Recurrent Acute Coronary Syndrome in Young Man with Familial Hypercholesterolemia: Efficacy of Evolocumab Add-On Treatment Demonstrated via Serial Coronary Angiography.

In patients with acute coronary syndrome (ACS), lipid-lowering therapy plays an important role in the prevention of the recurrence of cardiovascular disease. Recent guidelines recommend the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with ACS if their low-density lipoprotein cholesterol (LDL-C) levels are not adequately controlled with statins and ezetimibe. Based on this, we report a case in which administering a PCSK9 inhibitor successfully lowered the patient's LDL-C level to the target level and managed the coronary artery disease (CAD) recurrence. A 39-year-old man who was taking statins presented to the hospital with chest pain and was diagnosed with unstable angina. He started taking maximum doses of statins and ezetimibe to lower his LDL-C. However, the patient's unstable angina recurred 1 year later, and a de novo lesion with plaque rupture was demonstrated via coronary angiography. The LDL-C failed to reach the target level despite maintaining the maximum dose of statin and ezetimibe. Accordingly, evolocumab was initiated in addition to rosuvastatin/ezetimibe 20/10 mg daily. Subsequently, coronary angiography was performed twice, and on follow-up, the patient remained free of CAD recurrence. This case highlights the efficacy of lipid-lowering therapy with evolocumab in high-risk patients with repeated ACS.

Double-chambered left ventricle with a thrombus in an asymptomatic patient: A case report.

BACKGROUND: Double-chambered left ventricle (DCLV) is an extremely rare congenital disease in which the left ventricle (LV) is divided by abnormal muscle tissue. Due to its rarity, there is a lack of data on the disease, including its diagnosis, treatment, and prognosis. Accordingly, we report a case in which DCLV was diagnosed and followed up. CASE SUMMARY: A 45-year-old man presented to our hospital due to abnormal findings on an electrocardiogram recorded during a health check. He had no specific cardiac symptoms, comorbidities or relevant past medical history. Echocardiography revealed that the LV was divided into two by muscle fibers. There were no findings of ischemia on coronary angiography and coronary computed tomography angiography performed to exclude differential diagnoses. After comprehensive analysis of the images, DCLV was diagnosed. As it seemed to be asymptomatic DCLV, we decided the patient was to be observed without administering any medication. However, follow-up echocardiography revealed a thrombus in the accessory chamber (AC). Anticoagulant medication was initiated, the thrombus resolved, and the patient is currently undergoing follow-up without any specific symptoms. CONCLUSION: Asymptomatic, uncomplicated DCLV was diagnosed through multimodal imaging; however, a thrombus in the AC occurred during the follow-up. The findings highlight that multimodal imaging is essential in diagnosing DCLV, and that anticoagulation is important in its management.

Independent Clinical Impacts of Procedural Complexity on Ischemic and Bleeding Events in Patients with Acute Myocardial Infarction: Long-Term Clinical Study.

This study aimed to investigate the relationship between a complex percutaneous coronary intervention (C-PCI) and long-term clinical outcomes in the AMI cohort. A total of 10,329 patients were categorized into the C-PCI and non-C-PCI groups. The primary ischemic endpoint was a composite of major adverse cardiac events (MACEs, cardiac death, myocardial infarction, stent thrombosis and revascularization). The primary bleeding endpoint was the risk of overt bleeding (BARC 2, 3 or 5). The median follow-up duration was 4.9 (2.97, 7.16) years. The risks of MACEs and bleeding were significantly higher in the C-PCI group (hazard ratio (HR): 1.72; 95% confidence interval (CI): 1.60 to 1.85; p < 0.001; and HR: 1.32; 95% CI: 1.17 to 1.50; p < 0.001, respectively). After propensity score matching, compared to the non-C-PCI group, the adjusted MACE rate in C-PCI remained significantly higher (p < 0.001), but no significant interaction (p = 0.273) was observed for bleeding. Significant differences in overt bleeding were observed only within the first three months (p = 0.024). The MACEs were consistently higher in the C-PCI group with or without severe comorbid conditions (p < 0.001 for both). Patients with AMI who undergo C-PCI experience worse long-term ischemic outcomes after successful PCI, regardless of the presence of severe comorbidities.

Prognostic Impact of the HFA-PEFF Score in Patients with Acute Myocardial Infarction and an Intermediate to High HFA-PEFF Score.

This study aimed to investigate the efficacy of the HFA-PEFF score in predicting the long-term risks in patients with acute myocardial infarction (AMI) and an HFA-PEFF score ≥ 2. The subjects were divided according to their HFA-PEFF score into intermediate (2−3 points) and high (4−6 points) score groups. The primary outcome was all-cause mortality. Of 1018 patients with AMI and an HFA-PEFF score of ≥2, 712 (69.9%) and 306 (30.1%) were classified into the intermediate and high score groups, respectively. Over a median follow-up of 4.8 (3.2, 6.5) years, 114 (16.0%) and 87 (28.4%) patients died in each group. Multivariate Cox regression identified a high HFA-PEFF score as an independent predictor of all-cause mortality [hazard ratio (HR): 1.53, 95% CI: 1.15−2.04, p = 0.004]. The predictive accuracies for the discrimination and reclassification were significantly improved (C-index 0.750 [95% CI 0.712−0.789]; p = 0.049 and NRI 0.330 [95% CI 0.180−0.479]; p < 0.001) upon the addition of a high HFA-PEFF score to clinical risk factors. The model was better at predicting combined events of all-cause mortality and heart failure readmission (C-index 0.754 [95% CI 0.716−0.791]; p = 0.033, NRI 0.372 [95% CI 0.227−0.518]; p < 0.001). In the AMI cohort, the HFA-PEFF score can effectively predict the prognosis of patients with an HFA-PEFF score of ≥2.

Slow Heart Rate Recovery Is Associated with Increased Exercise-induced Arterial Stiffness in Normotensive Patients without Overt Atherosclerosis.

BACKGROUND: This study evaluated whether blunted autonomic activity as measured by heart rate recovery (HRR) was associated with increased arterial stiffness, especially increased exercise-induced arterial stiffness, in normotensive patients without overt atherosclerosis. METHODS: One hundred fifty-four normotensive patients without overt atherosclerosis who had undergone a treadmill exercise test were consecutively enrolled. HRR was measured at one minute after exercise. Brachial-ankle pulse wave velocity (baPWV) at rest was measured, and carotid arterial stiffness indices at rest (CSI at rest) and after exercise (CSI after exercise) were assessed. RESULTS: Patients with slow HRR were older and tended to be male, and they had diabetes, higher resting and peak systolic blood pressures, higher resting heart rate, lower peak heart rate, lower metabolic equivalents, increased baPWV, and increased CSIs at rest and after exercise. HRR was inversely associated with baPWV and CSI after exercise when established cardiovascular risk factors were adjusted as confounding factors, and HRR was associated with CSI after exercise when resting systolic blood pressure and metabolic equivalent of tasks on cardiovascular risk factors were added as confounding factors. CONCLUSIONS: Sympathovagal imbalance demonstrated by slow HRR was associated with increased arterial stiffness and, above all, was closely associated with exercise-induced arterial stiffness in normotensive patients without overt atherosclerosis. This phenomenon might have been observed because blunt carotid arterial vasomotion following exercise results from autonomic dysfunction as well as vascular endothelial dysfunction.

Acromegaly with Normal Insulin-Like Growth Factor-1 Levels and Congestive Heart Failure as the First Clinical Manifestation.

The leading cause of morbidity and mortality in patients with acromegaly is cardiovascular complications. Myocardial exposure to excessive growth hormone can cause ventricular hypertrophy, hypertension, arrhythmia, and diastolic dysfunction. However, congestive heart failure as a result of systolic dysfunction is observed only rarely in patients with acromegaly. Most cases of acromegaly exhibit high levels of serum insulin-like growth factor-1 (IGF-1). Acromegaly with normal IGF-1 levels is rare and difficult to diagnose. Here, we report a rare case of an acromegalic patient whose first clinical manifestation was severe congestive heart failure, despite normal IGF-1 levels. We diagnosed acromegaly using a glucose-loading growth hormone suppression test. Cardiac function and myocardial hypertrophy improved 6 months after transsphenoidal resection of a pituitary adenoma.

A latent autoimmune diabetes in adults patient manifesting severe musculoskeletal complications.

Patients with diabetes have many different kinds of complications involving multiple organs, but those involving the musculoskeletal system are relatively uncommon. Diabetic muscle infarction (DMI) is a rare, painful, and potentially serious condition in patients with poorly controlled diabetes mellitus. A 35-year-old man diagnosed with type 2 diabetes eight years ago, visited with severe muscle pain in the right anteromedial thigh without any event of trauma. He had been treated with metformin, but his glycemic control was very poor with a glycated hemoglobin of 14.5%. Evaluation of his painful thigh lesion did not reveal any evidence of infection or vasculitis, but the magnetic resonance imaging and bone scan showed findings of DMI at vastus medialis muscle and an insufficiency fracture at the right medial tibial condyle. He was diagnosed with retinopathy, neuropathy and microalbuminuria but not macrovascular complications. We also diagnosed his diabetes as latent autoimmune diabetes in adults (LADA) based on his low C-peptide level, positive anti-glutamic acid decarboxylase (GAD) antibody and early onset diabetes. Instead of antibiotics, bed rest, analgesics and strict blood glucose control with multiple daily insulin injections led to symptom improvement. This is an unusual case of a young man with LADA experiencing severe musculoskeletal complication of DMI and insufficiency fracture. If a poorly controlled diabetic patient appears to have unaccounted soft tissue pain, musculoskeletal complications such as DMI associated with hyperglycemia should be considered.

The value of assessing myocardial deformation at recovery after dobutamine stress echocardiography.

BACKGROUND: The purpose of this study was to evaluate whether performing an assessment of myocardial deformation using speckle tracking imaging during the recovery period after dobutamine stress echocardiography (DSE) allows detection of significant coronary artery disease (CAD) in patients with chest discomfort. METHODS: DSE and coronary angiography were performed in 44 patients with chest discomfort. The mean global longitudinal peak systolic strain (GLS) was measured at rest, at low stress (dobutamine infusion rate of 10 µg/kg/min) and at recovery (5 min after cessation of dobutamine infusion) of DSE using automated function imaging with apical views. Fractional flow reserve (FFR) was also performed in patients with intermediate coronary stenosis. CAD was defined as having a ≥ 70% diameter stenosis on coronary angiography or as having a FFR < 0.8. Patients were divided two groups based on the absence or presence of CAD [CAD (-) group vs. CAD (+) group]. RESULTS: There were no significant differences in the clinical characteristics and results of conventional echocardiography between the two groups. GLS at recovery was lower in the CAD (+) group than in the CAD (-) group (-18.0 ± 3.4% vs. -21.0 ± 1.9%, p = 0.003). The optimal cutoff of GLS at recovery for detection of CAD was -19% (sensitivity of 70.6%, specificity of 83.3%). CONCLUSION: Assessment of GLS at recovery of DSE is a reliable and objective method for detection of CAD. This finding may suggest that systolic myocardial stunning remains even after recovery of wall motion abnormalities in patients with CAD.

Evolutionary change mimicking apical hypertrophic cardiomyopathy in a patient with takotsubo cardiomyopathy.

In this report, we introduce a case of thickening of the involved left ventricular apical segment on echocardiography and deep T-wave inversions in precordial leads on electrocardiography transiently seen in the course of recovery from biventricular takotsubo cardiomyopathy, mimicking apical hypertrophic cardiomyopathy. This result suggests that the echocardiographic finding of transient myocardial edema can be identified by cardiac magnetic resonance imaging in takotsubo cardiomyopathy. Additionally, it persisted a few weeks after full functional recovery. We believe that this case will contribute in part toward clarifying the pathophysiology of takotsubo cardiomyopathy.

Biodegradable nanoparticles containing TLR3 or TLR9 agonists together with antigen enhance MHC-restricted presentation of the antigen.

The effects of intraphagosomal toll-like receptor (TLR) activation on the MHC-restricted presentation of exogenous antigen were examined in dendritic cells (DCs). For phagosomal targeting, nanoparticles containing both a TLR agonist and a model antigen, ovalbumin (OVA), were prepared using biodegradable polymer poly(D,L-lactic acid-co-glycolic acid) and were then opsonized with mouse IgG. After incubating mouse DCs with the nanoparticles, the efficacy of OVA peptide presentation was evaluated using OVA-specific CD8 and CD4 T cells. Inclusion of either the TLR3 agonist poly(I:C) or the TLR9 agonist CpG oligodeoxynucleotides (ODN) significantly increased and prolonged both MHC class I- and class II-restricted OVA presentation. Accordingly, the DCs that phagocytosed the nanoparticles containing poly(I:C) or CpG ODN together with OVA efficiently induced the proliferation of OVA-specific CD8 and CD4 T cells. The potency levels of poly(I:C) and CpG ODN in increasing the MHC-restricted presentation of the exogenous antigen appeared to be similar. A combination of the 2 TLR agonists was synergistic in increasing the MHC class I-restricted, but not the class II-restricted, presentation of exogenous antigen. These results show that IgG-opsonized biodegradable nanoparticles containing both intraphagosomal TLR agonists and antigens can be efficient carrier materials in inducing antigen-specific T cell responses.

Cyclosporin A and tacrolimus, but not rapamycin, inhibit MHC-restricted antigen presentation pathways in dendritic cells.

The main targets for the immunosuppressive calcineurin inhibitors, cyclosporin A (CsA) and tacrolimus, have been considered to be activated T cells, but not antigen-presenting cells. Here we demonstrate that CsA and tacrolimus, but not rapamycin, inhibit major histocompatibility complex (MHC)-restricted antigen presentation in dendritic cells (DCs). Microencapsulated ovalbumin (OVA) was efficiently captured, processed, and presented on both class I MHC molecules (cross-presentation) as well as on class II MHC molecules. Addition of CsA and tacrolimus, but not rapamycin, to cultures of DCs inhibited both the class I processing pathway and the class II processing pathway of exogenous OVA. In addition, CsA and tacrolimus, but not rapamycin, also inhibited the classic class I processing pathway of endogenous OVA. CsA and tacrolimus did not inhibit presentation of exogenously added OVA peptide, SIINFEKL, phagocytic activity of DCs, or the total level of expression of class I MHC (H-2Kb) molecules. CsA and tacrolimus, however, inhibited profoundly the expression of SIINFEKL-H-2Kb complexes in OVA-phagocytized DCs. These results demonstrate clearly that CsA and tacrolimus inhibit intracellular processing events of antigens, and further suggest that the immunosuppressive activity of CsA and tacrolimus is at least in part due to inhibition of antigen processing pathways.

Identification of hepatitis C virus core domain inducing suppression of allostimulatory capacity of dendritic cells.

Hepatitis C virus (HCV) is remarkably efficient at establishing chronic infection. One of the reasons for this appears to be the suppression of the accessory cell function of professional antigen presenting cells. In the present study, the immunosuppressive activity of HCV protein was examined on dendritic cells (DCs) generated from mouse bone marrow progenitor cells in vitro. We found that the DCs forced to express HCV protein have defective allostimulatory ability. DCs expressing HCV protein were phenotypically indistinguishable from normal DCs. However, they were unable to produce IL-12 effectively when stimulated with lipopolysaccharide. The functional domain of the HCV protein essential for immunosuppression was determined using a series of NH2-and C-terminal deletion mutants of HCV core protein. We found that amino acid residues residing between the 21st and the 40th residues from the NH2-terminus of HCV core protein are required for immunosuppression. These findings suggest that HCV core protein suppresses the elicitation of protective Th1 responses by the inhibition of IL-12 production by DCs.