Katsuharu Hatada

Thyroid hormone regulates mRNA expression and currents of ion channels in rat atrium.

Atrial fibrillation is one of the common arrhythmias associated with hyperthyroidism. This study examined the effects of thyroid hormone (T3) on mRNA expression and currents of major ionic channels determining the action potential duration (APD) in the rat atrium using the RNase protection assay and the whole-cell patch-clamp technique, respectively. T3 increased the Kv1.5 mRNA expression and decreased the L-type calcium channel mRNA expression, while the Kv4.2 mRNA expression did not change. APD was shorter in hyperthyroid than in euthyroid myocytes. The ultrarapid delayed rectifier potassium currents were remarkably increased in hyperthyroid than in euthyroid myocytes, whereas the transient outward potassium currents were unchanged. L-type calcium currents were decreased in hyperthyroid than in euthyroid myocytes. T3 shifted the current-voltage relationship for calcium currents negatively. In conclusion, T3 increased the outward currents and decreased the inward currents. The resultant changes of ionic currents shortened APD, providing a substrate for atrial fibrillation.

High-output heart failure caused by arteriovenous fistula long after nephrectomy

A 70-year-old Japanese woman was admitted to our hospital because of anasarca. At 32 years of age, she had undergone nephrectomy for renal tuberculosis. A continuous abdominal bruit was heard. The chest X-ray showed cardiomegaly and dilatation of the pulmonary artery. Abdominal three-dimensional computed tomography scanning clearly revealed an arteriovenous fistula. Cardiac catheterization disclosed cardiac output of 9.2 l/min and a step-up of oxygen saturation at the renal vein level of the inferior vena cava. Surgical closure of the fistula promptly decreased her cardiac output and improved the heart failure. This is a rare case of an arteriovenous fistula developing long after nephrectomy and causing high-output heart failure.

Genomic and Non-Genomic Regulation of L-Type Calcium Channels in Rat Ventricle by Thyroid Hormone

Hyperthyroidism is associated with low exercise tolerance despite high cardiac output and sometimes with the development of heart failure. L-type calcium channels may play a role in the mechanism, but this has not been fully understood. We examined the effects of thyroid hormone on gene expression and function of L-type calcium channels in rat ventricles by the ribonuclease protection assay and whole-cell patch-clamp technique, respectively. The effects of bisoprolol, beta-blocking agent, on the regulation of calcium channel by thyroid hormone was also studied. In hyperthyroid animals, the mRNA of the calcium channel alpha1c subunit was reduced on day 4, compared with that in euthyroid animals, and remained low on day 8. Bisoprolol did not affect the thyroid hormone mediated decrease in alpha1c subunit mRNA. While L-type calcium current was greater in hyperthyroid than euthyroid myocytes on day 4, it was smaller on day 8. In addition, the isoproterenol-induced increase in calcium current in euthyroid rats was attenuated in hyperthyroid rats. Acetylcholine decreased calcium current in hyperthyroid myocytes, but not in euthyroid myocytes. In conclusion, L-type calcium current was increased by thyroid hormone in rat ventricular myocytes by the activation of the adenylate cyclase cascade, despite a decreased calcium channel gene expression. These genomic and non-genomic modifications may play an important role in the association of high cardiac output with low exercise tolerance, and in the development of heart failure in hyperthyroidism.

Clinical characteristics of hemodialysis patients with atrial fibrillation: The RAKUEN (Registry of atrial fibrillation in chronic kidney disease under hemodialysis from Niigata) study

BACKGROUND Clinical characteristics, management, and outcomes in hemodialysis patients with atrial fibrillation (AF) remain unclear. METHODS AND RESULTS We studied 423 Japanese patients undergoing maintenance hemodialysis (age 65.2±12.4 years, male 70%, mean duration of hemodialysis 139±124 months). AF was present in 19% (n=82) and was independently related to increased age (odds ratio 1.070, 95% confidence interval 1.043-1.098), longer hemodialysis duration (odds ratio 1.006, 95% confidence interval 1.004-1.008), and congestive heart failure (odds ratio 2.749, 95% confidence interval 1.546-4.891). During observations lasting a mean of 36 months, the incidences of all-cause death, cardiovascular death, and major bleeding, in particular gastrointestinal bleeding, were significantly higher in the AF (n=82) than the non-AF (n=341) patients (p<0.001, p=0.004, p=0.002, p=0.027, respectively), but the incidence of ischemic stroke/systemic embolism was similar in the AF and non-AF patients. AF was independently associated with all-cause death (hazard ratio 1.728, 95% confidence interval 1.123-2.660) and major bleeding (hazard ratio 1.984, 95% confidence interval 1.010-3.896). Warfarin was prescribed in 33% of the AF patients, but the rates of all-cause death, ischemic stroke, and major bleeding during the study period were not significantly different between warfarin (n=27) and non-warfarin (n=55) groups. CONCLUSIONS In our hemodialysis patients, AF was a common comorbidity and was independently associated with all-cause death and major bleeding, but not with increased risk of ischemic stroke.

Comparison of clinical outcomes of coronary artery stent implantation in patients with end-stage chronic kidney disease including hemodialysis for three everolimus eluting (EES) stent designs: Bioresorbable polymer-EES, platinum chromium-EES, and cobalt c

BACKGROUNDS New-generation bioresorbable polymer-everolimus eluting stents (BP-EES) are available. This study aimed to compare the clinical outcomes for BP-EES compared to more established stent designs, namely the platinum chromium-EES (PtCr-EES) and cobalt chrome-EES(CoCr-EES) in patients with the end-stage chronic kidney disease (CKD) including hemodialysis (HD). METHODS One-hundred-forty-one consecutive stents (BP-EES [n = 44], PtCr-EES [n = 45], and CoCr-EES [n = 52]) were implanted in 104 patients with CKD. All patients underwent a follow-up coronary angiography at 12 months after implantation. End-stage CKD was defined as an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 , or the need for HD. The following outcome variables were compared among the three stent groups after implantation and the 12-month follow-up: target lesion revascularization (TLR), stent thrombosis (ST), and major adverse cardiac event (MACE). Minimal stent diameter (MSD) and %diameter-stenosis (%DS) were measured using quantitative coronary angiography. RESULTS The overall rate of TLR and MACE was 14.6% and 30.8%, respectively, with no incidence of ST. Immediately after implantation, the MSD (P = 0.22) and %DS (P = 0.42) were equivalent among the three groups. However, at the 12-month follow-up, a tendency towards higher TLR was observed for the BP-EES group (22.7%) compared with the PtCr-EES (8.8%) and CoCr-EES (9.6%) groups (P = 0.07). Late loss in lumen diameter was also significantly greater for the BP-EES (0.51 ± 0.64 mm) group than either the PtCr-EES (0.20 ± 0.61 mm) and CoCr-EES (0.25 ± 0.70 mm) groups (P = 0.03). CONCLUSIONS BP-EES might increase the risk of in-stent restenosis in patients with end-stage of CKD or the need for HD.

Atrial Fibrillation had Less Impact on the Risk of Ischemic Stroke in Non-anticoagulated Patients Undergoing Hemodialysis: Insight from the RAKUEN study

Objective The progress of non-anticoagulated patients with atrial fibrillation (AF) undergoing hemodialysis has not been determined. Using data from the RAKUEN (Registry of Atrial fibrillation in chronic Kidney disease Under hEmodialysis from Niigata) study, we examined the clinical characteristics and outcomes among hemodialysis patients with AF who were not receiving a vitamin K antagonist (VKA). Methods and Results Forty-three of 423 patients undergoing hemodialysis (-10%) were prescribed a VKA. The remaining 380 patients (age 64.8±12.8 years, male 70%) were enrolled in the present study. During a mean observation period of 36 months, AF (n=55) was independently associated with all-cause death (hazard ratio, 1.82; 95% confidence interval, 1.12-2.94; p=0.014), but was not associated with ischemic stroke (hazard ratio, 1.91; 95% confidence interval, 0.74-4.92; p=0.177) and major bleeding (hazard ratio, 1.80; 95% confidence interval, 0.80-4.08; p=0.150). The crude incidence rates of all-cause death and ischemic stroke in the AF patients were 15.75 (2.5-fold higher compared to the non-AF patients) and 3.63 (1.7-fold higher compared to the non-AF patients) per 100 person-years, respectively. Conclusion A great impact on death, but not ischemic stroke, was observed in non-anticoagulated hemodialysis patients with AF in comparison to those without AF from the analysis of the RAKUEN study.

Multiple bilateral coronary-biventricular fistulas with elevated left ventricular end-diastolic pressure

Arterioventricular fistulas are relatively rare abnormalities and the etiology may be congenital or traumatic. We report a case of a 51-year-old woman in which all three coronary arteries emptied into both ventricles via multiple small fistulas resulting in elevated left ventricular end-diastolic pressure.