Kadri Murat Gurses

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.

The association between circulating endothelial progenitor cells and coronary collateral formation

AIM We investigated the relationship between coronary collateral formation and circulating endothelial progenitor cells (EPC) in patients undergoing coronary angiography. METHODS AND RESULTS Circulating CD133(+)/34(+) and CD34(+)/KDR(+) EPCs were determined in 68 patients (normal coronary vessels in 24 patients and coronary artery disease (CAD) in 44 patients) (age: 58.7 ± 10.1, 64.7% male). Circulating EPCs were higher among patients with normal coronary vessels compared to patients with CAD for CD133(+)/34(+) (p < 0.05) and CD34(+)/KDR(+) cells (p < 0.05). The number of EPCs were significantly greater in patients with good coronary collateral formation (p < 0.05). EPC count was independent predictor for coronary collateral formation after adjustment for other cardiovascular risk factors and extent of CAD (p = 0.037). CONCLUSION In patients with severe coronary stenosis, those with increased circulating EPCs had better collateral formation compared to those with lower EPC counts. Our findings implicate that in addition to presence of critical stenosis, intact response of bone marrow is necessary for collateral formation in CAD.

The cardiovascular effects of premature ovarian failure

BACKGROUND Previous studies have shown that cardiovascular risk is increased in premature ovarian failure (POF). To determine the effects of POF on different parameters of cardiovascular health, we investigated the relationship between POF and circulating endothelial progenitor cells (EPC), endothelial function, carotid intima media thickness (CIMT) and left ventricular diastolic function. METHODS We compared 23 female POF patients (mean age; 37.8 ± 10.8 years) with 20 gender and age-matched healthy controls. Circulating CD133(+)/34(+) and CD34(+)/KDR(+) EPCs were determined by using flow-cytometry. Ultrasound assessment of endothelial function by brachial artery flow-mediated dilatation (FMD) and CIMT was made. Left ventricular systolic and diastolic function was assessed by standard 2D and M-mode echocardiography and tissue Doppler velocities. RESULTS Brachial artery FMD was significantly impaired in patients with POF compared with CG (6.3 ± 1.9% vs 10.4 ± 3.7%, p<0.05). Furthermore, circulating EPCs were lower among patients with POF compared to controls for CD133(+)/34(+) and CD34(+)/KDR(+) cells (p<0.05). There was a significant correlation between serum estradiol levels and EPC number (CD 133+/34+) (r=0.329, p<0.05). POF patients had increased CIMT compared to controls (0.67 ± 0.17 vs 0.43 ± 0.10, p<0.05). When diastolic functions were assessed, patients with POF had lower Epeak, Apeak and mitral CP and higher DT and IVRT (p<0.05, respectively). CONCLUSION Our findings indicate that endothelial function as well as circulating EPCs, CIMT and diastolic function are significantly affected in young women with POF which may have an adverse long-term effect on cardiovascular prognosis.

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.

Cardiovascular risk and coronary atherosclerotic plaques detected by multidetector computed tomography: Framingham and SCORE risk models underestimate coronary atherosclerosis in the symptomatic low-risk Turkish population.

ObjectiveIn this study, we investigated the association between cardiovascular (CV) risk factors and coronary atherosclerotic plaque (CAP) burden/subtypes shown by multidetector computed tomography in symptomatic patients free of known coronary artery disease (CAD). MethodsIn 662 consecutive outpatients (56.9±10.7 years, 50.8% men) without known CAD, 64-slice multidetector computed tomography coronary angiography was performed for detection of CAD. Risk estimation for CV outcomes was assessed using the Systematic Coronary Risk Evaluation (SCORE) and the Framingham Risk Score (FRS). Logistic regression analysis was used to evaluate the association of CV risk factors with the prevalence/extent of CAP. ResultsCAP was detected in 318 (48.0%) individuals. Male sex, older age, hypertension, diabetes mellitus, smoking, and dyslipidemia all increased the likelihood of the presence of CAP in univariate analysis (P<0.001). Older age, male sex, dyslipidemia, and diabetes mellitus independently increased the likelihood of the presence of CAP in multivariate analysis (P<0.005). Multinominal logistic regression analysis showed an association with older age, male sex, dyslipidemia, and smoking for noncalcified plaques; with older age, male sex, diabetes, and dyslipidemia for mixed plaques; and with older age and male sex for calcified plaque. Patients with low FRS and SCORE showed a large number of CAPs (33.8 and 40.4%), although CAP was more prevalent in the high-risk groups (67 and 78%, respectively). ConclusionCV risk stratification using only risk factor-based scores is a weak discriminator of the overall CAP burden in individual patients. Many patients with low FRS or SCORE with substantial CAP might be undertreated or not treated at all.

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.