Simple Symptom-Based Prediction of COVID-19: A Single-Center Study of Outpatient Fever Clinic in Japan.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) symptoms are not fully understood in non-hospitalized individuals in Japan, and COVID-19 differentiation by symptoms alone remained challenging. Therefore, this study aimed to examine COVID-19 prediction from symptoms using real-world data in an outpatient fever clinic. METHODS: We compared the symptoms of COVID-19-positive and negative patients who visited the outpatient fever clinic at Imabari City Medical Association General Hospital and tested for COVID-19 from April 2021 to May 2022. This retrospective single-center study enrolled 2,693 consecutive patients. RESULTS: COVID-19-positive patients had a higher frequency of close contact with COVID-19-infected patients compared with COVID-19-negative patients. Moreover, patients with COVID-19 had high-grade fever at the clinic compared with patients without COVID-19. Additionally, the most common symptom in patients with COVID-19 was sore throat (67.3%), followed by cough (62.0%), which was approximately twice as common in patients without COVID-19. COVID-19 was more frequently identified in patients having a fever (≥37.5℃) with a sore throat, a cough, or both. The positive COVID-19 rate reached approximately half (45%) when three symptoms were present. CONCLUSION: These results suggested that COVID-19 prediction by combinations of simple symptoms and close contact with COVID-19-infected patients might be useful and lead to recommendations for testing of COVID-19 in symptomatic individuals.

Evaluation of health utility in trial-based cost-utility analyses for major cardiovascular disease: protocol for a systematic review.

INTRODUCTION: The global incidence of cardiovascular disease (CVD) is high, and the medical costs associated with its management have been increasing. Cost-utility analyses (CUAs) are essential for understanding the value of healthcare interventions and for decision-making. A majority of the CUAs for CVD are model based and have cited health utilities from previously published data; standard health utilities for the CUAs of CVD have not been established yet. Thus, we aim to identify the standard utilities according to the patients' condition and disease severity in patients with major CVDs. METHODS AND ANALYSIS: We will search Medline and Evidence-Based Medicine Reviews for trial-based CUA studies that have reported on quality-adjusted life-years using original health utilities for patients with three major forms of CVD (coronary artery disease, heart failure and atrial fibrillation). Papers on trial-based CUAs will be included, while those on model-based CUAs will be excluded. No restrictions will be made in terms of intervention type. The main outcome comprises the health utilities calculated on a scale of 0-1 (irrespective of the measurement methods) at baseline and after treatment. Two independent investigators will screen the eligibility of articles; they will extract data, including health utilities, from the eligible articles for further analysis. The quality of the included studies will be assessed using the Consolidated Health Economic Evaluation Reporting Standards checklist. We will describe the means and SDs of the health utilities from all the included studies. The mean utility weights for individual studies will be combined through meta-analyses using a random-effects model to obtain the representative health utility value for each disease. Subgroup analyses will be conducted according to the severity and duration of each disease. ETHICS AND DISSEMINATION: Ethical approval is not required. The review will be submitted to an appropriate peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022316278.

LOX-1 deficiency increases ruptured abdominal aortic aneurysm via thinning of adventitial collagen.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a key mediator of inflammation and plays an important role in the pathogenesis of atherosclerosis. Conversely, LOX-1 deficiency has been shown to decrease inflammation and atherosclerosis, both of which have been proposed to contribute to abdominal aortic aneurysm (AAA) pathogenesis. However, the role of LOX-1 in AAA pathogenesis remains unknown. Here, we investigated the effects of Olr1 (which encodes LOX-1) deletion on angiotensin II (Ang II)-induced AAA in apolipoprotein E knockout (ApoE KO) mice to determine whether LOX-1 deficiency mitigates AAA development. To accomplish this, we used serial, non-invasive ultrasound assessment, which revealed that the incidence and expansion rate of AAA were similar regardless of Olr1 deletion. However, Olr1 deletion significantly increased severe AAAs, including ruptured AAAs resulting in death. Oil Red O staining of the harvested aortas showed that the extent of atheroma burden localized in aneurysmal lesions did not differ between LOX-1-deficient and control mice, suggesting that Olr1 deletion did not decrease atheroma burden in the aneurysmal wall. Further histopathological analysis revealed that aneurysmal lesions in LOX-1-deficient mice had fewer fibroblasts and myofibroblasts, as well as thinner adventitial collagen, although the degree of elastin fragmentation or disruption was similar between LOX-1-deficient and control mice. An in vitro study confirmed that the proliferation of adventitial fibroblasts collected from LOX-1-deficient mice was significantly attenuated despite Ang II stimulation. In conclusion, Olr1 deletion may not mitigate aneurysm development but rather increases the vulnerability of rupture by suppressing adventitial fibroblast proliferation and collagen synthesis.

Pseudoxanthoma elasticum resulting in acute coronary syndrome.

Pseudoxanthoma elasticum (PXE) is a rare hereditary disorder that causes elastic tissue degeneration in the skin, eyes, and cardiovascular system. Gastrointestinal bleeding and fundus hemorrhage are serious complications associated with PXE prognosis as well as cardiovascular involvement. This is a rare case of acute coronary syndrome in a PXE patient with high bleeding risk. Learning objective: Pseudoxanthoma elasticum (PXE) resulting in acute coronary syndrome (ACS) is rare. Given PXE patients are generally at very high bleeding risk, antithrombotic therapy as secondary prevention after ACS onset should be taken into full consideration.

Usefulness of intravascular ultrasound assessment after development of the slow flow phenomenon during percutaneous coronary intervention.

The slow flow phenomenon is a critical complication during percutaneous coronary intervention (PCI) that leads to poor outcomes. We aimed to evaluate the mechanisms underlying the slow flow phenomenon using intravascular ultrasound (IVUS). We retrospectively analyzed IVUS data from 62 lesions in 58 consecutive patients who experienced the slow flow phenomenon during PCI. IVUS was performed immediately after the development of the slow flow phenomenon to assess its cause. No IVUS-based evidence of mechanical obstruction was categorized as distal embolization. Distal embolization was observed in 46 lesions (74%). The slow flow phenomenon occurred in all these lesions after stent implantation. In addition to distal embolization, three different mechanisms underlying the induction of the slow flow phenomenon due to mechanical obstructions (16 lesions, 26%) were detected on IVUS, namely, medial dissection/hematoma (6 lesions), intimal flap (6 lesions), and thrombus obstruction (4 lesions). Most mechanical obstructions (13 lesions, 81%) could not be identified by angiography alone. In 15/16 lesions (94%) with mechanical obstruction, deteriorated flow improved immediately after balloon dilatation or bail-out stent implantation, although intracoronary vasodilator administration could not reestablish coronary flow. The frequency of mechanical obstruction as the cause of the slow flow phenomenon was relatively high. Given the difficulty in angiographical differentiation, IVUS-guided management of slow flow may be a useful strategy.

O-ring-induced transverse aortic constriction (OTAC) is a new simple method to develop cardiac hypertrophy and heart failure in mice.

Suture-based transverse aortic constriction (TAC) in mice is one of the most frequently used experimental models for cardiac pressure overload-induced heart failure. However, the incidence of heart failure in the conventional TAC depends on the operator's skill. To optimize and simplify this method, we proposed O-ring-induced transverse aortic constriction (OTAC) in mice. C57BL/6J mice were subjected to OTAC, in which an o-ring was applied to the transverse aorta (between the brachiocephalic artery and the left common carotid artery) and tied with a triple knot. We used different inner diameters of o-rings were 0.50 and 0.45 mm. Pressure overload by OTAC promoted left ventricular (LV) hypertrophy. OTAC also increased lung weight, indicating severe pulmonary congestion. Echocardiographic findings revealed that both OTAC groups developed LV hypertrophy within one week after the procedure and gradually reduced LV fractional shortening. In addition, significant elevations in gene expression related to heart failure, LV hypertrophy, and LV fibrosis were observed in the LV of OTAC mice. We demonstrated the OTAC method, which is a simple and effective cardiac pressure overload method in mice. This method will efficiently help us understand heart failure (HF) mechanisms with reduced LV ejection fraction (HFrEF) and cardiac hypertrophy.

Cost-Effectiveness of long-term tolvaptan administration for chronic heart failure treatment in Japan.

BACKGROUND: Tolvaptan (TLV) is effective for acute heart failure (HF) with congestion, but its long-term administration in patients with chronic HF (CHF) remains controversial. Moreover, the cost-effectiveness of TLV for CHF treatment has not yet been investigated. Thus, we sought to validate the cost-effectiveness of TLV for CHF treatment in Japan. METHODS: A Markov model was developed to compare total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) between long-term TLV strategy and the standard strategy using furosemide for CHF. The target population included 75-year-old patients with CHF. The effectiveness of the TLV strategy for CHF treatment was determined based on a systematic review and meta-analysis. We used a 10-year horizon, with sensitivity analyses for significant variables and a scenario analysis for patients with CHF receiving high-dose furosemide (≥60 mg per day). RESULTS: In the base case analysis, the total cost of the long-term TLV strategy was higher than that of the standard strategy (¥3,243,779 vs. ¥1,179,964). The total QALYs of the long-term TLV strategy were lower than those of the standard strategy (4.52 vs 4.59). Thus, a standard TLV prescription for CHF treatment has no clinical or economic benefit. In the scenario analysis (i.e. in patients with CHF receiving high-dose furosemide), the long-term TLV strategy was more effective (total QALYs, 5.10 vs. 4.41) but more expensive (total costs, ¥3,540,558 vs. ¥1,272,208) than the standard strategy. The ICER of the TLV strategy against the standard strategy (¥3,289,579/QALY) was below the willingness-to-pay of ¥5,000,000, which suggests that the long-term TLV strategy is cost-effective relative to the standard strategy in patients with CHF receiving high-dose furosemide. CONCLUSIONS: Long-term TLV administration did not provide a clear benefit for all patients with CHF. However, this treatment strategy may be a cost-effective therapeutic option for patients who require high-dose furosemide.

Plaque Characterization with Computed Tomography Angiography Based on a Diluted-contrast Injection Protocol.

Objective Coronary plaques with low attenuation on computed tomography (CT) angiography may indicate vulnerable plaques. However, plaque CT attenuation is reported to be significantly affected by intracoronary attenuation. Recently, the diluted-contrast injection protocol was established to facilitate more uniform intracoronary attenuation than can be achieved with the generally used body-weight-adjusted protocol. We validated the relationship between low-attenuation plaque on CT and lipid-rich plaque using integrated backscatter-intravascular ultrasound (IB-IVUS) as the standard reference. Methods Plaques were divided into tertiles (T1, T2, and T3) according to the plaque CT attenuation, calculated as the average of five intra-plaque regions of interest, and compared with the plaque characteristics noted on IB-IVUS. Patients Patients who underwent both CT angiography using a diluted-contrast injection protocol and IB-IVUS were retrospectively analyzed. Results Thirty-nine plaques in 32 patients were analyzed by CT angiography and IB-IVUS. The median plaque CT attenuation (Hounsfield units) of each tertile was 30 (T1), 48 (T2), and 68 (T3). Although no significant difference was noted in conventional quantitative IVUS parameters (e.g. plaque burden), the T1 with lowest plaque CT attenuation had the highest percentage lipid area by IB-IVUS [75.1% (T1), 57.8% (T2), and 50.8% (T3), respectively, p<0.01]. Furthermore, the plaque CT attenuation had a significant negative correlation with the percentage lipid area (r=-0.59, p<0.01). Conclusion CT angiography-based plaque characterization using a diluted-contrast injection protocol may aid in the quantitative detection of lipid-rich plaque.

Cardiac amyloidosis screening using a relative apical sparing pattern in patients with left ventricular hypertrophy.

BACKGROUND: Cardiac amyloidosis (CA) mimics left ventricular hypertrophy (LVH). It is treatable, but its prognosis is poor. A simple screening tool for CA would be valuable. CA is more precisely diagnosed with echocardiographic deformation parameters (e.g., relative apical sparing pattern [RASP]) than with conventional parameters. We aimed to 1) investigate incremental benefits of echocardiographic deformation parameters over established parameters for CA screening; 2) determine the resultant risk score for CA screening; and 3) externally validate the score in LVH patients. METHODS: We retrospectively studied 295 consecutive non-ischemic LVH patients who underwent detailed diagnostic tests. CA was diagnosed with biopsy or 99mTc-PYP scintigraphy. The base model comprised age (≥65 years [men], ≥70 years [women]), low voltage on the electrocardiogram, and posterior wall thickness ≥ 14 mm in reference to the literature. The incremental benefit of each binarized echocardiographic parameter over the base model was assessed using receiver operating characteristic curve analysis and comparisons of the area under the curve (AUC). RESULTS: Fifty-four (18%) patients had CA. RASP showed the most incremental benefit for CA screening over the base model. After conducting multiple logistic regression analysis for CA screening using four variables (RASP and base model components), a score was determined (range, 0-4 points). The score demonstrated adequate discrimination ability for CA (AUC = 0.86). This result was confirmed in another validation cohort (178 patients, AUC = 0.88). CONCLUSIONS: We developed a score incorporating RASP for CA screening. This score is potentially useful in the risk stratification and management of LVH patients.

Restricted left atrial dilatation can visually differentiate cardiac amyloidosis from hypertrophic cardiomyopathy.

AIMS: Cardiac amyloidosis (CA) is an infiltrative myocardial disease that occasionally mimics hypertrophic cardiomyopathy (HCM). The aim of this study is to investigate the discriminatory ability of visual assessment of left atrial (LA) function between CA and HCM on echocardiography. METHODS AND RESULTS: In total, 93 patients with cardiac magnetic resonance imaging (CMR)-confirmed HCM and 34 with cardiac biopsy-confirmed CA were retrospectively assessed. LA dilatation was assessed via echocardiography in an apical four-chamber view. Visual assessment was performed to identify LA dilatation grade (preserved = 1, abnormal = 2, and restricted = 3) based on the extent of outward expansion in the LA reservoir phase. Regarding the reproducibility of visually assessing LA dilatation grade, the kappa values between intra- and inter-observer measurements were 0.82 and 0.70, respectively. Of 127 participants, 57 (45%), 42 (33%), and 28 (22%) presented with LA dilatation Grades 1, 2, and 3, respectively. All 57 patients with preserved LA dilatation (Grade 1) had HCM, and 20 of 28 patients (71%) with restricted LA dilatation (Grade 3) presented with CA. Patients with CA had a higher LA dilatation grade than those with HCM (P < 0.01). LA emptying fraction and reservoir strain were also quantitatively evaluated. The area under the curves of LA dilatation grade (0.88) and LA emptying fraction (0.88) for differentiation of these two diseases were higher than that of LA reservoir strain (0.73) (P < 0.01, respectively). During follow-up, nine patients with HCM and 16 with CA experienced cardiac event (cardiac death or hospitalization due to heart failure). In Kaplan-Meier analysis including both groups of HCM and CA, the incidence of cardiac events was higher in patients with restricted LA dilatation than in those with preserved or abnormal LA dilatation (log-rank test, P < 0.01). CONCLUSIONS: Restricted LA dilatation is an indicator for the diagnosis of CA. Further, visual assessment of abnormal LA motion may facilitate diagnosis in patients with CA and high-risk patients with HCM.

Usefulness of contrast computed tomography for diagnosing left ventricular thrombus before impella insertion.

The Impella (Abiomed, Danvers, MA, USA) is a novel percutaneous heart pump device for left ventricular (LV) assistance; however, LV thrombus is a notable contraindication for this device. Contrast computed tomography assessment is useful for detecting LV thrombus and preventing thromboembolism in patients recommended for Impella use. .

Semiquantitative assessment of the relative apical sparing pattern of longitudinal strain for cardiac amyloidosis identification.

BACKGROUNDS: The relative apical sparing pattern (RASP) of left ventricular (LV) longitudinal strain (LS) is frequently associated with cardiac amyloidosis (CA). However, the visual assessment of RASP is inconsistent, and the quantitative assessment of RASP is time-consuming. This study aimed to compare assessments of RASP for the identification of CA with conventional assessments and investigate their reproducibility and relevance on the assessments. METHODS: Forty patients with biopsy-proven CA were compared with 80 hypertrophied patients matched for mean LV wall thickness. We compared the discriminative abilities of three assessments of RASP to identify CA (visual, quantitative, and semiquantitative). Nine patterns of semiquantitative RASP were investigated; finally, it was defined as "reduction of LS" (≥ -10%) in ≥5 (of 6) basal segments, relative to "preserved LS" (< -15%) in at least one apical segment. RESULTS: The concordance between the two observers for visual RASP was modest (κ = 0.65). On the other hand, the consistency for semiquantitative RASP was perfect (κ = 1.00). The discriminative ability of semiquantitative RASP (area under the curve [AUC]  = 0.74) was significantly better than that of visual RASP (AUC = 0.65) and equivalent to that of binary quantitative RASP. CONCLUSION: Semiquantitative RASP assessment is reproducible and accurately discriminates CA. This simple assessment may help readily refine the risk stratification of patients with diffuse LV hypertrophy.

Prognostic assessment of relative apical sparing pattern of longitudinal strain for severe aortic valve stenosis.

BACKGROUNDS: The relative apical sparing pattern (RASP) of left ventricular (LV) longitudinal strain (LS) is frequently associated with cardiac amyloidosis. Elderly patients with aortic valve stenosis (AS) complicated by transthyretin amyloid cardiomyopathy have poor prognosis. Furthermore, deteriorated basal LS in AS patients has been reported to be associated with adverse outcome. We investigated the association between RASP and outcomes in patients with severe AS. METHODS: We retrospectively studied 156 consecutive patients with severe AS and preserved LV ejection fraction. RASP was assessed by both of semi-quantitative (sRASP) and quantitative (qRASP) methods. sRASP was defined as a deterioration of LS (≥-10%) in ≥ 5 (of 6) basal segments, relative to preserved LS (<-15%) in at least 1 apical segment. qRASP was calculated using the following formula: average apical LS/(average basal LS + average mid-ventricle LS); qRASP ≥ 1 was defined as positive. Patients were followed up to determine outcomes, which included sudden cardiac death or unexpected admission due to heart failure, over a median of 1.9 years. RESULTS: sRASP and qRASP were assessed in all patients, but 24 and 42 patients fulfilled the criteria for sRASP and qRASP, respectively. Both assessments were significantly associated with outcomes (n = 44; 28%). Furthermore, sRASP was significantly associated with outcome after adjusting for EuroSCORE, NYHA ≥ II, or global longitudinal strain. A model based on these covariates for predicting outcomes significantly improved by adding sRASP. CONCLUSION: RASP is observed in some patients with severe AS and provides additive prognostic information over conventional parameters.

Refractoriness to subcutaneous implantable cardioverter defibrillator after frequent therapies for ventricular fibrillation storms in a Brugada syndrome case.

BACKGROUND: The subcutaneous implantable cardioverter defibrillator (S-ICD) is an alternative to the transvenous implantable cardioverter defibrillator for the prevention of sudden cardiac death. Here, we report a rare case of refractoriness to an S-ICD after frequent therapies for ventricular fibrillation (VF) storms. CASE PRESENTATION: A 24-year-old man underwent a bout of syncope with vomiting and incontinence at home. He was brought to the emergency room and was witnessed to spontaneously go into VF successfully converted by external defibrillation. Previously, he was diagnosed with a type I Brugada electrocardiogram pattern by a pilsicainide administration test in another hospital. Although he had a family history of sudden cardiac death in 3 relatives, including his brother, he was followed closely without any therapies because he had never had an episode of syncope. He was implanted with an S-ICD without any trouble. Seven months later, frequent S-ICD shocks for VF storms occurred. His VF was controlled by using intravenous amiodarone, which was converted to an oral preparation. However, his VF recurred after another 2 months. The analysis of his S-ICD data revealed that 4 consecutive shock deliveries could not terminate his VF and the final shock delivered could fortunately terminate it because of a high defibrillation threshold test (DFT) due to an increasing shock impedance (64 to 90 Ω). First, we performed an epicardial Brugada syndrome ablation and subsequently replaced and repositioned the S-ICD lead from a left to a right parasternal site. After the re-implantation of the S-ICD, the DFT test improved to within normal range. According to the pathological analysis, infiltration of inflammatory cells and extensive fibrosis were confirmed in the subcutaneous tissue around the shock lead and S-ICD body. CONCLUSION: Frequent S-ICD shocks for VF storms might cause various pathological changes around the device and lead to a high DFT.

Primary pericardial abscess caused by Staphylococcus aureus infection without a predisposing condition.

A 75-year-old man presented to the hospital with a low-grade fever and worsening dyspnea. Transthoracic echocardiogram and contrast-enhanced computed tomography revealed a 20 × 20 mm lesion adjacent to the left ventricle with pericardial effusion. We suspected pericardial abscess, but no bacteria were detected even after 6 consecutive blood cultures. Ultimately, we drained 500 mL serosanguinous fluid from the pericardial effusion on the 4th hospital day; a subsequent culture grew methicillin-sensitive Staphylococcus aureus. Although we performed percutaneous and surgical drainage and intravenous administration of antibiotics, he developed constrictive pericarditis, and died due to multi-organ failure on the 21st hospital day. On histological examination, neutrophil infiltration was noted in the thickened pericardium and the myocardium. To our knowledge, a purulent pericarditis complicated pericardial abscess can occur without bacteremia, and early diagnosis and aggressive management are necessary for a good prognosis. .