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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.

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.

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.

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.

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" (

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.

Objective To investigate a mechanistic determinant of left atrial (LA) reservoir function in patients presenting left ventricular (LV) hypertrophy, and clarify diagnostic and prognostic values of LA reservoir strain in patients with cardiac amyloidosis (CA). Methods Three-hundred sixty patients (median age: 68 years, male gender: 65%) with left ventricular hypertrophy (LVH) assessed by echocardiography were retrospectively included. The LVH etiologies were diagnosed by any of biopsy, cardiac magnetic resonance imaging or 99mTc-PYP scintigraphy. LV segmental longitudinal strain was estimated from apical three views, and LA reservoir strain was measured from an apical 4-chamber view. Results The LVH etiologies were confirmed with CA in 81 patients, hypertensive heart disease in 87 patients, hypertrophic cardiomyopathy in 143 patients, and miscellaneous disorders in 49 patients. The median (25th, 75th percentile) value of LV ejection fraction was 59% (48–67). LV basal longitudinal strain and LA reservoir strain were significantly reduced in patients with CA compared with those with other etiologies; LV basal strain: 5.4% (3.9–8.7) vs. 11.9% (9.3–14.6), LA reservoir strain: 9.2% (6.3–12.3) vs. 17.5% (11.3–24.1), p Conclusions The decrease of LV longitudinal shortening at cardiac base could worsen LA reservoir function especially in patients with CA. LA reservoir strain might be an alternative measure to identify CA etiology and have a predictive value of heart failure hospitalization in patients with LV hypertrophy. Funding Acknowledgement Type of funding sources: None.

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.

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.

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

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.

Background Tolvaptan (TLV), a vasopressin antagonist, can promote water diuresis and overcome various disadvantages associated with conventional diuretics by ameliorating congestive symptoms and improving hyponatremia while maintaining haemodynamics and renal function. Large-scale clinical trials conducted primarily in Western countries (e.g. EVEREST trial) failed to demonstrate the beneficial effect of TLV on prognosis in patients with heart failure (HF). However, even after these clinical trials, studies on the use of TLV add-on therapy and resultant prognosis have been reported in Asian countries. Racial differences can greatly affect drug efficacy and dosing. Purpose We sought to investigate the long-term prognostic effect of TLV add-on therapy in Asian patients with HF. Methods We searched MEDLINE, Scopus, Cochrane Central, and Google Scholar for articles published till 31 December 2019. Randomized controlled trials (RCTs) and matched case-control studies that had a follow-up period of at least 6 months and that compared TLV add-on therapy and conventional therapy (control group) in Asian patients with acute decompensated HF were included. Primary and secondary outcomes analysed were all-cause mortality and HF readmission, respectively. Pooled analysis was performed using univariate effect size with random effect models. Meta-regression was performed to assess the impact of potential covariates. Results Nine articles that enrolled 1010 patients (the range of patients in the enrolled studies: 58–217) were included in the systematic review. All studies were performed in Japan. The weighted mean follow-up period was 15 months. The weighted mean of sodium level and ejection fraction was 139 mEq/L and 47%, respectively. TLV dose at discharge was available only in five articles, and its weighted mean value was 8.8 mg/day. In the pooled analysis, TLV add-on therapy did not improve the incidence of all-cause mortality (OR: 1.02, 95% CI: 0.69–1.52, p=0.92, I2=23) and HF readmission (OR: 0.73, 95% CI: 0.24–2.22, p=0.58, I2=89) (Figure). Furthermore, the effect of TLV add-on therapy on all-cause mortality was significantly moderated by furosemide dose at discharge in the control group (p=0.03). Conclusions Similar to findings of previous RCTs completed in Western countries, we found that TLV add-on therapy did not improve long-term mortality and HF readmission in Japanese patients with HF; however, mostly small-scale studies were included in our review. TLV add-on therapy might contribute to the improvement in prognosis in HF patients taking large doses of furosemide. Forest plot of tolvaptan's effect Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Kitaishikai

Background Cardiac amyloidosis (CA), characterized by amyloid protein deposition in the heart, is a treatable disease. Although left ventricular (LV) wall thickness is the most established imaging predictor for CA, several echocardiographic indices including deformation parameters also contribute to the screening of CA. However, it is unclear whether additive values of echocardiographic indices have greater benefit over the conventional clinical predictors for the screening of CA. Therefore, we sought to compare the incremental benefits of echocardiographic indices over the clinical parameters for the screening of CA and externally validate their incremental benefits. Methods We retrospectively studied 295 consecutive patients (median age, 67 years; male, 65%; mean LV wall thickness (MWT), 12 mm) with LV hypertrophy who underwent echocardiography as well as the detailed work-up for myocardium (Biopsy, technetium pyrophosphate scintigraphy (99mTc-PYP) or cardiac magnetic resonance imaging). CA was diagnosed through biopsy or 99mTc-PYP. The clinical model considers patients' age and the low-voltage in electrocardiography in reference to previous studies. Continuous echocardiographic variables were represented in binary through generally accepted external cutoff points. The incremental benefits of the echocardiography findings over the clinical model were assessed using with the help of both receiver-operated characteristic curve analysis and comparison of area under the curves. Furthermore, these incremental benefits were validated in the external validation sample (median age, 70 years; male, 69%; MWT, 12 mm). Results Among the enrolled patients, CA was observed in 18% of cases. Table presents the results of this study. Of the echocardiographic parameters, relative apical sparing pattern (RASP) was the greatest contributor for improvement of diagnostic accuracy of the clinical model. The next greatest contributor was LV wall thickness, followed by left atrial reservoir strain (LAS), E/e', left atrial volume index, ejection fraction strain ratio, and pericardial effusion, respectively. Similarly, RASP, LV wall thickness, global longitudinal strain, ejection fraction, LAS, and granular sparkling showed significant incremental benefit in the validation cohort. Only mean wall thickness, LV wall thickness, LAS, E/e' and RASP consistently improved the diagnostic accuracy of the clinical model. Conclusion During the screening process, adding LV wall thickness, LAS, and RASP to the clinical parameters may be useful for the accurate diagnosis of CA in patients with LV hypertrophy. Figure 1 Funding Acknowledgement Type of funding source: None

Background Cardiac amyloidosis (CA) is an infiltrative disease mimicking left ventricular hypertrophy (LVH), although its prognosis is poorer than other diseases with LVH. Moreover, because CA is treatable, appropriate screening for CA is an important area of study for clinicians to prevent and treat the disease. Several imaging predictors of CA have been reported so far;. in particular, deformation parameters such as relative apical sparing patterns of longitudinal strain (RASP) may diagnose CA with better precision than conventional parameters. Accordingly, we hypothesized that the inclusion of deformation parameters into the established diagnostic parameters would permit derivation of a risk score for CA screening in patients with LVH. Thus, we aimed to 1) investigate the incremental benefits of deformation parameters over established diagnostic parameters for CA screening in patients with LVH; 2) determine the risk score to screen CA patients with LVH using all of these variables; and 3) externally validate the score. Methods We retrospectively studied 295 consecutive non-ischemic patients with LVH who underwent echocardiography as well as the detailed work-up for LVH (biopsy, technetium pyrophosphate scintigraphy (99mTc-PYP) or cardiac magnetic resonance imaging) (median age, 67 years; MWT, 12 mm). CA was diagnosed by biopsy or 99mTc-PYP. The base model consisted of age (≥65 [male], ≥70 [female]), low voltage in electrocardiography, and posterior wall thickness ≥14 mm in reference to previous studies. Continuous echocardiographic variables were binarized by the use of generally accepted external cutoff points to avoid best clinical scenario. Incremental benefits were assessed using receiver operating characteristic curve analysis and area under the curve (AUC) comparison. Multiple logistic regression analysis was performed to determine the risk score. The score was then validated in the external validation sample (N=178, median age, 70 years; MWT, 12 mm). Results CA was observed in 54 patients (18%) and of the several echocardiographic parameters studied, only RASP demonstrated a significant incremental benefit for the screening of CA over the base model (Figure A). After multiple logistic regression analysis in the prediction of CA with 4 variables (RASP and basal model components), each was assigned a numeric value based on its relative effect (Figure B). The incidence rate of CA clearly increased as the sum of the risk score increased (Figure C). The score had good discrimination ability, with an AUC of 0.87, a total score of ≥2 with 70% sensitivity and 90% specificity. Similarly, the discrimination ability of the score in the validation cohort was sufficient (AUC = 0.87). Conclusion Overall, we determined a simple risk score including RASP to screen CA. This score takes into account 4 common parameters used in daily practice, and therefore, has potential utility in risk stratification and management of patients with LVH. Figure 1 Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Kitaishikai

Background The relative apical sparing pattern (RASP) of left ventricular (LV) longitudinal strain (LS) is frequently associated with cardiac amyloidosis (CA). However, some patients with CA do not show the RASP, and their clinical characteristics have not been fully clarified. We sought to investigate the clinical significance of RASP in patients with CA. Methods One hundred consecutive CA patients who were diagnosed by biopsy or myocardial pyrophosphate scintigraphy and evaluated for RASP (mean age: 76 years, male: 77%, LV mean wall thickness: 13.5 mm, light-chain [AL] type: 33 cases, transthyretin [TTR] type: 67 cases) were retrospectively enrolled. The RASP was semi-quantitatively and quantitatively assessed. Semi-quantitative RASP was defined as reduction of LS (≥−10%) in ≥5 (of 6) basal segments relative to preserved LS (1.00, >0.90, and >0.87) according to the literature. Results Semi-quantitative and binalized quantitative RASP (>1.00, >0.90, and >0.87) were observed in 55, 55, 63, and 65 patients, respectively. RASP in each definition was more prevalent in the TTR group than in the AL group. Additionally, RASP was significantly associated with higher LV wall thickness even after adjustment for the CA subtypes (all, p Conclusions The incidence of RASP is low in the case of thin LV wall thickness in CA patients, which may indicate the difficulty of early diagnosis of CA using RASP in patients with mild LV hypertrophy. The prognostic prediction using RASP may be challenging in this cohort. Figure 1 Funding Acknowledgement Type of funding source: None

Magnetic resonance imaging has shown that cases of cardiac amyloidosis (CA), particularly transthyretin amyloid cardiomyopathy (TTR), may frequently involve asymmetric left ventricular (LV) septal hypertrophy (ASH). ASH is classically associated with hypertrophic cardiomyopathy (HCM). We sought to

Calcified nodules are known to be a rare cause of acute coronary syndrome.1 Calcified nodules are sometimes observed by intracoronary imaging modalities, such as coronary angioscopy, optical frequency domain imaging, and intravascular ultrasound during percutaneous coronary intervention procedures. The characteristics of the calcified nodules observed by intravascular ultrasound have been shown to have a convex shape with …

Some studies have suggested that radial access (RA) for percutaneous coronary intervention (PCI) reduces vascular complications and bleeding compared to femoral access (FA). The purpose of this study was to investigate the routine use of hemostatic devices and bleeding complications among RA, brachial access (BA), and FA. Between January 2015 and December 2015, 298 patients treated for PCI with RA were compared with 158 patients using BA and 206 patients using FA. The radial sheath was routinely removed with ADAPTY, the brachial sheath with BLEED SAFE, and the femoral sheath with Perclose ProGlide. In-hospital bleeding complications were investigated. Cardiogenic shock was most frequent in patients in the femoral group (RA 1.3%, BA 2.5%, FA 9.2%, p