The impact of percutaneous left atrial appendage closure on left ventricular diastolic function and natriuretic peptide levels.

OBJECTIVE: Although the efficacy and safety of left atrial (LA) appendage (LAA) closure in patients with atrial fibrillation (AF) have been well documented in randomized controlled trials and real-world experience, there are limited data in the literature about the impact of LAA closure on diastolic functions. The study aimed to examine the impact of LAA closure on diastolic function and natriuretic peptide levels in patients with AF. PATIENTS AND METHODS: Twelve non-valvular AF patients with high risk for developing cardioembolic stroke and contraindications to warfarin underwent LAA occlusion with the WATCHMAN device (Atritech Inc., Plymouth, MN, USA). B-type natriuretic peptide levels and detailed diastolic parameters (mitral inflow velocities, deceleration time (DT), flow propagation velocity (Vp), isovolumetric relaxation time (IVRT), mitral annular e', TE-e', IVRT/TE-e', E/Vp, E/e', pulmonary vein flow parameters consisting of S, D, and S/D) were evaluated at baseline and 45 days after LAA closure. RESULTS: The median age of the patients was 69 (54-78) years and 75% (n: 9) of them were male. All patients completed forty-five days of follow-up. Compared to the baseline values, E/Vp ratio and BNP levels (1.95 (0.94-3.32) vs. 2.37 (1.09-4.46), p= 0.015; 290.0 (90-1271) pg/ml vs. 322.00 (106-1635) pg/ml, p=0.018, respectively) increased, and pulmonary vein S wave and S/D ratio (0.67 (0.33-0.92) vs. 0.38 (0.23-0.91) m/sec, p=0.048; 1.62 (0.86-5.75) vs. 1.33 (0.11-3.35), p=0.019, respectively) decreased after LAA closure. CONCLUSIONS: In the present study, we demonstrated that patients with AF have shown impaired diastolic functions and elevated BNP levels after the percutaneous closure of the LAA.

The harm of anticoagulation in patients with low-risk by CHADS2 and reclassified as high-risk by CHA2DS2VASc: inferences from TRAF cohort.

OBJECTIVE: There is a gap in the knowledge concerning oral anticoagulation (OAC) in atrial fibrillation (AF) patients with a non-high risk of stroke. CHA2DS2VASc and CHADS2 scores generated imprecise risk estimates for low risk patients. We aimed to assess OAC in patients with low risk by CHADS2 and reclassified as high-risk by CHA2DS2VASc. PATIENTS AND METHODS: In this study, retrospective nationwide population-based study, data were obtained from the Turkish claims and utilization management system. Patients with non-valvular AF (n=451,113) between 2007 and 2012 sub-divided into those with a CHA2DS2VASc≥1 and CHADS2=0 (n=41,273) who were off-warfarin (n=29,448) and on-warfarin (n=11,825). Stroke and systemic embolism, major bleeding, all-cause mortality, net clinical benefit (NCB) and ultimate NCB (UNCB) were assessed. RESULTS: Of the total cohort (mean age 66.1 ± 14.1 years, 56.1% female), CHA2DS2VASc improved the net reclassification index of observed 5-year composite thromboembolic endpoint by 6.9% (p<0.05). CHA2DS2VASc reclassified 9.7% low risk patients as high risk. Among reclassified-high-risk category (patients with a CHA2DS2VASc score of ≥1 and CHADS2 score of 0), major bleeding for that prescribed warfarin was 3% and higher than the rate of thromboembolism among those off-warfarin. NCB (-0.035) and UNCB (-0.021) were negative. Death and hospitalization at 1 year were significantly higher for on-warfarin group. CONCLUSIONS: Clinical outcomes, net clinical benefit indices are negative; rates of death and hospitalization were significantly higher for OAC in reclassified category. This emphasizes the importance of greater attention to balancing the risks and benefits of OAC in patients with low risk by CHADS2 and reclassified as high-risk by CHA2DS2VASc.

Focal laser ablation as clinical treatment of prostate cancer: report from a Delphi consensus project.

PURPOSE: To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method. METHODS: A panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings. RESULTS: Thirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 [Gleason score (GS) 3+4]. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation. CONCLUSION: Focal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified.

High intensity focused ultrasound: The fundamentals, clinical applications and research trends.

Diagnostic ultrasound has been clinically used for decades. More recently, high intensity focused ultrasound (HIFU) has been developed for therapeutic use as a non-invasive technique for tissue ablation. HIFU is also being investigated for advanced applications at the cellular level. Under guidance by magnetic resonance or ultrasound imaging, HIFU can achieve precise biological effects in tissue with a high safety profile. In this article, we discuss the basic principles, advantages and limitations of HIFU. We will also address the food and drug administration (FDA) approved clinical applications in the United States and highlight active HIFU research with promising clinical outcomes.

Computerized dynamic pupillometry indices mirrors the heart rate variability parameters.

OBJECTIVE: Dynamic pupillometry (DP) is a simple, non-invasive computerized assessment of pupillary light response which provides data concerning both branches of the autonomous nervous system (ANS). Heart rate variability (HRV) analysis assess cardiac health and the ANS modulation on the heart. In this study, we aimed to evaluate the utility of DP as a predictor of cardiac autonomic activity assessed by HRV. PATIENTS AND METHODS: A total of 44 consecutive healthy subjects (mean age = 35.9 ± 7.4 years, 24 males) were enrolled. Pupil diameters (R0, R1, R2 and R%): latency (Lc), amplitude (Ac), velocity (Vc) and duration of pupil contraction (Tc): latency (Ld), velocity (Vd) and duration of pupil dilatation (Td) were measured in DP. Time and frequency domain indices of HRV were obtained from 24-h ambulatory electrocardiographic monitoring. RESULTS: There were strong significant correlations of Vc with LF/HF (r = -0.672, p = 0.001) and a measure of HRV: RMSDD (r = 0.654, p = 0.001). R% significantly correlated with PNN50 (r = -0.432, p = 0.003) and RMSDD (r = -0.422, p = 0.004) and LF/HF (r = 0.340, p = 0.024). Vc (ß = 0.647, p = 0.011) and Ac (ß = 0.320, p = 0.013) were found as independent predictors of RMSSD. Vc (ß = 0.578, p = 0.036) was found to be only significant predictor of PNN50. Vc (ß = -0.617, p = 0.008) and R% (ß = 0.309, p = 0.038) were found to be significant predictors of LF/HF. CONCLUSIONS: Pupillary autonomic functions assessed by DP correlates with cardiac autonomic functions evaluated by HRV. Among the DP parameters analyzed, Vc was a predictor of parasympathetic indices, and R% was a predictor of sympathetic indicators of cardiac autonomic functions.

Assessment of the relationship between dynamic pupillometry and exercise heart rate recovery among healthy subjects.

OBJECTIVE: Dynamic pupillometry (DP) is a simple, non-invasive computerized technique for assessment of pupillary light response which provides data concerning the balance of both branches of the autonomous nervous system (ANS). Heart rate (HR) recovery (HRR) after graded exercise reflects cardiac autonomic activity and predicts cardiovascular events. In this study, we aimed to evaluate the utility of DP as a predictor of cardiac autonomic activity assessed by HRR. PATIENTS AND METHODS: A total of 62 consecutive healthy subjects (mean age = 33.7 ± 8.6 years, 39 males and 23 females) were enrolled. Pupil diameters (R0, R1, R2 and R%): latency (Lc), amplitude (Ac), velocity (Vc) and duration of pupil contraction (Tc): latency (Ld), velocity (Vd) and duration of pupil dilatation (Td) were measured in DP. HRR indices were calculated by subtracting 1st (HRR1), 2nd (HRR2) and 3rd (HRR3) minute HR from the maximal HR during treadmill exercise stress test. RESULTS: HRR1 was 32.9 ± 8.0 bpm, HRR2 was 55.1 ± 11.6 bpm and HRR3 was 58.3 ± 12.7 bpm, respectively. Correlation analysis revealed significant positive correlations of HRR1 with Vc (r = 0.660, p = 0.001), Ac (r = 0.559, p = 0.001) and Vd (r = 0.412, p = 0.001). HRR had significant negative correlations with Lc (r = -0.442, p = 0.001), R% (r = -0.384, p = 0.002) and Ld (r = -0.286, p = 0.025). Vc [ß = 3.995 (1.040 to 6.951, 95% CI, p = 0.009)] and Lc [ß = -0.032 (-0.056 to -0.008, 95% CI, p = 0.01)] were found to be significant independent predictors of HRR1. CONCLUSIONS: Pupillary autonomic functions assessed by DP correlates with cardiac autonomic functions evaluated by HRR. Among the DP parameters analyzed, Vc and Lc were independent predictors of cardiac autonomic functions.

Assessment of cardiac arrhythmias in patients with ankylosing spondylitis by signal-averaged P wave duration and P wave dispersion.

OBJECTIVE: Aortic regurgitation, conduction disturbances, increased myocardial fibrosis and pericarditis could be seen in ankylosing spondylitis (AS). However, less attention has been paid to supraventricular arrhythmias (SVA) and atrial conduction system changes. We aimed to assess SVA and conduction system changes in patients with AS. PATIENTS AND METHODS: Twenty-eight patients (24 men; mean age, 28.7 ± 5.7 years) with AS and 30 healthy volunteers (26 men; mean age, 29.3 ± 5.8 years) were enrolled. All subjects were evaluated by 24-hour ambulatory electrocardiogram, 12 lead standard electrocardiogram (ECG) for P wave dispersion (Pd), and signal-averaged ECG (SAECG) for P wave duration (SAPWD). RESULTS: SVAs were detected in 9 patients with AS (32%) and 3 controls (10%; p =0.02). Mean SAPWD (115.7±28.6 ms vs. 100.2 ± 18.7 ms, p =0.017) and mean Pd (11.9±4.8 ms vs. 9.3±3.6 ms, 0.023) was longer in patients with AS than the control group. When patient with AS were divided into 2 subgroups as patients with or without SVA, the Pd (16.2±5.0 vs. 9.9±3.2, p =0.001), SAPWD (151.4±7.8 vs. 98.7±16.1, p =0.001) and Bath ankylosing spondylitis disease activity index (BASDAI) (5.1±1.6 vs. 3.7±1.0, p =0.014) were significantly greater in the subgroup with arrhythmias compared to the subgroup without arrhythmias. There was a moderate positive correlation between BASDAI and SAPWD (r=0.622, p =0.001). There was also a moderate positive correlation between BASDAI and Pd (r=0.479, p =0.01). CONCLUSIONS: SVA were detected more frequently in AS than control group. SAPWD and Pd were prolonged in patients with AS. Clinical severity assessed with BASDAI had a positive correlation with prolongation of SAPWD and Pd.

Comparative Effects of CT Imaging Measurement on RECIST End Points and Tumor Growth Kinetics Modeling.

Quantitative assessments of tumor burden and modeling of longitudinal growth could improve phase II oncology trials. To identify obstacles to wider use of quantitative measures we obtained recorded linear tumor measurements from three published lung cancer trials. Model-based parameters of tumor burden change were estimated and compared with similarly sized samples from separate trials. Time-to-tumor growth (TTG) was computed from measurements recorded on case report forms and a second radiologist blinded to the form data. Response Evaluation Criteria in Solid Tumors (RECIST)-based progression-free survival (PFS) measures were perfectly concordant between the original forms data and the blinded radiologist re-evaluation (intraclass correlation coefficient = 1), but these routine interrater differences in the identification and measurement of target lesions were associated with an average 18-week delay (range, -20 to 55 weeks) in TTG (intraclass correlation coefficient = 0.32). To exploit computational metrics for improving statistical power in small clinical trials will require increased precision of tumor burden assessments.

DW-MRI of liver lesions: can a single ADC-value represent the entire lesion?

AIM: To evaluate whether focal liver lesions (FLLs) exhibit a homogeneous appearance on apparent diffusion coefficient (ADC) maps and whether there is inter-section variation in the calculated ADC values of FLLs (inter-section range). MATERIALS AND METHODS: Eighty-eight patients with 128 FLLs (70 benign, 58 malignant) who underwent abdominal magnetic resonance imaging (MRI) including diffusion-weighted (DW)-MRI were included. Two observers evaluated variation of signal intensity of each FLL within each ADC map image (intra-section) and among different ADC map images through the lesion (inter-section). ADC values of each FLL and neighbouring liver parenchyma were measured on all sections. The inter-section range of FLLs was compared with the neighbouring liver parenchyma. RESULTS: Intra-section inhomogeneity was noted in 39.8% (97/244 sections) and 38.9% (95/244) of benign lesions, and 61% (114/187 sections) and 61.5% (115/187) of malignant lesions, by observer 1 and observer 2, respectively. Inter-section inhomogeneity was noted in 25.7% (18/70) and 27.1% (19/70) of benign lesions, and 51.7% (30/58) and 50% (29/58) of malignant lesions, by observer 1 and observer 2, respectively. The inter-section range for both benign (0.28 × 10(-3) mm(2)/s) and malignant (0.25 × 10(-3) mm(2)/s) FLLs were significantly greater than that of liver parenchyma surrounding benign (0.16 × 10(-3) mm(2)/s, p < 0.001) and malignant (0.14 × 10(-3) mm(2)/s, p = 0.01) FLLs. CONCLUSION: Due to intra-/inter-section variations in ADC values of benign and malignant FLLs, a single ADC value may not reliably represent the entire lesion.

Evaluation of cardiac autonomic functions in patients with systemic lupus erythematosus.

BACKGROUND: Cardiovascular involvement is one of the leading causes of death among patients with systemic lupus erythematosus (SLE). In this study, we aimed to investigate cardiac autonomic functions in SLE patients. METHODS: We enrolled 36 patients (25 female; mean age 34.2 ± 10.2 years) with SLE and 32 healthy subjects (23 female; mean age 35.0 ± 10.3 years). All participants underwent 24-h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting first, second, and third-minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV), heart rate turbulence (HRT) and QT dispersion analysis. The mean SLE duration was 8.4 ± 4.0 years. RESULTS: According to the baseline demographic characteristics, both groups were similar with regard to age, gender, body mass index and left ventricular ejection fraction. Mean HRR1 (32.6 ± 10.9 vs. 42.5 ± 6.5, p = 0.038), HRR2 (51.0 ± 16.9 vs. 61.0 ± 10.8, p = 0.01) and HRR3 (52.8 ± 17.5 vs. 65.8 ± 9.8, p < 0.001) values were significantly higher in control group. When HRV was considered, SDNN, SDANN, RMSSD, PNN50 and high frequency (HF) component were significantly decreased in patients with SLE compared with healthy controls, but low frequency (LF) component and LF/HF were significantly higher in SLE patients. In addition, HRT onset and HRT slope values were significantly less negative in SLE patients. QT dispersion was significantly greater in SLE patients than healthy subjects (81.3 ± 15.8 vs. 53.2 ± 13.1, p < 0.001). CONCLUSION: Our study results suggest that cardiac autonomic functions are impaired in SLE patients despite the absence of overt cardiac involvement and symptoms. Further studies are needed to elucidate the prognostic significance and clinical implications of impaired autonomic functions in patients with SLE.

Visualization of dual coronary artery fistulae drainage to the right ventricle by transthoracic echocardiography.

Coronary artery fistula is a rare abnormality of coronary circulation. It is mostly congenital but acquired forms can also occur. Fistulae are usually asymptomatic and can sometimes be visualized during cardiac imaging such as transthoracic echocardiogram, cardiac magnetic resonance imaging, coronary computed tomography angiography and coronary angiography.

The association between serum uric acid level and coronary artery disease.

OBJECTIVE: This study was designed to determine the relationship between serum uric acid level and the presence and severity of coronary artery disease (CAD). METHODS: A total of 1012 patients who underwent coronary angiography were included in this study. All patients were assessed for the presence of cardiovascular risk factors and ongoing medications. Serum uric acid and creatinine level, as well as a fasting lipid profile and fasting blood glucose, were measured in all patients before the procedure. The severity of CAD was assessed by the Gensini score. RESULTS: Of 1012 patients (mean age, 59.4 +/- 10.24 years), 680 were men (mean age, 58.7 +/- 10.5 years) and 332 were women (mean age, 61.0 +/- 9.51 years). Of the study patients, 703 (69%) were hypertensive, 292 (28.9%) were diabetic (DM), 304 (30%) had a smoking history, 306 (30%) had low high-density lipoprotein cholesterol levels and 350 (34%) had hypertriglyceridaemia. CAD was present in 689 (68%) patients who were assessed by coronary angiography. One-, two- and three-vessel disease was detected in 32.6%, 32.5% and 34.9% of the patients respectively; left main coronary artery lesion was detected in 15% of the patients. A statistically significant difference in the mean uric acid concentrations was found between the patients with or without CAD [380 +/- 121 micromol/l (6.39 +/- 2.04 mg/dl) vs. 323.5 +/- 83.2 micromol/l (5.44 +/- 1.40 mg/dl) p < 0.001]. Based on logistic regression analysis, the increased serum uric acid level was found to be associated with the presence of CAD in both men and women (p < 0.001). The increased serum uric acid level was also found to be associated with the severity of CAD in both men and women based on multivariate linear regression analysis (p < 0.001). CONCLUSION: In conclusion, serum uric acid level was found to be associated with the presence and severity of CAD.

The role of MR cholangiopancreatography in the evaluation of pregnant patients with acute pancreaticobiliary disease.

This study aimed to determine the usefulness of MR cholangiopancreatography (MRCP) in the evaluation of pregnant patients with acute pancreaticobiliary disease and its additional value over ultrasound. MRI studies of pregnant patients who were referred because of acute pancreaticobiliary disease were included. MR images and patient charts were reviewed retrospectively to determine clinical outcome and the results of other imaging studies. 18 pregnant patients underwent MRCP because of right upper quadrant pain (n = 6), pancreatitis (n = 9), cholangitis (n = 1) or jaundice (n = 2). 15 patients were also evaluated with ultrasound. Biliary dilatation was detected in eight patients by ultrasound, but the cause of biliary dilatation could not be determined by ultrasound in seven patients. MRCP demonstrated the aetiology in four of these patients (choledocholithiasis (n = 1), Mirizzi syndrome (n = 1), choledochal cyst (n = 1) and intrahepatic biliary stones (n = 1)) and excluded obstructive pathology in the other four patients. MRCP was unremarkable in the seven patients who had no biliary dilatation on ultrasound. Three patients underwent only MRCP; two had choledocholithiasis and one cholelithiasis and pancreatitis. Choledocholithiasis diagnosed with MRCP (n = 3) was confirmed by endoscopic retrograde cholangiopancreatography. Mirizzi syndrome (n = 1) and a choledochal cyst (n = 1) were confirmed by surgery. The patients with normal MRCP (n = 12) and one patient with intrahepatic stones improved with medical treatment. MRCP appears to be a valuable and safe technique for the evaluation of pregnant patients with acute pancreaticobiliary disease. Especially when ultrasound shows biliary dilatation, MRCP can determine the aetiology and save the patient from unnecessary endoscopic retrograde cholangiopancreatography by excluding a biliary pathology.

Advanced age is associated with endothelial dysfunction in healthy elderly subjects.

BACKGROUND: Aging is associated with an increased risk for atherosclerosis in which endothelial dysfunction is an early marker. OBJECTIVE: The purpose of this study was to determine if endothelial function is altered with increasing age in healthy subjects. METHOD: The study population consisted of 30 elderly and 36 younger subjects free from major cardiovascular risk factors. Transthoracic echocardiography was performed for each subject to rule out structural heart disease. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery via ultrasound. RESULTS: Baseline characteristics of the elderly and the younger group were similar, except for age (mean age: 71.3 +/- 5.8 vs. 26.5 +/- 7.2). Transthoracic echocardiography was normal in all subjects. FMD of the elderly group was significantly lower than the younger group (7.9 +/- 3.1 in the elderly, 10.8 +/- 1.9 in the younger group, p < 0.001). A negative relationship was found between FMD and age (r = -0.528, p < 0.001). CONCLUSION: It can be concluded that endothelial function detected by FMD declines with increasing age in healthy human subjects. Advanced age is a predictor of impaired endothelial function.

Determining the relationship between metabolic syndrome score and angiographic severity of coronary artery disease.

BACKGROUND: Cardiovascular disease is leading cause of mortality and morbidity in developed and developing countries. Metabolic syndrome (MS) is a risk factor for coronary artery disease (CAD). The effect of MS on angiographic severity of CAD is not well defined. The aim of this study was to examine the effect of MS on angiographic severity of CAD by using Gensini score. METHODS: The total number of 1003 patients who underwent elective coronary angiography in catheter laboratory were included in the study. MS score based on National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria which ranged between zero and five were calculated for each subject. Gensini scores were determined by examining coronary angiograms of the patients. RESULTS: The study population consisted of 634 (63%) male, and 369 (37%) female subjects. The mean age was 59 +/- 11. MS based on NCEP ATP III was present in 246 (25%) patients. CAD was present in 691 patients (69%). The median of Gensini score was five (0-192) in the total sample, 18 (1-192) in the patients with CAD and 25 (0-192) in the patients with MS. A positive correlation was found between MS score and Gensini score (r = 0.402, p < 0.001). CONCLUSIONS: In this study, it was determined that as the severity of MS increases, the angiographic severity of CAD increases as well. Besides, the most important factor on Gensini score was diabetes mellitus in male and hypertension in female subjects.