Teruo Takano

Clinical significance of elevated levels of cardiac troponin T in patients with chronic heart failure

Cardiac troponin T, measured by second-generation assay, is a highly sensitive and specific marker of minor myocardial damage. Cardiac troponin T was elevated in patients with severe chronic heart failure; it identifies those with latent and progressive myocardial damage and those who are at increased risk of cardiac events.

Application of NT-proBNP and BNP measurements in cardiac care: a more discerning marker for the detection and evaluation of heart failure.

Measurement of brain natriuretic peptide (BNP) has become a potent diagnostic aid as a means of identifying patients with systolic or diastolic dysfunction. Due to better stability in circulating blood, we reasoned that measurement of N‐terminal proBNP (NT‐proBNP) may be a more discerning marker for the detection and evaluation of chronic heart failure.

Acute decompensated heart failure syndromes (ATTEND) registry. A prospective observational multicenter cohort study: Rationale, design, and preliminary data

Acute heart failure syndromes (AHFS) are likely to increase in the future, and the high readmission rate of patients with AHFS is an important issue in Western countries. However, there are very few published epidemiological studies on AHFS in the Asia Pacific region. Because AHFS are heterogeneous, the characteristics, clinical profile, and management of AHFS should be clarified in an epidemiological study. The acute decompensated heart failure syndromes (ATTEND) registry is a prospective, observational, multicenter cohort study being performed in Japan and is the first epidemiological study of AHFS in the Asia Pacific region. This study is designed to investigate several aspects of AHFS as follows: (1) the registry allows patient-based data collection for precise evaluation of patient characteristics and short-term outcomes, including the readmission rate; (2) confirmation of clinical assessments can be performed, and new clinical assessments can be created; and (3) feedback allows the modification of guidelines for clinical management. The present report describes the clinical characteristics of patients with AHFS in Japan based on the preliminary data collected in this study, and the similarities and differences in characteristics of these patients compared with those in Western countries. Although most of the patient characteristics did not differ from those reported in Western studies, there are some unique findings in this study, including a high rate of treatment with carperitide (69.4%) and angiotensin II receptor blockers (53.9%) at discharge and a longer hospital stay (median 21 days). The ATTEND registry is designed to provide valuable information to clarify the characteristics of patients with AHFS to improve their management.

Use of cytosolic and myofibril markers in the detection of ongoing myocardial damage in patients with chronic heart failure.

PURPOSE Measurement of serum levels of cytosolic and myofibril components of cardiac tissue could indicate ongoing myocardial damage in patients with chronic heart failure. METHODS We correlated serum levels of a cytosolic marker (heart-type fatty acid-binding protein) and a myofibril marker (troponin T) with the severity of symptoms (based on the New York Heart Association [NYHA] class), neurohumoral derangement, and subsequent cardiac events in 56 patients with chronic heart failure. RESULTS Mean (+/- SD) levels of heart-type fatty acid-binding protein were greater in patients with NYHA class III or IV heart failure (9.9 +/- 5.2 ng/mL) than in those with NYHA class II (4.9 +/- 1.9 ng/mL, P <0.0001). Detection of troponin T (> or =0.02 ng/mL) was also more common in patients with worse heart failure (81% [13/16] in class III or IV vs. 43% [17/40] in class II, P = 0.02). Significant correlations were found between heart-type fatty acid-binding protein levels and plasma levels of A-type natriuretic peptide (r = 0.45, P = 0.0004), B-type natriuretic peptide (r = 0.66, P <0.0001), and norepinephrine (r = 0.36, P = 0.006). Male sex (hazard ratio [HR] = 5.0; 95% confidence interval [CI]: 1.3 to 19), detectable troponin T levels (HR = 7.0; 95% CI: 1.1 to 44), heart-type fatty acid-binding protein (HR = 2.6 per 3.9-ng/mL increase; 95% CI: 1.1 to 6.5), and left ventricular ejection fraction (HR = 3.6 per 15% decrease; 95% CI: 1.2 to 11) were independently associated with subsequent cardiac events (8 deaths or 10 readmissions because of worsening heart failure). CONCLUSION Heart-type fatty acid-binding protein and troponin T are markers of ongoing myocardial damage, and are associated with subsequent cardiac events in patients with chronic heart failure.

Use of a whole blood rapid panel test for heart-type fatty acid-binding protein in patients with acute chest pain: comparison with rapid troponin T and myoglobin tests.

PURPOSE We sought to determine the clinical utility of a newly developed qualitative test to measure heart-type fatty acid-binding protein levels in blood for the early identification of myocardial infarction. METHODS We measured heart-type fatty acid-binding protein levels in 371 consecutive patients with acute chest pain and suspected myocardial infarction, and compared the performance of this test with those of troponin T and myoglobin tests. Levels of heart-type fatty acid-binding protein >or=6.2 ng/mL were considered as positive results. RESULTS A final diagnosis of acute myocardial infarction was made in 181 patients (49%). Of the 68 patients who presented within 2 hours of the onset of symptoms, 37 (54%) had a final diagnosis of myocardial infarction. The sensitivity of the rapid heart-type fatty acid-binding protein test was 89% (33/37), significantly higher than for troponin T (22% [8/37]; P<0.001) and myoglobin (38% [14/37]; P<0.001). However, the specificity of troponin T (94% [29/31]) was significantly better than for heart-type fatty acid-binding protein (52% [16/31]; P= 0.002) within 2 hours. The area under the receiver operating characteristic curve for heart-type fatty acid-binding protein levels was greater than that for myoglobin (0.72 vs. 0.61, P = 0.01) among patients who presented within 2 hours. CONCLUSION A novel whole blood rapid heart-type fatty acid-binding protein test can be useful in the early evaluation of patients who present with acute chest pain.

Elevated Troponin T Levels and Lesion Characteristics in Non–ST-Elevation Acute Coronary Syndromes

Background—Elevated troponin T levels in non–ST-elevation acute coronary syndromes (NSTE-ACS) have been shown to predict an adverse outcome. Furthermore, it has been reported that troponin T could help improve the effectiveness of such new antithrombotic drugs as platelet GPIIb/IIIa antagonists and low-molecular-weight heparins. We hypothesized that such elevated troponin T levels in NSTE-ACS indicate the presence of thrombus at culprit lesions, and this hypothesis was verified through the use of coronary angioscopy. Methods and Results—We studied 57 consecutive patients with NSTE-ACS who underwent preinterventional angioscopy. Before catheterization, we obtained blood samples to determine troponin positivity, and the patients were then classified as either troponin-positive or troponin-negative groups (diagnostic threshold, 0.1 ng/mL). Using angioscopy at the culprit lesions, we examined the presence of coronary thrombus, yellow plaque, and complex plaque. Moreover, we compared the preinterventional angiographic parameters (thrombus and complexity of the culprit lesion, and TIMI flow) between the two groups. Twenty-two patients were troponin-positive and 35 patients were troponin-negative. Univariate analyses indicated that the TIMI flow and the incidence of coronary thrombus detected with angioscopy correlate with the elevated troponin T levels. A multivariate logistic regression analysis showed the presence of coronary thrombus detected with angioscopy to be the only independent factor associated with elevated troponin T levels in patients with NSTE-ACS (odds ratio, 22.1; 95% CI, 2.59 to 188.42; P =0.0046). Conclusions—Using angioscopy, the elevated troponin T levels in NSTE-ACS were confirmed to be strongly associated with the presence of coronary thrombus.

Therapeutic angiogenesis by autologous bone marrow cell implantation for refractory chronic peripheral arterial disease using assessment of neovascularization by 99mTc-tetrofosmin (TF) perfusion scintigraphy.

We investigated efficacy and safety of implantation of autologous bone marrow mononuclear cells plus platelets, including endothelial progenitor cells (EPCs), for recovering refractory chronic peripheral arterial disease (PAD) using visual and quantitative analyses by 99mTc-tetrofosmin (TF) perfusion scintigraphy, and also investigated various quantitative assessments objectively. We performed 12 consecutive cases and 19 limbs and hands with severe chronic PAD that were almost Fontaine class IV (11/12 cases, about 92%) in this trial. This treatment was very effective in relieving severe pain of PAD, especially for Buergers disease. We used a visual analog scale (VAS) for measurement of pain level. The maximum pain level before implantation was 66.5 ± 5.0 mm, and it decreased to 12.1 ± 2.2 mm after implantation (p < 0.001). Rest pain in legs and fingers was resolved in 11 cases (11/12 cases, 92%). All patients could measure pain-free walking time on a treadmill, which improved remarkably (140 ± 53 s before implantation vs. 451 ± 74 s after implantation, p = 0.034). Resting ankle brachial pressure index (ABI) in legs implanted with bone marrow mononuclear cells was also improved (0.65 ± 0.08 before implantation vs. 0.73 ± 0.07 after implantation, p = 0.055). According to 99mTc-TF perfusion scintigraphy, the proximal area (region from knee to ankle) was 1.32 ± 0.10 before implantation versus 1.56 ± 0.11 after implantation (p = 0.007). 99mTc-TF perfusion scintigraphy in the distal area (region from ankle to end of toes, or from wrist to end of fingers) was 0.79 ± 0.06 before implantation versus 0.83 ± 0.06 after implantation (p = 0.29). Ischemic legs and hands that were injected showed increased perfusion blood flow. 99mTc-TF perfusion scintigraphy was effective to estimate visual and quantitative analysis of collateral vessels in neovascularization. We were successful with this new treatment for the most severe, chronic PAD that was not curable by any of the current treatments. Thus, this therapeutic angiogenesis could be a new strategy for saving severe ischemic limbs and hands.

Alpha-human atrial natriuretic peptide, carperitide, reduces infarct size but not arrhythmias after coronary occlusion/reperfusion in dogs.

Carperitide, a recombinant form of alpha-hANP, possesses potent diuretic, natriuretic, and vasodilatory activity, and inhibits the renin-aldosterone system and sympathetic nervous activity. However, its beneficial effects on ischemic myocardium have not been studied fully. We examined carperitides effects on infarct size, hemodynamics, and arrhythmia frequency in anesthetized dogs (n = 20) subjected to a 90-min coronary artery occlusion/6-h reperfusion protocol. Intravenous infusion of carperitide (0.2 microg/kg/min) commenced 15 min after occlusion and continued during occlusion/reperfusion. Ventricular fibrillation developed in two of 10 control versus three of 10 treated dogs (p = NS). Hemodynamics, collateral blood flow to the ischemic wall measured 10 min after occlusion, and extent of area at risk were comparable for the two groups. Infarct size/area at risk was smaller in treated than in control dogs (4.5 +/- 2.1% vs. 27.8 +/- 7.8%, respectively; p < 0.05). During occlusion, carperitide tended to increase collateral blood flow (+39%) and significantly decreased left ventricular systolic pressure (-13%) and end-diastolic pressure (-40%) compared with baseline. In control dogs, collateral blood flow tended to decrease (-8.3%), whereas most hemodynamic parameters did not change significantly with respect to baseline. The number of arrhythmias recorded during occlusion/reperfusion was similar in the two groups. Intravenous administration of carperitide limited infarct size, but did not reduce incidence of ventricular arrhythmias after 90-min coronary occlusion/6-h reperfusion in anesthetized dogs. Although the beneficial effects of carperitide may be attributable to concomitant changes in hemodynamics and collateral blood flow, the precise mechanisms require further investigation.

Intrapulmonary vascular dilatation and nitric oxide in hypoxemic rats with chronic bile duct ligation.

BACKGROUND/AIMS Nitric oxide (NO) has been suggested as the major cause of pulmonary vascular dilatation and hypoxemia in hepatopulmonary syndrome (HPS). The aim of this study was to assess the effect of NO on arterial oxygenation in rats with common bile duct ligation (CBDL rats), a model of HPS. METHODS Arterial blood gases were measured in 44 CBDL rats and 44 Sham rats under unrestrained conditions. Intrapulmonary shunting was assessed with (141)Ce-labeled microspheres (15-mum diameter) and serum nitrate/nitrite levels were measured by HPLC. The effect of NOS inhibition on A-aDO(2) was studied using L-NAME. RESULTS A decrease of PaO(2) below 82.7 mmHg (the mean value-2sigma in Sham rats) was seen in 43% of CBDL rats. Intrapulmonary shunting was greater in CBDL rats than in Sham rats (P<0.001). A correlation between the extent of shunting and A-aDO(2) was found in all animals studied (r=0.89, P<0.001, n=16). Serum levels of nitrate/nitrite increased significantly across the lungs, and the increase was significantly correlated with A-aDO(2) in the total population of animals studied. Administration of L-NAME to CBDL rats achieved a significant improvement of A-aDO(2). CONCLUSIONS These results suggest that pulmonary vascular dilatation due to NO leads to hypoxemia in CBDL rats.

The effect of nasal continuous positive airway pressure on plasma endothelin-1 concentrations in patients with severe cardiogenic pulmonary edema.

We investigated the effects of nasal continuous positive airway pressure (CPAP) on plasma endothelin-1 (ET-1) concentrations in patients with cardiogenic pulmonary edema. Thirty patients were randomly assigned to two groups: 15 patients who received oxygen plus nasal CPAP (CPAP group), and 15 patients who received only oxygen by face mask (oxygen group). The heart rate and the mean pulmonary artery pressure decreased significantly in the CPAP group. The PaO2/fraction of inspired oxygen (FIO2) ratio increased in the CPAP group (163 +/- 70 to 332 +/- 104, P < 0.01) after 6 h and was significantly higher than that in the oxygen group. Arterial plasma ET-1 concentrations decreased from 6.2 +/- 2.0 pg/mL to 4.8 +/- 1.7 pg/mL (P < 0.05) after 6 h and to 3.3 +/- 0.7 pg/mL (P < 0.01) after 24 h in the CPAP group. Arterial plasma ET-1 concentrations in the CPAP group compared with the oxygen group were significantly lower at 24 h. There was a correlation between the arterial plasma ET-1 concentrations and mean pulmonary artery pressure (r = 0.62, P < 0.001), and PaO2/FIO2 (r = -0.46, P < 0.01). Nasal CPAP led to an early decrease in plasma ET-1 concentrations, and improvement in oxygenation and hemodynamics. (Anesth Analg 1997;84:1091-6)