Hiroyuki Yamagishi

Physiologic assessment of coronary artery stenosis by coronary flow reserve measurements with transthoracic doppler echocardiography: comparison with exercise thallium-201 single-photon emission computed tomography

OBJECTIVES We evaluated the value of coronary flow reserve (CFR), as determined by transthoracic Doppler echocardiography (TTDE), for physiologic assessment of coronary artery stenosis severity, and we compared TTDE measurements with those obtained by exercise thallium-201 (Tl-201) single-photon emission computed tomography (SPECT). BACKGROUND Coronary flow reserve measurements by TTDE have been reported to be useful for assessing angiographic left anterior descending coronary artery (LAD) stenosis. However, discrepancies exist between angiographic and physiologic estimates of coronary lesion severity. METHODS We studied 36 patients suspected of having coronary artery disease. The flow velocity in the distal LAD was measured by TTDE both at rest and during intravenous infusion of adenosine. Coronary flow reserve was calculated as the ratio of hyperemic to basal peak (peak CFR) and mean (mean CFR) diastolic flow velocities. The CFR measurements by TTDE were compared with the results of Tl-201-SPECT. RESULTS Complete TTDE data were acquired for 33 of 36 study patients. Of these 33 patients, Tl-201-SPECT confirmed reversible perfusion defects in the LAD territories in 12 patients (group A). Twenty-one patients had normal perfusion in the LAD territories (group B). Peak CFR and mean CFR (mean value +/- SD) were 1.5 +/- 0.6 and 1.5 +/- 0.7 in group A and 2.8 +/- 0.8 and 2.7 +/- 0.7 in group B, respectively. Both peak and mean CFR < or = 2.0 predicted reversible perfusion defects, with a sensitivity and specificity of 92% and 90%, respectively. CONCLUSIONS Noninvasive measurement of CFR by TTDE provides data equivalent to those obtained by Tl-201-SPECT for physiologic estimation of the severity of LAD stenosis.

Cardioprotective effect of the angiotensin II type 1 receptor antagonist TCV-116 on ischemia-reperfusion injury

We investigated the protective effect of angiotensin II (Ang II) type 1 receptor antagonist on myocardial ischemia-reperfusion injury and the role of exogenous Ang II to this injury in perfused hearts. We orally administered TCV-116 (Ang II type 1 receptor antagonist) and delapril (angiotensin converting enzyme inhibitor) to Wistar rats for 1 week and measured the immunoreactive cardiac Ang II. Immunoreactive cardiac Ang II (pg/gm tissue) was 14.3 +/- 2.0 in control group, 11.8 +/- 0.8 in TCV-116-treated group, and 7.3 +/- 0.6 in delapril-treated group (p < 0.05 compared to TCV-116-treated group; p < 0.01 compared to control group). The 15 hearts (five rats in each group) were perfused by a langendorff method and global ischemia was maintained for 30 min. Both TCV-116 and delapril were found to improve postischemic cardiac function and decrease reperfusion creatine kinase (CK) release. Ang II injection before ischemia worsened postischemic cardiac function and increased reperfusion CK release. Only TCV-116 prevented this injury. These data indicated that TCV-116 Ang II type 1 receptor antagonist was effective against myocardial ischemia-reperfusion injury, and exogenous Ang II accelerated this injury through Ang II type 1 receptor.

Effects of Candesartan and Cilazapril on Rats With Myocardial Infarction Assessed by Echocardiography

The purpose of this study was to compare the angiotensin II type 1 receptor antagonist candesartan cilexitil (candesartan) and the angiotensin-converting enzyme inhibitor cilazapril on cardiac function, assessed by Doppler echocardiography and cardiac gene expression associated with cardiac remodeling, in rats with myocardial infarction. Candesartan or cilazapril was administered after myocardial infarction. At 1 and 4 weeks after myocardial infarction, cardiac function and mRNA expression in noninfarcted myocardium were analyzed. Candesartan and cilazapril equally prevented increases in hypertrophy in noninfarcted myocardium, left ventricular dilatation, and ejection fraction at 4 weeks. The E-wave/A-wave velocity ratio and the rate of E-wave deceleration, measures of diastolic function, increased to 9.2+/-0.6 and 26.3+/-2. 6 m/s2 at 1 week after myocardial infarction. Candesartan and cilazapril, administered at a dose of 1 mg/kg per day, prevented increases in E-wave/A-wave velocity ratio and E-wave deceleration at 1 and 4 weeks. Candesartan and cilazapril significantly suppressed increased mRNA expression of beta-myosin heavy chain, alpha-skeletal actin, and atrial natriuretic peptide in noninfarcted ventricle at 1 and 4 weeks and expression of collagen I and III at 4 weeks to a similar extent. When given at a dose of 10 mg/kg per day, both candesartan and cilazapril prevented cardiac dysfunction and gene expression to the same extent as when given at 1 mg/kg per day. In conclusion, Doppler echocardiography showed that candesartan and cilazapril equally improved systolic and diastolic function and that ventricular remodeling accompanied modulation of cardiac gene expression.

An angiotensin II receptor antagonist attenuates left ventricular dilatation after myocardial infarction in the hypertensive rat

OBJECTIVE The aims were (1) to investigate the effect of hypertention on left ventricular dilatation and haemodynamic alterations following acute myocardial infarction in spontaneously hypertensive rats (SHR) and normotensive rats (WKY); (2) to compare haemodynamic indices between the two groups; (3) to assess whether the angiotensin II type 1 receptor antagonist (AIIA), TCV-116, prevented left ventricular dilatation after myocardial infarction; and (4) to compare the effect of AIIA with that of the angiotensin converting enzyme (ACE) inhibitor, delapril. METHODS Myocardial infarction was produced in SHR and WKY by coronary artery ligation. Haemodynamic measurements were obtained three weeks later in rats that had been treated from the next day after the operation for three weeks with TCV-116 (1 mg.kg-1.d-1) or delapril (1 g.litre-1 in drinking water), and in untreated controls. RESULTS After myocardial infarction, left ventricular weight, and left ventricular weight were greater in SHR than in normotensive rats. Right ventricular weight, left ventricular end diastolic pressure, and LVEDVI correlated positively with infarct size in both SHR and WKY and these slopes were steeper in SHR than in WKY (P < 0.05). TCV-116 and delapril each significantly attenuated the increases in left ventricular end diastolic pressure, left ventricular weight, right ventricular weight, and LVEDVI following myocardial infarction in both in WKY and SHR, and shifted pressure-volume curve significantly to the left. CONCLUSIONS Hypertension accelerates left ventricular dilatation and haemodynamic alterations following myocardial infarction in rats. These effects are attenuated by an angiotensin II type 1 receptor antagonist as well as by an ACE inhibitor.

Exercise four hour redistribution thallium-201 single photon emission computed tomography and exercise induced ST segment elevation in detecting the viable myocardium in patients with acute myocardial infarction

Objective To investigate the specificity and sensitivity of the combination of redistribution in exercise thallium-201 single photon emission computed tomography (SPECT) and exercise induced ST elevation for detecting the viable myocardium in patients with acute myocardial infarction. Design 37 patients were studied within seven weeks of onset of Q wave myocardial infarction (anterior in 22, inferior in 15). All patients underwent exercise four hour redistribution thallium-201 SPECT and positron emission tomography using fluorine-18-fluorodeoxyglucose (FDG) and nitrogen-13 ammonia under fasting conditions. Results Sixteen patients showed exercise induced ST elevation ⩾ 1.5 mm, and 15 of these had increased FDG uptake in the infarct region. Eleven of 16 patients (10 of 11 patients with anterior infarctions) with irreversible thallium-201 defects and increased FDG uptake showed exercise induced ST elevation. The sensitivity, specificity, and predictive accuracy of redistribution, exercise induced ST segment elevation, or both for detecting increased FDG uptake were 82%, 75%, and 67% (94%, 75%, and 91% for anterior infarctions), respectively. Conclusions In patients with acute Q wave myocardial infarction, the combination of redistribution in exercise thallium-201 SPECT and exercise induced ST elevation can detect the viable myocardium in the infarct region with high sensitivity and specificity, especially in patients with anterior infarctions.

Detecting Viable Myocardium and Predicting Functional Improvement

Background Low-dose dobutamine stress echocardiography (LDDE) has become a useful and safe method for identifying hibernating or stunned myocardium and for predicting improvement in wall motion after coronary revascularization. Methods and Results In the present study, fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), rest-redistribution thallium-201 (201Tl) single-photon emission computed tomography (RR-Tl SPECT), 123I-15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid (BMIPP) and LDDE were performed in 30 patients with acute myocardial infarction (AMI) at 10±3 days after the onset of AMI. Also, exercise 201Tl reinjection SPECT (RI-Tl SPECT) was performed at 14±2 days. Follow-up echocardiography was performed 5±3 months later in all patients after interventional therapy for the assessment of functional recovery. Of the 390 segments analyzed by echocardiography, 110 (28%) had abnormal wall motion. There were no significant differences between RR-Tl SPECT and LDDE in sensitivity, specificity, positive predictive value and negative predictive value using the χ2-test; however, in akinetic segments, there was a significant difference in sensitivity. Among FDG-PET, RI-Tl SPECT, BMIPP and LDDE, there were significant differences in 3 variables. In akinetic segments, LDDE is superior to RR-Tl SPECT in sensitivity and to FDG-PET in specificity. In hypokinetic segments, LDDE is superior to RI-Tl SPECT and BMIPP in sensitivity, and to FDG-PET and BMIPP in specificity. Conclusions LDDE could detect functional recovery of viable myocardium in the early period of AMI and can be performed easily and safely. (Circ J 2004; 68: 950 - 957)

Freehand three-dimensional echocardiography with rotational scanning for measurements of left ventricular volume and ejection fraction in patients with coronary artery disease.

Background: Measurement of left ventricular (LV) volumes and ejection fraction (EF) is important in managing patients with coronary artery disease (CAD). Introduction of free‐hand three‐dimensional echocardiography (3DE) system which is equipped with small magnetic tracking system and average rotational geometry for LV volumes may provide easy and accurate quantification of LV systolic function in CAD patients. Purpose: To evaluate the feasibility and accuracy of LV volumes and EF measurement by free‐hand 3DE with rotational geometry in patients with CAD. Methods and Results: The study subjects consisted of consecutive 25 patients with CAD who were scheduled for quantitative gated single‐photon emission computed tomography (QGS). LV end‐diastolic volume (EDV), end‐systolic volume (ESV), and EF were determined by conventional two‐dimensional echocardiography (2DE), 3DE, and QGS. Three‐dimensional echocardiography data acquisition and analysis were possible in 22 of 25 subjects (feasibility 88%). In this 3DE system, image acquisition time was 2 minutes, and 5 minutes were needed for off‐line analysis of LV volumes and EF. Correlations and the limits of agreement between 3DE and QGS (r = 0.97, 0.0 ± 9.1 ml for EDV, r = 0.99, 0.0 ± 5.0 ml for ESV, and r = 0.97, 0.5 ± 3.3% for EF, respectively) were superior to those between 2DE and QGS (r = 0.85, 12.6 ± 26.8 ml for EDV, r = 0.85, 9.7 ± 26.1 ml for ESV, and r = 0.90, −1.3 ± 6.9% for EF, respectively). Inter‐ and intra‐observer variabilities of 3DE were smaller than that of 2DE (5% vs 10%, 5% vs 10% for EDV, 6% vs 13%, 5% vs 9% for ESV, and 4% vs 11%, 4% vs 6% for EF, respectively). Conclusion: Three‐dimensional echocardiography using magnetic tracking system and average rotational geometry offered a feasible and accurate method for quantification of LV volumes and EF in patients with CAD.

Dobutamine-stress electrocardiographically gated positron emission tomography for detection of viable but dysfunctional myocardium

PurposeThis study was performed to determine whether low-dose dobutamine stress electrocardiography (ECG)-gated fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) can assess wall motion and identify myocardium without contractile reserve despite preserved FDG uptake.MethodsFifty-three patients with myocardial infarction and normal sinus rhythm underwent ECG-gated FDG-PET and transthoracic echocardiography. Wall motion of 10 segments of the left ventricle was graded as normal, hypokinetic, or akinetic/dyskinetic.ResultsIn 365 (76%) of 480 segments, assessment of wall motion was concordant between the 2 modalities. In 30 patients dobutamine-stress ECG-gated FDG-PET was performed. In 13 (50%) of 26 dysfunctional segments with normal FDG uptake, 16 (36%) of 44 dysfunctional segments with mildly reduced FDG uptake and 12 (25%) of 48 dysfunctional segments with moderately reduced FDG uptake, wall motion was improved by dobutamine infusion.ConclusionAssessment of left ventricular wall motion with ECG-gated FDG-PET is feasible, and dobutamine stress ECG-gated FDG-PET can simultaneously identify metabolic viability and contractile reserve.

Endomyocardial biopsy findings in patients with atrioventricular block in the absence of apparent heart disease.

SummaryThe purpose of this study was to examine the histopathological findings of right ventricular endomyocardial biopsies from ten patients less than 60 years of age (47 ± 9.8 (mean ± SD) years) with documented atrioventricular block but without apparent heart disease. They underwent electrophysiological testing, echocardiography, coronary angiography, and right ventricular endomyocardial biopsy. Biopsy specimens were assessed for morphologic changes in myocyte diameter, fibrosis, disarray, and degeneration. Electrophysiological testing demonstrated atrioventricular nodal block in 2, intra-His bundle block in 2, and infra-His bundle block in 6 patients. Histology revealed evidence of myocardial fibrosis with either myocyte hypertrophy or disarray in 7 of the 10 patients. The results of electrophysiological testing did not correlate with the histopathological findings or severity. In one patient, heart failure appeared during the follow-up period. We conclude that patients with atrioventricular block of unknown etiology have histological abnormalities of the ventricular endomyocardium in addition to the conduction system disturbances. We consider such cases as constituting one of the disease groups of cardiomyopathy, and suggest that it is necessary to follow up the clinical course in these patients.

Effects of Smoking on Myocardial Injury in Patients With Conservatively Treated Acute Myocardial Infarction

Many reports have demonstrated that smokers who have suffered an acute myocardial infarction (AMI) have a better prognosis than nonsmokers. The present study investigated the effects of current smoking on myocardial injury with resting 123I-15-iodophenyl 3-methyl pentadecanoic acid (BMIPP)/201Tl myocardial single photon emission computed tomography in 103 patients with conservatively treated AMI. The left ventricular myocardium was divided into 9 segments and BMIPP and 201Tl defects were scored using a 5-point grading system (0 = normal and 4 = no uptake). The sum of the defect scores was defined as the total defect score. There was no significant difference in either the baseline severity of the coronary artery disease or the total defect scores for BMIPP and 201Tl between the current smoker and nonsmoker groups. The difference between the total defect scores for BMIPP and 201Tl tended to be larger in the current smoker group than in the nonsmoker group (2.0 +/- 1.9 vs 1.3 +/- 1.6, p = 0.056). Forty-one (53%) of 77 patients in the current smoker group exhibited a BMIPP/201Tl mismatch, whereas only 8 (31%) of 26 patients in the nonsmoker group did (p = 0.047). In conclusion, current smokers had more likelihood of salvageable myocardium in areas at risk, as demonstrated by BMIPP/201Tl mismatch, in AMI than nonsmokers.