Hiroyuki Kurogane

Stromelysin promoter 5A/6A polymorphism is associated with acute myocardial infarction.

BACKGROUND Rupture of the fibrous cap of an atherosclerotic plaque is a key event that predisposes to acute myocardial infarction (AMI). Matrix metalloproteinases (MMPs) may contribute to weakening of the cap, which favors rupture. Stromelysin, a member of MMP family, is identified extensively in human coronary atherosclerotic lesions. It can degrade most of the constituents of extracellular matrix as well as activating other MMPs, which suggests that it may play an important role in plaque rupture. Recently, a common variant (5A/6A) in the promoter of the stromelysin gene has been identified. The 5A/6A polymorphism could regulate the transcription of the stromelysin gene in an allele-specific manner. METHODS AND RESULTS To investigate the relation between the 5A/6A polymorphism in the promoter of the stromelysin gene and AMI, we conducted a case-control study of 330 AMI patients and 330 control subjects. The prevalence of the 5A/6A+5A/5A genotype was significantly more frequent in the patients with AMI than in control subjects (48.8% vs 32.7%, P<0.0001). In logistic regression models, the odds ratio of the 5A/6A+5A/5A was 2.25 (95% CI, 1.51 to 3.35). The association of 5A/6A polymorphism with AMI was statistically significant and independent of other risk factors. CONCLUSIONS The 5A/6A polymorphism in the promoter of the stromelysin gene is a novel pathogenetic risk factor for AMI.

Impact of tranilast on restenosis after coronary angioplasty: Tranilast Restenosis Following Angioplasty Trial (TREAT)☆☆☆

BACKGROUND Tranilast is an antiallergic drug that suppresses the release of cytokines such as platelet-derived growth factor, transforming growth factor-beta1, and interleukin-1beta and prevents keloid formation after skin injury. Treatment with this drug reduced the restenosis rate after percutaneous transluminal coronary angioplasty in a preliminary study. METHODS AND RESULTS We conducted a multicenter, randomized, double-blind, placebo-controlled trial. A total of 255 patients with 289 lesions were randomly assigned to treatment with the oral administration of 600 mg/d tranilast, 300 mg/d tranilast, or a placebo for 3 months after successful angioplasty. Angiographic follow-up was done at 3 months, and a clinical follow-up examination was performed at 12 months. Two hundred ten (72.7%) lesions of 188 (73.7%) of the patients met the criteria and were eligible for the assessment of restenosis. The restenosis rates defined as >/=50% loss of the initial gain were 14.7% in the 600 mg/d tranilast group, 35.2% in the 300 mg/d tranilast group, and 46.5% in the placebo group (P <. 0001 for 600 mg/d tranilast vs placebo). The restenosis rates defined as percent diameter stenosis of >/=50% at follow-up were 17. 6% in the 600 mg/d tranilast group, 38.6% in the 300 mg/d tranilast group, and 39.4% in the placebo group (P =.005 for 600 mg/d tranilast vs placebo). CONCLUSIONS The oral administration of 600 mg/d of tranilast for 3 months markedly reduced the restenosis rate after percutaneous transluminal coronary angioplasty.

Effects of adjunctive balloon angioplasty after intravascular ultrasound-guided optimal directional coronary atherectomy: The result of adjunctive balloon angioplasty after coronary atherectomy study (ABACAS)☆

OBJECTIVES This study was conducted to evaluate: 1) the effect of adjunctive percutaneous transluminal coronary angioplasty (PTCA) after directional coronary atherectomy (DCA) compared with stand-alone DCA, and 2) the outcome of intravascular ultrasound (IVUS)-guided aggressive DCA. BACKGROUND It has been shown that optimal angiographic results after coronary interventions are associated with a lower incidence ofrestenosis. Adjunctive PTCA after DCA improves the acute angiographic outcome; however, long-term benefits of adjunctive PTCA have not been established. METHODS Out of 225 patients who underwent IVUS-guided DCA, angiographically optimal debulking was achieved in 214 patients, then theywere randomized to either no further treatment or to added PTCA. RESULTS Postprocedural quantitative angiographic analysis demonstrated an improved minimum luminal diameter (2.88 +/- 0.48 vs. 2.6 +/- 0.51 mm; p = 0.006) and a less residual stenosis (10.8% vs.15%; p = 0.009) in the adjunctive PTCA group. Quantitative ultrasound analysis showed a larger minimum luminal diameter (3.26 +/- 0.48 vs. 3.04 +/- 0.5 mm; p < 0.001) and lower residual plaque mass in the adjunctive PTCA group (42.6% vs. 45.6%; p < 0.001). Despite the improved acute findings in the adjunctive PTCA group, six-month angiographic and clinical results were not different. The restenosis rate (adjunctive PTCA 23.6%, DCA alone 19.6%; p = ns) and target lesion revascularization rate (20.6% vs. 15.2%; p = ns) did not differ between the groups. CONCLUSIONS With IVUS guidance, aggressive DCA can safely achieve optimal angiographic results with low residual plaque mass, and this was associated with a low restenosis rate. Although adjunctive PTCA after optimal DCA improved the acute quantitative coronary angiography and quantitative coronary ultrasonography outcomes, its benefit was not maintained at six months.

Sympathetic nervous system response to dynamic exercise in complete AV block patients treated with AV synchronous pacing with fixed AV delay or with auto-AV delay.

IGAWA, O., ET AL.: Sympathetic Nervous System Response to Dynamic Exercise in Complete AV Block Patients Treated with AV Synchronous Pacing with Fixed AV Delay or with Auto‐AV Delay. To investigate the sympathetic nervous system (SNS) responses and circulatory responses to exercise in eight patients (five male and three female) with complete atrioventricular block (CAVB) treated with atrio‐ventricular (AV) synchronous pacing, a symptom‐limited, multistaged treadmill stress test was performed, and plasma norepinephrine (NE) and circulatory parameters were measured at rest, at peak exercise, and in the recovery period. The eight patients were tested using the fixed AV interval (150 or 156 msec). Their exercise tolerance was generally poor. In all measured points, plasma NE levels were significantly higher in the eight study patients than those in the 12 normal subjects (eight male and four female). Systolic blood pressure (SBP) of CAVB patients elevated significantly after exercise compared to that at peak exercise. Heart rate (HR) responses of CAVB patients were characterized by their poor increase at peak exercise. These results suggest that some latent cardiac dysfunction continues in the CAVB patients however satisfactorily the AV synchronous pacing might perform. AV synchronous pacing with three different kinds of auto‐atrioventricular delay (auto‐AVD) was applied to three of the eight patients. In each AVD mode, a treadmill stress test was performed repeatedly according to the same protocol. Plasma NE concentrations under the condition with fixed AVD at peak exercise increased compared to those under the other two conditions with auto‐AVD. These findings suggest that AV synchronous pacing with auto‐AVD WQS better than that with fixed AVD during exercise. Plasma NE response to exercise seems to be a useful indicator for evaluating the condition of patients treated with DDD pacemakers and their adaptation for cardiac function.

Change of the new left ventricular function index (TEI INDEX) in acute myocardial infarction

It is well known that restrictive transmitral flow(TMF) pattern is predictive of higher cardiac mortality in patients(pts) with chronic heart failure(CHF). However, prognostic value of non-restrictive TMF pattem(NR) in pts with CHF is still unknown. We evaluated changes in left ventdcular(LV) filling with low dose dobutamine stress echocardiography(DSE) and assessed the prognostic significance of changes of LV filling in pts with CHF showing NR. Low dose (10mcg /kg/min) DSE was performed in 45 pts(36men, age 60+11 years) with CHF(35 pts with prior myocardial infarction, 10 with dilated cardiomyopathy) in NYHA class I1-111 with a mean LVEF of 40+13%. Pts were followed over 22+7 months for cardiac events. We measured peak velocities of eady(E) and late(A) diastolic TMF. Isovotumetdc relaxation time(IRT:msec) and deceleration time(DT:msec) of TMF were also measured. We obtained LV outflow time-velocity integrals(OTI) as an index of stroke volume. Then, we evaluated the relations between the changes(A) of these variables during DSE and cardiac events. Pts were subdivided into two groups who had cardiac events(CE:16pts) and had not(NCE:29pts)during followed period. In NCE, percent& IRT shortened significantly during DSE compared to that in CE (NCE:-25% vs CE:-2.4%, p<0.01).ADT,&A/E and AOTI did no~ differ between the two groups. Multivariate analysis showed thatA IRT was the only independent predictor of cardiac events (p<0.01). Conclusions: The shortening of IRT with dobutamine was significantly related to less cardiac event in pts with CHF, suggesting that preserved lusitropy might have favorable effects on the clinical outcome in pts with CHF. Assessment of LV diastolic property with DSE might be useful to predict the outcome in pts with mild to moderate CHF.

Increased 201Tl uptake by the chest wall following cardioversion.

A patient with acute inferior infarct is described who showed increased 201Tl uptake in the anterior chest wall following cardioversion which mimicked increased lung uptake of the tracer. The site of accumulation of 201Tl corresponded to that of 99mTc-pyrophosphate (PYP) and the right sided catheterization revealed almost normal hemodynamic data.