scholarly journals Rho Kinase Activity, Connexin 40, and Atrial Fibrillation: Mechanistic Insights from End-Stage Renal Disease on Dialysis Patients

2020 ◽  
Vol 9 (1) ◽  
pp. 165 ◽  
Author(s):  
Lorenzo A. Calò ◽  
Verdiana Ravarotto ◽  
Giovanni Bertoldi ◽  
Elisa Pagnin ◽  
Barbara Rossi ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Rho Kinase ◽  
Left Ventricular ◽  
Dialysis Patients ◽  
Systolic Volume ◽  
Lv Mass ◽  
Connexin 40

Evidence on cellular/molecular mechanisms leading to atrial fibrillation (AF) are scanty. Increased expression of Rho kinase (ROCK) and myosin-phosphatase-target subunit-1 (MYPT-1), ROCK activity’s marker, were shown in AF patients, which correlated with connexin 40 (Cx40) expression, membrane protein of heart gap junctions, key for rapid action potential’s cell–cell transfer. AF is the most frequent arrhythmia in dialysis patients who present increased MYPT-1 phosphorylation, which correlates with left ventricular (LV) mass. Given ROCK’s established role in cardiovascular–renal remodeling, induction of impaired cell-to-cell coupling/potential conduction promoting AF initiation/perpetuation, we evaluated in dialysis patients with AF, MYPT-1 phosphorylation, Cx40 expression, and their relationships to support their involvement in AF. Mononuclear cells’ MYPT-1 phosphorylation, Cx40 expression, and the ROCK inhibitor fasudil’s effect were assessed in dialysis patients with AF (DPAFs), dialysis patients with sinus rhythm (DPs), and healthy subjects (C) (western blot). M-mode echocardiography assessed LV mass and left atrial systolic volume. DPAF’s phospho-MYPT-1 was increased vs. that of DPs and C (1.57 ± 0.17 d.u. vs. 0.69 ± 0.04 vs. 0.51 ± 0.05 respectively, p < 0.0001). DP’s phospho-MYPT-1 was higher vs. that of C, p = 0.009. DPAF’s Cx40 was higher vs. that of DPs and C (1.23 ± 0.12 vs. 0.74 ± 0.03 vs. 0.69 ± 0.03, p < 0.0001). DPAF’s phospho-MYPT-1 correlated with Cx40 (p < 0.001), left atrial systolic volume (p = 0.013), and LV mass (p = 0.014). In DPAFs, fasudil reduced MYPT-1 phosphorylation (p < 0.01) and Cx40 expression (p = 0.03). These data point toward ROCK and Cx40’s role in the mechanism(s) leading to AF in dialysis patients. Exploration of the ROCK pathway in AF could contribute to AF generation’s mechanistic explanations and likely identify potential pharmacologic targets for translation into treatment.

scholarly journals P353 Structural, functional, and electromechanical alterations in patients with paroxysmal atrial fibrillation compared to healthy controls

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
S Trivedi ◽  
L Stefani ◽  
P Brown ◽  
E Kizana ◽  
S Kumar ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Paroxysmal Atrial Fibrillation ◽  
Inverse Correlation ◽  
Left Ventricular ◽  
P Value ◽  
Healthy Controls ◽  
Systolic Volume ◽  
Mechanical Dispersion ◽  
Lv Mass ◽  
Echocardiographic Parameters

Abstract Background and Methods We sought to evaluate the clinical and echocardiographic differences between healthy controls and paroxysmal atrial fibrillation (AF) patients. Clinical and echocardiographic parameters (performed in sinus rhythm) in 46 paroxysmal AF patients were compared with a departmental database of 83 health controls. Results AF patients were older and had increased body size (Table 1). 39/46 (84%) of AF patients had hypertension and 23/46 (50%) had diabetes mellitus. AF patients had increased left ventricular (LV) mass, and reduced diastolic function (lower e’ and increased E/e’ ratio) when compared to healthy controls. Left atrial (LA) volumes were significantly increased in the AF group. All strain parameters – reservoir, conduit, and contractile strain – were impaired in AF patients compared to controls. LA mechanical dispersion (MD) was significantly increased in AF patients. A ratio of indexed LA volume/LA reservoir strain was significantly higher in AF patients over controls. The duration of AF had an inverse correlation with LA reservoir strain (Fig 1) (r=–0.78; p &lt; 0.001). Conclusions Compared to healthy controls, patients with paroxysmal AF have significant structural, functional and electromechanical alterations. LA strain is significantly impaired in paroxysmal AF and correlates with AF duration. Table 1. Echocardiographic parameters Parameter Controls (mean ± SD) AF patients (mean ± SD) P value Age (years) 48 ± 18 58 ± 14 0.001 Body surface area (m2) 1.9 ± 0.2 2 ± 0.2 0.014 LV mass (g) 178 ± 48 223 ± 68 &lt;0.001 Average e’ velocity (cms-1) 10.3 ±2.7 8.1 ± 2.2 &lt;0.001 E/e’ 7.4 ± 1.9 9.3 ± 3.4 0.001 Indexed LA end systolic volume (ml/m2) 27.2 ± 7.1 39.0 ± 11.6 &lt;0.001 LA ejection fraction 55.2 ± 10.4 48.5 ± 14.0 0.007 LA functional index 43.7 ± 14.6 29.8 ± 14.3 &lt;0.001 LA reservoir strain (%) 34.3 ± 6.8 27.9± 8.1 &lt;0.001 LA conduit strain (%) 18.4 ± 6.2 13.5 ± 4.7 &lt;0.001 LA contractile strain (%) 15.9 ± 3.9 14.4 ± 5.5 0.007 LA mechanical dispersion (ms) 25.8 ± 9.6 30.9 ± 11.6 0.018 Indexed LA volume / Reservoir strain ratio 0.8 ± 0.3 1.6 ± 0.9 &lt;0.001 LV = left ventricular; LA = left atrium; SD = standard deviation Abstract P353 Figure. Fig 1. AF duration vs. Reservoir strain

P2464Reduction in left atrial reservoir strain is an independent predictor of atrial fibrillation in patients with arterial hypertension and preclinical diastolic disfunction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A L Chilingaryan ◽  
L G Tunyan ◽  
K G Adamyan
Keyword(s):  
Atrial Fibrillation ◽  
Arterial Hypertension ◽  
Left Atrial ◽  
Independent Predictor ◽  
Systolic Function ◽  
Holter Monitoring ◽  
Left Ventricular ◽  
Volume Index ◽  
Systolic Pulmonary Artery Pressure ◽  
Systolic Volume

Abstract Left atrial (LA) dimensions, wall composition and function strongly depend on left ventricular (LV) diastolic function and impaired in patients with preclinical diastolic disfunction (PDD), which increases the likelihood of atrial fibrillation (AF) occurrence. LA longitudinal strain (LALS) is a sensitive parameter of subclinical myocardial changes and its reduction might be predictive for AF. Methods 168 patients (90 female) 68±9 years with arterial hypertension in sinus rhythm with preserved systolic function (LVEF>50%) and PDD and without renal or valvular disease and 45 age and sex matched healthy controls were followed up for 2 years. PDD was diagnosed at stress echocardiography (SE) if E/e' ≥13, transmittal E wave deceleration time reduction >50ms, systolic pulmonary artery pressure (sPAP) >30 mmHg, and patients remained asymptomatic. LALS was measured by speckle tracking echocardiography as average value of two basal segments in 4 chamber view along with LA end-systolic volume index (LAVi), LA EF, LV mass index (LVMi), and LVLS. 72 hours Holter monitoring was performed every 6 months. Results Patients with PDD had larger LAVi, less LALS, higher LVLS and bigger LVMi compared with controls (LAVi 30.5±4.9 ml/m2 vs 23.1±4.8 ml/m2, p<0.001; LALS 34.7±6.9% vs 45±4.3%, p<0.001; LVLS –17.4±2.4% vs –20.8±2.1%, p<0.002; LVMi 81.8±12.3 g/m2 vs 68±9.2 g/m2, p<0.001). AF was registered in 42 (25%) patients with PDD. LAVi, LVLS and LVMi did not significantly differ in PDD patients with or without incidents of AF however LALS was significantly less in patients with AF (26.8±7.5% vs 37.2±8.1%, p<0.01). Multivariate analysis defined LALS as an independent predictor of AF development (OR=2.4; 95% CI=2.41–5.96; p<0.01) with the cut-off value of 28.9%. Conclusion LA peak reservoir LS is an independent predictor of AF development in patients with PDD.

Use of echocardiography in the diagnosis of dilated cardiomyopathy in Irish wolfhounds

1999 ◽  
Vol 35 (4) ◽  
pp. 279-283 ◽  
Author(s):  
AC Vollmar
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Dilated Cardiomyopathy ◽  
Left Atrial ◽  
Left Ventricular ◽  
Volume Index ◽  
Left Atrial Diameter ◽  
Systolic Volume ◽  
End Systolic Volume ◽  
Fractional Shortening

The purpose of this study was to compare the echocardiographic features of Irish wolfhounds with clinically inapparent dilated cardiomyopathy (DCM) (n = 33) to dogs with advanced DCM (n = 33) and to normal dogs (n = 262). Significant differences were detected between the three groups. In dogs with DCM, the most sensitive diagnostic measurements were: end-systolic volume index (ESVI), E-point to septal separation (EPSS), fractional shortening (FS), and left ventricular internal dimensions (LVIDd and LVIDs). Left atrial diameter was increased markedly in dogs with DCM and 83.3% of affected Irish wolfhounds had concurrent atrial fibrillation. Compared with early DCM, in advanced DCM there was a significant increase in end-diastolic right ventricular diameter, often combined with extensive pleural effusion, the leading sign of congestive heart failure in Irish wolfhounds.

Consideration of non-valvular atrial fibrillation with left atrial appendage thrombus formation despite under appropriate oral anticoagulation therapy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Shiraki ◽  
H Tanaka ◽  
K Yamashita ◽  
Y Tanaka ◽  
K Sumimoto ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Oral Anticoagulation ◽  
Left Atrial ◽  
Thrombus Formation ◽  
Anticoagulation Therapy ◽  
Left Ventricular ◽  
Volume Index ◽  
Oral Anticoagulation Therapy

Abstract Background Atrial fibrillation (AF) is the most frequently sustained cardiac arrhythmia, with a prevalence of about 2–3% in the general population. In accordance with CHADS2 or CHA2DS2-VASc score, appropriate oral anticoagulation therapy such as warfarin or direct oral anticoagulants (DOAC) significantly reduced the risk of thromboembolic events. However, left atrial (LA) thrombus can be detected in the LA appendage (LAA) in AF patients despite appropriate oral anticoagulation therapy. Purpose Our purpose was to investigate the associated factors of LAA thrombus formation in non-valvular atrial fibrillation (NVAF) patients despite under appropriate oral anticoagulation therapy. Methods We retrospectively studied consecutive 286 NVAF patients for scheduled catheter ablation or electrical cardioversion for AF in our institution between February 2017 and September 2019. Mean age was 67.1±9.4 years, 79 patients (29.5%) were female, and 140 (52.2%) were paroxysmal AF. All patients underwent transthoracic and transesophageal echocardiography before catheter ablation or electrical cardioversion. All patients received appropriate oral anticoagulation therapy including warfarin or DOAC for at least 3 weeks prior to transesophageal echocardiography based on the current guidelines. LAA thrombus was defined as an echodense intracavitary mass distinct from the underlying endocardium and not caused by pectinate muscles by at least three senior echocardiologists. Results Of 286 NVAF patients with under appropriate oral anticoagulation therapy, LAA thrombus was observed in 9 patients (3.3%). Univariate logistic regression analysis showed that age, paroxysmal AF, CHADS2 score ≥3, left ventricular end-diastolic volume index (LVEDVI), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), LA volume index (LAVI), mitral inflow E and mitral e' annular velocities ratio (E/e'), and LAA flow were associated with LAA thrombus formation. It was noteworthy that multivariate logistic regression analysis showed that LAA flow was independent predictor of LAA thrombus (OR: 0.72, 95% CI: 0.59–0.89, p&lt;0.005) as well as LVEF. Furthermore, receiver operating characteristic (ROC) curve analysis identified the optimal cutoff value of LAA flow for predicting LAA thrombus as ≤15cm/s, with a sensitivity of 88%, specificity of 93%, and area under the curve (AUC) of 0.95. Conclusions LAA flow was strongly associated with LAA thrombus formation even in NVAF patients with appropriate oral anticoagulation therapy. According to our findings, further strengthen of oral anticoagulation therapy or percutaneous transcatheter closure of the LAA may be considered in NVAF patients with appropriate oral anticoagulation therapy but low LAA flow, especially &lt;15cm/s. Funding Acknowledgement Type of funding source: None

scholarly journals Feasibility and accuracy of the automated software for dynamic quantification of left ventricular and atrial volumes and function in a large unselected population

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
G Italiano ◽  
G Tamborini ◽  
V Mantegazza ◽  
V Volpato ◽  
L Fusini ◽  
...  
Keyword(s):  
Machine Learning ◽  
Atrial Fibrillation ◽  
Image Quality ◽  
Normal Subjects ◽  
Left Ventricular ◽  
Systolic Volume ◽  
Unselected Population ◽  
Lv Volumes ◽  
Time Required ◽  
2D Images

Abstract Funding Acknowledgements Type of funding sources: None. Objective. Preliminary studies showed the accuracy of machine learning based automated dynamic quantification of left ventricular (LV) and left atrial (LA) volumes. We aimed to evaluate the feasibility and accuracy of machine learning based automated dynamic quantification of LV and LA volumes in an unselected population. Methods. We enrolled 600 unselected patients (12% in atrial fibrillation) clinically referred for transthoracic echocardiography (2DTTE), who also underwent 3D echocardiography (3DE) imaging. LV ejection fraction (EF), LV and LA volumes were obtained from 2D images; 3D images were analysed using Dynamic Heart Model (DHM) software (Philips) resulting in LV and LA volume-time curves. A subgroup of 140 patients underwent also cardiac magnetic resonance (CMR) imaging. Average time of analysis, feasibility, and image quality were recorded and results were compared between 2DTTE, DHM and CMR. Results. The use of DHM was feasible in 522/600 cases (87%). When feasible, the boundary position was considered accurate in 335/522 patients (64%), while major (n = 38) or minor (n = 149) borders corrections were needed. The overall time required for DHM datasets was approximately 40 seconds, resulting in physiologically appearing LV and LA volume–time curves in all cases. As expected, DHM LV volumes were larger than 2D ones (end-diastolic volume: 173 ± 64 vs 142 ± 58 mL, respectively), while no differences were found for LV EF and LA volumes (EF: 55%±12 vs 56%±14; LA volume 89 ± 36 vs 89 ± 38 mL, respectively). The comparison between DHM and CMR values showed a high correlation for LV volumes (r = 0.70 and r = 0.82, p &lt; 0.001 for end-diastolic and end-systolic volume, respectively) and an excellent correlation for EF (r= 0.82, p &lt; 0.001) and LA volumes. Conclusions. The DHM software is feasible, accurate and quick in a large series of unselected patients, including those with suboptimal 2D images or in atrial fibrillation. Table 1 DHM quality Adjustment Feasibility Good Suboptimal Minor Major Total of patients (n, %) 522/600 (87%) 327/522 (62%) 195/522 (28%) 149/522 (29%) 38/522 (6%) Normal subjects (n, %) 39/40 (97%) 23/39 (57%) 16/39 (40%) 9/39 (21%) 1/39 (3%) Atrial Fibrillation (n, %) 59/73 (81%)* 28/59 (47%) 31/59 (53%) 15/59 (25%) 6/59 (10%) Valvular disease (n, %) 271/312 (87%) 120/271 (%) 151/271 (%) 65/271 (24%) 16/271 (6%) Coronary artery disease (n, %) 47/58 (81%)* 26/47 (46%) 21/47 (37%) 16/47 (34%) 5/47 (11%) Miscellaneous (n, %) 24/25 (96%) 18/24 (75%) 6/24 (25%) 5/24 (21%) 3/24 (12%) Feasibility of DHM, image quality and need to adjustments in global population and in each subgroup. Abstract Figure 1

P613Cardiac magnetic resonance imaging derived left ventricular mechanical function in patients with atrial fibrillation and left atrial low voltage zones

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Ulbrich ◽  
R S Schoenbauer ◽  
B Kirstein ◽  
J Tomala ◽  
Y Huo ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Atrial Fibrillation ◽  
Magnetic Resonance ◽  
Stroke Volume ◽  
Left Atrial ◽  
Low Voltage ◽  
Left Ventricular ◽  
Left Ventricular Stroke Volume ◽  
Resonance Imaging ◽  
Ventricular Filling

Abstract Background The relation of left atrial low voltage zones (LVZ) to left ventricular function in patients undergoing pulmonary vein isolation (PVI) is not known. Objective To explore the relationship of left atrial low voltage zones (LVZ) on left ventricular function in patients with atrial fibrillation. Methods From June to Nov. 2018, 107 (mean age 67y, 70 men, 73 persistent AF) consecutive patients with symptomatic AF underwent a PVI with LVZ mapping. Before PVI the left ventricular ejection fraction (EF) and stroke volume (SV) were measured by cardiac magnetic resonance imaging (CMR). From feature-tracking of CMR-cine images left ventricular global, systolic and diastolic longitudinal strains (GLS), circumferential strains (GCS) and radial strains (GRS) were calculated. Results Of 59 patients CMR scanning in sinus rhythm was performed, LVZ were present in 24 patients. LVEF was significantly lower in patients with left atrial LVZ (62±9% vs. 55±15%) (p=0,03). Left ventricular stroke volume was significantly decreased by the extent of LVZ (94±23 vs. 72±21ml), (p=0,03). The left ventricular diastolic strains during ventricular filling (caused by atrial contraction) of GLS (r=−0,52), GCS (r=−0,65) and GRS (r=−0,65) were highly signifcantly correlated to the occurence and extent of LVZ (each p<0,001 respectively). The only systolic ventricular strain was GLS, which decreased (r=−0,3, p=0,03) by the occurance of atrial low voltage. Conclusion The active, atrial part of diastolic left ventricular filling properties is impaired by the occurrence and extent of left atrial LVZ. In patients with left atrial LVZ the left ventricular stroke volume and ejection fraction is decreased already in sinus rhythm. It seems possible that atrial mechanical dysfunction and presence of atrial low voltage maybe predicted by LV diastolic strain analysis.

Abstract P709: Risk Factors Associated With Atrial Fibrillation Detection by Mobile Cardiac Outpatient Telemetry Following Acute Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Ovais Inamullah ◽  
Alec McConnell ◽  
Hussein Al-khalidi ◽  
Gerald S Bloomfield ◽  
Shreyansh Shah
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Patient Selection ◽  
Left Atrial ◽  
Cryptogenic Stroke ◽  
Left Ventricular ◽  
Stepwise Logistic Regression ◽  
Internal Diameter ◽  
Atrial Area

Background: Mobile Cardiac outpatient telemetry (MCOT) is often used for patients (pts) with cryptogenic ischemic stroke following hospital discharge to detect atrial fibrillation (AFib) but criteria for patient selection remains a subject of debate. Methods: We identified 297 pts hospitalized with acute ischemic stroke who had an inpatient transthoracic echocardiogram (TTE) and underwent MCOT upon discharge between 2016 and 2018 at a large academic comprehensive stroke center. Pts characteristics between AFib vs. no AFib were compared by Fisher’s exact test for categorical and Wilcoxon rank-sum test for continuous variables. A multivariable stepwise logistic regression model was developed to determine the predictors of AFib detection. Statistical hypotheses were tested as two-sided at 0.05 level of significance. Results: Of the 297 pts, AFib was detected in 24 (8.1%) on 30-day MCOT. Pts with AFib detected were older, white, and have had a larger left atrial area (Table). The final logistic model demonstrated that white race (vs. non-white) (OR 4.86, 1.53-15.41), left atrial area (OR 1.15, 1.05-1.25) and left ventricular internal diameter in diastole (OR 0.33, 0.16-0.67) were associated with AFib detection by MCOT. Conclusion: Although rates of AFib detection on 30-day MCOT post-discharge was low, there are important patient characteristics and TTE features that can improve patient selection. Further studies are needed to determine if this data can be used prospectively to clinically decide which pts with cryptogenic stroke should be given 30-day MCT to detect atrial fibrillation.

Abstract 649: Increased Left Ventricular Filling Pressure is Associated with Left Atrial Thrombus in Patients with Atrial Fibrillation.

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Katsuomi Iwakura ◽  
Hiroshi Ito ◽  
Atsunori Okamura ◽  
Yasushi Koyama ◽  
Motoo Date ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Diastolic Function ◽  
Left Atrial ◽  
Multivariate Logistic Regression Analysis ◽  
Left Ventricular ◽  
Filling Pressure ◽  
Diastolic Filling ◽  
Ventricular Filling Pressure ◽  
Lv Diastolic Dysfunction ◽  
Ventricular Filling

Patients with atrial fibrillation (AF) are frequently associated with reduced left ventricular (LV) diastolic dysfunction. It is still unclear whether reduced diastolic function is associated with the risk of left atrial (LA) thrombus in AF. The ratio of transmitral E velocity to mitral annular velocity (e′) is an echocardiographic estimate of diastolic LV filling pressure even under AF rhythm. We investigated whether reduced LV diastolic function is associated with the risk of LA thrombus in AF patients, using E/e′ ratio as an index. We enrolled consecutive 405 patients with non-valvular, paroxysmal or chronic AF, who underwent both transthoracic- (TTE) and transesophagial echocardiography (TEE) examination within a month. We measured LA and LV dimensions, LV ejection fraction (%EF), wall thickness, E and e′ velocities on TTE, and determined E/e′ ratio. LA appendage thrombus was found in 33 patients (8.1%). Patients with LA thrombus showed lower e′ velocity (5.3±1.8 vs. 7.0±2.2 cm/s, p<.0001) and higher E/e′ ratio (17.2±9.2 vs. 11.5±5.9, p<.0001) than those without it. Using 12.4 as an optimal cutoff point, E/e′ predicted LA thrombus with 70% sensitivity and 70% specificity (AUC=0.72). Odds ratio for LA thrombus in patients in the highest quartile of E/e′ was 6.38 (3.06–13.9). Multivariate logistic regression analysis indicated that the highest quartiles of E/e′ ratio was an independent predictor of LA thrombus among echocardiographic parameters, along with LA dimension and %EF, whereas e′ was not. LA appendage flow velocity was significantly correlated with E/e′ ratio (p<.0001), implying that increased diastolic filling pressure could be associated with impaired blood flow within LA. Increased LV filling pressure increased the risk of LA thrombus in patients with AF, partially through impaired LA hemodynamics. E/e′ ratio on TTE could be useful for detecting high-risk patients for LA thrombus.

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