Abstract Background The findings of our recent study entitled, “Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS)” showed that myocardial perfusion ...single photon emission computed tomography (MPS) can detect coronary artery disease (CAD) and help to predict future cardiac events in patients with suspected or extant CAD. However, the extent of the benefit conferred by percutaneous coronary intervention (PCI) as an initial management strategy compared with optimal medical therapy remains controversial. Little evidence supports the notion that myocardial ischemia identified using MPS is an alternative target of coronary revascularization to reduce the likelihood of developing cardiac events. Methods The multicenter, prospective cohort J-ACCESS 4 study aims to clarify the prognostic impact of reducing myocardial ischemia determined using electrocardiogram-gated MPS in Japanese patients with coronary artery disease. We started to register patients in J-ACCESS 4 at 74 facilities during June 2012 and will continue to do so until December 2013 or until the cohort comprises 500 patients who will participate in the study from one month before, until two months after stress/rest MPS assessment. Imaging data, the background of the patients including coronary risk factors and treatment before MPS assessments will be analyzed. The patients will undergo coronary revascularization within two months after MPS and/or receive appropriate medical therapy. The second stress/rest MPS will be performed from 4 to 10 months after coronary revascularization or registration. They will be followed up for over one year after the second MPS assessment. The primary endpoints will be cardiac death, sudden death of unknown cause, non-fatal myocardial infarction, and hospitalization for heart failure. The secondary endpoints will comprise death due to all causes including non-cardiac death and any cardiovascular events. This study will be completed in 2015. Here, we describe the design of the J-ACCESS 4 study.
Abstract Background and purpose An early diagnosis is essential for therapeutic decision and risk stratification in patients with suspected acute myocardial infarction (AMI). We analyzed and compared ...the diagnostic value of high-sensitivity troponin T (hs-TnT) and other cardiac markers in patients with an initially negative troponin T test at presentation. Methods and subjects The present study was a prospective, multicenter study including five participating emergency cardiovascular tertiary centers in Japan. From November 2009 through January 2011, patients with suspected AMI at the emergency room with an initial troponin T (c-TnT) test <100 ng/L were enrolled. Results A total of 85 patients were prospectively assigned from five participating emergency cardiovascular tertiary centers in Japan. The median time from the onset of chest pain to the T0 sampling was 165 min IQR 120–180. The final diagnoses according to the recent universal definition and other standard cut-off values were AMI in 47, unstable angina in 12, and non AMI in 38 patients. The overall ROC-AUC value of hs-TnT, c-TnT, creatine kinase MB, and heart-type fatty acid-binding protein were 0.810, 0.716, 0.782, and 0.880, respectively. The diagnostic sensitivity and negative predictive value of hs-TnT were both 100% for the patients admitted more than 120 min from the onset, however the specificity was limited for the whole time-windows (71%). The absolute value change of the hs-TnT from T0 to T3 sampling 3 h later improved the ROC-AUC up to 0.972 and the specificity was 92% at 22 ng/L (ROC-optimized cut-off) and 100% at 105 ng/L (rule-in cut-off). Conclusions The hs-TnT displayed 100% sensitivity and negative predictive value for the patients admitted more than 120 min from the onset, however the specificity was limited. The absolute change from T0 to T3 (22 ng/L) improved the total diagnostic performance.
Abstract Background Despite the introduction of the novel cadmium–zinc–telluride (CZT) single-photon emission computed tomography (SPECT) in Japan; its diagnostic value in clinical practice remains ...largely unknown. Methods The Semiconductor SPECT Study group is a multicenter Japanese registry which registered 1000 patients to evaluate the diagnostic utility of the CZT camera system (Discovery NM530c; GE Healthcare, Haifa, Israel). The patients underwent stress myocardial SPECT and coronary angiography within a 3-month interval. A significant stenosis was defined as ≥75% diameter narrowing based on the American Heart Association classification. Results Technetium (99m Tc) radiotracer (555–1110 MBq) was used in 71% and thallium-201 (201 Tl) (74–148 MBq) in 29%. The scan times with99m Tc-radiotracer were 5–10 min for stress and 3–10 min for rest, whereas those with201 Tl were 5–9 min for stress and 8–10 min for rest. To detect individual coronary stenosis, the respective sensitivities, specificities, and accuracies were 74%, 85%, and 81% for left anterior descending coronary artery (LAD) stenosis, 76%, 89%, and 85% for left circumflex stenosis, and 72%, 86%, and 82% for right coronary artery stenosis. However, 66% sensitivity and 91% specificity for LAD stenosis were observed with99m Tc-radiotracer, whereas 88% sensitivity and 63% specificity were found with201 Tl. Conclusions The novel CZT SPECT system facilitated a short scan time with reduced radiotracer dose, yielding an acceptable diagnostic performance for angiographical coronary artery disease, although the low sensitivity for LAD detection with99m Tc-radiotracer needs to be refined.
Abstract Background We examined the following: (1) whether the new simple markers related to the arterial stiffness/central hemodynamics i.e. arterial pressure-volume index (API) and arterial ...velocity pulse index (AVI) are clinically interchangeable with the commonly used markers brachial-ankle pulse wave velocity (baPWV) and radial augmentation index (rAI); (2) whether the new simple markers reflect vascular damage as reliably as the commonly used markers; (3) which cardiovascular risk factors are reflected by these new simple markers. Methods API, AVI, baPWV, and rAI were measured simultaneously in consecutive patients admitted for the management of cardiovascular disease and/or cardiovascular risk factors ( n = 322). Results The API was correlated with the baPWV ( R = 0.492, p < 0.001) and the AVI correlated with the rAI ( R = 0.462, p < 0.001). The API, AVI, baPWV, and rAI were higher in the patients admitted for coronary angiography (CAG group: n = 152) than in those admitted for reasons other than coronary angiography (nonCAG group: n = 170). After adjustments for confounding factors, only the AVI was found to be higher in the CAG group than in the nonCAG group. Multivariate linear regression analysis revealed that age and the systolic blood pressure were independently associated with the API and AVI after adjustments. Conclusion In patients with cardiovascular diseases or cardiovascular risk factors, the new simple markers and the commonly used markers are not interchangeable for assessing vascular damage and/or cardiovascular risk. Further study is proposed to examine whether AVI is higher in subjects with cardiovascular disease than in those without a history of cardiovascular disease. Similar to the case for the commonly used markers, age and the blood pressure significantly influenced both the new markers; therefore, age and the blood pressure need to be taken into account while interpreting the changes in these new simple markers.
Abstract Objective The purpose of this study was to examine the cardiovascular protective effects of candesartan in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting ...stents (DESs). Background Candesartan has been reported to reduce cardiovascular events when therapy was started 6 months after PCI with bare-metal stents in patients who survived restenosis. Candesartan started immediately after PCI with DESs was also effective in preventing cardiovascular events. Methods The 4C trial was a multicenter, prospective, randomized, open-label study. A total of 1145 patients at 39 centers in Japan were randomly assigned to receive candesartan plus standard medical treatment or standard medical treatment alone. The primary endpoints were all-cause death, and a composite of non-fatal myocardial infarction (MI), unstable angina pectoris (uAP), congestive heart failure (CHF), and non-fatal cerebrovascular events. The follow-up period was up to 3 years after the index PCI (ClinicalTrials.gov NCT00139386 ). Results The incidence of total death, one of the primary endpoints, was comparable between the two treatment groups (3.8% each, p = 0.9702). Another primary endpoint, non-fatal major cardiovascular events, tended to occur more often in the control group than in the candesartan group (9.2% vs. 12.5%, p = 0.0985). In contrast, candesartan significantly reduced one of the pre-specified secondary endpoints: cardiovascular events that included non-fatal MI, uAP, and CHF (4.4% vs. 6.7%, p = 0.0136). Furthermore, candesartan significantly reduced another secondary endpoint that included cardiovascular events and cardiovascular death (5.0% vs. 7.7%, p = 0.0493). Conclusions The 4C trial showed that candesartan administered immediately after PCI with DESs did not improve the prognosis after the index procedure, but did reduce some cardiac-related events for 3 years.
Abstract Background Elevated serum levels of cardiac troponin T (cTnT) and N-terminal fragment of B-type natriuretic peptide (NT-proBNP), and also increased arterial stiffness/abnormal central ...hemodynamics, are well-known risk factors for future cardiovascular events. The present study was conducted to clarify which of the two – the serum level of cTnT or that of NT-proBNP – might be more closely associated with the arterial stiffness/central hemodynamics. Methods In 2374 male employees of a company (46 ± 9 years), the following parameters were measured: second peak of the radial systolic pressure waveform (SP2), radial augmentation index (rAI), PP2 (SP2 minus the diastolic blood pressure), brachial-ankle pulse wave velocity (baPWV), and serum levels of cTnT and NT-pro BNP. Results After adjustments for confounding variables, binary logistic regression analyses demonstrated that baPWV was associated with a significant odds ratio for serum NT-proBNP ≥125 pg/mL (1.690; 95% confidence interval = 1.136–2.514, p = 0.002) and rAI was associated with a significant odds ratio for serum NT-proBNP ≥55 pg/mL (1.205; 95% confidence interval = 1.012–1.435, p = 0.036). The baPWV, rAI, SP2, and PP2 were not associated with significant odds ratios for elevated serum cTnT levels (≥0.014 ng/mL and ≥0.010 ng/mL). Conclusions In the middle-aged male worksite cohort studied, increased arterial stiffness/abnormal central hemodynamics appeared to be associated with elevated serum NT-proBNP levels, rather than with minimally elevated serum cTnT levels. This difference may be one of the plausible explanations for the independency of the predictive values of the two serum markers for future cardiovascular events.
Summary Background The presence and severity of coronary artery disease may be underestimated in patients who do not reach significant end-points of stress testing during myocardial perfusion ...imaging. We examined how the effect of the level of exercise may affect the ability of the quantitative gated single-photon emission computed tomography (SPECT) imaging to predict the future cardiac events (cardiac death, non-fatal myocardial infarction and severe heart failure). Method Of the 4629 consecutively registered patients for J-ACCESS (Japanese-assessment of cardiac event and survival study by quantitative gated SPECT), 2821 patients who underwent the exercise test were selected, and divided into two groups, which reached a target heart rate (group; n = 925) or not ( n = 1896). Leg fatigue was the most common reason for stopping the exercise test in non-reaching groups, we conducted a study comparing group with leg fatigue group (group II). Results During a 3-year follow-up period, total of 25 cardiac events (2.7%) occurred in group I and total of 73 events (3.9%) occurred in group II. The incidence of cardiac death was slightly but significantly higher in group II (P.04). A summed stress score (SSS) was able to separate the high-risk from low-risk patients in group II. The maximal heart rate was not an independent predictor for cardiac events. In Cox multivariate regression analysis, higher age (70 years), history of DM, EDV at rest and LVEF at rest were predictor of cardiac major events (cardiac death, myocardial infarction, heart failure), and higher age (70 years), ESV at rest were independent predictor of cardiac hard events (cardiac death, myocardial infarction) in group II. Conclusion Exercise SPECT imaging provides the useful prognostic information in patients who do not reach a significant end-point due to the leg fatigue. In such patients, those with normal SSS score and normal resting ESV have also a most favorable prognosis.
Summary Background Although stress-induced myocardial stunning often develops after exercise testing, determinants of this phenomenon have not been evaluated. Methods and results Thirty-one patients ...with 1-vessel coronary artery disease, limited to the left anterior descending artery (LAD), were evaluated by quantitative coronary angiography (QCA) and intracoronary pressure measurements to calculate fractional flow reserve (FFR). In addition, electrocardiogram-gated technetium-99m sestamibi myocardial imaging was acquired >30 min after exercise and 4 h later to assess the development of stunning. Exercise-induced myocardial stunning was observed in 11 patients (35%). In patients with myocardial stunning, a summed stress score (17.3 ± 7.1 vs. 8.1 ± 6.2, p < 0.001), summed difference score (10.3 ± 4.1 vs. 2.7 ± 1.9, p < 0.0001), and wall motion difference score (4.8 ± 2.8 vs. 0.9 ± 1.1, p < 0.0001) were greater than in those without, while diameter stenosis calculated by QCA (55.1 ± 17.3% vs. 29.8 ± 17.3%, p < 0.0001) was greater and FFR reduced significantly (0.54 ± 0.13 vs. 0.83 ± 0.06, p < 0.0001). Of note, 4 out of 21 patients (19%) with <50% LAD stenosis developed myocardial stunning, whereas only one patient with FFR of 0.64 or greater showed stunning. The best cut-off value was determined as 0.64 for FFR and 46% for QCA, providing 91% sensitivity and 100% specificity for FFR (chi-square = 57.2), but 91% sensitivity and 80% specificity for diameter stenoses measured by QCA (chi-square = 17.8). Conclusions The major determinant for exercise-induced myocardial stunning was a severe flow-limiting coronary stenosis, which was more important than anatomical evaluation based on luminal narrowing alone.
Abstract Background There are some cases in whom a sufficient improvement in fractional flow reserve (FFR) could not be achieved even if anatomical results indicated satisfactory stent deployment. We ...investigated the relation of abnormal findings between intravascular ultrasound (IVUS) and coronary pressure pullback measurement (CP-PB). Methods IVUS and CP-PB were investigated after stent deployment in 60 vessels in 53 patients. CP-PB criterion for adequate stent deployment was defined as a ratio of coronary pressure at the stent distal edge to the proximal edge (Psd/Psp) that is greater than 0.95. Results Residual pressure gradient across the stent which was indicated by Psd/Psp ≤ 0.95 was present in 11 (18%), and four of them were caused by insufficient stent expansion (incomplete apposition and asymmetric dilation), and five of them were caused by issues with stent edge (edge dissection and incomplete coverage of the plaques). Insufficient FFR recovery which was recorded at distal part of target vessel was present in 10 (17%), and the main causes corresponded to inadequate stent deployment in half of the lesions, and presence of residual lesion at a non-stent segment in the other half. There were six lesions in whom Psd/Psp was ≤0.95 but FFR was ≥0.80. Disagreement between IVUS and CP-PB findings was seen in 12 (20%). Conclusions Residual pressure gradient across the stent can reflect not only an insufficient stent expansion but also issues with stent edges. The decision of optimum stent deployment as assessed by IVUS and CP-PB was mismatched in 20% of cases, therefore careful attention should be paid to decoding the CP-PB findings.
Summary Adenosine is widely used as a pharmacologic agent for stress myocardial perfusion imaging. Vasospasm as a side effect of adenosine has been reported a few times in other countries, but it has ...not been reported in Japan. A 65-year-old woman was admitted to our hospital because of chest pain at rest and during exercise. She underwent myocardial scintigraphy, to rule out myocardial ischemia. After adenosine infusion, she felt chest pain and the electrocardiogram (ECG) showed ST elevation in inferior leads. Adenosine infusion was stopped immediately. Her chest pain resolved, and the ECG reverted to baseline. Perfusion image presented reverse redistribution in inferior segments, and coronary angiography revealed insignificant lesions. Transient ST elevation during adenosine infusion is thought to be due to coronary vasospasm, judging from scintigraphic and angiographic findings.
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