Transcatheter cryo-ablation of septal accessory pathways, multicenter observational study in Japan.

BACKGROUND: Ablation using radiofrequency energy has to be carefully performed when the arrhythmia substrate is located in close proximity to the atrioventricular (AV) node due to the risk of inadvertent permanent AV block. The aim of this study was to evaluate the efficacy and safety of catheter-based cryo-therapy for septal accessory pathways (APs). METHODS: A total of eleven patients (median = 56.3 years, range 13-74 years) with septal APs underwent cryoablation. Ice-mapping was performed during sinus rhythm and an AV reciprocating tachycardia utilizing the APs as a requisite limb with cooling of the catheter tip temperature to a maximum of -30℃ for less than 45 s. Cryo-ablation was performed for 4 min at a temperature of -80℃ only if ice-mapping abolished the pre-excitation or retrograde conduction over the AP without injury to the AV nodal conduction. RESULTS: Cryo-ablation was acutely successful in all eleven patients. No permanent cryo-related complications or adverse outcomes were reported. During the follow-up (range 14-26 months), no patients experienced any arrhythmia recurrences. CONCLUSION: Ice-mapping was a feasible and reliable method to determine the exact location of the APs owing to the possibility of validating the ablation site. Cryo-ablation of APs located near the AV junction is a safe and efficacious technique with a high success rate over the long term. IRB INFORMATION: Ethical Committee of Japan Red Cross Yokohama City Bay Hospital #2018-19.

Author Correction: Randomized Evaluation of Anagliptin vs Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) Trial: A 52-week, open-label, randomized clinical trial.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Randomized Evaluation of Anagliptin vs Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) Trial: A 52-week, open-label, randomized clinical trial.

Additional reductions in low-density lipoprotein-cholesterol (LDL-C) via antidiabetic therapies should be considered in statin-using patients with sub-optimal LDL-C levels. We compared the efficacy of anagliptin and sitagliptin, two antidiabetic therapies, in reducing LDL-C in type 2 diabetic patients. A randomized, open-label, parallel-group trial was conducted at 17 centres in Japan between April 2015 and January 2018. Adults (age ≥20 years) with type 2 diabetes, any atherosclerotic vascular lesions, and statin prescriptions were included. Anagliptin or sitagliptin were administered for 52 weeks. Primary and secondary endpoints were changes in LDL-C and haemoglobin A1C (HbA1c) levels, respectively. We assessed the superiority (primary endpoint) and non-inferiority (secondary endpoint) of anagliptin over sitagliptin. This study was registered at Clinicaltrials.gov (NCT02330406). Of 380 participants, 353 were eligible and randomized. Mean participant age was 68 years, and 61% were males. Baseline median LDL-C and HbA1c were 108 mg/dL and 6.9%, respectively. Changes in LDL-C were -3.7 mg/dL with anagliptin and +2.1 mg/dL with sitagliptin at 52 weeks, and the estimated treatment difference was a significant -4.5 mg/dL (P = 0.01 for superiority). Changes in HbA1c were +0.02% with anagliptin and +0.12% with sitagliptin (P < 0.0001 for non-inferiority). Overall, anagliptin was superior to sitagliptin in lowering LDL-C without deteriorating HbA1c.

Respiratory Collapse of the Inferior Vena Cava Reflects Volume Shift and Subsequent Fluid Refill in Acute Heart Failure Syndrome.

BACKGROUND: Fluid redistribution rather than fluid accumulation plays an important role in the development of acute heart failure (HF) syndrome. Patients with fluid redistribution develop acute HF without prominent volume overload. We investigated volume status by measuring the diameter of the inferior vena cava (IVC) and examining variations in hemoglobin and hematocrit. METHODS AND RESULTS: Seventy-four consecutive patients admitted for acute HF syndrome were analyzed. Blood tests and measurement of IVC diameter after stabilization of respiratory distress were performed on admission and were repeated after 24 h. IVC collapsibility index (IVC-CI) was calculated as (maximum IVC-minimum IVC)/maximum IVC. According to the initial IVC-CI, the patients were divided into the collapse group (IVC-CI ≥0.5: n=34) and the non-collapse group (IVC-CI <0.5: n=40). Initial blood pressure was higher in the collapse group (P<0.001). Although 24-h urine volume did not differ between the groups, hemoglobin (P<0.001) and hematocrit (P<0.001) decreased significantly in the collapse group but not in the non-collapse group after 24 h. Furthermore, IVC-CI significantly decreased in the collapse group after 24 h (P=0.003). CONCLUSIONS: In acute HF syndrome, IVC-CI ≥0.5 on admission suggests a volume shift from the central vein into the pulmonary vasculature. Fluid refill occurs within 24 h after admission. This observation could be helpful in selecting strategies for diuretic use. (Circ J 2016; 80: 1171-1177).

Eicosapentaenoic Acid supplementation changes Fatty Acid composition and corrects endothelial dysfunction in hyperlipidemic patients.

We investigated the effects of purified eicosapentaenoic acid (EPA) on vascular endothelial function and free fatty acid composition in Japanese hyperlipidemic subjects. In subjects with hyperlipidemia (total cholesterol ≥220 mg/dL and/or triglycerides ≥150 mg/dL), lipid profile and forearm blood flow (FBF) during reactive hyperemia were determined before and 3 months after supplementation with 1800 mg/day EPA. Peak FBF during reactive hyperemia was lower in the hyperlipidemic group than the normolipidemic group. EPA supplementation did not change serum levels of total, HDL, or LDL cholesterol, apolipoproteins, remnant-like particle (RLP) cholesterol, RLP triglycerides, or malondialdehyde-modified LDL cholesterol. EPA supplementation did not change total free fatty acid levels in serum, but changed the fatty acid composition, with increased EPA and decreased linoleic acid, γ-linolenic acid, and dihomo-γ-linolenic acid. EPA supplementation recovered peak FBF after 3 months. Peak FBF recovery was correlated positively with EPA and EPA/arachidonic acid levels and correlated inversely with dihomo-γ-linolenic acid. EPA supplementation restores endothelium-dependent vasodilatation in hyperlipidemic patients despite having no effect on serum cholesterol and triglyceride patterns. These results suggest that EPA supplementation may improve vascular function at least partly via changes in fatty acid composition.

Impaired glucose tolerance, but not impaired fasting glucose, underlies left ventricular diastolic dysfunction.

OBJECTIVE: Glucose intolerance is recognized as a predictor of congestive heart failure (CHF). However, the association of postprandial hyperglycemia or fasting hyperglycemia with CHF has not been clarified. We determined the impact of the total spectrum of glucose abnormalities on left ventricular (LV) geometry and diastolic function. RESEARCH DESIGN AND METHODS: Two hundred and eighty-seven Japanese subjects who visited the university hospital to be checked for glucose intolerance or known type 2 diabetes were consecutively recruited. Participants underwent an oral glucose tolerance test if they had no history of diabetes, and LV geometry and LV systolic and diastolic function were analyzed by Doppler echocardiography. RESULTS: The frequency of LV diastolic dysfunction in subjects with normal glucose tolerance, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), newly detected diabetes, and known diabetes were 13, 22, 50, 51, and 61%, respectively (χ(2) = 54.2, P < 0.0001). IGT was a predictor for LV diastolic dysfunction after adjusting for age, sex, systolic blood pressure, and heart rate (odds ratio 3.43 [95% CI 1.09-11.2]), but IFG was not (0.49 [0.06-3.08]). IGT was a predictor after adjusting for established CHF risk factors but was no longer significant after adjusting for BMI and homeostasis model assessment of insulin resistance. CONCLUSIONS: In this hospital-based registry of subjects without CHF, the prevalence of LV diastolic dysfunction was higher in subjects with IGT but not in those with IFG. Results suggest that IGT, as well as newly detected and known diabetes, could be linked to an increased risk of cardiovascular events, partly through LV diastolic dysfunction.

Fluvastatin improves endothelial dysfunction in overweight postmenopausal women through small dense low-density lipoprotein reduction.

Small dense low-density lipoprotein (sdLDL), which are often associated with obesity, are considered as the most atherogenic and have been shown to impair endothelial function. It is not known whether reduction of sdLDL by pharmacological intervention can improve endothelial function. Thirty-four consecutive postmenopausal women with >/=5.70 mmol/L total cholesterol were placed into either an overweight (body mass index [BMI] >/= 25.0, n = 22) or a normal-weight (BMI < 25.0, n = 12) group, and forearm blood flow (FBF) was measured using strain-gauge plethysmography during reactive hyperemia before and after fluvastatin treatment. At baseline, the peak FBF during reactive hyperemia in the overweight group was less than that in the normal-weight group (mean +/- SD, 13.6 +/- 4.4 v 22.2 +/- 4.0 mL/min/100 mL, P <.01). The maximal FBF after nitroglycerin was similar in both groups. In the stepwise multiple regression analysis, only the concentration of sdLDL was the predictor for peak FBF (standard coefficient = -0.517, P =.0115). The nonsignificant parameters for the correlations in the model were age, BMI, systolic blood pressure, the homeostasis model assessment of insulin resistance (HOMA-IR), hemoglobin A(1c) (HbA(1c)), and LDL-cholesterol. Fluvastatin treatment was associated with the recovery of the peak FBF in the overweight group but it did not influence that of the normal-weight group. Changes in sdLDL fractions by fluvastatin correlated well with the peak FBF recovery. These results suggested that an increased sdLDL was linked to endothelial dysfunction in overweight postmenopausal women and fluvastatin treatment improved endothelial dysfunction by decreasing the atherogenic sdLDL fraction in this population.

Hypoadiponectinemia is closely linked to endothelial dysfunction in man.

Vascular endothelial dysfunction has been demonstrated in overweight or obese patients, but the molecular basis for this link has not been clarified. We asked what the relationship was between adiponectin, an adipose-specific molecule, and endothelial function. Forearm blood flow (FBF) was measured during reactive hyperemia by using strain-gauge plethysmography in 76 Japanese subjects without a history of cardiovascular or cerebrovascular disease, diabetes mellitus, hepatic, or renal disease. The peak FBF and total reactive hyperemic flow [flow debt repayment (FDR)] during reactive hyperemia were correlated with waist circumference (r = -0.418 and -0.414, respectively) and body mass index (r = -0.597 and -0.626, respectively). After correcting for age, gender, and body mass index, the peak FBF was correlated with systolic blood pressure (r = -0.294; P = 0.010), free fatty acid (FFA) (r = -0.331; P = 0.004), and adiponectin in log 10 (r = 0.492; P < 0.001), and FDR was correlated with adiponectin in log 10 (r = 0.462; P = 0.001). In stepwise multiple regression analyses, predictive variables for peak FBF were adiponectin in log 10 (r = 0.468) and FFA (r = -0.292; r(2) = 0.487; P < 0.0001); and predictive variables for FDR were adiponectin in log 10 (r = 0.474) and FFA (r = -0.275; r(2) = 0.346, P < 0.0001). Endothelial function was impaired in proportion to the severity of obesity, and the level of severity was closely related to plasma adiponectin levels. Adiponectin may play a protective role against the atherosclerotic vascular change, and loss of effects enhances endothelial dysfunction, as in obese people.