Wnt signaling in cardiac development and heart diseases.

The Wnt signaling pathway is a fundamental cellular communication system with extensive implications in various organs including the heart. In cardiac homeostasis, it governs essential processes like cellular proliferation, differentiation, and apoptosis, ensuring the heart's structural and functional integrity from embryonic stages and throughout life. Both canonical and non-canonical Wnt signaling pathways play a critical role during embryonic heart development in a region- and stage-specific manner. Canonical Wnt signaling also plays a significant role in heart diseases such as myocardial infarction and heart failure. However, the role of non-canonical Wnt signaling in heart diseases has not been fully elucidated. Wnt5a is a major ligand that activates non-canonical Wnt pathway, and recent studies start to clarify the role of the Wnt5a signaling axis in cardiac health and disease. In this review, we will briefly summarize the previous findings on the role of Wnt signaling pathways in heart development and diseases, and then focus on the role of Wnt5a signaling in heart failure progression. The multifaceted roles of the Wnt signaling pathway highlight its therapeutic potential for various types of heart diseases.

Incremental value of diastolic wall strain in predicting heart failure events in patients with atrial fibrillation.

Diastolic wall strain (DWS), an echocardiographic index based on linear elasticity theory, has been identified as a predictor of heart failure (HF) in patients with sinus rhythm. However, its effectiveness in atrial fibrillation (AF) patients remains uncertain. This study aims to assess DWS as a predictor of HF in AF patients with preserved ejection fraction. We analysed a prospective database of AF patients undergoing transthoracic echocardiography. AF patients with reduced left ventricular ejection fraction (< 50%), posterior wall motion abnormality, hypertrophic cardiomyopathy, valvular heart disease, pericardial disease, congenital heart disease, or history of pacemaker/implantable cardioverter-defibrillator implantation or cardiac surgery were excluded. The study followed patients until HF development, death, or last visit. Follow-up for patients who underwent catheter ablation was censored on the date of their procedure. HF was ascertained based on the Framingham criteria. DWS was calculated using a validated formula: DWS = (PWs -PWd)/PWs, where PWs is the posterior wall thickness at end-systole and PWd is the posterior wall thickness at end-diastole. Among 411 study patients (mean age 69.6 years, 66% men), 20 (5%) was underwent catheter ablation and 57 (14%) developed HF during a mean follow-up of 82 months. Cox-proportional hazards demonstrated that low DWS (≤ 0.33) significantly predicted HF events (hazard ratio [HR] 3.28, 95% confidence interval [CI]) 1.81-5.94, P < 0.0001), independent of age (per 10 years; HR 1.99, 95% CI 1.35-2.93, P < 0.001), indexed left ventricular mass (per 10 g/m2; HR 1.16, 95% CI 1.05-1.27, P < 0.01), and indexed left atrial volume (per 10 mL/m2; HR 1.14, 95% CI 1.04-1.24, P < 0.01). Additionally, global log-likelihood ratio chi-square statistics indicated that DWS incrementally predicts HF development beyond age, indexed left ventricular mass, and left atrial volume (P < 0.001).

Frequency and Distribution of Sheet and Nodular Calcification in Coronary Arteries in Japanese Patients.

Whether a nodular calcification (NC), which is the precursor to intracoronary thrombosis, is focally or diffusely distributed in the coronary tree has major implications for ongoing efforts to identify. This study aimed to investigate the frequency and spatial distribution patterns of sheet calcification (SC) and NC in a 3-vessel examination of autopsied human hearts.A total of 323 coronary artery specimens from 110 cadavers were obtained from autopsy cases. After fixation and decalcification, the coronary artery trees were cut every 5 mm into 4-µm transverse cross-sections for histological assessment. An SC was defined as a plate-like calcification of > 1 quadrant of the vessel or > 3 mm in diameter, and NC as nodular calcium deposits separated by fibrin, and a deposit size > 1 mm in diameter.Of the 6,306 histological cross-sections, SCs and NCs were identified in 1,627 (26%) and 233 (4%) cross-sections, respectively. SCs and NCs had a similar distribution pattern in all 3 coronary arteries. In the left anterior descending artery (LAD), NCs were predominantly located in the proximal segment: the first 45 mm from the LAD ostium (72%) and the first 60 mm from the LAD ostium (84%), respectively. However, NCs were evenly distributed throughout the length of the coronary artery in the right coronary artery (RCA) and left circumflex artery (LCX).NCs coexisted with SCs, and tended to cluster in predictable parts within the proximal segments of the LAD, but were evenly distributed throughout the RCA and LCX in coronary arteries from cadavers.

Efficacy of Intravascular Ultrasound-Based 3D Wiring Using the Tip Detection Method for CTO Intervention.

To perform intravascular ultrasound (IVUS)-based real-time 3-dimensional wiring in chronic total occlusion percutaneous coronary intervention, we devised a tip detection method and developed AnteOwl WR (AO)-IVUS, which is an upgraded version of Navifocus WR (Navi)-IVUS with an added pull back transducer system. We compared the procedural outcomes of AO-IVUS-based 3-dimensional wiring using the tip detection method (n = 30) and Navi-IVUS-based conventional wiring (n = 17) in chronic total occlusion percutaneous coronary intervention. The success rate of IVUS-guided wiring was markedly improved in the AO-IVUS group compared with the Navi-IVUS group (93% vs 59% of cases, respectively; P = 0.007). In cases of successful IVUS-guided wiring, the IVUS-guided wiring time was markedly improved in the AO-IVUS group compared with the Navi-IVUS group (9 ± 8 minutes vs 24 ± 26 minutes, respectively; P = 0.001). There were 2 successful cases of tip detection-antegrade dissection and re-entry in the AO-IVUS group.

Wnt5a-YAP signaling axis mediates mechanotransduction in cardiac myocytes and contributes to contractile dysfunction induced by pressure overload.

Non-canonical Wnt signaling activated by Wnt5a/Wnt11 is required for the second heart field development in mice. However, the pathophysiological role of non-canonical Wnt signaling in the adult heart has not been fully elucidated. Here we show that cardiomyocyte-specific Wnt5a knockout mice exhibit improved systolic function and reduced expression of mechanosensitive genes including Nppb when subjected to pressure overload. In cultured cardiomyocytes, Wnt5a knockdown reduced Nppb upregulation induced by cyclic cell stretch. Upstream analysis revealed that TEAD1, a transcription factor that acts with Hippo pathway co-activator YAP, was downregulated both in vitro and in vivo by Wnt5a knockdown/knockout. YAP nuclear translocation was induced by cell stretch and attenuated by Wnt5a knockdown. Wnt5a knockdown-induced Nppb downregulation during cell stretch was rescued by Hippo inhibition, and the rescue effect was canceled by knockdown of YAP. These results collectively suggest that Wnt5a-YAP signaling axis mediates mechanotransduction in cardiomyocytes and contributes to heart failure progression.

Elevated Aminotransferase Levels and Intracerebral Hemorrhage Deaths in a General Japanese Population.

Although chronic liver disease has been associated with cardiovascular disease, to which metabolic syndrome might be related, intracerebral hemorrhage (ICH) generally has not been focused. Associations of chronic liver disease assessed by aspartate (AST) and alanine (ALT) aminotransferase levels with ICH deaths were examined using 15,952 subjects without a history of cardiovascular disease who underwent annual health checkups in 1997 in Japan. Proportional hazards regression analyses adjusted for age, sex, hypertension, current smoking, diabetes mellitus, drinking habits, excess body weight, and hypercholesterolemia were performed. During a mean follow-up of 18.6 ± 7.2 years, there were 227 stroke deaths (including 124 ischemic and 60 ICH deaths) and 135 coronary deaths. Elevated aminotransferase levels, defined as a serum AST or ALT level of ≥ 30 IU/L were significantly associated with ICH deaths (hazard ratio (HR) = 2.72, 95% confidence interval (CI) = 1.56-4.73, P = 0.0004). Because elevated aminotransferase levels are frequently observed in alcoholic or metabolic liver diseases, additional analyses were performed to examine the effect of drinking habits and/or metabolic syndrome on the association of elevated aminotransferase levels with ICH deaths. After exclusion of subjects with any drinking habit (n = 9,941), elevated aminotransferase levels were significantly associated with ICH deaths (HR = 2.88, 95%CI = 1.44-5.76, P = 0.0028). After exclusion of subjects with at least one metabolic syndrome component (n = 5,672), elevated aminotransferase levels were significantly associated with ICH deaths (HR = 6.47, 95% CI = 1.85-22.6, P = 0.0035). Elevated aminotransferase levels were not associated with ischemic stroke or coronary deaths in any models. Elevated aminotransferase levels were significantly associated with ICH deaths, independent of drinking habits, or metabolic syndrome.

H2ARDD score as a feasible predictor of heart failure events in patients with atrial fibrillation: a validation study.

It was reported that the H2ARDD score (organic heart diseases = 2 points, anemia = 1 point, renal dysfunction = 1 point, diabetes = 1 point, and diuretic use = 1point; range 0 to 6 points) may help identify patients with AF at high risk for HF events. However, this score has not been externally validated. The objective of this study was to evaluate the usefulness of H2ARDD score in predicting HF events in patients with AF. We used a prospective database of patients with AF, and Cox-proportional hazards models were used to assess the risk of HF events. The outcome of interest was defined as HF events including new-onset HF and death from HF. Of 562 AF patients, 518 (mean 69.7 ± 9.7 years-old, 64.9% men) met study criteria, and 84 (16.2%) developed HF events during a mean follow-up of 54 ± 42 months. In multivariable analyses, H2ARDD score was shown as a significant predictor for HF events [hazard ratio (HR): 1.56, 95% confidence interval (CI): 1.36-1.79], independent of age (per 10 years, HR: 1.35, 95% CI: 1.03-1.78). In the Kaplan-Meier analyses stratified by H2ARDD score categories (0-2, 3-4, 5-6), the patients with higher H2ARDD scores had significantly worse HF event-free survival (log-rank P < 0.0001). The area under the ROC curve was 0.71 (95% CI: 0.65-0.77, P < 0.0001). The sensitivity and specificity at a cut-off score of ≥ 3 were 60% and 71%, respectively. In conclusion, the H2ARDD score may be feasible for HF risk stratification in patients with AF.

Diagnostic accuracy and clinical usefulness of erythrocyte creatine content to predict the improvement of anaemia in patients receiving maintenance haemodialysis.

BACKGROUND: The improvement of anaemia over time by erythropoiesis stimulating agent (ESA) is associated with better survival in haemodialysis patients. We previously reported that erythrocyte creatine content, a marker of erythropoietic capacity, was a reliable marker to estimate the effectiveness of ESA. The aim of this study was to examine the accuracy and clinical usefulness of erythrocyte creatine content to predict the improvement of anaemia in haemodialysis patients. METHODS: ESA dose was fixed 3 months prior to the enrollment and was maintained throughout the study period. Erythrocyte creatine content and haematologic indices were measured at baseline in 92 patients receiving maintenance haemodialysis. Haemoglobin was also measured 3 months after. Improvement of anaemia was defined as ≥ 0.8 g/dL change in haemoglobin from baseline to 3 months. RESULTS: Erythrocyte creatine content was significantly higher in 32 patients with improvement of anaemia compared to 60 patients with no improvement of anaemia (2.47 ± 0.74 vs. 1.57 ± 0.49 µmol/gHb, P = 0.0001). When 9 variables (erythrocyte creatine content, ESA dose, reticulocyte, haptoglobin, haemoglobin at baseline, serum calcium, intact parathyroid hormone, transferrin saturation and serum ferritin) were used in the multivariate logistic regression analysis, erythrocyte creatine emerged as the most important variable associated with the improvement of anaemia (P = 0.0001). The optimal cut-off point of erythrocyte creatine content to detect the improvement of anaemia was 1.78 µmol/gHb (Area under the curve: 0.86). Sensitivity and specificity of erythrocyte creatine content to detect the improvement of anaemia were 90.6% and 83.3%. CONCLUSION: Erythrocyte creatine content is a reliable marker to predict the improvement of anaemia 3 months ahead in patients receiving maintenance haemodialysis.

Increased Incidence of ECG Abnormalities in the General Population During the COVID-19 Pandemic.

To examine the effect of the COVID-19 pandemic on the cardiovascular system in the general population, we compared ECG changes after the onset of the COVID-19 pandemic with those before the pandemic period. The incidence of newly appeared ECG abnormalities (T wave abnormalities, ST-segment depression including minor changes, and abnormal Q waves) from 2019 to 2020 (COVID-19 period) was compared with that from 2018 to 2019 (control period) in subjects 40 to 74 years of age without a history of cardiovascular disease who had 12-lead ECG recordings during annual health checkups offered to adult citizens of Moriguchi City, Osaka, Japan. Logistic regression analyses were performed after adjusting for cardiovascular risk factors. There were 5,221 eligible subjects in the control period and 4,100 eligible subjects in the COVID-19 period. The incidences of newly appeared ECG abnormalities were 5.2% for T wave abnormalities, 2.8% for ST-segment depression, and 1.1% for abnormal Q waves in the control period, whereas they were 5.8%, 4.3%, and 1.7% respectively, in the COVID-19 period. The incidence of ST-segment depression (odds ratio (OR) = 1.59, 95% confidence interval (CI) = 1.27-1.98, P < 0.0001) and that of abnormal Q waves (OR = 1.56, 95%CI = 1.09-2.22, P = 0.0149) in the COVID-19 period were significantly higher compared to those of the control period. In conclusion, increased incidences of newly appeared ST-segment depression and abnormal Q waves were observed during the COVID-19 pandemic period.

Analysis of site-specific late potentials using a novel Holter signal-averaged electrocardiography in patients with Brugada syndrome.

BACKGROUND: The utility of late potentials on signal-averaged electrocardiography (SAECG) for risk stratification in patients with Brugada syndrome (BrS) remains controversial. Late potentials on conventional SAECG with Frank leads may be insufficiently sensitive to detect site-specific late potentials in right precordial leads. OBJECTIVE: The purpose of this study was to evaluate the utility of site-specific late potentials using a novel unipolar Holter-SAECG system for risk stratification in patients with BrS. METHODS: Consecutive symptomatic (n = 20) and asymptomatic (n = 21) patients with BrS who underwent investigation using conventional SAECG and a novel unipolar Holter-SAECG system were enrolled. We evaluated clinical characteristics and outcomes and compared late potentials on the 2 SAECGs between both groups and patients with and without cardiac events (CEs) (sudden cardiac death or sustained ventricular tachyarrhythmias) during the follow-up period. RESULTS: During mean follow-up of 76 months, 10 patients (24%) had CEs. There were no significant differences in late potentials on conventional SAECG between symptomatic and asymptomatic patients. On the Holter-SAECG system, RMS40 in lead V2 in the third intercostal space (3L-V2) at the nighttime was significantly lower in the symptomatic group than in the asymptomatic group (5.5 ± 0.8 µV and 8.2 ± 0.8 µV, respectively; P = .027). Univariate analysis of predictive values for CE showed that hazard ratios of daytime and nighttime RMS40 in lead 3L-V2 of <7.7 µV and <6.1 µV were 7.58 and 6.14, respectively. CONCLUSION: Site-specific late potentials in lead 3L-V2 measured using the novel Holter-SAECG system may be a useful marker for high-risk patients with BrS.

Prediction of medial damage by rotational atherectomy using intravascular ultrasound.

OBJECTIVE: This study evaluated whether intravascular ultrasound (IVUS) images before rotational atherectomy (RA) can predict medial injury caused by RA burr passage in advance. METHODS: Thirty-three patients with de-novo lesions located in the left anterior descending coronary artery (LAD) who underwent IVUS before and immediately after RA were enrolled. The spatial axes of the two matched pre- and post-RA IVUS cross-sectional images were merged. The segment was considered to have medial damage when the continuity of the intimal layer was disrupted and the medial layer was in direct contact with the lumen on post-RA IVUS. RESULTS: Medial injuries on post-RA IVUS were identified in seven segments of five patients. All segments with medial injury were located near the bifurcation of the LAD and the diagonal branch, and the spatial orientations of the medial injury region were mostly distributed in the lateral side with a diagonal branch take-off. The lumen area was significantly smaller in segments with medial injury than in those without medial injury (P < 0.01). The IVUS catheter was in contact with the healthy side of the arterial wall on pre-RA IVUS images for more than 1 mm in length in all segments with medial injury. CONCLUSION: When the guidewire and IVUS catheter are close to the healthy side of the arterial wall on pre-RA IVUS images, there is a higher risk of medial injury due to the RA procedure, especially near the bifurcation of the LAD and diagonal branch.

Atrial fibrillation and stroke: importance of left atrium as assessed by echocardiography.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, which has been increasing dramatically. AF has unfavorable consequences, such as stroke, heart failure, and cardiovascular death. Of these, stroke has been considered to be the serious complication. Recently, direct oral anticoagulation or new technologies, such as the WATCHMAN left atrium (LA) appendage closure device, have emerged to prevent stroke. Therefore, the accurate estimation of thromboembolic risk and appropriate prevention are essential for high-risk patients with AF. Although CHADS2 and CHA2DS2-VASc scores has been widely used to predict the risk of stroke in patients with AF, some researchers showed that there was no relationship between CHADS2 and CHA2DS2-VASc scores and LA appendage thrombus formation. Recent studies have reported that combination of echocardiographic parameters to CHADS2 or CHA2DS2-VASc scores can stratify high risk groups for LA appendage thrombus formation and onset of stroke. In this review, we focus on the epidemiological, pathophysiological, and prognostic associations between AF and stroke, and review the clinical and echocardiographic predictors for stroke in patients with AF.

Factors Associated with Coronary In-Stent Restenosis after Drug-Eluting Stent Implantation in Patients on Chronic Hemodialysis.

AIMS: Recently, drug-eluting stents (DESs) have been widely adopted for patients on chronic hemodialysis (HD). However, whether DES implantation is associated with a reduced rate of in-stent restenosis (ISR) is unclear. We investigated the incidence of ISR and its predictors in patients on HD after DES implantation. METHODS AND RESULTS: We analyzed 194 consecutive patients (331 lesions) on HD who underwent follow-up angiography after DES implantation. ISR was observed in 74 lesions (22.4%). Angiographically, the relative incidence of AHA/ACC type C lesion was increased (47 vs. 32%; p = 0.043), the minimal lumen diameter (MLD) before DES implantation was smaller (0.82 ± 0.49 vs. 0.97 ± 0.45 mm; p < 0.01), and the lesion length (LL) was increased (30.2 ± 16.1 vs. 24.4 ± 12.1 mm; p = 0.023) in lesions with ISR compared to those without ISR. The rate of rotational atherectomy use was also increased in lesions with ISR compared to those without ISR (50% vs. 25%; p < 0.01). In a multivariate analysis, the MLD before DES implantation (odds ratio [OR] = 0.50, 95% confidence interval [CI] 0.27-0.91, p = 0.024), LL (OR = 1.02, 95% CI 1.00-1.04, p = 0.030) and the use of rotational atherectomy (OR = 2.71, 95% CI 1.55-4.72, p < 0.01) were independent predictors of ISR. The incidence of ISR was similar between lesions treated with the first-generation (25.8%) and the second-generation DESs (20.4%). CONCLUSIONS: ISR was observed in 74 lesions (22.4%). A small MLD, long LL, and the use of rotational atherectomy were independent predictors of ISR after DES implantation in patients on HD. There was no significant difference in the ISR rate between the first- and the second-generation DESs.

Evaluation of recombinant human erythropoietin responsiveness by measuring erythrocyte creatine content in haemodialysis patients.

BACKGROUND: One of the main causes of anaemia in patients with end-stage renal disease is relative deficiency in erythropoietin production. Eythropoiesis stimulating agent (ESA), a potent haematopoietic growth factor, is used to treat anaemia in haemodialysis patients. The effect of ESA is usually assessed by haematological indices such as red blood cell count, haemoglobin concentration and haematocrit, but erythrocyte indices do not provide information of the rapid change in erythropoietic activity. As erythrocyte creatine directly assess erythropoiesis, the aim of this study was to evaluate the effect of ESA in haemodialysis patients by measuring the erythrocyte creatine content. METHODS: ESA dose was fixed 3 months prior to the enrollment and was maintained throughout the entire study period. Erythrocyte creatine was measured with haematologic indices in 83 haemodialysis patients. Haemoglobin was also measured 3 months after. RESULTS: ESA dose (152.4 ± 62.9 vs. 82.2 ± 45.5 units/kg/week, P = 0.0001) and erythrocyte creatine (2.07 ± 0.73 vs. 1.60 ± 0.41 µmol/gHb, p = 0.0003) were significantly higher in 27 patients with haemoglobin <10 g/dL compared to 56 patients with haemoglobin ≥10 g/dL. There was a fair correlation between ESA dose and the concentration of creatine in the erythrocytes (r = 0.55, P < 0.0001). Increase in haemoglobin (>0.1 g/dL) was observed in 37 patients, whereas haemoglobin did not increase in 46 patients. Erythrocyte creatine levels were significantly higher in those patients with an increase in haemoglobin compared to those without (2.04 ± 0.64 vs. 1.52 ± 0.39 µmol/gHb, p < 0.0001). When 8 variables (ESA dose, erythropoietin resistance index, C-reactive protein, intact parathyroid hormone, iron supplementation, presence of anaemia, erythrocyte creatine and reticulocyte) were used in the multivariate logistic analysis, erythrocyte creatine levels emerged as the most important variable associated with increase in haemoglobin (Chi-square = 6.19, P = 0.01). CONCLUSION: Erythrocyte creatine, a useful marker of erythropoietic capacity, is a reliable marker to estimate ameliorative effectiveness of ESA in haemodialysis patients.

Repetitive spikes of glucose and lipid induce senescence-like phenotypes of bone marrow stem cells through H3K27me3 demethylase-mediated epigenetic regulation.

Bone marrow-derived endothelial progenitor cells (EPCs) contribute to endothelial repair and angiogenesis. Reduced number of circulating EPCs is associated with future cardiovascular events. We tested whether dysregulated glucose and/or triglyceride (TG) metabolism has an impact on EPC homeostasis. The analysis of metabolic factors associated with circulating EPC number in humans revealed that postprandial hyperglycemia is negatively correlated with circulating EPC number, and this correlation appears to be further enhanced in the presence of postprandial hypertriglyceridemia (hTG). We therefore examined the effect of glucose/TG spikes on bone marrow lineage-sca-1+ c-kit+ (LSK) cells in mice, because primitive EPCs reside in bone marrow LSK fraction. Repetitive glucose + lipid (GL) spikes, but not glucose (G) or lipid (L) spikes alone, induced senescence-like phenotypes of LSK cells, and this phenomenon was reversible after cessation of GL spikes. G spikes and GL spikes differentially affected transcriptional program of LSK cell metabolism and differentiation. GL spikes upregulated a histone H3K27 demethylase JMJD3, and inhibition of JMJD3 eliminated GL spikes-induced LSK cell senescence-like phenotypes. These observations suggest that postprandial glucose/TG dysmetabolism modulate transcriptional regulation in LSK cells through H3K27 demethylase-mediated epigenetic regulation, leading to senescence-like phenotypes of LSK cells, reduced number of circulating EPCs, and development of atherosclerotic cardiovascular disease.NEW & NOTEWORTHY Combination of hyperglycemia and hypertriglyceridemia is associated with increased risk of atherosclerotic cardiovascular disease. We found that 1) hypertriglyceridemia may enhance the negative impact of hyperglycemia on circulating EPC number in humans and 2) metabolic stress induced by glucose + triglyceride spikes in mice results in senescence-like phenotypes of bone marrow stem/progenitor cells via H3K27me3 demethylase-mediated epigenetic regulation. These findings have important implications for understanding the pathogenesis of atherosclerotic cardiovascular disease in patients with T2DM.

Serum Angiopoietin-Like Protein 2 and NT-Pro BNP Levels and Their Associated Factors in Patients with Chronic Heart Failure Participating in a Phase III Cardiac Rehabilitation Program.

Angiopoietin-like protein 2 (ANGPTL2) promotes chronic inflammation and plays a key role in the pathogenesis of heart failure. Cardiac rehabilitation (CR) is an integral component of heart failure management and has been shown to have anti-inflammatory effects. However, ANGPTL2 concentration in chronic heart failure patients undergoing CR has not been evaluated. This study aimed to investigate serum ANGPTL2 levels and their associated factors and compare the results with those of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with chronic heart failure undergoing phase III CR.A total of 56 patients were enrolled. Clinical characteristics including body composition, grip strength, exercise tolerance, duration of CR, blood counts and biochemistry, and echocardiographic parameters were evaluated for their association with serum ANGPTL2 and NT-proBNP levels.The median (first and third quartiles) value of ANGPTL2 was 4.05 (2.70-5.57) ng/mL. Clinical parameters that correlated with serum ANGPTL2 levels were body weight, body mass index, body fat mass, body fat percentage, anaerobic threshold (AT), C-reactive protein, and total protein (TP), which were mostly distinct from those that correlated with serum NT-proBNP levels. A multivariate analysis revealed that AT and TP were independent factors related to ANGPTL2 levels, whereas age, left ventricular ejection fraction, and left atrial dimension were independently related to NT-proBNP levels.These observations suggest that CR increases the exercise tolerance and exhibits anti-inflammatory effects simultaneously, and this situation is reflected by decreased serum ANGPLT2 and TP levels. ANGPTL2 may be a useful marker of inflammation and impaired exercise tolerance in patients with chronic heart failure.

Diagnostic Accuracy of Optical Frequency Domain Imaging for Identifying Necrotic Cores with Intraplaque Hemorrhage in Advanced Human Carotid Plaques.

This study investigated whether optical frequency domain imaging (OFDI) can identify carotid artery vulnerable plaque characteristics, focusing on lipid-rich necrotic core (NC) and intraplaque hemorrhage (IPH). Fourteen patients scheduled for carotid endarterectomy underwent OFDI scan during preoperative angiography. Atherosclerotic plaque specimens obtained from carotid endarterectomy were cut every 3-4 mm into 4-µm transverse cross-sections and stained with standard methods. Each cross-section was matched with OFDI, and histologically classified into either fibrous, calcific, pathological intimal thickening (PIT), and NC. Of 75 histologic cross-sections, 6 were categorized as fibrous (8%), 18 as calcific (24%), 9 as PIT (12%), and 42 as NC (56%). Tissues categorized as NC had significantly higher OFDI signal attenuation rates than the other tissues (p <0.001), followed by PIT, calcific, and fibrous tissues. The receiver operating characteristic analysis indicated that attenuation rates of >0.023 and >0.031 predicted the presence of NC and IPH with high areas under the curve of 0.91 and 0.88, respectively. OFDI provides potential capability for the detection of NCs with IPH of carotid artery plaques by quantitatively analyzing the attenuation rate.

Automated classification of coronary atherosclerotic plaque in optical frequency domain imaging based on deep learning.

BACKGROUND AND AIMS: We developed a deep learning (DL) model for automated atherosclerotic plaque categorization using optical frequency domain imaging (OFDI) and performed quantitative and visual evaluations. METHODS: A total of 1103 histological cross-sections from 45 autopsy hearts were examined to compare the ex vivo OFDI scans. The images were segmented and annotated considering four histological categories: pathological intimal thickening (PIT), fibrous cap atheroma (FA), fibrocalcific plaque (FC), and healed erosion/rupture (HER). The DL model was developed based on pyramid scene parsing network (PSPNet). Given an input image, a convolutional neural network (ResNet50) was used as an encoder to generate feature maps of the last convolutional layer. RESULTS: For the quantitative evaluation, the mean F-score and IoU values, which are used to evaluate how close the predicted results are to the ground truth, were used. The validation and test dataset had F-score and IoU values of 0.63, 0.49, and 0.66, 0.52, respectively. For the section-level diagnostic accuracy, the areas under the receiver-operating characteristic curve produced by the DL model for FC, PIT, FA, and HER were 0.91, 0.85, 0.86, and 0.86, respectively, and were comparable to those of an expert observer. CONCLUSIONS: DL semantic segmentation of coronary plaques in OFDI images was used as a tool to automatically categorize atherosclerotic plaques using histological findings as the gold standard. The proposed method can support interventional cardiologists in understanding histological properties of plaques.