Liver-specific Lxr inhibition represses reverse cholesterol transport in cholesterol-fed mice.

BACKGROUND AND AIMS: High density lipoprotein (HDL) exerts an anti-atherosclerotic effect via reverse cholesterol transport (RCT). Several phases of RCT are transcriptionally controlled by Liver X receptors (Lxrs). Although macrophage Lxrs reportedly promote RCT, it is still uncertain whether hepatic Lxrs affect RCT in vivo. METHODS: To inhibit Lxr-dependent pathways in mouse livers, we performed hepatic overexpression of sulfotransferase family cytosolic 2B member 1 (Sult2b1) using adenoviral vector (Ad-Sult2b1). Ad-Sult2b1 or the control virus was intravenously injected into wild type mice and Lxrα/ß double knockout mice, under a normal or high-cholesterol diet. A macrophage RCT assay and an HDL kinetic study were performed. RESULTS: Hepatic Sult2b1 overexpression resulted in reduced expression of Lxr-target genes - ATP-binding cassette transporter G5/G8, cholesterol 7α hydroxylase and Lxrα itself - respectively reducing or increasing cholesterol levels in HDL and apolipoprotein B-containing lipoproteins (apoB-L). A macrophage RCT assay revealed that Sult2b1 overexpression inhibited fecal excretion of macrophage-derived 3H-cholesterol only under a high-cholesterol diet. In an HDL kinetic study, Ad-Sult2b1 promoted catabolism/hepatic uptake of HDL-derived cholesterol, thereby reducing fecal excretion. Finally, in Lxrα/ß double knockout mice, hepatic Sult2b1 overexpression increased apoB-L levels, but there were no differences in HDL levels or RCT compared to the control, indicating that Sult2b1-mediated effects on HDL/RCT and apoB-L were distinct: the former was Lxr-dependent, but not the latter. CONCLUSIONS: Hepatic Lxr inhibition negatively regulates circulating HDL levels and RCT by reducing Lxr-target gene expression.

Two Cases of Acquired High-Density Lipoprotein Deficiency with Immunoglobulin G4-Related Lecithin-Cholesterol Acyltransferase Autoantibody.

Lecithin-cholesterol acyltransferase (LCAT) plays a significant role in the progression from premature to mature high-density lipoprotein (HDL) in circulation. Consequently, primary or secondary LCAT deletion or reduction naturally results in low serum HDL cholesterol levels. Recently, rare cases of acquired HDL deficiency with LCAT autoantibodies have been reported, mainly from Japan, where LCAT autoantibodies of immunoglobulin G (IgG) caused the HDL deficiency. Here to our knowledge, we report for the first time two cases of acquired HDL deficiency caused by IgG4 linked LCAT autoantibodies with or without a high serum IgG4 level. Furthermore, these cases can extend to a new concept of "IgG4 autoimmune disease" from the viewpoint of verifying the serum autoantibody and/or renal histopathology.

Incidence and Risk Factors of Immediate Hypersensitivity Reactions and Immunization Stress-Related Responses With COVID-19 mRNA Vaccine.

BACKGROUND: With the implementation of mass vaccination campaigns against COVID-19, the safety of vaccine needs to be evaluated. OBJECTIVE: We aimed to assess the incidence and risk factors for immediate hypersensitivity reactions (IHSR) and immunization stress-related responses (ISRR) with the Moderna COVID-19 vaccine. METHODS: This nested case-control study included recipients who received the Moderna vaccine at a mass vaccination center, Japan. Recipients with IHSR and ISRR were designated as cases 1 and 2, respectively. Controls 1 and 2 were selected from recipients without IHSR or ISRR and matched (1 case: 4 controls) with cases 1 and cases 2, respectively. Conditional logistic regression analysis was used to identify risk factors associated with IHSR and ISRR. RESULTS: Of the 614,151 vaccine recipients who received 1,201,688 vaccine doses, 306 recipients (cases 1) and 2478 recipients (cases 2) showed 318 events of IHSR and 2558 events of ISRR, respectively. The incidence rates per million doses were estimated as IHSR: 266 cases, ISRR: 2129 cases, anaphylaxis: 2 cases, and vasovagal syncope: 72 cases. Risk factors associated with IHSR included female, asthma, atopic dermatitis, thyroid diseases, and a history of allergy; for ISRR, the risk factors were younger age, female, asthma, thyroid diseases, mental disorders, and a history of allergy and vasovagal reflex. CONCLUSION: In the mass vaccination settings, the Moderna vaccine can be used safely owing to the low incidence rates of IHSR and anaphylaxis. However, providers should be aware of the occurrence of ISRR. Although recipients with risk factors are associated with slightly increased risks of IHSR and ISRR, this is not of sufficient magnitude to warrant special measures regarding their vaccination.

Assessment of Delayed Large Local Reactions After the First Dose of the SARS-CoV-2 mRNA-1273 Vaccine in Japan.

Importance: A delayed large local reaction (DLLR) is a delayed-onset adverse skin reaction that may occur after injection of the mRNA-1273 vaccine against SARS-CoV-2. Objective: To examine the associations between sex and age and susceptibility of DLLRs after mRNA-1273 vaccination. Design, Setting, and Participants: This retrospective cross-sectional study was conducted at the Self-Defense Forces large-scale vaccination center in Tokyo, Japan, from May 24 to November 30, 2021. Participants were recipients of the second dose of the mRNA-1273 vaccine who had received the first dose 4 to 6 weeks earlier. Five experienced dermatologists interviewed participants to assess whether they had experienced symptoms of DLLR after administration of the first dose of the vaccine. Exposure: Receipt of the first dose of the mRNA-1273 vaccine. Main Outcomes and Measures: The primary outcome was the incidence rate of DLLR stratified by sex and age group. Odds ratios (ORs) were calculated to evaluate the differences between groups. Outcomes were tested for significance using the Pearson χ2 test with 95% CIs. Results: Of 5893 participants in the study, 3318 (56.3%) were male (median age, 55 years [IQR, 38-68 years]) and 2575 (43.7%) were female (median age, 50 years [IQR, 34-67 years]). A total of 747 participants (12.7%) experienced DLLR symptoms after the first dose of the mRNA-1273 vaccine. Symptoms were mild and not considered as contraindications to the vaccine. The incidence rate was significantly higher among females (22.4% [577 participants]; OR, 5.30; 95% CI, 4.42-6.34) than among males (5.1% [170 participants]; reference). Moreover, the incidence rate was significantly higher among participants aged 30 to 39 years (14.3% [129 participants]; OR, 1.68; 95% CI, 1.25-2.26), 40 to 49 years (15.8% [136 participants]; OR, 1.89; 95% CI, 1.41-2.53), 50 to 59 years (14.9% [104 participants]; OR, 1.76; 95% CI, 1.29-2.40), and 60 to 69 years (12.6% [182 participants]; OR, 1.45; 95% CI, 1.10-1.91) than among participants aged 18 to 29 years (9.0% [81 participants]; reference). Conclusions and Relevance: In this cross-sectional study, the first dose of the SARS-CoV-2 mRNA-1273 vaccine was associated with a higher incidence of DLLR among females and among individuals aged 30 to 69 years. The findings suggest that DLLR may be a type IV allergic skin reaction.

Improvement of left ventricular function after successful radiofrequency catheter ablation in persistent atrial fibrillation with preserved left ventricular ejection fraction: a comprehensive echocardiographic assessment using two-dimensional speckle tracking analysis.

BACKGROUND: A limited number of studies have investigated the effects of radiofrequency catheter ablation (RFCA) on left ventricular (LV) function and the left atrial (LA) size in patients with atrial fibrillation (AF). The purpose of this study was to conduct a comprehensive assessment of LV function in patients with AF with preserved left ventricular ejection fraction (LVEF) before and after RFCA. METHOD: A total of 30 consecutive patients with no recurrences after RFCA for persistent AF (age, 57.7 ± 8.4 years) were enrolled. Transthoracic echocardiography was performed at the baseline and 6 months after the final RFCA using speckle tracking derived LV strain analysis. RESULTS: After RFCA, we measured decreases in the LA volume index (33.7 ± 10.4 ml/m2 vs. 24.6 ± 8.6 ml/m2, p < 0.0001), while we observed improvements in systolic indices such as LVEF (56.8 ± 9.8% vs. 65.1 ± 9.1%, p < 0.0001), global longitudinal strain (- 16.8 ± 4.4% vs. - 18.8 ± 3.4%, p = 0.0055) and twist (8.12 ± 3.66° vs. 12.33 ± 6.75°, p = 0.0050), and also in diastolic indices such as strain rate during early diastole (SRE) (0.73 ± 0.10 s-1 vs. 1.32 ± 0.29 s-1, p < 0.0001) and early transmitral inflow velocity (E)/SRE (1.11 ± 0.36 m vs. 0.61 ± 0.19 m, p < 0.0001). Logistic regression analysis showed that ΔE/SRE was a contributing factor for improvement in LVEF (odds ratio 126.9; p = 0.021). CONCLUSION: In persistent AF with preserved LVEF, further improvement in LVEF and reverse remodeling of the LA are achieved after RFCA. LV filling pressure may play significant roles in the mechanisms.

The impact of left ventricular deformation and dyssynchrony on improvement of left ventricular ejection fraction following radiofrequency catheter ablation in Wolff-Parkinson-White syndrome: A comprehensive study by speckle tracking echocardiography.

PURPOSE: The purpose of this study was to evaluate left ventricular (LV) deformation and LV dyssynchrony in patients with Wolff-Parkinson-White (WPW) syndrome and to identify the factors that affect the efficacy of radiofrequency catheter ablation (RFCA). METHODS: Thirty patients (26 men, mean age 40 ± 12 years) with WPW syndrome were prospectively recruited for this study. They underwent 2-dimensional transthoracic echocardiography with speckle tracking analysis before RFCA and again within 48 hours after RFCA. Control group consisted of 15 age and sex-matched healthy volunteers. RESULTS: The patients had significantly lower LV ejection fraction (LVEF), global longitudinal strain (Sl ), and global circumferential strain (Sc ) compared with healthy controls (64% ± 8% vs 68% ± 5%, P = .049; -17.6% ± 3.2% vs -19.9% ± 3.3%, P = .037, -15.2% ± 2.5% vs -19.4% ± 2.5%, P < .0001, respectively). Patients had a significantly higher dyssynchrony index relative to healthy controls (58.4 ± 49.0 ms vs 36.4 ± 31.1 ms, P = .031). After RFCA, there was a significant increase in LVEF and global Sc (68% ± 8% vs 64% ± 8%, P = .005; -17.3% ± 2.0% vs -15.2% ± 2.5%, P < .0001, respectively), along with a significant decrease in the dyssynchrony index (36.9 ± 36.3 ms vs 58.4 ± ms, P < .001) relative to the baseline values. Logistic regression revealed that the baseline dyssynchrony index was a predictor of LVEF improvement after RFCA (odds ratio: 1.060, P = .038). CONCLUSION: In WPW syndrome, impaired LV circumferential deformation can be restored by RFCA with concomitant improvement in LV dyssynchrony and LVEF.

Systolic collapse of aortic composite graft after Bentall operation: A sign of pseudoaneurysm formation.

Although aortic root replacement using a composite graft including the Bentall operation is the treatment of choice for a diseased aortic valve and root dilatation, composite graft endocarditis can occur as a life-threatening complication with a high mortality rate. When aortic pseudoaneurysm occurs due to composite graft endocarditis, it usually indicates that saccular bulging of the surrounding tissue of the composite graft is present. Furthermore, another sign and a clue of the diagnosis of pseudoaneurysm is the collapse of the composite graft due to the outer compression pressure of the leaking blood flow. Additionally, right parasternal view is useful to get the clear images of this phenomenon. Echocardiographic evaluation will contribute to the early recognition of this highly critical pathology.

Primary Mural Endocarditis Without Valvular Involvement.

Primary mural endocarditis is an extremely rare infection in which nonvalvular endocardial involvement is seen without any cardiac structural abnormalities such as ventricular septal defects. The rapid and precise diagnosis of this disease remains challenging. We present 2 cases (67- and 47-year-old male patients) of pathologically confirmed primary mural endocarditis that could have been detected by initial transthoracic echocardiography in the emergency department. Transthoracic echocardiography and transesophageal echocardiography play critical roles in the early recognition and confirmation of primary mural endocarditis.

Visualization of Recanalized Coronary Occlusion with Dissection by Optical Frequency Domain Imaging.

A 43-year-old asymptomatic male patient with a positive stress myocardial perfusion imaging result was admitted to our institution. Although no organic lesion was detected by 64-row coronary computed tomography angiography (CCTA), invasive coronary angiography revealed a unique anatomy with a long lesion in the middle of the left anterior descending artery. Optical frequency domain imaging (OFDI) demonstrated the details of the recanalized occlusion with coronary dissection. OFDI provides in vivo coronary images with high spatial resolution and better three-dimensional reconstructions and supports invasive coronary angiography to elucidate infinitesimal and complicated intraluminal morphology that might be missed by CCTA alone.

Cardiac Asystole Triggered by Temporal Lobe Epilepsy with Amygdala Enlargement.

A 25-year-old previously healthy man was hospitalized for syncope. While standing, he suddenly lost consciousness, followed by a generalized tonic clonic seizure. An electrocardiogram demonstrated asystole. No cardiac abnormalities were detected on the echocardiogram, cardiac magnetic resonance imaging (MRI), positron emission tomography, or a coronary angiogram. An electrophysiological study showed normal sinus node and atrioventricular node function. An electroencephalogram revealed small spike waves in the fronto-temporal region. Brain MRI demonstrated a left-sided amygdala enlargement. To the best of our knowledge, this is the first case of temporal lobe epilepsy with an amygdala enlargement that induced cardiac asystole.

Successful Endovascular Removal of a Perforated Inferior Vena Cava Filter Complicated by a Large Retroperitoneal Hematoma: Pitfall of Catheter-Directed Thrombolysis.

Symptomatic caval perforation is rare complication after inferior vena cava (IVC) filter insertion. A 44-year-old woman developed back pain after the placement of retrieval IVC filter during catheter-directed thrombolysis (CDT). Her computed tomography showed a large right-sided retroperitoneal hematoma. After 2 weeks, endovascular removal of the perforated filter was successfully performed without complication. Because thrombolytic agents can accelerate bleeding caused by endovascular procedures, the bleeding rate of the IVC filter deployment during CDT might be higher than expected.

A novel cardiac ryanodine receptor gene (RyR2) mutation in an athlete with aborted sudden cardiac death: a case of adult-onset catecholaminergic polymorphic ventricular tachycardia.

Sudden cardiac death (SCD) in athletes <35 years of age are mostly due to congenital or acquired cardiac malformations or hypertrophic cardiomyopathy. However, ion channelopathies such as catecholaminergic polymorphic ventricular tachycardia (CPVT) or long-QT syndromes, which are less frequently observed, are also potential pathogenesis of SCD in young athletes. CPVT is an inherited arrhythmia that is induced by physical or emotional stress and may lead to ventricular fibrillation syncope or SCD. Here, we report a case of athlete woman with adult-onset CPVT and aborted SCD who has a novel missense mutation (K4392R) in the cardiac RyR2 gene.

'Honeycomb appearance' on three-dimensional transthoracic echocardiography as the landmark of left ventricular non-compaction: two case reports.

INTRODUCTION: Left ventricular non-compaction is a rare congenital heart disease, and is most commonly diagnosed via two-dimensional echocardiography according to echocardiographic criteria. Recently, transthoracic three-dimensional echocardiography has become available in the clinical setting. CASE PRESENTATION: We present two isolated cases of left ventricular non-compaction from Japan (in an 84-year-old woman and 47-year-old man) that were confirmed by two-dimensional echocardiography, contrast-enhanced two-dimensional echocardiography, three-dimensional echocardiography and cardiac magnetic resonance imaging. In both cases, three-dimensional echocardiography successfully demonstrated the trabecular meshwork of the left ventricle, referred to as a 'honeycomb appearance'. CONCLUSIONS: Three-dimensional echocardiography has the advantage of visualizing an en-face view of the trabecular meshwork, which is not possible with two-dimensional echocardiography. We further emphasize the clinical utility of three-dimensional echocardiography, which is not limited to just the observation of the trabeculations and inter-trabecular recesses, but can also visualize the trabecular meshwork with a 'honeycomb appearance'.

Newly developed mobile mass superimposed on mitral annulus calcification in patient with cerebral infarction: Documentation of a unique embolic source.

Mitral annulus calcification (MAC) has been recognized as a potent risk factor to cause cerebral infarction. There has been suggested possible linkage between mass on MAC and systemic embolic events. We report a case of cerebral infarction with newly developed mobile mass superimposed on MAC.