Among many diseases, coronary artery disease (CAD) is the primary cause of mortality and morbidity worldwide. With the aim of revealing the underlying genetic characteristics of the CAD subtypes, we recruited patients with CAD and categorized them into subgroups according to the transcriptome expression profiles of the adipose tissue.

With the removal of the batch effect, consensus clustering was employed to determine the subgroup numbers. Subgroup-specific genes were determined to conduct analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Weighted gene co-expression network analysis (WGCNA) revealed the subgroup-specific WGCNA modules. Moreover, gene set enrichment analysis (GSEA) was conducted. Overrepresentation enrichment analysis (OEA) of subgroup-specific signatures was also conducted to reveal the significant gene module associated with the corresponding clinical characteristics.

After the removal of the batch effect, 77 CAD objects were divided into three subgroups. It was observed that the patients in subgroup III tended to be fat. After analyzing the dominant pathways of each subgroup, we discovered that the protein digestion and absorption pathway was specifically upregulated in subgroup I, which might result from the lowest proportion of the epicardial adipose tissue (EAT) sample. Moreover, subgroup II patients had genetic characteristics of high expression of complement and coagulation cascades and TNF signaling pathway. Furthermore, Th17 cell differentiation was significantly upregulated in subgroup III, indicating that Th17 cell differentiation is related to the clinical characteristics of body mass index (BMI).

In conclusion, the genetic classification of CAD subjects indicated that subjects from different subgroups may exhibit specific gene expression patterns, suggesting that more personalized treatment should be applied to patients in each subgroup.

Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein known for its role in inflammation. However, plasma FSTL1 levels in patients with coronary artery disease (CAD) have not been fully elucidated. Thus, in this study, we investigated the plasma FSTL1 levels of 350 patients who underwent elective coronary angiography. The severity of CAD was represented as the numbers of > 50% stenotic vessels and segments and the severity score. CAD was detected in 196 patients, of whom 84 had 1-vessel disease (1-VD), 62 had 2-VD, and 50 had 3-VD. Plasma high-sensitivity C-reactive protein (hsCRP) levels were higher in patients with CAD than in those without CAD (median 0.56 versus 0.44 mg/L, P < 0.01). Notably, plasma FSTL1 levels were higher in patients with CAD than in those without CAD (median 4.05 versus 3.47 ng/mL, P < 0.02). A stepwise increase in FSTL1 levels was found depending on the number of > 50% stenotic vessels: 3.47 in CAD (−), 3.74 in 1-VD, 4.42 in 2-VD, and 4.65 ng/mL in 3-VD (P < 0.05). FSTL1 levels also correlated with the number of > 50% stenotic segments and the severity score (r = 0.14 and r = 0.15, respectively, P < 0.005) and hsCRP levels (r = 0.10, P < 0.05). In the multivariate analysis, FSTL1 levels were an independent factor associated with CAD. The odds ratio for CAD was 1.61 (95% CI = 1.01-2.58) for high FSTL1 level of > 3.6 ng/mL (P < 0.05). In conclusion, plasma FSTL1 levels in patients with CAD were found to be high and associated with the presence and severity of CAD, thus, suggesting that FSTL1 may play a role in the progression of coronary atherosclerosis.

Drug-coated balloon (DCB) has emerged as an alternative therapeutic choice for in-stent restenosis (ISR) lesions. Cutting balloon angioplasty (CBA) is also a strategy utilized to treat tight stenotic lesions or ISR lesions. Few studies have focused on whether CBA plus DCB could achieve a better result in lowering the incidence of recurrent ISR. This study aimed to evaluate the efficacy of CBA plus DCB for ISR lesions.

Between August 2011 and December 2017, 681 patients (937 lesions) were diagnosed with ISR and treated with DCBs in our hospital. The CBA plus DCB group comprised 90 patients who underwent PCI with further CBA plus DCB, and the DCB alone group comprised 591 patients who underwent percutaneous coronary intervention (PCI) with DCB alone.

Baseline characteristics, the types of previous stents, lesion type, prevalence of ostial lesion and left main lesion, and pre-PCI and post-PCI stenotic percentage showed no significant difference between the two groups. Only post-PCI reference luminal diameter and size of DCB were larger in the CBA plus DCB group. During the one-year follow-up period, late loss and clinical outcomes did not differ between the two groups before and after propensity score matching. The incidence of subtotal/total occlusion with delay flow was lower in the CBA plus DCB group after propensity score matching (4.1% versus 10.9%; P = 0.030).

In these patients with ISR lesions, the clinical outcomes and the incidence of repeat target lesion revascularization were similar after treatment with CBA plus DCB versus DCB alone. Further study is warranted, including prospective, randomized comparisons.

Inflammation and lipid signaling are involved in the pathogenesis and progression of coronary artery disease (CAD). We proposed that high-sensitivity C-reactive proteins, as a marker of the pro-inflammatory state, and high-density lipoprotein cholesterol (HDL-C), as an anti-atherosclerosis component, should be integrated into a single novel biomarker. Our work was conducted to discuss and compare the predictive ability of the high-sensitivity C-reactive protein to high-density lipoprotein cholesterol ratio (CHR) with other existing indices, for example, neutrophil high-density lipoprotein ratio (NHR) and neutrophil lymphocyte ratio (NLR), in the severity of CAD patients.

Based on the results of coronary angiography, patients were divided into the CAD⁺ group, CAD⁻ group, and control group. The relationship between various serum markers and the severity of coronary artery disease was examined via Spearman's correlation analysis. Logistic regression analysis was conducted to identify the influencing factors of the coronary artery disease severity.

This study included 420 patients. The Gensini score was positively correlated with CHR. Multiple regression analysis revealed that the CHR was significantly associated with CAD. CHR is an independent predictor of CAD. The receiver operating characteristic (ROC) analysis provided a cut-off value of 1.17 for CHR to predict CAD, with a specificity of 86.7%, Yoden index of 0.264, and area under the ROC curve of 0.662 (95% confidence intervals 0.606-0.719, P < 0.001). At the same time, the area under the ROC curve of the NHR was 0.652, and that of the NLR was 0.579. The results of the DeLong test indicated that the area under the ROC curve of the CHR was larger than that of the NLR (P = 0.0306). This suggests that the CHR as a predictor of CAD has better diagnostic performance than the NLR.

CHR was not only closely related to the presence and severity of CAD but also an independent predictor of severe CAD.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, patients with ST-elevation myocardial infarction (STEMI) should be treated as possibly infected individuals. Therefore, more time is considered necessary to conduct primary percutaneous coronary intervention (PCI). In this study, we sought to evaluate the impact of the SARS-CoV-2 pandemic on primary PCI for STEMI. Between March 2019 and March 2021, 259 patients with STEMI underwent primary PCI. Patients were divided into 2 groups: the pre-pandemic group (March 2019-February 2020) and the pandemic group (March 2020-February 2021). The patient demographics, reperfusion time including onset-to-door time, door-to-balloon time (DTBT), computed tomography (CT), peak creatinine phosphokinase (CPK), and 30-day mortality rate were investigated. The mean age of the patients was 70.4 ± 12.9 years, and 71.6% were male. There were 117 patients before the pandemic and 142 during the pandemic. The median DTBT was 29 (21.25-41.25) minutes before the pandemic and 48 minutes (31-73 minutes) during the pandemic (P < 0.001). The median door-to-catheter-laboratory time was 13.5 (10-18.75) minutes before the pandemic and 29.5 (18-47.25) minutes during the pandemic (P < 0.001). CT evaluation was performed before PCI in 39 (33.3%) patients and 63 (44.4%) patients (P = 0.08); their peak CPK levels were 1480 (358-2737.5) IU and 1363 (621-2722.75) IU (P = 0.56), and the 30-day mortality rates were 4.3% and 2.1% (P = 0.48), respectively. The SARS-CoV-2 pandemic changed the diagnostic procedure in the emergency department and affected the DTBT in patients with STEMI. Nonetheless, no adverse effects on the 30-day mortality rate were observed.

Cardiovascular diseases (CVDs) including myocardial infarction (MI) and stroke are often diagnosed in patients with abdominal aortic aneurysm (AAA). However, little has been reported regarding the incidence.

Patients with AAA were selected from the National Health Insurance system in South Korea between 2009 and 2015. A total of 10,822 participants with a new diagnosis of AAA were included. Propensity score matching by age and sex with patients in whom AAA was not diagnosed was used to select the control group of 32,466 participants. Primary endpoints included the diagnosis of CVD and death. Cox proportional hazard models were used to compare the risk of disease incidence.

The incidence of CVD was 16.573 per 1,000 person-years in the AAA group, which was higher than that of the control group's 9.30 per 1,000 person-years. The incidence of MI (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.479-1.953), stroke (HR, 1.629; 95% CI, 1.443-1.839), and CVD (HR, 1.672; 95% CI, 1.522-1.835) was significantly higher in patients with AAA. Mortality rate was also elevated in the AAA group (HR, 2.544; 95% CI, 2.377-2.722).

The incidence of CVD was significantly more frequent in patients with AAA. The AAA group had consistently higher risks regarding CVD and mortality than the control group.

The side branch (SB) provisional stenting strategy is currently the recommended approach for most coronary bifurcation lesions. However, this strategy may result in SB deterioration, which is associated with an increased incidence of periprocedural myocardial infarction (PMI) and may adversely affect the long-term prognosis. Various techniques for SB protection (SB-P) have been developed to reduce SB occlusion and improve the clinical prognosis. This meta-analysis was performed to compare the outcomes of an active SB-P strategy of jailed balloon technique, balloon-stent kissing technique, and jailed Corsair technique versus the conventional SB-P strategy based on jailed wire technique.

This meta-analysis included 5 studies (4 randomized and 1 observational) involving a total of 1,174 patients in whom the active and conventional SB-P strategies were compared. Fixed- and random-effects models were used to calculate summary risk ratios (RRs).

The risk of SB occlusion was significantly lower in active SB-P strategy [RR 0.47, 95% confidence interval (CI) 0.30-0.73 in fixed-effect model; RR 0.52, 95% CI 0.31-0.87 in random-effect model]. The risk of PMI was similar between the two strategies (RR 0.63, 95% CI 0.30-1.33 in fixed-effect model; RR 0.71, 95%CI 0.20-2.48 in random-effect model). The rate of long-term major adverse cardiovascular events was similar between the groups (RR 0.48, 95% CI 0.15-1.48 in fixed-effect model; RR 0.49, 95% CI 0.16-1.52 in random-effect model).

The active SB-P strategy in coronary bifurcation lesions is associated with reduced SB deterioration, but it does not decrease PMI or improve the long-term prognosis.

Electrical storm (ES), defined by 3 or more occurrences of ventricular arrhythmias within 24 hours, has been shown to be associated with an increased risk of mortality; however, detailed information remains lacking. We aimed to examine the incidence and determinants of ES and its impact on mortality in patients enrolled in the nationwide implantable cardioverter-defibrillator (ICD) registry.

We studied 1,256 patients (age 65 ± 12 years) who had structural heart disease with an ICD. The patients were classified into reduced ejection fraction (EF < 35%; 657 (52%) patients) and preserved or moderately reduced EF (EF ≥ 35%; 599 (48%) patients).

ES occurred in 49 (7%) and 36 (6%) patients in the EF < 35% and EF ≥ 35% groups (log-rank P = 0.297) during the median follow-up of 2.3 years. ICD with resynchronization therapy was associated with a lower incidence of ES in patients with EF < 35%. Non-ischemic heart disease and diuretics were associated with ES in patients with EF ≥ 35%. During the follow-up, 10/49 (20%) patients with ES and 80/608 patients (13%) without ES died in patients with EF < 35%, while 7/36 (19%) patients with ES and 38/563 patients (7%) without ES died in those with EF ≥ 35%. We have created 4 Cox multivariate models. All models showed approximately 2-fold higher hazard ratios in patients with EF ≥ 35% compared to EF < 35%.

Our study showed that the determinants of ES differed between EF < 35% and EF ≥ 35%. The impact of ES for mortality was numerically higher in EF ≥ 35% than in EF < 35%, although a significant interaction was not detected.

Catheter ablation is a treatment modality which has been increasingly used for cardiac arrhythmias. However, it is not complication-free, and cardiac perforation is one of its most life-threatening complications. As surgery is usually not the first-line treatment for this emergent episode, there were only very few sporadic surgical reports in the literature. This systemic review primarily aims to collect different surgical approaches for catheter-induced cardiac perforation to help surgeons manage this kind of uncommon and critical patients. Of the 452 initially screened articles, 22 studies (38 patients) were included in the systemic review. Of all the included patients, 84% (32/38) were found to have pericardial effusion acutely following catheter-related procedures, and 16% (6/38) experienced delayed-onset episodes. Regarding the surgical procedures, four patients underwent removal of clots only, eight patients underwent suture repair of the left ventricle (LV), nine patients underwent suture repair of the right ventricle (RV), five patients underwent suture repair of the LA, and four patients underwent sutureless repair of the LV and pulmonary vein (LV 1, RV 1, pulmonary vein 1). In addition to repair of perforation sites, the concomitant combined procedures included repair of intercostal vessels (complication of pericardiocentesis) for one patient, cryoablation for two patients, and maze procedure for one patient. For cardiac perforation following catheter ablation or electrophysiology study, although the majority of the patients are treated with pericardiocentesis and medical management at first, cardiovascular surgeons have to prepare to take over if the bleeding is persistent or if the cardiac tamponade is not relieved.

This study assesses the long-term outcomes of patients who suffered from self-expandable transcatheter heart valve (THV) embolized in the aorta in transcatheter aortic valve implantation (TAVI).

We retrospectively reviewed the patients with self-expandable THV embolized in the aorta. Follow-up computed tomography was performed to assess the THV migration, struct fractures, and device-related aortic complications.

Of the 539 TAVI patients, 11 suffered from self-expandable THV embolized in the aorta. Two patients underwent open-heart surgery to remove the embolized THVs in the ascending aorta. Embolized THVs were repositioned in the aortic arch distal to the left subclavian artery (n = 3) and the thoracic descending aorta (n = 6). Three patients died during a median follow-up time of 40 months. The remaining eight survivors presented with New York Heart Association functional class I or II at the last follow-up. Degeneration of embolized prostheses with thick leaflets and rolled cusp edges was observed in three patients. There was no evidence of valve migration, strut fracture, prosthesis-associated aortic complication, and thrombosis attached on embolized valve for all patients with THVs repositioned in the aorta.

Self-expandable THV embolization can be effectively managed in TAVI. Although some embolized valves exhibited leaflet degeneration, the long-term safety of repositioning embolized self-expandable THV in the aorta is assured.

In this study, we hypothesized that post-operative aorto-mitral angle might be associated to the occurrence of post-operative atrial arrhythmia (AA), including atrial fibrillation and atrial tachycardia, after mitral valve repair in patients with mitral regurgitation (MR). Thus, this present study aims to determine the effects of post-operative aorto-mitral angle on new-onset AA after mitral valve repair with mitral annuloplasty for the treatment of MR.

In total, 172 patients without any history of AA underwent mitral valve repair with mitral annuloplasty in our institution between 2008 and 2017. Patient information, including medical records and echocardiographic data, were retrospectively studied.

As per our findings, AA occurred in 15 (8.7%) patients during the follow-up period (median, 35.7 months; range, 0.5-132 months). The patients with AA were noted to have a longer cardiopulmonary bypass time and a smaller aorto-mitral angle at post-operative TTE than the others (119 ± 6° versus 125 ± 10°, P = 0.003). No significant difference was noted in the degree of post-operative residual MR or functional MS between the groups. In a multivariate Cox proportional hazards analysis, the longer cardiopulmonary bypass time and the smaller post-operative aorto-mitral angle were independent predictors of the occurrence of AA during the follow-up period (odds ratio per 10 minutes 1.11; 95% CI 1.02-1.22, P = 0.019: odds ratio 0.91; 95% CI 0.85-0.98, P = 0.012).

A small aorto-mitral angle at post-operative TTE was determined to be a predictor of new-onset AA after a mitral valve repair for treating MR.

Little is known as regards frailty in patients with functional tricuspid regurgitation (FTR). Thus, in this study, we aimed to investigate the prevalence, characteristics, and impact of frailty on patients with severe FTR.

This prospective study included 110 consecutive patients with severe FTR who were assessed via transthoracic echocardiography at an outpatient clinic. Patients were dichotomized using short physical performance battery (SPPB). To better understand the whole picture of frailty in patients with FTR, other frailty scales were also assessed (frailty checklist, clinical frailty scale, gait speed, and Columbia frailty scale). The primary endpoint was the combination of all-cause mortality and heart failure hospitalization.

According to each definition of frailty, 28%-46% were identified to be frail. Those with SPPB score of < 9 were older, had greater New York Heart Association (NYHA) functional classification, and had lower albumin level and estimated glomerular filtration rate compared with those with SPPB score of ≥ 9. They also have smaller tricuspid valve coaptation depth and worse right ventricular fractional area change (RV-FAC) than those with SPPB score of ≥ 9 despite having similar TR severity. The primary endpoint at 1 year was noted in 31% of patients. The SPPB score has excellent discriminatory performance for predicting the primary endpoint (area under the curve 0.82, 95% confidence interval [CI] 0.76-0.91) in receiver operating characteristic analysis and was independently associated with the primary endpoint after adjustment in multivariate analysis (adjusted hazard ratio 0.81, 95% CI, 0.73-0.90; P < 0.001).

Frailty has been widely prevalent in the elderly patient population with FTR; in fact, it has been determined to be strong parameter for poor outcomes.

Left ventricular thrombus (LVT) has been identified to be crucial in patients with reduced ejection fraction (EF). Three-dimensional cine phase-contrast magnetic resonance imaging (4D flow MRI) can visualize the intra-LV vortex during diastole and quantify the maximum flow velocity (Vmax) at the apex. In this study, we investigated whether the change in the intra-LV vortex was associated with the presence of LVT in patients with cardiac disease.

In total, 36 patients (63.5 ± 11.9 years, 28 men, 12/24 with/without LVT) with diffuse LV dysfunction underwent 4D flow MRI. The relative vortex area using streamline images and Vmax of blood flow toward the apex at the apical left ventricle were evaluated. The correlation between the relative vortex area and Vmax was assessed using Pearson's correlation coefficient. The ability to detect LVT was evaluated using the area under the curve (AUC) of the receiver operating characteristic.

The relative vortex area was found to be smaller (27 ± 10% versus 45 ± 11%, P = 0.000026), whereas Vmax at the apical left ventricle was lower (19.1 ± 4.4 cm/second versus 27.4 ± 8.9 cm/second, P = 0.0006) in patients with LVT. Vmax at the apical left ventricle demonstrated significant correlations with the relative vortex area (r = 0.43, P = 0.01) and relative transverse length of the vortex (r = 0.45, P = 0.007). The AUC was 0.91 for the relative vortex area, whereas it was 0.80 for Vmax in the apical left ventricle.

A smaller LV vortex and lower flow velocity at the LV apex were associated with LVT in patients with reduced EF.

Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) frequently induce cardiovascular adverse events, though VEGFR-TKIs contribute to the improvement of the prognosis of patients with malignancies. It is widely accepted that VEGFR-TKIs impair left ventricular systolic functions; however, their effects on diastolic functions remain to be fully elucidated. The purpose of this study was to analyze the impact of VEGFR-TKIs on left ventricular diastolic functions. This study was designed as a retrospective single-center cohort study in Japan. We assessed 24 cases who received VEGFR-TKI monotherapy (sunitinib, sorafenib, pazopanib, axitinib) with left ventricular ejection fraction (LVEF) above 50% during the therapy at the Osaka University Hospital from January 2008 to June 2019. Left ventricular diastolic functions were evaluated by the change in echocardiographic parameters before and after the VEGFR-TKI treatment. Both septal e' and lateral e's decreased after treatment (septal e': before, 6.1 ± 1.8; after, 5.0 ± 1.9; n = 21, P < 0.01; lateral e': before, 8.7 ± 2.8; after, 6.9 ± 2.3; n = 21, P < 0.01). E/A declined after VEGFR-TKIs administration, though not statistically significantly. In 20 cases with at least one risk factor for heart failure with preserved ejection fraction (HFpEF), E/A significantly decreased (0.87 ± 0.34 versus 0.68 ± 0.14; P < 0.05) as well as the septal and lateral e's. These results suggest that treatment with VEGFR-TKIs impairs left ventricular diastolic functions in patients with preserved LVEF, especially in those with risk factors for HFpEF.

Ivabradine, which reduces heart rate (HR) without affecting sympathetic nerve activity, improves mortality and morbidity in patients with systolic dysfunction. However, its impact on up-titrating a concomitant beta-blocker dose in such a cohort, via increasing cardiac output and blood pressure and improving tolerability to beta-blockers, remains unknown. In this single-center, prospective, randomized control trial, patients with systolic dysfunction, defined as left ventricular ejection fraction < 50%, sinus rhythm, heart rate > 75 bpm, systolic blood pressure between 90 and 110 mmHg, and New York Heart Association functional class III or IV, who are refractory to up-titration of a beta-blocker due to symptomatic hypotension, dizziness, or worsening heart failure, were assigned to the 20 ivabradine arm or the 20 conventional therapy arm and followed-up for 6 months. The primary outcome is the daily dose of beta-blocker at 6-months follow-up. The secondary outcomes are echocardiographic parameters including overlap between E-wave and A-wave in transmitral diastolic filling flow, plasma B-type natriuretic peptide level, 6-minute walk distance, and heart failure readmission rate. By conducting this study, we hope to demonstrate the clinical benefit of ivabradine therapy in up-titrating beta-blockers and improving clinical outcomes in patients with systolic dysfunction.

The prognostic impact of transfer to another hospital among acute heart failure (AHF) patients has not been well elucidated.

Of the 800 AHF patients analyzed, 682 patients were enrolled in this study for analysis. The subjects were divided into two groups according to their discharge location: discharge home (Group-H, n = 589) or transfer to another hospital for rehabilitation (Group-T, n = 93). The Kaplan-Meier curves revealed a poorer prognosis, including all-cause death and heart failure (HF) events (death, readmission-HF), in Group-T than that in Group-H (P < 0.001, respectively). A multivariate Cox regression model showed that Group-T was an independent predictor of 365-day all-cause death (hazard ratio: 2.618, 95% confidence interval [CI]: 1.510-4.538, P = 0.001). The multivariate logistic regression analysis showed that aging (per 1-year-old increase, odds ratio [OR]: 1.056, 95% CI: 1.028-1.085, P < 0.001), female gender (OR: 2.128, 95% CI: 1.287-3.521, P = 0.003), endotracheal intubation during hospitalization (OR: 2.074, 95% CI: 1.093-3.936, P = 0.026), and increased Controlling Nutritional Status score on admission (per 1.0-point increase, OR: 1.247, 95% CI: 1.131-1.475, P < 0.001) were associated with transfer to another hospital after AHF admission. The prognosis, including all-cause death, was determined to be significantly poorer in patients who were transferred to another hospital, as their activities of daily living were noted to lessen before discharge (n = 11) compared to others (n = 82).

Elderly AHF patients suffering from malnutrition were difficult to discharge home after AHF admission, and transfer to another hospital only led to adverse outcomes. Appropriate rehabilitation during definitive hospitalization appears necessary for managing elderly patients in the HF pandemic era.

Data examining the relationship between arterial stiffness and triglyceride (TG) and other cardiovascular risk factors have remained to be sparse.

Of the 5,109 patients with any cardiovascular risk factors in the Cardiovascular Prognostic Coupling Study in Japan (the Coupling Registry), the data of 1,534 patients who had no history of cardiovascular disease and were without low-density lipoprotein cholesterol (LDL-C) -lowering therapy (average age 67.9 ± 12.0 years, 55% males) were analyzed. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI). Among the clinical and behavioral cardiovascular risk factors, the significant factors that constituted the CAVI value were smoking, diabetes, lower high-density lipoprotein cholesterol, and higher TG. After adjustment for age, sex, and body mass index (BMI), only TG (odds ratio [OR] per 1 standard deviation, 1.26 [95% confidence interval, 1.12-1.44]) and diabetes (OR, 1.52 [1.22-1.90]) were found to be associated with a risk of higher CAVI (≥ 9.0). TG (C-statistic, 0.80 [0.78-0.82]; P = 0.040) and diabetes (C-statistic, 0.80 [0.78-0.82]; P = 0.038) significantly improved the discrimination of the risk of a higher CAVI beyond the model that included age, sex, and BMI.

TG was associated with a risk of arterial stiffness, and its contribution was slight but almost the same as that of diabetes among patients who had cardiovascular risk without a history of cardiovascular disease and LDL-C-lowering therapy.

The aim of this study is to explore the association of atrial fibrillation (AF) among physicians in Taiwan.

We used Cox proportional hazards models to estimate the incidence rate and the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) to determine the risk of AF in the physician study cohort relative to the comparison cohort.

A total of 22,479 physicians and 22,479 matched controls for comparison were included in the study. The Cox proportional hazard regression model revealed that male physician was associated with a trend toward increased risk of AF than nonphysician after adjusting for potential confounders (aHR, 1.05; 95% CI: 1.00-1.11). In age-specific analysis, male physicians aged ≤ 45 years showed the stronger association with AF (aHR, 1.33; 95% CI: 1.22-1.45). Further stratification with medical categories, surgeons had a significantly higher risk of AF than nonphysicians group (aHR, 1.28; 95% CI: 1.18-1.39).

We reported a pivotal study that showed possible relation between physician specialists and AF in the large cohort.

Deep learning models can be applied to electrocardiograms (ECGs) to detect left ventricular (LV) dysfunction. We hypothesized that applying a deep learning model may improve the diagnostic accuracy of cardiologists in predicting LV dysfunction from ECGs. We acquired 37,103 paired ECG and echocardiography data records of patients who underwent echocardiography between January 2015 and December 2019. We trained a convolutional neural network to identify the data records of patients with LV dysfunction (ejection fraction < 40%) using a dataset of 23,801 ECGs. When tested on an independent set of 7,196 ECGs, we found the area under the receiver operating characteristic curve was 0.945 (95% confidence interval: 0.936-0.954). When 7 cardiologists interpreted 50 randomly selected ECGs from the test dataset of 7,196 ECGs, their accuracy for predicting LV dysfunction was 78.0% ± 6.0%. By referring to the model's output, the cardiologist accuracy improved to 88.0% ± 3.7%, which indicates that model support significantly improved the cardiologist diagnostic accuracy (P = 0.02). A sensitivity map demonstrated that the model focused on the QRS complex when detecting LV dysfunction on ECGs. We developed a deep learning model that can detect LV dysfunction on ECGs with high accuracy. Furthermore, we demonstrated that support from a deep learning model can help cardiologists to identify LV dysfunction on ECGs.

The aim of the present study was to determine whether the addition of an oral nutritional supplement with whey peptides and branched-chain amino acids for cardiac rehabilitation improves cardiopulmonary function, skeletal muscle function, and metabolism in CHF patients.

In this randomized, parallel-group comparative pilot study, 20 CHF patients were randomly assigned to the nutrition group (n = 10) or the control group (n = 10). At baseline and 12 weeks, we performed physical examinations, motor function evaluation, clinical laboratory tests, nutritional status assessment, and echocardiography. The primary outcome was exercise tolerance, as determined by the cardiopulmonary stress test (CPX), 6-minute walking test (6MWT), and brain natriuretic peptide (BNP) levels.

During follow-up, body weight, body mass index, total muscle mass, and total lean mass did not change significantly in either group. The total fat mass significantly increased in the nutrition group (14.3 ± 5.4 kg versus 16.1 ± 5.5 kg, P < 0.001) but did not change in the control group, and the difference in the changes in total fat mass between groups was significant (−0.26 ± 0.96 kg versus 1.49 ± 0.63 kg, P < 0.001). The peakVO₂ and 6-minute walk test (6 MWT) significantly increased in the nutrition group (14.6 ± 3.4 mL/minute/kg versus 15.8 ± 3.8 mL/minute/kg, P = 0.029; 346.9 ± 103.1 m versus 382.7 ± 102.1 m, P = 0.048; respectively) but did not change in the control group. The changes in peakVO₂ and 6MWT did not significantly differ between the groups.

The oral nutritional supplement for the treatment of CHF was effective for cardiac rehabilitation in terms of fat mass and exercise capacity.

The present study demonstrated that oral nutritional supplements with whey peptides and branched-chain amino acid (BCAA) for cardiac rehabilitation in patients with chronic heart failure (CHF) increased fat mass and exercise capacity. We conclude that whey peptides and BCAA supplementation may be a useful treatment for CHF patients.

Inward rectifier potassium channels (I_K1, Kir) are known to play critical roles in arrhythmogenesis. Thus, how I_K1 agonist affects reperfusion arrhythmias needs to be clarified, and its underlying mechanisms should be determined. Reperfusion arrhythmias were modeled by coronary ligation (ischemia, 15 minutes) and release (reperfusion, 15 minutes). Zacopride (1.5-50 μg/kg in vivo, or 0.1-10 μmol/Lex vivo) was applied in the settings of pretreatment (3 minutes before coronary ligation) and posttreatment (5 minutes after coronary ligation). Hypoxia (45 minutes) /reoxygenation (30 minutes) model was established in cultured H9c2 (2-1) cardiomyocytes. Zacopride or KN93 was applied before hypoxia (pretreatment). In the setting of pre- or posttreatment, zacopride at 15 μg/kg in vivo or 1 μmol/Lin vitro exhibited superlative protections on reperfusion arrhythmias or intracellular calcium overload. Western blot data from ex vivo hearts or H9c2 (2-1) cardiomyocytes showed that I/R (H/R) induced the inhibition of Kir2.1 (the dominant subunit of I_K1 channel in ventricle), phosphorylation and oxidation of CaMKII, downregulation of SERCA2, phosphorylation of phospholamban (at Thr17), and activation of caspase-3. Zacopride treatment (1 μmol/L) was noted to strikingly restore the expression of Kir2.1 and SERCA2 and decrease the activity of CaMKII, phospholamban, and caspase-3. These effects were largely eliminated by co-application of I_K1 blocker BaCl₂. CaMKII inhibitor KN93 attenuated calcium overload and p-PLB (Thr17) in an I_K1-independent manner. I_K1-depedent inhibition of CaMKII activity is found to be a key cardiac salvage signaling under Ca²⁺ dyshomeostasis and reactive oxygen species (ROS) stress. I_K1 might be a novel target for pharmacological conditioning of reperfusion arrhythmia, especially for the application after unpredictable ischemia.

Transcription factor E3 (TFE3), which is a key regulator of cellular adaptation, is expressed in most tissues, including the heart, and is reportedly overexpressed during cardiac hypertrophy. In this study, TFE3's role in cardiac hypertrophy was investigated. To understand TFE3's physiological importance in cardiac hypertrophy, pressure-overload cardiac hypertrophy was induced through transverse aortic constriction (TAC) in both wild-type (WT) and TFE3 knockout mice (TFE3^−/−). Eleven weeks after TAC induction, cardiac hypertrophy was observed in both WT and TFE3^−/− mice. However, significant reductions in ejection fraction and fractional shortening were observed in WT mice compared to TFE3^−/− mice. To understand the mechanism, we found that myosin heavy chain (Myh7), which increases during hemodynamic overload, was lower in TFE3^−/− TAC mice than in WT TAC mice, whereas extracellular signal-regulated protein kinases (ERK) phosphorylation, which confers cardioprotection, was lower in the left ventricles of WT mice than in TFE3^−/− mice. We also found high expressions of TFE3, histone, and MYH7 and low expression of pERK in the normal human heart compared to the hypertensive heart. In the H9c2 cell line, we found that ERK inhibition caused TFE3 nuclear localization. In addition, we found that MYH7 was associated with TFE3, and during TFE3 knockdown, MYH7 and histone were downregulated. Therefore, we showed that TFE3 expression was increased in the mouse model of cardiac hypertrophy and tissues from human hypertensive hearts, whereas pERK was decreased reversibly, which suggested that TFE3 is involved in cardiac hypertrophy through TFE3-histone-MYH7-pERK signaling.

Coronary artery disease (CAD) is a high-incidence of heart disease. We aimed to identify potential biomarkers linked to the progression of CAD using multiple sets of data mining analysis methods. The long noncoding RNA (lncRNA) + messenger RNA (mRNA) data set GSE113079 and microRNA (miRNA) data set GSE28858 were downloaded from Gene Expression Omnibus. After data preprocessing, differentially expressed mRNA, lncRNA, and miRNA were identified using limma software. In addition, weighted gene co-expression network analysis (WGCNA) was used for the construction and screening of modules related to disease states. Besides, key mRNAs and lncRNAs were extracted for protein-protein interaction (PPI) network construction and lncRNA-mRNA co-expression analysis. Additionally, the final integration resulted in the lncRNA-miRNA-mRNA relationship pairs (competing endogenous RNA (ceRNA) network). Finally, CTD 2020 update database was used for the verification of the expression level of the candidate genes. A total of 1319 differentially expressed mRNAs and 1983 lncRNAs were screened. After WGCNA, a total of 234 mRNAs and 546 lncRNAs were identified. A PPI network including 127 mRNA corresponding proteins was constructed. The ceRNA network included 24 up-regulated lncRNAs, 16 down-regulated miRNAs, and 42 up-regulated mRNAs. Through the validation of CTD 2020 update database, 21 CAD related mRNAs, and four important ceRNAs those may be participated in the pathogenesis of CAD were obtained. In this study, through multiple sets of data mining methods, the regulatory relationship of lncRNA, miRNA, and mRNA was comprehensively analyzed, and the important role of lncRNA-miRNA-mRNA in the pathogenesis of CAD was emphasized.

Clinical studies have indicated that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, can potentially inhibit chronic heart failure. In the Stat-LVDF study, a difference was noted in terms of the effect of lipophilic pitavastatin (PTV) and hydrophilic rosuvastatin (RSV) on plasma BNP, suggesting that statin lipophilicity and pharmacokinetics change the pleiotropic effect on heart failure in humans. Therefore, we assessed the beneficial effects of PTV on hypertrophy in cardiac myocytes compared with RSV at clinically used doses. Cultured cardiomyocytes were stimulated with 30 μM phenylephrine (PE) in the presence of PTV (250 nM) or RSV (50 nM). These doses were calculated based on the maximum blood concentration of statins used in clinical situations in Japan. The results showed that PTV, but not RSV, significantly inhibits the PE-induced increase in cell size and leucine incorporation without causing cell toxicity. In addition, PTV significantly suppressed PE-induced mRNA expression of hypertrophic response genes. PE-induced ERK phosphorylation was inhibited by PTV, but not by RSV. Furthermore, PTV significantly suppressed the angiotensin-II-induced proline incorporation in primary cultured cardiac fibroblasts. In conclusion, a clinical dose of PTV was noted to directly inhibit cardiomyocyte hypertrophy and cardiac fibrosis, suggesting that lipophilic PTV can be a potential drug candidate against chronic heart failure.

Circular RNAs (circRNAs) have been implicated in the dysfunction of vascular smooth muscle cells (VSMCs), which is linked with the development of abdominal aortic aneurysm (AAA). Herein, we explored the precise action of circRNA fibronectin type III domain containing 3B (circ-FNDC3B) in VSMC injury triggered by angiotensin II (Ang-II).

Circ-FNDC3B, microRNA (miR) -143-3p, and a disintegrin and metalloproteinase 10 (ADAM10) were quantified by quantitative real-time polymerase chain reaction or western blot assay. Ribonuclease R and subcellular localization assays were applied to characterize circ-FNDC3B. Cell viability, apoptosis, and proliferation were assessed by the Cell Counting Kit-8 assay, flow cytometry, and 5-Ethynyl-2' -Deoxyuridine assay, respectively. The levels of tumor necrosis factor alpha, interleukin-6, superoxide dismutase, and malonaldehyde were estimated by enzyme-linked immunosorbent assay. Direct relationship miR-143-3p and circ-FNDC3B or ADAM10 was verified by dual-luciferase reporter and RNA immunoprecipitation assays.

Circ-FNDC3B was highly expressed in AAA tissues and Ang-II-treated VSMCs. Knocking down circ-FNDC3B alleviated Ang-II-induced VSMC injury. Mechanistically, circ-FNDC3B directly targeted miR-143-3p, and miR-143-3p was a downstream mediator of circ-FNDC3B in regulating cell injury induced by Ang-II. ADAM10 was directly targeted and inhibited by miR-143-3p. MiR-143-3p-mediated inhibition of ADAM10 relieved Ang-II-induced VSMC injury. Furthermore, circ-FNDC3B acted as a competing endogenous RNA for miR-143-3p to modulate ADAM10 expression.

Our findings suggested that circ-FNDC3B silencing ameliorated cytotoxicity triggered by Ang-II in VSMCs at least partially depending on the regulation of the miR-143-3p/ADAM10 axis.

Kawasaki disease (KD) is an acute self-limited syndrome that predominantly affects children. Coronary sequelae have been identified to be responsible for a small, but significant percentage of young adults who present with myocardial ischemia. In this study, we present a case of an elderly patient with possible coronary sequelae of KD. A 76-year-old man was referred to our outpatient department for silent myocardial ischemia. Axial images of coronary computed tomography showed multiple lumens in the proximal left anterior descending (LAD) artery. Coronary angiography demonstrated braid-like appearance in the proximal and distal segment of the LAD. Coronary intervention was successfully performed for the proximal LAD lesion using directional atherectomy (DCA) catheter. Microscopic examination of the DCA specimens showed the following histological features: tissues in densely hyalinized fibrosis with occasional microcalcification, or those containing a number of smooth muscle cells (SMCs) with myxoid extracellular matrix. There was paucity of cholesterin crystals and aggregation of foamy cells. In addition, scarcely any inflammatory cell filtration was identified. In the section of SMC-containing samples, formation of multiple re-canalized vessels embracing endothelial cells was confirmed. These histopathologic findings indicated that the present coronary artery lesion has a high possibility of very late cardiovascular sequelae caused by arteritis due to KD, rather than arteriosclerosis. This is the oldest adult case with coronary artery disease possibly resulting from KD sequelae. This case highlights that KD sequelae must be considered as a cause of coronary artery lesion even in older patients.

Significant paravalvular leak regurgitation (PVLR) after transcatheter aortic valve replacement (TAVR) is a well-known complication associated with disabling symptoms related to heart failure and hemolysis or both, with poor prognostic implications. Although challenging and technically demanding, percutaneous closure is an effective treatment option for high-risk patients with symptomatic PVLR. Here, we present two cases of transcatheter PVLR closure after replacement of third-generation (one self-expandable and one balloon-expandable) transcatheter aortic valves, each with peculiar challenges, and the strategies adopted to increase the success rate of percutaneous closure.

A 27-year-old Caucasian male traveler with well-controlled asthma was admitted to our hospital because of severe heart failure (HF). He had a history of cocaine use. Transthoracic echocardiography (TTE) showed severe diffuse hypokinesis of the left ventricle (LV) and a large mobile thrombus in the LV. He was treated with diuretics, inotropes and anticoagulants which led to small improvements in the HF and LV thrombus, however, he needed to undergo left ventricular assist device (LVAD) implantation and surgical removal of a residual LV thrombus due to inotrope-dependency.

It is necessary to consider the possibility of cocaine or illicit drug use in a young individual with cardiovascular disease or sudden death even in Japan where cocaine and drugs are prohibited by law, as recreational drug use has been increasing in many countries around the world.

A few studies have reported on recurrent myocarditis occurring more than twice in one patient. In this study, we present a recurrent "third time" acute myocarditis in a young female Japanese patient with a history of a definitive diagnosis of lymphocytic myocarditis by endomyocardial biopsy, cardiac magnetic resonance imaging (CMR), and catheter examination twice in the past. Although chest pain and an increase in the cardiac enzymes were observed the third time, no significant changes were noted in the 12-lead electrocardiogram (ECG), and a definitive diagnosis could be achieved by CMR. This case suggested that in patients with a history of myocarditis, if there is chest pain and elevated cardiac enzymes even without any changes in the 12-lead ECG, acute myocarditis should be considered, and CMR is useful for the differentiation.

Only four case reports including this present case were found through the previous literatures. More than two recurrent episodes of myocarditis have been extremely rare, but all cases have typical chest symptoms and a troponin level increase, leading to a relatively benign prognosis.

Left ventricular noncompaction cardiomyopathy (LVNC) is a heart muscle disorder morphologically characterized by reticulated trabeculations and intertrabecular recesses in the left ventricular (LV) cavity. LVNC is a genetically and phenotypically heterogeneous condition, which has been increasingly recognized with the accumulation of evidence provided by genotype-phenotype correlation analyses. Here, we report 2 sporadic adult cases of LVNC; both developed acute heart failure as an initial clinical manifestation and harbored causal sarcomere gene mutations. One case was a 57-year-old male with digenic heterozygote mutations, p.R1344Q in myosin heavy chain 7 (MYH7) and p.R144W in troponin T2, cardiac type (TNNT2), who showed morphological characteristics of LVNC in the lateral to apical regions of the LV together with a comorbidity of non-transmural myocardial infarction, resulting from a coronary artery stenosis. After the removal of ischemic insult and standard heart failure treatment, LVNC became less clear, and LV function gradually improved. The other case was a 36-year-old male with a heterozygote mutation, p.E334K in myosin binding protein C3 (MYBPC3), who exhibited cardiogenic shock on admission with morphological characteristics of LVNC being most prominent in the apical segment of the LV. The dosage of beta-blocker was deliberately increased in an outpatient clinic over 6 months following hospitalization, which remarkably improved the LV ejection fraction from 21% to 54.3%. Via a combination of imaging and histopathological and genetic tests, we have found that these cases are not compatible with a persistent phenotype of primary cardiomyopathy, but their morphological features are changeable in response to treatment. Thus, we point out phenotypic plasticity or undulation as a noticeable element of LVNC in this case report.

Reportedly, approximately 9.9%-12.4% of patients with Takotsubo syndrome (TTS) are complicated with cardiogenic shock (CS) and its prognosis remains poor even with the support of conventional mechanical circulatory assist devices including intra-aortic balloon pumping and venoarterial extracorporeal membrane oxygenation. Impella, a novel percutaneous left ventricular assist device, provides strong circulatory support together with the unloading of the left ventricle, and it is theoretically a promising mechanical circulatory assist device for TTS. In this case study, we report four consecutive patients with TTS complicated with CS who were successfully resuscitated using the Impella support.

Anti-HER2 therapy has greatly improved the long-term prognosis of patients with HER2-positive breast cancer. Meanwhile, by interfering with the protective effects of neuregulin-1/HER2 signaling on stressed cardiomyocytes, anti-HER2 therapy occasionally induces reversible cancer therapeutics-related cardiac dysfunction (CTRCD). Cardiac magnetic resonance (CMR) parametric mapping or myocardial feature-tracking, in combination with late gadolinium enhancement (LGE) imaging, has the potential to detect changes in the myocardium in anti-HER2 therapy-related cardiac dysfunction. Here we report a breast cancer patient who experienced life-threatening CTRCD after treatment with trastuzumab plus pertuzumab. This case showed multiple transmural LGE-positive myocardial lesions in CMR imaging and high native T1 and T2 values in CMR parametric mapping, which was apparently more extensive than those observed in most patients with anti-HER2 therapy-related cardiac dysfunction. Consistent with profound myocardial damage indicated by CMR, her cardiac function was not fully restored despite intensive care and cardioprotective drug therapy. These findings suggest the potential usefulness of LGE imaging and parametric mapping by CMR for the assessment of myocardial injury to determine the clinical severity of anti-HER2 therapy-related cardiac dysfunction.

Transthoracic, transesophageal, and intracardiac echocardiography are applicable imaging tools used for increasing the accuracy of tumor positioning during transvenous intracardiac tumor biopsy. However, incorporating echo-images in the extremely rare procedures is usually not easy. By using a contralateral catheter for simultaneous contrast injection and tip positioning, we demonstrated tumor biopsy safely and effectively in 4 cases without the guidance of echocardiography.

An error appeared in the article entitled "High Apolipoprotein E Levels Predict Adverse Limb Events in Patients with Peripheral Artery Disease Due to Peripheral Artery Disease Undergoing Endovascular Treatment and On-Statin Treatment" by Tatsuya Fukase, Tomotaka Dohi, Yoshiteru Kato, Yuichi Chikata, Norihito Takahashi, Hirohisa Endo, Shinichiro Doi, Hiroki Nishiyama, Iwao Okai, Hiroshi Iwata, Shinya Okazaki, Kikuo Isoda, Katsumi Miyauchi, Hiroyuki Daida, and Tohru Minamino (Vol. 62, No. 4, 872-878, 2021). The title of this article should be "High Apolipoprotein E levels Predict Adverse Limb Events in Patients with Intermittent Claudication Due to Peripheral Artery Disease Undergoing Endovascular Treatment and On-Statin Treatment".

The editorial office of International Heart Journal would like to inform our readers that the experimental study titled "LncRNA DIGIT Accelerates Tube Formation of Vascular Endothelial Cells by Sponging miR-134" written by Chaofeng Miao, Haixia Cao, Yonggan Zhang, Xueli Guo, Zifan Wang, Jiaxiang Wang and published in the September 2018 issue of International Heart Journal (Int Heart J 2018; 59: 1086-1095) has been retracted upon request from the authors.

We are pleased to announce that the following 3 articles have been selected for the UEDA Heart Awards for the Year 2021.

FIRST PLACE

Age-Dependent Echocardiographic and Pathologic Findings in a Rat Model with Duchenne Muscular Dystrophy Generated by CRISPR/Cas9 Genome Editing

Hidetoshi Sugihara, Koichi Kimura, Keitaro Yamanouchi, Naomi Teramoto, Tomoko Okano, Masao Daimon, Hiroyuki Morita, Katsu Takenaka, Takanori Shiga, Jun Tanihata, Yoshitsugu Aoki, Tokiko Inoue-Nagamura, Hiroshi Yotsuyanagi, Issei Komuro

Int Heart J 2020; 61 (6): 1279-1284.

SECOND PLACE

Expression of Cyclophilin A in Coronary Artery Plaque with Intraplaque Hemorrhage Is More Frequent in Deceased Patients Who Had Impaired Kidney Function

Mai Nakai, Aiko Shimokado, Takashi Kubo, Yosuke Katayama, Tsuyoshi Nishiguchi, Manabu Kashiwagi, Kunihiro Shimamura, Yasutsugu Shiono, Akio Kuroi, Takashi Yamano, Takashi Tanimoto, Yoshiki Matsuo, Hironori Kitabata, Yasushi Ino, Tomoyuki Yamaguchi, Atsushi Tanaka, Takeshi Hozumi, Takashi Akasaka

Int Heart J 2020; 61 (6): 1129-1134.

THIRD PLACE

Diagnosing Heart Failure from Chest X-Ray Images Using Deep Learning

Takuya Matsumoto, Satoshi Kodera, Hiroki Shinohara, Hirotaka Ieki, Toshihiro Yamaguchi, Yasutomi Higashikuni, Arihiro Kiyosue, Kaoru Ito, Jiro Ando, Eiki Takimoto, Hiroshi Akazawa, Hiroyuki Morita, Issei Komuro

Int Heart J 2020; 61 (4): 781-786.