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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.

ObjectsThe purpose was to determine whether the epicardial adipose tissue (EAT) area on low-dose chest CT (LDCT) could be used to predict coronary atherosclerosis in an asymptomatic population considered for lung cancer screening.MethodsSubjects aged 55-80 years with smoking history who underwent both LDCT and coronary CT angiography (CCTA) were retrospectively enrolled. Correlation between the EAT volume in CCTA and EAT area in LDCT was evaluated. Coronary risk factors including the body surface area (BSA) indexed EAT area were compared between coronary plaque negative and positive groups. Significant factors for predicting coronary atherosclerosis were analyzed with logistic regression analysis. Receiver-operating characteristic curve analysis was performed to determine the cutoff value.ResultsA total of 438 subjects were enrolled, including 299 subjects with coronary atherosclerosis. There was a good correlation between the EAT volume in CCTA and EAT area in LDCT (ρ = 0.712, p < 0.001). There were significant differences in age, systolic blood pressure, all BSA indexed EAT area, sex, and hypertension between plaque negative and positive groups. In multivariate logistic regression for the BSA indexed EAT area in LDCT at the RCA level, sex (OR: 11.168, 95% CI: 2.107-59.201, p = 0.005), systolic blood pressure (OR: 1.021, 95% CI: 1.005-1.036, p = 0.009), hypertension (OR: 1.723, 95% CI: 1.103-2.753, p = 0.017), and EAT area (OR: 1.273, 95% CI: 1.154-1.405, p < 0.001) were significant. The area under the curve of the BSA indexed EAT area in LDCT at the RCA level for coronary atherosclerosis was 0.657, and the cut-off value was 7.66 cm2/m2.ConclusionThe EAT area in LDCT could be used to predict coronary atherosclerosis in an asymptomatic population considered for lung cancer screening.Key Points• To quantify EAT, the EAT area in LDCT can be used instead of the EAT volume in CCTA.• The EAT area measured in LDCT can be used as a predictor of coronary artery disease.• The extensive CAD group tended to have a greater EAT area than the non-extensive CAD group.

Although potent P2Y12 inhibitor-based dual antiplatelet therapy (DAPT) has replaced clopidogrel-based therapy as the standard treatment in patients with acute myocardial infarction (AMI), there is a concern about the risk of bleeding in East Asian patients. We compared the efficacy and safety of cilostazol-based triple antiplatelet therapy (TAT) with potent P2Y12 inhibitor-based DAPT in Korean patients. A total of 4152 AMI patients who underwent percutaneous coronary intervention (PCI) in the Korea Acute Myocardial Infarction Registry were analyzed retrospectively. Patients were divided into two groups: the TAT group (aspirin + clopidogrel + cilostazol, n  = 3161) and the potent DAPT group (aspirin + potent P2Y12 inhibitors [ticagrelor or prasugrel], n  = 991). Major clinical outcomes at 30 days and 2 years were compared between the two groups using propensity score matching (PSM) analysis. After PSM (869 pairs), there were no significant differences between the two groups in the incidence of total death, cardiac death, myocardial infarction (MI), target vessel revascularization, stent thrombosis, and stroke at 30 days and 2 years. However, the Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding rates were significantly lower in the TAT group compared with the potent DAPT group at 2 years (6.4% vs. 3.6%, p  = 0.006). In Korean AMI patients undergoing PCI, TAT with cilostazol was associated with lower bleeding than the potent P2Y12 inhibitor-based DAPT without increased ischemic risk. These results could provide a rationale for the use of TAT in East Asian AMI patients.

To investigate whether specific time series patterns for blood pressure (BP), heart rate (HR), and sympathetic tone are associated with metabolic factors and the 10-year risk of atherosclerotic cardiovascular disease (ASCVD). A total of 989 patients who underwent simultaneous 24-hour ambulatory BP and Holter electrocardiogram monitoring were enrolled. The patients were categorized into sixteen groups according to their circadian patterns using the consensus clustering analysis method. Metabolic factors, including cholesterol profiles and apolipoprotein, were compared. The 10-year ASCVD risk was estimated based on the Framingham risk model. Overall, 16 significant associations were found between the clinical variables and cluster groups. Age was commonly associated with all clusters in systolic BP (SBP), diastolic BP (DBP), HR, and sympathetic tone. Metabolic indicators, including diabetes, body mass index, total cholesterol, high-density lipoprotein, and apolipoprotein, were associated with the four sympathetic tone clusters. In the crude analysis, the ASCVD risk increased incrementally from clusters 1 to 4 across SBP, DBP, HR, and sympathetic tone. After adjustment for multiple variables, however, only sympathetic tone clusters 3 and 4 showed a significantly high proportion of patients at high risk (≥7.5%) of 10-year ASCVD (odds ratio OR=5.90, 95% confidential interval CI=1.27–27.46, and P value = 0.024 and OR=15.28, 95% CI=3.59–65.11, and P value < 0.001, respectively). Time series patterns of BP, HR, and sympathetic tone can serve as an indicator of aging. Circadian variations in sympathetic tone can provide prognostic information about patient metabolic profiles and indicate future ASCVD risk.

The phase angle (PhA) in bioelectrical impedance analysis (BIA) reflects the cell membrane integrity or body fluid equilibrium. We examined how the PhA aligns with previously known markers of acute heart failure (HF) and assessed its value as a screening tool. PhA was measured in 50 patients with HF and 20 non-HF controls along with the edema index (EI), another BIA parameter suggestive of edema. Chest computed tomography-measured lung fluid content (LFC) was used to assess pulmonary congestion. A correlation analysis was conducted to evaluate the relationships between PhA and EI, NT-proBNP, and LFC. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-off values for PhA and EI for classifying patients with HF. The area under the curve (AUC) was compared using the DeLong test to evaluate the performance of PhA and EI compared to that of LFC in correctly classifying HF. The PhA levels were significantly lower in the HF group. Whole-body PhA was 4.49° in the HF group and 5.68° in the control group. Moderate and significant correlation was observed between PhA measured at 50-kHz and both NT-proBNP (-0.56 to -0.27, all p-values<0.05) and LFC (-0.52 to -0.41, all p-values <0.05). The AUC for whole-body PhA was 0.827 (confidence interval [CI] 0.724-0.931, p<0.01) and was 0.883 (CI 0.806-0.961, p<0.01) for EI, and the optimal cutoffs were estimated as 5° (sensitivity 0.84, specificity 0.80) and 0.394 (sensitivity 0.78, specificity 0.95), respectively. When both PhA and EI were included in the model, the AUC increased to 0.905, and this was comparable to that of LFC (AUC = 0.913, p = 0.857). PhA exhibited a correlation with known markers of HF and demonstrated its potential as a non-invasive screening tool for the early detection of HF exacerbation. The combined use of PhA and EI can provide a robust alternative for routine self-monitoring in patients with HF, thereby enhancing early intervention.

•IRB/AML fixed-dose regimens show superior antihypertensive efficacy over IRB monotherapy.•A potential benefit of IRB/AML regimens was noted in the elderly and T2DM patients.•IRB/AML combinations are well-tolerated and have comparable safety to IRB monotherapy. This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy. Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP [MSSBP] ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography. In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were −14.78 (12.35) mmHg, −21.47 (12.78) mmHg, and −8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were −13.30 (12.47) mmHg and −7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study. The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability. ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).

Statin is crucial for acute myocardial infarction (AMI) patients. However, the risk of new-onset diabetes mellitus (NODM) associated with statin is a concern. This study aimed to determine the incremental diabetogenic effects of statins according to their intensity and dose in AMI patients undergoing percutaneous coronary intervention (PCI). Among 13,104 patients enrolled in the Korea AMI Registry between 2011 and 2015, 6152 patients without diabetes mellitus (DM) who underwent PCI and received moderate-to-high-intensity atorvastatin and rosuvastatin were selected for the study. The endpoints were NODM and major adverse cardiovascular events (MACE), composite of all-cause mortality, recurrent MI, and revascularization up to 3 years. Among the participants, 3747 and 2405 received moderate- and high-intensity statins, respectively. The Kaplan–Meier curves demonstrated a higher incidence of NODM in patients with high-intensity statins than those with moderate-intensity. High-intensity statin was a significant predictor of NODM after adjusting for other co-variables (HR = 1.316, 95% CI 1.024–1.692; P < 0.032). Higher dose of rosuvastatin was associated with a higher cumulative incidence of NODM, but this dose-dependency was not apparent with atorvastatin. Cumulative incidence of MACE decreased dose-dependently only with atorvastatin. High-intensity statin was associated with a higher cumulative incidence of NODM in AMI patients, and this association was more evident in rosuvastatin. The different diabetogenic effects of the two statins provide supporting evidence for understanding the nuanced nature of statin treatment in relation to NODM.

The six-minute walk test (6MWT) is a convenient method for evaluating functional capacity in daily living. We evaluated the prognostic value of the 6MWT in patients with cardiovascular disease to predict the incidence of MACE. Patients with prevalent cardiovascular diseases were enrolled in the cardiac rehabilitation registry. 6MWT was measured at baseline, and incidences of all-cause death, coronary intervention, admission due to heart failure, and stroke were monitored. Odds ratios (OR) and hazard ratios (HR) for MACE were compared, and cutoff distance of 6MWT according to endpoint diseases were calculated for both common and disease-specific thresholds. A total of 1,374 patients were enrolled, with 105 (7.6%) MACE events. The MACE group walked shorter 6MWT distances (329 ± 110 m) compared to controls (396 ± 114 m, p < 0.001). Each 50-meter increase in 6MWT distance was associated with a lower OR (0.78, p < 0.001) and HR (0.83, p < 0.001) for the MACE. Cutoff distance for MACE was 392 m, with sensitivity of 76% and specificity of 53%. The disease-specific cutoffs provided better classification of individual outcomes for all-cause death, coronary intervention, and stroke. The 6MWT has a prognostic value for predicting MACE in patients with prevalent cardiovascular diseases. Different thresholds should be applied for specific diseases to enhance the predictive accuracy.

Although statin use in patients with acute myocardial infarction (AMI) is mandatory, it has been suggested to be associated with new-onset diabetes mellitus (NODM). In real world practice, moderate-intensity statin therapy is more commonly used than high-intensity statin therapy. In this study, we investigated the impact of moderate-intensity pitavastatin (2 to 4 mg) compared with moderate-intensity atorvastatin (10 to 20 mg) and rosuvastatin (5 to 10 mg) on the development of NODM during a follow-up period of up to 3years. Between November 2011 and May 2015, 2001 patients with AMI who did not have diabetes mellitus were investigated. The cumulative incidence of NODM was evaluated in all groups. To adjust for potential confounders, multinomial propensity scores were used. Cox proportional hazard models were used to assess the hazard ratio of NODM in the atorvastatin and rosuvastatin groups compared with pitavastatin group. The cumulative incidence of NODM was significantly lower in pitavastatin group compared with the atorvastatin and rosuvastatin groups (3.0% vs 8.4% vs 10.4%, respectively; Log-rank p value = 0.001). After weighting the baseline characteristics of the 3 statin groups by multinomial propensity scores, atorvastatin (hazard ratio: 2.615, 95% confidence interval: 1.163 to 5.879) and rosuvastatin (hazard ratio: 3.906, 95% confidence interval: 1.756 to 8.688) were found to be associated with a higher incidence of NODM compared with pitavastatin therapy on multivariable analysis. Moderate-intensity pitavastatin therapy is associated with a lower incidence of NODM in patients with AMI andhas similar clinical outcomes to moderate-intensity atorvastatin and rosuvastatin therapy.

Background Sodium-glucose co-transporter-2 inhibitors displayed cardiovascular benefits in type 2 diabetes mellitus in previous studies; however, there were some heterogeneities regarding respective cardiovascular outcomes within the class. Furthermore, their efficacies in Asians, females, and those with low cardiovascular risks were under-represented. Thus, we compared the cardiovascular outcomes between new users of dapagliflozin and empagliflozin in a broad range of patients with type 2 diabetes mellitus using a nationwide population-based real-world cohort from Korea. Methods Korean National Health Insurance registry data between May 2016 and December 2018 were extracted, and an active-comparator new-user design was applied. The primary outcome was a composite of heart failure (HF)-related events (i.e., hospitalization for HF and HF-related death), myocardial infarction, ischemic stroke, and cardiovascular death. The secondary outcomes were individual components of the primary outcome. Results A total of 366,031 new users of dapagliflozin or empagliflozin were identified. After 1:1 nearest-neighbor propensity score matching, 72,752 individuals (mean age approximately 56 years, 42% women) from each group were included in the final analysis, with a follow-up of 150,000 ~ person-years. Approximately 40% of the patients included in the study had type 2 diabetes mellitus as their sole cardiovascular risk factor, with no other risk factors. The risk of the primary outcome was not different significantly between dapagliflozin and empagliflozin users (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.855–1.006). The risks of secondary outcomes were also similar, with the exception of the risks of HF-related events (HR 0.84, 95% CI 0.714–0.989) and cardiovascular death (HR 0.76, 95% CI 0.618–0.921), which were significantly lower in the dapagliflozin users. Conclusions This large-scale nationwide population-based real-world cohort study revealed no significant difference in composite cardiovascular outcomes between new users of dapagliflozin and empagliflozin. However, dapagliflozin might be associated with lower risks of hospitalization or death due to HF and cardiovascular death than empagliflozin in Asian patients with type 2 diabetes mellitus.