Atrial Stunning Research Articles

Abstract Mo118: Myofilament proteolysis may underlie contractile remodeling in atrial fibrillation

Atrial fibrillation (AFib) is the most common cardiac rhythm disturbance. Treatment of AFib involves restoration of the atrial electrical rhythm. Following rhythm restoration, a period of depressed mechanical function, including decreased blood flow velocity and reduced atrial contractility, known as atrial stunning, occurs. This suggests that defects in contractility occur in AFib and are revealed upon restoration of rhythm. To assess contractile function, we used a canine atrial tachypacing model of induced AFib. Mass spectrometry analysis showed dysregulation of contractile proteins in samples from AFib compared to sinus rhythm atria. In atrial cardiomyocytes that were useable for skinned single cardiomyocyte force-calcium studies, we found reduced force of contraction. There were no significant differences in myosin heavy chain isoform expression. Resting tension is decreased in the AFib samples correlating with reduced full-length titin in the sarcomere. We measured degradation of other myofilament proteins including cMyBP-C, actinin, MHC, and cTnI, showing significant degradation in the AFib samples compared to sinus rhythm atria. Many of the protein degradation products appeared as discrete cleavage products that are generated by calpain proteolysis. We assessed calpain activity and found it to be significantly increased. Skinned cardiomyocytes from AFib atria showed increased calcium sensitivity that was consistent with increased cTnI degradation and decreased TnI phosphorylation. These results provide an understanding of the contractile remodeling that occurs in AFib.

Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation.

Atrial fibrillation (AFib) is the most common cardiac rhythm disturbance, often treated via electrical cardioversion. Following rhythm restoration, a period of depressed mechanical function known as atrial stunning occurs, suggesting that defects in contractility occur in AFib and are revealed upon restoration of rhythm. This project aims to define the contractile remodeling that occurs in AFib. To assess contractile function, we used a canine atrial tachypacing model of induced AFib. Mass spectrometry analysis showed dysregulation of contractile proteins in samples from AFib compared with sinus rhythm atria. Atrial cardiomyocytes show reduced force of contraction, decreased resting tension, and increased calcium sensitivity in skinned single cardiomyocyte studies. These alterations correlated with degradation of myofilament proteins including myosin heavy chain altering force of contraction, titin altering resting tension, and troponin I altering calcium sensitivity. We measured degradation of other myofilament proteins, including cardiac myosin binding protein C and actinin, that show degradation products in the AFib samples that are absent in the sinus rhythm atria. Many of the degradation products appeared as discrete cleavage products that are generated by calpain proteolysis. We assessed calpain activity and found it to be significantly increased. These results provide an understanding of the contractile remodeling that occurs in AFib and provide insight into the molecular explanation for atrial stunning and the increased risk of atrial thrombus and stroke in AFib.NEW & NOTEWORTHY Atrial fibrillation is the most common cardiac rhythm disorder, and remodeling during atrial fibrillation is highly variable between patients. This study has defined the biophysical changes in contractility that occur in atrial fibrillation along with identifying potential molecular mechanisms that may drive this remodeling. This includes proteolysis of several myofilament proteins including titin, troponin I, myosin heavy chain, myosin binding protein C, and actinin, which is consistent with the observed contractile deficits.

Epicardial fat and left atrial mechanical dispersion in patients with hypertension with persistent atrial fibrillation and without cardiac arrhythmia

Aim. To study the relationship between the amount of epicardial left atrial fat and left atrial mechanical dispersion (LAMD) in hypertensive patients with persistent atrial fibrillation (AF) and without cardiac arrhythmias.Material and methods. The main group included 100 hypertensive patients with persistent AF, who underwent transesophageal echo cardiography (TEE) before the elective cardioversion, and transthoracic echocardiography (TTE) after cardioversion and disappearance of atrial stunning. The control group included 24 hypertensive patients without cardiac arrhythmias, who underwent TEE for other indication. The thickness of atrial septum and left lateral ridge was measured by TEE. The average thickness of these structures was designated as left atrial fat. The time to peak of longitudinal myocardial strain in 6 left atrium segments was determined by speckle-tracking echocardiography. LAMD was calculated as a percentage of the standard deviation of the obtained values to cardiac cycle duration.Results. The median left atrial fat thickness in the main and control groups was 8,03 [6,78; 8,95] and 5,23 [4,48; 5,80] mm (p<0,0001), median LAMD — 2,68 [2,41; 2,83] and 0,95 [0,62; 1,11]% (p<0,0001). There was a positive correlation between left atrial fat thickness and LAMD in the main group (r=0,556; p<0,0001). This relationship did not reach the level of statistical significance in the control group, (r=0,358; p=0,0860). There was no independent relationship between body mass index and left atrial fat thickness in the patients (r=0,027; p=0,7651).Conclusion. In hypertensive patients with persistent AF, compared with patients without rhythm disturbances, the average values of left atrial fat thickness and LAMD are significantly higher. The increase in left atrial fat thickness is associated with the increase in LAMD in hypertensive patients with AF. There was no correlation between left atrial fat thickness and LAMD in hypertensive patients without rhythm disturbances. There was no effect of body mass index on left atrial fat thickness in the present study.

In Situ Transesophageal Echocardiography During Electrical Cardioversion in Patients With Atrial Fibrillation—Safety and Echocardiographic Findings

Transesophageal echocardiography (TEE) can reliably detect left atrial (LA) and LA appendage (LAA) thrombus in patients with atrial fibrillation (AF) before electrical cardioversion (ECV). However, evaluating cardiac and valve function pre-ECV can be challenging due to the increased and irregular heart rate. Additionally, post-ECV atrial stunning increases the risk of LAA thrombosis. Therefore, post-ECV TEE may allow for useful appendage, ventricular, and valve function assessment. However, the safety and usefulness of leaving the TEE probe in situ during ECV for post-ECV cardiac evaluation in clinical practice have not been previously evaluated. We analyzed 37 out of 86 consecutive patients who had the TEE probe left in situ, for clinical reasons, during ECV by a single operator between February 20, 2019, and January 3, 2023. We examined changes in left ventricular (LV) function, dynamic changes in valvular regurgitation, electromechanical coupling of the left atrium, and qualitative spontaneous echo contrast. We also assessed the presence of any complications related to the periprocedural TEE exam. The mean age of the patients was 74±9.65years, and 29 (78%) were male. The periprocedural TEE time ranged from 7 to 55minutes, with an average of 20.78minutes. Immediately after ECV and restoration of normal sinus rhythm, there was an improvement in LV ejection fraction (47%±11.9% vs 40%±15.8%; P=.035). There was also a reduction in baseline mitral regurgitation of greater than moderate degree. However, spontaneous echo contrast worsened in the LAA in 11 (31.4%) patients. Additionally, 1 patient developed a new LAA thrombus, and 24 patients (72%) had evidence of electromechanical coupling with Doppler evidence of LA contraction. Clinically significant degenerative aortic and mitral stenosis were identified in 8% and mild or greater aortic regurgitation in 8% of patients post-ECV. No procedural complications were observed. In situ TEE before, during, and after ECV is safe and provides useful clinical information regarding immediate cardiac changes after ECV, with diagnostic and therapeutic implications.

Abstract 16107: Post-Cardioversion Device-Related Thrombus in a Patient With Left Atrial Appendage Occlusion Device on Apixaban

Introduction and Importance: Current guidelines recommend against pre-procedural transesophageal echocardiogram (TEE) prior to cardioversion in atrial fibrillation patients compliant with oral anticoagulants for at least 3 weeks. The relevance of these guidelines remain unclear in those undergoing repeat cardioversion. Case Presentation: 66-year-old male with a history of atrial fibrillation and an implanted left atrial appendage occlusion device(LAAO), compliant with apixaban, presented with dyspnea and lightheadedness. He was cardioverted into sinus rhythm 10 days prior to symptom onset with TEE unremarkable for thrombus. Vitals were remarkable for tachycardia and electrocardiogram revealed that the patient converted back into atrial fibrillation. Patient was then scheduled for cardioversion. At the patient’s request, a TEE was obtained which revealed a new thrombus in the left atrium located on his WATCHMAN device. Cardioversion was canceled and patient was admitted for coumadin initiation with lovenox bridge along with neurological monitoring due to increased stroke risk. Clinical Discussion: Restoration of sinus rhythm after cardioversion can lead to thrombus formation due to atrial stunning, a transitory dysfunction of the atrial appendage and atrium.Atrial stunning occurs immediately after cardioversion and can persist for several weeks. Time-span of preceding atrial fibrillation, presence of structural cardiovascular disease, and atrial size impact severity of atrial stunning and duration of anticoagulation needed.While anticoagulation decreases the risk of thrombus formation, it does not completely eliminate it, especially in those with increased stroke risk factors. Conclusion: Atrial fibrillation patients are susceptible to thrombus formation after cardioversion.Further studies should be done to assess the need for routine TEE after cardioversion in those with increased risk for stroke on anticoagulants or who have LAAO.

Transesophageal Echocardiogram Before Cardioversion in Atrial Fibrillation Patients.

Transesophageal echocardiography (TEE) offers an invaluable, non-invasive avenue for diagnosing and managing various cardiac conditions, including atrial fibrillation (AF). As the most common cardiac arrhythmia, AF affects millions and can lead to severe complications. Cardioversion, a procedure to restore the heart's normal rhythm, is frequently conducted on AF patients resistant to medication. Due to inconclusive data, TEE's utility prior to cardioversion in AF patients remains ambiguous. Understanding TEE's potential benefits and limitations in this population could significantly influence clinical practice. This review aims to scrutinize the current literature on the use of TEE before cardioversion in AF patients. The principal objective is to understand TEE's potential benefits and limitations comprehensively. The study seeks to offer a clear understanding and practical recommendations for clinical practice, thereby improving the management of AF patients before cardioversion using TEE. A literature search of databases was conducted using the keywords "Atrial Fibrillation," "Cardioversion" and "Transesophageal echocardiography," resulting in 640 articles. These were narrowed to 103 following title and abstract reviews. After applying exclusion and inclusion criteria with a quality assessment, 20 papers were included: seven retrospective studies, 12 prospective observational studies, and one randomized controlled trial (RCT). Stroke risk associated with direct-current cardioversion (DCC) potentially results from post-cardioversion atrial stunning. Thromboembolic events occur post cardioversion, with or without prior atrial thrombus or cardioversion complications. Generally, cardiac thrombus localizes in the left atrial appendage (LAA), a clear contraindication to cardioversion. Atrial sludge without LAA thrombus in TEE is a relative contraindication. TEE before electrical cardioversion (ECV) in anticoagulated AF individuals is uncommon. In AF patients planned for cardioversion, contrast enhancement facilitates thrombus exclusion in TEE images, reducing embolic events. Left atrial thrombus (LAT) frequently occurs in AF patients, necessitating TEE examination. Despite the increased use of pre-cardioversion TEE, thromboembolic events persist. Notably, patients with post-DCC thromboembolic events had no LA thrombus or LAA sludge. The use of TEE-guided DCC has grown due to its ability to detect atrial thrombi pre-cardioversion, aiding risk stratification. Thrombus in the left atrium also signals an elevated risk of future thromboembolic events in AF patients. While atrial stunning post cardioversion detected by TEE is a significant risk factor for future thromboembolic events, further evidence is required. Therapeutic anticoagulation is essential during and post cardioversion, even if no atrial thrombus is detected. Current data recommends cardioversion guided by TEE, particularly in outpatient settings.

LA strain helps identifying the cardioembolic etiology of transient ischemic attacks

Abstract Background Patients who have transient ischemic attacks (TIA) often suffer from asymptomatic and paroxysmal atrial fibrillation (AF). Due to the fact that AF is located in the atria, we sought to determine whether abnormalities in left atrial (LA) structure and function could help identify the cardioembolic cause of TIA in patients with sinus rhythm but with documented episodes of paroxysmal AF. Methods The research included 190 individuals with TIA and classified them into two groups based on the presence (group I) or absence (group II) of confirmed paroxysmal AF. The diagnosis of paroxysmal AF was established by an assessment of medical records. To prevent assessing atrial stunning, cardiac ultrasonography was conducted in sinus rhythm at least 14 days following the initiation the TIA. Results The results indicated that patients in group I were older, more often female, had a history of stroke or TIA, and had a higher CHA2DS2-VASc score. Additionally, they exhibited increased LA volumes, a decreased LA emptying fraction, and markedly altered LA deformation patterns. Three factors were found as being independently associated with paroxysmal AF using multivariate logistic regression: age, LA reservoir strain, and LA emptying fraction (P<0.0001). The variables had as cut-off values: age >55 years, LA reservoir strain<−17%, and LA emptying fraction <51%. Conclusion The current research establishes that LA strains are independently associated with paroxysmal AF in patients with TIA and may aid in determining the cardioembolic origin of these events. Our findings have considerable clinical implications because, until now, LA 2D-STE was not included in the usual evaluation of TIA patients, but it may be the ideal next step in this regard. Funding Acknowledgement Type of funding sources: None.

NO CLOT, NO PROBLEM? NOT EXACTLY

NO CLOT, NO PROBLEM? NOT EXACTLY

Changes in left atrial function in patients undergoing cardioversion for atrial fibrillation: relevance of left atrial strain in heart failure

BackgroundLeft atrial (LA) reservoir strain provides prognostic information in patients with and without heart failure (HF), but might be altered by atrial fibrillation (AF). The aim of the current study was to investigate changes of LA deformation in patients undergoing cardioversion (CV) for first-time diagnosis of AF.Methods and resultsWe performed 3D-echocardiography and strain analysis before CV (Baseline), after 25 ± 10 days (FU-1) and after 190 ± 20 days (FU-2). LA volumes, reservoir, conduit and active function were measured. In total, 51 patients were included of whom 35 were in SR at FU-1 (12 HF and preserved ejection fraction (HFpEF)), while 16 had ongoing recurrence of AF (9 HFpEF). LA maximum volume was unaffected by cardioversion (Baseline vs. FU-2: 41 ± 11 vs 40 ± 10 ml/m2; p = 0.85). Restored SR led to a significant increase in LA reservoir strain (Baseline vs FU-1: 12.9 ± 6.8 vs 24.6 ± 9.4, p < 0.0001), mediated by restored LA active strain (SR group Baseline vs. FU-1: 0 ± 0 vs. 12.3 ± 5.3%, p < 0.0001), while LA conduit strain remained unchanged (Baseline vs. FU-1: 12.9 ± 6.8 vs 13.1 ± 6.2, p = 0.78). Age-controlled LA active strain remained the only significant predictor of LA reservoir strain on multivariable analysis (β 1.2, CI 1.04–1.4, p < 0.0001). HFpEF patients exhibited a significant increase in LA active (8.2 ± 4.3 vs 12.2 ± 6.6%, p = 0.004) and reservoir strain (18.3 ± 5.7 vs. 22.8 ± 8.8, p = 0.04) between FU-1 and FU-2, associated with improved LV filling (r = 0.77, p = 0.005).ConclusionReestablished SR improves LA reservoir strain by restoring LA active strain. Despite prolonged atrial stunning following CV, preserved SR might be of hemodynamic and prognostic benefit in HFpEF.Graphical abstract

Timing and degree of left atrial stunning and reverse functional remodeling following electrical cardioversion in patients with recent onset atrial fibrillation

Abstract Background Atrial fibrillation (AF) results in left atrial electrical, structural and functional remodeling. Restoration of sinus rhythm hallmarks the beginning of reverse remodeling, the extent of which may depend on the type of AF. Purpose The aim of the study was to assess resumption of left atrial function after electric cardioversion in patients with recent onset AF and to explore the association between reverse remodeling and the type of atrial fibrillation. Methods Patients with AF duration &amp;lt;48 hours were prospectively included. Trans-thoracic echocardiography was performed prior, immediately after (2–4 hours) and 7–10 days following CV. Left atrial volume index (LAVI), left atrial global longitudinal strain during reservoir (LAGLS-res), conduit (LAGLS-cond) and contractile (LAGLS-contr) phases, left atrial ejection fraction (LAEF) and left ventricular ejection fraction (LVEF) were measured. Results Forty-three patients (84% males) aged 55±9.6 years, (mean±SD), with median CHA2DS2-VASc score 1 (interquartile range 0–1) were included. Repeated measure analysis of variance revealed a statistically significant overall change for LAGLS-res F(2,78)=55.4, p&amp;lt;0,001, LAGLS-cond F(2,78)=23.3, p&amp;lt;0,001, LAGLS-contr F(2,78)=39.7, p&amp;lt;0,001, LAEF F(2,80)=28.5, p&amp;lt;0.001 and LVEF F(2,80)=8.4, p&amp;lt;0.001. At 7–10 days, LAGLS-contr 12±4%, LAEF 53±9% and LVEF 60±6 (mean±SD) return within normal reference intervals. Notably left atrial recovery seems to precede left ventricular recovery. No statistical significant interaction with the type of atrial fibrillation could be shown. Conclusion Left atrial functional reverse remodeling occurs within ten days after successful electric cardioversion of patients with recent onset atrial fibrillation. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swedish Heart-Lung Foundation, Correvio International Sárl (Geneva Switzerland), Selanders Stiftelse

Transient atrial mechanical dysfunction assessed in acute phase of embolic stroke of undetermined source

Background and Purpose: Paroxysmal atrial fibrillation (PAF) has been suggested as a major cause of embolic stroke of undetermined source (ESUS). Transient atrial mechanical dysfunction (stunning) frequently occurs after conversion of atrial fibrillation to sinus rhythm. The study aim was to determine if reversible atrial mechanical dysfunction in ESUS could help elucidate the mechanism of stroke. Methods: Eighty-five consecutive patients with acute ischemic stroke were enrolled according to the following inclusion criteria: [1] ≥55 years old; [2] normal sinus rhythm upon admission; [3] no apparent embolic source; and [4] transthoracic echocardiographic evaluation had been performed in both the early phase (<72 h) and late phase (>7 days) after stroke onset. There were 27 patients in the lacunar or atherothrombotic infarction group (controls), 22 in the PAF group, and 36 in the ESUS group. To determine atrial stunning, transmitral flow velocity profiles (Doppler peak E- [early diastolic] and A- [atrial systolic] waves) were obtained. Results: In the early phase, an E/A velocity ratio ≥ 1.0 was less common in the control group (1 patient, 3.7%) than in the PAF group (19 patients, 86.4%; p < 0.001) and ESUS group (10 patients, 27.8%; p < 0.05). In the late phase, the E/A ratio decreased to less than 1.0 in six patients (31.6%) who had PAF and in eight patients (80.0%) who had ESUS. Conclusion: Transient atrial mechanical dysfunction could be a helpful finding for elucidating the stroke mechanism in patients with ESUS, and early echocardiographic assessment could improve its detection.

Left But Not Right Ventricular Abnormal Doppler Waves

The presence of a normal atrial electrical activity together with the absence of mechanical atrial activity has been reported after successful cardioversion and is named atrial stunning. In this observation, we report the existence of left but not right atrial stunning.

415 The Immediate Impact of Electrical Cardioversion on Right Ventricular Systolic Function in Patients With Non-Valvular Atrial Fibrillation

Successful electrical cardioversion (ECV) for atrial fibrillation (AF) is often followed by a transient period of atrial stunning, where depressed mechanical atrial function persists despite reversion to sinus rhythm (SR). Left ventricular (LV) changes following ECV are well characterised, but knowledge of early changes to right ventricular (RV) function is lacking. We aimed to assess the immediate impact of ECV on right heart function. Patients referred for ECV with non-valvular AF between Jan 2017 to Jan 2018 were assessed. Patients without history of heart failure, normal left ventricular ejection fraction, and who successfully reverted to SR following ECV were prospectively recruited. RV metrics of systolic function including 2-dimensional RV free wall longitudinal strain (RV-FWLs) was measured offline from transthoracic echocardiogram images obtained prior to and immediately following ECV (TomTec Imaging system). Of 50 patients (64.14±11.01yrs, 60% male) assessed, 28% had a history of ischaemic heart disease and 5% had obstructive sleep apnoea. Paired T-test analysis showed a significant improvement in RV-FWLs (pre-ECV: 14.18±4.42 vs post-ECV: 21.02±6.80; p<0.01) and RV-FAC (pre-ECV: 36.77±8.85 vs post-ECV: 40.80±10.16; p=0.02) following ECV. Based on a cut-off value of ≥23% for RV-FWLs, 10% of the cohort had normal RV-FWLs pre-ECV which significantly increased to 36% post-ECV (p<0.01). A similar trend was observed with RV-FAC (cut-off value of ≤35%), although not statistical significant (pre-ECV: 60% normal RV-FAC, post-ECV: 74% normal RV-FAC; p=0.17). Improvements in RV-FWLs and RV-FAC was observed following ECV, suggesting that there are immediate improvements in RV function in this population.

Post-cardioversion Improvement in LV Function Defined by 4D Flow Patterns and Energetics in Patients With Atrial Fibrillation.

BackgroundAtrial fibrillation (AF) is a prevalent cause of cardiovascular morbidity, including thromboembolism and heart failure. Left ventricular dysfunction (LVD) detected in AF patients may be either precursor or consequence of the arrythmia. Successful cardioversion of chronic AF is often followed by a transient period of left atrial (LA) stunning, where depressed mechanical atrial contraction persists despite reinstitution of sinus rhythm. To determine if AF-associated LVD would improve with resolution of LA dysfunction, AF patients were examined immediately and 4 weeks after cardioversion to sinus rhythm. 4D flow cardiovascular magnetic resonance (CMR) assesses ventricular function according to the volumes and energetics of functional components of the LV volume. Previously, described 4D CMR markers of LVD include decreased volume and end-diastolic kinetic energy (KE) of the Direct flow, which is the portion of LV volume that passes directly from inflow to outflow in a single cycle. We hypothesize that impaired LV flow patterns and energetics will be found immediately after cardioversion during atrial stunning, and that those parameters will improve as atrial function returns.MethodsTen patients with a history of AF underwent CMR 2–3 h (Time-1) and 4 weeks (Time-2), following electrical cardioversion to sinus rhythm. 4D phase-contrast velocity data and morphological images were acquired at a 3T CMR system. Using a previously evaluated method, pathlines were emitted from the LV end diastolic volume (LVEDV) and traced forward and backward in time until end-systole. The LVEDV was automatically separated into four functional flow components whose volume and KE were calculated.ResultsLeft atrial fractional area change increased over the follow-up period (P = 0.001), indicating recovery of LA mechanical function. LVEF increased between Time-1 and Time-2 (P = 0.003); LVEDVI did not change (P = 0.319). Over that interval, the ratios of Direct flow/LVEDV volume and KE increased (P = 0.001 and P = 0.003, respectively), while the ratios of Residual volume/LVEDV volume and KE decreased (P = 0.001 and P = 0.005, respectively).ConclusionPost-cardioversion recovery of LA function was associated with improvements in conventional and 4D CMR markers of LV function. Flow-specific measures demonstrate the negative but potentially reversible impact of LA dysfunction on volume and energetic aspects of LV function.

Clinical outcomes after AF cardioversion in patients presenting left atrial sludge in trans-esophageal echocardiography.

Direct-current cardioversion (DCC) for atrial fibrillation carries a risk of stroke, probably associated with the temporary atrial stunning following cardioversion. The presence of a cardiac thrombus, usually localized in the left atrial appendage (LAA), is recognized as a clear contra-indication to the cardioversion. However, the presence of atrial sludge without LAA thrombus in trans-esophageal echocardiography (TEE) remains, for many cardiologists, a relative contra-indication to the cardioversion. The aim of this study was to evaluate the safety of DCC in patients presenting atrial sludge without LAA thrombus. We prospectively included all consecutive patients demonstrating atrial sludge without LAA thrombus in TEE and undergoing DCC for persistent atrial fibrillation (AF). Safety of DCC was evaluated by the occurrence of clinical events at 1month following cardioversion, i.e., up to the end of the atrial stunning period, as assessed by clinical examination and the standardized and validated Questionnaire for Verifying Stroke-Free Status (QVSFS). Over a period of 2years, 21 patients presenting atrial sludge without LAA thrombus underwent DCC for AF. During the follow-up period of 1month after DCC, no clinical embolic event, cardiac event, or unscheduled consultations/hospitalizations occurred. At 1month, 67% of the patients remained in sinus rhythm. No clinical event occurred in patients demonstrating atrial sludge without thrombus and undergoing DCC for AF. These findings support current guidelines that only keep atrial thrombus as a contraindication to cardioversion, but warrant further investigation in large studies.

Abstract 304: Protein Phosphatase 1 Contributes to Atrial Stunning in Atrial Fibrillation

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF increases stroke risk 5-fold, and is partially mediated by reduced atrial contractility (stunning). However, it’s mechanism is relatively unknown. Recent data from our lab indicate protein phosphatase 1 (PP1) dephosphorylation of myosin light chain 2a (MLC2a) as contributor to Atrial stunning in AF Aim: To determine role of PP1 regulatory subunit (PPP1R12C) and catalytic subunit (PP1c) in modifying atrial sarcomere phosphorylation in AF Methods: We analyzed protein binding and phosphorylation of PPP1R12C, PP1c, and MLC2a in transfected HL1 and HEK cells, and AF prone Pitx2 null+/– mice. We also characterized the MRCK site on PPP1R12C that regulates PP1c and MLC2a phosphorylation using BDP5290 (PPP1R12C phosphorylation inhibitor), phosphomimetic (T560D) and phospho-ablated (T560A) versions of PPP1R12C Results: In Pitx2 null +/– mice, PPP1R12C increased by 2-fold ( P &lt;0.01) and had a 40% reduction in S-19-MLC2a phosphorylation ( P &lt;0.058). BDP5290 increased binding of PPP1R12C-PP1c and MLC2a &gt;3-fold in HL1 and HEK cells ( P &lt;0.01). Also, the constitutively activated T560A site on PPP1R12C significantly increased binding of PPP1R12C-MLC2a and PP1c Conclusion: In Pitx2 null+/- mice, increased expression of PPP1R12C is associated with PP1 holoenzyme targeting to sarcomeric MLC2a, and is associated with reduced S19-MLC2a phosphorylation. Additionally, BDP5290 and PPP1R12C (T560A) enhanced PPP1R12C-PP1c interaction and decreased MLC2a phosphorylation, thereby modelling PP1 activity in AF. Future studies will examine effects of altered Ppp1r12c expression on atrial contractility in vivo

677Left atrial stunning as a predictor of atrial fibrillation occurrence after cryptogenic stroke

677Left atrial stunning as a predictor of atrial fibrillation occurrence after cryptogenic stroke

Left Atrial 4D Blood Flow Dynamics and Hemostasis following Electrical Cardioversion of Atrial Fibrillation.

Background: Electrical cardioversion in patients with atrial fibrillation is followed by a transiently impaired atrial mechanical function, termed atrial stunning. During atrial stunning, a retained risk of left atrial thrombus formation exists, which may be attributed to abnormal left atrial blood flow patterns. 4D Flow cardiovascular magnetic resonance (CMR) enables blood flow assessment from the entire three-dimensional atrial volume throughout the cardiac cycle. We sought to investigate left atrial 4D blood flow patterns and hemostasis during left atrial stunning and after left atrial mechanical function was restored.Methods: 4D Flow and morphological CMR data as well as blood samples were collected in fourteen patients at two time-points: 2–3 h (Time-1) and 4 weeks (Time-2) following cardioversion. The volume of blood stasis and duration of blood stasis were calculated. In addition, hemostasis markers were analyzed.Results: From Time-1 to Time-2: Heart rate decreased (61 ± 7 vs. 56 ± 8 bpm, p = 0.01); Maximum change in left atrial volume increased (8 ± 4 vs. 22 ± 15%, p = 0.009); The duration of stasis (68 ± 11 vs. 57 ± 8%, p = 0.002) and the volume of stasis (14 ± 9 vs. 9 ± 7%, p = 0.04) decreased; Thrombin-antithrombin complex (TAT) decreased (5.2 ± 3.3 vs. 3.3 ± 2.2 μg/L, p = 0.008). A significant correlation was found between TAT and the volume of stasis (r2 = 0.69, p < 0.001) at Time-1 and between TAT and the duration of stasis (r2 = 0.34, p = 0.04) at Time-2.Conclusion: In this longitudinal study, left atrial multidimensional blood flow was altered and blood stasis was elevated during left atrial stunning compared to the restored left atrial mechanical function. The coagulability of blood was also elevated during atrial stunning. The association between blood stasis and hypercoagulability proposes that assessment of left atrial 4D flow can add to the pathophysiological understanding of thrombus formation during atrial fibrillation related atrial stunning.

Abstract 70: Protein Phosphatase 1 Contributes to Atrial Stunning in Atrial Fibrillation

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia, and increases a patient’s stroke risk five-fold. Reduced atrial contractility (stunning) is observed in AF and contributes to stroke risk; however, the mechanisms responsible for atrial stunning in AF are unknown. Recent data from our laboratory indicate that protein phosphatase 1 (PP1) dephosphorylation of myosin light chain 2a (MLC2a) may contribute to atrial stunning in AF. Objective: To determine how the PP1 regulatory subunit 12C (PPP1R12C) and catalytic (PPP1c) subunits modify atrial sarcomere phosphorylation in AF. Methods: We evaluated the protein expression, binding and phosphorylation among PPP1R12C, PPP1c, and MLC2a in transfected HL-1 cells, murine atrial tissue (Pitx2null +/– mice, with a genetic predisposition AF), and in HEK cells. An inhibitor of PPP1R12C phosphorylation, BDP5290, was used to enhance the PPP1R12C-PPP1C interaction. Results: In Pitx2 null +/– mice, PPP1R12C was increased by 2-fold ( P &lt;0.01) and associated with a 40% reduction in S-19-MLC2a phosphorylation versus WT mice ( P &lt;0.058). BDP5290 increased PPP1R12C-PPP1C binding by &gt;3-fold in HL-1 cells ( P &lt;0.01). BDP5290 reduced MLC2a phosphorylation by 40% through an enhanced interaction with PPP1R12C by &gt;3-fold in HEK cells ( P &lt;0.01). Conclusion: In Pitx2 null+/- mice, increased expression of PPP1R12C is associated with PP1 holoenzyme targeting to sarcomeric MLC2a, and is associated with reduced S19-MLC2a phosphorylation. Additionally, BDP5290 enhances the PPP1R12C-PPP1C interaction and models PP1 activity in AF. Future studies will examine the effects of both AF and BDP5290 upon atrial contractility in vitro.

Atorvastatin can ameliorate left atrial stunning induced by radiofrequency ablation for atrial fibrillation.

The objective of this study was to study the functional changes of the left atrium after radiofrequency ablation treatment for atrial fibrillation and the therapeutic effect of atorvastatin. Fifty-eight patients undergoing radiofrequency ablation for atrial fibrillation were randomly divided into non-atorvastatin group and atorvastatin group. Patients in the atorvastatin group were treated with atorvastatin 20 mg p.o. per night in addition to the conventional treatment of atrial fibrillation; patients in the non-atorvastatin group received conventional treatment of atrial fibrillation only. Echocardiography was performed before radiofrequency ablation operation and 1 week, 2 weeks, 3 weeks, and 4 weeks after operation. Two-dimensional ultrasound speckle tracking imaging system was used to measure the structural indexes of the left atrium. Results indicated that there was no significant change for indexes representing the structural status of the left atrium within a month after radiofrequency ablation (P > 0.05); however, there were significant changes for indexes representing the functional status of the left atrium. There were also significant changes in indexes reflecting left atrial strain status: the S and SRs of atorvastatin group were higher than those of non-atorvastatin group (P < 0.05). In summary, atorvastatin could improve left atrial function and shorten the duration of atrial stunning after radiofrequency ablation of atrial fibrillation.