Effect of a 3-Month Single-Drug Approach Using Rivaroxaban for Symptomatic Proximal Deep Vein Thrombosis.

Background: Factor Xa inhibitors, such as rivaroxaban, are increasing the convenience of treatment for deep vein thrombosis (DVT). Limited evidence exists regarding clot evaluation at 3 months after treatment for DVT. Methods and Results: We retrospectively analyzed the clinical course of symptomatic proximal DVT in patients who received 3 months of anticoagulation treatment at our hospital. Patients treated with the rivaroxaban single-drug approach were classified as group A (n=42). Patients treated with unfractionated heparin (UFH) or subcutaneous fondaparinux followed by vitamin K antagonist comprised group B (n=60) as an historical cohort. The quantitative ultrasound thrombosis (QUT) score was used to quantify clot burden before and after treatment. No significant differences were observed in patient characteristics between the groups. Serum D-dimer levels in both groups significantly improved after treatment. Clot volume assessed using QUT also reduced significantly in both groups. The QUT score in groups A and B improved from 7.5 [4.8, 12.0] to 3.0 [1.8, 5.0; P=0.000] and 7.0 [4.0, 9.8] to 3.0 [2.0, 5.0; P=0.000], respectively. The change in QUT (∆QUT) was significantly greater in group A compared with group B (-4.5 [-8.25, -2.0] vs. -2.0 [-6.0, 0.0]; P=0.005). Conclusions: We were able to demonstrate the effectiveness of DVT treatment using rivaroxaban over a period of 3 months from onset, in terms of clot regression evaluated using the QUT score.

Determination of lipid-rich plaques by artificial intelligence-enabled quantitative computed tomography using near-infrared spectroscopy as reference.

BACKGROUND AND AIMS: Artificial intelligence quantitative CT (AI-QCT) determines coronary plaque morphology with high efficiency and accuracy. Yet, its performance to quantify lipid-rich plaque remains unclear. This study investigated the performance of AI-QCT for the detection of low-density noncalcified plaque (LD-NCP) using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). METHODS: The INVICTUS Registry is a multi-center registry enrolling patients undergoing clinically indicated coronary CT angiography and IVUS, NIRS-IVUS, or optical coherence tomography. We assessed the performance of various Hounsfield unit (HU) and volume thresholds of LD-NCP using maxLCBI4mm ≥ 400 as the reference standard and the correlation of the vessel area, lumen area, plaque burden, and lesion length between AI-QCT and IVUS. RESULTS: This study included 133 atherosclerotic plaques from 47 patients who underwent coronary CT angiography and NIRS-IVUS The area under the curve of LD-NCP<30HU was 0.97 (95% confidence interval [CI]: 0.93-1.00] with an optimal volume threshold of 2.30 mm3. Accuracy, sensitivity, and specificity were 94% (95% CI: 88-96%], 93% (95% CI: 76-98%), and 94% (95% CI: 88-98%), respectively, using <30 HU and 2.3 mm3, versus 42%, 100%, and 27% using <30 HU and >0 mm3 volume of LD-NCP (p < 0.001 for accuracy and specificity). AI-QCT strongly correlated with IVUS measurements; vessel area (r2 = 0.87), lumen area (r2 = 0.87), plaque burden (r2 = 0.78) and lesion length (r2 = 0.88), respectively. CONCLUSIONS: AI-QCT demonstrated excellent diagnostic performance in detecting significant LD-NCP using maxLCBI4mm ≥ 400 as the reference standard. Additionally, vessel area, lumen area, plaque burden, and lesion length derived from AI-QCT strongly correlated with respective IVUS measurements.

Rationale and design of the INVICTUS Registry: (Multicenter Registry of Invasive and Non-Invasive imaging modalities to compare Coronary Computed Tomography Angiography, Intravascular Ultrasound and Optical Coherence Tomography for the determination of Severity, Volume and Type of coronary atherosclerosiS).

BACKGROUND: Coronary CT angiography (CCTA) is a first-line noninvasive imaging modality for evaluating coronary artery disease (CAD). Recent advances in CCTA technology enabled semi-automated detection of coronary arteries and atherosclerosis. However, there have been to date no large-scale validation studies of automated assessment of coronary atherosclerosis phenotype and coronary artery dimensions by artificial intelligence (AI) compared to current standard invasive imaging. METHODS: INVICTUS registry is a multicenter, retrospective, and prospective study designed to evaluate the dimensions of coronary arteries, as well as the characteristic, volume, and phenotype of coronary atherosclerosis by CCTA, compared with the invasive imaging modalities including intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS)-IVUS and optical coherence tomography (OCT). All patients clinically underwent both CCTA and invasive imaging modalities within three months. RESULTS: Patients data are sent to the core-laboratories to analyze for stenosis severity, plaque characteristics and volume. The variables for CCTA are measured using an AI-based automated software and assessed independently with the variables measured at the imaging core laboratories for IVUS, NIRS-IVUS, and OCT in a blind fashion. CONCLUSION: The INVICTUS registry will provide new insights into the diagnostic value of CCTA for determining coronary atherosclerosis phenotype and coronary artery dimensions compared to IVUS, NIRS-IVUS, and OCT. Our findings will potentially shed new light on precision medicine informed by an AI-based coronary CTA assessment of coronary atherosclerosis burden, composition, and severity. (ClinicalTrials.gov: NCT04066062).

Serum IgG4-negative IgG4-related disease with a cardiac mass: A case report.

RATIONALE: Although IgG4-related disease (IgG4-RD) can affect various organs, its association with a cardiac mass is exceptionally rare. Here, we report a case of a woman with IgG4-RD and a cardiac mass and discuss 10 similar cases reported previously. PATIENT CONCERNS: A 65-year-old woman was referred to our hospital for chest discomfort and back pain. DIAGNOSES: In accordance with the 2019 ACR/EULAR diagnostic criteria for IgG4-RD, she was diagnosed with IgG4-RD based on dense lymphocytic infiltration on histopathology, IgG/IgG4-positive cell ratio <40%, >10/hpf IgG4-positive cells on immunostaining, and paraspinal zone soft tissue lesions in the chest. INTERVENTIONS: An external pacemaker was implanted for the complete atrioventricular block on the electrocardiogram. After the diagnosis of IgG4-RD, she was treated with glucocorticoids and rituximab. OUTCOMES: She remains under observation without disease recurrence. LESSONS: IgG4-RD are usually treated with glucocorticoids; however, in cases of a cardiac mass, life-threatening complications may occur and surgery is often needed. Combination therapy with glucocorticoids and rituximab may be effective even in patients with IgG4-RD and cardiac mass, which may avoid the need of invasive treatments, such as surgery.

Determination of Peak Oxygen Uptake in Patients with Acute Myocardial Infarction: The Role of Arterial Stiffness in Cardio-Vascular-Skeletal Muscle Coupling.

The relationship between arterial stiffness and oxygen uptake (VO2) in patients with acute myocardial infarction (AMI) remains unclear. We aimed to investigate this relationship and factors contributing to VO2 in patients with AMI. The role of arterial stiffness in cardio-skeletal muscle coupling during exercise was then elucidated. Upon discharge, we measured exercise capacity using cardiopulmonary exercise testing (CPX), assessed arterial stiffness with the cardio-ankle vascular index (CAVI), and determined body composition to assess the skeletal muscle mass of 101 patients with AMI. Patients were categorized based on their CAVI scores into three groups: (i) normal (CAVI: ≤7.9), (ii) borderline (CAVI: 8.0-8.9), and (iii) abnormal (CAVI: ≥9.0). Subsequently, VO2 was compared among these groups. The relationship between the CAVI and VO2 Peak during CPX and factors contributing to VO2 Peak were investigated. The abnormal CAVI group had a significantly lower VO2 Peak than the normal and borderline groups. The CAVI was associated with VO2 Peak. Furthermore, the CAVI was found to be a factor contributing to VO2 Peak. These findings suggest that arterial stiffness in tissue blood distribution and blood supply causes systemic exercise limits in patients with AMI. This suggests that arterial stiffness plays a significant role in cardio-vascular-skeletal muscle coupling.

Effect of nicorandil administration on cardiac burden and cardio-ankle vascular index after coronary intervention.

Myocardial injury is a problem associated with percutaneous coronary intervention (PCI). This study aimed to clarify the role of nicorandil administration in preventing myocardial injury. This study included patients with stable angina who underwent PCI from November 2013 to June 2016. Of 58 consecutive patients, the first 20 patients received only saline infusion after PCI (control group); the other 38 patients received a continuous intravenous infusion of nicorandil and saline after PCI (nicorandil group). Troponin I and brain natriuretic peptide (BNP) levels were measured. Vascular parameters, such as blood pressure (BP), cardiac output, cardio-ankle vascular index (CAVI), and estimated systemic vascular resistance (eSVR), were measured. Troponin I of both groups increased 12 h after PCI. Changes in BNP levels between immediately after PCI and 12 h after PCI were significantly higher in the control than in the nicorandil group (10.8 ± 44.2 vs. - 2.6 ± 14.6 pg/ml, p = 0.04). In the nicorandil group, BP, eSVR, and CAVI decreased significantly at 12 h after PCI compared with those immediately after PCI (p < 0.0001), whereas no change was observed in the control group. In a single linear analysis, the change in BP (r = 0.36, p < 0.01) and nicorandil administration (r = - 0.47, p < 0.001) was significantly correlated with the change in CAVI, multiple regression analysis revealed that the changes in CO and eSVR were significant contributing factors for the changes in CAVI. PCI could result in myocardial injury and/or cardiac burden in patients with stable angina. Nicorandil administration after PCI may be effective in relieving the burden by decreasing arterial stiffness (CAVI).

A Case Demonstrating the Cardio-Vascular Interaction by a New Cardio-Ankle Vascular Index During the Treatment of Concentric Hypertrophy.

A 42-year-old hypertensive woman came to our hospital suffering from shortness of breath. Her left ventricular mass index (LVMI) was increased, and a new arterial stiffness index, cardio-ankle vascular index (CAVI), was also elevated. By treating hypertension (HT), diabetes mellitus (DM) and obstructive sleep apnea (OSA), her left ventricular concentric hypertrophy was improved, accompanying with a decrease in CAVI. These observations suggested that arterial stiffness monitored with CAVI might be involved in cardiac hypertrophy. This cardio-vascular interaction could be demonstrated at the first time by monitoring CAVI, which is not affected by blood pressure (BP) at measuring time.

Susceptibilities of epicardial and subcutaneous fat tissue for browning-gene expression and diet-induced volume reduction are different.

The upregulation of brown or brown-like beige adipocytes is a potential strategy for the prevention or treatment of diabetes and coronary artery diseases in obese patients. Epicardial adipose tissue (EAT) differs significantly from subcutaneous fat tissue (SAT) in metabolic properties. To investigate properties of EAT further, thermogenesis gene expression was investigated in human autopsy and murine samples, and adipocytes differentiated from EAT mesenchymal cells. Subsequently, analyzed EAT volume alterations were observed to be associated with weight reduction in obese patients by imaging. Gene expression analyses of autopsy samples revealed that UCP­1 mRNA levels in EAT were significantly increased compared with SAT, and ß3­adrenergic receptor (AR) levels tended to be increased; this finding was verified in comparing EAT with SAT in mice. Browning stimulation of human EAT­derived MCs increased uncoupling protein­1 and ß3­AR levels by 3.2 fold­ and 12.6­fold compared with SAT­derived MCs, respectively. Subsequent imaging for EAT volume measurement using multi­detector computed tomography in 10 obese patients revealed that mean EAT volumes did not significantly decrease following weight loss therapy. The EAT volume alterations were not correlated with weight changes, whereas positive correlations were observed in SAT and visceral adipose tissue. Therefore, the studies in man and mouse on EAT properties demonstrated that susceptibilities of EAT and SAT for browning­gene expression and diet­induced volume reduction were grossly different. The data suggest a potential association of EAT with local thermogenetic and metabolic homeostasis in cardiac and/or cardiovascular cells, in conjunction with systemic energy metabolism.

The clinical course of symptomatic deep vein thrombosis after 3 months of anticoagulant therapy using fondaparinux/edoxaban or fondaparinux/vitamin K antagonist.

BACKGROUND: For the management of venous thromboembolism (VTE), providing anticoagulant therapy within the therapeutic range has been a major challenge, as conventional therapy with unfractionated heparin (UFH) and vitamin K antagonist (VKA) requires frequent laboratory monitoring and dose adjustment. Recently, fondaparinux and edoxaban are being used as beneficial alternatives to UFH and VKA. METHODS: We evaluated the clinical course of symptomatic deep vein thrombosis (DVT) in patients who received the 3-month anticoagulation therapy with fondaparinux/edoxaban (Group A; n=40) in comparison with the findings from our previous experience of patients who received the fondaparinux/VKA combination (Group B; n=33). RESULTS: In both Groups A and B, serum D-dimer was significantly improved after treatment (p<0.001). The thrombus volume assessed by quantitative ultrasound thrombosis (QUT) score was significantly reduced in both groups (p<0.001). There was no difference in the proportion of patients who were normalized (ie, disappearance of DVT) between the groups, although Group A had significantly more patients who were normalized or improved (ie, disappearance and reduction of DVT) (p<0.001). No bleeding event was observed in either group. However, in one patient in Group B, worsening of DVT and development of symptomatic PE were observed. CONCLUSION: Fondaparinux/edoxaban therapy is as effective as fondaparinux/VKA. This treatment has the possible advantage in thrombus regression. This would be a beneficial therapeutic option for both patients and physicians.

Cardio-ankle vascular index relates to left ventricular ejection fraction in patients with heart failure. A retrospective study.

The cardio-ankle vascular index (CAVI) has been proposed as a new noninvasive marker of arterial stiffness independent of blood pressure. Arterial stiffness is closely related to afterload, and elevated afterload aggravates heart failure. We hypothesized that CAVI is a potential marker of afterload in patients with heart failure. Thirty patients who were admitted because of acute heart failure were identified retrospectively from a review of clinical records. Plasma brain natriuretic peptide (BNP) levels, CAVI, cardiothoracic ratio (CTR), and echocardiographic parameters obtained during acute and chronic phases of heart failure were analyzed. Left ventricular ejection fraction (LVEF) increased significantly and CTR, BNP and CAVI decreased significantly after treatment of heart failure. A significant negative correlation was observed between the change in CAVI and change in LVEF in all subjects (r = -0.3272, P < 0.05). To examine the relationship between CAVI and LVEF, we divided the patients into two subgroups (∆CAVI < -0.5; CAVI decrease group, ∆CAVI ≥ -0.5; CAVI non-decrease group). CAVI was significantly improved after heart failure treatment only in the CAVI decrease group. LVEF decreased significantly in both groups, but the P value was smaller in the CAVI decrease group than in the CAVI non-decrease group. The change in LVEF correlated significantly with the change in CAVI in the CAVI decrease group (r = -0.4201, P < 0.05), whereas no significant correlation was found in the CAVI non-decrease group. CAVI correlates inversely with LVEF after heart failure treatment. Our results suggest that CAVI might partially reflect the afterload in patients with heart failure.

Changes in cardio-ankle vascular index in smoking cessation.

AIM: To investigate the effect of smoking and smoking cessation on cardio-ankle vascular index (CAVI). METHODS: The subjects were 82 smokers (77 men, 64+/-10 years) and 20 non-smokers (18 men, 61+/-7 years). CAVI was measured every 3 months and CAVI severity was classified into 3 levels. Decreased, unchanged, and increased CAVI severity levels were coded as "improvement," "no change," and "exacerbation," respectively. Smoking status was coded as "success" for complete abstinence, "partial success" for a reduced number of cigarettes, and "failure" for an unchanging number of cigarettes. RESULTS: Compared with non-smokers, smokers showed a higher CAVI (p<0.05) prior to smoking cessation. Post-cessation, CAVI improved from 9.4 to 8.6 (p<0.01) in "success" cases (n=22), and the significant pre-cessation difference from non-smokers (n=20, CAVI=8.8) disappeared. With regard to the change in CAVI severity of each smoking status, "improvement" occurred in 17%, 24%, and 68% of "failure" (n=35), "partial success" (n=25), and "success" (n=22) groups, respectively, and the "success" group was significantly higher than the other two groups. CONCLUSION: The study showed that CAVI was increased by smoking, and complete smoking cessation improved CAVI.

Bidirectional precordial ST changes during angioplasty to right coronary artery.

Emergency coronary angiography of a 53-year-old man with acute coronary syndrome revealed stenosis in right coronary artery. During angioplasty, the ECG change showed three kind of ST deviation, namely inferior ST elevation with precordial ST depression, inferior ST elevation with precordial ST elevation, and inferior ST depression with precordial ST elevation. The present case shows that the ST deviation of the inferior ischemia with right ventricular ischemia takes various patterns. This phenomenon is decided by degree of right main coronary and right side branch blood flow.

Association between cardio-ankle vascular index and serum cystatin C levels in patients with cardiovascular risk factor.

AIM: The aim of this study was to clarify the relationship between CAVI and serum cystatin C levels to understand the role of arterial stiffness in the presence of renal insufficiency. METHODS: We enrolled 206 consecutive patients with cardiovascular risk factors and/or coronary artery disease (CAD) in the study. Serum cystatin C, estimated glomerular filtration rate (eGFR), and plasma levels of von Willebrand factor (vWF) and plasminogen activator inhibitor (PAI-1) were measured. CAVI was determined as an index of arterial stiffness. RESULTS: For all patients, the mean serum cystatin C level was 0.81+/-0.21 mg/L and mean eGFR was 65.8+/-15.5 mL/min per 1.73 m(2). In univariate analysis, CAVI levels significantly correlated with cystatin C levels (r=0.414, p<0.001), eGFR (r=-0.315, p<0.01), PAI-1 (r=0.269, p<0.01), and vWF (r=0.207, p<0.01). Multiple regression analysis showed that age, cystatin C, PAI-1, and a history of CAD were independent variables of CAVI. Age-adjusted CAVI was highest in the presence of both CAD and renal impairment. CONCLUSION: CAVI was closely associated with cystatin C levels. These results suggest a significant role of arterial stiffness in renal insufficiency.