Transcatheter Aortic Valve Implantation in Patients with Connective Tissue Disease.

BACKGROUND: There is still no consensus on the treatment of patients with connective tissue disease (CTD) with severe symptomatic aortic stenosis (AS). The aim of this study was to evaluate the feasibility and safety of transcatheter aortic valve implantation (TAVI) in patients with CTD. METHODS: Five hundred and fifty consecutive symptomatic severe AS patients who underwent TAVI between 2011 and 2019 were included in this retrospective study, of whom 14 had CTD. Follow-up was performed 30 days, 6 months, and 1 year after the procedure. RESULTS: Of the 14 (2.5%) patients who had CTD, most had rheumatoid arthritis (n = 10), followed by lupus erythematosus (n = 2), scleroderma (n = 1) and mixed (n = 1) CTD. The mean age was 77.6 ± 7.9 years, and there was no statistical difference between the CTD and no-CTD groups. In addition, significantly more of the CTD patients (85.7%) were female compared to the no-CTD group (p = 0.018). None of the patients in the CTD group had acute kidney injury, stroke, major bleeding, or pericardial effusion. However, significantly more patients in the CTD group (n = 4) needed permanent pacemaker implantation than in the no-CTD group (p = 0.008). There were no significant differences between the two groups in terms of mean discharge time (CTD 4.6 ± 2.0, no-CTD 4.5 ± 2.3 days, p = 0.926) and in-hospital mortality [CTD 1 (7.1%), no-CTD 21 (3.9%); p = 0.542]. CONCLUSIONS: In this study, we presented the results of TAVI in patients with and without CTD. The TAVI procedure had similar mid-term outcomes in the two groups, and the CTD group had numerically lower rates of major complications at the cost of a higher incidence of pacemaker implantation.

A simple method to detect leaks after left atrial appendage occlusion with Watchman.

BACKGROUND: We evaluated the efficacy of a new method in identifying peri-device leak (PDL) using morphology of the thrombus formed inside the left atrial appendage (LAA) as seen on follow-up transesophageal echo (TEE). METHOD: A total of 291 consecutive patients undergoing Watchman procedure were included in this analysis. TEE was performed at 45 days postprocedure. Based on the presence of the thrombus inside the LAA behind the device, patients were grouped as (1) white (W) group: LAA completely filled with thrombus (n = 101), 2) nonwhite (NW) group: LAA completely black or mixed (part black and part white; n = 190). Follow-up TEE was repeated at 6 and 12 months. RESULTS: Baseline characteristics were comparable between groups except the device size, number of patients with chicken-wing morphology, and prevalence of left atrial "smoke" that were significantly higher in the NW group. Detection of black appearance was comparable between the pre-coil closure image and the NW population (26/36 [72.2%] vs 99/154 [64.3%], p = .37). After adjusting for clinically relevant covariates, NW appearance of the LAA was associated with the presence of significant leak (odds ratio: 47.96, 95% confidence interval: 2.91-790.2, p < .001). The 11 patients with mixed appearance at the 6-month TEE remained unchanged (part black and part white) at the 12-month TEE. LAA appearance was white in all 36 patients following coil closure. CONCLUSION: Our findings demonstrated white and nonwhite appearance of the appendage on TEE to be reliable markers of complete closure and leak respectively, following LAA occlusion with the Watchman device.

Stenotic double-orifice mitral valve after surgical repaired partial atrioventricular septal defect.

Double-orifice mitral valve (DOMV) is an uncommon congenital anomaly account for 1% of congenital heart disease. However, accurate diagnosis and evaluation of valve stenosis or regurgitation and other concomitant congenital anomalies due to DOMV are required to obtain suitable treatment. Two- and three-dimensional echocardiography can contribute valuable functional and anatomic information that can support to reach this goal. Here, we present a case of complete bridge-type DOMV that causes mitral stenosis after surgical repair of the partial atrioventricular septal defect in childhood.

Left ventricular geometry as a predictor of carotid artery stenosis severity in patients undergoing carotid artery stenting.

BACKGROUND AND AIM: Cerebrovascular diseases are the second most common cause of death worldwide. Moderate and severe carotid artery stenosis causes nearly 10% of all strokes. LV geometry is a familiar prognostic and diagnostic factor in several populations; yet, data on its role in carotid artery stenosis are unknown. In our study, we investigated the prognostic value of LV geometry in predicting carotid artery stenosis severity in patients undergoing carotid artery stenting. METHODS: Patients who underwent carotid artery stenting between January 2012 and January 2016 at our tertiary care center were evaluated retrospectively. Two hundred fifty-five patients who underwent carotid artery stenting were included in the study. Accessible echocardiographic documentation of ninety-eight patients was accessed and evaluated. RESULTS: LV normal geometry was detected in 37 (37.7%) of the 98 carotid artery stenting (CAS) patients, concentric hypertrophy in 13 (13.2%), eccentric hypertrophy in 9 (9.1%), and concentric remodeling in 39 (39.7%). By a majority, distal filter was used in normal geometry and eccentric hypertrophy groups (82.9% vs 100%, P: .017). Considering the relationship between carotid artery stenosis severity and LV geometry, we determined that the stenosis severity was statistically significantly higher in the concentric hypertrophy group (p:0.012). However, although no complications were detected in the concentric hypertrophy group, it did not reach statistical significance between the groups (P: .058). LVMi and as expected, Doppler velocity showed a significant correlation with stenosis severity (r = .23 vs .54; P: .021, <.001, respectively). CONCLUSION: Echocardiographic evaluation of LV geometry provided prognostic information in the development of carotid artery stenosis. Abnormal LV geometry is an independent predictor in detecting the severity of carotid artery stenosis undergoing carotid artery stenting.

Transcatheter valve-in-valve implantation Edwards Sapien XT in a direct flow valve after early degeneration.

In recent years, the use of bioprosthetic valve (BPV) has increased significantly with both surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) due to reasons such as the advantage of not using anticoagulants. Nevertheless, major disadvantage of all BPV is the risk of early structural valve deterioration, leading to valve dysfunction, and requires reoperation, which significantly increases the risk of mortality or major morbidity especially after SAVR. There are a limited number of TAV-in-TAV case reports due to TAVI BPV degeneration. In our knowledge, this is the second report of TAV-in-TAV implantation wherein a previously implanted transfemoral 25-mm nonmetallic Direct Flow SVD valve treated with ViV TAVI via Edwards Sapien XT.

Association between monocyte to high-density lipoprotein cholesterol ratio and bicuspid aortic valve degeneration

Background/aim: From a pathophysiological point of view, inflammation is thought to be more dominant in bicuspid aortic valve (BAV) stenosis than tricuspid aortic valve (TAV) stenosis. Our study aimed to determine the association between monocyte to high- density lipoprotein cholesterol (HDL-C) ratio (MHR), a new inflammatory marker, and the speed of progression of stenosis and pathophysiology of BAV stenosis. Materials and methods: A total of 210 severe aortic stenosis patients (70 consecutive BAV patients, 140 matched TAV patients) were retrospectively enrolled in the study. Clinical and echocardiographic data and laboratory results related to our research were collected retrospectively from the patients' records. MHR was measured as the ratio of the absolute monocyte count to the HDL-C value. Results: Seventy BAV (mean age: 72.0 ± 9.1 years, 42.9% female) and 140 TAV patients (mean age: 77.9 ± 8.3 years, 51.4% female) with severe aortic stenosis were enrolled in this study. There was no difference between the two groups in terms of another baseline demographic or clinic findings except age (P < 0.001). Monocyte count, hemoglobin level, mean platelet volume was significantly higher, and HDL-C level was significantly lower in the BAV group, while other lipid and CBC parameters were found to be similar. In the multivariate analysis, MHR (P = 0.005, 95% CI: 0.90­0.98) and, as expected, age (P = 0.001, 95% CI: 1.02­1.11) were found to be significant as the independent predictor of BAV, after adjusting for other risk factors. Conclusion: Our study showed a significant correlation between increased MHR and BAV. MHR was determined as a significant independent predictor for the speed of progression and diagnosis of severe BAV stenosis in multivariate analysis.

The triglyceride-glucose index predicts peripheral artery disease complexity

Background/aim: High levels of triglyceride (TG) and fasting blood glucose (FBG) values increase atherosclerosis risk. This study evaluates the relationship between peripheral artery disease (PAD) severity and complexity, as assessed by TransAtlantic InterSociety Consensus-II (TASC-II) classification and the triglyceride-glucose (TyG) index. Materials and methods: A total of 71 consecutive patients with PAD (males 93%, mean age 63.3 ± 9.7), who underwent percutaneous peripheral intervention were included retrospectively. The patients were divided into two groups according to the angiographically detected lesions. Those with TASC A-B lesions were included in Group 1, and those with TASC C-D lesions were included in Group 2. TyG index was calculated as formula: ln[fasting TG (mg/dL) × fasting plasma glucose (mg/dL)/2]. Results: There were 40 patients in Group 1 (90.3% men, with a mean age of 63.6 ± 9.3 years) and 31 patients in Group 2 (96.8% men, with a mean age of 62.0 ± 8.6 years). In the majority of patients in both groups, the target vessels are iliac arteries and femoral arteries. In Group 2, platelet count and TyG index were significantly high, according to Group 1. The TyG index was significantly correlated with TASC-II, Rutherford category, HbA1c, and HDL-C. Conclusion: In this present study, we showed that the TyG index was an independent predictor of peripheral artery disease complexity, according to TASC-II classification, for the first time in the literature.

Potential Protective Role of SDF-1 and CXCR4 Gene Variants in the Development of Dementia.

BACKGROUND: The aim of this study was to evaluate the role of polymorphisms of stromal cell-derived factor-1 (SDF-1) and chemokine receptor-4 (CXCR4) genes in dementia susceptibility in a Turkish population. SUBJECTS AND METHODS: The study group included 61 dementia patients, while the control group comprised 82 healthy individuals. Gene polymorphisms of SDF-1 3'A G801A (rs1801157) and CXCR4 C138T (rs2228014) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: A significantly reduced risk for developing dementia was found for the group bearing an A allele for SDF-1 3'A polymorphism (p=0.009; χ2=6.812; OR=0.626; 95%CI= 0.429-0.913). The frequency of the CXCR4 TT and TC genotype was significantly lower in patients with dementia compared to controls (p=0.028; χ2=5.583; OR=0.215; 95%CI=0.05-0.914); (p=0.027; χ2=4.919; OR=0.484; 95% CI=0.246-0.955). Additionally, combined genotype analysis showed that the frequency of SDF1 GA-CXCR4 CC was significantly lower in patients with dementia in comparison with those of controls (p=0.049; OR=0.560; 95% CI= 0.307±1.020). CONCLUSIONS: Our study provides new evidence that SDF1 A and CXCR4 T alleles may be associated with a decreased dementia risk. The present study is important because to our knowledge, it is the first one to be conducted in a Turkish population to date, but we believe that more patients and controls are needed to obtain statistically significant results.

An unusual presentation of papillary fibroelastoma originating from right ventricular outflow tract.

Papillary fibroelastomas (PFEs) are primary cardiac tumors with a benign and avascular nature. Majority of the PFEs are originated from the valvular endocardium, while the most common site is aortic valve. In this case, we present a patient with multiple PFEs originating from the right ventricular outflow tract who was admitted to our clinic with exertional dyspnea. As far as we know, this is the first case of this unusual presentation of multiple PFEs and also had a history of breast cancer and permanent pacemaker reported in the literature.

Ventricular Embolization of Two Edwards SAPIEN XT Prosthetic Valves During Trans-Subclavian Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) is an alternative treatment method in high-risk patients with severe aortic stenosis (AS). Although TAVI is a minimally invasive procedure it is not free from complications. Here, the case is presented of a 61-year-old woman who underwent trans-subclavian aortic valve implantation to treat severe symptomatic rheumatic AS. The procedure was complicated by the ventricular embolization of two Edwards SAPIEN XT valves during the procedure, but was successfully managed with emergency open-heart surgery.

The effect of transcatheter aortic valve implantation on pulmonary hypertension.

BACKGROUND AND AIM: Pulmonary hypertension (PH) is common in patients with severe aortic stenosis (AS). The prognostic effect of PH in high-risk patients undergoing transcatheter aortic valve implantation (TAVI) remains unknown. The aim of this study was to examine the feasibility of TAVI in patients with PH and to determine the effect of TAVI on PH. METHODS AND RESULTS: TAVI was performed in 70 patients (mean age, 77.6 years; 51 females and 19 males) between July 2011 and December 2012, in our hospital. The patients were divided into three groups based on their systolic pulmonary artery pressure (sPAP) values. Group 1 comprised patients with sPAP values <40 mmHg; group 2 included patients with sPAP values ranging from 40 to 59 mmHg; and group 3 included patients with sPAP values >60 mmHg. Seventy percent of the patients were in groups 2 and 3. After TAVI, the sPAP values of the patients in groups 2 and 3 were significantly decreased (47.4 ± 4.6 and 36.6 ± 6.3, P < 0.001 and 64.5 ± 4.7 and 43.2 ± 9.2, P < 0.001, respectively). However, this reduction was sustained for 6 months in group 2 (P = 0.006), whereas the reduction lost its statistical significance (P = 0.07) after 1 month in group 3 (64.5 ± 4.7 and 40.8 ± 8.0, P = 0.001). Significant differences between the sPAP values in all three groups before the procedure were sustained after TAVI (P ≤ 0.001) and after the 1st month (P = 0.02); however, no statistically significant difference was observed after the 6th month (P = 0.06). CONCLUSION: In this study, we demonstrated that TAVI could be reliably and successfully performed in PH patients with severe AS and that TAVI results in a permanent and significant reduction in sPAP.

The Relationship between Epicardial Fat Thickness and Endothelial Dysfunction in Type I Diabetes Mellitus.

BACKGROUND AND AIM: Epicardial adipose tissue (EAT) is a new independent marker of coronary artery disease (CAD). The aim of this study was to investigate the relationship between epicardial fat thickness (EFT) and endothelial dysfunction (ED) in patients with type I diabetes mellitus (TIDM). METHODS AND RESULTS: Seventy-six type I diabetic patients (diabetes duration 11.7 ± 8,1 years, aged 30.6 ± 10 years; female/male: 38/38) and 36 healthy controls were enrolled into the study. Fasting plasma glucose (FPG), lipid panel, glycosylated hemoglobin (HbA1C), high-sensitive C-reactive protein (hsCRP), and fibrinogen levels were determined. EFT was measured via two-dimensional (2D) M-mode echocardiography. Endothelial function was assessed as flow-mediated dilatation (FMD) at the brachial artery using high-resolution ultrasound. EFT was significantly higher in patients compared to controls (3.56 ± 0.48 mm vs. 3.03 ± 0.48 mm, P < 0.001). In addition, significant differences were observed between the patient and control groups in terms of FMD (6.70% ± 1.63 vs. 9.99% ± 1.84, respectively, P < 0.001). EFT was shown to be correlated negatively with FMD (r: -0.94, P < 0.001) and positively with hsCRP (r: 0.41, P < 0.001) and fibrinogen (r: 0. 31, P = 0.007). Multiple regression analysis showed EFT to be an independent factor influencing the endothelial function. CONCLUSION: There was inverse relationship between EFT and endothelial function in this study. EFT measured easily by transthoracic echocardiography may be a useful parameter in the assessment of patients with TIDM.

Transcatheter aortic valve implantation in the presence of hematologic malignancies.

OBJECTIVE: Cardiac surgery may be performed in patients with hematologic disorders, but carries an increased risk of morbidity. This series describes an experience of transcatheter aortic valve implantation (TAVI) in patients with hematologic malignancies, and highlights the technical considerations to be kept in mind. METHODS: Between June 2011 and April 2014, 133 consecutive high-risk patients with symptomatic severe aortic stenosis were treated with TAVI at our centre. Based on consensus among the local heart team, five patients with hematologic malignancies (myelodysplastic syndrome [2],chronic lymphocytic leukemia [2], Hodgkin lymphoma [1]) were considered high risk for surgery (Logistic EUROSCORE 17.2±14.0% and STS score 5.8±4.3%). Serial echocardiographic and clinical follow-ups were done pre- and post-procedure, at discharge, and at 1, 3, 6 and 12 months. RESULTS: Our procedural success rate was 80%. Two heart valves were implanted in one patient due to aortic embolization of the previous valve. Perforation of the right ventricle and cardiac tamponade occurred in the same patient. Mean blood transfusion requirement was 1.0±1.4 U (range: 0 to 3 U). Mean aortic valve gradient was reduced from baseline to 9.2±3.27 mmHg, and the effective orifice area was significantly increased to 1.96±0.29 cm2. Paravalvular aortic regurgitation (AR) was absent-mild in all the patients. CONCLUSION: This present series demonstrates that TAVI with a balloon-expandable valve can be performed safely and effectively and is technically feasible in high-risk patients with hematologic malignancies.

Optimal timing of valve replacement in asymptomatic severe aortic stenosis.

Patients with asymptomatic severe aortic stenosis (AS) constitute a heterogeneous group which includes not only certain cases who are at high risk of sudden death and valve-related heart failure, but also those at low risk for these events. Degenerative AS, which includes a majority of patients with AS, is characterized by stricture of the valve, increased arterial stiffness, and diverse left ventricular response to the valvular plus arterial vascular load. In addition to using traditional primary parameters, the severity of AS and the total left ventricular load should be assessed using new measures such as energy loss index and valvulo-arterial impedance. Natriuretic peptide levels and global longitudinal strain imaging may also be used as secondary parameters to obtain information about left ventricular systolic function, although these parameters do not correlate with the severity of AS. Exercise stress testing and exercise echocardiography are also beneficial when assessing the patient if they are symptomatic, and for determining valvular and left ventricular contractile reserves. The aim of this review was to emphasize the importance of risk stratifications in asymptomatic severe AS cases, and to assess the severity of AS using not only conventional methods but also new methods on which much emphasis has been placed during recent years.

Improvement of right ventricular function with transcatheter aortic valve implantation.

BACKGROUND AND AIM: It has been demonstrated that right ventricular systolic dysfunction develops soon after surgical aortic valve replacement (s-AVR). While the impact of s-AVR or TAVI on the function of the left ventricle has been studied with various imaging modalities, little is known about the impact on right ventricular function (RVF). In the current study, we evaluated the impact of TAVI on RVF using conventional echocardiography parameters. METHODS AND RESULTS: Echocardiography was performed prior to 24 h, 1 month and 6 months after TAVI. RVF was assessed using (1) tricuspid annular plane systolic excursion (TAPSE); (2) RV Tissue Doppler Imaging (S'); (3) right ventricular systolic pressure (RVSP); (4) Fractional area change (FAC); and (5) RV ejection fraction (RVEF). TAVI was performed through the subclavian artery in two patients and femoral artery in 48 patients with an Edwards Sapien XT valve. TAVI was performed on 50 patients between the dates of December 2012 and June 2013. After TAVI, a statistically significant improvement was observed for all parameters related to RVF (RVSP, RVEF, TAPSE, FAC, RVTDI S'). During the 1st and 6th months this statistically significant improvement continued in TAPSE and FAC, and there was no deterioration in RVSP, RVEF, and RVTDI S during the 1st month but a statistically significant improvement continued in the 6th month. CONCLUSION: RVF assessed by conventional echocardiography did not deteriorate after TAVI in early and midterm follow-up. Further, TAVI provides improvement of RVF and can safely and efficiently be performed in patients with impaired RVF.

The importance of echocardiography in transcatheter aortic valve implantation.

Valvular heart diseases cause serious health problems in Turkey as well as in Western countries. According to a study conducted in Turkey, aortic stenosis (AS) is second after mitral valve disease among all valvular heart diseases. AS is frequently observed in elderly patients who have several cardiovascular risk factors and comorbidities. In symptomatic severe AS, surgical aortic valve replacement (AVR) is a definitive treatment. However, in elderly patients with left ventricular dysfunction and comorbidities, the risk of operative morbidity and mortality increases and outweighs the gain obtained from AVR surgery. As a result, almost one-third of the patients with serious AS are considered ineligible for surgery. Transcatheter aortic valve implantation (TAVI) is an effective treatment in patients with symptomatic severe AS who have high risk for conventional surgery. Since being performed for the first time in 2002, with a procedure success rate reported as 95% and a mortality rate of 5%, TAVI has become a promising method. Assessment of vascular anatomy, aortic annular diameter, and left ventricular function may be useful for the appropriate selection of patients and may reduce the risk of complications. Cardiac imaging methods including 2D and 3D echocardiography and multidetector computed tomography are critical during the evaluation of suitable patients for TAVI as well as during and after the procedure. In this review, we describe the role of echocardiography methods in clinical practice for TAVI procedure in its entirety, i.e. from patient selection to guidance during the procedure, and subsequent monitoring.

Simultaneously successful transfemoral aortic valve implantation and endovascular repair of thoracic aortic saccular aneurysm.

The prevalence of aortic stenosis (AS) increases in the elderly. They present high surgical risk due to comorbid factors that increase with age. Transcatheter aortic valve implantation (TAVI) is an effective method in patients who present with severe aortic stenosis with a higher surgical risk or who cannot undergo surgical aortic valve replacement (s-AVR). In our case, the presence of saccular thoracic aortic aneurysm with severe AS, which is a vital co-morbidity, requires the treatment of both. The rise in systolic pressure following the TAVI procedure increases the saccular thoracic aneurysm rupture risk and this is why the timing and method of the two treatments become crucial. In this case, which is as far as we know the fi rst and only report in the literature, both TAVI and endovascular thoracic aortic saccular aneurysm repair were applied simultaneously and successfully to the patient via the same transfemoral route. After 1 month, the patient had good functional capacity and there were no complications in control tomography and echocardiography. In this way, we attempted to emphasize with a multidisciplinary study that the patients be assessed carefully before the procedure, and found that even in patients with common peripheral vascular diseases, a transfemoral route could be used together with the proper methods, and that both procedures could be performed simultaneously.

Coronary Slow Flow is Associated with Depression and Anxiety.

BACKGROUND: There is an established relationship between depression/anxiety disorders and cardiovascular morbidity and mortality which has been previously documented. However, there has been no study evaluating coronary slow flow in association with depression and anxiety. METHODS AND RESULTS: A total of consecutive 90 patients were included in the study. All patients completed scoring scales for depression [Hamilton Rating Scale for Depression (HAMD)] and anxiety (STAI-1, State anxiety subscale of State-Trait Anxiety Inventory; STAI-2, Trait anxiety subscale of State-Trait Anxiety Inventory). Thereafter, they underwent selective coronary angiography and 2 groups were formed: coronary slow flow (n = 42), and normal coronary flow (n = 48). The two groups had comparable baseline characteristics. However, significant differences were found between coronary slow flow and normal coronary flow groups regarding depression (13.1 ± 8.2 and 6.9 ± 6.7, p < 0.001 for HAMD, respectively) and anxiety (46.2 ± 15.0 vs. 32.6 ± 9.9, p < 0.001 for STAI-1 and 51.0 ± 16.7 vs. 43.0 ± 10.7, p = 0.009 for STAI-2, respectively) scores. There were also significant positive correlations between depression/anxiety scores and TIMI frame counts of all major epicardial coronary arteries. In addition, after adjustment for smoking, hypertension, scoring scales, and the presence of depressive mood, all scoring scales and depressive mood were found to be independent risk factors for coronary slow flow in multivariable logistic regression analysis. CONCLUSIONS: Significant association was found among coronary slow flow, depression/anxiety scores and depressive mood. KEY WORDS: Anxiety; Coronary slow flow; Depression; Scale.

[Bonsai induced acute myocardial infarction]. / Bonzai kullanimi sonrasi ortaya çikan akut miyokart enfarktüsü

Incidences of drug abuse and cannabis have increased in young adults, recently. Cannabis induced myocardial infarction has rarely been reported in these people. There is no any literature about a synthetic cannabinoid, being recently most popular Bonsai, to cause myocardial infarction. In this case report we presented a 33-year-old male patient who developed acute myocardial infarction after taking high doses of Bonsai.

Transcatheter Aortic Valve Implantation in Bicuspid Aortic Valve Patients with Coagulation Factor 7 and 11 Deficiency and Atrial Fibrillation.

Although transcatheter aortic valve implantation (TAVI), which is a less invasive standard treatment for aortic stenosis than surgery, has been recommended even in low-risk patients, its effectiveness in bicuspid aortic valve is still unclear. Cardiac surgery has been proven to cause serious complications in hematological diseases with factor deficiency or bleeding diathesis. In this case, which is the first in the literature to our knowledge, we tried to present the successful TAVI procedure in a young patient with bicuspid aortic stenosis and factor 7, 11 deficiency complicated by atrial fibrillation.