Protective effect of high diastolic blood pressure during exercise against exercise-induced myocardial ischemia.

BACKGROUND: Hypertension is one of the risk factors for coronary artery disease. However, because most coronary blood flow to the left ventricle occurs during diastole, high diastolic blood pressure during exercise may have a protective effect against exercise-induced myocardial ischemia. The aim of the present study was to test this hypothesis. METHODS AND RESULTS: We identified 469 patients with sinus rhythm and known or suspected coronary artery disease who underwent exercise thallium-201 myocardial single-photon emission computed tomography and coronary arteriography. High diastolic blood pressure during exercise was defined as diastolic blood pressure at peak exercise > or = 90 mm Hg. There was no significant difference in medications, number of diseased vessels, or Gensini score between patients with high (n = 228) and normal (n = 241) diastolic blood pressure during exercise, whereas patients with high diastolic blood pressure during exercise exhibited a higher pressure-rate product during exercise than patients with normal diastolic blood pressure during exercise. The reversibility score on thallium-201 myocardial scan was significantly smaller in patients with high diastolic blood pressure during exercise than in patients with normal diastolic blood pressure during exercise (P = .021). CONCLUSIONS: High diastolic blood pressure during exercise has a potential protective effect against exercise-induced ischemia, although the mechanism of such effects remains to be determined.

Involvement of c-Jun NH2 terminal kinase and p38MAPK in rapamycin-mediated inhibition of neointimal formation in rat carotid arteries.

OBJECTIVE: Rapamycin-coated stents in coronary artery lesions have recently been shown to be effective in inhibiting neointimal formation. However, little is known about the effects of rapamycin on mitogen-activated protein kinase (MAPK), which is an important signal for neointimal formation. Therefore, we examined the effects of rapamycin on MAPK and transcriptional factors in cultured human coronary artery smooth muscle cells (CASMC) and in balloon-injured rat carotid arteries. METHODS AND RESULTS: Activation of ERK, JNK, p38MAPK, AP-1, and NF-kB in coronary artery smooth muscle cells was increased by 2% fetal bovine serum. Ten nmol/L of rapamycin prevented the activation of JNK, p38MAPK, AP-1, and NF-kB (65%, 65%, 67%, and 26% respectively, P<0.01). In an in vivo study, remarkable neointimal formation was observed 14 days after injury. Coating Pluronic gel with 20 and 50 mug rapamycin around the injured artery significantly decreased the intimal area/medial area ratio, compared with vehicle (0.75 vs. 1.2, P<0.01). Rapamycin prevented the increase in activation of JNK, p38MAPK, AP-1, and NF-kB in injured artery (42%, 70%, 75%, and 60% respectively, P<0.05). CONCLUSIONS: Neointimal formation after balloon injury is inhibited by rapamycin, which is partially mediated by inhibition of JNK and p38MAPK, followed by AP-1 and NF-kB.

Granulocyte-colony stimulating factor augments neovascularization induced by bone marrow transplantation in rat hindlimb ischemia.

Because granulocyte-colony stimulating factor (G-CSF) mobilizes bone marrow cells including endothelial progenitor cells, we examined whether G-CSF augments angiogenesis and collateral vessel formation induced by bone marrow-mononuclear cells transplantation (BMT). Unilateral hindlimb ischemia was surgically induced in Lewis rats. One week after surgery, administration of 100 mg/kg per day G-CSF significantly increased the laser Doppler blood perfusion index (LDBPI), number of angiographically detectable collateral vessels (angiographic score), and capillary density determined by alkaline phosphatase staining. In the BMT group (1 x 10(7) cells/rat) and the group with combined G-CSF treatment and BMT, LDBPI was significantly increased compared with that in the vehicle-treated group. In the BMT group, neovascularization was significantly increased as evidenced by the angiographic score and capillary density compared with the vehicle-treated group. Furthermore, the combination of G-CSF treatment and BMT augmented neovascularization compared with BMT alone, as evidenced by the angiographic score and capillary density. Moreover, G-CSF significantly increased vascular endothelial growth factor mRNA and fibroblast growth factor-2 mRNA in hindlimb muscle. In conclusion, G-CSF was found to augment neovascularization in rat hindlimb ischemia. Combined use of G-CSF treatment and BMT may be a useful strategy for therapeutic neovascularization in ischemic tissues.

Angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium after myocardial infarction.

Osteopontin has been reported to have an important role in cardiac fibrosis. However, little is known about the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin type 1 receptor blockers (ARB) on osteopontin expression in infarcted myocardium. The purpose of this study was to elucidate the effects of an ACEI (perindpril) and an ARB (candesartan cilexitil) on cardiac function as assessed by Doppler echocardiography and cardiac osteopontin expression associated with cardiac remodeling in myocardial infarcted rats. ACEI or ARB was administered after myocardial infarction (MI). At 4 weeks after MI, cardiac function, and mRNAs in non-infarcted myocardium were analyzed. ACEI and ARB equally prevented left ventricular dilatation, reduction of ejection fraction, and the increase in E/A wave velocity ratio and the rate of E wave deceleration by MI. ACEI and ARB significantly suppressed increased mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, osteopontin, and collagen I and III in the non-infarcted ventricle at 4 weeks. Immunohistochemically stained osteopontin was increased in interstitial fibrosis of non-infarcted myocardium. Both ACEI and ARB significantly prevented cardiac fibrosis and osteopontin expression. In conclusion, angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium and prevents cardiac remodeling after MI.

Role of c-Jun NH2-terminal kinase in G-protein-coupled receptor agonist-induced cardiac plasminogen activator inhibitor-1 expression.

Plasminogen activator inhibitor-1 (PAI-1) has been implicated as a contributing risk factor for cardiovascular disease. However, little is known about molecular mechanisms of cardiac PAI-1 gene expression. To elucidate these mechanisms, dominant negative mutants of c-Jun NH(2)-terminal kinase (JNK), p38MAPK, apoptosis signal-regulating kinase-1 (ASK-1) and c-Jun were overexpressed in rat neonatal ventricular cardiac myocytes and fibroblasts by adenovirus vector to abrogate the activation of the corresponding endogenous proteins. One hundred nmol/l of angiotensin II significantly enhanced the JNK and p38MAPK activities of cardiomyocytes (2.3-fold and 1.9-fold, P < 0.05) and fibroblasts (3.2-fold and 2.5-fold, P < 0.05). At 3 h after stimulation, angiotensin II was found to have significantly increased PAI-1 mRNA, by 5.2-fold in cardiomyocytes and by 9.7-fold in fibroblasts. Dominant negative mutants of JNK, ASK-1 and c-Jun significantly inhibited PAI-1 mRNA expression and protein synthesis in both cardiomyocytes and fibroblasts, whereas a dominant negative mutant of p38MAPK did not change this expression. Moreover, a dominant negative mutant of JNK also significantly prevented the induction of PAI-1 mRNA expression by 100 nmol/l endothelin-1 and 10 micromol/l phenylephrine. In conclusion, G-protein-coupled receptor agonist-induced PAI-1 expression is partially mediated through JNK activation.

Vascular endothelial growth factor-expressing mesenchymal stem cell transplantation for the treatment of acute myocardial infarction.

OBJECTIVE: Vascular endothelial growth factor (VEGF) plays an important role in inducing angiogenesis. Mesenchymal stem cells (MSCs) may have potential for differentiation to several types of cells, including myocytes. We hypothesized that transplantation of VEGF-expressing MSCs could effectively treat acute myocardial infarction (MI) by providing enhanced cardioprotection, followed by angiogenic effects in salvaging ischemic myocardium. METHODS AND RESULTS: The human VEGF165 gene was transfected to cultured MSCs of Lewis rats using an adenoviral vector. Six million VEGF-transfected and LacZ-transfected MSCs (VEGF group), LacZ-transfected MSCs (control group), or serum-free medium only (medium group) were injected into syngeneic rat hearts 1 hour after left coronary artery occlusion. At 1 week after MI, MSCs were detected by X-gal staining in infarcted region. High expression of VEGF was immunostained in the VEGF group. At 28 days after MI, infarct size, left ventricular dimensions, ejection fraction, E wave/A wave ratio and capillary density of the infarcted region were most improved in the VEGF group, compared with the medium group. Immunohistochemically, alpha-smooth muscle actin-positive cells were most increased in the VEGF group. CONCLUSIONS: This combined strategy of cell transplantation with gene therapy could be a useful therapy for the treatment of acute MI.

Effects of granulocyte-colony stimulating factor on cardiac remodeling after myocardial infarction.

BACKGROUND: Recent studies suggest that granulocyte colony-stimulating factor (G-CSF) may be beneficial in the treatment of myocardial infarction (MI). However, the effects of G-CSF on MI are still controversial and the molecular mechanism of G-CSF treatment for repair of the infarcted heart is not fully understood. METHODS: Mice were divided into three groups: Control, MI and MI treated with G-CSF. Four weeks after MI, we examined cardiac function by Doppler echocardiography and measured non-infarcted myocardial mRNA expression by northern blot analysis. RESULTS: Cardiac function decreased significantly in the MI groups compared with the sham-operated groups. Additionally, the ratios of E wave to A wave peak velocity (E/A) in the MI groups were higher than in the control group. E/A in G-CSF MI mice was significantly lower than in control MI mice (p<0.01). Matrix metalloproteinase-2 (MMP-2) mRNA expression was significantly increased in the MI groups compared with the control group (p<0.01). Furthermore, mRNA expression in the G-CSF MI group was significantly higher than in the Control MI group (p<0.05). CONCLUSIONS: G-CSF can prevent the LV remodeling process after MI that accompanies progressive cardiac dysfunction. One of the mechanisms of G-CSF treatment for cardiac remodeling after MI may be overexpression of MMP-2 in non-infarcted myocardium.

Long-term beneficial effect of infarct-related artery patency in acute anterior myocardial infarction in patients with poor myocardial viability in the region-at-risk.

BACKGROUND: Several studies have demonstrated the benefit of the patency of infarct-related artery (IRA) in acute myocardial infarction (AMI). However those studies have not been concerned with myocardial viability in the region-at-risk. In the present study the effect of the patency of IRA was investigated in the setting of anterior AMI with poor viable myocardium in the risk region. METHODS AND RESULTS: From 1993 to 1996 patients with a first time anterior AMI and poor viable myocardium in the region-at-risk at 1 month after onset were identified and enrolled. Patients with a totally occluded IRA were included in the Non-Open group (n=44), and patients with a reperfused IRA were included in the Open group (n=49). At 5 years after onset, left ventricular function was better preserved in the Open group than in the Non-Open group (p<0.05). Kaplan-Meier survival curves for cardiac mortality and event-free survival curves revealed poor prognoses in the Non-Open group over a 5-year period (p<0.05, respectively). The advantages of a patent IRA were further seen in health-related quality-of-life outcomes (p<0.05). CONCLUSIONS: Even in patients with poor myocardial viability after an anterior AMI, the patency of the IRA is strongly associated with improved long-term survival, independent of residual myocardium viability.

Effect of azithromycin therapy on coronary circulation in patients with coronary artery disease.

This study examined the effect of azithromycin therapy on the coronary microcirculation using measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography in 35 patients with coronary artery disease. CFVR increased significantly after azithromycin therapy (3.0 +/- 0.7 vs 3.5 +/- 0.7, p <0.001). The changes in CFVR were negatively correlated with changes in high-sensitivity C-reactive protein levels in patients receiving azithromycin.

Detecting viable myocardium and predicting functional improvement: comparisons of positron emission tomography, rest-redistribution thallium-201 single-photon emission computed tomography (SPECT), exercise thallium-201 reinjection SPECT, I-123 BMIPP SPECT and dobutamine stress echocardiography.

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 ((201)Tl) single-photon emission computed tomography (RR-Tl SPECT), (123)I-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 (201)Tl 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 chi(2)-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.

Fabry disease female proband with clinical manifestations similar to hypertrophic cardiomyopathy.

Fabry's disease is an X-linked inborn error of glycosphingolipid catabolism, resulting from a deficiency in alpha-galactosidase A (alpha-Gal A). A 56-year-old Japanese woman was at first suspected of having hypertrophic cardiomyopathy. The patient and her son had alpha-Gal A activity in leukocytes that was remarkably below the limit of controls. DNA analysis of the alpha-Gal A gene revealed a novel missense mutation at codon 19 in exon 1, resulting in leucine-to-proline substitution. As a result she was confirmed as a classic Fabry heterozygote. Recent advances in enzyme replacement therapy can reverse the storage of glycosphingolipids in Fabry's disease. Thus, in patients with cardiac hypertrophy, it is important to differentiate Fabry's disease from other causes of hypertrophy. Therefore, it is necessary to measure alpha-Gal A activity in all suspected cases and to analyze genetic abnormalities in heterozygotes.

Effects of aldosterone receptor antagonist and angiotensin II type I receptor blocker on cardiac transcriptional factors and mRNA expression in rats with myocardial infarction.

BACKGROUND: Because the effects of an aldosterone receptor antagonist on transcriptional factors and mRNA expression have not been fully examined in myocardial infarction (MI), the present study examined the effects of spironolactone (SPIRO) and candesartan cilexitil (CAN) on activation of activator protein-1 (AP-1), nuclear factor-kappaB (NF-kappaB) and mRNA expression in the non-ischemic myocardium after MI. METHODS AND RESULTS: MI was induced by ligation of the coronary artery in Wistar rats, which were separated into (1) vehicle-treated group, (2) CAN-treated group (10 mg/kg per day), (3) SPIRO-treated group (100 mg/kg per day) and (4) CAN + SPIRO-treated group. The activity of both AP-1 and NF-kappaB was significantly increased at 4 weeks after MI. CAN or SPIRO significantly prevented the cardiac remodeling and activity of AP-1 and NF-kappaB. Furthermore, CAN + SPIRO prevented the cardiac remodeling and activation of AP-1 and NF-kappaB, compared with CAN or SPIRO alone. Myocardial atrial natriuretic peptide, brain natriuretic peptide, collagen I and III mRNAs were enhanced by MI, and CAN or SPIRO alone significantly reduced the mRNAs. CAN + SPIRO significantly prevented these mRNAs, compared with CAN or SPIRO alone. CONCLUSIONS: Both aldosterone and angiotensin II are involved in the myocardial transcriptional activation of AP-1, NF-kappaB and the cardiac remodeling-related mRNAs. The combination of CAN and SPIRO may be a potent therapeutic strategy for preventing cardiac remodeling after MI.

Involvement of apoptosis signal-regulating kinase-1 on angiotensin II-induced monocyte chemoattractant protein-1 expression.

OBJECTIVE: Monocyte chemoattractant protein 1 (MCP-1) could contribute to enhanced leukocyte recruitment and activation resulting in chronic tissue damage. However, little is known about the molecular mechanisms of cardiac MCP-1 expression. To elucidate these molecular mechanisms, angiotensin II-induced expression of MCP-1 was examined in cultured rat neonatal ventricular cardiomyocytes and fibroblasts by adenovirus gene transfer. METHODS AND RESULTS: MCP-1 mRNA increased 3.6-fold in cardiac fibroblasts at 3 hours after 100 nmol/L angiotensin-II stimulation (P<0.01), whereas MCP-1 mRNA in cardiomyocytes was unchanged. Angiotensin II significantly enhanced JNK, p38MAPK, and nuclear factor-kappaB (NF-kappaB) activities of cardiac fibroblasts. Wild-type ASK-1 increased MCP-1 expression of cardiac fibroblasts, whereas dominant negative mutant of ASK-1 (DN-ASK), dominant negative mutant of p38MAPK (DN-p38MAPK), and pyrrolidine dithiocarbamate significantly inhibited such expression. The increased MCP-1 mRNA expression in wild-type ASK-1 transfected fibroblasts was inhibited by cotransfection with adenovirus expressing DN-p38MAPK. On the contrary, the decreased MCP-1 mRNA expression in DN-ASK transfected cells was increased by cotransfection with adenovirus expressing constitutively active MKK6. CONCLUSIONS: Angiotensin II induced MCP-1 gene expression in cardiac fibroblasts. The angiotensin II-induced activation of ASK-1 followed by p38MAPK and NF-kappaB signaling in cardiac fibroblasts is partially involved in myocardial MCP-1 expression.

Prevalence of hepatitis C virus infection among patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is defined as inappropriate ventricular hypertrophy without a cardiac or systemic cause. On the other hand, hepatitis C virus (HCV) causes extrahepatic manifestations as well as chronic persistent infection in hepatocytes. We studied the association of HCV infection with HCM, comparing the prevalence of HCV antibodies between HCM patients and age- and gender-matched controls with other cardiovascular diseases at a single institution, for reasons of exclusion of bias. We then described the clinical features and genotype analysis of HCV RNA in HCM. The diagnosis of HCM was established by echocardiographic demonstration of a hypertrophied (> or =15 mm), nondilated left ventricle in the absence of another systemic or cardiovascular disease capable of producing the magnitude of hypertrophy observed. The study population consisted of 80 patients with HCM, in whom HCV antibody was examined (55 men and 25 women; mean age 56.6 +/- 12.4 years; ranging from 19 to 80 years), compared with a total of 80 age- and gender-matched controls without HCM. The prevalence of HCV infection in patients with HCM (18/80) was significantly higher than in control subjects (5/80) (Chi(2) = 7.312, P = 0.007). Of the 12 patients in whom the genotype of HCV was analyzed, 7 had type 1b and 5 had type 2a. The prevalence of HCV infection was higher in patients with HCM than in age- and gender-matched control subjects with other cardiovascular diseases. The result suggests that HCV may play an important role in these HCV-positive HCM patients.

Impact of diabetes mellitus on worsening of the left ventricular ejection fraction in exercise-gated 201Tl myocardial single photon emission computed tomography in patients with coronary artery disease.

It remains uncertain whether factors other than the severity of coronary artery disease (CAD) are associated with the worsening of the left ventricular ejection fraction (LVEF) by exercise. In the present study the impact of coronary risk factors on the worsening of LVEF by exercise was investigated in 391 patients with known or suspected CAD using exercise-gated (201)Tl scanning to calculate the LVEF. Significant worsening of the LVEF by exercise was defined as >4.7% (mean plus 1 SD of the value in 116 patients without CAD). Multivariate analysis revealed that diabetes mellitus (DM) was an independent risk factor for the worsening of LVEF by exercise in patients with multivessel (2- or 3-vessel) CAD with an odds ratio (95% confidence interval) of 2.2 (1.1-4.5, p=0.037). In 157 patients with 2- or 3-vessel CAD, 20 (23.5%) of 85 nondiabetic patients and 31 (43.1%, p=0.009 vs nondiabetic patients) of 72 diabetic patients showed significant worsening of LVEF by exercise. In patients with 2- or 3-vessel CAD, there was no significant difference in Gensini score or reversibility of perfusion defects between nondiabetic and diabetic patients. Thus, DM is a risk factor for worsening LVEF by exercise in addition to the severity of CAD.

Identification of cardiac sarcoidosis with (13)N-NH(3)/(18)F-FDG PET.

UNLABELLED: To our knowledge, no study investigating the usefulness of cardiac PET for detection of myocardial involvement of sarcoidosis is available. We investigated whether (13)N-NH(3)/(18)F-FDG PET could identify cardiac involvement in patients with sarcoidosis. METHODS: Seventeen patients with cardiac sarcoidosis underwent cardiac (13)N-NH(3)/(18)F-FDG PET under fasting condition. Systemic sarcoidosis was diagnosed by histologically proven noncaseating epithelioid granuloma, and cardiac sarcoidosis was diagnosed according to the Japanese Ministry of Health and Welfare guidelines for diagnosing cardiac sarcoidosis. RESULTS: Only 6 patients exhibited myocardial (201)Tl defects and only 3 patients exhibited abnormal (67)Ga accumulation in the heart. Thirteen patients exhibited (13)N-NH(3) defects, and 14 patients exhibited increased (18)F-FDG uptake in the heart; 12 patients exhibited both (13)N-NH(3) defects and increased (18)F-FDG uptake, 2 patients exhibited increased (18)F-FDG uptake but no (13)N-NH(3) defect, and 1 patient exhibited (13)N-NH(3) defects but no increased (18)F-FDG uptake. (13)N-NH(3) defects were observed frequently in the basal anteroseptal wall of the left ventricle, and increased (18)F-FDG uptake was observed frequently in the basal and midanteroseptal-lateral wall of the left ventricle. Involvement of the apex was rare. Seven patients were treated with steroid hormone and underwent follow-up cardiac PET 1 mo after steroid therapy. (13)N-NH(3) defects exhibited no significant change after steroid therapy, whereas increased (18)F-FDG uptake was markedly diminished in size and intensity in 5 patients and disappeared completely in 2 patients. CONCLUSION: Our findings suggest that cardiac (13)N-NH(3)/(18)F-FDG PET is the most useful method both for the identification of cardiac involvement of sarcoidosis and for the assessment of cardiac sarcoidosis disease activity.

Unruptured aneurysm of the sinus of valsalva with Behçet's disease.

A 52-year-old Japanese man who had suffered from Behçet's disease since the age of 45 years was admitted to hospital for evaluation of syncope and heart murmur. Echocardiography and aortography revealed severe aortic regurgitation and cystic masses under the right coronary cusp and the left ventricular outflow tract, but no shunt jet. He was diagnosed with unruptured aneurysm of the sinus of Valsalva, and surgical closure of the orifice of the aneurysm was performed. The diameter of the orifice was 11 mm and the aneurysm was 15 mm in depth, and consisted of 2 chambers. Because the aortic regurgitation was reduced after patch closure of the orifice, aortic valve replacement was not performed. Unruptured aneurysm of the sinus of Valsalva is a rare clinical lesion, but patients with active inflammatory disease of the aorta, such as in Behçet's disease, should have periodic echocardiography for early detection of an aneurysm or valvular involvement, even if there are not any symptoms.

Incremental value of assessment of regional wall motion for detection of multivessel coronary artery disease in exercise (201)Tl gated myocardial perfusion imaging.

UNLABELLED: Assessment of reversible perfusion defects in exercise (201)Tl perfusion SPECT has low sensitivity and high specificity for detection of multivessel coronary artery disease (CAD). The goal of this study was to evaluate whether worsening of left ventricular regional wall motion assessed by an automated algorithm in exercise (201)Tl electrocardiography-gated SPECT had incremental diagnostic value over perfusion data for detection of multivessel CAD. METHODS: Two hundred one patients underwent exercise (201)Tl gated SPECT. Software that automatically analyzes left ventricular function was used to assess exercise and rest regional wall motion. Regional wall motion on initial images was compared with that on rest images, that is, delayed images for patients without reinjection images and reinjection images for patients with reinjection images. The left ventricle was divided into 9 segments, with individual segments assigned to 3 coronary territories. Worsening of wall motion was defined as worsening in any segment on initial images compared with rest images. RESULTS: Of 73 patients with multivessel CAD, 20 (27.4%) had reversible perfusion defects in multiple coronary territories, 26 (35.6%) exhibited worsening of regional wall motion in multiple territories, and 37 (50.7%) had reversible perfusion defects or worsening of regional wall motion in multiple territories. The sensitivity of the combination of reversible perfusion defect and worsening of regional wall motion was significantly higher than that of reversible perfusion defect alone for detection of multivessel CAD (50.7% vs. 27.4%, P < 0.05). The specificity of the combination of reversible perfusion defect and worsening of regional wall motion for detecting multivessel CAD did not differ from that of reversible perfusion defect alone and that of worsening of regional wall motion alone (94.5% vs. 99.2% and 97.7%, respectively, P = not statistically significant). CONCLUSION: Combined assessment of worsening of left ventricular regional wall motion by exercise and perfusion data in exercise (201)Tl gated myocardial SPECT was more sensitive, with acceptable specificity, than was assessment with perfusion data alone for detection of multivessel CAD.

Incremental value of left ventricular ejection fraction for detection of multivessel coronary artery disease in exercise (201)Tl gated myocardial perfusion imaging.

UNLABELLED: Assessment of reversible defects in exercise (201)Tl perfusion SPECT has low sensitivity and high specificity for detection of multivessel coronary artery disease (CAD). The goal of this study was to evaluate whether the left ventricular ejection fraction (LVEF) in exercise (201)Tl gated SPECT had incremental diagnostic value over perfusion data for detection of multivessel CAD. METHODS: One hundred eighty-two patients underwent exercise (201)Tl gated SPECT. Automated LV function analysis software was used for calculation of the postexercise and the rest LVEF. The best threshold between 0- to 1-vessel CAD and 2- to 3-vessel CAD was determined as the cutoff that on receiver-operating-characteristic analysis resulted in the best sensitivity for detection of multivessel CAD with an associated specificity of >90%. RESULTS: Only 18 (26.9%) of 67 patients with multivessel CAD had reversible defects in multiple territories. Sensitivities of the postexercise and the rest LVEF and the worsening of the LVEF by exercise did not differ from those of perfusion data alone. Sensitivities of the combination of perfusion data and the postexercise and rest LVEF did not differ from those of perfusion data alone, whereas the sensitivity of the combination of perfusion data and worsening of the LVEF (i.e., reversible defects in multiple territories or worsening of the LVEF >5.6% [or both]) was significantly greater than that of perfusion data alone (43.3% vs. 26.9%; P < 0.05), with an acceptable level of specificity (90.4%). CONCLUSION: The worsening of the LVEF by exercise has the potential to detect patients with multivessel CAD among those without multivessel patterns of reversible defects.