Honin Kanaya

Intermediate-density lipoprotein and cholesterol-rich very low density lipoprotein in angiographically determined coronary artery disease.

The relationship between the concentrations of intermediate-density lipoprotein (IDL) and other lipoproteins and the extent of coronary artery disease (CAD) was studied in 182 consecutive patients evaluated by selective coronary cineangiography. On univariate analysis, the extent of CAD correlated significantly and positively with very low density lipoprotein (VLDL) cholesterol, IDL cholesterol and lowdensity lipoprotein (LDL) cholesterol, and negatively with high-density lipoprotein (HDL) cholesterol. Analysis of four subgroups divided by IDL cholesterol and LDL cholesterol levels indicated that moderately increased levels of IDL cholesterol were closely associated with a high frequency of CAD. Moreover, multivariate regression analysis demonstrated that IDL cholesterol for men, LDL cholesterol for men and women and HDL cholesterol for men were significant variables of use in the final weighting procedure. IDL cholesterol was closely associated with cholesterol-rich VLDL. This study shows that IDL and cholesterol-rich VLDL combine to contribute to the development of CAD.

Probucol aggravates long QT syndrome associated with a novel missense mutation M124T in the N-terminus of HERG.

Patients with LQTS (long QT syndrome) with a mutation in a cardiac ion channel gene, leading to mild-to-moderate channel dysfunction, may manifest marked QT prolongation or torsade de pointes only upon an additional stressor. A 59-year-old woman had marked QT prolongation and repeated torsade de pointes 3 months after initiation of probucol, a cholesterol-lowering drug. We identified a single base substitution in the HERG gene by genetic analysis. This novel missense mutation is predicted to cause an amino acid substitution of Met(124)-->Thr (M124T) in the N-terminus. Three other relatives with this mutation also had QT prolongation and one of them had a prolonged QT interval and torsade de pointes accompanied by syncope after taking probucol. We expressed wild-type HERG and HERG with M124T in Xenopus oocytes and characterized the electrophysiological properties of these HERG channels and the action of probucol on the channels. Injection of the M124T mutant cRNA into Xenopus oocytes resulted in expression of functional channels with markedly smaller amplitude. In both HERG channels, probucol decreased the amplitude of the HERG tail current, decelerated the rate of channel activation, accelerated the rate of channel deactivation and shifted the reversal potential to a more positive value. The electrophysiological study indicated that QT lengthening and cardiac arrhythmia in the two present patients were due to inhibition of I(Kr) (rapidly activating delayed rectifier K(+) current) by probucol, in addition to the significant suppression of HERG current in HERG channels with the M124T mutation.

Intravascular ultrasound appearance of scattered necrotic core as an index for deterioration of coronary flow during intervention in acute coronary syndrome

In acute coronary syndrome (ACS) patients with deterioration of coronary flow during percutaneous coronary intervention (PCI), a scattered necrotic core pattern (SNC) is observed by intravascular ultrasound virtual histology (VH-IVUS). The purpose of this study was to evaluate the impact of SNC on deterioration of coronary flow during PCI in ACS. A total of 38 ACS patients were imaged using VH-IVUS before PCI. In addition to conventional definitions of thin-cap fibroatheroma by VH-IVUS (ID-TCFA), the SNC was defined as necrotic core foci with a maximum diameter of <14 pixels on a 400 × 400 VH-IVUS image in the presence of >50% plaque burden except in the ID-TCFA frame. Patients were divided into deterioration of coronary flow group (n = 15) and normal-reflow group (n = 23). The incidence of residual thrombus and plaque rupture, the external elastic membrane, plaque and fibrous volumes, the incidence of ID-TCFA and the average number of SNC per frame was significantly greater in deterioration of coronary flow group than in normal-reflow group (all parameters P < 0.05). Multivariate analysis revealed that the average number of SNC per frame was independently associated with deterioration of coronary flow in ACS patients (odds ratio 1.18, P < 0.05). In conclusion, an increased number of SNC is associated with deterioration of coronary flow during PCI in ACS patients.

A KCR1 variant implicated in susceptibility to the long QT syndrome.

The acquired long QT syndrome (aLQTS) is frequently associated with extrinsic and intrinsic risk factors including therapeutic agents that inadvertently inhibit the KCNH2 K(+) channel that underlies the repolarizing I(Kr) current in the heart. Previous reports demonstrated that K(+) channel regulator 1 (KCR1) diminishes KCNH2 drug sensitivity and may protect susceptible patients from developing aLQTS. Here, we describe a novel variant of KCR1 (E33D) isolated from a patient with ventricular fibrillation and significant QT prolongation. We recorded the KCNH2 current (I(KCNH2)) from CHO-K1 cells transfected with KCNH2 plus wild type (WT) or mutant KCR1 cDNA, using whole cell patch-clamp techniques and assessed the development of I(KCNH2) inhibition in response to well-characterized KCNH2 inhibitors. Unlike KCR1 WT, the E33D variant did not protect KCNH2 from the effects of class I antiarrhythmic drugs such as quinidine or class III antiarrhythmic drugs including dofetilide and sotalol. The remaining current of the KCNH2 WT+KCR1 E33D channel after 100 pulses in the presence of each drug was similar to that of KCNH2 alone. Simulated conditions of hypokalemia (1mM [K(+)](o)) produced no significant difference in the fraction of the current that was protected from dofetilide inhibition with KCR1 WT or E33D. The previously described α-glucosyltransferase activity of KCR1 was found to be compromised in KCR1 E33D in a yeast expression system. Our findings suggest that KCR1 genetic variations that diminish the ability of KCR1 to protect KCNH2 from inhibition by commonly used therapeutic agents constitute a risk factor for the aLQTS.

Impact of severe coronary disease associated or not associated with diabetes mellitus on outcome of interventional treatment using stents: results from HERZ (Heart Research Group of Kanazawa) analyses.

Percutaneous coronary intervention (PCI) using a drug-eluting stent (DES) leads to less re-stenosis than PCI using a bare metal stent (BMS), however there is still controversy whether use of a DES for severe coronary disease leads to an acceptable outcome in patients with diabetes mellitus (DM). In this study 8159 lesions were treated in 6739 patients (mean age 68.9 years) with coronary artery disease. Use of a DES significantly decreased the re-stenosis rate compared with BMS in both DM (9.6% versus 21.3%) and non-DM (9.5% versus 17.1%) patients. The re-stenosis rate was significantly higher in DM than in non-DM patients in the BMS group but not in the DES group. There was no statistically significant difference in event-free survival after stenting of patients with left main coronary artery (LMCA) disease between the BMS and DES groups. It was concluded that, compared with BMS, DES reduced re-stenosis in patients with DM, however, we advise careful treatment after using DES for severe coronary disease, including LMCA lesions, in patients with DM.

Impact of Distal Protection with Filter-Type Device on Long-term Outcome after Percutaneous Coronary Intervention for Acute Myocardial Infarction: Clinical Results with Filtrap(®).

Aim: Although distal embolization during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) deteriorates cardiac function, whether distal protection (DP) can improve prognosis is still controversial. We investigated whether a filter-type DP device, Filtrap®, could improve long-term outcomes after PCI for AMI. Method: We studied 164 patients (130 men, mean age: 65.7 years) who underwent PCI. Patients were divided into two groups based on the use of Filtrap®. The occurrence of congestive heart failure (CHF) and major adverse cardiac events (MACE) defined as cardiac death, recurrent AMI, and target vessel revascularization were compared. Result: Between DP (n = 53, 41 men, mean age: 65.5 years) and non-DP (n = 111, 89 men, mean age: 65.8 years) groups, although there was significantly greater plaque area in the DP group than in the non-DP group, there were no significant differences in coronary reperfusion flow after PCI. Interestingly, patients with CHF in the non-DP group exhibited a higher CK level than those in the DP group. During a 2-year follow-up period, cumulative CHF was significantly lower in the DP group than in the non-DP group (log-rank p = 0.018), and there was no significant difference in the MACE rate (log-rank p = 0.238). The use of DP device could not predict MACE, but could predict CHF by multivariate analysis (odds ratio = 0.099, 95% CI: 0.02–0.42, p = 0.005). Conclusion: These results demonstrate that favorable clinical outcomes could be achieved by the filter-type DP device in AMI, particularly in patients with CHF.

Spontaneous healing of posttraumatic focal coronary aneurysm: A case report

We report on the spontaneous healing of a posttraumatic focal coronary aneurysm in a previously healthy 61-year-old man after his involvement in a motor vehicle accident, resulting in blunt chest trauma that injured the anterior wall of his left ventricle. Left-sided cardiac catheterization and selective coronary angiography 1 month after the accident showed an aneurysm in the proximal part of the left anterior descending artery, and normal coronary arteries otherwise. Intravascular ultrasound revealed that the lesion was a pseudoaneurysm protruding toward the myocardium. Surgical removal of the aneurysm was not considered, and the patient was discharged after 2 months of uneventful hospitalization. Follow-up coronary angiography and intravascular ultrasound at 3 months and 1 year after the accident showed a total regression of the aneurysm. The patient has remained asymptomatic, with no residual ischemia 3 years after the accident. This case indicates that careful conservative treatment is a therapeutic option for posttraumatic coronary pseudoaneurysms.

A suspective case of coronary spasm associated with anaphylactic shock.

症例は52歳男性.鰯の刺し身を食した後下痢,嘔吐,発疹出現.さらに胸痛とともにショックとなり救急入院.心電図上II, III, aVFで一過性のST上昇が認められた.冠動脈造影上,有意狭窄を認めなかったが,エルゴノビン負荷により右冠動脈に冠〓縮が認められた.本例は食物アレルギーによるアナフィラキシーショックに伴い冠〓縮をきたした症例と考えられた.

A case of mumps myocarditis associated with coronary artery involvements

症例は26才男性で,急性左心不全で入院した.心電図は心室内伝導傷害と前側壁心筋梗塞の所見を示した. CPKは最高10470IUに上昇し, LDHは6620IUに上昇した.入院第51病日に心臓カテーテル検査を施行した.左室造影では心筋収縮能はび漫性に低下していた.選択的冠動脈造影では左冠動脈主幹部に長さ1.6cmの辺縁が平滑な50%の狭窄を認めた.また,前下行枝に長さ2.8cmにわたり冠動脈内陰影欠損を認めた.血中ウイルス学的検査でムンプスウイルス抗体価が有意に変動した.発症1年後の右室心内膜心筋生検から心筋炎と診断した.以上より,冠動脈病変を呈したムンプスウイルス心筋炎と診断し,冠動脈病変の病因として冠動脈炎が考えられた.