Low-Dose Erythropoietin in Patients With ST-Segment Elevation Myocardial Infarction (EPO-AMI-II)　- A Randomized Controlled Clinical Trial.

BACKGROUND: Erythropoietin (EPO) has antiapoptotic and tissue-protective effects, but previous clinical studies using high-dose EPO have not shown cardioprotective effects, probably because of platelet activation and a lack of knowledge regarding the optimal dose. In contrast, a small pilot study using low-dose EPO has shown improvement in left ventricular function without adverse cardiovascular events.Methods and Results:We performed a multicenter (25 hospitals), prospective, randomized, double-blind, placebo-controlled, dose-finding study to clarify the efficacy and safety of low-dose EPO in patients with ST-segment elevation myocardial infarction (STEMI) under the Evaluation System of Investigational Medical Care of the Ministry of Health, Labor and Welfare of Japan. In total, 198 STEMI patients with low left ventricular ejection fraction (LVEF <50%) were randomly assigned to receive intravenous administration of EPO (6,000 or 12,000 IU) or placebo within 6 h of successful percutaneous coronary intervention. At 6 months, there was no significant dose-response relationship in LVEF improvement among the 3 groups tested (EPO 12,000 IU: 5.4±9.3%, EPO 6,000 IU: 7.3±7.7%, Placebo: 8.1±8.3%, P=0.862). Low-dose EPO also did not improve cardiac function, as evaluated by 99 mTc-MIBI SPECT or NT-proBNP at 6 months and did not increase adverse events. CONCLUSIONS: Administration of low-dose EPO did not improve LVEF at 6 months in STEMI patients (UMIN000005721).

Reconstruction of semiautomated cardiac regions of interest using iodine-123 metaiodobenzylguanidine myocardial scintigraphy.

INTRODUCTION: Analysis using cardiac iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy with regions of interest (ROIs) is useful for assessing myocardial sympathetic activity. However, manual placement of the cardiac ROI is sometimes difficult because myocardial MIBG uptake is reduced in patients with heart failure. A new method was developed to reconstruct the semiautomated cardiac ROI in a sympathetic denervated heart. MATERIALS AND METHODS: Using dynamic planar data, a summed image was generated and the matrix size was changed. Then, the radial count profiles originating from the center of the left ventricle were generated to extract the myocardial count profiles. An asymmetric Gaussian distribution was fitted to each profile and the epicardial border was defined by the threshold method. This program was tested in 50 patients, and its reproducibility was validated when compared with the manual tracing method. RESULTS: The semiautomated method yielded a better quality image compared with the standard image with higher counts. Cardiac ROIs were generated successfully in each patient within normal limits. The intraobserver and interobserver agreements were excellent (P<0.0001 each). This approach showed a significantly higher consistency in measuring the heart-to-mediastinum ratio as compared with the manual tracing method (P<0.05). CONCLUSION: The semiautomated method is useful in generating cardiac ROIs with high reproducibility in myocardial MIBG imaging.

Angioscopic assessment of peri-stent contrast staining following drug-eluting stent implantation.

BACKGROUND: Peri-stent contrast staining (PSS) has been recognized as a predictor of late stent thrombosis following drug-eluting stent (DES) implantation. However, the intravascular conditions at PSS sites remain unclear. METHODS AND RESULTS: We evaluated 10 patients (median age 72 years, 80% male) with stable angina pectoris by coronary angioscopy. The patients had a total of 11 DES implantations (5 sirolimus-eluting stents; 4 paclitaxel-eluting stents; 2 everolimus-eluting stents) that showed PSS. Neointimal coverage (NIC), presence of thrombus, and yellow plaques underneath the stent were compared between PSS and non-PSS sites for each stent. NIC was graded as: grade 0, struts exposed; grade 1, struts bulging into the lumen, although covered; grade 2, struts embedded by neointima, but translucent; grade 3, struts fully embedded and invisible. Mean follow-up was 394±206 days (median: 289). NIC grade was lower at PSS sites (P=0.021) with 8 out of 11 stents (73%) having grade 0. Angioscopy detected a thrombus more frequently at PSS sites than at non-PSS sites (64% vs. 9%, P=0.012). Yellow plaques tended to be more significant at PSS sites than at non-PSS sites (82% vs. 45%, P=0.091). CONCLUSIONS: The angioscopic findings suggest high thrombogenicity at PSS sites.

Arterial repair 4 months after zotarolimus-eluting stent implantation observed on angioscopy.

BACKGROUND: Arterial repair in the early phase following implantation of a zotarolimus-eluting stent (ZES) remains unknown. METHODS AND RESULTS: Following implantation of 49 Endeavor ZES in 33 patients, follow-up angioscopy was performed in 13 patients (26 ZES) in the early phase (EP; 123±24 days) and in 20 patients (23 ZES) in the middle phase (MP; 247±17 days). Neointimal coverage (NIC) was graded as follows: grade 0, stent struts exposed; grade 1, struts bulging into the lumen, although covered; grade 2, struts were embedded by the neointima but were seen translucently; grade 3, struts fully embedded and invisible. NIC was defined as heterogeneous for NIC grade variation≥1. The presence of thrombus and yellow plaque was also investigated. Although NIC heterogeneity tended to be more frequent in EP than in MP (50% vs. 22%, P=0.070), and yellow plaque significantly more frequent (58% vs. 13%, P=0.0025), the majority of stents were dominant NIC grade 3 at both follow-up periods (73% in EP vs. 78% in MP, P=0.75). There was no significant difference in thrombus (23% in EP vs. 4% in MP, P=0.10) between the follow-ups. CONCLUSIONS: Sufficient arterial repair may have occurred by 4 months after ZES implantation.

Usefulness of scintigraphy to predict electrical storms in severe idiopathic dilated cardiomyopathy.

BACKGROUND: Although several predictors of an electrical storm (ES) are indicated in patients with idiopathic dilated cardiomyopathy (IDCM), whether the severity of the myocardial tissue damage (SMTD) evaluated by myocardial perfusion SPECT (MPS) has an association with an ES remains unclear. The purpose of this study was to elucidate the clinical significance of SMTD for the prediction of ES in IDCM patients with an ICD. METHODS: Thirty-seven (27 men, mean age 58 ± 15 years) IDCM patients receiving ICD implantations for secondary prevention with preoperative MPS were enrolled in this study. The medical history, physical and laboratory findings, electrocardiograms, echocardiograms and MPS findings were evaluated. The SMTD was assessed by the summed scores of 17 segments using a 4-point system (0, normal ~3, severe defect). RESULTS: During a mean follow-up of 43.9 ± 30.7 months, an ES developed in 12/37 (32.4 %) patients. The SMTD score predicted an ES with a 92 % sensitivity and 56 % specificity, at a cut-off score of 10. In addition, a multivariate analysis showed that the SMTD score remained an independent predictor of an ES (HR 1.09/score 1 increase, 95 % CI 1.01-1.19, p = 0.02). The SMTD score was significantly associated with three indices of late potentials on the signal-averaged electrocardiograms, and was significantly higher in patients with positive late potentials (p = 0.0006). CONCLUSION: SMTD score assessed by MPS has a strong correlation to the late potentials and higher SMTD score may increase the risk of ES among patients with IDCM and an ICD.

Successful outside-the-stent stenting for in-stent chronic total occlusion in the common iliac artery.

Several studies showed durable long-term clinical benefit of endovascular therapy with stenting in aorto-iliac occlusive disease. Although in-stent restenosis is easily treated in routine practice, we experienced an uncommon case of failed reconstitution of in-stent total occlusion at the common iliac artery (CIA). The case was treated with nitinol stent implantation outside of the in-stent occlusion site, and good vessel patency was observed at 14 months after the procedure. Nitinol stent implantation outside of an in-stent occlusion in the CIA is a novel reconstitution strategy when the guide wire cannot pass the occlusion site within a previously implanted stent.

Novel algorithm for quantitative assessment of left ventricular dyssynchrony with ECG-gated myocardial perfusion SPECT: useful technique for management of cardiac resynchronization therapy.

OBJECTIVES: Cardiac resynchronization therapy (CRT) is the established treatment for patients with chronic and severe heart failure, and it has been reported that the presence of left ventricular (LV) dyssynchrony is one of the most important factors which predict positive response of this therapy. In the present study, we developed new software algorithm for quantitative assessment of LV dyssynchrony from ECG-gated myocardial perfusion SPECT (GMPS), and evaluated its utility for the management of CRT. METHODS: Thirty-three patients with chronic severe heart failure were studied. GMPS was performed with 16 frame per-cardiac-cycle before and 6 months after CRT and LV end-diastolic volume, end-systolic volume (LVESV), ejection fraction (LVEF) were calculated by QGS software. We generated the time-activity curve per-cardiac-cycle in 4 myocardial segments by Fourier transform curve-fitting of the 16 serial count values, and measured the time from R-wave to the maximum-count point [time to end-systole (TES)] in each. For the evaluation of the degree of LV dyssynchrony, we used the maximum difference in TES (ΔTES) among the 4 segments which corrected for R-R time as dyssynchrony index (DI). Moreover, DI at baseline evaluated by GMPS was compared with the echocardiographic index of LV dyssynchrony; maximum difference of time to peak velocity (ΔTPV) evaluated by tissue Doppler imaging (TDI). RESULTS: DI before CRT showed a significant correlation with the LV function, such as LVEF, LVESV (DI vs. LVEF; r = 0.57, P < 0.0001. DI vs. LVESV; r = 0.64, P < 0.0001). The study subjects were divided into 2 groups, responder group (R-Gp) with LVEF increase >10% or LVESV decrease >10% and non-responder group (NR-Gp). DI before CRT was significantly larger in R-Gp than in NR-Gp (25.9 ± 22.2 vs. 10.8 ± 8.9, P = 0.01). In R-Gp, DI showed a significant decrease after CRT (25.9 ± 22.2 → 13.6 ± 10.9, P < 0.05). DI at baseline measured by GMPS correlated significantly with ΔTPV at baseline measured by TDI (r = 0.38, P < 0.05). CONCLUSIONS: This new algorithm for the estimation of LV dyssynchrony might be comparable to TDI, and contributes to the prediction and the evaluation for the response of CRT.

Angioscopic assessment of arterial repair following biodegradable polymer-coated biolimus A9-eluting stent implantation. - Comparison with durable polymer-coated sirolimus-eluting stent-.

BACKGROUND: Second-generation drug-eluting stents (DES) are expected to show better arterial repair than older DES. We angioscopically compared the biodegradable polymer-coated biolimus A9-eluting stent (BES) and durable polymer-coated sirolimus-eluting stent (SES) to explore differences in arterial repair. METHODS AND RESULTS: Angioscopy was performed 9 ± 1 months after 15 BES and 16 SES were implanted initially in the native coronary artery. Heterogeneity of neointimal coverage (NIC) as well as the dominant NIC grade was examined. NIC was defined as: grade 0 = fully visible struts; grade 1 = struts bulging into the lumen, but covered; grade 2 = embedded, but translucent struts; grade 3 = invisible struts. Heterogeneity was judged when the NIC grade varied ≥ 1. In-stent late loss (0.06 ± 0.23 vs. 0.07 ± 0.18 mm, P = 0.80), and dominant NIC grade (1.5 ± 0.8 vs. 1.3 ± 0.7, P = 0.45) were similar for BES and SES. Within the stents, NIC was more heterogeneous in SES than in BES (P = 0.035). 80% of BES showed homogeneous NIC, while 56% of SES had heterogeneous NIC. CONCLUSIONS: BES showed limited late loss similar to that for SES. Nonetheless, the NIC with BES was more homogeneous than that with SES. Biodegradable polymer-coated BES may have an advantage in homogeneous NIC.

Transient constrictive pericarditis diagnosed by cardiac magnetic resonance, 67Ga scintigraphy, and positron emission tomography.

Constrictive pericarditis occurs following pericardial fibrosis and often leads to refractory right side heart failure. Surgical relief is often required for correction of hemodynamic abnormalities. Two recent reports described a transient form of constrictive pericarditis that resolved without surgical intervention. In this case, we present representative images of transient constrictive pericarditis detected by late gadolinium enhancement of cardiac magnetic resonance, 67Ga scintigraphy, and 18FDG positron emission tomography before and after corticosteroid therapy. This is the first demonstration of the utility of imaging modalities in the diagnosis of transient constrictive pericarditis, and we document radiologic changes in pericardial inflammation after medical therapy.

Prediction of functional recovery after revascularization using quantitative gated myocardial perfusion SPECT: a multi-center cohort study in Japan.

BACKGROUND: Prediction of left ventricular functional recovery is important after myocardial infarction. The impact of quantitative perfusion and motion analyses with gated single-photon emission computed tomography (SPECT) on predictive ability has not been clearly defined in multi-center studies. METHODS: A total of 252 patients with recent myocardial infarction (n = 74) and old myocardial infarction (n = 175) were registered from 25 institutions. All patients underwent resting gated SPECT using (99m)Tc-hexakis-2-methoxy-isobutyl isonitrile (MIBI) and repeated the study after revascularization after an average follow-up period of 132 +/- 81 days. Visual and quantitative assessment of perfusion and wall motion were performed in 5,040 segments. RESULTS: Non-gated segmental percent uptake and end-systolic (ES) percent uptake were good predictors of wall motion recovery and significantly differed between improved and non-improved groups (66 +/- 17% and 55 +/- 18%, p < 0.0001 for non-gated; 64 +/- 16% and 51 +/- 17% for ES percent uptake, p < 0.0001). The area under the curve of receiver operating characteristics curve for non-gated percent uptake, ES percent uptake, end-diastolic percent uptake and visual perfusion defect score was 0.70, 0.71, 0.61, and 0.56, respectively. Sensitivity and specificity of percent uptake were 68% and 64% for non-gated map and 80% and 52% for ES percent uptake map. An optimal threshold for predicting segmental improvement was 63% for non-gated and 52% for ES percent uptake values. CONCLUSION: Segmental (99m)Tc-MIBI uptake provided a useful predictor of wall motion improvement. Application of quantitative approach with non-gated and ES percent uptake enhanced predictive accuracy over visual analysis particularly in a multi-center study.

Myocardial scintigraphy after pacemaker implantation for congenital complete atrioventricular block.

Patients with isolated congenital complete atrioventricular block (CCAVB) occasionally develop dilated cardiomyopathy (DCM), despite early pacemaker implantation. However, the etiology of the DCM and its relationship to permanent ventricular pacing are not fully understood. Twenty-five patients with CCAVB underwent (99m) technetium (Tc) myocardial perfusion scintigraphy. Five patients were studied before and after pacing, providing a total of 30 image sets, which were divided into three groups; group 1: CCAVB before pacemaker implantation (PMI) (n = 11); group 2: CCAVB after PMI who did not subsequently develop DCM (n = 13); group 3: CCAVB after PMI who subsequently developed DCM (n = 6). Perfusion defects on single-photon-emission computed tomography (SPECT) were identified in group 1, 0 of 11 patients; group 2, 85% of patients; and group 3, 100% of patients. In groups 2 and 3, in patients with right ventricular pacing, the perfusion defects were mainly in the septum or between the apex and septum. On 20 segments' polar maps, the distribution of %uptake showed a similar pattern in groups 2 and 3, the degree of decreased %uptake and the number of segments with decreased %uptake being more severe in group 3. "Artificial" left bundle branch block (LBBB) pattern myocardial contraction induced by right ventricular pacing decreased myocardial perfusion around the apex and septum. Some patients with CCAVB will develop left ventricular dysfunction caused by artificial LBBB-induced interventricular asynchrony.

Creation and characterization of Japanese standards for myocardial perfusion SPECT: database from the Japanese Society of Nuclear Medicine Working Group.

OBJECTIVE: Standards for myocardial single-photon emission computed tomography (SPECT) adapted for a Japanese population were not available. The purpose of this study was to create standard files approved by the Japanese Society of Nuclear Medicine and to make known the characteristics of the myocardial perfusion pattern of this population. METHODS: With the collaboration of nine hospitals, a total of 326 sets of exercise-rest myocardial perfusion images were accumulated from subjects with a low likelihood of cardiac diseases. The normal database included a (99m)Tc-MIBI/tetrofosmin myocardial perfusion study with 360 degrees (n = 80) and 180 degrees (n = 56) rotations, (201)Tl study with 360 degrees (n = 115) and 180 degrees rotations (n = 54) and a dual-isotope study with 360 degrees rotation (n = 27). The projection images were transferred by digital imaging and communications in medicine (DICOM) format and reconstructed and analyzed with polar maps. RESULTS: The projection data from multiple centers were successfully transferred to a common format for SPECT reconstruction. When the average values were analyzed using a 17-segment model, myocardial counts in the septal segment differed significantly between 180 degrees and 360 degrees rotation acquisitions. Regional differences were observed between men and women in the inferior and anterior regions. A tracer difference between (99m)Tc and (201)Tl was also observed in some segments. The attenuation patterns differed significantly between subjects from the United States and those from Japan. CONCLUSIONS: Myocardial perfusion data that were specific for the Japanese population were generated. The normal database can serve a standard for nuclear cardiology work conducted in Japan.

[Clinical evaluation of cellular pathophysiology in cardiovascular diseases with radionuclide biochemical imaging].

Myocardial imaging with radionuclide biochemical tracers has provided advanced diagnostic approaches for patients with coronary artery disease and heart failure. Since the biochemical information includes cellular events such as metabolism, inflammation, and sympathetic drive, it can be regarded as one of 'Molecular Imaging'. In this chapter, I introduce topics on clinical evaluation of cellular pathophysiology in cardiovascular diseases with radionuclide biochemical imaging: detection of coronary vulnerable plaque to predict the occurrence of acute coronary syndrome and estimation of altered myocardial metabolism and sympathetic drive to estimate the severity of myocardial failure.