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.

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.

Successful Catheter Ablation for Paroxysmal Atrial Fibrillation in a Patient with Double-chambered Right Ventricle.

We herein describe an adult case of double-chambered right ventricle (DCRV) with symptomatic drug-intolerant paroxysmal atrial fibrillation (PAf). The woman was referred to undergo radiofrequency ablation (RFA), and mapping of the pulmonary veins (PVs) demonstrated that a spontaneous spike potential originating from the left inferior PV (LIPV) induced sustained Af in the second procedure. Accordingly, the LIPV was regarded as the arrhythmogenic PV. Since complete isolation of the PVs, the sinus rhythm has been maintained for at least two years. This is the first report to describe that RFA for drug-intolerant PAf was useful in a patient with DCRV.

Aortic valve replacement with a 17-mm mechanical prosthesis in octogenarian or older patients.

OBJECTIVE: Few studies have reported on aortic valve replacement (AVR) in patients aged >80 years who have small aortic annuli. Various surgical techniques have been proposed for treating such patients. We investigated AVR using small-diameter mechanical valves, in patients aged >80 years, to determine its effectiveness. METHODS: Eighteen consecutive patients (15 women; 3 men) aged >80 (mean: 83.3 ± 2.7) years underwent surgical AVR with a 17-mm prosthesis. The clinical status and results of pre- and post-operative echocardiography were evaluated. Midterm examination was conducted at 12.0 ± 1.0 months after AVR. RESULTS: The average preoperative body surface area of the patients was 1.39 ± 0.15 m(2); the average New York Heart Association functional class was 3.28 ± 0.75. Echocardiography showed a peak pressure gradient of 99.1 ± 38.4 mm Hg. Operative mortality was absent. A significant decrease in the peak pressure gradient was found on early (22.6 ± 7.2 mm Hg) and midterm (22.2 ± 8.0 mm Hg) postoperative echocardiography, compared with that in the preoperative period. During this follow-up, 16 patients improved to class I, a significant change in each perioperative period compared with the preoperative period. No mortality was observed at 1 year postoperatively. CONCLUSIONS: In patients aged >80 years who have small aortic annuli, AVR using a 17-mm prosthesis showed satisfactory clinical and hemodynamic results and provided a satisfactory remote prognosis.

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.

Therapy with immunoglobulin in patients with acute myocarditis and cardiomyopathy: analysis of leukocyte balance.

Intravenous immunoglobulin (IVIG) therapy has been used to treat several autoimmune or inflammatory diseases. We conducted a clinical trial of immunoglobulin therapy for acute myocarditis. The study consisted of two projects: (1) a comparison of prognosis between patients treated with and those not treated with IVIG in a multi-center study; (2) analyses of inflammatory cytokines and blood cell profiles in a substudy. In (1), 15 patients were treated with IVIG (1-2 g/kg, over 2 days), whereas 26 were untreated. There was a statistically significant difference between the survival curves of the patients treated with IVIG and the survival curves of those not treated with IVIG. There was no significant difference between the IVIG-treated and untreated groups in terms of clinical parameters of the acute and chronic phases. In (2), 10 patients were treated with IVIG and 6 were untreated. In both groups, all of the data except for changes in the fraction of lymphocytes and the fraction of monocytes decreased due to the treatment or during the course. In patients in the IVIG group, the percentage of peripheral eosinophils was decreased and the percentage of peripheral monocytes was increased by this treatment when they were compared with the pretreatment data. Therefore, therapy with IVIG seems to be a promising treatment for acute myocarditis given that it improves the clinical course, which may be due to modulation of inflammatory cytokines and the peripheral leukocyte balance.

Immunoglobulin treatment ameliorates myocardial injury in experimental autoimmune myocarditis associated with suppression of reactive oxygen species.

AIMS: We tested the hypothesis that immunoglobulin ameliorated experimental autoimmune myocarditis (EAM) in mice attributing to the suppression of reactive oxygen species (ROS)-mediated myocardial injury. METHODS: We intraperitoneally administered intact type of human immunoglobulin (Ig) or F(ab')2 fragments of human immunoglobulin, 1g/kg/day daily for 3 weeks, to male BALB/c mice with heart failure due to EAM. RESULTS: The results showed that intact type of Ig, but not F(ab')2 type, reduced the severity of myocarditis by comparing the heart weight/body weight and lung weight/body weight ratios, pericardial effusion score, macroscopic and microscopic scores. Tissue superoxide production was marked in untreated mice with EAM, which was suppressed by the treatment of immunoglobulins. The cytotoxic activities of lymphocytes in mice with EAM treated with Ig were reduced compared with untreated controls. The shift from Th1 toward Th2 cytokine balance was demonstrated by the treatment of immunoglobulins both in vitro and in vivo. CONCLUSION: ROS may be involved in the development of myocarditis. Intact Ig ameliorates myocardial damage in mice with myocarditis associated with suppression of ROS and cytotoxic activity of lymphocytes.

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.

Determinant factors of plasma B-type natriuretic peptide levels in patients with persistent nonvalvular atrial fibrillation and preserved left ventricular systolic function.

BACKGROUND AND OBJECTIVE: Plasma B-type natriuretic peptide (BNP) levels are determined by several factors. The presence of atrial fibrillation (AF) is one of these factors. Meanwhile, plasma BNP levels are well correlated with left ventricular (LV) filling pressure in patients with sinus rhythm. Furthermore, LV filling pressure can be estimated by the ratio of early diastolic transmitral velocity to early diastolic mitral annular velocity (E/e' ratio) in patients with sinus rhythm or with AF. However, it is still unclear if elevated plasma BNP levels reflect increases in LV filling pressure in patients with AF, especially with preserved LV systolic function. This study was designed to examine which factors determine plasma BNP levels in patients with persistent nonvalvular AF and preserved LV systolic function. METHODS AND RESULTS: We examined 195 clinically stable outpatients with persistent nonvalvular AF and preserved LV systolic function. They underwent comprehensive 2-dimensional and Doppler echocardiography, plasma BNP and creatinine levels, clinical history, and heart rate were determined. Then we statistically analyzed the correlation between plasma BNP levels and several variables including E/e' ratio. On univariate analyses, plasma BNP levels were significantly correlated with age, LV diastolic diameter (LVDd), E/e' ratio, and mitral E wave deceleration time. In addition, plasma BNP levels were significantly higher in males and in patients with a history of congestive heart failure and those who had been administered a ß-blocker. On multiple linear regression analyses, E/e' ratio, age, LVDd, and administration of ß-blocker were independent determinant factors of plasma BNP levels. CONCLUSIONS: Plasma BNP levels in patients with persistent AF and preserved LV systolic function are affected by E/e' ratio, age, LVDd, and administration of ß-blockers.

The importance of serial cardiac troponin measurement for evaluating the response to immunosuppressive therapy for myocarditis.

A 71-year-old woman was admitted to our department because of acute myocarditis. She was ameliorated with conventional heart failure treatment, however she developed left ventricular dilatation and cardiac troponin T (cTnT) was elevated again to >1.0 ng/ml 6 month after the first admission. She was re-admitted because of recurrent decompensated heart failure in spite of conventional treatment. Right ventricular endomyocardial biopsy revealed active myocarditis. Immunosuppressive therapy with prednisolone and azathioprine improved her symptoms and left ventricular function accompanied by a striking decrease of cTnT levels. The decreased cTnT level indicated an effective response to immunosuppression early after the beginning of treatment. These findings suggested that it is possible to evaluate the response to immunosuppressive therapy by serial measurement of cardiac troponin.

Relationship of cardio-ankle vascular index (CAVI) to carotid and coronary arteriosclerosis.

BACKGROUND: The cardio-ankle vascular index (CAVI) has been recently reported as a new index of aortic stiffness, which is less influenced by blood pressure than pulse wave velocity (PWV). The present study investigated the relationship between the levels of CAVI and carotid and coronary arteriosclerosis. METHODS AND RESULTS: The 443 consecutive patients who underwent CAVI, carotid sonography, and coronary angiography in hospital were examined. Intima-media thickness (IMT) and carotid plaque were evaluated by ultrasonography. The severity of coronary artery disease (CAD) was evaluated by coronary angiography and the subjects were divided into 4 groups (0, no significant organic stenosis: 1, 1-vessel disease: 2, 2-vessel disease: 3, 3-vessel disease). Univariate analyses showed that both CAVI and brachial-ankle PWV (baPWV) were associated with IMT and the presence of carotid plaque. Multiple stepwise regression analyses revealed that CAVI (p=0.0427), but not baPWV, was associated with the IMT. Both CAVI (p<0.0001) and baPWV (p=0.0140) were significantly associated with the severity of CAD. Multiple logistic analyses revealed that CAVI (p=0.0342), but not baPWV (p=0.8027), was associated with the presence of multivessel disease. CONCLUSION: High CAVI implies progression of carotid and coronary arteriosclerosis. CAVI may be more closely linked with arteriosclerosis than baPWV.

Long-term effects of early statin therapy for patients with acute myocardial infarction treated with stent implantation.

OBJECTIVES: Statins are widely administered to patients with acute myocardial infarction (AMI), but knowledge of the effects of early statin therapy on the long-term mortality of AMI patients after stent implantation is still limited, especially for beyond low-density lipoprotein cholesterol (LDL-C) lowering effects. METHODS: Our 378 consecutive AMI patients who were discharged alive from the hospital with successful stent implantation between 1997 and 2005 were included. We retrospectively evaluated the effects of statin therapy on major adverse cardiovascular events (MACE), including all-cause death, reinfarction, coronary artery bypass grafting, heart failure requiring rehospitalization, and target lesion revascularization. RESULTS: Statins were given to 271 patients according to the physician to achieve a LDL-C level of less than 100mg/dL. The achieved LDL-C levels in the statin group were 100.7, 95.1, 96.7, and 102.8mg/dL at discharge, 6 months, 1 year, and 3 years, respectively, whereas those in the non-statin group were 103.2, 107.3, 102.8, and 103.0mg/dL. These levels were not significantly different between the groups during 3 years. Based on Kaplan-Meier estimates, statin therapy was associated with a reduction of long-term mortality (log-rank test P=0.007). Multivariate Cox regression analysis revealed that statin therapy (P=0.015, hazard ratio: 0.10; 95% confidence interval: 0.01-0.64) was a significant predictor of favorable prognosis. Multivariate analysis revealed that statin treatment had a beneficial effect against MACE over 3 years (P=0.008). CONCLUSIONS: Early statin therapy was beneficial for long-term mortality of AMI patients treated with stenting.

From oxygen sensing to heart failure: role of thioredoxin.

Oxidative stress has been widely recognized to be involved in the pathogenesis of cardiopulmonary disorders. In ischemic heart diseases, it is involved not only in the development of atherosclerosis but also in ongoing ischemic injury, especially in the reperfusion process. Cardiomyopathy is another cardiac disorder in which oxidative stress is involved. In diabetic cardiomyopathy, homocysteine, a well-known source of oxidative stress, is believed to play major roles in its development. Thioredoxin (TRX) is a redox-acting protein ubiquitously present in the human body. It also is inducible by a wide variety of oxidative stresses. TRX is a multifunctional protein and has anti-inflammatory and antiapoptotic effects, as well as antioxidative effects. It is therefore feasible to think that TRX is a potential therapy for cardiac disease. Moreover, serum TRX is a well-recognized biomarker of various diseases involving oxidative stress, and this is also the case for cardiac disorders. Here we discuss how TRX is useful as a biomarker of and therapeutic agent for cardiopulmonary disorders, especially focusing on ischemic heart disease, myocarditis and oxygen sensing, and acute respiratory distress syndrome.

Relationship of serum adiponectin level to adverse cardiovascular events in patients who undergo percutaneous coronary intervention.

BACKGROUND: Hypoadiponectinemia has been reported to indicate an increased risk of cardiovascular disease, so the present study investigated the significance of serum adiponectin (APN) levels for predicting clinical outcomes after percutaneous coronary intervention (PCI). METHODS AND RESULTS: The APN levels were evaluated in 184 consecutive patients who underwent PCI. The patients were divided into Group A [the lowest quartile of APN levels (APN < or =4.5 microg/ml), n=46] and Group B [the upper 3 quartiles of APN levels (APN >4.5 microg/ml), n=138]. During a mean follow-up period of 27.3 months, the rate of major adverse cardiac and cerebrovascular events (MACCE: death from any cause, re-infarction, repeat coronary revascularization, hospitalization because of congestive heart failure, and cerebral infarction) was higher in Group A (58.7%) than in Group B (37.0%, p=0.0101). Moreover, when the APN levels were calculated by adjusting for sex, age, body mass index, and triglyceride levels, patients in the lowest quartile of residual APN levels had a higher risk of MACCE (p=0.0405). Multiple logistic analyses showed that hypoadiponectinemia (APN < or =4.5 microg/ml) was independently correlated with MACCE. Kaplan-Meier analysis demonstrated a higher MACCE rate in Group A than in Group B (Log-rank chi(2)=7.89, p=0.0050). CONCLUSION: The APN level may be helpful for predicting clinical outcomes after PCI.

Validation of the association between the gene encoding proteasome subunit alpha type 6 and myocardial infarction in a Japanese population.

BACKGROUND: Recently, a large case-control study (2,851 cases and 2,592 controls) reported that a functional single nuclear polymorphism (SNP) in the proteasome subunit alpha type 6 gene (PSMA6) conferred a risk of myocardial infarction (MI) in a Japanese population. The SNP (exon 1, -8C/G) is located in the 5' untranslated region of exon 1, and the risk-conferring allele G appears to enhance the transcription of PSMA6, which may exaggerate inflammation through activation of nuclear factor-kappa beta protein. The frequency of the risk conferring genotype (GG) in cases was reported to be greater than that in controls (12.4% vs 8.9%). The purpose of the present study was to validate this observation in our study population. METHODS AND RESULTS: Subjects with MI (n=433) were recruited from the outpatient clinic of the National Cardiovascular Center. Control subjects (n=2,186) were recruited from the Suita study. The frequencies of the GG genotype did not significantly differ between the control (9.8%) and MI groups (10.6%). Moreover, this genotype was not associated with C reactive protein levels in the Suita study. However, the GG genotype was significantly associated with greater intima-media thickness (n=2,051, p=0.015) after adjusting for blood pressure, sex, body mass index and age in the Suita study. CONCLUSION: The reported genotype in PSMA6 appears not to contribute appreciably to MI, but may contribute slightly to atherosclerosis in the present study population.

[Hypoadiponectinemia implies the development of atherosclerosis in carotid and coronary arteries].

OBJECTIVES: Adiponectin is an adipocyte-derived endocrine factor. Hypoadiponectinemia has been observed in obese patients, and plasma adiponectin levels are reported to increase during weight reduction. Moreover, hypoadiponectinemia has also been observed in patients with coronary artery diseases. The present study investigated the relationships between levels of adiponectin and carotid intimal-medial thickness, a marker of early vascular disease, and carotid artery plaque and the severity of coronary artery disease, a marker of advanced vascular disease. METHODS: Four hundred thirty-one consecutive patients were enrolled from inpatients without acute coronary syndrome who underwent coronary angiography between August 2001 and August 2003. The residual adiponectin levels were calculated by adjusting for sex, age, and body mass index, and a logarithmic transformation was applied. The severity of coronary artery disease was evaluated by coronary angiography and divided into four groups (Group 0: no significant organic stenosis, Group 1: 1-vessel disease, Group 2: 2-vessel disease, Group 3: 3-vessel disease or left main coronary trunk disease). Carotid plaque was evaluated by ultrasonography and divided into two groups [Group(-) : patients without carotid plaque, Group (+): patients with carotid plaque]. The intimal-medial thickness was measured on a longitudinal scan of the common carotid artery at a point 1 cm proximal from the bifurcation bulb. RESULTS: The logarithmic-transformed levels of residual adiponectin were associated with severity of coronary artery disease (Group 0: 0.18 +/- 0.59 microg/ml, Group 1: -0.02 +/- 0.56 microg/ml, Group 2: - 0.09 +/- 0.58 microg/ml, Group 3: - 0.10 +/- 0.66 microg/ml, p = 0.0013). The logarithmic-transformed levels of residual adiponectin were decreased in patients with carotid plaque [Group (-): 0.08 +/- 0.59 microg/ml, Group (+): - 0.08 +/- 0.59 microg/ml, p = 0.045]. However, the logarithmic-transformed levels of residual adiponectin were not associated with intimal-medial thickness (p = 0.6398). CONCLUSIONS: Hypoadiponectinemia adjusted for sex, age, body mass index implies the progression of carotid and coronary sclerosis.

Assessment of MEF2A mutations in myocardial infarction in Japanese patients.

BACKGROUND: Recently, a mutation in the human MEF2A gene was reported to be responsible for an autosomal dominant form of coronary artery disease, so the purpose of the present study was to assess the significance of MEF2A mutations in Japanese subjects with myocardial infarction (MI). METHODS AND RESULTS: The study population consisted of 589 control subjects recruited from the Suita study and 379 subjects with MI. The promoter, all the exons, and 3'-UTR regions of MEF2A were sequenced in 190 subjects with myocardial infarction. We found 2 amino acid length polymorphisms, a 7-amino acid deletion polymorphism, and a nonsense mutation (R447X) in exon 12. The length and deletion polymorphisms did not confer susceptibility to MI. Although the nonsense mutation was detected in 1 subject with MI, and in none of the control subjects, the impact of this mutation does not appear to be great; the subject had the MI while in his 70 s, had 2 major risk factors, and no family history of ischemic heart disease. CONCLUSION: MEF2A polymorphism does not contribute appreciably to MI in the Japanese population.