Association between frailty and physical performance in older patients with heart failure.

BACKGROUND: Frailty is an issue in patients with heart failure (HF). A Korean version of the frailty scale (K-FRAIL) has been developed. HYPOTHESIS: We aimed to analyze the relationship between the K-FRAIL scale and physical performance in patients with HF. METHODS: This study included 142 patients with HF aged ≥65 years from a single center. Muscular fitness was assessed using the handgrip test and knee extensor strength measurement. Aerobic capacity was assessed using the cardiopulmonary exercise test and 6-min walk test (6MWT). Frailty was assessed using the K-FRAIL questionnaire. RESULTS: Peak VO2 and 6MWT scores significantly decreased as frailty worsened, but handgrip and knee extensor strength did not. In the multivariate analysis, peak VO2 (ß = -.31; p = .002) and 6MWT score (ß = -.38; p < .001) showed significant inverse associations with the K-FRAIL score. Based on the receiver operating characteristic curve analysis, the cut-off values of peak VO2 (hazard ratio, 5.08; p = .023) and 6MWT (hazard ratio, 3.99; p = .020) were independent predictors of frailty. CONCLUSION: In older patients with HF, physical performance correlates with the degree of frailty. The K-FRAIL scale is correlated with the peak VO2 and 6MWT.

Critical roles of parkin and PINK1 in coxsackievirus B3-induced viral myocarditis.

Viral myocarditis is an inflammatory disease of the myocardium, often leads to cardiac dysfunction and death. PARKIN (PRKN) and PINK1, well known as Parkinson's disease-associated genes, have been reported to be involved in innate immunity and mitochondrial damage control. Therefore, we investigated the role of parkin and PINK1 in coxsackievirus B3 (CVB3)-induced viral myocarditis because the etiology of myocarditis is related to abnormal immune response to viral infection and mitochondrial damage. After viral infection, the survival was significantly lower and myocardial damage was more severe in parkin knockout (KO) and PINK1 KO mice compared to wild-type (WT) mice. Parkin KO and PINK1 KO showed defective immune cell recruitment and impaired production of antiviral cytokines such as interferon-gamma, allowing increased viral replication. In addition, parkin KO and PINK1 KO mice were more susceptible to CVB3-induced mitochondrial damage than WT mice, resulting in susceptibility to viral-induced cardiac damage. Finally, using publicly available RNA-seq data, we found that pathogenic mutants of the PRKN gene are more common in patients with dilated cardiomyopathy and myocarditis than in controls or the general population. This study will help elucidate the molecular mechanism of CVB3-induced viral myocarditis.

Epicardial Adipose Tissue Thickness Is Related to Plaque Composition in Coronary Artery Disease.

(1) Background: Currently, limited data are available regarding the relationship between epicardial fat and plaque composition. The aim of this study was to assess the relationship between visceral fat surrounding the heart and the lipid core burden in patients with coronary artery diseases; (2) Methods: Overall, 331 patients undergoing coronary angiography with combined near-infrared spectroscopy and intravascular ultrasound imaging were evaluated for epicardial adipose tissue (EAT) thickness using transthoracic echocardiography. Patients were divided into thick EAT and thin EAT groups according to the median value; (3) Results: There was a positive correlation between EAT thickness and maxLCBI4mm, and maxLCBI4mm was significantly higher in the thick EAT group compared to the thin EAT group (437 vs. 293, p < 0.001). EAT thickness was an independent predictor of maxLCBI4mm ≥ 400 along with age, low-density lipoprotein-cholesterol level, acute coronary syndrome presentation, and plaque burden in a multiple linear regression model. Receiver operating characteristic curve analysis showed that EAT thickness was a predictor for maxLCBI4mm ≥ 400; (4) Conclusions: In the present study, EAT thickness is related to the lipid core burden assessed by NIRS-IVUS in patients with CAD which suggests that EAT may affect the stability of the plaques in coronary arteries.

Neuronal ApoE Regulates the Cell-to-Cell Transmission of α-Synuclein.

The presence of protein inclusions, called Lewy bodies (LBs) and Lewy neurites (LNs), in the brain is the main feature of Parkinson's disease (PD). Recent evidence that the prion-like propagation of α-synuclein (α-syn), as a major component of LBs and LNs, plays an important role in the progression of PD has gained much attention, although the molecular mechanism remains unclear. In this study, we evaluated whether neuronal ApoE regulates the cell-to-cell transmission of α-syn and explored its molecular mechanism using in vitro and in vivo model systems. We demonstrate that neuronal ApoE deficiency attenuates both α-syn uptake and release by downregulating LRP-1 and LDLR expression and enhancing chaperone-mediated autophagy activity, respectively, thereby contributing to α-syn propagation. In addition, we observed that α-syn propagation was attenuated in ApoE knockout mice injected with pre-formed mouse α-syn fibrils. This study will help our understanding of the molecular mechanisms underlying α-syn propagation.

Efficacy and Safety of 3 Versus 6 Months of Dual-Antiplatelet Therapy in Patients Implanted With a Coroflex ISAR Stents: A Prospective, Multicenter, Randomized Clinical Trial.

BACKGROUND: The optimal duration of dual-antiplatelet therapy (DAPT) after implantation of a drug-eluting stent (DES), especially recently developed polymer-free DESs, is unknown. This study examined the efficacy and safety of 3- versus 6-month DAPT in patients implanted with Coroflex ISAR polymer-free DESs. METHODS: Between May 2015 and August 2020, 488 patients who underwent Coroflex ISAR stent implantation were enrolled in the study and randomly assigned to the 3-month (n=244) or 6-month (n=244) DAPT group. RESULTS: At 1 year, the primary endpoint (composite of cardiovascular death, myocardial infarction, target vessel revascularization, and Bleeding Academic Research Consortium [BARC] type 2-5 bleeding) occurred in 9 (3.7%) patients in the 3-month DAPT group and in 7 (2.9%) patients in the 6-month DAPT group (hazard ratio 1.31; P=.60). There was no difference between the 3- and 6-month DAPT groups in either BARC type 2-5 bleeding (1.6% vs 0.8%; hazard ratio 2.00; P=.42) or any bleeding (2.9% vs 3.3%; hazard ratio 0.87; P=.80). CONCLUSION: Compared with 6 months of DAPT, 3 months of DAPT did not increase the risk of primary endpoint 1 year after Coroflex ISAR stent implantation, although it should be noted that the trial has limited power to see differences due to low event rate and low recruitment rate.

An artificial intelligence electrocardiogram analysis for detecting cardiomyopathy in the peripartum period.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a fatal maternal complication, with left ventricular systolic dysfunction (LVSD; Left ventricular ejection fraction 45% or less) occurring at the end of pregnancy or in the months following delivery. The scarcity of screening tools for PPCM leads to a delayed diagnosis and increases its mortality and morbidity. We aim to evaluate an electrocardiogram (ECG)-deep learning model (DLM) for detecting cardiomyopathy in the peripartum period. METHODS: For the DLM development and internal performance test for detecting LVSD, we obtained a dataset of 122,733 ECG-echocardiography pairs from 58,530 male and female patients from two community hospitals. For the DLM external validation, this study included 271 ECG-echocardiography pairs (157 unique pregnant and postpartum period women) examined in the Ajou University Medical Center (AUMC) between January 2007 and May 2020. All included cases underwent an ECG within two weeks before or after the day of transthoracic echocardiography, which was performed within a month before delivery, or within five months after delivery. Based on the diagnostic criteria of PPCM, we analyzed the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to evaluate the model effectiveness. RESULTS: The ECG-based DLM detected PPCM with an AUROC of 0.877. Moreover, its sensitivity, specificity, PPV, and NPV for the detection of PPCM were 0.877, 0.833, 0.809, 0.352, and 0.975, respectively. CONCLUSIONS: An ECG-based DLM non-invasively and effectively detects cardiomyopathies occurring in the peripartum period and could be an ideal screening tool for PPCM.

Electrocardiographic biomarker based on machine learning for detecting overt hyperthyroidism.

Aims: Although overt hyperthyroidism adversely affects a patient's prognosis, thyroid function tests (TFTs) are not routinely conducted. Furthermore, vague symptoms of hyperthyroidism often lead to hyperthyroidism being overlooked. An electrocardiogram (ECG) is a commonly used screening test, and the association between thyroid function and ECG is well known. However, it is difficult for clinicians to detect hyperthyroidism through subtle ECG changes. For early detection of hyperthyroidism, we aimed to develop and validate an electrocardiographic biomarker based on a deep learning model (DLM) for detecting hyperthyroidism. Methods and results: This multicentre retrospective cohort study included patients who underwent ECG and TFTs within 24 h. For model development and internal validation, we obtained 174 331 ECGs from 113 194 patients. We extracted 48 648 ECGs from 33 478 patients from another hospital for external validation. Using 500 Hz raw ECG, we developed a DLM with 12-lead, 6-lead (limb leads, precordial leads), and single-lead (lead I) ECGs to detect overt hyperthyroidism. We calculated the model's performance on the internal and external validation sets using the area under the receiver operating characteristic curve (AUC). The AUC of the DLM using a 12-lead ECG was 0.926 (0.913-0.94) for internal validation and 0.883(0.855-0.911) for external validation. The AUC of DLMs using six and a single-lead were in the range of 0.889-0.906 for internal validation and 0.847-0.882 for external validation. Conclusion: We developed a DLM using ECG for non-invasive screening of overt hyperthyroidism. We expect this model to contribute to the early diagnosis of diseases and improve patient prognosis.

Interaction between coxsackievirus B3 infection and α-synuclein in models of Parkinson's disease.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. PD is pathologically characterized by the death of midbrain dopaminergic neurons and the accumulation of intracellular protein inclusions called Lewy bodies or Lewy neurites. The major component of Lewy bodies is α-synuclein (α-syn). Prion-like propagation of α-syn has emerged as a novel mechanism in the progression of PD. This mechanism has been investigated to reveal factors that initiate Lewy pathology with the aim of preventing further progression of PD. Here, we demonstrate that coxsackievirus B3 (CVB3) infection can induce α-syn-associated inclusion body formation in neurons which might act as a trigger for PD. The inclusion bodies contained clustered organelles, including damaged mitochondria with α-syn fibrils. α-Syn overexpression accelerated inclusion body formation and induced more concentric inclusion bodies. In CVB3-infected mice brains, α-syn aggregates were observed in the cell body of midbrain neurons. Additionally, α-syn overexpression favored CVB3 replication and related cytotoxicity. α-Syn transgenic mice had a low survival rate, enhanced CVB3 replication, and exhibited neuronal cell death, including that of dopaminergic neurons in the substantia nigra. These results may be attributed to distinct autophagy-related pathways engaged by CVB3 and α-syn. This study elucidated the mechanism of Lewy body formation and the pathogenesis of PD associated with CVB3 infection.

Translesional Fractional Flow Reserve is Related to Plaque Components in Coronary Artery Disease: A Study Combining Pressure Wire and NIRS-IVUS Analysis.

OBJECTIVES: It remains unclear whether atherosclerotic plaque structure or composition is related to translesional biomechanical stresses in coronary artery disease. The aim of this study was to evaluate the association between translesional pressure parameters (using a pressure wire) and plaque characteristics (using a combined near-infrared spectroscopy [NIRS] and intravascular ultrasound [IVUS] imaging catheter). METHODS: Fractional flow reserve (FFR), delta (Δ) FFR, and Δ pressure were obtained during adenosine-induced maximum hyperemic status. Lipid core burden index (LCBI) and maximum LCBI within 2 mm (maxLCBI2mm) and tomographic anatomy were evaluated by NIRS-IVUS. RESULTS: Sixty-six lesions from 57 patients were analyzed (57 lesions for FFR, 45 lesions for ΔFFR). There was a negative correlation between FFR and maxLCBI2mm (r=-0.264; P=.049) and a positive correlation between ΔFFR and maxLCBI2mm (r=0.299; P=.049). ΔFFR of lesions with maxLCBI2mm ≥500 was significantly higher than maxLCBI2mm <500 (0.159 ± 0.085 vs 0.104 ± 0.075, respectively; P=.04). By receiver-operating characteristic curve analysis, ΔFFR ≥0.1 was a predictor for maxLCBI2mm ≥500 (area under curve, 0.707; 95% confidence interval, 0.552-0.862; P=.03). On multivariate analysis, ΔFFR was the only predictor of maxLCBI2mm (ß=0.347; P=.03). CONCLUSION: ΔFFR across a coronary artery lesion is related to lipid core burden assessed using NIRS-IVUS and might be a meaningful predictor of high-risk plaque (plaque with high lipid content).

Prediction of Major Depressive Disorder Following Beta-Blocker Therapy in Patients with Cardiovascular Diseases.

Incident depression has been reported to be associated with poor prognosis in patients with cardiovascular disease (CVD), which might be associated with beta-blocker therapy. Because early detection and intervention can alleviate the severity of depression, we aimed to develop a machine learning (ML) model predicting the onset of major depressive disorder (MDD). A model based on L1 regularized logistic regression was trained against the South Korean nationwide administrative claims database to identify risk factors for the incident MDD after beta-blocker therapy in patients with CVD. We identified 50,397 patients initiating beta-blockers for CVD, with 774 patients developing MDD within 365 days after initiating beta-blocker therapy. An area under the receiver operating characteristic curve (AUC) of 0.74 was achieved. A history of non-selective beta-blockers and factors related to anxiety disorder, sleeping problems, and other chronic diseases were the most strong predictors. AUCs of 0.62-0.71 were achieved in the external validation conducted on six independent electronic health records and claims databases in the USA and South Korea. In conclusion, an ML model that identifies patients at high-risk for incident MDD was developed. Application of ML to identify susceptible patients for adverse events of treatment may serve as an important approach for personalized medicine.

Cholesterol Metabolism in the Brain and Its Association with Parkinson's Disease.

Parkinson's disease (PD) is the second most progressive neurodegenerative disorder of the aging population after Alzheimer's disease (AD). Defects in the lysosomal systems and mitochondria have been suspected to cause the pathogenesis of PD. Nevertheless, the pathogenesis of PD remains obscure. Abnormal cholesterol metabolism is linked to numerous disorders, including atherosclerosis. The brain contains the highest level of cholesterol in the body and abnormal cholesterol metabolism links also many neurodegenerative disorders such as AD, PD, Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The blood brain barrier effectively prevents uptake of lipoprotein-bound cholesterol from blood circulation. Accordingly, cholesterol level in the brain is independent from that in peripheral tissues. Because cholesterol metabolism in both peripheral tissue and the brain are quite different, cholesterol metabolism associated with neurodegeneration should be examined separately from that in peripheral tissues. Here, we review and compare cholesterol metabolism in the brain and peripheral tissues. Furthermore, the relationship between alterations in cholesterol metabolism and PD pathogenesis is reviewed.

Relationship of body mass index and waist circumference with clinical outcomes following percutaneous coronary intervention.

BACKGROUND: A biphasic, U-shape relationship has been reported between body mass index (BMI) and clinical outcomes following percutaneous coronary intervention (PCI). However, the relationship between waist circumference (WC) and the cardiovascular risk following PCI has not been reported. METHODS: A prospective cohort study was performed. A major adverse cardiac event (MACE) was defined as a composite of cardiac death (CD), nonfatal myocardial infarction (NFMI) and target vessel revascularization (TVR). Patients were evenly divided into 4 groups according to BMI (Q1BMI, Q2BMI, Q3BMI and Q4BMI) and WC (Q1WC, Q2WC, Q3WC and Q4WC). RESULTS: A total of 1,421 patients were observed for 5 years. The risk of the composite events of CD and NFMI (CD/NFMI) was lower in the Q3WC and Q4WC groups than in the Q1WC group, whereas it was only marginally lower in the Q2BMI group than in the Q1BMI group (ANOVA, p = 0.062). The risk of MACE was highest in the Q1WC group and lowest in the Q3WC group; however, the risk of MACE did not differ among the 4 groups, according to BMI. Multivariate Cox-regression analyses showed that the risk of CD/NFMI gradually decreased with BMI (linear p = 0.030) and with WC (linear p = 0.015). The risks of TVR and MACEs that were driven by TVRs showed a distinguishing biphasic, U-shaped relationship with WC (nonlinear p = 0.009) but not with BMI (nonlinear p = 0.439). Landmark survival analysis showed that the incidences of CD and NFMI were higher in the lower BMI groups and lower WC groups than in the higher BMI groups and higher WC groups, respectively, until 1 year and did not differ afterward. In contrast, the incidence of MACE was highest in Q1WC and lowest in Q3WC (log-rank p = 0.003), whereas the incidence was not different among the groups according to BMI. CONCLUSIONS: Both BMI and WC were associated with a lower risk of early episodes of CD and NFMI after PCI. In the late period after PCI, WC demonstrated a biphasic, U-shaped association between cardiovascular outcomes and adiposity, whereas BMI did not.

The potential utility of iodinated contrast media (ICM) skin testing in patients with ICM hypersensitivity.

Both immediate and delayed hypersensitivity reactions to iodinated contrast media (ICM) are relatively common. However, there are few data to determine the clinical utility of immunologic evaluation of ICM. To evaluate the utility of ICM skin testing in patients with ICM hypersensitivity, 23 patients (17 immediate and 6 delayed reactions) were enrolled from 3 university hospitals in Korea. With 6 commonly used ICM including iopromide, iohexol, ioversol, iomeprol, iopamidol and iodixanol, skin prick (SPT), intradermal (IDT) and patch tests were performed. Of 10 patients with anaphylaxis, 3 (30.0%) and 6 (60.0%) were positive respectively on SPTs and IDTs with the culprit ICM. Three of 6 patients with urticaria showed positive IDTs. In total, 11 (64.7%) had positive on either SPT or IDT. Three of 6 patients with delayed rashes had positive response to patch test and/or delayed IDT. Among 5 patients (3 anaphylaxis, 1 urticaria and 1 delayed rash) taken subsequent radiological examinations, 3 patients administered safe alternatives according to the results of skin testing had no adverse reaction. However, anaphylaxis developed in the other 2 patients administered the culprit ICM again. With 64.7% (11/17) and 50% (3/6) of the sensitivities of corresponding allergic skin tests with culprit ICM for immediate and delayed hypersensitivity reactions, the present study suggests that skin tests is useful for the diagnosis of ICM hypersensitivity and for selecting safe ICM and preventing a recurrence of anaphylaxis caused by the same ICM.

Hanging-associated left ventricular systolic dysfunction.

BACKGROUNDS: Although hanging injury is infrequent, its clinical course is usually devastating. Hanging patients usually need cardiopulmonary resuscitation (CPR). However, hanging-associated cardiovascular damage has not been fully established. The aim of this study was to evaluate echocardiographic findings in patients with hanging injury. METHODS: We enrolled 25 patients (nine males and 16 females with mean age of 33±15 years) with hanging injury. Echocardiography was performed within 2 weeks after admission. Clinical, demographic, and laboratory data as well as transthoracic echocardiographic findings were analyzed. RESULTS: Of the 25 patients, eight (two males and six females with mean age of 34±13 years) showed left ventricular systolic dysfunction (LVSD). Mean LV ejection fraction was 34±16%. Global hypokinesia was present in one patient. Apical ballooning with sparing of the basal segment was present in two patients. Basal akinesia and apical hyperkinesia were present in one patient. Four patients showed regional wall motion abnormalities unmatched with coronary territories. The duration of suspension or CPR was not significantly different according to the presence of LVSD. CONCLUSION: This study showed the echocardiographic findings in considerable numbers of patients with hanging injury for the first time. Variable patterns of LVSD were present in patients with hanging injury.