updated Recommendations for the assessment and grading of diastolic dysfunction (DD). We aimed to assess the applicability of this DD grading method and its association with prognosis in patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve implantation (TAVI). We retrospectively identified 237 consecutive patients with severe AS who underwent trans-femoral TAVI. Baseline transthoracic echocardiography was evaluated to assess pre- and post-TAVI diastolic function according to the current ASE/EACVI Recommendations. Prior to TAVI, 41 (17%) patients were diagnosed as having grade I DD, 111 (47%) patients had grade II DD, 80 (34%) had grade III DD. DD grade after TAVI decreased (p < 0.001) with 75 patients (32%) reclassified to a lower DD grade. During the median follow-up of 1,320 days, 136 (57%) patients died. In univariable Cox proportional hazards model analysis, neither pre- nor post-TAVI DD grade were associated with prognosis. However, patients with grade III DD detected before TAVI and AR≥ 2 after TAVI had poorer survival (p<0.008). Patients with grade III DD detected after TAVI and AR≥ 2 after TAVI had poorer prognosis (p = 0.002). TAVI improves DD grade. While poor DD grade was not associated with mortality after treatment of AS by TAVI, concomitant presence of DD and post-procedural AR carried a poor prognosis. [ABSTRACT FROM AUTHOR]

Objectives: We sought to investigate the short-term and midterm effects of left atrial appendage exclusion on left atrial function. Left atrial appendage exclusion is considered a possible therapeutic option for stroke prevention in patients with atrial fibrillation. Favorable outcomes have encouraged widespread use of left atrial appendage exclusion for cardiac surgical patients—even for patients in sinus rhythm who have stroke risk factors; however, the chronic effects on left atrial function of left atrial appendage exclusion are unclear. Methods: Nineteen mongrel dogs (29.7 ± 5.2 kg) in sinus rhythm were studied. The Doppler signals from the pulmonary venous flow, transmitral flow, and tissue Doppler imaging of mitral annular motion were obtained before and after left atrial appendage exclusion. Dogs were evaluated in the same manner at 7 days (n = 2), 30 days (n = 7), or 90 days (n = 10) after left atrial appendage exclusion. Results: Except for a significant increase in early diastolic transmitral flow velocity after left atrial appendage exclusion (P = .01), no significant differences were found in any parameters related to the transmitral flow and tissue Doppler imaging measurements throughout follow-up. The systolic components of pulmonary venous flow at follow-up revealed a significant reduction relative to baseline (peak systolic velocity P < .0001, systolic velocity-time integral P < .0001), despite the lack of significant changes in left atrial pressure, left ventricular volume, and stroke volume. Conclusion: Left atrial appendage exclusion may affect left atrial reservoir function in the short-term and midterm periods. Further long-term studies with more clinically relevant models are needed. [Copyright &y& Elsevier]

Background: The left atrial appendage is a frequent source of thromboemboli in patients with atrial fibrillation. Exclusion of the left atrial appendage may reduce the risk of stroke in patients with atrial fibrillation. The atrial exclusion device, previously developed to perform left atrial appendage exclusion on a beating heart, was modified to accommodate different anatomic patterns of the human left atrial appendage and to ensure uniform pressure and occlusion. The purpose of this study was to evaluate this second-generation atrial exclusion device during a midterm period in a canine model. Methods: Ten mongrel dogs (mean weight 28.9 ± 4.6 kg) were used in this study. The atrial exclusion device, constructed from two parallel and rigid titanium tubes and two nitinol springs with a knit-braided polyester fabric, was implanted at the base of the left atrial appendage through a left thoracotomy on a beating heart using a specially designed delivery tool. Dogs were evaluated at 30 days (n = 4) and 90 days (n = 6) by epicardial echocardiography, left atrial and coronary angiography, gross pathology, and histologic inspection. Results: Device implantation was performed without complications in all dogs. Complete left atrial appendage exclusion without device migration or hemodynamic instability was confirmed, and there was no damage to the left circumflex artery or pulmonary artery. Macroscopic and microscopic assessments revealed favorable biocompatibility during midterm follow-up. Conclusion: The atrial exclusion device enabled rapid, reliable, and safe exclusion of the left atrial appendage. Clinical application may provide a new therapeutic option for reducing the risk of stroke in patients with atrial fibrillation. [Copyright &y& Elsevier]

Objective: The left atrial appendage is a frequent source of thromboemboli in patients with atrial fibrillation. Exclusion or excision of the left atrial appendage may reduce the risk of stroke in patients with atrial fibrillation. We evaluated the ability of a novel device to exclude the left atrial appendage during early and intermediate follow-up periods in a canine model. Methods: Eight mongrel dogs (mean weight 29.1 ± 4.0 kg) were used in this study. The occlusion device, constructed from 2 stainless steel strips covered with a knit braided polyester fabric, was implanted at the base of the left atrial appendage through a left thoracotomy on a beating heart. Dogs were evaluated at 7 days (n = 2), 30 days (n = 2), and 90 days (n = 4) by epicardial echocardiography, left atrial angiography, histologic inspection, and gross pathology. Results: Device implantation was performed without complications in all animals. Complete exclusion of the left atrial appendage from the circulation was confirmed acutely and chronically by echocardiographic and angiographic evaluations. There was no device migration or damage to adjacent structures. Conclusion: This novel device enables rapid, reliable, and safe exclusion of the left atrial appendage. The device provides a new therapeutic option for reducing the risk of stroke in patients with atrial fibrillation. [Copyright &y& Elsevier]