Predictors of left atrial volume index reduction following cryoballoon-based pulmonary vein isolation.

AIMS: Ablation for atrial fibrillation (AF) has been suggested to be associated with 'reverse left atrial remodelling'. Reduction in left atrial volume index (LAVIR) is regarded as a determinant of reverse remodelling following pulmonary vein isolation (PVI). However, there is paucity on data about the predictors for LAVIR after PVI. In this study, we aimed to investigate predictors of LAVIR at 12 months in AF patients undergoing cryoballoon-based PVI. METHODS AND RESULTS: Patients with symptomatic paroxysmal or persistent AF despite ≥1 antiarrhythmic drug(s), who were scheduled for cryoballoon-based AF ablation procedure per the recent consensus recommendations, were enrolled and followed-up for 12 months in this prospective observational study. Left atrial volume was derived using the biplane area-length method. A total of 160 patients (54.25 ± 7.66 years, 44.40% female) were involved in the study. Reduction in left atrial volume index occurred in 120 patients. Age [hazard ratio (HR): 0.901, 95% confidence interval (CI): 0.828-0.981, P = 0.017], hypertension (HR: 0.151, 95% CI: 0.048-0.471, P = 0.001), mild mitral regurgitation (MR) (HR: 5.327, 95% CI: 1.489-19.058, P = 0.010), and AF recurrence (HR: 0.017, 95% CI: 0.005-0.065, P< 0.001) were found to be independent predictors for LAVIR. CONCLUSION: To the best of our knowledge, this is the largest study in the literature investigating the predictors of LAVIR following AF ablation. According to this data, younger patients without hypertension or moderate MR are most likely to experience LAVIR following ablation.

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

INTRODUCTION: 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-ß1-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-ß1-R and anti-M2-R levels for AF recurrence. METHODS: Eighty patients (mean age 54.25 ± 7.70 years; 40% female) with paroxysmal AF and preserved left ventricular function who underwent cryoballoon-based PVI were included in the study. Preprocedural anti-M2-R and anti-ß1-R levels were measured with ELISA. RESULTS: At 1-year follow-up after ablation, late AF recurrence was observed in 17 (21.25%) patients. In the Cox regression model, including number of antiarrhythmic drugs, early AF recurrence, anti-ß1-R levels >159.88 ng/mL, anti-M2-R levels >277.65 ng/mL, AF duration, and left atrial volume index, only anti-ß1-R levels >159.88 ng/mL (HR: 4.281, P = 0.039) and anti-M2-R levels >277.65 ng/mL (HR: 4.313, P = 0.030) were found to be independent predictors of late AF recurrence. Anti-ß1-R level >159.88 ng/mL was shown to predict late AF recurrence with a sensitivity of 70.59% and specificity of 90.48%. A cut-off value of 277.65 ng/mL for anti-M2-R level predicted AF recurrence with a sensitivity of 70.59% and specificity of 95.24%. CONCLUSION: Preprocedural serum anti-ß1-R and anti-M2-R levels are independent predictors of late AF recurrence following cryoballoon-based PVI in paroxysmal AF patients. Detection of preprocedural anti-ß1-R and anti-M2-R levels may serve as a novel method for determination of paroxysmal AF patients who may not benefit from cryoballoon-based PVI.

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.

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.

Acute Coronary Syndrome in Cancer Patients.

Cardiologists are seeing an increasing number of oncology patients every day, and acute coronary syndrome (ACS) is one of the problems patients encounter during follow-up. Cardio-oncology is the care of patients with cancer and cardiovascular disease, whether overt or occult, already established or acquired during treatment. Cardiovascular complications can occur acutely during or shortly after treatment and persist as long-term effects for months to years after treatment. As a delayed effect of cancer treatment, cardiovascular damage can occur months to years after the initial treatment. Vasospasm, thrombosis, and radiation-induced cardiovascular diseases can all cause ACS. Careful surveillance of ACS symptoms and regular screening during follow-up of patients with malignancy are suggested. In this review, we summarize the ACS we usually encounter during a range of cancer treatments or post cancer survival by providing illustrative case examples.

Vagal denervation in atrial fibrillation ablation: A comprehensive review.

Although pulmonary vein isolation is accepted as an established interventional treatment in paroxysmal atrial fibrillation (AF), alternative modalities are being investigated because of the high recurrence rates of nonparoxysmal forms. One of the alternative ablation approaches is ablation or modification of vagal ganglionated plexi (VGP). The technique has not only been used in vagally mediated AF but also investigated in paroxysmal and nonparoxysmal AF. Clinical studies demonstrate significant discrepancy related with detection of VGP sites or ablation targets and definition of procedurel end-points, so far. In this review, we aimed to discuss the current data on the role of VGP in the pathogenesis of AF and potential therapeutic implications of ablation of these ganglia.

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.

Enhanced Platelet Toll-like Receptor 2 and 4 Expression in Acute Coronary Syndrome and Stable Angina Pectoris.

Evidence is accumulating that toll-like receptors (TLR) are involved in the initiation and progression of cardiovascular disease. Enhanced expression of these receptors on monocytes has been shown in patients with acute coronary syndrome (ACS). However, expression on platelets in this group of patients has not been evaluated yet. We aimed to demonstrate the possible relationship of platelet TLR-2 and TLR-4 expressions with stable coronary artery disease and ACS pathogenesis. In this observational case-control study, 40 patients diagnosed with ACS (unstable angina pectoris, non-ST-segment elevation and ST-segment elevation ACS), 40 patients diagnosed with stable coronary artery disease, and 40 age- and gender-matched subjects with normal coronary arteries were involved. Platelet TLR-2 and TLR-4 expressions were evaluated by flow cytometry in peripheral venous blood samples obtained before coronary angiography. A total of 120 patients (60.7 ± 12.3 years, 50% men) were included. Median platelet TLR-2 and TLR-4 expressions were greater in patients with ACS compared to those with stable angina pectoris and normal coronary arteries (29.5% vs 10.5% vs 3.0%, p <0.001 and 40.5% vs 11.5% vs 3.0%, p <0.001, respectively). Median platelet TLR-2 and TLR-4 expressions were also greater in patients with stable angina pectoris compared to those with normal coronary arteries (p <0.05). In conclusion, this is the first study demonstrating enhanced TLR-2 and TLR-4 expressions on platelets in patients with ACS. These findings may suggest that platelet TLR expression as a novel potential prophylactic and therapeutic target in ACS.

Safety and efficacy outcomes of protamine administration for heparin reversal following cryoballoon-based pulmonary vein isolation.

PURPOSE: Anticoagulation with heparin is required during catheter ablation of atrial fibrillation (AF) to reduce systemic thromboembolism. In this study, we aim to compare safety and efficacy outcomes between patients who receive protamine administration for reversal of heparin and those who do not, following cryoballoon-based pulmonary vein isolation (PVI) for AF. METHODS: Patients with symptomatic paroxysmal or persistent AF despite ≥1 antiarrhythmic drug(s) were scheduled for PVI per the recent consensus recommendations. Some patients were administered protamine at the end of the procedure depending on the operator's choice. RESULTS: Among 380 patients [48.2% male, 56 (20-86) years] that were enrolled, 188 patients received protamine at the end of the procedure. Baseline characteristics did not differ between groups (p > 0.05). Mean protamine dose was 39.1 ± 6.4 mg. Only 1 patient developed rash following protamine infusion. Hospital stay was significantly shorter in patients who were administered protamine (1 [1-5] vs. 2 [1-7] days, p < 0.001). Hematoma/pseudoaneurysm or femoral AV fistula requiring surgical or interventional repair in the femoral access site occurred in 2 (1.1 %) patients who received protamine and 12 (6.3%) patients who did not (p = 0.011). Deep vein thrombosis was seen in 1 patient in whom protamine was not administered (p = 0.499). CONCLUSION: To the best of our knowledge, this is one of the largest series showing that protamine administration for heparin reversal in patients undergoing cryoballoon-based PVI allows quicker sheath removal and minimizes the risk of potential vascular complications without causing an increase in thrombotic events.

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.

Red blood cell distribution width predicts outcome of cryoballoon-based atrial fibrillation ablation.

PURPOSE: Elevated red blood cell distribution width (RDW) has been associated with atrial fibrillation (AF) in cross-sectional and prospective studies. In this study, we aim to evaluate the relation of preablation RDW levels to late AF recurrence following cryoablation. METHODS: A total of 299 patients with symptomatic paroxysmal or persistent AF despite ≥ 1 antiarrhythmic drug(s) who were scheduled for cryoballoon-based AF ablation were enrolled in this prospective study. RESULTS: A total of 299 patients (55.40 ± 10.60 years, 49.20 % male) were involved and followed up at a median time of 24 (6-44) months. Patients with late AF recurrence had higher RDW levels (14.30 ± 0.93 vs. 13.52 ± 0.93 %, p < 0.001). Multivariate Cox proportional hazard regression analysis showed that RDW level was an independent predictor for late AF recurrence (HR 1.88, 95 % CI 1.41-2.50, p < 0.001) along with left atrial (LA) diameter (HR 3.09, 95 % CI 1.81-5.27, p < 0.001), duration of AF (HR 1.04, 95 % CI 1.01-1.07, p = 0.02), and early AF recurrence (HR 6.39, 95 % CI 3.41-11.97, p < 0.001). A cut-off level of 13.75 % for RDW predicted late AF recurrence following cryoballoon-based pulmonary vein isolation (PVI) with a sensitivity and specificity of 78.00 and 70.00 %, respectively. CONCLUSION: These findings suggest that elevated RDW may be a predictor of late recurrence following cryoballoon-based AF ablation. Further studies are needed to establish its exact pathophysiologic and prognostic roles.

Effects of persistent atrial fibrillation on serum galectin-3 levels.

Galectin-3 is known to play an important role in a number of fibrotic conditions, including cardiac fibrosis. Many studies have focused on the association between galectin-3 levels and cardiac fibrosis in heart failure. However, the role of galectin-3 in the pathogenesis of atrial fibrillation (AF) has not been evaluated thoroughly yet. The aim of this study was to determine whether serum galectin-3 levels were elevated in patients with AF and preserved left ventricular function. Seventy-six patients with paroxysmal or persistent AF and preserved left ventricular systolic function and 75 age- and gender-matched control subjects were enrolled in this observational study. Galectin-3 levels were measured by enzyme-linked immunosorbent assay. Serum galectin-3 (median 0.6 ng/ml [interquartile range 0.2 to 1.4] vs 0.5 ng/ml [interquartile range 0.1 to 0.7], p <0.001) and left atrial volume index (LAVI) (mean 29.5 ± 3.5 vs 26.5 ± 2.5 ml/m(2), p <0.001) were significantly greater in patients with AF compared with the control group. Serum galectin-3 levels were also significantly higher in patients with persistent AF than those with paroxysmal AF (median 0.8 ng/ml [interquartile range 0.4 to 1.4] vs 0.5 ng/ml [interquartile range 0.2 to 0.9], p <0.001). Multivariate regression analysis demonstrated that serum galectin-3 (odds ratio 87.53, 95% confidence interval 6.06 to 1,265.03, p = 0.001) and LAVI (odds ratio 1.38, 95% confidence interval 1.19 to 1.60, p <0.001) were independent predictors of AF. Only LAVI was independently correlated with serum galectin-3 levels in patients with AF in linear regression analysis. In conclusion, serum galectin-3 is significantly elevated and is also significantly correlated with LAVI in patients with AF with preserved left ventricular function.