Shigefumi Morioka

Noninvasive assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery by Doppler echocardiography: Comparison with invasive technique

OBJECTIVES The purpose of this study was to evaluate whether transthoracic Doppler echocardiography (TTDE) can reliably measure coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD) in the clinical setting. BACKGROUND Coronary flow velocity measurement has provided useful clinical and physiologic information. Advancement in TTDE provides noninvasive measurement of CFV and CFVR in the distal LAD. METHODS In 23 patients, CFV in the distal LAD was measured by TTDE (5 or 3.5 MHz) under the guidance of color Doppler flow mapping at the time of Doppler guide wire (DGW) examination. Coronary flow velocity in the distal LAD were measured at baseline and hyperemic conditions (intravenous administration of adenosine 0.14 mg/kg/min) by both TTDE and DGW techniques. Coronary flow velocity reserve was defined as the ratio of peak hyperemic to basal averaged peak velocity in the distal LAD. RESULTS Clear envelopes of basal and hyperemic CFV in the distal LAD were obtained in 18 (78%) of 23 study patients by TTDE. There were excellent correlations between TTDE and DGW methods for the measurements of CFV (averaged peak velocity: r=0.97, y=0.94x + 0.40; averaged diastolic peak velocity: r=0.97, y=0.94x + 0.69; systolic peak velocities: r=0.97, y=0.91x + 0.87; diastolic peak velocity: r=0.98, y=0.95x + 1.10). Coronary flow velocity reserve from TTDE correlated highly with those from DGW examinations (r=0.94, y=0.95x + 0.21). CONCLUSIONS Noninvasive measurement of CFV and CFVR in the distal LAD using TTDE accurately reflects invasive measurement of CFV and CFVR by DGW method.

Noninvasive Assessment of Significant Left Anterior Descending Coronary Artery Stenosis by Coronary Flow Velocity Reserve With Transthoracic Color Doppler Echocardiography

BACKGROUND Coronary flow reserve has been considered an important diagnostic index of the functional significance of coronary artery stenosis. With Doppler technique, it has been assessed as the ratio of hyperemic to basal coronary flow velocity (coronary flow velocity reserve [CFVR]) by invasive or semiinvasive methods with a Doppler catheter, a Doppler guide wire, and a transesophageal Doppler echocardiographic probe. Recent technological advancement in transthoracic Doppler echocardiography (TTDE) provides measurement of coronary flow velocity in the distal portion of the left anterior descending coronary artery (LAD) and may be useful in the noninvasive CFVR measurement. The purpose of this study was to evaluate the value of CFVR determined by TTDE for the assessment of significant LAD stenosis. METHODS AND RESULTS We studied 36 patients who underwent coronary angiography for the assessment of coronary artery disease. The study population consisted of 12 patients with significant LAD stenosis (group A) and 24 patients without significant LAD stenosis (group B). With TTDE, coronary flow velocities in the distal LAD were recorded at rest and during hyperemia induced by intravenous infusion of adenosine (0.14 mg x kg(-1) x min(-1)) under the guidance of color Doppler flow mapping. Adequate spectral Doppler recordings of coronary flow in the distal LAD for the assessment of CFVR were obtained in 34 of 36 study patients (94%). The peak and mean diastolic coronary flow velocities at baseline did not differ between groups A and B (23.6+/-10.3 versus 22.9+/-6.6 cm/s and 16.4+/-8.6 versus 14.5+/-4.0 cm/s, respectively). However, the peak and mean coronary flow velocities during hyperemia in group A were significantly smaller than those in group B (35.6+/-16.3 versus 54.2+/-16.3 cm/s and 24.7+/-13.1 versus 37.9+/-13.0 cm/s, respectively; P<.01). There were significant differences in CFVR obtained from peak and mean diastolic velocity between groups A and B (1.5+/-0.2 versus 2.4+/-0.4 and 1.5+/-0.2 versus 2.6+/-0.4, respectively; P<.001). A CFVR from peak diastolic velocity <2.0 had a sensitivity of 92% and a specificity of 82% for the presence of significant LAD stenosis. A CFVR from mean diastolic velocity <2.0 had a sensitivity of 92% and a specificity of 86% for the presence of significant LAD stenosis. CONCLUSIONS CFVR determined by TTDE is useful in the noninvasive assessment of significant stenotic lesion in the LAD.

Long-Term Prognosis of Patients With Type A Aortic Intramural Hematoma

Background—The long-term clinical course of patients with type B aortic intramural hematoma (IMH) and predictors for progression remains unknown. The difference of aortic pathology may have a different impact on clinical course compared with classic aortic dissection (AD). The purpose of this study was to investigate long-term clinical course and predictors of progression in patients with type B IMH. Methods and Results—Clinical data were compared retrospectively between 53 patients with acute type B IMH (IMH group) and 57 patients with acute type B AD (AD group). All patients were treated initially with medical therapy. Two patients in IMH group and 14 patients in AD group underwent surgical repair because of aortic enlargement. The in-hospital mortality rate in IMH group was significantly lower than that in AD group (0% and 14%, P =0.006). Mean follow-up periods were 53±43 months, which revealed 3 and 5 late deaths, respectively. Eleven patients with IMH showed progression (development of aortic dissection or aortic enlargement) in follow-up imaging study. The actuarial survival rates in IMH group were 100%, 97%, and 97% at 1, 2, and 5 years, which were significantly higher than those in AD group (83%, 79%, and 79%) (P =0.009). Multivariate analysis identified age >70 years and new appearance of an ulcerlike projection as the strongest predictors of progression in patients with IMH. Conclusions—Patients with type B IMH have better long-term prognosis than patients with AD. Older age and appearance of an ulcerlike projection are predictive for progression in patients with type B IMH.

Pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus: an intravascular ultrasound scanning study

BACKGROUND It has been reported that pioglitazone reduces neointimal hyperplasia after balloon-induced vascular injury in an experimental model. METHODS To determine whether pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus, we studied 44 stented lesions in 44 patients with diabetes mellitus who underwent successful coronary stent implantation. Study patients were randomized into 2 groups: the pioglitazone group (23 patients with 23 lesions) and the control group (21 patients with 21 lesions). All patients underwent serial quantitative coronary angiography and serial intravascular ultrasound scanning studies. With a motorized pullback system, multiple image slices within the stent were obtained at every 1 mm. The stent area and lumen area were measured, and the neointimal area was calculated. Measurements were averaged over the number of selected image slices. The neointimal index was calculated as the averaged neointimal area divided by the averaged stent area multiplied by 100 (%). RESULTS After 6 months of treatment, angiographic in-stent restenosis (17% vs 43%, respectively, P =.0994) and target lesion revascularization (13% vs 38%, respectively, P =.0835) were less frequent in the pioglitazone group than the control group; however, these differences did not reach significance. The intravascular ultrasound scanning study demonstrated that the neointimal index in the pioglitazone group was significantly smaller than that in the control group (28% +/- 9% vs 48% +/- 15%, respectively, P <.0001). CONCLUSION A serial intravascular ultrasound scanning assessment demonstrated that pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus.

Intravascular Ultrasound Analysis of Reduction in Progression of Coronary Narrowing by Treatment With Pravastatin

Serial intravascular ultrasound studies were performed to evaluate the effect of pravastatin on coronary atherosclerotic plaque. Administration of pravastatin reduced serum lipid levels and progression of coronary artery atherosclerotic plaque.

Retinopathy Identifies Marked Restriction of Coronary Flow Reserve in Patients With Diabetes Mellitus

OBJECTIVES This study sought to assess the differences in coronary flow reserve in patients with and without diabetic retinopathy. BACKGROUND Microvascular abnormalities throughout the body and impairment of coronary flow reserve have been described in patients with diabetes mellitus. However, the relation between diabetic retinopathy and coronary microvascular disease has not been investigated. METHODS The study included 29 patients with diabetes mellitus (18 with and 11 without diabetic retinopathy) and 15 control patients with chest pain and normal coronary arteries. Diabetic retinopathy was nonproliferative in all 18 patients with this disorder (8 had background, 10 preproliferative retinopathy). Five minutes after injection of 3 mg of isosorbide dinitrate, phasic flow velocities were recorded in the proximal segment of the angiographically normal left anterior descending coronary artery at rest and during hyperemia (0.14 mg/kg body weight per min of adenosine infused intravenously) using a 0.014-in. 15-MHz Doppler guide wire. Coronary blood flow was calculated, and coronary flow reserve was obtained from the hyperemic/baseline flow ratio. RESULTS Coronary blood flow was significantly lower during hyperemia ([mean +/- SD] 107 +/- 23 and 116 +/- 18 vs. 136 +/- 17 ml/min, respectively) and higher at baseline (58 +/- 16 and 45 +/- 12 vs. 37 +/- 10 ml/min, respectively) in diabetic patients with and without retinopathy than in control subjects (p < 0.05 for both diabetic groups). As a result, coronary flow reserve in both groups of diabetic patients was significantly lower than in control patients (1.9 +/- 0.4 and 2.8 +/- 0.3 vs. 3.3 +/- 0.4, respectively, p < 0.01 for both diabetic groups), and its reduction was greater in patients with than without retinopathy (p < 0.01). Furthermore, in patients with diabetic retinopathy, maximal hyperemic coronary flow (102 +/- 11 vs. 114 +/- 16 ml/min, p < 0.05) and flow reserve (1.6 +/- 0.2 vs. 2.3 +/- 0.2, p < 0.01) were significantly lower in those with preproliferative than background retinopathy. CONCLUSIONS Coronary flow reserve is significantly restricted in patients with diabetes mellitus, and its reduction is more marked in those with diabetic retinopathy, especially in advanced retinopathy. Thus, diabetic retinopathy should identify marked restriction of coronary flow reserve in patients with diabetes mellitus.

Relationship Between Progressive Microvascular Damage and Intramyocardial Hemorrhage in Patients With Reperfused Anterior Myocardial Infarction Myocardial Contrast Echocardiographic Study

BACKGROUND Recent studies indicated that ischemic microvascular damage may be reversible or progressive after coronary reflow. Intramyocardial hemorrhage is a phenomenon that reflects severe microvascular injury. We examined the relationship between temporal changes in microvascular perfusion patterns detected by myocardial contrast echocardiography (MCE) and intramyocardial hemorrhage detected by magnetic resonance imaging (MRI) in patients with acute myocardial infarction (AMI). METHODS AND RESULTS The study population consisted of 24 patients with anterior AMI. All patients underwent MCE shortly after reflow and in the chronic stage (a mean of 31 days after reflow). Wall motion score (WMS) was determined as the sum of 16 segmental scores (dyskinetic/akinetic=3 to normal=0) at days 1 and 31. Gradient-echo acquisition and gadolinium-DTPA-enhanced spin-echo MRI were performed within 10 days after reflow. In MCE shortly after reflow, 16 patients (67%) showed contrast enhancement and the other 8 patients (33%) showed a sizable contrast defect. In the chronic stage, a persistent contrast defect was observed in 7 of 8 patients with a contrast defect shortly after reflow. Consistent contrast enhancement was observed in 12 of 16 patients (75%) with contrast enhancement shortly after reflow, indicating that a contrast defect newly appeared in 4 patients (25%). Intramyocardial hemorrhage was detected in 9 patients (38%): 5 of 7 patients with a persistent contrast defect and in all 4 patients with a new appearance of a contrast defect during the chronic stage. The patients without hemorrhage showed a significant improvement in WMS compared with patients with hemorrhage at day 31 (5+/-5 versus 19+/-6, P<.0005). CONCLUSIONS These results suggest that irreversible microvascular damage to the ischemic myocardium may cause intramyocardial hemorrhage after reflow, associated with impaired recovery of left ventricular function. Contrast enhancement within the risk area shortly after reflow does not necessarily indicate long-term microvascular salvage.

Prominent inhibitory effects of tranilast on migration and proliferation of and collagen synthesis by vascular smooth muscle cells

To obtain some ideas about prevention of restenosis after percutaneous transluminal coronary angioplasty (PTCA), we examined the effects of transilast (anti-allergic agent) on migration and proliferation of, and collagen synthesis by, cultured vascular smooth muscle cells (VSMC) from the thoracic aorta of WKY rats. Tranilast was added to culture medium containing 10% fetal calf serum (FCS). The cultures were pulse-labeled with 3H-thymidine (TdR) or 3H-proline (Pro). TdR and Pro uptake into VSMC were measured. The effect of tranilast on migration of VSMC was examined by using culture dishes of an original design. We also examined the inhibitory effects of various drugs, such as a Ca antagonist, an angiotensin converting enzyme (ACE) inhibitor, a phosphodiesterase inhibitor, elastase, colchicine, and mitomycin C, on proliferation and migration of VSMC. Our data showed that the inhibitory effects of tranilast on migration and proliferation of, and collagen synthesis by, VSMC were prominent. Maximal percentage inhibition of proliferation, migration and collagen synthesis was 60.8 +/- 2.3%, 52.7 +/- 14.7% and 62.1 +/- 8.1%, respectively. On the other hand, the inhibitory effects of other drugs, with the exception of colchicine and mitomycin C, on proliferation and/or migration of VSMC were not very strong. Although the inhibitory effects of colchicine and mitomycin C were strong in vitro, their clinical usefulness may be limited by systemic side-effects. These results indicate the potential usefulness of tranilast for prevention of restenosis of coronary arteries after PTCA.

Impact of troglitazone on coronary stent implantation using small stents in patients with type 2 diabetes mellitus

In summary, troglitazone reduces angiographic in-stent restenosis and target lesion revascularization rates after coronary stent implantation using 2.5-mm stents in patients with type 2 DM. Serial IVUS assessment demonstrates that the reduction in neointimal tissue proliferation in the troglitazone group is associated with the angiographic results.

Increased renal plasma flow in long‐term enalapril treatment of hypertension

The renal effects of long‐term antihypertensive treatment with enalapril were evaluated in 34 subjects (age, 53 yr; range, 27 to 65) with mild, uncomplicated hypertension. After receiving placebo for 4 wk, subjects were randomly assigned to groups receiving incremental doses of enalapril (10, 20, or 40 mg/day for 4 wk each) in a single morning dose or two divided doses, or of placebo. One subject who received enalapril developed acute renal failure by the end of the study. There was no evidence of glomerular or tubular damage in the other subjects; as measured by 24‐hr urinary protein excretion, urinary activity of N‐acetyl‐β‐D‐glucosaminidase, and uric acid clearance. During treatment with enalapril, renal plasma flow (measured with 131l‐iodohippurate sodium) and glomerular filtration rate increased by 12.1% and 6.8%. Changes in renal plasma flow correlated inversely with age and final mean arterial pressure and correlated positively with initial plasma renin activity of subjects. Except for an occasional idiosyncratic adverse reaction, enalapril is a safe and effective antihypertensive drug with the unique ability to increase renal function despite a fall in renal perfusion pressure.