Koichi Ochiai

Diagnosis of cardiac sarcoidosis and evaluation of the effects of steroid therapy by gadolinium-DTPA–enhanced magnetic resonance imaging

BACKGROUND Cardiac involvement is an important prognostic factor in patients with sarcoidosis. In this study, we evaluated the usefulness of gadolinium-DTPA (diethylene triamine pentaacetic acid)-enhanced magnetic resonance imaging (Gd-MRI) for diagnosing cardiac sarcoidosis and evaluating the effects of steroid therapy. METHODS Sixteen patients with sarcoidosis diagnosed by histology or by Japanese Ministry of Health and Welfare criteria for cardiac sarcoidosis underwent Gd-MRI with a 1.5-Tesla superconducting magnet system using a T1-weighted spin-echo sequence. RESULTS Gd-MRI showed localized enhancement of signal intensity, indicating interstitial edema, in the left ventricle in 8 of the 16 patients. Two patients with enhancement also had thinning of the left ventricular septal wall. After 1 month of prednisolone therapy (60 mg every other day or 30 to 40 mg every day), the localized high-intensity signals were markedly diminished in all 8 patients. CONCLUSIONS Images of the heart obtained by Gd-MRI may reflect active inflammation with interstitial edema in patients with sarcoidosis. Gd-MRI may be a useful noninvasive method for early detection of cardiac sarcoidosis and for evaluating the effects of steroid therapy.

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.

High-Energy Phosphate Metabolism and Creatine Kinase in Failing Hearts A New Porcine Model

BackgroundThis study aimed to create a pig model of heart failure secondary to severe aortic stenosis and to examine the relationship between the alterations in myocardial high-energy phosphate (HEP) metabolism and protein expression of creatine kinase (CK) isoforms. Methods and ResultsSixteen pigs with left ventricular hypertrophy (LVH) secondary to ascending aortic banding and 10 normal pigs (N) were studied. Myocardial protein levels of CK isoforms (Western blot), HEP levels, and CK kinetics (31P MR spectroscopy) were measured under basal conditions. Nine of the 16 animals with LVH developed congestive heart failure (CHF), as evidenced by ascites (100 to 2000 mL). LV weight/body weight ratio (g/kg) was 2.18±0.15 in N hearts, 3.04±0.14 in hearts with LVH (P <0.01), and 4.23±0.36 in hearts with CHF (P <0.01 versus LVH). Right ventricle weight/body weight ratio and LV end-diastolic pressure were significantly higher in hearts with CHF (each P <0.01 versus N or LVH). Myocardial phosphocreatine/ATP ratios and the CK forward flux rates were decreased in LVH hearts, most severely in hearts with CHF. CK-M/&bgr;-actin ratios were 2.21±12 (N), 1.69±0.15 (LVH), and 1.39±0.27 (CHF, P <0.05 versus N). CK-mitochondria (CK-Mt)/&bgr;-actin ratios were 1.40±0.09 (N), 1.24±0.09 (LVH), and 1.02±0.08 (CHF, P <0.05 versus N or LVH). The severity of the reduction of CK flux rate was linearly related to the severity of the decrease of CK-Mt/&bgr;-actin (r =0.68, P <0.01). ConclusionsIn this new model of heart failure/hypertrophy, the abnormal myocardial HEP metabolism is related to the decreased CK-Mt protein level, which in turn is related to the severity of the hypertrophy.

Hemorrhagic Myocardial Infarction After Coronary Reperfusion Detected In Vivo by Magnetic Resonance Imaging in Humans: Prevalence and Clinical Implications

With the advent of thrombolytic therapy, hemorrhagic myocardial infarction (HMI) has been observed in experimental and human autopsy studies. However, its clinical implications remain undetermined, because of the absence of a reliable method to detect its presence in vivo. This study was designed to evaluate the clinical implications of HMI detected by magnetic resonance (MR) imaging in vivo after coronary reperfusion. Thirty-nine patients with acute myocardial infarction (AMI) were studied. Percutaneous transluminal coronary angioplasty (PTCA) was used to reopen the occluded coronary artery. Electrocardiogram (ECG)-gated T2*-weighted gradient-echo MR imaging was performed to detect intramyocardial hemorrhage, using a 1.5-T magnet within 2 weeks after coronary reperfusion (average, 5.7 days). Thirteen patients (33%) showed intramyocardial hemorrhage as a distinct hypointense zone by gradient-echo MR imaging and 26 patients showed homogeneous intensity consistent with absence of intramyocardial hemorrhage. Coronary angiograms showed lesser development of collateral flow in the patients with HMI than in those without (81% vs. 37%). Infarct size, estimated 1 month after coronary reperfusion by thallium-201 scintigraphy, was larger among patients with HMI than in those without (37 +/- 14% vs. 21 +/- 14%, respectively, p < 0.05). Left ventricular ejection fraction at 1 month follow-up showed less recovery in patients with HMI than in those without (47 +/- 9 to 51 +/- 10%; p = 0.47, vs. 53 +/- 10 to 60 +/- 9%, respectively, p < 0.05). ECG-gated T2*-weighted gradient-echo MR imaging offers a noninvasive means of detection of intramyocardial hemorrhage in patients with reperfused AMI. HMI occurred even after primary PTCA and may be a common finding associated with severely injured myocardium.

Subendocardial enhancement in gadolinium-diethylene-triamine-pentaacetic acid-enhanced magnetic resonance imaging in aortic stenosis

We investigated the usefulness of magnetic resonance imaging (MRI) with gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA) in assessing myocardial damage from valvular aortic stenosis (AS). Cardiac catheterization and echocardiography were performed in 17 patients with AS. T1-weighted spin-echo sequence was used to obtain magnetic resonance images of short-axis planes of the left ventricle before and after intravenous Gd-DTPA injection in all patients using a 1.5 Tesla imager. Patients were divided into 2 groups according to the presence or absence of regional myocardial enhancement in the images. The Gd-DTPA-enhanced magnetic resonance images of 7 patients showed circumferential subendocardial enhancement. All patients with enhancement had a history of heart failure and were in New York Heart Association functional class III or IV, whereas patients without enhancement were in New York Heart Association functional class I or II. Patients with enhancement had a smaller aortic valve area (0.28 +/- 0.09 vs 0.38 +/- 0.07 cm2/m2, p <0.05), a higher transvalvular pressure gradient (109 +/- 40 vs 68 +/- 18 mm Hg, p <0.05), greater elevation of left ventricular end-diastolic pressure (22 +/- 11 vs 12 +/- 2 mm Hg, p <0.05), and greater reduction in left ventricular ejection fraction (40 +/- 9 vs 59 +/- 10%, p <0.05). Subendocardial enhancement by Gd-DTPA-enhanced MRI was thus shown to be closely related to the severity of AS. In conclusion, Gd-DTPA-enhanced MRI is a new noninvasive tool that can provide useful information about myocardial damage in AS.

Functional and bioenergetic consequences of AT1 antagonist olmesartan medoxomil in hearts with postinfarction LV remodeling.

The structural left ventricular (LV) remodeling and contractile dysfunction of hearts with postinfarction LV remodeling are benefited by angiotensin II type 1 receptor (AT1) blocker. However, the myocardial bioenergetic consequences of AT1 blocker in these hearts are not known. To investigate, we used a porcine model of postinfarction LV remodeling produced by ligation of the left circumflex coronary artery. After infarction, 7 pigs received olmesartan medoxomil (2 mg/kg) for comparison against 9 untreated and 10 normal pigs. Measurements of hemodynamics, myocardial perfusion, and myocardial bioenergetics were taken 7 weeks postinfarction. The treated group had an LV-to-body weight ratio significantly lower than the untreated group (2.69±0.70, 2.96±0.51, 3.66±0.60 g/kg for control, treated, and untreated groups, respectively). The untreated group had a mean aortic pressure significantly higher than the control (73±16, 86±14, and 94±20 mm Hg, respectively). The subendocardial phosphocreatine-to-ATP ratios of the treated group were significantly higher than that of the untreated group. The untreated group, but not the treated group, had significant reductions in mitochondrial F0F1-ATPase subunits compared with controls. Congestive heart failure as evidenced by significant ascites (100 to 2000 mL) developed in 4 of the 9 untreated animals, but was absent in the treated group. Animals with heart failure demonstrated reductions in both mitochondrial F0F1-ATPase expression and myocardial high-energy phosphate levels. Thus, severe LV dysfunction and accompanying abnormal myocardial bioenergetic phenotype were prevented by the AT1 antagonist olmesartan medoxomil.

Nicorandil improves myocardial high-energy phosphates in postinfarction porcine hearts

1. Nicorandil is a potent vasodilator combining the effects of a nitrate with an ATP‐sensitive potassium channel (KATP) opener. Because the postinfarct remodelled heart has increased vulnerability to subendocardial hypoperfusion, it is possible that the vasodilator effects of nicorandil could cause transmural redistribution of blood flow away from the subendocardium. Alternatively, the KATP channel opening effects of nicorandil could exert a beneficial effect on mitochondrial respiration. Consequently, the present study was performed to examine the effect of nicorandil on energy metabolism in the postinfarct heart.