Fumihiko Miyake's research while affiliated with St. Marianna University School of Medicine and other places

Purpose Contrast medium (CM) induces tubular hypoxia via endothelial damage due to direct cytotoxicity or viscosity. Urinary liver-type fatty acid binding protein (L-FABP) increases along with tubular hypoxia and may be a detector of systemic circulation injury. The aim of this study was to evaluate the clinical usefulness of detecting increases in urinary L-FABP levels due to administration of CM, as a prognostic biomarker for cardiovascular disease in patients without occurrence of CM-induced nephropathy undergoing cardiac catheterization procedure (CCP). Methods Retrospective longitudinal analyses of the relationship between urinary L-FABP levels and occurrence of cardiovascular events were performed (n=29). Urinary L-FABP was measured by ELISA before CCP, and at 6, 12, 24, and 48 hours after CCP. Results Urinary L-FABP levels were significantly higher at 12 hours (P<0.05) and 24 hours (P<0.005) after CCP compared with before CCP, only in the patients with occurrence of cardiovascular events (n=17), but not in those without cardiovascular events (n=12). The parameter with the largest area under the curve (0.816) for predicting the occurrence of cardiovascular events was the change in urinary L-FABP at 24 hours after CCP. The difference in urinary L-FABP levels (ΔL-FABP ≥11.0 μg/g creatinine) between before CCP and at 24 hours after CCP was a risk factor for the occurrence of cardiovascular events (hazard ratio, 4.93; 95% confidence interval, 1.27–19.13; P=0.021). Conclusion Measurement of urinary L-FABP before CCP and at 24 hours after CCP in patients with mild to moderate renal dysfunction may be an important indicator for risk stratification of onset of cardiovascular events.

Treatment of congestive heart failure (CHF) with loop diuretics, such as furosemide, may be associated with complications, including worsening renal function and metabolic or electrolyte disturbances. Coadministration of tolvaptan, a selective vasopressin V2 receptor antagonist, can ameliorate such adverse events by reducing the required dose of loop diuretics; however, the safety of tolvaptan in patients with reduced renal function is not known. As a result, we conducted an exploratory clinical trial of tolvaptan in 22 patients with CHF and advanced chronic kidney disease (CKD). We classified these patients into three groups according to their estimated glomerular filtration rate, namely, CKD stages G3b, G4, and G5. Patients were coadministered tolvaptan 15 mg once daily for 7 days after single administration of furosemide. We assessed patients' hemodynamic parameters, serum chemistry values, and body fluid status during the study. On day 8, serum sodium and potassium concentrations were significantly higher than baseline values in the G3b (p = 0.020) and G5 groups (p = 0.037), respectively. Although serum urea nitrogen and creatinine concentrations increased significantly in the G4 group (p = 0.017 and p = 0.012, respectively), no patient in any of the three groups showed decreased renal function on days 2 and 3. In addition, no significant changes in serum uric acid, blood pressure, or heart rate were observed in any patient in this study. In this short-term pilot study, coadministration of tolvaptan and furosemide appears to be safe in patients with heart failure and CKD.

Accurate assessment of disease severity is critical for appropriate treatment of patients with aortic stenosis (AS). This study investigated the influence of aortic-valve morphology on the determination of anatomical aortic-valve area (AVA) in patients with AS. This prospective study included 126 patients with AS who underwent transoesophageal echocardiography (TEE). Aortic-valve area was measured using (i) planimetric two-dimensional (2D) TEE, (ii) volumetric three-dimensional (3D) TEE, and (iii) the continuity equation (CE) obtained with transthoracic echocardiography. Of these, 20 patients also underwent contrast-enhanced multidetector computed tomography (MDCT). Aortic-valve area was measured from multiplanar reconstruction of the MDCT images. Of the 126 patients, 20 (15.9%) were diagnosed with bicuspid AS and 106 were diagnosed with tricuspid AS. There was an excellent correlation between AVAADCT and AVA3DTEE (r = 0.83, P < 0.001) and a somewhat lower correlation between AVAADCT and AVA2DTEE (r = 0.63, P = 0.006). In the tricuspid AS group, both AVA2DTEE and AVA3DTEE significantly correlated with AVACE (r = 0.63, mean difference 0.13 ± 0.24 cm(2), and r = 0.83, mean difference 0.03 ± 0.12 cm(2), respectively, both P < 0.001). In contrast, in the bicuspid AS group, AVA3DTEE significantly correlated with AVACE (r = 0.83, mean difference 0.10 ± 0.18 cm(2), P < 0.001), whereas AVA2DTEE did not (r = 0.42, mean difference 0.48 ± 0.32 cm(2), P = 0.066). Aortic-valve morphology influenced the assessment of anatomical AVA in patients with AS, and 3D TEE is useful for assessing anatomical AVA regardless of aortic-valve morphology. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Background and objectives: The pharmacokinetics and pharmacodynamics of tolvaptan (7.5 or 15 mg/day) in combination with furosemide have been investigated in heart failure (HF) patients with normal kidney function but not in HF patients with advanced kidney dysfunction. This study evaluated the efficacy of tolvaptan in HF patients with advanced kidney dysfunction (estimated glomerular filtration rate <45 mL/min/1.73 m(2)) by conducting a pharmacokinetic and pharmacodynamic study in these patients. Methods: Tolvaptan (15 mg once daily) was administered orally for 7 days in combination with furosemide (40-200 mg). Results: The peak plasma tolvaptan concentration and area under the plasma concentration-time curve were 379.41 ± 149.69 ng/mL and 4,657.38 ± 2,741.79 ng·h/mL, respectively, in HF patients with advanced kidney dysfunction. These values were greater in HF patients with advanced kidney dysfunction than values reported in the literature for healthy subjects and HF patients with normal kidney function. Urine volume increased and body weight decreased significantly compared with those before tolvaptan administration in HF patients with advanced kidney dysfunction. Conclusion: This study showed that adding tolvaptan to furosemide was effective in HF patients with advanced kidney dysfunction. This study also suggests that in these patients 15 mg/day of tolvaptan should be sufficient, and increasing the dose or the frequency of dosing to overcome diuretic resistance should not be necessary, and consideration should be given to using a lower dose and/or prolonging the dosing interval.

The aim of this study was to determine the diagnostic accuracy of early/delayed (123)I-β-methyl-iodophenyl pentadecanoic acid ((123)I-BMIPP) planar images to detect disrupted fatty acid metabolism in patients with vasospastic angina (VSA). Heart-to-mediastinum (H/M) ratios and washout rates were calculated from early and late (15 minutes and 4 hours after tracer injection, respectively) planar (123)I-BMIPP images from 13 hypertensive control individuals (mean age, 69.5 years) and 37 patients with VSA (mean age, 62.8 years) 10.5 (mean) days after administering the intracoronary acetylcholine provocation test. Patients with VSA had significantly lower early H/M and delayed H/M ratios (early; 2.2 ± 0.3 versus 2.7 ± 0.5, P = 0.007; delayed: 1.8 ± 0.3 versus 2.4 ± 0.4, P < 0.001) and significantly greater washout rates (39.8 ± 11.8% versus 29.3 ± 11.7%, P = 0.011) than controls. The overall area under the curve defi ning the accuracy of diagnostic performance was 0.76 (95% confidence interval (CI): 0.59-0.92) and 0.85 (95% CI, 0.73-0.98) for the early and delayed H/M ratios and 0.74 (95% CI, 0.73-0.90) for washout rates. Planar (123)I-BMIPP imaging can diagnose coronary artery spasm with acceptable diagnostic performance and indicates that the delayed H/M ratio has a powerful ability to assess recent ischemia. This technique might be useful in the face of apparently normal coronary angiographic fi ndings during the subacute and chronic phases after ischemic events.

The following three case reports present the effects of 6-month continuous positive airway pressure (CPAP) therapy on blood pressure (BP) in severe obstructive sleep apnea patients with resistant hypertension. Case 1 A 58-year-old woman exhibited a decreased 24-hour BP and changes in the nocturnal BP dipping pattern from non-dipper to dipper. Case 2 A 64-year-old man showed no improvements in nocturnal BP. Case 3 A 78-year-old man with ischemic cardiomyopathy exhibited changes in the nocturnal BP dipping pattern from non-dipper to dipper. These results suggest that 6-month CPAP therapy improves the nocturnal BP dipping status in some patients with obstructive sleep apnea and resistant hypertension.

Stentless coronary angioplasty, plain old balloon angioplasty (POBA) using a Lacrosse® non-slip element (NSE), was performed in 4 patients (aged 60 to 79 years old, 2 males and 2 females) who were diagnosed with having acute coronary infarction (AMI). The all culprit lesions were located in the left circumflex artery and successfully reperfused by emergent percutaneous coronary intervention using a Lacrosse® non slip element (NSE) 2.0 mm/ 2.25 mm/2.5 mm. Cardiac enzymes were peaked in the early phase; no complications were found after PCI. The follow-up assessment using coronary angiography and optical coherence tomography performed about 2 weeks later showed the large dissection in 1 patient, resulting in the stent deployment. The remaining 3 patients required no stent implantation because the elements placed along the outside of Lacrosse® NSE ensured successful deliverability with shallow cuts and uniform expansion in the culprits. Here, we report the usefulness of POBA using a Lacrosse® NSE in AMI with small vessel desese.

Background: Adenosine-sensitive reentrant atrial tachycardia (AT) originating from vicinity of the atrioventricular (AV) node and inside of the triangle of Koch was previously demonstrated. However, limited information is available on an AT with similar properties from the AV annulus. Objectives: The purpose of this study was to examine and compare ATs originating from the AV annulus and the atrial septum in electrophysiologic characteristics, pharmacological response and efficacy of radiofrequency ablation. Methods: In consecutive 21 patients with an AT that terminated with adenosine or verapamil intravenously given, the electrophysiological study and catheter ablation were performed. Results: In all patients, a targeted AT was inducible by atrial extrastimulation (AES) with an inverse relationship between the coupling and the post-pacing intervals. The mean tachycardia cycle length (TCL) was 396±49 ms. In 16 of 21 patients, the site of earliest activation was observed on the tricuspid annulus (annular AT). In the remaining 5 patients an AT occurred from the site in the triangle of Koch (septal AT). A single AES delivered from the site of earliest activation reset all ATs with an increasing or mixed pattern of response. Concealed entrainment was observed by rapid atrial pacing from the site of earliest activation for all ATs. These findings suggest that these ATs are due to reentry. Between the annular and septal AT, no significant difference was observed in the TCL, the percentage of the excitable gap to TCL, and other electrophysiologic characteristics. All ATs terminated by intravenous administration of verapamil (3.5±1.2 mg) and adenosine triphosphate (2.2±1.2 mg), indicating that a calcium channel–dependent substrate is involved in the AT circuit. ATs were successfully ablated at the atrial site of earliest activation in all patients. Conclusion: Adenosine-sensitive reentrant AT originates from either the AV annulus or the atrial septum. Both types of AT show similar electrophysiologic characteristics and response to catheter ablation.