Shunichi Tamaki

Detection and evaluation of tricuspid regurgitation using a real-time, two-dimensional, color-coded, Doppler flow imaging system: Comparison with contrast two-dimensional echocardiography and right ventriculography

To detect and evaluate regurgitant flow in tricuspid regurgitation (TR) with a newly developed, realtime, 2-dimensional (2-D), color-coded, Doppler flow imaging system (Doppler 2-D echo), 27 patients (18 with suspected TR and 9 normal subjects) were examined and the findings were compared with those obtained using contrast 2-D echocardiography (contrast 2-D echo) and right ventriculography. In 16 of 18 patients with suspected TR, Doppler 2-D echo easily visualized the color-coded regurgitant flow in the right atrium and estimated the severity of TR from the distance of the visible TR jet. On the basis of the QRS synchronized appearance of contrast in the inferior vena cava by the subxiphoid approach or of the negative contrast effect above the tricuspid valve just after the contrast entered the right ventricle with its subsequent back-and-forth movements across the tricuspid valve, Doppler 2-D echo was more sensitive and specific in detecting TR (100% and 100%) than contrast 2-D echo (75% and 82% in the subxiphoid view, 56% and 100% in the 4-chamber view) when the fast Fourier transformation frequency analysis was used as the standard of TR, and it was more sensitive in detecting TR (85%) than contrast 2-D echo (69% in the subxiphoid approach, 46% in the 4-chamber view) when right ventriculography was used as the standard of TR. Additionally, the severity of TR as shown by Doppler 2-D echo correlated fairly well with that shown by right ventriculography. Thus, Doppler 2-D echo is clinically useful for detecting and evaluating TR.

Elevated basic fibroblast growth factor in pericardial fluid of patients with unstable angina

BACKGROUND Collateral growth is induced by chemical signals from the ischemic myocardium. We hypothesized that angiogenic growth factors are produced by cardiac tissue; they are diffusible, more concentrated in pericardial fluids, and are increased by myocardial ischemia. METHODS AND RESULTS With the use of an enzyme-linked immunosorbent assay, we measured the concentrations of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in pericardial fluids of 12 patients with unstable angina (group 1) and of 8 patients with nonischemic heart diseases (group 2). The levels of protein in pericardial fluids were quite comparable between the two groups (34 +/- 2 versus 32 +/- 4 mg/mL). The concentration of bFGF in pericardial fluids in group 1 was 2036 +/- 357 pg/mL, significantly (P < .001) higher than the 289 +/- 72 pg/mL in group 2. The amount of bFGF per milligram of protein was also significantly (P < .05) higher in group 1 than in group 2 (67 +/- 15 versus 12 +/- 4 pg/mg). The concentration of VEGF in pericandial fluids tended to be higher in group 1, but the difference was statistically insignificant (39 +/- 7 versus 22 +/- 6 pg/mL). The amount of VEGF per milligram of protein was 1.2 +/- 0.3 pg/mg in group 1, similar to the 0.8 +/- 0.4 pg/mg in group 2. CONCLUSIONS This finding provides new evidence that bFGF plays an important role in mediating collateral growth in humans.

Stress scintigraphy using single-photon emission computed tomography in the evaluation of coronary artery disease

Twenty-seven patients with angina pectoris, 24 with postmyocardial infarction angina and 7 with normal coronary arteries were examined by exercise thallium-201 emission computed tomography (SPECT) and planar scintigraphy. Exercise SPECT was compared with the reperfusion imaging obtained approximately 2 to 3 hours after exercise. The sensitivity and specificity of demonstrating involved coronary arteries by identifying the locations of myocardial perfusion defects were 96 and 87% for right coronary artery, 88 and 89% for left anterior descending artery (LAD) and 78 and 100% for left circumflex artery (LC). These figures are higher than those for planar scintigraphy (85 and 87% for right coronary artery, 73 and 89% for LAD and 39 and 100% for LC arteries). In patients with 3-vessel disease, sensitivity of SPECT (100, 88 and 75% for right coronary artery, LAD and LC, respectively) was higher than planar imaging (88, 63 and 31%, respectively), with a significant difference for LC (p less than 0.05). In 1, 2 and 0-vessel disease the sensitivity and specificity of the 2 techniques were comparable. Multivessel disease was more easily identified as multiple coronary involvement than planar imaging with a significant difference in 3-vessel disease (p less than 0.05). In conclusion, stress SPECT provides useful information for the identification of LC lesions in coronary heart disease, including 3-vessel involvement.

Assessment of transesophageal Doppler echography in dissecting aortic aneurysm.

To assess the clinical value of transesophageal Doppler echography in the diagnosis of dissecting aortic aneurysm, both transesophageal and conventional echograms were performed in 22 cases of dissecting aortic aneurysm. Of the 22 patients, 17 underwent angiography; 8, X-ray computed tomography; 4, both; and 12, surgery. The performance of each method was assessed in the following four segments: A, ascending aorta; B, aortic arch; C, thoracic descending aorta; and D, upper abdominal aorta. The results by angiography were presumed to be correct. In the group of 17 patients who underwent angiography, the rate of correct detection of an intimal flap using the transesophageal approach was 100% in all four segments, significantly better than detection by the conventional approach (segment A, 65%; segment B, 47%; segment C, 35%; segment D, 53%) (p less than 0.01), and the rate of correct detection of the entry sites using the transesophageal approach was 100%, significantly better than that by conventional approach (42%) (p less than 0.05). X-ray computed tomography was not capable of detecting the site of entry in all cases. The presence of thrombus, aortic regurgitation and pericardial hemorrhage were all revealed clearly by the transesophageal approach, and the results were partly proved by other methods. In conclusion, transesophageal Doppler echography provides a rapid and accurate method of diagnosing and evaluating dissecting aortic aneurysm and permits prompt initiation of appropriate treatment.

Collateral function in early acute myocardial infarction

The role of the collateral circulation less than 6 hours after the onset of acute myocardial infarction (MI) was evaluated in 34 consecutive patients without previous MI. There were 19 patients with and 15 without collaterals. The group was subdivided into those with nonjeopardized collaterals (group A, 14 patients) and those with jeopardized collaterals (group B, 5 patients), and the group without collaterals into those with partially obstructed coronary arteries (group C, 5 patients) and those with totally obstructed coronary arteries (group D, 10 patients). These groups had similar sites of coronary stenoses and MI. Eleven of 14 collaterals in group A were poor, but MI mass measured by peak creatine kinase (CK) was smaller in group A than in group B (p less than 0.01) or group D (p less than 0.01), and cardiac function was significantly better in group A than in group D (cardiac index, p less than 0.05; stroke index, p less than 0.01; ejection fraction, p less than 0.01; regional wall motion, p less than 0.01). Group C was not statistically different from group A in myocardial function and CK. Group B was similar to group D in MI mass and cardiac function (cardiac index, stroke index, ejection fraction and regional wall motion). Thus, patients with nonjeopardized collaterals and those with partially obstructed coronary arteries had less myocardial damage and better cardiac function than did those with jeopardized collaterals and those with totally obstructed coronary arteries. A nonjeopardized collateral circulation may play a role in limiting MI mass and preserving myocardial function in the early stages of acute MI.

Effects of coronary artery reperfusion on relation between creatine kinase-MB release and infarct size estimated by myocardial emission tomography with thallium-201 in man.

The quantitative relations between serum creatine kinase-MB isoenzyme (CK-MB) release and the final infarct size estimated by myocardial emission computed tomography with thallium-201 was assessed in 37 patients with a first acute transmural myocardial infarction who underwent intracoronary thrombolysis using urokinase 4.6 +/- 1.9 hours after the onset of symptoms. Serial CK-MB determinations were used to calculate the accumulated release of CK-MB (sigma CK-MB). Myocardial emission tomography with thallium-201 was performed 4 weeks after the onset, and infarct volume was measured from reconstructed tomographic images by computerized planimetry. The results are presented for two groups of patients: 11 patients with unsuccessful thrombolysis (group A) and 26 patients with successful thrombolysis (group B). An excellent linear relation was found for group A (sigma CK-MB = 6.4 X infarct volume + 47.7, r = 0.91), whereas a different linear relation was observed for group B (sigma CK-MB = 10.5 X infarct volume + 89.1, r = 0.80). Moreover, serum CK-MB activity reached a peak at 21.1 +/- 2.2 hours after the onset in group A and reached an earlier peak at 12.5 +/- 2.9 hours in group B (p less than 0.001). These data suggest that acute coronary recanalization alters the kinetics of CK-MB release, resulting in greater CK-MB release into the serum for equivalent infarct volume estimated by myocardial emission tomography with thallium-201. Thus, serum CK-MB time-activity curves after acute myocardial infarction may be influenced considerably by acute reperfusion, which is an important factor that should be incorporated in the interpretation of enzymatic estimates of infarct size in human patients.

Treatment of acute inflammatory cardiomyopathy with intravenous immunoglobulin ameliorates left ventricular function associated with suppression of inflammatory cytokines and decreased oxidative stress

Although an autoimmune mechanism has been postulated for myocarditis and dilated cardiomyopathy, immunosuppressive agents had not been shown to be effective. Potential benefits of intravenous immunoglobulin (IVIg) in the therapy of patients with myocarditis and recent onset of dilated cardiomyopathy were reported. Also, experimental studies showed that IVIg is an effective therapy for viral myocarditis by antiviral and anti-inflammatory effects. Accordingly, in the current study, the effects of IVIg in the patients were investigated with the analyses of inflammatory cytokines and oxidative stress. Nine patients (six in myocarditis, three in acute dilated cardiomyopathy) were treated with high-dose intravenous IVIg (1-2 g/kg, over 2 days). All were hospitalized with New York Heart Association (NYHA) class III to IV heart failure, left ventricular ejection fraction (LVEF) <40%, and symptoms for <6 months at the time of presentation. Five patients were diagnosed using endomyocardial biopsy. LVEF determined by echocardiography improved from 19.0+/-7.5% (mean+/-S.D.) at baseline to 35.4+/-9.1% at follow up (12.2+/-5.8 days after the treatment) (P<0.01). C-reactive protein and plasma inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) were decreased by this treatment. In addition, plasma level of thioredoxin, which regulates the cellular state of oxidative stress, was decreased by the treatment. All nine patients improved functionally to NYHA class I to II, and were discharged without side-effects. There have been no subsequent hospitalizations for heart failure during the course of follow-up (3 months-4.5 years). LVEF improved 16% of EF in the patients with myocarditis and acute dilated cardiomyopathy with the reduction of cytokines associated with improvement of oxidative stress state by high-dose of IVIg. Thus, IVIg seems to be a promising agent in the therapy of acute inflammatory cardiomyopathy in view of not only suppression of inflammatory cytokines but a reduction of oxidative stress.

Effects of posture on cardiac autonomic nervous activity in patients with congestive heart failure.

OBJECTIVES We aimed to clarify which recumbent position is preferred by patients with congestive heart failure (CHF) and to evaluate whether cardiac autonomic nervous activity is different among three recumbent positions (supine, left lateral decubitus, right lateral decubitus) in patients with CHF. BACKGROUND It remains unclear whether cardiac autonomic nervous activity is different among three recumbent positions in patients with CHF. METHODS We studied 17 male CHF patients (66+/-7 years) and 17 age- and gender-matched healthy subjects (66+/-7 years). Each subject underwent 24-h ambulatory electrocardiographic monitoring. A channel was used to record the CM5 lead, and another to record the signal of the patients posture with use of a newly developed small-sized detector (3.2 cm x 3.2 cm). By using spectral analysis of heart rate variability, frequency-domain measures were calculated and compared among the three recumbent positions. Normalized high-frequency (HF: 0.15 to 0.40 Hz) power was used as an index of vagal activity and the low frequency (0.04 to 0.15 Hz)/HF power ratio was used as an index of sympathovagal balance. RESULTS In patients with CHF, the time for the right lateral decubitus position was two-fold longer than that for the supine and left lateral decubitus positions. The increased cardiac sympathetic activity and decreased vagal tone in CHF patients were normalized in the right lateral decubitus position. CONCLUSIONS The right lateral decubitus position in patients with CHF may be a self-protecting mechanism of attenuating the imbalance of cardiac autonomic nervous activity.

Improvement of exercise capacity by sarpogrelate as a result of augmented collateral circulation in patients with effort angina.

OBJECTIVES The purpose of this study was to evaluate whether a serotonin blocker, sarpogrelate, improves exercise capacity as a result of vasodilation of coronary collateral channels in patients with effort angina. BACKGROUND Serotonin has been reported to decrease coronary collateral blood flow by collateral vasoconstriction in a canine model, suggesting that platelet activation in feeding coronary arteries of the collateral network has the potential to cause collateral vasoconstriction. METHODS The subjects consisted of 22 patients with effort angina and reproducible ischemic threshold (group A, 11 patients with thrombolysis in myocardial infarction (TIMI) grade 2 or 3 flow of the ischemia-related coronary artery and Rentrops collateral index 0 or 1; group B, 11 patients with TIMI grade 0 or 1 flow and Rentrops collateral index 2 or 3). We repeated the symptom-limited treadmill exercise test using the Balke-Ware protocol and exercise tetrofosmin myocardial perfusion scintigraphy with and without pretreatment with 200 mg orally administered sarpogrelate. Each exercise test was performed at 9:00 a.m. on different days. The order of tests with and without sarpogrelate was randomized. RESULTS In group A, sarpogrelate increased neither exercise time at 0.1 mV ST depression nor double product at 0.1 mV ST depression. In contrast, in group B sarpogrelate increased the exercise duration at 0.1 mV ST depression from 181+/-112 (SD) to 248+/-131 s (p < 0.05) and also increased the double product at 0.1 mV ST depression by 21% (p < 0.01). The severity score using myocardial perfusion scintigraphy at the same workload was significantly (p < 0.01) decreased by 37% in group B, but not in group A (11%), due to the sarpogrelate treatment. CONCLUSIONS Sarpogrelate augments flow reserve of the collateral circulation and improves exercise capacity in anginal patients with well-developed collaterals. These findings indicate that a serotonin blocker, sarpogrelate, is useful not only as an antiplatelet drugs, but as an antianginal drug.

Marked Elevation of Brain Natriuretic Peptide Levels in Pericardial Fluid Is Closely Associated With Left Ventricular Dysfunction

OBJECTIVES The purpose of this study was to investigate whether atrial and brain natriuretic peptides (ANP and BNP, respectively) represent autocrine/paracrine factors and are accumulated in pericardial fluid. BACKGROUND ANP and BNP, systemic hormones produced by the heart, have elevated circulating levels in patients with heart failure. Recent evidence suggests that the heart itself is one of the target organs for these peptides. METHODS With an immunoreactive radiometric assay, we measured the concentrations of these peptides in plasma and pericardial fluid simultaneously in 28 patients during coronary artery bypass graft surgery. RESULTS The pericardial levels of BNP were markedly elevated in patients with impaired left ventricular function. We investigated the correlation of ANP and BNP levels in plasma or pericardial fluid with left ventricular hemodynamic variables. None of the hemodynamic variables correlated with ANP levels in plasma or pericardial fluid. Both plasma and pericardial fluid levels of BNP were significantly related to left ventricular end-diastolic and systolic volume indexes (LVEDVI and LVESVI, respectively). In addition, BNP pericardial fluid levels had closer relations with LVEDVI (r = 0.679, p < 0.0001) and LVESVI (r = 0.686, p < 0.0001) than did BNP plasma levels (LVEDVI: r = 0.567, p = 0.0017; LVESVI: r = 0.607, p = 0.0010). BNP levels in pericardial fluid but not in plasma correlated with left ventricular end-diastolic pressure (r = 0.495, p = 0.0074). CONCLUSIONS BNP levels in pericardial fluid served as more sensitive and accurate indicators of left ventricular dysfunction than did BNP levels in plasma. Thus, BNP may be secreted from the heart into the pericardial space in response to left ventricular dysfunction, and it may have a pathophysiologic role in heart failure as an autocrine/paracrine factor.