Duygu Kocyigit

Safety and efficacy outcomes in patients undergoing pulmonary vein isolation with second-generation cryoballoon

AIMS The second-generation cryoballoon (Arctic Front Advance™) (Arc-Adv-CB) has a redesigned injection system which distributes the refrigerant homogenously to the frontal balloon surface. The aim of this study was to compare the efficacy and safety of the Arc-Adv-CB and its predecessor (Arctic Front™) (Arc-CB) in patients who underwent pulmonary vein isolation (PVI) for atrial fibrillation (AF). METHODS AND RESULTS Three hundred and six patients (55.35 ± 10.60 years, 47.05% male) were included in the study. A total of 1205 pulmonary veins were attempted for PVI with either Arc-CB or Arc-Adv-CB. The follow-up durations were 30 (23-38) and 10 (8-13) months in Arc-CB and Arc-Adv-CB groups, respectively (P < 0.001). When the blanking period was considered, freedom from AF after a single ablation procedure was 68.53 and 90.83% in patients undergoing PVI with Arc-CB and Arc-Adv-CB, respectively. The most frequent complication was transient phrenic nerve palsy (PNP) which occurred in five(2.54%) and nine(8.26%) of patients undergoing PVI with Arc-CB and Arc-Adv-CB, respectively (P = 0.040). Left atrial (LA) diameter (hazard ratio, HR: 3.552, 95% CI: 2.034-6.201, P < 0.001), smoking history (HR:1.643, 95% CI: 1.011-2.671, P = 0.045), persistent AF (HR:1.725, 95% CI: 1.021-2.915, P = 0.041), duration of AF (HR:1.039, 95% CI: 1.000-1.080, P = 0.047), and early AF recurrence (HR:2.399, 95% CI: 1.443-3.989, P < 0.001) were associated with increased late AF recurrence. On the other hand, intraprocedural vagal reactions (HR: 0.550, 95% CI: 0.331-0.915, P = 0.021) and Arc-Adv-CB use (HR: 0.441, 95% CI: 0.225-0.866, P = 0.017) were associated with lower late AF recurrence. Left atrial diameter (HR: 3.072, 95% CI: 1.646-5.732, P < 0.001), early AF recurrence (HR: 1.906, 95% CI: 1.103-3.291, P = 0.021), and Arc-Adv-CB use (HR: 0.472, 95% CI: 0.239-0.931, P = 0.030) were independent predictors for late AF recurrence. CONCLUSION Our study has shown that Arc-Adv-CB use is associated with lower late AF recurrences at the cost of an increased risk for PNP.

Left atrial appendage isolation in addition to pulmonary vein isolation in persistent atrial fibrillation: one-year clinical outcome after cryoballoon-based ablation

Aims In this study, we sought to evaluate the safety and efficacy of cryoballoon (CB) based empirical left atrial appendage (LAA) isolation as an adjunct to pulmonary vein isolation (PVI) compared to the PVI-only strategy in patients with persistent AF. Objectives Clinical outcomes of catheter ablation were less beneficial for persistent atrial fibrillation (AF) than paroxysmal AF. Methods and results A total of 100 consecutive patients with persistent AF underwent both PVI and additional LAA isolation using CB (Group II). As a control group (Group I), among persistent AF patients, we conducted a retrospective, propensity-score matched cohort, in whom only PVI was performed using CB. Recurrence of atrial tachyarrhythmia (Ata) at the 12th month follow-up was the primary endpoint. Baseline demographic and clinical characteristics were similar between two groups. At the 12th month follow-up, 67 (67%) patients in Group I and 86 (86%) patients in Group II were free of ATa after the index procedure (P < 0.001). As a unique complication of LAA isolation, left circumflex artery spasm was observed in 4% of the Group II. After adjusting for several baseline variables, PVI-only strategy was found as a significant predictor for recurrence (HR: 3.37; 95% CI: 1.73-6.56; P < 0.001). Transoesophageal echocardiography examination during the follow-up revealed no thrombus in the LAA. Conclusion Our findings indicated that LAA isolation as an adjunct to PVI improved 1-year outcomes in persistent AF compared with the PVI-only strategy using CB without an increase in thromboembolic complications.

Periatrial epicardial adipose tissue thickness is an independent predictor of atrial fibrillation recurrence after cryoballoon-based pulmonary vein isolation.

BACKGROUND Epicardial adipose tissue (EAT) is a metabolically active fat depot. Studies have investigated the effect of EAT thickness on outcomes of radiofrequency catheter ablation of atrial fibrillation (AF). However, data on the relationship between EAT thickness and outcome of cryoballoon-based pulmonary vein isolation (PVI) are lacking. OBJECTIVE In this study, we investigate the association between EAT thickness and AF recurrence after cryoballoon-based PVI. METHODS Patients with symptomatic paroxysmal or persistent AF despite ≥1 antiarrhythmic drug(s) were scheduled for cryoballoon-based PVI for AF per the recent recommendations. Periatrial, periventricular, and total EAT thickness measurements were obtained from preprocedural multidetector CT scans. RESULTS A total of 249 patients (55.6 ± 10.7 years; 48.2% male; 18.5% persistent AF) were involved in the study. Patients were followed-up for 29 months (8-48 months). When blanking period was considered, freedom from AF after the ablation procedure was 75.9% at a median follow-up of 29 months. Total periatrial EAT thickness (18.1 ± 6.2 vs. 14.7 ± 4.7 mm; P < .001) was greater in patients with late AF recurrence when compared to those without. On the other hand, periventricular or total EAT thickness measurements did not differ between both groups (P > .05). Multivariate Cox proportional hazard regression analysis showed that periatrial EAT thickness (hazard ratio, 1.086; P = .001) and left atrial volume index (hazard ratio, 1.144; P < .001) were independent predictors for late AF recurrence. CONCLUSION Quantification of EAT thickness from preprocedural multidetector CT scans may serve as a beneficial parameter for prediction of AF recurrence after cryoballoon-based PVI.

Markers of subclinical atherosclerosis in premenopausal women with vitamin D deficiency and effect of vitamin D replacement.

BACKGROUND Recent studies have revealed a relationship between vitamin D deficiency and atherosclerosis. This study aims to investigate the impact of vitamin D deficiency and replacement on markers of subclinical atherosclerosis in young premenopausal women in whom vitamin D deficiency is prevalent. METHODS Thirty-one premenopausal vitamin D deficient women and 27 age and gender-matched control subjects were enrolled in this study. Markers of subclinical atherosclerosis including carotid intima-media thickness (cIMT), flow-mediated dilatation (FMD), endothelial progenitor cell (EPC) count and cytokine levels were determined at baseline. All measurements were repeated at 6-month follow-up in vitamin D-deficient subjects after vitamin D replacement. RESULTS Vitamin D deficient premenopausal women had lower FMD (9.9 ± 1.3 vs. 13.8 ± 1.7%, p < 0.001) and EPC counts at baseline. This population also had lower IL-10 and higher IL-17 levels. A 6-month vitamin D replacement therapy resulted in a significant increase in FMD (9.9 ± 1.3 vs. 11.4 ± 1.4%, p < 0.001) and EPC counts. Furthermore, cytokine profile shifted toward a more anti-inflammatory phenotype including elevated IL-10 and decreased IL-17 levels. cIMT was not different between patient and control groups and did not change following vitamin D replacement. Change in 25(OH)D and IL-17 levels were independent predictors of the change in FMD measurements following vitamin D replacement. CONCLUSION This study demonstrates that endothelial function is impaired in otherwise healthy vitamin D deficient young premenopausal women and improves with 6-month replacement therapy. Immune-modulatory effects of vitamin D may, at least partly, be responsible for its beneficial effects on vascular health.

M2-muscarinic acetylcholine receptor autoantibody levels predict left atrial fibrosis severity in paroxysmal lone atrial fibrillation patients undergoing cryoablation

AIMS Atrial fibrosis has been found to be associated with recurrent atrial fibrillation (AF) following catheter ablation. Autoantibodies against M2-muscarinic receptors (anti-M2-R) may play a role in the development of AF by inducing left atrial (LA) fibrosis. In this study, we aim to compare anti-M2-R levels between paroxysmal lone AF patients and healthy control subjects and to investigate the relationship between pre-ablation anti-M2-R level, LA fibrosis quantified by delayed enhancement magnetic resonance imaging (DE-MRI), and AF recurrence following cryoablation. METHODS AND RESULTS Thirty-one patients with paroxysmal lone AF (53.4 ± 8.0 years, 61% male), who underwent cryoballoon-based ablation, along with 31 healthy control subjects were included. Enzyme-linked immunosorbent assay tests to measure serum anti-M2-R levels were performed in both groups and DE-MRI was done to quantify LA fibrosis prior to the ablation in the patients. Anti-M2-R levels were higher in the study population when compared with control subjects [212.4 (103.2-655.5) vs. 73.0 (39.5-299.1) ng/mL, P < 0.001]. Anti-M2-R level predicted moderate-extensive LA fibrosis independent of other measures [odds ratio: 1.26 (95% confidence interval (CI): 1.04-1.53), P = 0.017]. At a mean follow-up of 35.2 ± 3.5 months, nine patients (29.0%) had AF recurrence. In the Cox regression model including pre-ablation anti-M2-R level, LA diameter, LA volume index, and moderate-extensive LA fibrosis, only moderate-extensive LA fibrosis predicted late AF recurrence independent of other measures [hazard ratio: 29.41 (95% CI: 3.52-250.00), P = 0.002]. CONCLUSION Serum anti-M2-R levels may be associated with the severity of LA fibrosis and may be implicated in the pathophysiology of AF recurrence following cryoablation. Detection of anti-M2-R levels may help select appropriate patients for the procedure.

Monocyte Toll-Like Receptor Expression in Patients With Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia. Inflammation has been suggested to play a vital role in the pathogenesis. Previous studies have investigated expression of inflammatory markers in AF. Several studies have focused on the effects of toll-like receptors (TLRs) on heart in terms of capability of modulating inflammation. In this study, we aimed to investigate whether peripheral monocyte TLR expression was associated with the AF presence, and recurrence of AF after cryoablation, as a reflection of inflammatory status. Patients with AF who were scheduled for cryoballoon-based ablation for AF and age- and gender-matched subjects in sinus rhythm were included. Peripheral monocyte TLR-2 and TLR-4 expressions were evaluated by flow cytometric analysis in peripheral venous blood samples obtained during evaluation in outpatient clinics: 172 patients (56.5 ± 6.6 years, 52.3% men) were included in the study. Peripheral monocyte TLR-2 and TLR-4 expression levels were significantly higher in patients with AF (p <0.05). Among patients with AF, 12 patients (14.0%) developed AF recurrence at a follow- up of 17 months. Multivariate Cox regression analysis showed that left atrial volume index (hazard ratio 2.040, 95% CI 1.197 to 3.477, p = 0.009) and monocyte TLR-4 expression (hazard ratio 1.226, 95% CI 1.042 to 1.443, p = 0.014) were independent predictors of AF recurrence after blanking period following second-generation cryoballoon-based pulmonary vein isolation for paroxysmal AF. In conclusion, our study highlights the role of TLR-mediated inflammation in the pathogenesis of AF. This link may also constitute a therapeutic target in patients with AF.

Cardiac Autoantibody Levels Predict Recurrence Following Cryoballoon-Based Pulmonary Vein Isolation in Paroxysmal Atrial Fibrillation Patients.

Recent evidence has suggested that autoantibodies may play an important role in the development of atrial fibrillation (AF). The predictive value of preprocedural autoantibodies against beta‐1 adrenergic receptor (anti‐β1‐R) and M2‐muscarinic acetylcholine receptor (anti‐M2‐R) for AF recurrence following cryoballoon‐based pulmonary vein isolation (PVI) is still unclear. We aimed to determine the predictive value of preprocedural anti‐β1‐R and anti‐M2‐R levels for AF recurrence.

Epicardial Fat Thickness is Increased in Vitamin D Deficient Premenopausal Women and does not Decrease after Short-term Replacement

AIM Vitamin D deficiency, which is prevalent among young women in Middle Eastern populations, has been linked to cardiovascular disease. Epicardial adipose tissue (EAT) has also been found to be associated with coronary artery disease. However, data on the relationship between vitamin D status and epicardial adiposity is limited. This study aims to investigate the effect of vitamin D deficiency and replacement therapy on EAT thickness in healthy, young premenopausal women. METHODS Thirty-one premenopausal women with vitamin D deficiency and 31 age-matched women with normal vitamin D levels were enrolled in this study. EAT thickness was measured echocardiographically. Measurements were performed at baseline in both groups and were repeated at the 6-month follow-up in vitamin D deficient subjects after vitamin D replacement therapy. RESULTS The baseline plasma 25-hydroxyvitamin D levels were lower in the vitamin D deficient group compared to the control group and were significantly improved following replacement therapy. EAT thickness was significantly higher in the vitamin D deficient group, and no significant change occurred following replacement therapy. In the linear regression analysis, waist circumference (β=0.031 [0.005-0.057], p=0.020) and 25(OH)D level (β=－0.020 [(－0.028)－(－0.013)], p＜0.001) independently correlated with EAT thickness. CONCLUSION Vitamin D deficiency is associated with a significant increase in EAT thickness in premenopausal women; however, a net beneficial response to adequate replacement therapy was not observed during the short period of therapy during our study. Longer periods of replacement therapy and follow-up may be useful to demonstrate the potential beneficial effects of vitamin D replacement on epicardial adiposity.

Netrin-1 is associated with macrophage infiltration and polarization in human epicardial adipose tissue in coronary artery disease

BACKGROUND Inflammatory activity originating from the epicardial adipose tissue (EAT) may have a role in coronary artery disease (CAD) pathogenesis. The relationship between macrophage infiltration, polarization in the EAT, and netrin-1 gene expression was investigated. METHODS Macrophage infiltration and polarization were examined by immunohistochemical methods and expression levels of netrin-1, Unc5b, and cytokines related with M1-macrophage subtype (IL-12 and IL-18) were determined by quantitative polymerase chain reaction in subcutaneous and epicardial adipose tissue obtained from patients undergoing coronary artery bypass grafting and non-coronary cardiac surgery. RESULTS CAD patients had higher CD68+ (p=0.005) and CD11c+ (p<0.001) macrophage count in EAT when compared to the controls. CD11c+/CD206+ macrophage ratio, which reflects dominancy of M1-macrophage phenotype, was significantly increased in EAT of CAD patients when compared to that of the controls (p=0.008). CAD patients had significantly higher netrin-1, Unc5b, and IL-18 gene expression in the EAT when compared to the control group (p<0.001, p<0.001, and p=0.006 respectively). Increased macrophage infiltration and polarization were associated with higher netrin-1, Unc5b, and IL-12 gene expression in EAT (p<0.05). CONCLUSIONS Findings suggest a link between enhanced netrin-1 expression in EAT and macrophage infiltration and polarization in patients with CAD.

Elevated Serum Beta‐Trace Protein Levels are Associated With the Presence of Atrial Fibrillation in Hypertension Patients

Beta‐trace protein (BTP) has emerged as a novel biomarker of cardiovascular risk. In this study, the authors aimed to assess the relationship between BTP levels and presence of atrial fibrillation in patients who had controlled hypertension (HTN) and normal renal function. A total of 80 controlled HTN patients with paroxysmal atrial fibrillation (PAF) and 80 age‐ and sex‐matched controls with controlled HTN were enrolled. Serum BTP levels were measured by enzyme‐linked immunosorbent assay. BTP levels were found to be significantly higher in patients with PAF (P<.001). Other parameters including mean systolic and diastolic blood pressure values, serum creatinine levels, and glomerular filtration rate were similar between the two groups. Along with left atrial diameter (odds ratio, 1.504; P<.001), BTP levels (odds ratio, 1.015; P<.001) were independently associated with the presence of PAF. BTP levels were increased in controlled HTN patients with PAF compared with controls, and this association was observed within normal renal functions as reflected by normal glomerular filtration rate.