Kotaro Sumii

Prediction of short- and intermediate-term prognoses of patients with acute myocardial infarction using myocardial contrast echocardiography one day after recanalization

OBJECTIVES This study sought to determine whether microvascular integrity in the risk area (RA) for myocardial infarction (MI) one day after recanalization predicts the outcome in patients with first acute MI. BACKGROUND Immediately after recanalization, microcirculation in the RA is modified by both hyperemic response and microvascular impairment. METHODS Fifty consecutive patients who underwent serial myocardial contrast echocardiography before and one day after recanalization (day 2) were studied. All patients had a completely occluded lesion in the left anterior descending coronary artery alone, and underwent successful reperfusion therapy. The relative size of the initial RA (RA ratio) and peak gray scale ratio (PGSR) within the RA on day 2 were determined. Patients were followed for a median of 22 months to evaluate clinical outcome. RESULTS On day 2, PGSR was a median of 0.46. Study patients were subdivided into two groups, group A of 24 patients with acceptable opacification (PGSR > 0.46 on day 2) and group B of 26 patients without it. Major cardiac events (cardiac death, nonfatal MI and repeat admission for congestive heart failure) were more frequently observed in group B (28% vs. 4%, Cox hazard ratio=8.5, p=0.05, 95% confidence interval [CI] 1.03 to 69.9). The median value of the RA ratio was 0.45. Patients (n=15) with RA ratio > 0.45 on day 1 and PGSR on day 2 < or = 0.46 exhibited a 10.7-fold relative risk for major cardiac events (p=0.005, 95% CI 2.06 to 55.8) and a 3.69-fold relative risk for composite cardiac events (major cardiac events and target lesion revascularizations) after the initial intervention (p=0.004, 95% CI 1.51 to 9.04). CONCLUSIONS The assessment of both the size of the initial RA and microvascular integrity on day 2 enables precise determination of the efficacy of reperfusion therapy and prediction of the short- and intermediate-term prognoses of patients with recanalized MI.

Optimal time for predicting myocardial viability after successful primary angioplasty in acute myocardial infarction : A study using myocardial contrast echocardiography

This study sought to elucidate serial changes in microvascular integrity during papaverine-induced hyperemia in the risk area for myocardial infarction. In addition, we attempted to determine the optimal time for predicting myocardial viability. Seventy-two patients who underwent serial myocardial contrast echocardiography (MCE) before and shortly after (day 1), 1 day (day 2), and 3 weeks (day 21) after recanalization were studied. In 18 of 72 patients, MCE was performed at baseline and during hyperemia using selective intracoronary infusion of papaverine. Both the peak grayscale ratio (PGSR) within the risk area, and the no- and low-reflow ratio (LR ratio) were analyzed in each stage. Left ventricular regional wall motion (RWM) was determined 6 months after recanalization. The correlation coefficient between PGSR with papaverine on day 1 and that on day 2 was 0.54 (p = 0.02); it was 0.50 (p = 0.04) between day 1 and day 21, and 0.82 (p = 0.001) between day 2 and day 21. On day 1, the correlation coefficient between the LR ratio with papaverine and RWM was 0.60 (p = 0.02), which changed to 0.72 (p = 0.003) on day 2 and 0.54 (p = 0.04) on day 21, respectively. The best time to predict viable myocardium was established on day 2 by receiver operating characteristics curves. ST-segment re-elevation, elapsed time from onset to recanalization, and antecedent angina pectoris were independent factors for PGSR on day 2 using stepwise and multiple linear regression analysis. This study suggests that the optimal time to estimate microvascular integrity for predicting myocardial viability might be 1 day after recanalization, which is neither shortly after recanalization nor during the convalescent stage.

Influence of type 2 diabetes mellitus on cardiovascular disease mortality: findings from the Hawaii-Los Angeles-Hiroshima study.

The present study addressed whether diabetes mellitus was a strong risk factor for cardiovascular disease (CVD) death. Between 1976 and 1984, 927 (404 men) Japanese-Americans in Hawaii aged 40-79 years participated at baseline examination including a 75 g oral glucose tolerance test. Diabetes was defined as fasting serum glucose >or=140 mg/dl, 2 h postload glucose >or=180 mg/dl, or the use of drugs for diabetes. Causes of death were classified by ICD-9 codes on the reports from the Hawaii State Public Health Bureau. Until 1994, 178 individuals suffered death; 81 were attributed to CVD and 43 to coronary heart disease (CHD). The age-adjusted and coronary risk factors-adjusted relative risks for CHD and CVD mortality were significant for diabetes both in men and women. The impact of diabetes on CHD mortality was greater for women. However, no gender difference in the contribution of diabetes to fatal CVD was observed. Serum fasting glucose levels tended to be associated with CHD death and were associated with CVD death in diabetic subjects. In conclusion, diabetes is a strong independent risk factor for CVD mortality in Japanese-American men and women. Hyperglycemia is associated with CVD mortality in diabetic subjects.

Influence of angiotensinogen M253T gene polymorphism and an angiotensin converting enzyme inhibitor on restenosis after percutaneous coronary intervention.

We studied the relation between renin-angiotensin system (RAS) related gene polymorphisms, such as angiotensin converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M253T and angiotensin II type 1 receptor (AT1R) A1166C, and the effect of quinapril, an ACE inhibitor with high tissue-binding affinity, on preventing restenosis after percutaneous coronary intervention (PCI). A total of 253 patients successfully treated for coronary artery disease were randomly assigned to quinapril or control. Of the 215 patients who completed the follow-up, we determined gene polymorphisms in 204 patients with 241 lesions who provided blood samples for genotype determination. In the control, the ACE D homozygotes showed a smaller minimal lumen diameter (MLD) at follow-up (P=0.063). The other two genotypes of AGT and AT1R did not affect restenosis after PCI. According to quinapril treatment, the AGT T homozygotes significantly showed a beneficial effect of quinapril on MLD (P=0.013) and late lumen loss (P=0.013). The ACE I homozygotes also exhibited beneficial effects of quinapril on larger MLD (P=0.065). The AT1R genotype did not influence the quinapril effect. In conclusion, the AGT T homozygotes might benefit from effects of quinapril on preventing restenosis after PCI.

Quinapril with High Affinity to Tissue Angiotensin-Converting Enzyme Reduces Restenosis after Percutaneous Transcatheter Coronary Intervention

Experimental studies have demonstrated that vascular injury resulted in an induction of vascular angiotensin-converting enzyme (ACE), and have suggested that inhibition of vascular ACE might be important in the prevention of restenosis. The present study aimed to determine the effect of quinapril, an ACE inhibitor with high affinity to tissue ACE, on restenosis following coronary intervention. The design of this study was a prospective, randomized, open, and non-placebo controlled trial. Patients with ischemic heart disease were enrolled after successful percutaneous transluminal coronary angioplasty or stent implantation at 7 participating institutions. Two hundred and fifty-three patients with 294 lesions were randomly assigned to the quinapril (10–20 mg per day) group or control group. Administration of quinapril was continued for 3–6 months of the follow-up. Quantitative coronary angiography was performed before and after angioplasty and at follow-up. Core laboratory measurements were performed independently and blinded. Follow-up angiography was performed in 108 patients with 124 lesions in the quinapril group and in 107 patients with 130 lesions in the control group. The baseline characteristics and findings of angioplasty showed no significant differences between the two groups. However, in the quinapril group, restenosis per patient and per lesion was significantly lower (34.3% vs. 47.7%, p < 0.05 and 30.6% vs. 43.8%, p < 0.05). Multivariable analysis revealed that administration of quinapril independently contributed to reducing the restenosis per patient and per lesion (odds ratio, 0.73; 95% confidence interval, 0.54–0.99 and odds ratio, 0.75; 95% confidence interval, 0.57–0.99). In conclusion, quinapril significantly reduces restenosis following coronary intervention.

Characteristics of two slow inactivation mechanisms and their influence on the sodium channel activity of frog ventricular myocytes

Abstract Inactivation of the fast Na+ current of heart muscle occurs in two kinetically distinct phases: a fast process operating on a millisecond time scale and a considerably slower process, the kinetic properties of which have not been explored fully. In this study, we analysed the slow inactivation process in isolated frog ventricular myocytes using the whole-cell variation of the patch-clamp method. Slow inactivation of the Na+ current followed a double-exponential time course, corresponding to slow and ultraslow components of Na+ channel inactivation. The individual time constants were 2–7 s (slow component) and 40–560 s (ultraslow component). Recovery from these slow inactivation processes also followed a double-exponential time course, but was characterized by significantly briefer time constants than those for the inactivation process. The relationship between transmembrane potential and steady-state slow or ultraslow inactivation was well described by the Boltzmann equation. The membrane potential at which half the Na+ channels are inactivated (V1/2) and the slope factor were estimated to be –48.1 and 13.6 mV, respectively, for the slow component alone. Under conditions in which the slow and ultraslow inactivation components were both present, these parameters were –53.1 and 8.7 mV respectively. When the fast and the two slow inactivation processes occurred concomitantly, the resultant steady-state inactivation curves were shifted to more negative potentials and the slope factor was decreased. Treatment with 1 mM Cd2+ externally did not affect the time course of slow inactivation, but produced a 3–7 mV depolarizing shift in its steady-state voltage dependency by virtue of cadmium’s known effect on the cell surface potential. This study has thus identified two components of slow Na+ inactivation in heart muscle, operating on a time scale of seconds (slow inactivation) and minutes (ultraslow inactivation).

Effect of N-feruloyl tyramine (an analogue of tyramine) on inwardly rectifying potassium channel in frog ventricular myocytes

Electrophysiological effects of N-feruloyl tyramine (NFT), an analogue of tyramine, on potassium currents in frog ventricular myocytes were examined using single-channel recording and whole-cell voltage clamp technique. Extracellular application of NFT induced a concentration-dependent decrease of macroscopic inward rectifier potassium current (iK1) with ID50 of 198 microM, while tyramine (100 microM) was ineffective in producing an inhibitory effect on iK1. NFT reduced the mean open time of iK1 to 1.3 ms from 3.1 ms in control without affecting the amplitude of single-channel conductance. It is indicated that boi containing NFT produces a prolongation of the plateau phase caused by the suppression of inwardly rectifying K channel. Thus, this prolongation may induce an increase in the inflow of Ca ions, which in turn leads to a positive inotropic effect.