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Objective We aimed to reveal detailed on-treatment lipid profiles, lipid-related surrogate markers, and factors predicting failure to achieve the guideline-recommended lipid management goal following guideline-recommended statin treatment in Japanese patients with acute myocardial infarction (AMI). Methods Sixty AMI patients who underwent coronary intervention and had received rosuvastatin 10 mg/day since the start of their hospitalization were assessed for on-treatment lipid-related profiles, including high-sensitivity C-reactive protein, small dense low-density lipoprotein cholesterol (sd LDL-C), and lipoprotein (a), at the 12-week follow-up. Patients who failed to achieve the guideline-recommended lipid management at 12 weeks were defined as the "unachieved group." Univariate and multivariate logistic regression analyses were performed to evaluate the predictors of inclusion in the unachieved group after high-dose statin treatment. Results Despite the use of high-dose rosuvastatin, 61.7% of the enrolled AMI patients were included in the unachieved group. In addition, the unachieved group had higher sd LDL-C and lipoprotein (a) levels than the achieved group. Logistic regression analyses demonstrated that low baseline high-density lipoprotein cholesterol (HDL-C) levels and the absence of diabetes were predictors of inclusion in the unachieved group. Conclusion More than half of the Japanese AMI patients treated with rosuvastatin 10 mg/day did not achieve the guideline-recommended goal of lipid management and still had lipid-related residual risk at 12 weeks. Particular attention should be paid to patients with low baseline HDL-C levels and those without diabetes with regard to their on-treatment lipid profiles.

Objective This study examined variations in in-hospital mortality causes and identified independent mortality predictors among patients with acute myocardial infarction (AMI) with and without diabetes mellitus (DM). Methods We examined factors influencing in-hospital mortality in a single-center retrospective observational study. Separate multivariate analyses were conducted for both groups to identify independent predictors of in-hospital mortality. Patients This study included consecutive patients admitted to Iwate Medical University Hospital between January 2012 and December 2017 with a diagnosis of AMI. Results Of 1,140 patients meeting the AMI criteria (average age: 68.2±12.8 years old, 75% men), 408 (35.8%) had diabetes. The DM group had a 1.87-times higher 30-day mortality rate, a lower prevalence of ST-elevated MI (56.6% vs. 65.3% in non-DM, p=0.004), and more frequent non-cardiac causes of death (32% vs. 14% in non-DM, p=0.046) than the non-DM group. Independent predictors of in-hospital mortality in both groups were cardiogenic shock (CS) [DM: hazard ratio (HR) 6.59, 95% confidence interval (CI) 2.90-14.95; non-DM: HR 4.42, 95% CI 1.99-9.77] and renal dysfunction (DM: HR 5.64, 95% CI 1.59-20.04; non-DM: HR 5.92, 95% CI 1.79-19.53). Among patients with DM, a history of stroke was an additional independent predictor of in-hospital mortality (HR 2.59, 95% CI 1.07-6.31). Conclusion Notable disparities were identified in the causes of death and predictive factors of mortality between these two groups of patients with AMI. To further improve AMI outcomes, individualized management and prioritizing non-cardiac comorbidities during hospitalization may be crucial, particularly in patients with DM.

Background: Heart failure (HF) is a major cause of death worldwide. The most effective treatment for HF is heart transplantation, but its use is limited by the scarcity of donor hearts. Recently, stem cell-based therapy has emerged as a promising approach for treating myocardial infarction. Our research group has been investigating the use of human induced pluripotent stem cell-derived cardiomyocyte patches as a potential therapeutic candidate. We have successfully conducted eight cases of clinical trials and demonstrated the safety and effectiveness of this approach. However, further advancements are necessary to overcome immune rejection and enhance therapeutic efficacy. In this study, we propose a novel and efficient technique for constructing mesenchymal stem cell (MSC) tissue sheets, which can be transplanted effectively for treating myocardial infarction repair., Methods: We applied a one-step method to construct the human adipose-derived mesenchymal stem cell (hADSC) tissue sheet on a poly(lactic-co-glycolic acid) fiber scaffold. Histology, immunofluorescence, and paracrine profile assessment were used to determine the organization and function of the hADSC tissue sheet. Echocardiography and pathological analyses of heart sections were performed to evaluate cardiac function, fibrosis area, angiogenesis, and left ventricular remodeling., Results: In vitro, the hADSC tissue sheet showed great organization, abundant ECM expression, and increased paracrine secretion than single cells. In vivo, the hADSC tissue sheet group demonstrated improved cardiac functional recovery, less ventricular remodeling, decreased fibrosis, and enhanced angiogenesis than the MI group., Conclusions: We developed thick and functional hADSC tissue sheets via the one-step strategy. The hADSC tissue sheet showed excellent performance in treating myocardial infarction in the rat model., (© 2023. The Author(s).)

Background: It has been reported that patients with acute myocardial infarction (AMI) transferred to low-volume primary percutaneous coronary intervention (PCI) hospitals (<115/year) in low population density areas experience higher in-hospital mortality rates. This study compared in-hospital outcomes of patients admitted to high-volume primary PCI hospitals (≥115/year) with those for other regional general hospitals., Methods and results: Retrospective analysis was conducted on data obtained from 2,453 patients with AMI admitted to hospitals in Iwate Prefecture (2014-2018). Multivariate analysis revealed that the in-hospital mortality rate of AMI among patients in regional general hospitals was significantly higher than among patients in high-volume hospitals. However, no significant difference in mortality rate was observed among patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI. Although no significant difference was found in the in-hospital mortality rate of patients with Killip class I STEMI, significantly lower in-hospital mortality rates were observed in patients admitted in high-volume hospitals for Killip classes II, III, and IV., Conclusions: Although in-hospital outcomes for patients with STEMI undergoing primary PCI were similar, patients with heart failure or cardiogenic shock exhibited better in-hospital outcomes in high-volume primary PCI hospitals than those in regional general hospitals.

Background: The accumulation of advanced glycation end products (AGEs) is associated with cardiovascular events in patients with cardiovascular disease (CVD). However, the relationship between the AGEs measured by an AGEs sensor noninvasively at the fingertip and prognosis in patients with CVD remains unclear. Therefore, this study aimed to determine the relationship between AGEs score and prognosis among patients with CVD., Methods: A total of 191 outpatients with CVD were included. AGEs score were measured using an AGEs sensor and the patients were classified into groups by the median value of AGEs score. The incidence of major adverse cardiovascular and cerebrovascular events (MACCE) at 30 months was compared between high- and low-AGEs score groups. In addition, receiver operating characteristic (ROC) curve analysis was used to calculate cutoff value for the AGEs score, which discriminates the occurrence of MACCE. Cox regression analysis was performed to identify the factors associated with the presence of MACCE. MACCE included cardiac death, myocardial infarction, percutaneous coronary intervention, heart failure, and stroke., Results: AGEs score was normally distributed, with a median value of 0.51. No significant intergroup differences were found in laboratory findings, physical functions, or medications. The high-AGEs score group had a significantly higher incidence of MACCE than the low-AGEs score group (27.1 vs. 10.5%, P = 0.007). A high-AGEs score was a risk factor for MACCE (hazard ratio, 2.638; 95% confidence interval, 1.271-5.471; P = 0.009). After the adjustment for confounders other than 6-min walking distance, the AGEs score remained a factor associated with the occurrence of MACCE. The best cutoff AGEs score for the detection of MACCE was 0.51 (area under the curve, 0.642; P = 0.008; sensitivity, 72.2%; specificity, 54.8%)., Conclusions: AGEs score measured at the fingertip in patients with CVD is associated with MACCE. AGEs score, which can be measured noninvasively and easily, may be useful as an assessment for the secondary prevention of CVD in patients with CVD., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Transplanting human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) tissue sheets effectively treat ischemic cardiomyopathy. Cardiac functional recovery relies on graft survival in which angiogenesis played an important part. ONO-1301 is a synthetic prostacyclin analog with proangiogenic effects. We hypothesized that transplantation of hiPSC-CM tissue sheets with slow-release ONO-1301 scaffold could promote hostgraft angiogenesis, enhance tissue survival and therapeutic effect., Methods: We developed hiPSC-CM tissue sheets with ONO-1301 slow-release scaffold and evaluated their morphology, gene expression, and effects on angiogenesis. Three tissue sheet layers were transplanted into a rat myocardial infarction (MI) model. Left ventricular ejection fraction, gene expression in the MI border zone, and angiogenesis effects were investigated 4 weeks after transplantation., Results: In vitro assessment confirmed the slow-release of ONO-1301, and its pro-angiogenesis effects. In addition, in vivo data demonstrated that ONO-1301 administration positively correlated with graft survival. Cardiac tissue as thick as ∼900 μm was retained in the ONO (+) treated group. Additionally, left ventricular ejection fraction of the ONO (+) group was significantly enhanced, compared to ONO (-) group. The ONO (+) group also showed significantly improved interstitial fibrosis, higher capillary density, increased number of mature blood vessels, along with an enhanced supply of oxygen, and nutrients., Conclusions: Slow-release ONO-1301 scaffold provided an efficient delivery method for thick hiPSC-CM tissue. ONO-1301 promotes angiogenesis between the host and graft and improves nutritional and oxygen supply, thereby enhancing the survival of transplanted cells, effectively improving ejection fraction, and therapeutic effects., Competing Interests: Disclosure statement The authors declare no competing nonfinancial interests, but the following competing financial interests. Y.S.’s laboratory received funding from the Cuorips Company. We greatly appreciate the researchers who contributed to the experiments: N. S., N. Y., A. T., and M. W. for supplying the cells and fabricating the scaffold. M. I., Y. S., and M. K. for their support in animal experiments and sample processing. This study was supported by the Japan Agency for Medical Research and Development (AMED) and the Japan Society for the Promotion of Science (JSPS): Grant-in-Aid for Scientific Research (A) (20H00542 to Y. S. and L. L.) and Grants-in-Aid for Scientific Research (C) (19K12801 to J. L.). X. Q. was supported by the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) scholarship., (Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

In recent years, there have been several reports on robotic-assisted percutaneous coronary intervention (R-PCI), but few studies have been conducted on R-PCI performed under intravascular imaging guidance. To elucidate the periprocedural and postoperative 30-day outcomes of intravascular imaging-guided R-PCI, we performed a retrospective observational study on all patients in 102 consecutive cases who underwent R-PCI under intravascular imaging guidance at a single center in Japan from June 12, 2019 to February 18, 2021. The primary end point was 30-day survival, and the secondary end point was the incidence of complications. Intravascular imaging-guided R-PCI was performed 110 times in total on 125 lesions. The medians of procedural time, fluoroscopy time, contrast volume, patient entrance skin dose, and radiation exposure to the main operator were 49 min, 16 min, 67 mL, 0.62 Gy, and 0 μSv, respectively. Furthermore, 60.0% of target lesion branches were American College of Cardiology Foundation/American Heart Association classification type B2 or type C. However, in all cases, lesion dilatation was successful, and the final Thrombolysis in Myocardial Infarction flow grade was 3. The combination of manual operation was required in 12.7% of all cases, but 30-day survival was confirmed in all cases. There were two problems at the puncture site. One small distal branch artery dissection occurred due to manual operation, but no cardiovascular events (myocardial infarction, stroke) occurred and no target lesion restenosis was observed within 30 days of R-PCI. Hence, R-PCI using intravascular imaging demonstrated highly satisfactory treatment outcomes, and no complication caused by robotic operation was observed., (© 2022. The Author(s).)

Myocardial extracellular volume (ECV) by cardiac magnetic resonance (CMR) in the acute phase of acute myocardial infarction (MI) more precisely predicts the functional recovery of infarct-related wall motion abnormalities and left ventricular (LV) remodeling than late gadolinium enhancement (LGE). The purpose of this study was to evaluate the prognostic importance of acute phase ECV in patients with AMI. We evaluated 61 consecutive AMI patients using 3.0 T CMR. CMR examination was performed median 10 days (7-15 days) after PCI. Primary endpoint was defined as major adverse cardiac event (MACE). The median follow-up duration was 3.1 years, and MACE occurred in 11 (18%) patients. Although LVEF and % infarct LGE volume were not associated with MACE in this study population, higher infarct ECV predicted the MACE with a hazard ratio (HR) of 4.04 (P = 0.02). High global ECV, which was a combined assessment of infarct ECV and remote ECV, also predicted MACE with a HR of 5.24 (P = 0.035). The addition of infarct ECV to remote ECV (global chi-squared score: 1.4) resulted in a significantly increased global chi-squared score (6.7; P = 0.017). Furthermore, after adjusting for the calculated propensity score for high global ECV, it remained an independent predictor of MACE with HR of 5.10 (P = 0.04). The quantification of ECV in the acute phase among AMI patients may provide an incremental prognostic value for predicting MACE beyond that of clinical, angiographic, and functional variables., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Although a history of cancer is a poor prognostic factor in patients with acute myocardial infarction (AMI), the clinical importance of coexisting active cancer remains unclear., Methods: In this single-center retrospective study, we reviewed an AMI registry and assessed the prevalence and predictors of active cancer, 1-year incidence of cardiac death or major bleeding events (defined as a Bleeding Academy Research Consortium type 3 or 5), and the impact of coexisting active cancer on clinical outcomes. Active cancer was defined as either an already-diagnosed or undiagnosed occult cancer., Results: Between January 2012 and December 2017, 1140 AMI patients (median age, 69 years; male, 76.0%) were enrolled. Active and historical cancers were diagnosed in 63 patients (5.5%) and 50 patients (4.4%), respectively. The most common location was the urinary tract (n=21). In the Kaplan-Meier analysis, the active cancer group had a higher incidence of 1-year cardiac death (17.5% vs. 5.3%, p < 0.001) and major bleeding events (19.0% vs. 5.6%, p < 0.001) than the non-cancer group. In the multivariate Cox proportional hazards regression models, active cancer was an independent predictor of both cardiac death and major bleeding at 1 year. Specifically, gastrointestinal tract and advanced-stage cancers had the poorest outcomes. Compared to the non-cancer group, the 1-year major bleeding rate was higher for all cancer types and stages. In contrast, early-stage cancers had a weaker impact on the 1-year cardiac mortality compared to advanced-stage cancers. Similarly, cardiac death during 1-year also occurred less frequently in occult cancers than in already-known cancers., Conclusions: In patients with AMI, coexisting active cancer was rare, but it significantly impacted cardiac death and major bleeding events., (Copyright © 2021 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Atrial fibrillation (AF) is a common complication of acute myocardial infarction (AMI). Although previous studies have investigated mortality rates and the incidences of adverse events associated with new-onset AF (NOAF) in patients with AMI, the effects of emergency percutaneous coronary intervention (PCI) on the incidence of NOAF in patients with AMI remain unclear. The purpose of this study was to investigate the relationship of clinical characteristics, medical history, and the coronary flow disturbance phenomenon (TIMI < 3) following emergency PCI with NOAF in patients with AMI. Between 2012 and 2016, 731 patients with AMI underwent PCI at our facility. Among these, 52 had a history of chronic/paroxysmal AF before admission and were excluded. The remaining 679 patients (mean age 66.4 years, 532 males) were analyzed in this retrospective observational study.New-onset AF was observed in 45 patients (6.6%). In univariate analysis, the hazard ratios (HRs) for patient age (HR 1.04, 95%CI 1.02-1.07), Killip II-IV (HR 2.34, 95%CI 1.29-4.23), elevated D-dimer level (> 1.0 μg/mL; HR 3.32; 95%CI 1.77-6.23), and coronary flow disturbance phenomenon (HR 5.61; 95%CI 2.88-10.9) were significantly higher in the NOAF group. In multivariate analysis, an elevated D-dimer level (> 1.0 μg/mL; HR 2.44; 95%CI 1.17-5.11) and coronary flow disturbance phenomenon (HR 4.61; 95%CI 2.29-9.27) were found to be independent risk factors for NOAF. An elevated D-dimer level at admission and the presence of coronary flow disturbance phenomenon after PCI were risk factors for NOAF following emergency PCI in patients with AMI.

Background: Somatic stem cell (SC) therapy can improve cardiac performance following ischemic injury. In this study, we investigated whether induced pluripotent SC-derived cardiomyocytes (iPS-CMs) are more effective than somatic SCs, such as skeletal myoblasts (SM) and mesenchymal (M)SCs, in promoting functional recovery upon transplantation in a porcine model of myocardial infarction., Methods: Myocardial injury was induced by ameroid ring placement in immunosuppressed female mini pigs; after 1 month, epicardial cell transplantation was performed with iPS-CMs (n = 7), SMs (n = 7), and MSCs (n = 7). Control pigs underwent sham operation (n = 8)., Results: Cell therapy improved functional recovery 2 months after myocardial infarction, as evidenced by increased ejection fraction (iPS-CM, +7.3% ± 2.2% and SM, +5.8% ± 5.4% vs control, -4.4% ± 3.8%; P < 0.05). The analysis of regional contractile function in the infarcted zone revealed an increase in transverse peak strain (iPS-CM, +4.6% ± 2.2% vs control, -3.8% ± 4.7%; P < 0.05). The C-11 acetate kinetic analysis by positron emission tomography showed that the work-metabolic cardiac energy efficacy increased by the transplantation of iPS-CMs, but was reduced by the other cell types. This was accompanied by decreased myocardial wall stress in the infarcted zone (iPS-CM, -27.6 ± 32.3 Pa and SM, -12.8 ± 27 Pa vs control, +40.5 ± 33.9 Pa; P < 0.05)., Conclusions: The iPS-CM is superior to other somatic cell sources in terms of improving regional contractile function and cardiac bioenergetic efficiency, suggesting greater clinical benefits in severely damaged myocardium.

The aim of this study was to compare myocardial strain by cardiovascular magnetic resonance feature tracking (CMR-FT) to those derived from displacement encoding with stimulated echoes (DENSE) in patients with acute myocardial infarction (AMI). Twenty patients (65 pa13 years) with AMI underwent cine, DENSE, black-blood T2-weighted and late gadolinium enhancement CMR at 1.5 T. Global and segmental strain was determined by CMR-FT analysis and DENSE on matched 3 short-axis planes. Global circumferential strain by CMR-FT showed a good agreement with that by DENSE (r = 0.85, p <0.001; bias 0.02, limits of agreement -0.03 to 0.06). For segmental circumferential strain, r coefficient between CMR-FT and DENSE was 0.61 (p <0.001) with bias of 0.02, limits of agreement of -0.07 to 0.11. Regional circumferential strain determined by CMR-FT in infarct segments (-0.08 ± 0.05) was significantly altered compared with that in remote normal segments (-0.15 ± 0.05, p <0.001). CMR-FT measurement of regional and global circumferential strain showed good agreement with DENSE in patients with AMI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

T1 or longitudinal relaxation time is one of the very fundamental magnetic resonance imaging (MRI) time constants and a tissue characterizing parameter. Only during the last decade did it become possible to quantify T1 values of the myocardium through T1 mapping. Evolving from only region of interest analysis and long acquisition times to the pixel-based parametric mapping and short breath-hold sequences, T1 mapping is reaching maturity among cardiac magnetic resonance (CMR) techniques. Both inversion recovery methods such as MOdified Look-Locker Inversion (MOL-LI) and Shortened MOLLI (ShMOLLI) and saturation recovery methods such as Saturation recovery Single-Shot Acquisition (SASHA) are available for T1 quantification with variable degrees of accuracy, precision, and reproducibility. Native (non-contrast) T1 values increase with edema, amyloid deposition, and fibrosis, while they decrease in fat or iron deposition in the myocardium. These features enabled significant expansion of the clinical applications of native T1 mapping where it provides high sensitivity and specificity and even acts as a disease biomarker or a predictor of prognosis. It is of particular usefulness in diffuse myocardial diseases where conventional CMR techniques might be deceiving. A brighter future for the technique is expected if certain challenges are to be faced, examples of which are the need for standardization of normal values, acquisition techniques, and improving analysis tools.

Background: Clinical utility of myocardial delayed-enhancement CT is currently limited because of relatively poor contrast-to-noise ratio (CNR) and artifacts. Targeted spatial-frequency filtration (TSFF) is a hybrid algorithm of half- and full-scan reconstruction that can achieve both high temporal resolution and improved stability of myocardial signal., Objective: The purpose of this study was to evaluate image quality of delayed-enhancement CT using TSFF with image averaging and its reproducibility in infarct assessment in comparison with conventional half-scan reconstruction (HALF)., Methods: Forty patients with suspected coronary artery disease underwent delayed-enhancement CT with HALF and TSFF using dual-source CT. Two blinded readers independently determined the presence and size of delayed enhancement. Image quality, signal-to-noise ratio and CNR were assessed. The presence of delayed enhancement on CT was compared with magnetic resonance imaging in 12 patients., Results: TSFF with averaging of 4 image stacks acquired during 1 breathhold demonstrated significantly better image quality compared with HALF. Good left ventricular lumen-myocardium contrast was consistently achieved with TSFF in patients who received iodine dose of >600 mg I/kg. The signal-to-noise ratio and CNR were 11.3 ± 4.2 and 4.5 ± 1.6 by TSFF, being significantly higher than those by HALF (7.9 ± 2.9 and 3.3 ± 1.8; P < .01 for both). Interobserver reproducibility of infarct sizing was markedly improved by using TSFF instead of HALF (intraclass correlation coefficient: 0.86 vs 0.50). Agreement with magnetic resonance imaging by kappa statistics was 0.85 with TSFF and 0.74 with HALF., Conclusions: TSFF with image averaging can significantly improve image quality of delayed-enhancement CT and considerably enhances interobserver reproducibility of infarct sizing., (Copyright © 2014 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

To determine the diagnostic performance and reproducibility of strain assessment with displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance (CMR) in identifying contractile abnormalities in myocardial segments with late gadolinium enhancement (LGE). DENSE CMR was obtained on short-axis planes of the left ventricle (LV) in 24 patients with suspected coronary artery disease. e1 and e2 strains of LV wall were quantified. Cine MRI was acquired to determine percent systolic wall thickening (%SWT), followed by (LGE) CMR. The diagnostic performance of e1, e2 and %SWT for predicting the presence of LGE was evaluated by receiver operating characteristics (ROC) analysis. Myocardial scar on LGE CMR was observed in 91 (24 %) of 384 segments. The area under ROC curve for predicting the segments with LGE was 0.874 by e1, 0.916 by e2 and 0.828 by %SWT (p = 0.001 between e2 and %SWT). Excellent inter-observer reproducibility was found for strain [Intraclass correlation coefficient (ICC) = 0.962 for e1, 0.955 for e2] as compared with %SWT (ICC = 0.790). DENSE CMR can be performed as a part of routine CMR study and allows for quantification of myocardial strain with high inter-observer reproducibility. Myocardial strain, especially e2 is useful in detecting altered abnormal systolic contraction in the segments with myocardial scar.

Late gadolinium enhancement (LGE) is widely used to precisely localize and determine the extent and transmurality of myocardial scarring. Performing LGE imaging at end-systole may reduce motion artefacts. It is therefore important to know whether end-systolic imaging influences infarct transmurality in patients with ischemic scar. 107 dysfunctional segments were studied in 20 consecutive patients with established coronary artery disease. Patient specific trigger delays were used to obtain end-diastolic and end-systolic LGE images (LGE(ed), LGE(es)). Wall thickness (WT(ed), WT(es)), thickness of the remaining viable rim (RIM(ed), RIM(es)) and end-diastolic scar thickness were measured manually. There was LGE in 84% of all dysfunctional segments with a mean scar of 3.4 ± 2.5 mm. Total wall thickness and the thickness of the remaining viable rim increased from diastole to systole (WT(ed) 7.8 ± 1.9 vs. WT(es) 8.4 ± 2.2; P < 0.001; RIM(ed) 4.4 ± 3.1 vs. RIM(es) 5 ± 3.4; P < 0.001). Transmurality of scar decreased from end-diastole to end-systole (LGE(ed) 46 ± 33% vs. LGE(es) 44 ± 33%; P < 0.001). This was most pronounced in a subgroup of segments (n = 15) with visual scar transmurality between 50 and 75% (LGE(ed) 75 ± 15% vs. LGE(es) 70 ± 16%; P < 0.001). The change in transmurality was inversely correlated with the change of the thickness of the remaining viable rim between diastole and systole (r = -0.7; P < 0.001). Scar transmurality was reduced by up to 12% in the individual patient. Scar transmurality changes due to thickening of the remaining viable rim. Whereas these differences might not impact on clinical decision-making in most patients, there will be an occasional misclassification if cut-off values are used (e.g. scar <50 or >50%) or if exact data is required for research studies.

Background: Novel cardiovascular magnetic resonance (CMR) techniques and imaging biomarkers are often validated in small animal models or empirically in patients. Direct translation of small animal CMR protocols to humans is rarely possible, while validation in humans is often difficult, slow and occasionally not possible due to ethical considerations. The aim of this study is to overcome these limitations by introducing an MR-compatible, free beating, blood-perfused, isolated pig heart model for the development of novel CMR methodology., Methods: 6 hearts were perfused outside of the MR environment to establish preparation stability. Coronary perfusion pressure (CPP), coronary blood flow (CBF), left ventricular pressure (LVP), arterial blood gas and electrolyte composition were monitored over 4 hours. Further hearts were perfused within 3T (n = 3) and 1.5T (n = 3) clinical MR scanners, and characterised using functional (CINE), perfusion and late gadolinium enhancement (LGE) imaging. Perfusion imaging was performed globally and selectively for the right (RCA) and left coronary artery (LCA). In one heart the RCA perfusion territory was determined and compared to infarct size after coronary occlusion., Results: All physiological parameters measured remained stable and within normal ranges. The model proved amenable to CMR at both field strengths using typical clinical acquisitions. There was good agreement between the RCA perfusion territory measured by selective first pass perfusion and LGE after coronary occlusion (37% versus 36% of the LV respectively)., Conclusions: This flexible model allows imaging of cardiac function in a controllable, beating, human-sized heart using clinical MR systems. It should aid further development, validation and clinical translation of novel CMR methodologies, and imaging sequences.

Objective: In experimental animal models and human autopsy studies, hemorrhagic infarction caused by microvascular injury has been detected after coronary reperfusion. The purpose of this study was to determine whether detection of myocardial edema with T2-weighted MRI is influenced by the presence of microvascular obstruction., Subjects and Methods: Thirty-seven patients underwent black-blood fat-suppressed T2-weighted, rest perfusion, and late gadolinium-enhanced MRI 5.4 +/- 3.1 days after the onset of acute myocardial infarction. On T2-weighted MR images, the signal intensity in relation to that of remote myocardium was determined in the late gadolinium-enhanced and periinfarction areas. Segment-based analysis was performed to determine whether the presence of microvascular obstruction influences the detection of myocardial edema., Results: The averaged signal intensity in the late gadolinium-enhanced area without microvascular obstruction was significantly higher than the signal intensity in remote normal myocardium (relative signal intensity, 1.83 +/- 0.50; p < 0.001). In contrast, the signal intensity in the microvascular obstruction area on T2-weighted images was not significantly different from the signal intensity in remote myocardium (relative signal intensity, 1.14 +/- 0.26). The percentages of late gadolinium-enhanced segments with high signal intensity on T2-weighted MR images were 95% (73/77) without microvascular obstruction and 30% (22/73) with microvascular obstruction., Conclusion: With T2-weighted MRI, infarction-associated edema can be reliably detected in infarct lesions without microvascular obstruction. Microvascular obstruction, however, does not necessarily exhibit high signal intensity on T2-weighted MRI. Careful attention is required in interpretation of cardiac MR images of patients who have experienced acute myocardial infarction and undergone percutaneous coronary intervention. The findings on T2-weighted MR images can be substantial underestimates of the extent of acute myocardial infarction.

Objectives: Our aim was to investigate the frequency of left ventricular (LV) and right ventricular adipose tissue on multislice computed tomography (CT) in patients with a history of myocardial infarction (MI) and to determine correlations with infarct age., Background: Fat deposition in the ventricular wall has frequently been observed in post-infarct myocardial tissue. However, the in vivo relevance of adipose tissue in MI on CT and correlations with infarct age have not been determined., Methods: Fifty-three patients with a history of MI (mean age 66 +/- 10 years; 38 men, 15 women) and 63 subjects with no history of MI or coronary revascularization (mean age 65 +/- 12 years; 37 men, 26 women) were retrospectively studied for intramyocardial fat on 64-slice cardiac CT. Presence or absence, distribution, and correlations with infarct age of LV adipose tissue were evaluated., Results: Compared with noninfarct control subjects, the MI group showed a significantly higher prevalence of fat deposition within LV myocardium on CT (MI group, 62% [33 of 53] vs. control group, 3% [2 of 63]; p < 0.0001). In 32 of 33 patients (97%) with MI and LV fat deposition on CT, adipose tissue was observed in the region perfused by the infarct-related artery and was located in the subendocardium in 30 patients (94%), the middle layer in 1 patient (3%), and the subepicardium in 1 patient (3%). Mean infarct age was significantly higher in patients with LV adipose tissue (8.2 +/- 4.4 years) than in those without adipose tissue (2.2 +/- 2.6 years, p < 0.001). Thirty of 35 patients (89%) with infarct age >or=3 years showed adipose tissue in MI. Conversely, none of 9 patients with infarct age <10 months showed fatty replacement., Conclusions: Myocardial adipose tissue is common in patients with infarct age >or=3 years. CT evaluation of myocardial adipose tissue may be important for accurate interpretation of CT perfusion and infarct imaging of the heart.

Background: The present study examined whether a bioengineered polyglycolic acid cloth (PGAC) impregnated with bone marrow cells (BMC) improved the function and angiogenesis of the infarcted heart., Methods and Results: The coronary artery was ligated in Lewis rats and the infarcted area was covered with a PGAC in group 1 (n=8), with a PGAC containing basic-fibroblast growth factor (b-FGF) in group 2 (n=11) and a PGAC containing b-FGF and freshly isolated BMC in group 3 (n=10). In addition, BMC derived from transgenic mice expressing green fluorescent protein (GFP)-BMC were seeded into a PGAC, which was sutured over the infarcted area of C57BL/6 mice (n=5). In the rat study, developed and systolic pressures, dp/dt max and dp/dt min) were the highest in group 3, as were the capillary density in the PGAC and infarcted area. In the mouse study, there were few GFP-BMC in the PGAC, but none in the infarcted area., Conclusions: A PGAC with BMC improved cardiac function by inducing angiogenesis without migration of BMC. Freshly isolated BMC work as angiogenic inducers and a PGAC is useful as a "drug delivery system".

A recent study showed that granulocyte-colony stimulating factor (G-CSF) treatment improved the infarcted cardiac function. Although mobilized stem cells may affect it, the mechanism is unclear. In this study, we investigated the origins of stem cells and phenotypic changes of the migrated cells, and evaluated the efficacy of G-CSF. Eighteen C57BL/6 mice were irradiated (900 cGy) and GFP mouse-derived bone marrow cells (GFP-BMC: 10(6) cells) were injected via a tail vein followed by splenectomy 4 weeks later. Ligation of the left descending coronary artery was performed 2 weeks later. Recombinant human G-CSF (200 microg/kg/day) was injected for 3 days before and 5 days after ligation (group 1, n = 10). Saline was injected in group 2 (n = 8). Four weeks after infarction, hearts and other organs were fixed for histology. The survival rate after postoperative day 3 in group 1 was 100%, while that in group 2 was 50% (p = 0.03). Bone marrow-derived GFP cells (BMD-GFP) in group 1 (103.3+/-71.9/mm2) were located at the infarcted border area significantly more than those in group 2 (43.6+/-23.7/mm2) (p < 0.0001). BMD-GFP cells were positive for troponin I (16.6%), myosin heavy chain-slow (16.7%), and nestin (8.8%) in group 1. Ki-67-positive BMD-GFP in group 1 (10.0+/-7.0/mm2) were significantly more than those in group 2 (4.8+/-6.1/mm2) (p = 0.01). G-CSF increased the survival rate after infarction. G-CSF promoted BMC to migrate into the infarcted border area. Bone marrow was one of the origins of regenerated cardiomyocytes.

For the first time in Japan, off-pump coronary artery bypass grafting (OPCAB) was compared with the conventional on-pump technique, retrospectively examining the morbidity associated with coronary artery bypass grafting (CABG) and assessing the efficacy of OPCAB. In 2000, 158 patients underwent CABG: 95 patients (60%) had OPCAB (Group I) and 63 patients (40%) had conventional CABG (Group II). The operating time, length of intensive care unit (ICU) stay, ventilation time, postoperative bleeding, transfusion, postoperative renal function, occurrence of stroke, and early graft patency were examined in both groups. There were no hospital deaths in either group. The operating time, ICU stay, and ventilation time were significantly (p < 0.0001, p = 0.013, and p < 0.0001, respectively) shorter in Group I (351 +/- 85 min, 3.0 +/- 1.4 days, and 5.1 +/- 2.8h) than in Group II (449 +/- 112 min, 3.6 +/- 1.8 days, and 13.7 +/- 18.0 h). The postoperative blood loss within 12h and the transfusion volume were significantly (p = 0.0004 and p < 0.0001, respectively) smaller in Group I (480 +/- 210 ml and 300 +/- 490ml) than in Group II (720 +/- 430ml and 1,230 +/- 1,180 ml). Peak serum blood urea nitrogen and creatinine concentrations (excluding patients with preoperative chronic renal failure, ie a preoperative serum creatinine > 1.5 mg/dl) were significantly (p < 0.0001 and p < 0.0001, respectively) lower in Group I (16.2 +/- 15.2mg/dl and 0.81 +/- 0.72 mg/dl) than in Group II (19.2 +/- 7.6 mg/dl and 0.92 +/- 0.28 mg/dl). There were no perioperative strokes in Group I, but 6.4% of Group II patients suffered a stroke. There was no significant difference in graft patency between the groups (95.6% vs 94.9%). OPCAB reduced the mortality and morbidity of coronary revascularization, with a shorter operating time and more rapid recovery from surgery.

Failure to Reduce Infarct Size by Intracoronary Infusion of Recombinant Human Superoxide Dismutase at Reperfusion in the Porcine Heart: Immunohistochemical and Histological Analysis. Journal of Molecular and Cellular Cardiology (1991) 23, 1287-1296. We quantitatively determined the extent of infarction and contraction band necrosis in porcine hearts, and analyzed the distribution of administered recombinant human superoxide dismutase (h-SOD) in the myocardium using a polyclonal antibody to h-SOD. After 1 hour of occlusion, h-SOD was infused for the first 30 min of reperfusion in SOD group, while pigs received only arterial blood in control group. The extent of infarction or contraction band necrosis was not significantly different between SOD group and control group. Positive staining by polyclonal antibody to h-SOD was detected only in the infarcted area in SOD group. Thus, h-SOD only entered irreversibly damaged myocytes and neither diminished reperfusion injury nor reduced infarct size in pigs.

The time course of hypertrophy of surviving myocytes overlying the infarct after the onset was examined and the hypertrophy was analyzed in relation to the transmural extent of infarct in 34 autopsied hearts with Q wave infarction. The 34 hearts were divided into 4 groups according to the length of time between the onset of infarction and death. This was less than 5 days in group 1 (n = 10), 20-30 days in group 2 (n = 7), 40-60 days in group 3 (n = 7), and 12-24 months in group 4 (n = 10). To clarify the regional hypertrophy of myocytes overlying the infarct, the size of the surviving myocytes in the outer third of the left ventricular wall in the 1-cm wide central zone of the infarct was compared with that of the myocytes in the outer third of the left ventricular wall without infarction (control wall) in the same heart. To exclude factors which stimulate the hypertrophy of the whole left ventricle, the ratio of the monocyte diameter in the infarcted wall to that in the control wall was examined. It was 1.0 +/- 0.0 (mean +/- SD) in group 1, 1.0 +/- 0.1 in group 2, 1.2 +/- 0.1 in group 3, and 1.3 +/- 0.1 in group 4. The ratio was significantly higher in group 3 than in group 1 and 2, and was highest in group 4. In group 4, the corrected percentage transmural extent of infarct indicating the original transmural extent of infarct at the acute stage was 63 + 8%, and this transmural extent correlated positively with the ratio of myocyte diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

To clarify whether or not reperfusion injury occurs in the permanent occlusion of a coronary artery, we analyzed quantitatively contraction band necrosis as an indicator of early recanalization, coagulation necrosis, infarct size and measured regional blood flow in dog hearts with collateral circulation. Fifty mongrel dogs were divided into four groups: 15 dogs with a 24-hour occlusion of the left anterior descending coronary artery just distal to the first diagonal branch (permanent occlusion group): 15 dogs a with 3-hour occlusion followed by 24-hour recanalization (recanalization group); 10 dogs with a 2-hour occlusion without recanalization (transient occlusion group); 10 dogs with a 4-hour occlusion without recanalization (transient occlusion group). The regional blood flow in the subepicardium and subendocardium determined by the generated hydrogen gas clearance method was greatly decreased 30 minutes after occlusion (14 + 8%/12 +/- 9%) and was relatively restored from 180 minutes (31 +/- 21%/21 +/- 14%) to 24 hours later (41 + 19%/26 + 16%) in spite of complete occlusion of the coronary artery. The percentage infarct area in the risk area was significantly greater in the permanent occlusion group (60 +/- 26%) than in the recanalization group (35 +/- 31%). Although most of the infarct was occupied by contraction band necrosis in the recanalization group (86 +/- 12%), contraction band necrosis was diffusely seen even in the permanent occlusion group (54 +/- 27%). In both the permanent and recanalization groups, contraction band necrosis was the main histological feature of small infarcts occupying less than 30% of the risk area, while coagulation necrosis was the main feature in very large infarcts occupying more than 80% of the risk area. In the occlusion groups without recanalization, the percentage area of contraction band necrosis in the risk area was 6 +/- 8% after the 2-hour occlusion, 23 +/- 17% after the 4-hour occlusion and 31 +/- 21% after permanent occlusion; the difference between the 4-hour and permanent occlusion groups was not significant. In the permanent occlusion group, the percentage infarct area in the risk area was inversely correlated with regional blood flow during occlusion, an indicator of collateral flow. It was concluded that reperfusion injury occurs even in hearts without recanalization. The pathogenesis may involve reperfusion in the risk area via collateral circulation. Protection against reperfusion injury is important to minimize the infarct size even in hearts with permanent occlusion, although the presence of collateral flow is an important factor in limiting infarct size.

In order to clarify the pathogenesis of acute myocardial infarction (MI) in hearts with normal coronary arteries, infarct size, and the extent of contraction band necrosis (CBN), coagulation necrosis, and hemorrhage were quantitatively examined using an image analyzer in 5 autopsy cases of MI with normal or nearly normal extracardiac coronary arteries. One patient died 40 h after acute MI. A second patient with acute MI due to severe spasm of segment 6, confirmed by cineangiography, died three days later. The third patient had already suffered a subarachnoid hemorrhage, and died 10 h after the onset of acute MI. The fourth patient had aortic stenosis and regurgitation. She developed acute MI due to total occlusion of segment 6, confirmed by cineangiography 4 h after the onset, and died 61 days later. Autopsy revealed old anteroseptal MI with normal coronary arteries and valvular thrombi. The fifth patient had a malignancy, and died one day after the onset of acute MI. Autopsy revealed multiple occlusive thrombi in the small intramural coronary arteries of the left ventricular wall supplied by segment 14, without any stenosis in the feeding vessel. Most infarcts were localized in the territory supplied by 1 or 2 of the 3 epicardial coronary arteries, and coincided with the clinically diagnosed infarct site. The infarct size ranged from 3%-26% of the left ventricular wall, and infarcts were generally localized to the inner third of the wall (67 +/- 20%). Histological examination of the four patients with acute MI revealed diffuse CBN (86 +/- 14% of the infarcted area) and/or hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine whether or not male (NZWXBXSB)F1 [WXB)F1) mice exhibiting a lupus-like syndrome died of acute myocardial infarction (MI), and whether acute MI is directly related to small coronary artery disease, acute and old MIs were examined histologically in 55 dead (WXB)F1 male mice and 30 age-matched, surviving (WXB)F1 male mice used as a control group. In each heart from the 15 dead mice with MI and the five surviving mice without MI, 300 to 400 5-microns-thick serial sections were made; every fourth section was stained. Acute MI was found in 35 (64%) dead mice and in one (3%) survivors, whereas old MI was found in 50 (91%) dead mice and 17 (57%) survivors: a significant difference between the dead and surviving mice. The MIs were numerous, scattered, and small in most mice. Quantitative analysis revealed that the percentage of acute MI and old MI in the left ventricular (LV) wall was 6% +/- 11% and 3% +/- 3% in the dead group, and 0.4% and 2% +/- 3% in the control group. This indicated that recurrent acute MI is a major factor in the death of the mice. Although all the epicardial major coronary arteries of the (WXB)F1 male mice were intact, significant stenoses were noted in the intramyocardial small arteries. The serial sections in the 15 dead mice with MI revealed 1) segmental occlusive thrombi in the infarct-related small coronary artery in 14 of the 20 foci of acute anemic MIs, two of the 18 foci of acute hemorrhagic MIs, and four of the 58 foci of old MIs; and 2) segmental intimal thickenings in the infarct-related small artery in six of the 20 foci of acute anemic MIs, two of the 18 foci of acute hemorrhagic MIs, and 56 of the 58 foci of old MIs. There was no evidence of small coronary artery disease in the surviving mice without MI. The thrombus would result in thickened intima as MI progresses from the acute to the old stage. Because it was established that acute MI of hemorrhagic type follows reperfusion after transient occlusion of the coronary artery, hemorrhagic acute MI with rare incidence of thrombi in this mouse suggests that thrombolysis occurs after occlusion due to thrombus formation. Thus, the pathogenesis of multiple MIs is occlusive thrombi, recanalization in small coronary arteries or both. Some of the mice had dilated cardiomyopathy (DCM)-like features (marked LV dilatation).(ABSTRACT TRUNCATED AT 400 WORDS)

To define the histopathogenesis of successful and unsuccessful recanalization following selective intracoronary thrombolysis, coronary angiography (CAG) in thrombolysis and histologic findings were compared in 13 patients who died within four days (mean 1.5 days) after the procedure. Thirteen infarct-related arteries were evaluated in respect to recanalization; presence of an intraluminal thrombus, and rupture and hemorrhage of atheromatous plaques were histologically evaluated in serial sections. Intraluminal thrombi of the infarct-related coronary artery were found in all of the five cases with unsuccessful recanalization and in none of the eight cases with successful recanalization. Rupture and hemorrhage of atheromatous plaques in infarct-related arteries were observed in all of the five cases with unsuccessful recanalization and in seven of the eight cases with successful recanalization. It was concluded that 1) in recanalized cases, thrombi are considered to be lysed; 2) unsuccessful recanalization does not necessarily indicate the absence of thrombi; and 3) rupture and hemorrhage of atheromatous plaques do not affect recanalization.

To define whether recanalization after occlusion can reduce the myocardial infarct size, we compared the infarct size in 25 pig hearts without collateral circulation, 35 dog hearts with collateral circulation and 11 human autopsied hearts with coronary thrombolysis at 2 to 6 hours after the onset of acute myocardial infarction. The data showed that % infarct size in the risk area increased according to the duration of occlusion. In the pig, % infarct size was 80 +/- 9% in the recanalization after 1 hour occlusion and 96 +/- 2% in the recanalization after 2 hour occlusion. There was no significant difference between these and the permanent occlusion group (95 +/- 3%). In the dog, % infarct size was 35 +/- 31% in the recanalization after 4 hour occlusion and 59 +/- 27% in the permanent occlusion group. In human autopsied hearts, the infarct size was the same between the recanalization group (82 +/- 6%) and the permanent occlusion group (80 +/- 11%). The % infarct size in the recanalization groups was less than or the same as that in the hearts with permanent occlusion in dog, pig and human. Thus, it is concluded that, to reduce conclusively the infarct size, recanalization should be done within 1 hour after the occlusion in the hearts without collateral circulation and within 4 hours in the hearts with collateral circulation. So called reperfusion injury which means the greater expansion of the % infarct size than that in the permanent occlusion is not present.

The postmortem histology and the results of cineangiography after selective intracoronary thrombolysis in vessels that were recanalized and in those that were not were compared in 21 patients who died within seven days (mean 2 days) of selective intracoronary thrombolysis. There was a persistent intraluminal thrombus in the infarct related coronary artery in five of six segments in which recanalisation was unsuccessful and in one of 15 segments in which recanalisation was successful. Rupture and haemorrhage of the atheromatous plaque were seen in most of the infarct related segments, both in those in which recanalisation was achieved and in those in which it was not. Irregular narrowing and filling defects on the coronary cineangiograms were associated with rupture and haemorrhage of the atheromatous plaque. These results suggest that failure of coronary thrombolysis to recanalize the infarct related artery does not indicate that the occlusion was not caused by thrombus.

Severe myocardial hemorrhage can occur as a potential adverse effect of reperfusion therapy in evolving myocardial infarction. This report describes a 83-year-old man, who showed angiographic evidence of extravasation of contrast medium from the reperfused right coronary artery into the inferoposterior left ventricular wall. At autopsy, severe hemorrhage was transmurally observed in the inferoposterior wall of the left ventricle. The finding of extravasation is a useful angiographic sign of the production of hemorrhage during coronary reperfusion therapy, and great attention should be focused to the existence of this sign to prevent further hemorrhage.

Coronary angiography and percutaneous transluminal coronary angioplasty (PTCA) were performed in 32 patients with evolving acute myocardial infarction. Of the 25 patients with complete occlusion of an infarct-related coronary artery, in 18 (72%) the occluded vessel was successfully opened by an intracoronary infusion of urokinase. With a small dose of urokinase the successful recanalization was achieved in only 25%; with a larger dose it was achieved in 94%. After PTCA, all patients received glucose-insulin-potassium solution for 76 hours. Repeat angiography 42 days later showed a patent coronary artery in 12 (group A) of 18 patients with successful PTCA. In group A, left ventricular ejection fraction increased from 51 +/- 13% to 72 +/- 10% (p less than 0.01) and regional wall shortening from 4.5 +/- 9.5% to 29 +/- 19% (p less than 0.01). In contrast, these variables did not change significantly in patients with unsuccessful PTCA or late reocclusion of an infarct-related vessel (group B). These data suggest that successful PTCA with sustained patency of an infarct-related coronary artery has a beneficial effect on the salvage of the jeopardized myocardium, and glucose-insulin-potassium therapy may enhance the beneficial effect of PTCA.