Toshimitsu Kosaka

Adaptive servo-ventilation therapy improves cardiac sympathetic nerve activity in patients with heart failure.

This study investigated whether abnormal cardiac sympathetic nerve activity (SNA) is associated with the severity of central sleep apnoea (CSA) and whether adaptive servo‐ventilation (ASV) therapy can improve cardiac SNA in heart failure (HF) patients with predominant CSA.

Comparison of anti-inflammatory effects and high-density lipoprotein cholesterol levels between therapy with quadruple-dose rosuvastatin and rosuvastatin combined with ezetimibe

BackgroundStatins are frequently administered to reduce low-density lipoprotein cholesterol (LDL-C) and vascular inflammation, because LDL-C and high sensitive C-reactive protein (hs-CRP) are associated with high risk for cardiovascular events. When statins do not reduce LDL-C to desired levels in high-risk patients with coronary artery disease (CAD), ezetimibe can be added or the statin dose can be increased. However, which strategy is more effective for treating patients with CAD has not been established. The present study compares anti-inflammatory effects and lipid profiles in patients with CAD and similar LDL-C levels who were treated by increasing the statin dose or by adding ezetimibe to the original rosuvastatin dose to determine the optimal treatment for such patients.Methods46 patients with high-risk CAD and LDL-C and hs-CRP levels of >70 mg/dL and >1.0 mg/L, respectively, that were not improved by 4 weeks of rosuvastatin (2.5 mg/day) were randomly assigned to receive 10 mg (R10, n = 24) of rosuvastatin or 2.5 mg/day of rosuvastatin combined with 10 mg/day of ezetimibe (R2.5/E10, n = 22) for 12 weeks. The primary endpoint was a change in hs-CRP.ResultsBaseline characteristics did not significantly differ between the groups. At 12 weeks, LDL-C and inflammatory markers (hs-CRP, interleukin-6, tumour necrosis factor-alpha and pentraxin 3) also did not significantly differ between the two groups (LDL-C: R10 vs. R2.5/E10: -19.4 ± 14.2 vs. -22.4 ± 14.3 mg/dL). However, high-density lipoprotein cholesterol (HDL-C) was significantly improved in the R10, compared with R2.5/E10 group (4.6 ± 5.9 vs. 0.0 ± 6.7 mg/dL; p < 0.05).ConclusionBoth enhanced therapies exerted similar anti-inflammatory effects under an equal LDL-C reduction in patients with high-risk CAD despite 2.5 mg/day of rosuvastatin. However, R10 elevated HDL-C more effectively than R2.5/E10.Trial registrationUMIN000003746

Cardioprotective effect of an L/N-type calcium channel blocker in patients with hypertensive heart disease.

BACKGROUND Left ventricular (LV) diastolic dysfunction is related to increased cardiac sympathetic activity. We investigated the effect of cilnidipine, an L/N-type calcium channel blocker, on LV diastolic function and cardiac sympathetic activity in patients with hypertensive heart disease (HHD) using radionuclide myocardial imaging. METHODS AND RESULTS Thirty-two frame electrocardiography (ECG) -gated (99m)Tc-sestamibi (MIBI) myocardial single photon emission computed tomography (SPECT), and (123)I-metaiodobenzylguanidine (MIBG) imaging were performed before and 6 months after drug administration in 32 outpatients with HHD. Sixteen of the patients were treated with cilnidipine and the other 16 were treated with nifedipine retard. The parameters for assessing LV diastolic function evaluated using ECG-gated (99m)Tc-MIBI SPECT were peak filling rate (PFR), first-third filling rate (1/3FR), and time to peak filling (TPF). Cardiac sympathetic activity was assessed as early and delayed heart to mediastinum (H/M) ratios and a washout rate (WR), using (123)I-MIBG imaging. The PFR and 1/3FR significantly increased after 6 months of treatment with cilnidipine (p<0.05 for both), but did not with nifedipine retard. The H/M ratios significantly increased (p<0.05 for both) in conjunction with a decreased WR (p<0.05) in the cilnidipine group. Moreover, a significant positive correlation was seen between the rate of change in PFR and the rate of change in early and delayed H/M ratios in the cilnidipine group (p<0.05 for both). The same results were obtained for the relationship between the rate of change in 1/3FR and the rate of change in H/M ratios (p<0.05 for both). However, no such relationship was seen in the nifedipine group. CONCLUSION These data indicate that cilnidipine seems to suppress cardiac sympathetic overactivity via blockade of N-type calcium channels and improves LV diastolic function in patients with HHD.

The Prevalence of Apical Wall Motion Abnormalities in Patients with Long-Term Right Ventricular Apical Pacing

BACKGROUND Long-term right ventricular apical pacing (RVAP) can lead to adverse clinical outcomes. Although left ventricular (LV) dyssynchrony is the major causative factor, other potential mechanisms are not fully understood. We sought to clarify whether RVAP elicits apical wall motion abnormalities that contribute to LV contractile dysfunction. METHODS We studied annual echocardiographic data over a 5-year period after pacemaker implantation (PMI) for 74 patients who underwent RVAP. The patients were divided into two groups according to the percentage of ventricular pacing: right ventricular (RV) pacing < 50% and RV pacing ≥ 50%. We assessed LV ejection fraction, LV end-diastolic volume, and left atrial dimension. To assess regional wall motion abnormalities, the wall motion score index was calculated. RESULTS LV wall motion abnormality was observed in 64% of the subjects and was more pronounced in apical segments than in other segments. At 2 years after PMI, brain natriuretic peptide levels were significantly higher in the group with RV pacing ≥ 50% than in the group with RV pacing < 50%. The subjects with RV pacing ≥ 50% had higher LV end-diastolic dimension and lower ejection fraction at 3 years after PMI. CONCLUSION Long-term RVAP elicits apical wall motion abnormalities that could in part contribute to LV contractile dysfunction.

Candesartan improves impaired endothelial function in the human coronary artery.

BackgroundEndothelial dysfunction is closely related to cardiovascular events. Several studies have documented that angiotensin II type 1 receptor blockers (ARB) improve peripheral endothelial dysfunction. However, the effect of ARB on coronary endothelial function remains elusive. The purpose of this study was to ascertain the beneficial effects of ARB on human coronary artery endothelial function. Methods and ResultsTwenty-seven patients were randomly assigned to either the candesartan group (n=14) or the control group (n=13) and followed for 12 months. Coronary blood flow velocity was measured in the left anterior descending artery without stenosis using an intracoronary Doppler-tipped guide-wire. We evaluated coronary endothelial function as the coronary blood flow velocity reserve (CFR), which was defined as the percent change in the coronary blood flow velocity after an intracoronary acetylcholine infusion. At baseline, the CFR in both groups was below 300%, implying that these patients had endothelial dysfunction. After treatment with candesartan for 6 months, the CFR increased significantly from 199±20 to 337±27% (P<0.001), whereas the CFR did not change in the control group (194±32 vs. 185±41%, P=0.52). During 12 months of observation, the cardiovascular event-free survival rate of the patients with an increased CFR was significantly greater than the rate in patients with a decreased CFR (P=0.02). Moreover, the cardiovascular event-free survival rate was greater in the candesartan group than in the control group (P=0.04). ConclusionOur results suggest that candesartan improves coronary endothelial dysfunction of human coronary arteries and may prevent cardiac events.

Position-Dependent Right-to-Left Shunt Causing a Brain Abscess

A 50-year-old man suffering from generalized convulsions and right quadrantic hemianopia was admitted to the hospital. Contrast-enhanced magnetic resonance imaging showed an enhanced ring in the left parieto-occipital lobe, suggesting a brain abscess (Figure 1). The patient underwent an immediate craniotomy and drainage. Culture of pus yielded α-hemolytic streptococci. Brain abscesses are often caused by hematogenous spread of bacteria from a primary source. Although much effort was expended seeking the primary infection, the origin of the brain abscess in this patient remained unclear. After almost complete relief of his neurological symptoms, the patient was referred for further diagnostic workup in our hospital. Chest contrast-enhanced computed tomography in the arterial phase revealed an anomalous vessel bridging from …

P-350 Double Transgenic Mice Crossing Alpha MyHC-mCherry-LC3 Mice with CAG-GFP-LC3 Mice is a New Method to Analyze Autophagy in Cardiomyocytes

P-350 Double Transgenic Mice Crossing Alpha MyHC-mCherry-LC3 Mice with CAG-GFP-LC3 Mice is a New Method to Analyze Autophagy in Cardiomyocytes Mai Terada, Kiyoshi Nobori, Yoshiko Munehisa, Manabu Kakizaki, Takayoshi Ohba, Takashi Koyama, Yoichiro Takahashi, Masaru Ishida, Kenji Iino, Toshimitsu Kosaka, Hiroyuki Watanabe, Hitoshi Hasegawa, Hiroshi Ito. Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Akita University School of Medicine, Japan