Concomitant Mitral Regurgitation in Severe Aortic Stenosis　- Insights From the CURRENT AS Registry-2.

BACKGROUND: Data on concomitant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) are scarce.Methods and Results: We investigated the risk of concomitant MR in patients with severe AS in the CURRENT AS Registry-2 according to initial treatment strategy (transcatheter aortic valve implantation [TAVI], surgical aortic valve replacement [SAVR], or conservative). Among 3,365 patients with severe AS, 384 (11.4%) had moderate/severe MR (TAVI: n=126/1,148; SAVR: n=68/591; conservative: n=190/1,626). The cumulative 3-year incidence for death or heart failure (HF) hospitalization was significantly higher in the moderate/severe than no/mild MR group in the entire population (54.6% vs. 34.3%, respectively; P<0.001) and for each treatment strategy (TAVI: 45.0% vs. 31.8% [P=0.006]; SAVR: 31.9% vs. 18.7% [P<0.001]; conservative: 67.8% vs. 41.6% [P<0.001]). The higher adjusted risk of moderate/severe MR relative to no/mild MR for death or HF hospitalization was not significant in the entire population (hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.95-1.39; P=0.15); however, the risk was significant in the SAVR (HR 1.92; 95% CI 1.04-3.56; P=0.04) and conservative (HR 1.30; 95% CI 1.02-1.67; P=0.04) groups, but not in the TAVI group (HR 1.03; 95% CI 0.70-1.52; P=0.86), despite no significant interaction (Pinteraction=0.37). CONCLUSIONS: Moderate/severe MR was associated with a higher risk for death or HF hospitalization in the initial SAVR and conservative strategies, while the association was less pronounced in the initial TAVI strategy.

In-hospital outcomes after SAVR or TAVI in patients with severe aortic stenosis.

There were no data comparing the in-hospital outcomes after transcatheter aortic valve implantation (TAVI) with those after surgical aortic valve replacement (SAVR) in Japan. Among consecutive patients with severe AS between April 2018 and December 2020 in the CURRENT AS Registry-2, we identified 1714 patients who underwent aortic valve replacement (TAVI group: 1134 patients, and SAVR group: 580 patients). Patients in the TAVI group were much older (84.4 versus 73.6 years, P < 0.001) and more often had comorbidities than those in the SAVR group. In-hospital death rate was numerically lower in the TAVI group than in the SAVR group (0.6% versus 2.2%). After excluding patients with dialysis, in-hospital death rate was very low and comparable in the TAVI and SAVR groups (0.6% versus 0.8%). The rates of major bleeding and new-onset atrial fibrillation during index hospitalization were higher after SAVR than after TAVI (72% versus 20%, and 26% versus 4.6%, respectively), while the rate of pacemaker implantation was higher after TAVI than after SAVR (8.1% versus 2.4%). Regarding the echocardiographic data at discharge, the prevalence of patient-prosthesis mismatch was lower in the TAVI group than in the SAVR group (moderate: 9.0% versus 26%, and severe: 2.6% versus 4.8%). In this real-world data in Japan, TAVI compared with SAVR was chosen in much older patients with more comorbidities with severe AS. In-hospital death rate was numerically lower in the TAVI group than in the SAVR group.

A 17-year-old male with acute myocarditis following mRNA-1273 vaccination in Japan.

Vaccinations are the main tool being used to control the COVID-19 pandemic. When the Japanese Ministry of Health approved the Moderna mRNA-1273 vaccination in May 2021, it was limited to patients over 18 years old; however, using the additional data of efficacy and safety from clinical trials, vaccination was approved for 12- to 17-year-olds in Japan in July 2021. A previous study reported that myocarditis after the mRNA-1273 vaccination was more prevalent in young men; however, no patients under 18 years old with myocarditis diagnosed by cardiovascular magnetic resonance (CMR) findings after mRNA-1273 vaccination have been reported in Japan. In the present case, a 17-year-old healthy male developed arthralgia and had fever on the day of the second mRNA-1273 vaccination for severe acute respiratory syndrome coronavirus 2. Three days after the vaccination, the patient felt severe chest pain with broad ST elevations on electrocardiography and troponin T elevations. Symptoms and findings rapidly improved; however, on CMR, myocarditis remained. Thus, it is necessary to be vigilant of potential acute myocarditis in young men following mRNA-1273 vaccination. Learning objective: Although it is very rare, acute myocarditis after mRNA-1273 (Moderna) vaccination developed within 3-5 days following the second dose of the vaccine.Most reported cases were mild or moderate in severity, but there were cases of cardiogenic shock. We need to be vigilant of acute myocarditis in young men following mRNA-1273 vaccination.

Rationale, Design, and Baseline Characteristics of the CURRENT AS Registry-2.

BACKGROUND: There is scarce data evaluating the current practice pattern and clinical outcomes for patients with severe aortic stenosis (AS), including both those who underwent surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) and those who were managed conservatively in the TAVI era.Methods and Results: The Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis (CURRENT AS) Registry-2 is a prospective, physician-initiated, multicenter registry enrolling consecutive patients who were diagnosed with severe AS between April 2018 and December 2020 among 21 centers in Japan. The rationale for the prospective enrollment was to standardize the assessment of symptomatic status, echocardiographic evaluation, and other recommended diagnostic examinations such as computed tomography and measurement of B-type natriuretic peptide. Moreover, the schedule of clinical and echocardiographic follow up was prospectively defined and strongly recommended for patients who were managed conservatively. The entire study population consisted of 3,394 patients (mean age: 81.6 years and women: 60%). Etiology of AS was degenerative in 90% of patients. AS-related symptoms were present in 60% of patients; these were most often heart failure symptoms. The prevalence of high- and low-gradient AS was 58% and 42%, respectively, with classical and paradoxical low-flow low-gradient AS in 4.6% and 6.7%, respectively. CONCLUSIONS: The CURRENT AS Registry-2 might be large and meticulous enough to determine the appropriate timing of intervention for patients with severe AS in contemporary clinical practice.

Lionheart LincRNA alleviates cardiac systolic dysfunction under pressure overload.

Recent high-throughput approaches have revealed a vast number of transcripts with unknown functions. Many of these transcripts are long noncoding RNAs (lncRNAs), and intergenic region-derived lncRNAs are classified as long intergenic noncoding RNAs (lincRNAs). Although Myosin heavy chain 6 (Myh6) encoding primary contractile protein is down-regulated in stressed hearts, the underlying mechanisms are not fully clarified especially in terms of lincRNAs. Here, we screen upregulated lincRNAs in pressure overloaded hearts and identify a muscle-abundant lincRNA termed Lionheart. Compared with controls, deletion of the Lionheart in mice leads to decreased systolic function and a reduction in MYH6 protein levels following pressure overload. We reveal decreased MYH6 results from an interaction between Lionheart and Purine-rich element-binding protein A after pressure overload. Furthermore, human LIONHEART levels in left ventricular biopsy specimens positively correlate with cardiac systolic function. Our results demonstrate Lionheart plays a pivotal role in cardiac remodeling via regulation of MYH6.

Ventricular Fibrillation Induced by Takotsubo Syndrome with Congenital Long QT Syndrome.

We herein report a case of congenital long QT syndrome (LQTS) in which the QT interval was prolonged by Takotsubo syndrome (TTS), inducing ventricular fibrillation (VF). The patient was a 55-year-old woman who had been diagnosed with LQTS. Cardiopulmonary arrest occurred while coughing during sleep. VF was observed, and her heartbeat returned after two defibrillations. An electrocardiogram showed marked QT prolongation and large negative T waves. Echocardiography demonstrated hyperkinesis at the base of the left ventricle and akinesis at the apex. As there was no significant stenosis in the coronary artery, she was diagnosed with TTS.

Therapeutic angiogenesis by local sustained release of microRNA-126 using poly lactic-co-glycolic acid nanoparticles in murine hindlimb ischemia.

OBJECTIVE: Recent studies demonstrate that microRNAs show promising potential, including angiogenesis, in therapeutic intervention. MicroRNA-126 (miR-126) is reported to regulate angiogenesis by blocking Sprouty-related EVH1 domain-containing protein 1 (SPRED1), an endogenous inhibitor of vascular endothelial cell growth factor. In this study, we investigated the angiogenic effects of the sustained release of miR-126 loaded with poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) in a murine hindlimb ischemia model. METHODS: We induced mice hindlimb ischemia through femoral artery excision. We randomly assigned the mice to two groups and performed an intramuscular injection of miR-126-loaded PLGA NPs (miR-126) or scrambled miR-loaded PLGA NPs (control) shortly after induction of ischemia. RESULTS: The miR-126 expression levels in the ischemic limb at 3 days after treatment were significantly higher in mice treated with miR-126-loaded PLGA NPs than in those with scrambled miR, indicating the fair efficiency of local miR transduction (control vs miR-126: 0.33 ± 0.12 vs 0.74 ± 0.42; P < .05; n = 6). Laser Doppler perfusion imaging revealed that limb blood flow in mice treated with miR-126-loaded PLGA NPs was significantly higher at 14 days after treatment (sham vs control vs miR-126: 0.62 ± 0.09 vs 0.58 ± 0.05 vs 0.72 ± 0.07; P < .001; n = 12). Immunohistochemical analysis indicated that CD31-positive cell density and α-smooth muscle actin-positive vessel density were significantly higher in miR-126-treated mice (control vs miR-126: 0.33 ± 0.12 vs 0.74 ± 0.42; P < .05; n = 6). SPRED1 messenger RNA expression levels were significantly lower in miR-126-treated mice (control vs miR-126: 1.00 ± 0.05 vs 0.81 ± 0.07; P < .05; n = 6). Western blotting indicated that protein levels of pERK/ERK mediated by SPRED1 were significantly higher in miR-126-treated mice (control vs miR-126: 0.29 ± 0.10 vs 0.54 ± 0.21; P < .05; n = 6). CONCLUSIONS: This study suggests that sustained release of miR-126-loaded PLGA NPs might be an effective method in therapeutic angiogenesis for hindlimb ischemia.

Preclinical evaluation of a paclitaxel-incorporated nanoparticle-coated balloon in rabbit and porcine models.

BACKGROUND: The main drawback of current available drug coated balloons (DCB) is that a certain percentage of the coated drug is lost in the bloodstream during its delivery to the target lesion. We integrated the nanoparticle-mediated drug delivery technology and polydimethylsiloxane (PDMS) as a new excipient to facilitate an efficient drug delivery and uptake by endothelial cells. The present study aimed to evaluate the efficacy of the new DCB. METHOD AND RESULTS: The novel DCB were coated with 5.6mg of paclitaxel-incorporated nanoparticles using PDMS. The efficacy of the new DCB was examined in rabbit iliac stent model (n=12) and in the swine in-stent restenosis model (n=8) by quantitative coronary angiography (QCA) and optical coherence tomography (OCT). At 28days follow-up in the swine in-stent restenosis model, the area stenosis was significantly lower in DCB group as compared with that of the control group in OCT analysis (0.31±0.05 vs 0.49±0.06, p=0.04) though there was no significant differences observed in the rabbit iliac stent model in QCA and OCT analysis. CONCLUSION: The study results indicated that the paclitaxel-incorporated nanoparticle-coated balloon using PDMS has an inhibitory effect for the proliferation of smooth muscle cell in a swine coronary in-stent restenosis model.

Genetic Ablation of MicroRNA-33 Attenuates Inflammation and Abdominal Aortic Aneurysm Formation via Several Anti-Inflammatory Pathways.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is an increasingly prevalent and ultimately fatal disease with no effective pharmacological treatment. Because matrix degradation induced by vascular inflammation is the major pathophysiology of AAA, attenuation of this inflammation may improve its outcome. Previous studies suggested that miR-33 (microRNA-33) inhibition and genetic ablation of miR-33 increased serum high-density lipoprotein cholesterol and attenuated atherosclerosis. APPROACH AND RESULTS: MiR-33a-5p expression in central zone of human AAA was higher than marginal zone. MiR-33 deletion attenuated AAA formation in both mouse models of angiotensin II- and calcium chloride-induced AAA. Reduced macrophage accumulation and monocyte chemotactic protein-1 expression were observed in calcium chloride-induced AAA walls in miR-33-/- mice. In vitro experiments revealed that peritoneal macrophages from miR-33-/- mice showed reduced matrix metalloproteinase 9 expression levels via c-Jun N-terminal kinase inactivation. Primary aortic vascular smooth muscle cells from miR-33-/- mice showed reduced monocyte chemotactic protein-1 expression by p38 mitogen-activated protein kinase attenuation. Both of the inactivation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase were possibly because of the increase of ATP-binding cassette transporter A1 that is a well-known target of miR-33. Moreover, high-density lipoprotein cholesterol derived from miR-33-/- mice reduced expression of matrix metalloproteinase 9 in macrophages and monocyte chemotactic protein-1 in vascular smooth muscle cells. Bone marrow transplantation experiments indicated that miR-33-deficient bone marrow cells ameliorated AAA formation in wild-type recipients. MiR-33 deficiency in recipient mice was also shown to contribute the inhibition of AAA formation. CONCLUSIONS: These data strongly suggest that inhibition of miR-33 will be effective as a novel strategy for treating AAA.

Prevention of neointimal formation using miRNA-126-containing nanoparticle-conjugated stents in a rabbit model.

BACKGROUND: Despite recent progress with drug-eluting stents, restenosis and thrombosis after endovascular intervention are still major limitations in the treatment of cardiovascular diseases. These problems are possibly caused by inappropriate inhibition of neointimal formation and retardation of re-endothelialization on the surface of the stents. miR-126 has been shown to have the potential to enhance vascular endothelial cell proliferation. METHODS AND RESULTS: We designed and constructed a 27-nt double strand RNA (dsRNA) conjugated to cholesterol, which has high membrane permeability, and formed mature miR-126 after transfection. For site-specific induction of miR-126, we utilized poly (DL-lactide-co-glycolide) nanoparticles (NPs). miR-126-dsRNA-containing NPs (miR-126 NPs) significantly reduced the protein expression of a previously identified miR-126 target, SPRED1, in human umbilical vascular endothelial cells (HUVECs), and miR-126 NPs enhanced the proliferation and migration of HUVECs. On the other hand, miR-126 NPs reduced the proliferation and migration of vascular smooth muscle cells, via the suppression of IRS-1. Finally, we developed a stent system that eluted miR-126. This delivery system exhibited significant inhibition of neointimal formation in a rabbit model of restenosis. CONCLUSIONS: miR-126 NP-conjugated stents significantly inhibited the development of neointimal hyperplasia in rabbits. The present study may indicate the possibility of a novel therapeutic option to prevent restenosis after angioplasty.

Expression Patterns of miRNA-423-5p in the Serum and Pericardial Fluid in Patients Undergoing Cardiac Surgery.

BACKGROUND: Recently, it has been reported that specific microRNA (miRNA) levels are elevated in serum and can be used as biomarkers in patients with cardiovascular diseases. However, miRNAs expression profiles and their sources in pericardial fluid (PF) are unclear. METHODS AND RESULTS: The purpose of this study was to identify the levels of miRNAs in PF in relation to those in the serum in patients undergoing cardiac surgery. Serum (S) and PF from patients undergoing coronary artery bypass graft (CABG) due to stable angina pectoris (sAP) and unstable AP (uAP) and aortic valve replacement due to aortic stenosis (AS) were analyzed for the detection of miRNAs. We named these samples S-sAP, S-uAP, S-AS, PF-sAP, PF-uAP, and PF-AS, respectively. We first measured the levels of miR-423-5p, which was recognized previously as a biomarker for heart failure. miR-423-5p levels were significantly higher in PF than serum. Although there was no difference in miR-423-5p levels among the PF-AS, PF-sAP, and PF-uAP, its levels were significantly elevated in S-uAP compared with those in S-AS and S-sAP. In order to clarify the source of miR-423-5p in PF, we measured the levels of muscle-enriched miR-133a and vascular-enriched miR-126 and miR-92a in the same samples. miR-133a levels were significantly higher in serum than in PF, and it was elevated in S-uAP compared with S-AS. miR-126 level was significantly increased in serum compared with PF, and the level of miR-92a the similar tendency. miR-423-5p is located in the first intron of NSRP1. There is another miRNA, miR-3184, encoded in the opposite direction in the same region. In vitro experiments indicated that the duplex of miR-423-5p and miR-3184-3p was more resistant to RNase than the duplex of miR-423-5p and miR-133-3p, which may help to stabilize miR-423-5p in the PF. CONCLUSIONS: Our results suggested that miR-423-5p is enriched in PF, and serum miR-423-5p may be associate with uAP. Its expression pattern was different to that of muscle- and vascular-enriched miRNAs, miR-133a, miR-126, and miR-92a.

High-density lipoprotein cholesterol levels and cardiovascular outcomes in Japanese patients after percutaneous coronary intervention: a report from the CREDO-Kyoto registry cohort-2.

OBJECTIVE: To determine whether low HDL-C is a risk factor for adverse cardiovascular events in patients with known CAD. METHODS: We evaluated 10,391 patients who underwent PCI from January 2005 to December 2007. In total, 3838 (36.9%) patients had low HDL-C (HDL-C <40 mg/dL in males and <50 mg/dL in females) and 6553 (63.1%) patients had normal HDL-C based on measurements on admission. RESULTS: The unadjusted 5-year incidence of major adverse cardiac events (MACE: composite of cardiovascular death, myocardial infarction or stroke) was significantly higher in the low HDL-C group than in the normal HDL-C group (17.6% vs. 14.0%, P < 0.0001). However, after adjusting for confounders, low HDL-C was not associated with a higher risk of MACE (adjusted hazard ratio [HR] 1.07, 95% confidence interval (CI) 0.97-1.19; P = 0.19). There was no significant interaction between the effect of low HDL-C on MACE and several subgroup factors including age, sex, clinical presentation of CAD, statins use, serum low-density lipoprotein cholesterol level, and serum triglycerides level. CONCLUSION: Low HDL-C, as compared with normal HDL-C, was not associated with higher 5-year risk of MACE in patients who underwent PCI.

MicroRNA-451 exacerbates lipotoxicity in cardiac myocytes and high-fat diet-induced cardiac hypertrophy in mice through suppression of the LKB1/AMPK pathway.

RATIONALE: In some patients with type 2 diabetes mellitus (DM) without hypertension, cardiac hypertrophy and attenuated cardiac function are observed, and this insult is termed diabetic cardiomyopathy. To date, microRNA (miRNAs or miR) functions in diabetic cardiomyopathy remain to be elucidated. OBJECTIVE: To clarify the functions of miRNAs involved in diabetic cardiomyopathy caused by type 2 DM. METHODS AND RESULTS: C57BL/6 mice were fed a high-fat diet (HFD) for 20 weeks, which induced obesity and type 2 DM. miRNA microarray analyses and real-time polymerase chain reaction revealed that miR-451 levels were significantly increased in the type 2 DM mouse hearts. Because excess supply of saturated fatty acids is a cause of diabetic cardiomyopathy, we stimulated neonatal rat cardiac myocytes with palmitic acid and confirmed that miR-451 expression was increased in a dose- and time-dependent manner. Loss of miR-451 function ameliorated palmitate-induced lipotoxicity in neonatal rat cardiac myocytes. Calcium-binding protein 39 (Cab39) is a scaffold protein of liver kinase B1 (LKB1), an upstream kinase of AMP-activated protein kinase (AMPK). Cab39 was a direct target of miR-451 in neonatal rat cardiac myocytes and Cab39 overexpression rescued the lipotoxicity. To clarify miR-451 functions in vivo, we generated cardiomyocyte-specific miR-451 knockout mice. HFD-induced cardiac hypertrophy and contractile reserves were ameliorated in cardiomyocyte-specific miR-451 knockout mice compared with control mice. Protein levels of Cab39 and phosphorylated AMPK were increased and phosphorylated mammalian target of rapamycin (mTOR) was reduced in cardiomyocyte-specific miR-451 knockout mouse hearts compared with control mouse hearts. CONCLUSIONS: Our results demonstrate that miR-451 is involved in diabetic cardiomyopathy through suppression of the LKB1/AMPK pathway.

MicroRNA-33b knock-in mice for an intron of sterol regulatory element-binding factor 1 (Srebf1) exhibit reduced HDL-C in vivo.

MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports, including ours, indicated that miR-33a located within the intron of sterol regulatory element-binding protein (SREBP) 2 controls cholesterol homeostasis and can be a possible therapeutic target for treating atherosclerosis. Primates, but not rodents, express miR-33b from an intron of SREBF1. Therefore, humanized mice, in which a miR-33b transgene is inserted within a Srebf1 intron, are required to address its function in vivo. We successfully established miR-33b knock-in (KI) mice and found that protein levels of known miR-33a target genes, such as ABCA1, ABCG1, and SREBP-1, were reduced compared with those in wild-type mice. As a consequence, macrophages from the miR-33b KI mice had a reduced cholesterol efflux capacity via apoA-I and HDL-C. Moreover, HDL-C levels were reduced by almost 35% even in miR-33b KI hetero mice compared with the control mice. These results indicate that miR-33b may account for lower HDL-C levels in humans than those in mice and that miR-33b is possibly utilized for a feedback mechanism to regulate its host gene SREBF1. Our mice will also aid in elucidating the roles of miR-33a/b in different genetic disease models.

Achievement rates of Japan Atherosclerosis Society Guidelines 2007 LDL-cholesterol goals with rosuvastatin or atorvastatin in patients who had not achieved their goal with atorvastatin.

BACKGROUND: The Japan Atherosclerosis Society's 2007 Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases (JAS2007GL) advocate reducing LDL cholesterol (LDL-C) to target levels in patients with dyslipidemia, but achievement rates are frequently unsatisfactory even in the presence of lipid-lowering therapy. This multicenter, open-label, randomized, parallel-group study compared the efficacy of rosuvastatin and atorvastatin on JAS2007GL LDL-C goals in Japanese patients not achieving their target goal with atorvastatin treatment. METHODS: The study involved 20 clinical institutes in Japan (Kishiwada Atherosclerosis Prevention Study [KAPS] Group). Patients with category II or III risk of coronary artery disease (CAD), or those with a history of CAD (secondary prevention), who had not achieved their JAS2007GL LDL-C goals during treatment with atorvastatin for at least 4 weeks were switched either to rosuvastatin 5 mg/day (from atorvastatin 10 mg/day) or rosuvastatin 10 mg/day (from atorvastatin 20 mg/day) (n = 75) or continued to receive atorvastatin (n = 77). The primary endpoint was achievement of LDL-C goals at 3 months. The main secondary endpoint was achievement of LDL-C goal + high-sensitivity C-reactive protein level <1.0 mg/L at 3 months. RESULTS: Achievement rates for the primary endpoint were 49.3% in the rosuvastatin group and 31.7% in the atorvastatin group (P = 0.022). Achievement rates for the main secondary endpoint were 40.0% in the rosuvastatin group and 20.8% in the atorvastatin group (P = 0.010). Rosuvastatin and atorvastatin were both well tolerated in this study. CONCLUSIONS: Rosuvastatin is a useful treatment option for Japanese patients who are not achieving their JAS2007GL LDL-C goal with atorvastatin.

MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice.

MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports have indicated that miR-33, which is located within the intron of sterol regulatory element-binding protein (SREBP) 2, controls cholesterol homoeostasis and may be a potential therapeutic target for the treatment of atherosclerosis. Here we show that deletion of miR-33 results in marked worsening of high-fat diet-induced obesity and liver steatosis. Using miR-33(-/-)Srebf1(+/-) mice, we demonstrate that SREBP-1 is a target of miR-33 and that the mechanisms leading to obesity and liver steatosis in miR-33(-/-) mice involve enhanced expression of SREBP-1. These results elucidate a novel interaction between SREBP-1 and SREBP-2 mediated by miR-33 in vivo.

The association between post-load low insulin level and high mortality rates in patients with no previous diagnosis of diabetes mellitus.

BACKGROUND: Hyperinsulinemia and insulin resistance have been proposed as having a causal role in pathogenesis of atherosclerosis; however, the relationship between post-load insulin levels and long-term survival is not clear. We investigated whether post-load insulin response is a predictor of outcome in patients without previously recognized diabetes. METHODS: Data from 933 Japanese patients who underwent both a 75 g oral glucose tolerance test and coronary angiography with suspected coronary artery disease were analyzed. The determinant factors in association with all-cause death or cardiovascular events, including reinfarction, heart failure or angina requiring re-hospitalization, and coronary revascularization were examined by multivariate Cox regression analysis. RESULTS: The numbers of patients with normal glucose tolerance, impaired glucose regulation and diabetes were 326, 408 and 199, respectively. During the follow-up period (median 1113 days), death occurred in 37 patients including 13 cardiac causes. There were no significant differences in mortality or cardiovascular event incidence between glucose tolerance status. Kaplan-Meier curves indicated that the lower-response group of 2-hour insulin levels (<75.3 mU/L; median) was associated with higher mortality rates (Log-rank P=0.006). Multivariate Cox regression analysis revealed that 2-hour insulin level was an independent predictor of all-cause death (P=0.026) after adjustment for age, gender, number of stenosed vessels, ejection fraction, metabolic factors, and treatments. CONCLUSIONS: Post-load low insulin response is seen as a predictor of mortality rates for patients with no previous diagnosis of diabetes mellitus.

A case of right atrial angiosarcoma: The utility of PET and CT fusion imaging in detecting a malignant cardiac tumor.

A 49-year-old woman was admitted to the hospital because of cardiac tamponade. The hemorrhagic pericardial effusion was cytologically negative for malignant cells. Cardiac magnetic resonance imaging showed two masses in the anterior and lateral right atrium; however, positron emission tomography (PET) image using 18F-fluorodeoxyglucose revealed strong uptake in the anterior right atrium, without other tumors or metastasis. Intraoperatively, the lateral mass was confirmed as a thrombus, whereas the anterior mass was removed surgically and was diagnosed as an angiosarcoma with histopathological examination. However, she was re-admitted to the hospital 1 month after the operation because of cerebral hemorrhage, suspicious of distant metastasis. PET is useful for the detection of cardiac angiosarcoma.

A case of marked ST depression and myocardial injury as a result of disulfiram-ethanol reaction.

We report a case of a 50-year-old man with intractable hypotension, which led to ischemic electrocardiogram (ECG) changes and myocardial injury due to relative myocardial ischemia as a result of a disulfiram-ethanol reaction. This is the first report that assessed cardiac function during hypotension and ischemic ECG changes by emergency coronary angiography, left ventriculography, and right heart catheterization. This case indicates that disulfiram potentially has fatal side effects due to a disulfiram-ethanol reaction.