Prognosis After Withdrawal of Cardioprotective Therapy in Patients With Improved Cancer Therapeutics-Related Cardiac Dysfunction.

Background: The long-term prognosis after the discontinuation of cardioprotective therapy (CPT) in patients with cancer therapeutics-related cardiac dysfunction (CTRCD) that has shown improvement remains unclear. Objectives: This study aims to assess the prognosis after CPT withdrawal in patients exhibiting improved CTRCD. Methods: In this retrospective analysis of a single-center prospective cohort study, patients with improved CTRCD, defined as an increase in left ventricular ejection fraction (LVEF) ≥10 percentage points from the time of CTRCD diagnosis, were included. We analyzed their clinical outcomes, which included hospitalization for heart failure or a decrease in LVEF ≥10 percentage points within 2 years after CTRCD improvement, alongside echocardiographic changes. Results: The cohort comprised 134 patients with improved CTRCD. The median follow-up duration after CTRCD diagnosis was 368.3 days (Q1-Q3: 160-536 days). After improvement, 90 patients continued CPT (continued group [CG]) and 44 withdrew CPT (withdrawn group [WG]). Among patients whose baseline LVEF at CTRCD diagnosis ranged from 45% to 55%, the final mean LVEF was comparable between both groups (CG: 64.9% ± 4.4% vs WG: 62.9% ± 4.2%; P = 0.059). However, for patients with a baseline LVEF <45%, the final mean LVEF was significantly lower in the WG (CG: 53.3% ± 6.4% vs WG: 48.2% ± 6.9%; P < 0.001). The occurrence of composite major clinical events was notably higher in the WG (HR: 3.06; 95% CI: 1.51-7.73; P = 0.002). Conclusions: Patients who withdrew CPT after demonstrating improvement in CTRCD experienced worse clinical outcomes. Notably, a significant decrease in LVEF was observed after CPT withdrawal in patients with a baseline LVEF <45%.

COVID-19 Vaccination-Related Pericarditis: A Korean Nationwide Study.

OBJECTIVE: To investigate the incidence, characteristics, and outcomes of COVID-19 vaccine-related pericarditis (VRP) without myocarditis, we analyzed nationwide Korean data. PATIENTS AND METHODS: This is a retrospective nationwide report including all vaccinated Koreans with COVID-19 vaccine of any platform (BNT162b2, mRNA-1273, ChAdOx1, or Ad26.COV2.S) from February 26 to December 31, 2021. We analyzed the confirmed cases of COVID-19 VRP by the Expert Adjudication Committee. The incidence, clinical characteristics, and outcomes of COVID-19 VRP were analyzed. RESULTS: Among 44,322,068 Koreans with least one dose of COVID-19 vaccination, COVID-19 VRP was confirmed in 179 cases, with 1.73 per million shots (95% CI, 1.48 to 2.00 per million shots). The incidence of VRP was significantly higher in males than females (2.01 per 1 million doses vs 1.45 per 1 million doses, respectively; P=.029), in mRNA vaccines than in other vaccines (2.09 per 1 million doses vs 0.36 per 1 million doses, respectively; P<.001), and in those younger than 40 years of age than those older than 40 years of age (3.52 per 1 million doses vs 0.89 per 1 million doses, respectively; P<.001). The incidence of VRP was highest in males between the ages of 12 and 17 years (7.38 per 1 million doses; 95% CI, 2.01 to 16.07). Although there was no case of mortality, hemodynamically significant pericardial effusion requiring pericardial drainage was noted in 10 cases (5.6%). CONCLUSION: COVID-19 VRP was very rare and developed mainly in association with mRNA vaccines, especially in males younger than 40 years of age. The clinical course of VRP was excellent, and there were no cases of mortality. However, the development of hemodynamically significant pericardial effusion should be carefully monitored.

Early menopause is associated with abnormal diastolic function and poor clinical outcomes in women with suspected angina.

Early identification of women at high risk for cardiovascular diseases (CVD), with subsequent monitoring, will allow for improved clinical outcomes and generally better quality of life. This study aimed to identify the associations between early menopause, abnormal diastolic function, and clinical outcomes. This retrospective study included 795 menopausal women from is a nationwide, multicenter, registry of patients with suspected angina visiting outpatient clinic. The patients into two groups: early and normal menopause (menopausal age ≤ 45 and > 45 years, respectively). If participants met > 50% of the diastolic function criteria, they were classified as having normal diastolic function. Multivariable-adjusted Cox models were used to test associations between menopausal age and clinical outcomes including the incidence of major adverse cardiovascular events (MACE), over a median follow-up period of 771 days. Early menopause was associated with increased waist circumference (p = 0.001), diabetes prevalence (p = 0.003), obstructive coronary artery disease (p = 0.005), abnormal diastolic function (p = 0.003) and greater incidences of MACE, acute coronary syndrome, and hospitalization for heart failure. In patients with abnormal diastolic function, early menopause increased MACE risk significantly, with no significant difference in normal diastolic function. These findings highlight early menopause and abnormal diastolic function as being potential risk markers in women for midlife CVD events.

Differences in coronary angiographic findings and outcomes between men and postmenopausal women with stable chest pain.

BACKGROUND: Despite the significant increase in cardiovascular events in women after menopause, studies comparing postmenopausal women and men are scarce. METHODS: We analyzed data from a nationwide, multicenter, prospective registry and enrolled 2412 patients with stable chest pain who underwent elective coronary angiography. Binary coronary artery disease (b-CAD) was defined as the ≥50% stenosis of epicardial coronary arteries, including the left main coronary artery. RESULTS: Compared with the men, postmenopausal women were older (66.6 ±â€…8.5 vs. 59.5 ±â€…11.4 years) and had higher high-density lipoprotein cholesterol levels (49.0 ±â€…12.8 vs. 43.6 ±â€…11.6 mg/dl, P  < 0.01). The prevalence of diabetes did not differ significantly ( P  = 0.40), and smoking was more common in men than in postmenopausal women ( P  ≤ 0.01). At enrollment, b-CAD and revascularization were more common in men than in postmenopausal women (50.3% vs. 41.0% and 14.4% vs. 9.7%, respectively; both P  < 0.01). However, multivariate analyses revealed that revascularization [odds ratio (OR): 0.72; 95% confidence interval (CI): 0.49-1.08] was not significantly related to sex and a similar result was found in age propensity-matched population (OR: 0.80; 95% CI: 0.52-1.24). During the follow-up period, the secondary composite cardiovascular outcomes were lower in postmenopausal women than in men (OR: 0.55; 95% CI: 0.31-0.98), also consistent with the result using the age propensity-mated population (OR: 0.33; 95% CI: 0.13-0.85). CONCLUSION: Postmenopausal women experienced coronary revascularization comparable to those in men at enrollment, despite the average age of postmenopausal women was 7 years older than that of men.Postmenopausal women exhibit better clinical outcomes than those of men if optimal treatment is provided.

Temporal Changes in Demography and Genetic Diversity of Oriental Storks at the Stage of Long-Term Captive Propagation and Reintroduction Initiation.

Captive propagation and reintroduction are the major steps in the ex-situ conservation of locally extirpated endangered species in a historical region. In a species restoration project conducted in South Korea, we examined temporal changes in demographics and genetic diversity of oriental storks (Ciconia boyciana). Demographic and genetic data from 1996-2018 were analyzed for 80% of all captive and recently reintroduced individuals. Founder establishment and pair formation induced increases in population size and genetic diversity during the early stage of captive propagation. The degree of genetic diversity was found to become saturated and stable with long-term captive propagation. However, this might be a concern for future genetic diversity of both captive and reintroduced populations simultaneously due to the extraction of captive populations at the early stage of reintroduction. Our findings suggest that periodic evaluation of genetic diversity and selection for releasing individuals, using effective genetic markers, would assist in balancing the genetic diversity of the captive and reintroduced oriental storks at the early stage of reintroduction.

Timing of heart failure development and clinical outcomes in patients with acute myocardial infarction.

Background and objectives: To investigate the clinical relevance of the timing of heart failure (HF) development on long-term outcome in patients with acute myocardial infarction (AMI). Materials and methods: A total of 1,925 consecutive AMI patients were divided into 4 groups according to the timing of HF development; HF at admission (group I, n = 627), de novo HF during hospitalization (group II, n = 162), de novo HF after discharge (group III, n = 98), no HF (group IV, n = 1,038). Major adverse cardiac events (MACE) defined as the development of death, re-hospitalization, recurrent MI or revascularization were evaluated. Results: HF was developed in 887 patients (46.1%) after an index AMI. HF was most common at the time of admission for AMI, but the development of de novo HF during hospitalization or after discharge was not uncommon. MACE was developed in 619 out of 1,925 AMI patients (31.7%). MACE was highest in group I, lowest in group IV, and significantly different among groups; 275 out of 627 patients (43.9%) in group I, 64 out of 192 patients (39.5%) in group II, 36 out of 98 patients (36.7%) in group III, and 235 out of 1,038 patients (22.6%) in group IV (P < 0.001). MACE free survival rates at 3 years were 56% in group I, 62% in group II, 64% in group III, and 77% in group IV (P < 0.001). Conclusions: HF was not uncommon and can develop at any time after an index AMI, and the development of HF was associated with poor prognosis. The earlier the HF has occurred after AMI, the poorer the clinical outcome was. To initiate the guideline directed optimal medical therapy, therefore, the development of HF should be carefully monitored even after the discharge from an index AMI.

Association between the number of pregnancies and cardiac target organ damages: a cross-sectional analysis of data from the Korean women's chest pain registry (KoROSE).

BACKGROUND: Pregnancy increases long-term cardiovascular risk after childbirth, but the mechanisms are unclear. This study was performed to investigate the association between the number of pregnancies and several cardiac target organ damage (TOD) in middle-aged and elderly women. METHODS: Using the database of the nation-wide registry, a total of 1,137 women (mean age 63.0 ± 10.9 years) with stable chest pain undergoing invasive coronary angiography (CAG) were analyzed. Information on the number of pregnancies was obtained through a questionnaire. Obstructive coronary artery disease (CAD), left ventricular (LV) mass index (LVMI) and LV septal annular (e') velocity were assessed as indicators of cardiac TOD. RESULTS: Women with higher number of pregnancies (≥ 3) were older (66.3 ± 9.6 vs. 57.4 ± 10.7 years; P < 0.001), had more cardiovascular risk factors, and took more cardiovascular medications than those with lower number of pregnancies (< 3). In multivariable analyses, higher number of pregnancies (≥ 3) was associated with obstructive CAD (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.21-2.17; P = 0.001), a higher LVMI (> 95 g/m2) (OR, 1.46; 95% CI, 1.08-1.98; P = 0.013) and a lower septal e' velocity (< 7 cm/s) (OR, 1.55; 95% CI, 1.12-2.14; P = 0.007) even after controlling for potential confounders. As the number of pregnancies increased, the prevalence of CAD and LVMI increased, and the septal e' velocity gradually decreased (P < 0.001 for each). CONCLUSIONS: In women with chest pain undergoing invasive CAG, higher number of pregnancies was associated with multiple cardiac TOD. Parity information should be checked when assessing a woman's cardiovascular risk.

COVID-19 vaccination-related myocarditis: a Korean nationwide study.

AIMS: A comprehensive nationwide study on the incidence and outcomes of COVID-19 vaccination-related myocarditis (VRM) is in need. METHODS AND RESULTS: Among 44 276 704 individuals with at least 1 dose of COVID-19 vaccination, the incidence and clinical courses of VRM cases confirmed by the Expert Adjudication Committee of the Korea Disease Control and Prevention Agency were analyzed. COVID-19 VRM was confirmed in 480 cases (1.08 cases per 100 000 persons). Vaccination-related myocarditis incidence was significantly higher in men than in women (1.35 vs. 0.82 per 100 000 persons, P < 0.001) and in mRNA vaccines than in other vaccines (1.46 vs. 0.14 per 100 000 persons, P < 0.001). Vaccination-related myocarditis incidence was highest in males between the ages of 12 and 17 years (5.29 cases per 100 000 persons) and lowest in females over 70 years (0.16 cases per 100 000 persons). Severe VRM was identified in 95 cases (19.8% of total VRM, 0.22 per 100 000 vaccinated persons), 85 intensive care unit admission (17.7%), 36 fulminant myocarditis (7.5%), 21 extracorporeal membrane oxygenation therapy (4.4%), 21 deaths (4.4%), and 1 heart transplantation (0.2%). Eight out of 21 deaths were sudden cardiac death (SCD) attributable to VRM proved by an autopsy, and all cases of SCD attributable to VRM were aged under 45 years and received mRNA vaccines. CONCLUSION: Although COVID-19 VRM was rare and showed relatively favorable clinical courses, severe VRM was found in 19.8% of all VRM cases. Moreover, SCD should be closely monitored as a potentially fatal complication of COVID-19 vaccination.

Sex-Specific Predictors of Long-Term Mortality in Elderly Patients with Ischemic Cardiomyopathy.

Ischemic heart failure (HF) is one of the most common causes of morbidity and mortality in the world-wide, but sex-specific predictors of mortality in elderly patients with ischemic cardiomyopathy (ICMP) have been poorly studied. A total of 536 patients with ICMP over 65 years-old (77.8 ± 7.1 years, 283 males) were followed for a mean of 5.4 years. The development of death during clinical follow up was evaluated, and predictors of mortality were compared. Death was developed in 137 patients (25.6%); 64 females (25.3%) vs. 73 males (25.8%). Low-ejection fraction was only an independent predictor of mortality in ICMP, regardless of sex (HR 3.070 CI = 1.708-5.520 in female, HR 2.011, CI = 1.146-3.527 in male). Diabetes (HR 1.811, CI = 1.016-3.229), elevated e/e' (HR 2.479, CI = 1.201-5.117), elevated pulmonary artery systolic pressure (HR 2.833, CI = 1.197-6.704), anemia (HR 1.860, CI = 1.025-3.373), beta blocker non-use (HR2.148, CI = 1.010-4.568), and angiotensin receptor blocker non-use (HR 2.100, CI = 1.137-3.881) were bad prognostic factors of long term mortality in female, whereas hypertension (HR 1.770, CI = 1.024-3.058), elevated Creatinine (HR 2.188, CI = 1.225-3.908), and statin non-use (HR 3.475, CI = 1.989-6.071) were predictors of mortality in males with ICMP independently. Systolic dysfunction in both sexes, diastolic dysfunction, beta blocker and angiotensin receptor blockers in female, and statins in males have important roles for long-term mortality in elderly patients with ICMP. For improving long-term survival in elderly patients with ICMP, it may be necessary to approach sex specifically.

Predictors of Progression of Tricuspid Regurgitation in Patients with Persistent Atrial Fibrillation.

Previous studies have shown that tricuspid regurgitation (TR) can be developed in patients with atrial fibrillation (AF) due to annular dilatation. This study aimed to investigate the incidence and predictors of the progression of TR in patients with persistent AF. A total of 397 patients (66.9±11.4 years, 247 men; 62.2%) with persistent AF were enrolled between 2006 and 2016 in a tertiary hospital, and 287 eligible patients with follow-up echocardiography were analyzed. They were divided into two groups according to TR progression (progression group [n=68, 70.1±10.7 years, 48.5% men] vs. non-progression group [n=219, 66.0±11.3 years, 64.8% men]). Among 287 patients in the analysis, 68 had worsening TR severity (23.7%). Patients in the TR progression group were older and more likely to be female. Patients with left ventricular ejection fraction <50% were less frequent in the progression group than those in the non-progression group (7.4% vs. 19.6%, p=0.018). Patients with mitral valve disease were more frequent in the progression group. Multivariate analysis with COX regression demonstrated independent predictors of TR progression, including left atrial (LA) diameter >54 mm (HR 4.85, 95%CI 2.23-10.57, p<0.001), E/e' (HR 1.05, 95%CI 1.01-1.10, p=0.027), and no use of antiarrhythmic agents (HR 2.20, 95%CI 1.03-4.72, p=0.041). In patients with persistent AF, worsening TR was not uncommon. The independent predictors of TR progression turned out to be greater LA diameter, higher E/e', and no use of antiarrhythmic agents.

WNK3 inhibition elicits antitumor immunity by suppressing PD-L1 expression on tumor cells and activating T-cell function.

Immune checkpoint therapies, such as programmed cell death ligand 1 (PD-L1) blockade, have shown remarkable clinical benefit in many cancers by restoring the function of exhausted T cells. Hence, the identification of novel PD-L1 regulators and the development of their inhibition strategies have significant therapeutic advantages. Here, we conducted pooled shRNA screening to identify regulators of membrane PD-L1 levels in lung cancer cells targeting druggable genes and cancer drivers. We identified WNK lysine deficient protein kinase 3 (WNK3) as a novel positive regulator of PD-L1 expression. The kinase-dead WNK3 mutant failed to elevate PD-L1 levels, indicating the involvement of its kinase domain in this function. WNK3 perturbation increased cancer cell death in cancer cell-immune cell coculture conditions and boosted the secretion of cytokines and cytolytic enzymes, promoting antitumor activities in CD4+ and CD8+ T cells. WNK463, a pan-WNK inhibitor, enhanced CD8+ T-cell-mediated antitumor activity and suppressed tumor growth as a monotherapy as well as in combination with a low-dose anti-PD-1 antibody in the MC38 syngeneic mouse model. Furthermore, we demonstrated that the c-JUN N-terminal kinase (JNK)/c-JUN pathway underlies WNK3-mediated transcriptional regulation of PD-L1. Our findings highlight that WNK3 inhibition might serve as a potential therapeutic strategy for cancer immunotherapy through its concurrent impact on cancer cells and immune cells.

A Case Report for Acute Myopericarditis After NVX-CoV2373 (Novavax®) COVID-19 Vaccination.

Post-vaccination myocarditis after administration of the NVX-CoV2373 coronavirus disease 2019 (COVID-19) vaccine has been reported in a limited population. We report the first biopsy-proven case of myopericarditis after administration of second dose of NVX-CoV2373 COVID-19 vaccine (Novavax®) in Korea. A 30-year-old man was referred to emergency department with complaints of chest pain and mild febrile sense for two days. He received the second dose vaccine 17 days ago. Acute myopericarditis by the vaccination was diagnosed by cardiac endomyocardial biopsy. He was treated with corticosteroid 1 mg/kg/day for 5 days and tapered for one week. He successfully recovered and was discharged on the 12th day of hospitalization. The present case suggests acute myopericarditis as a vaccination complication by Novavax® in Korea.

Snail acetylation by autophagy-derived acetyl-coenzyme A promotes invasion and metastasis of KRAS-LKB1 co-mutated lung cancer cells.

BACKGROUND: Autophagy is elevated in metastatic tumors and is often associated with active epithelial-to-mesenchymal transition (EMT). However, the extent to which EMT is dependent on autophagy is largely unknown. This study aimed to identify the mechanisms by which autophagy facilitates EMT. METHODS: We employed a liquid chromatography-based metabolomic approach with kirsten rat sarcoma viral oncogene (KRAS) and liver kinase B1 (LKB1) gene co-mutated (KL) cells that represent an autophagy/EMT-coactivated invasive lung cancer subtype for the identification of metabolites linked to autophagy-driven EMT activation. Molecular mechanisms of autophagy-driven EMT activation were further investigated by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting analysis, immunoprecipitation, immunofluorescence staining, and metabolite assays. The effects of chemical and genetic perturbations on autophagic flux were assessed by two orthogonal approaches: microtubule-associated protein 1A/1B-light chain 3 (LC3) turnover analysis by Western blotting and monomeric red fluorescent protein-green fluorescent protein (mRFP-GFP)-LC3 tandem fluorescent protein quenching assay. Transcription factor EB (TFEB) activity was measured by coordinated lysosomal expression and regulation (CLEAR) motif-driven luciferase reporter assay. Experimental metastasis (tail vein injection) mouse models were used to evaluate the impact of calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) or ATP citrate lyase (ACLY) inhibitors on lung metastasis using IVIS luciferase imaging system. RESULTS: We found that autophagy in KL cancer cells increased acetyl-coenzyme A (acetyl-CoA), which facilitated the acetylation and stabilization of the EMT-inducing transcription factor Snail. The autophagy/acetyl-CoA/acetyl-Snail axis was further validated in tumor tissues and in autophagy-activated pancreatic cancer cells. TFEB acetylation in KL cancer cells sustained pro-metastatic autophagy in a mammalian target of rapamycin complex 1 (mTORC1)-independent manner. Pharmacological inhibition of this axis via CAMKK2 inhibitors or ACLY inhibitors consistently reduced the metastatic capacity of KL cancer cells in vivo. CONCLUSIONS: This study demonstrates that autophagy-derived acetyl-CoA promotes Snail acetylation and thereby facilitates invasion and metastasis of KRAS-LKB1 co-mutated lung cancer cells and that inhibition of the autophagy/acetyl-CoA/acetyl-Snail axis using CAMKK2 or ACLY inhibitors could be a potential therapeutic strategy to suppress metastasis of KL lung cancer.

Awareness of cardiovascular disease among Korean women: Results from a nationwide survey.

Women underestimate the risk of cardiovascular disease (CVD). It is essential to assess and raise awareness regarding CVD among women to reduce disease burden and mortality. Therefore, we investigated the awareness regarding CVD among Korean women. We conducted a nationwide survey between December 2020 and January 2021 among a representative sample of Korean women using random-digit-dialing telephonic interviews. We sought information regarding the awareness of CVD risk; recognition of symptoms and signs; and knowledge of the cause and prevention of and appropriate response to CVD. A total of 1,050 women (mean age, 60.2 ± 11.9 years) participated in the study. Approximately 52.0% of participants were unaware of CVD, and only 26% of participants had heard of CVD. Participants considered that compared to other diseases, CVD was not an important health issue for women, and few of them thought that cerebrovascular diseases and CVD were the leading causes of death (10.9% and 7.6%, respectively). After adjustment for possible confounding factors, age >70 years, rural residence, and educational attainment below college were independently associated with a lack of awareness regarding CVD. The awareness regarding CVD being the leading cause of death in women is low, and most women do not consider it an important health issue. Therefore, special attention must be paid to educate the public regarding CVD in women.

A Prospective Randomized, Double-Blind, Multi-Center, Phase III Clinical Trial Evaluating the Efficacy and Safety of Olmesartan/Amlodipine plus Rosuvastatin Combination Treatment in Patients with Concomitant Hypertension and Dyslipidemia: A LEISURE Study.

BACKGROUND: This study was a multicenter, randomized, double-blinded, placebo-controlled phase III clinical trial to investigate the efficacy and safety of an olmesartan/amlodipine single pill plus rosuvastatin combination treatment for patients with concomitant hypertension and dyslipidemia. METHODS: Patients with both hypertension and dyslipidemia aged 20-80 were enrolled from 36 tertiary hospitals in Korea from January 2017 to April 2018. Patients were randomized to three groups in a 1:1:0.5 ratio, olmesartan/amlodipine single pill plus rosuvastatin (olme/amlo/rosu) or olmesartan plus rosuvastatin (olme/rosu) or olmesartan/amlodipine single pill (olme/amlo) combination. The primary endpoints were change of sitting systolic blood pressure (sitSBP) from baseline in the olme/amlo/rosu vs. olme/rosu groups and the percentage change of low-density lipoprotein cholesterol (LDL-C) from baseline in the olme/amlo/rosu vs. olme/amlo groups after 8 weeks of treatment. RESULTS: A total of 265 patients were randomized, 106 to olme/amlo/rosu, 106 to olme/rosu and 53 to olme/amlo groups. Baseline characteristics among the three groups did not differ. The mean sitSBP change was significantly larger in the olme/amlo/rosu group with -24.30 ± 12.62 mmHg (from 153.58 ± 10.90 to 129.28 ± 13.58) as compared to the olme/rosu group, -9.72 ± 16.27 mmHg (from 153.71 ± 11.10 to 144.00 ± 18.44 mmHg). The difference in change of sitSBP between the two groups was -14.62± 1.98 mmHg with significance (95% CI -18.51 to -10.73, p < 0.0001). The mean LDL-C reduced significantly in the olme/amlo/rosu group, -52.31 ± 16.63% (from 154.52 ± 30.84 to 72.72 ± 26.08 mg/dL) as compared to the olme/amlo group with no change, -2.98 ± 16.16% (from 160.42 ± 32.05 to 153.81 ± 31.57 mg/dL). Significant difference in change was found in LDL-C between the two groups with -50.10 ± 2.73% (95% CI -55.49 to -44.71, p < 0.0001). Total adverse drug reaction rates were 10.48%, 5.66% and 3.7% in the olme/amlo/rosu, olme/rosu and olme/amlo groups, respectively with no statistical significance among the three groups. Serious adverse drug reactions did not occur. CONCLUSIONS: Olmesartan/amlodipine single pill plus rosuvastatin combination treatment for patients with both hypertension and dyslipidemia is effective and safe as compared to either olmesartan plus rosuvastatin or olmesartan plus amlodipine treatment.

Sex differences in coronary angiographic findings in patients with stable chest pain: analysis of data from the KoRean wOmen'S chest pain rEgistry (KoROSE).

BACKGROUND: Focused evaluations on potential sex differences in the angiographic findings of the coronary arteries are scarce. This study was performed to compare the angiographic extent and localization of coronary stenosis between men and women. METHODS: A total of 2348 patients (mean age 62.5 years and 60% women) with stable chest pain undergoing invasive coronary angiography (CAG) were recruited from the database of the nation-wide chest pain registry. Obstructive coronary artery disease (CAD) was defined as ≥ 50% stenosis of the left main coronary artery and/or ≥ 70% stenosis of any other epicardial coronary arteries. RESULTS: Although women were older than men (64.4 ± 10.3 vs. 59.5 ± 11.4 years, P < 0.001), men had worse risk profiles including high blood pressure, more frequent smoking and elevated triglyceride and C-reactive protein. The prevalence of obstructive CAD was significantly higher in men than in women (37.0% vs. 28.4%, P < 0.001). Men had a higher prevalence of LM disease (10.3% vs. 3.5%, P < 0.001) and three-vessel disease (16.1% vs. 9.5%, P = 0.007) compared to women. In multiple binary logistic regression analysis, the risk of men having LM disease or three-vessel disease was 7.4 (95% confidence interval 3.48-15.97; P < 0.001) and 2.7 (95% confidence interval 1.57-4.64; P < 0.001) times that of women, respectively, even after controlling for potential confounders. CONCLUSIONS: In patients with chest pain undergoing invasive CAG, men had higher obstructive CAD prevalence and more high-risk angiographic findings such as LM disease or three-vessel disease.

Characteristics and Clinical Outcomes of Cancer Patients who Developed Constrictive Physiology After Pericardiocentesis.

BACKGROUND AND OBJECTIVES: This study aimed to identify the characteristics and clinical outcomes of cancer patients who developed constrictive physiology (CP) after percutaneous pericardiocentesis. METHODS: One-hundred thirty-three cancer patients who underwent pericardiocentesis were divided into 2 groups according to follow-up echocardiography (CP vs. non-CP). The clinical history, imaging findings, and laboratory results, and overall survival were compared. RESULTS: CP developed in 49 (36.8%) patients after pericardiocentesis. The CP group had a more frequent history of radiation therapy. Pericardial enhancement and malignant masses abutting the pericardium were more frequently observed in the CP group. Fever and ST segment elevation were more frequent in the CP group, with higher C-reactive protein levels (6.6±4.3mg/dL vs. 3.3±2.5mg/dL, p<0.001). Pericardial fluid leukocytes counts were significantly higher, and positive cytology was more frequent in the CP group. In baseline echocardiography before pericardiocentesis, medial e' velocity was significantly higher in the CP group (8.6±2.1cm/s vs. 6.5±2.3cm/s, p<0.001), and respirophasic ventricular septal shift, prominent expiratory hepatic venous flow reversal, pericardial adhesion, and loculated pericardial fluid were also more frequent. The risk of all-cause death was significantly high in the CP group (hazard ratio, 1.53; 95% confidence interval,1.10-2.13; p=0.005). CONCLUSIONS: CP frequently develops after pericardiocentesis, and it is associated with poor survival in cancer patients. Several clinical signs, imaging, and laboratory findings suggestive of pericardial inflammation and/or direct malignant pericardial invasion are frequently observed and could be used as predictors of CP development.

Post-operative Atrial Fibrillation Impacts on Outcomes in Transcatheter and Surgical Aortic Valve Replacement.

Background: Atrial fibrillation (AF) in severe aortic stenosis (AS) has poor outcomes after transcatheter and surgical aortic valve replacement (TAVR and SAVR, respectively). We compared the incidence of AF after aortic valve replacement (AVR) according to the treatment method and the impact of AF on outcomes. Methods: We investigated the incidence of AF and clinical outcomes of AVR according to whether AF occurred after TAVR and SAVR after propensity score (PS)-matching for 1 year follow-up. Clinical outcomes were defined as death, stroke, and admission due to heart failure. The composite outcome comprised death, stroke, and admission due to heart failure. Results: A total of 221 patients with severe AS were enrolled consecutively, 100 of whom underwent TAVR and 121 underwent SAVR. The incidence of newly detected AF was significantly higher in the SAVR group before PS-matching (6.0 vs. 40.5%, P < 0.001) and after PS-matching (7.5 vs. 35.6%, P = 0.001). TAVR and SAVR showed no significant differences in outcomes except in terms of stroke. In the TAVR group, AF history did not affect the outcomes; however, in the SAVR group, AF history affected death (log rank P = 0.038). Post-AVR AF had a worse impact on admission due to heart failure (log rank P = 0.049) and composite outcomes in the SAVR group. Post-AVR AF had a worse impact on admission due to heart failure (log rank P = 0.008) and composite outcome in the TAVR group. Conclusion: Post-AVR AF could be considered as a predictor of the outcomes of AVR. TAVR might be a favorable treatment option for patients with severe symptomatic AS who are at high-risk for AF development or who have a history of AF because the occurrence of AF was more frequent in the SAVR group.

Usefulness of Diastolic Function Score as a Predictor of Long-Term Prognosis in Patients With Acute Myocardial Infarction.

Background: Left ventricular diastolic function (LVDF) evaluation using a combination of several echocardiographic parameters is an important predictor of adverse events in patients with acute myocardial infarction (AMI). To date, the clinical impact of each individual LVDF marker is well-known, but the clinical significance of the sum of the abnormal diastolic function markers and the long-term clinical outcome are not well-known. This study aimed to investigate the usefulness of LVDF score in predicting clinical outcomes of patients with AMI. Methods: LVDF scores were measured in a 2,030 patients with AMI who underwent successful percutaneous coronary intervention from 2012 to 2015. Four LVDF parameters (septal e' ≥ 7 cm/s, septal E/e' ≤ 15, TR velocity ≤ 2.8 m/s, and LAVI ≤ 34 ml/m2) were used for LVDF scoring. The presence of each abnormal LVDF parameter was scored as 1, and the total LVDF score ranged from 0 to 4. Mortality and hospitalization due to heart failure (HHF) in relation to LVDF score were evaluated. To compare the predictive ability of LVDF scores and left ventricular ejection fraction (LVEF) for mortality and HHF, receiver operating characteristic (ROC) curve and landmark analyses were performed. Results: Over the 3-year clinical follow-up, all-cause mortality occurred in 278 patients (13.7%), while 91 patients (4.5%) developed HHF. All-cause mortality and HHF significantly increased as LVDF scores increased (all-cause mortality-LVDF score 0: 2.3%, score 1: 8.8%, score 2: 16.7%, score 3: 31.8%, and score 4: 44.5%, p < 0.001; HHF-LVDF score 0: 0.6%, score 1: 1.8%, score 2: 6.3%, score 3: 10.3%, and score 4: 18.2%, p < 0.001). In multivariate analysis, a higher LVDF score was associated with significantly higher adjusted hazard ratios for all-cause mortality and HHF. In landmark analysis, LVDF score was a better predictor of long-term mortality than LVEF (area under the ROC curve: 0.739 vs. 0.640, p < 0.001). Conclusion: The present study demonstrated that LVDF score was a significant predictor of mortality and HHF in patients with AMI. LVDF scores are useful for risk stratification of patients with AMI; therefore, careful monitoring and management should be performed for patients with AMI with higher LVDF scores.

Incremental value of QT interval for the prediction of obstructive coronary artery disease in patients with chest pain.

Identification of obstructive coronary artery disease (OCAD) in patients with chest pain is a clinical challenge. The value of corrected QT interval (QTc) for the prediction of OCAD has yet to be established. We consecutively enrolled 1741 patients with suspected angina. The presence of obstructive OCAD was defined as ≥ 50% diameter stenosis by coronary angiography. The pre-test probability was evaluated by combining QTc prolongation with the CAD Consortium clinical score (CAD2) and the updated Diamond-Forrester (UDF) score. OCAD was detected in 661 patients (38.0%). QTc was longer in patients with OCAD compared with those without OCAD (444 ± 34 vs. 429 ± 28 ms, p < 0.001). QTc was increased by the severity of OCAD (P < 0.001). QTc prolongation was associated with OCAD (odds ratio (OR), 2.27; 95% confidence interval (CI), 1.81-2.85). With QTc, the C-statistics increased significantly from 0.68 (95% CI 0.66-0.71) to 0.76 (95% CI 0.74-0.78) in the CAD2 and from 0.64 (95% CI 0.62-0.67) to 0.74 (95% CI 0.72-0.77) in the UDF score, respectively. QT prolongation predicted the presence of OCAD and the QTc improved model performance to predict OCAD compared with CAD2 or UDF scores in patients with suspected angina.