Assessment of Left Atrial Function in Patients with Paroxysmal, Persistent, and Permanent Atrial Fibrillation using Two-Dimensional Strain.
Lenart-Migdalska Aleksandra,Kaźnica-Wiatr Magdalena,Drabik Leszek,Knap Klaudia,Smaś-Suska Monika,Podolec Prof Piotr,Olszowska Prof Maria
Journal of atrial fibrillation
Background and purpose:Atrial fibrillation (AF) has a progressive nature, leading to structural, functional, and electrical changes in the left atrium (LA). Enhanced response to treatment in patients with AF can be achieved through improved knowledge of atrial structure and a better understanding of its function. The aim of this study was to assess LA strain and its determinants in patients with paroxysmal (PAF), persistent (PsAF), and permanent AF (PmAF). Methods:Fifty-eight patients with registered non-valvular AF were divided into 3 groups depending on the type of AF. The participants underwent transthoracic echocardiography to assess the anatomy and function of heart chambers. Left atrial longitudinal strain (LALS) was measured in four-chamber projections using two-dimensional speckle tracking echocardiography. Results:Patients with PAF had higher LALS (15.7±12.0) when compared to those with PsAF (4.3±7.9) and PmAF (5.8±7.8, all P=0.003). Multiple linear regression showed that the independent predictors of LALS were diastolic blood pressure (β=0.95, R2=0.88) in the PAF group; left atrial area (β=-0.56) and creatinine (β=-0.63, R2=0.58) in the PsAF group; AF duration (β=0.89) in the PmAF group (R2=0.72). Conclusion:LA strain has different determinants depending on AF type. LA size, renal function, and AF duration determine LALS in long-lasting AF. LA strain is a simple and accurate technique to estimate LA dysfunction in patients with long-lasting AF.
Decreased left atrial strain parameters are correlated with prolonged total atrial conduction time in lone atrial fibrillation.
Guo Chunyan,Liu Jiexin,Zhao Shumei,Teng Yixing,Shen Luhua
The international journal of cardiovascular imaging
To investigate left atrium (LA) strain properties of patients with lone atrial fibrillation (LAF) and to assess relationships between LA strain parameters and total atrial conduction time measured with tissue Doppler imaging (PA-TDI). The study population consisted of 53 patients with LAF. The control group was comprised of 50 normal volunteers. Conventional echocardiography indices were measured. Mitral annular velocities and PA-TDI were assessed with TDI. Two-dimensional speckle-tracking echocardiography (2D-STE) was used to assess LA segmental strain and strain rate. Compared with the control group, PA-TDI was significantly prolonged and LA myocardial Ss, SRs, Sa, and SRa were significantly decreased in the LAF group (all P < 0.001). In the control group, LA myocardial Ss (γ = -0.486, P < 0.01), SRs (γ = -0.436, P < 0.01), and Sa (γ = -0.360, P < 0.05) were correlated negatively with PA-TDI. LA myocardial SRa (γ = 0.377, P < 0.01) was correlated positively with PA-TDI. In the LAF group, LA myocardial Ss (γ = -0.429, P < 0.01), SRs (γ = -0.468, P < 0.01), and Sa (γ = -0.380, P < 0.05) were also correlated negatively, and SRa (γ = 0.390, P < 0.01) was correlated positively, with PA-TDI. Multivariate logistic regression identified PA-TDI as the only predictor of AF onset (OR 1.39; 95 % CI 1.02-1.54; P < 0.01). LA strain parameters were decreased and PA-TDI was prolonged in patients with LAF. Structural remodeling of the LA, assessed by 2D-STE, was correlated with electrical remodeling, determined by PA-TDI. Prolonged PA-TDI was independently associated with AF onset.
Effects of different ablation strategies on long-term left atrial function in patients with paroxysmal atrial fibrillation: a single-blind randomized controlled trial.
You Ling,Yao Lixia,Zhou Bolun,Jin Lili,Yin Honglin,Wu Jinglan,Yin Guangli,Yang Ying,Zhang Chenfeng,Liu Yue,Xie Ruiqin
Restoration of sinus rhythm in atrial fibrillation (AF) by radiofrequency catheter ablation (RFCA) is associated with a transient stunning of left atrial (LA) function. However, the long-term effects of different ablation strategies on LA function remain undetermined. We performed randomized controlled trial to evaluate the effects of RFCA, cryoablation, and 3D mapping-guided cryoablation on LA function of proximal AF patients within 1 year. The 3D mapping-guided cryoablation was defined as a maximum of two cryoablation procedures for each pulmonary vein accompanied by RFCA for additional points until complete pulmonary vein isolation was achieved. Conventional and speckle tracking echocardiographic analyses were performed to evaluate LA function. Among the 210 patients (70 in each group) included, a trend of decreasing LA systolic and diastolic function was observed in all groups, as evidenced by decreases in peak A-wave velocity, the global LA peak systolic strain, the peak strain rate, the peak early diastolic strain rate, and the peak late diastolic strain rate within 7 days to 3 months after ablation followed by gradual recovery thereafter. However, the temporal changes in the above four strain parameters among the three groups did not differ significantly within 1 year after ablation (all p > 0.05). Parameters of the LA emptying fraction and LA dimensions were not significantly affected. These results suggested that stunning of LA function occurred within 7 days to 3 months after ablation, and different strategies of AF ablation did not differentially affect the temporal changes in LA function up to 1 year after ablation.
Comparisons of the underlying mechanisms of left atrial remodeling after repeat circumferential pulmonary vein isolation with or without additional left atrial linear ablation in patients with recurrent atrial fibrillation.
Yang Chia-Hung,Chou Chung-Chuan,Hung Kuo-Chun,Wen Ming-Shien,Chang Po-Cheng,Wo Hung-Ta,Lee Cheng-Hung,Lin Fen-Chiung
International journal of cardiology
BACKGROUND:Radiofrequency catheter ablation (RFCA) is a potentially curative treatment for atrial fibrillation (AF), however, whether or not additional left atrial (LA) linear ablation for recurrent AF adversely affects LA remodeling is unknown. METHODS:Thirty-eight patients experiencing AF recurrence after the 1st circumferential pulmonary vein isolation (CPVI) underwent a repeat RFCA, including 20 and 18 patients receiving a repeat CPVI (group I) or CPVI plus LA linear ablation (group II), respectively. 2-D echocardiography was performed during sinus rhythm within 24h, at 1-m and 6-m after RFCA. Longitudinal strains and strain rate were measured with speckle-tracking echocardiography. The standard deviation of contraction duration was defined as LA mechanical dispersion. RESULTS:One and two patients experienced AF recurrence after the 2nd RFCA in group I and II, respectively (P=NS). The 1st CPVI with AF recurrence did not reduce LA size significantly in two groups. After a repeat CPVI, LA diameter but not LA maximal and minimal volume was significantly reduced in group I; additional LA linear ablation significantly decreased LA diameter, maximal and minimal volume in group II. However, there was no significant difference in LA emptying function, global and segmental LA strain and strain rate among the baseline, 1-m and 6-m follow-up in two groups. RFCA did not significantly increase LA mechanical dispersion regardless of the AF ablation strategies. CONCLUSIONS:In patients with recurrent AF, a successful repeat CPVI with or without additional LA linear ablation reduced LA size without significant deleterious effects on LA function and mechanical dispersion.
Non-invasively estimated left atrial stiffness is associated with short-term recurrence of atrial fibrillation after electrical cardioversion.
Marino Paolo Nicola,Degiovanni Anna,Baduena Lara,Occhetta Eraldo,Dell'Era Gabriele,Erdei Tamas,Fraser Alan G,
Journal of cardiology
BACKGROUND:As atrial stiffness (K) is an important determinant of cardiac pump function, better mechanical characterization of left atrial (LA) cavity would be clinically relevant. Pulmonary venous ablation is an option for atrial fibrillation (AF) treatment that offers a powerful context for improving our understanding of LA mechanical function. We hypothesized that a relation could be detected between invasive estimation of K and new non-invasive deformation parameters and traditional LA and left ventricular (LV) function descriptors, so that K can be estimated non-invasively. We also hypothesized that a non-invasive surrogate of K would be useful in predicting AF recurrence after cardioversion. METHODS:In 20 patients undergoing AF ablation, LA pressure-volume curves were derived from invasive pressure and echocardiographic images; K was calculated during ascending limb of V-loop as ΔLA pressure/ΔLA volume. 2D-speckle-tracking echocardiographic LA and LV longitudinal strains and volumes, ejection fraction (EF) and ventricular stiffness (K), as obtained from mitral deceleration time, were tested as non-invasive K predictors. In 128 sinus rhythm patients 1 month after electrical cardioversion for persistent AF, non-invasively estimated K (computed-K) was tested as predictor of recurrence at 6 months. RESULTS:Tertiles of mean LA pressure correlated with increasing K (trend, p=0.06) and decreasing LA peak strain, LVEF, and LV longitudinal strain (p=0.029, p=0.019, and p=0.024). There were no differences in LA and LV volumes and K across groups. Multiple regression analysis identified LV longitudinal strain as the only independent predictor of K (p=0.014). Patients in highest quartile of computed-K (estimated as [log]=0.735+0.051×LV strain) tended to have highest AF recurrence rate (25%) as compared with remaining 3 quartiles (9%, 9%, 3%, p=0.09). CONCLUSION:K can be assessed invasively in patients undergoing AF ablation and it can be estimated non-invasively using LV strain. AF recurrence after cardioversion tends to be highest in highest quartile of computed-K.
Left atrial function, inflammation, and prothrombotic response after radiofrequency ablation for atrial fibrillation.
Yin Guangli,Xie Ruiqin,You Ling,Yin Hongning,Sun Yucui,Wu Jinglan,Zhao Yansha,Geng Xue,Zhang Yanan
Journal of the Chinese Medical Association : JCMA
BACKGROUND:The conversion of atrial fibrillation (AF) to sinus rhythm is associated with transient dysfunction of the left atrium (LA). This study aimed to investigate the time course of LA function and inflammation after radiofrequency (RF) ablation for paroxysmal AF. METHODS:Fifty-three patients with paroxysmal AF undergoing RF ablation were recruited. White blood cells were counted and high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and D-dimer levels were measured. LA emptying fraction, strain, and strain rate were evaluated before RF ablation and at 1, 2, 3, and 4 weeks and 2 and 3 months after ablation using conventional Doppler echocardiography and two-dimensional speckle-tracking echocardiography. RESULTS:LA emptying fraction sharply decreased at day 7 after ablation and then slowly increased (p < 0.05) and returned to the baseline value at day 28. LA strain and strain rate values sharply decreased at day 7 after the procedure and then slowly increased (p < 0.05). A significant correlation between hs-CRP level and LA emptying fraction was found at day 7. CONCLUSION:Reduced LA function and increased prothrombotic tendency were found at ∼1 week after AF ablation for paroxysmal AF. Therefore, monitoring the time and degree of anticoagulation after ablation for paroxysmal AF might effectively prevent thromboembolic events and reduce anticoagulant cost and bleeding risk.
Left Atrial Mechanical Dispersion Assessed by Strain Echocardiography as an Independent Predictor of New-Onset Atrial Fibrillation: A Case-Control Study.
Kawakami Hiroshi,Ramkumar Satish,Nolan Mark,Wright Leah,Yang Hong,Negishi Kazuaki,Marwick Thomas H
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
BACKGROUND:Left atrial (LA) enlargement is associated with atrial fibrillation (AF), but new-onset AF often occurs in the absence of LA enlargement. AF may be related to myocardial fibrosis, and even though left ventricular fibrosis is associated with mechanical dispersion, this phenomenon is not well studied in AF. We hypothesized that detection of LA dysfunction and mechanical dispersion using strain echocardiography is useful for predicting new-onset AF. METHODS:Baseline echocardiography was performed at entry in 576 community-based participants at risk of heart failure or AF. In this case-control study, we compared 35 individuals with new-onset AF (age 70 ± 4 years; 57% men) over 2 years of follow-up with 35 age- and sex-matched individuals who did not develop AF from the same cohort. Using speckle-tracking echocardiography, we measured the LA strain in each of 12 segments in the two- and four-chamber views. LA mechanical dispersion was defined as the SD of time to peak positive strain corrected by the R-R interval (SD-TPS, %). RESULTS:There was no significant difference in LA volume index (32.5 ± 9.2 mL/m vs 29.5 ± 8.3 mL/m; P = .16); patients with new-onset AF had significantly worse LA pump strain (16.6% ± 4.3% vs 20.6% ± 4.3%; P < .01) and reservoir strain (31.4% ± 7.7% vs 38.0% ± 7.3%; P < .01) than those without AF. SD-TPS was significantly higher in patients with AF than in those without it (6.3% ± 2.3% vs 3.9% ± 1.6%; P < .01). SD-TPS was independently associated with new-onset AF after adjustment for patient characteristics, LA volume, and strain (hazard ratio = 1.26; 95% CI, 1.10-1.45; P < .01). In the nested Cox models, the model based on the LA volume and strain for predicting new onset AF was significantly improved by adding SD-TPS (P < .01). CONCLUSIONS:LA dispersion obtained from strain echocardiography seems to provide incremental information about LA volume and function in the prediction of new-onset AF and warrants testing in a larger study.
Clinical implication of disturbed left atrial phasic functions in the heterogeneous population associated with hypertension or atrial fibrillation.
Zhu Mengruo,Chen Haiyan,Liu Yang,Shu Xianhong
BACKGROUND:To evaluate left atrial (LA) phasic functions in patients with hypertension and/or paroxysmal atrial fibrillation (PAF) and its clinical significance. METHODS:LA strain was studied in 77 patients (25 hypertension, 24 lone AF, and 28 with both hypertension and PAF) and 28 controls using two-dimensional speckle-tracking echocardiography (2D STE). The following indexes during atrial reservoir, conduit and pump phase were analyzed respectively: (1) peak atrial longitudinal strain (PALS) and strain rate (PALSR), (2) the standard deviation of time to PALS and PALSR of all LA segments (TpS-SD% and TpSR-SD%). RESULTS:Compared with controls, PALS, PALS and PALSR were significantly reduced in patients with isolated hypertension (all P < 0.01) but no significant differences were observed in PALS, PALSR and TpS-SD% between them (all P > 0.05). PALS, PALSR and PALSR were significantly lower in patients with both hypertension and PAF than in those with isolated hypertension (all P < 0.05). PALS and PALSR were significantly decreased, and TpS-SD% was significantly increased during each phase in lone AF patients than in controls (all P < 0.05), and PALSR was further depressed in patients with both hypertension and PAF (P = 0.029). PALSR ≤ 1.475 s combined with TpS-SD% ≥ 3.25% (sensitivity, 85%; specificity, 71%; AUC = 0.845, P < 0.001) could distinguish lone AF from healthy subjects effectively, while in hypertensive patients, PALS ≤ 14.2% was found to be an independent differentiator for occurrence of AF or not with sensitivity of 81% and specificity of 84% (AUC = 0.838, P < 0.001). LAVI≥29.3 mL/m was an independent characteristic for reflecting different LA remodeling in lone AF or hypertension with AF. CONCLUSIONS:The impairment of LA phasic functions was varied in patients with hypertension and/or AF. The disturbed LA phasic functions were proved to have independent abilities of differential diagnosis in this heterogeneous population associated with hypertension or AF.
Renalase is associated with adverse left atrial remodelling and disease burden in patients with atrial fibrillation undergoing pulmonary vein isolation.
Wybraniec Maciej T,Wieczorek Joanna,Woźniak-Skowerska Iwona,Hoffmann Andrzej,Nowak Seweryn,Cichoń Małgorzata,Szydło Krzysztof,Wnuk-Wojnar Anna,Chudek Jerzy,Więcek Andrzej,Mizia-Stec Katarzyna
BACKGROUND:Renalase is a catecholamine-metabolising enzyme, but its possible association with atrial fibrillation (AF) remains unknown. AIM:We sought to evaluate plasma renalase concentration in patients with AF undergoing pulmonary vein isolation (PVI) with respect to AF clinical characteristics, left atrial (LA) remodelling, and PVI efficacy. METHODS:This case-control study included 69 patients (median age 58 years) with either paroxysmal (89%) or persistent (11%) AF, referred for PVI, and a control group consisting of 15 patients without AF, matched for age, sex, and comorbidi-ties. An evaluation of transthoracic echocardiography with LA speckle tracking and plasma renalase concentration using an enzyme-linked immunosorbent assay was performed. AF recurrence was defined as any AF episode on seven-day electro-cardiographic monitoring at six-month follow-up. RESULTS:Renalase level was higher in the study group than in the control group (mean 27.99 vs. 21.48 μg/mL, p = 0.004), but it was lower in patients with persistent AF (19.05 vs. 28.77 μg/mL; p = 0.023) and among patients with AF episodes di-rectly preceding PVI (24.50 vs. 29.66 μg/mL; p = 0.04). Renalase concentration within the first quartile was associated with higher mean heart rate (70 vs. 61 bpm, p = 0.029), greater AF burden (36.9% vs. 9.3%, p = 0.027), greater LA diameter (41.1 vs. 37.9 mm, p = 0.011), and a trend towards less negative global LA strain (-9.4 vs. -13.5, p = 0.082). Logistic regres-sion revealed that global four-chamber LA strain was the only independent predictor of renalase variability (p = 0.0045). Renalase concentration did not predict AF recurrence at six-month follow-up (area under curve [AUC] = 0.614, p = 0.216). CONCLUSIONS:Low renalase level may be associated with impaired rate control, higher AF burden, and advanced LA remodel-ling in AF patients undergoing PVI, but it does not predict sinus rhythm maintenance.
Association between left atrial function assessed by speckle-tracking echocardiography and the presence of left atrial appendage thrombus in patients with atrial fibrillation.
Kupczynska Karolina,Michalski Blazej W,Miskowiec Dawid,Kasprzak Jaroslaw D,Wejner-Mik Paulina,Wdowiak-Okrojek Katarzyna,Lipiec Piotr
Anatolian journal of cardiology
OBJECTIVE:The aim of the study was to investigate whether the deformation of left atrium (LA) measured by speckle-tracking analysis (STE) is associated with the presence of LA appendage thrombus (LAAT) during non-valvular atrial fibrillation (AF). METHODS:Eighty-seven patients (mean age 67 years, 59% men) were included to retrospective cross-sectional study. On top of standard echocardiography we assessed: LA longitudinal systolic strain (LS), systolic (LSSR) and early diastolic strain rate (LESR) in four-chamber and twochamber apical views. All patients underwent transesophageal echocardiography disclosing LAAT in 36 (41%) patients. RESULTS:Subgroups with and without thrombi did not differ with regard to clinical characteristics. Univariate factors associated with LAAT were as follows: CH2ADS2-VASc Score, left ventricular ejection fraction (LVEF), LV mass, and STE measurements. In a multivariate model only LVEF (p=0.002), LS (p=0.02), LESR (p=0.008), and LSSR (p=0.045) were independently associated with LAAT presence. Moreover, LVEF and LA STE measurements provided incremental value over the CH2ADS2-VASc Score. CONCLUSION:Speckle-tracking TTE may be used to describe LA reservoir and conduit function during AF, allowing the identification of patients with higher risk of LAAT and providing incremental value over the CH2ADS2-VASc Score.
Atrial Function Assessed by Speckle Tracking Echocardiography Is a Good Predictor of Postoperative Atrial Fibrillation in Elderly Patients.
Verdejo Hugo E,Becerra Elia,Zalaquet Ricardo,Del Campo Andrea,Garcia Lorena,Troncoso Rodrigo,Chiong Mario,Marin Arnaldo,Castro Pablo F,Lavandero Sergio,Gabrielli Luigi,Corbalán Ramón
Echocardiography (Mount Kisco, N.Y.)
OBJECTIVE:Advanced age is an independent predictor of postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass surgery. We evaluated whether left atrial (LA) dysfunction assessed by strain contributes to identifying elderly patients prone to POAF. METHODS:Case-control study of 70 subjects undergoing coronary artery bypass surgery. Clinical and laboratory characteristics were recorded at baseline and 72 hours after surgery. Echocardiography was performed during the preoperative period; LA dimensions and deformation by strain (systolic wave [LASs]) as well as strain rate (systolic wave [LASRs] and atrial contraction wave [LASRa]) were assessed. RESULTS:Postoperative atrial fibrillation occurred in 38.5% of patients within the first 72 hours after surgery (28.5% of the younger vs. 48.6% of the older group). Baseline and postoperative inflammatory markers as well as total surgical and aortic clamp time were similar between groups. LA function was markedly impaired in subjects with POAF. Age correlated with LASs, LASRs, and LASRa. These associations remained consistent when subjects 75 years or older were considered separately. Both LASs and LASRa for patients with or without POAF, respectively, were significantly impaired in elderly subjects with POAF. Multivariate analysis provided further evidence that both LASs and age are independent predictors for POAF. CONCLUSION:Age-related changes in atrial function preceding atrial dilation are evident only upon LA strain analysis. LA strain impairment is an independent predictor of POAF irrespective of age and may serve as a surrogate marker for biological processes involved in establishing the substrate for POAF.
Three-Dimensional Speckle Tracking Imaging for Assessing Left Atrial Function in Hypertensive Patients With Paroxysmal Atrial Fibrillation.
Furukawa Atsuko,Ishii Katsuhisa,Hyodo Eiichi,Shibamoto Megumi,Komasa Akihiro,Nagai Takahiro,Tada Eiji,Seino Yutaka,Yoshikawa Junichi
International heart journal
Hypertension (HT) is known to be the most prevalent risk factor for paroxysmal atrial fibrillation (PAF), however, its mechanisms have not been fully clarified. Our aim was to investigate the differences in left atrial (LA) function between healthy subjects, and hypertensive patients without PAF (HT-PAF(-)) and with PAF (HT-PAF(+)) using 3-dimensional (3D) speckle tracking imaging (STI). A total of 144 subjects were enrolled: 44 HT-PAF(+) (27 males; mean age 69 ± 10 years), 50 HT-PAF(-) (31 males; mean age 63 ± 11 years), and 50 controls (31 males; mean age 51 ± 14 years). All subjects were in sinus rhythm during the examination. LA volume, LA emptying fraction (LAEF), and LA wall strain were analyzed by 3D area tracking imaging. The maximal value of the global strain curve was defined as the peak global strain. The standard deviation of the time from the R-wave on the electrocardiogram to peak positive values of the segmental strain curves corrected by the R-R' interval in 6 mid LA segments (TP-SD) was calculated to assess LA dyssynchrony. LAEF and peak global strain were lower in HT-PAF(+) than in HT-PAF(-) (P < 0.01) and in the control (P < 0.01). Moreover, TP-SD was higher in HT-PAF(+) than in HT-PAF(-) (P < 0.05) and in the control (P < 0.01). Multivariate analysis revealed LA volume index, peak global strain, and TP-SD were independent determinants of HT-PAF(+). The presence of PAF is associated with diminished LA compliance and advanced mechanical dyssynchrony, as well as LA geometric deformation.
Mechanical and substrate abnormalities of the left atrium assessed by 3-dimensional speckle-tracking echocardiography and electroanatomic mapping system in patients with paroxysmal atrial fibrillation.
Watanabe Yoshikazu,Nakano Yukiko,Hidaka Takayuki,Oda Noboru,Kajihara Kenta,Tokuyama Takehito,Uchimura Yuko,Sairaku Akinori,Motoda Chikaaki,Fujiwara Mai,Kawazoe Hiroshi,Matsumura Hiroya,Kihara Yasuki
BACKGROUND:Left atrial (LA) remodeling progresses to electrical remodeling, contractile remodeling, and subsequently structural remodeling. Little is known about the relationship between LA electrical and anatomical remodeling and LA mechanical function. OBJECTIVES:We aimed to clarify the relationship between LA mechanical function using 3-dimensional speckle-tracking echocardiography (3D-STE) and LA electrical remodeling using an electroanatomic mapping system (CARTO 3) and to estimate atrial fibrillation (AF) substrate in patients with paroxysmal AF (PAF). METHODS:A total of 52 patients with PAF (41 (79%) men; mean age 61 ± 11 years) undergoing their initial pulmonary vein isolation (PVI) were examined. The standard deviation of the time to peak strain in each LA segment (%SD-TPS) was analyzed as an index of LA dyssynchrony using 3D-STE before PVI. Contact LA bipolar voltage and activation maps were constructed during sinus rhythm before PVI using CARTO 3. The LA total activation time was measured and low-voltage zones (LVZs) were determined with a local bipolar electrogram amplitude of <0.5 mV. The patients were divided into those with an LVZ (LVZ group; n = 23) and those without an LVZ (non-LVZ group; n = 29). RESULTS:The %SD-TPS was significantly higher (14.1 ± 5.7 vs 8.0 ± 5.1; P=.0002) in the LVZ group than in the non-LVZ group and was an independent determinant of the LVZ (odds ratio 1.21; 95% confidence interval 1.04-1.49; P=.01). In addition, the LA total activation time was weakly correlated with the %SD-TPS. CONCLUSION:LA dyssynchrony and conduction delay exist in patients with PAF. The 3D-STE enabled noninvasive estimation of LA electrical remodeling and AF substrate.
Clinical Utility of Atrial Electromechanical Conduction Time Measured with Speckle Tracking Echocardiography after Catheter Ablation in Patients with Atrial Fibrillation: A Validation Study with Electroanatomical Mapping.
Fujii Akira,Inoue Katsuji,Nagai Takayuki,Nishimura Kazuhisa,Uetani Teruyoshi,Suzuki Jun,Funada Jun-Ichi,Okura Takafumi,Higaki Jitsuo,Ogimoto Akiyoshi
Echocardiography (Mount Kisco, N.Y.)
PURPOSE:Our recent report demonstrated that atrial electromechanical conduction time (EMT-ε) measured with speckle tracking echocardiography could predict cardiac events in patients with pathological left ventricular hypertrophy. This study aimed to validate EMT-ε by comparison with electroanatomical mapping and to investigate the clinical utility of EMT-ε in patients with atrial fibrillation (AF) undergoing catheter ablation. METHODS:Forty-six patients with preserved LV ejection fraction (LVEF ≥ 50%) undergoing pulmonary vein isolation (PVI) for AF were studied. Atrial electrical conduction delay was determined by measuring atrial electrical activation time (EAT) using three-dimensional electroanatomical mapping just after PVI. Echocardiographic parameters were acquired within 24 hours and at 6 months after PVI. The study also included 10 control subjects. RESULTS:AF patients had a larger left atrial (LA) volume index (LAVI) and more prolonged EMT-ε compared with control subjects. According to the validation study, EAT was closely related to EMT-ε and a', and this association was independent of LAVI and the presence of persistent AF (EMT-ε: R(2) = 0.342, P < 0.0001, a': R(2) = 0.337, P < 0.0001). At 6 months after PVI, LAVI and EMT-ε were significantly improved. During continued follow-up beyond 6 months (total follow-up, 26 ± 12 months), the EMT-ε shortening at 6 months after PVI was significantly greater in AF-free patients than patients with AF recurrence. CONCLUSIONS:This study suggested that the EMT-ε could be a useful echocardiographic marker of LA electromechanical abnormalities in patients with AF.
Evaluation of left atrial remodeling by 2D-speckle-tracking echocardiography versus by high-density voltage mapping in patients with atrial fibrillation.
Laish-Farkash Avishag,Perelshtein Brezinov Olga,Valdman Andrei,Tam Dudi,Rahkovich Michael,Kogan Yonatan,Marincheva Gergana
Journal of cardiovascular electrophysiology
BACKGROUND:Strain imaging during left atrial (LA) reservoir phase (LASr) is used as a surrogate for LA structural remodeling and fibrosis. Atrial fibrillation (AF) patients with >5% low-voltage zones (LVZs) obtained by 3D-electro-anatomical-mapping have higher recurrence rate post-ablation. We investigated the relationship between LA remodeling using two-dimensional-speckle-tracking echocardiography (2D-STE) and high-density voltage mapping in AF patients. METHODS:A prospective study of 42 consecutive patients undergoing AF ablation. 2D-echo, 2D-STE, and high-density contact LA bipolar voltage maps were constructed before ablation. LVZs were determined with different bipolar amplitudes and their ratio per patient's LA area were investigated for correlation with LASr. We compared 2D-LASr results in patients with LVZs ≥ 5% (LVZs group) versus those with LVZ < 5% (non-LVZs group). RESULTS:Compared with non-LVZs group (n = 15), LVZs group (n = 27) included significantly older patients, more women, more persistent AF, higher CHA DS -VASc score, higher E/A ratio and higher LA volume index (p < .05). LVZs group had lower %LASr values (12.4 ± 5.9% vs. 21.1 ± 6.3, respectively; p<.001). LVZs% in different amplitudes (<0.1 mV, <0.2 mV, and <0.5 mV) were negatively correlated with %LASr (r = -.63, r = -.68, and r = -.72, respectively; p< .001). Atrial strain thresholds for LVZs ≥ 5% in amplitudes <0.1 mV, <0.2 mV, and <0.5 mV were associated with %LASr 12.98, 16.16 and 19.55, respectively; p< .05). In a multivariate analysis, %LASr was the only independent indicator of LVZs (OR, 0.8; 95% CI, 0.6-0.9; p= .04). CONCLUSIONS:LVZs ≥ 5% has a negative association with atrial %LASr. Thus, a simple 2D-STE measurement of %LASr can be used as a noninvasive method to evaluate significant LA remodeling and fibrosis in AF patients.
Improvement of left ventricular function after successful radiofrequency catheter ablation in persistent atrial fibrillation with preserved left ventricular ejection fraction: a comprehensive echocardiographic assessment using two-dimensional speckle tracking analysis.
Nagai Tomoo,Arakawa Junko,Hamabe Akira,Tabata Hirotsugu
Journal of echocardiography
BACKGROUND:A limited number of studies have investigated the effects of radiofrequency catheter ablation (RFCA) on left ventricular (LV) function and the left atrial (LA) size in patients with atrial fibrillation (AF). The purpose of this study was to conduct a comprehensive assessment of LV function in patients with AF with preserved left ventricular ejection fraction (LVEF) before and after RFCA. METHOD:A total of 30 consecutive patients with no recurrences after RFCA for persistent AF (age, 57.7 ± 8.4 years) were enrolled. Transthoracic echocardiography was performed at the baseline and 6 months after the final RFCA using speckle tracking derived LV strain analysis. RESULTS:After RFCA, we measured decreases in the LA volume index (33.7 ± 10.4 ml/m vs. 24.6 ± 8.6 ml/m, p < 0.0001), while we observed improvements in systolic indices such as LVEF (56.8 ± 9.8% vs. 65.1 ± 9.1%, p < 0.0001), global longitudinal strain (- 16.8 ± 4.4% vs. - 18.8 ± 3.4%, p = 0.0055) and twist (8.12 ± 3.66° vs. 12.33 ± 6.75°, p = 0.0050), and also in diastolic indices such as strain rate during early diastole (SR) (0.73 ± 0.10 s vs. 1.32 ± 0.29 s, p < 0.0001) and early transmitral inflow velocity (E)/SR (1.11 ± 0.36 m vs. 0.61 ± 0.19 m, p < 0.0001). Logistic regression analysis showed that ΔE/SR was a contributing factor for improvement in LVEF (odds ratio 126.9; p = 0.021). CONCLUSION:In persistent AF with preserved LVEF, further improvement in LVEF and reverse remodeling of the LA are achieved after RFCA. LV filling pressure may play significant roles in the mechanisms.
Right atrial myocardial deformation by two-dimensional speckle tracking echocardiography predicts recurrence in paroxysmal atrial fibrillation.
Govindan Malini,Kiotsekoglou Anatoli,Saha Samir K,Camm A John
Journal of echocardiography
BACKGROUND:Atrial fibrillation (AF) is a bi-atrial disease yet little attention has been given to right heart function in AF. We propose that the assessment of right atrial (RA) and right ventricular function (RV) using two-dimensional speckle tracking echocardiography (2D-STE) could be valuable in predicting AF recurrence in patients with paroxysmal AF (PAF). METHODS:Thirty patients with PAF were prospectively recruited from a dedicated AF clinic. Right atrial size, volume, and area and RV dimensions were analyzed along with RA and RV strain derived from 2D-STE at baseline and at 3 and 12 months. RESULTS:Higher RA booster strain independently predicted sinus rhythm (SR) maintenance for up to 1 year (P = 0.001). RV strain was impaired in patients with recurrent AF compared to those in SR (P < 0.05) but did not predict AF recurrence. Two-dimensional STE for RA and RV function was simple to perform with excellent reproducibility (adjusted R 0.92-0.99). CONCLUSIONS:Two-dimensional STE is useful and highly reproducible in assessing right heart function in AF patients. RA booster strain function was predictive of sinus rhythm maintenance for up to 1 year.
Improving performance of 3D speckle tracking in arterial hypertension and paroxysmal atrial fibrillation by using novel strain parameters.
Esposito G,Piras P,Evangelista A,Nuzzi V,Nardinocchi P,Pannarale G,Torromeo C,Puddu P E
The function of left atrium (LA) is closely related to LA remodeling and one of the most important mechanisms is an increased deposition of fibrous tissue that often is the basis for LA electro-mechanical changes before the onset of atrial fibrillation (AF). This study evaluated LA shape and function, by investigating standard and novel strain parameters calculated by a new approach based on homologous times derived from 3D speckle tracking echocardiography (3DSTE) in hypertensive (HT) and paroxysmal atrial fibrillation (PAF) patients with or without left ventricular hypertrophy (LVH), compared to control (C) subjects. LA function was assessed using homologous times to compare strain variables among different individuals, acquired at different physiological time periods. Standard global longitudinal (GLS) and circumferential (GCS) strains were measured at peak of atrial diastole, while longitudinal and circumferential strains (GLSh, GCSh), strain rate (GLSr, GCSr), volume (Vh) and volume rate (Vr) were measured during the atrial telediastolic phase (fifth homologous time) and atrial pre-active phase (tenth homologous time). Using ANOVA, we found an impaired LA deformation detected by standard, interpolated strains and strain rates in both HT and PAF groups compared to C. We also performed ROC analysis to identify different performances of each parameter to discriminate groups (GLSr10 + GCSr10: C vs PAF 0.935; C vs PAF_LVH 0.924; C vs HT_LVH 0.844; C vs HT 0.756). Our study showed anatomical and functional LA remodeling in patients with PAF and HT. 3D strains and strain rates derived from the homologous times approach provide more functional information with improved performance to identify among the explored groups, in particular PAF patients.
Left atrial longitudinal strain by speckle tracking as independent predictor of recurrence after electrical cardioversion in persistent and long standing persistent non-valvular atrial fibrillation.
Moreno-Ruiz Luis Antonio,Madrid-Miller Alejandra,Martínez-Flores Jerónimo Enrique,González-Hermosillo Jesús Antonio,Arenas-Fonseca Jorge,Zamorano-Velázquez Noé,Mendoza-Pérez Beatriz
The international journal of cardiovascular imaging
Atrial fibrillation (AF) is the most common arrhythmia in humans. After successful cardioversion, there is a recurrence of 60% due to atrial remodeling, and it has been shown that the global peak atrial longitudinal strain (GPALS) is decreased in these subjects. The aim of this study was to evaluate the predictive value of GPALS for AF recurrence. A prospective cohort of patients with persistent (PnVAF) and long standing persistent non-valvular AF (LSPnVAF) which underwent electrical cardioversion was evaluated with standard echocardiographic variables and GPALS quantification. The primary endpoint was AF recurrence at 6 months. We included PnVAF (n = 50, aged 68.4 ± 10.2 years, female 46%, lasted AF 6 months) and LSPnVAF (n = 81, aged 66.5 ± 13.1 years, female 36%, lasted AF 18 months). At 6 months there were a 68% of recurrence of AF in PnVAF and 53% in LSPnVAF group. GPALS was lower in recurrence 7.8 ± 2.0% versus 21.2 ± 8.9% (p < 0.001) for PnVAF and 7.3 ± 2.7% versus 20.7 ± 7.6% (p < 0.001) in LSPnVAF. GPALS ≤ 10.75% discriminates recurrence at 6 months with a sensitivity of 85%, specificity 99%, PPV 85%, NPV 90%, LR + 8.5 and LR- 0.17. The independent predictors of recurrence in PnVAF were GPALS ≤ 10.75% HR 8.89 [(2.2-35.7), p < 0.01] meanwhile in LSPnVAF were age HR 1.039 [(1.007-1.071), p = 0.01], and GPALS ≤ 10.75% HR 28.1 [(7.2-109.1), p < 0.001]. In subjects with PnVAF and LSPnVAF with successful electrical cardioversion, GPALS ≤ 10.75% predicts arrhythmia recurrence at 6-month follow-up.
Left atrial strain assessed by three-dimensional speckle tracking echocardiography predicts atrial fibrillation recurrence after catheter ablation in patients with paroxysmal atrial fibrillation.
Mochizuki Atsushi,Yuda Satoshi,Fujito Takefumi,Kawamukai Mina,Muranaka Atsuko,Nagahara Daigo,Shimoshige Shinya,Hashimoto Akiyoshi,Miura Tetsuji
Journal of echocardiography
BACKGROUND:Several studies have shown the utility of left atrial (LA) function determined by two-dimensional or three-dimensional speckle tracking echocardiography (2D- or 3D-STE) for identifying patients with paroxysmal atrial fibrillation (AF). However, whether 3D-STE is applicable for prediction of the recurrence of AF after catheter ablation (CA) remains unknown. We examined whether any 3D-STE parameters are better than 2D-STE parameters for the prediction of AF recurrence. METHODS:Forty-two patients with paroxysmal AF (58 ± 10 years old, 69% male) underwent 2D- and 3D-STE within 3 days before first-time CA. The global peak LA longitudinal, circumferential, and area strains during systole (3D-GLSs, -GCSs, and -GASs, respectively) and those just before atrial contraction (3D-GLSa, -GCSa, and -GASa, respectively) were determined by 3D-STE and standard deviations of times to peaks of regional LA strains were calculated as indices of LA dyssynchrony. In 2D-STE, global LA longitudinal strains during systole and just before atrial contraction (2D-GLSs and -GLSa) were determined. RESULTS:During follow-up of 441 ± 221 days, 12 patients (29%) had AF recurrence. In the univariate Cox proportional hazard analysis, age [hazard ratio (HR): 1.08, p = 0.04], 3D-GCSs (HR: 0.91, p = 0.03), and 3D-GASs (HR: 0.95, p = 0.01) were predictors of AF recurrence, though associations of recurrence with 2D-STE parameters, indices of LA synchrony, and LA volume were not significant. Multivariable analysis showed that 3D-GASs was an independent predictor of AF recurrence (HR: 0.96, p = 0.048). CONCLUSIONS:LA strain determined by 3D-STE is a novel and better predictor of AF recurrence after CA than that determined by 2D-STE or other known predictors.
Usefulness of left atrial speckle tracking echocardiography in predicting recurrence of atrial fibrillation after radiofrequency ablation: a systematic review and meta-analysis.
Nielsen Anne Bjerg,Skaarup Kristoffer Grundtvig,Lassen Mats Christian Højbjerg,Djernæs Kasper,Hansen Morten Lock,Svendsen Jesper Hastrup,Johannessen Arne,Hansen Jim,Sørensen Samuel Kiil,Gislason Gunnar,Biering-Sørensen Tor
The international journal of cardiovascular imaging
The usefulness of peak atrial longitudinal strain (PALS) in identifying patients at high risk of atrial fibrillation (AF) recurrence after radiofrequency ablation (RFA) has been investigated in several small AF populations. The aim of this systematic review and meta-analysis was to investigate whether PALS predicts recurrence of AF after RFA treatment. MEDLINE, EMBASE and the Cochrane Library were searched. Studies investigating the value of PALS in predicting successful RFA in AF patients were selected. Patients underwent echocardiography prior to RFA. Risk of bias was evaluated using the Quality in Prognosis Studies (QUIPS) Tool. Twelve studies and a total of 1025 patients suffering from paroxysmal or persistent AF were included. Odds ratios (OR) were assessed in a random and fixed effects model for univariable and multivariable pooled analyses respectively. PALS was found to be a significant predictor of AF recurrence after RFA across study populations (Univariable: OR: 1.17, CI95% [1.03-1.34], p = 0.018, per 1% decrease) (Multivariable: OR: 1.16, CI95% [1.09-1.24], p < 0.001, per 1% decrease). Patients with recurrence had significantly lower PALS prior to RFA than patients who maintained sinus rhythm (15.7 ± 5.7% vs. 23.0 ± 7.0%, p = 0.016). A pooled analysis of weighted mean differences (WMD) also showed a significant difference in PALS between the two groups (WMD: - 6.57, CI95% [- 8.49: - 4.65], p < 0.001). Lower values of PALS are associated with an increased risk of AF recurrence after RFA. PALS provides prognostic value in clinical practice.
[Evaluation of Left Atrial Structure and Function with Two-dimensional Speckle Tracking Imaging and Real-time Three-dimensional Imaging in Patients with Paroxysmal Atrial Fibrillation After Radiofrequency Catheter Ablation].
Yan Yan,Li Xin-Li
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition
Objective:To observe the changes of left atrial structure and function in patients with paroxysmal atrial fibrillation (PAF) after radiofrequency catheter ablation by two-dimensional speckle tracking imaging (STI) and real-time three-dimensional imaging technology (RT-3D) in order to provide basis for clinical evaluation of surgery. Methods:Thirty two (32) cases of PAF patients with catheter ablation from October 2016 to December 2017 in our hospital were enrolled. According to sinus rhythm whether or not be restored after operation, the patients were divided into sinus rhythm group (SR group, 24 cases) and atrial brillation group (AF group, 8 cases). All PAF patients received echocardiography before and 1, 6 months after surgery. Left atrial structure and functional parameters were measured by STI and RT-3D, including left atrial diameter, volume, left ventricular systole, early diastolic, left atrial systolic peak strain rate and ejection fraction. Results:All parameters in AF group were not changed significantly after surgery ( >0.05). In SR group, at 6 month after surgery, the levels of Left atrial anteroposterior diameter (LAAPD), Left atrial up and down diameter (LAUDD), Left atrial left and right diameter (LALRD), minimum volume of left atrium (LAV ), Left atrial presystolic volume (LAV ) and max volume of left atrium (LAV ) were significantly decreased, the levels of Left atrial ejection fraction (LAEF), Left atrial active ejection fraction (LAAEF), Left atrial passive ejection fraction (LAPEF) were significantly increased, the strain rates (SRS, SRE, SRA) in the lateral wall base segment, interval middle segment and middle segment of the lateral wall and overall strain parameters (GLSR , GLSR , GLSR ) were significantly increased (all <0.05); and the other segment strain rates were not significantly changed ( >0.05). In AF group, at 6 month after surgery, the levels of LAV , LAV and LAV were significantly decreased at 6 month after operation, the levels of LAEF, LAAEF were significantly increased, all above had statistical difference ( <0.05); and the other parameters were not significantly changed ( >0.05). Conclusion:STI and RT-3D could quantitatively analyze the structure and function of left atrium before and after radiofrequency ablation in PAF patients. After ablation, the diameter of LA decreases and the ejection fraction increases in the patients with sinus rhythm; the volume of LA increases and the function reduces in the patients with atrial fibrillation recurrence.
Usefulness of left ventricular speckle tracking echocardiography and novel measures of left atrial structure and function in diagnosing paroxysmal atrial fibrillation in ischemic stroke and transient ischemic attack patients.
Skaarup Kristoffer Grundtvig,Christensen Hanne,Høst Nis,Mahmoud Masti Mahdy,Ovesen Christian,Olsen Flemming Javier,Jensen Jan Skov,Biering-Sørensen Tor
The international journal of cardiovascular imaging
Asymptomatic paroxysmal atrial fibrillation (PAF) is often assumed to be the cause of cryptogenic ischemic strokes (IS) and transient ischemic attacks (TIA). We examined the usefulness of measures obtained by 2D speckle tracking echocardiography and novel left atrial measurements, in the diagnosis of PAF in patients with IS and TIA. We retrospectively included 205 patients who after acute IS or TIA underwent an echocardiogram in sinus rhythm. Patients were designated as PAF-patients if they had one or more reported incidents of AF before or after their echocardiographic examination. None of the conventional echocardiographic parameters were significantly associated with PAF. Of the speckle tracking measurements, only early diastolic strain rate (0.7±0.2 s vs. 0.8±0.3 s, p = 0.048) and global longitudinal displacement (GLD) (3.15 ± 1.40 mm vs. 3.87 ± 1.56 mm, p = 0.007) proved significantly different. Of the left atrial parameters both minimal and maximal left atrium volume divided by left ventricular length (min LAV/LVL and max LAV/LVL, respectively) were significantly impaired (min LAV/LVL: 3.7 ± 2.1 cm vs. 2.8 ± 1.11 cm, p = 0.012; max LAV/LVL: 6.6 ± 3.1 cm vs. 5.6 ± 1.7 cm, p = 0.012). GLD, min max LAV/LVL proved significant after adjustment for age, gender, CHADS-VASc and NIHSS. By combining information regarding age, GLD, min and max LAV/LVL the diagnostic accuracy of PAF improved, resulting in a significantly increased area under the curve (p = 0.037). In patients with IS and TIA GLD, min and max LAV/LVL were independently associated with the presence of PAF.
Assessment of left atrial remodeling in paroxysmal atrial fibrillation with speckle tracking echocardiography: a study with an electrophysiological mapping system.
Chen Yilin,Li Zheng,Shen Xuedong,Wang Wei,Kang Yu,Qiao Zhiqing,Wang Xinhua,Pu Jun
The international journal of cardiovascular imaging
This study aimed to evaluate left atrial (LA) remodeling and fibrosis in paroxysmal atrial fibrillation (AF) using speckle tracking echocardiography (STE) based on the findings with radiofrequency catheter ablation (RFCA) so as to predict atrial remodeling prior to ablation. A total of 40 patients with paroxysmal AF were enrolled and divided into two groups based on LA bipolar voltage detected during RFCA: those with low-voltage zone (LVZ) (LV group, n = 19) and those without LVZ (non-LV group, n = 21). The segmental and global LA reservoir, conduit and contractile strain (εs, εe, εa) were analyzed using two-dimensional STE before RFCA. The segmental and global εs, εe, εa (%) decreased in the LV group. Especially, the εs in anteroseptal upper (18.32 ± 7.94 vs. 31.61 ± 9.39) and lower segments (16.60 ± 7.23 vs. 29.23 ± 9.81), posteroseptal upper (22.24 ± 6.65 vs. 32.23 ± 10.57) and lower segments (18.24 ± 6.49 vs. 26.40 ± 7.12), and the global εs (23.85 ± 6.74 vs. 30.48 ± 8.67) significantly decreased in the LV group than in the non-LV group (all P < 0.05). The εs ≤ 24.07 in the anteroseptal upper segment was an effective parameter to differentiate the LV group (sensitivity, 84%; specificity, 81%, P < 0.001). Besides, global εs tended to be an independent determinant of the LVZ (odds ratio 1.347, P = 0.046). STE enables a noninvasive method to evaluate LA remodeling prior ablation.
Mechanical atrial recovery after cardioversion in persistent atrial fibrillation evaluated by bidimensional speckle tracking echocardiography.
Vincenti Antonio,Genovesi Simonetta,Sonaglioni Andrea,Binda Giulia,Rigamonti Elisabetta,Lombardo Michele,Anzà Claudio
Journal of cardiovascular medicine (Hagerstown, Md.)
BACKGROUND:Atrial fibrillation induces reversible electrical and mechanical modifications (atrial remodeling). Atrial stunning is a mechanical dysfunction with preserved bioelectrical function, occurring after successful atrial fibrillation electrical cardioversion (ECV). Two-dimensional speckle tracking echocardiography is a new technology for evaluating atrial mechanical function. We assessed atrial mechanical function after ECV with serial two-dimensional speckle tracking echocardiography evaluations. The investigated outcome was left atrium mechanical recovery within 3 months. METHODS:A total of 36 patients [mean age 73 (7.9) years, 23 males] with persistent atrial fibrillation underwent conventional transthoracic and transesophageal echocardiography before ECV. Positive global atrial strain (GSA+) was assessed at 3 h, 1, 2, 3, 4 weeks and 3 months after ECV. Mechanical recovery was defined as the achievement of a GSA+ value of 21%. RESULTS:Independent predictors of GSA+ immediately after ECV (basal GSA+) were E/e' ratio and left atrial appendage anterograde flow velocity. During the follow-up, 25% of patients suffered atrial fibrillation recurrence. In 12/36 patients (33%) left atrium mechanical recovery was detected (mechanical recovery group), while in 15/36 (42%) recovery did not occur (no atrial mechanical recovery group). At univariate analysis, the variables associated with recovery, were basal GSA+ (P = 0.015) and maximal velocity left atrial appendage (P = 0.022). Female sex (P = 0.038), N-terminal pro-B type natriuretic peptide (P = 0.013), E/e' (P = 0.042) and the indexed left atrium volume (P = 0.019) were associated with the lack of left atrium mechanical recovery. CONCLUSION:In almost half of the patients, the left atrium did not resume mechanical activity within the 3 months after ECV, despite sinus rhythm recovery. The left atrium of these patients was larger, stiffer and their E/E' was higher, suggesting a higher endocavitary pressure compared with mechanical recovery patients. These findings might suggest an increased thromboembolic risk.