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Aims We aimed to investigate whether long-term exposure to particulate matter with an aerodynamic diameter <2.5 μm (PM2.5) in the ambient air is related to the development or growth of coronary plaques. Methods and results This study involved 364 residents of Seoul, Korea, who underwent serial coronary computed tomographic angiography (CCTA) at an interval of ≥2 years. Each participant's average concentration of residential PM2.5 between the two CCTAs was calculated. Primary endpoint was the development of high-risk plaque (HRP), defined as a plaque with low attenuation, spotty calcium, and positive remodelling. Secondary endpoints were the volume increase of total plaque and its component volume. Among those without HRP at baseline (n  = 341), 20 patients developed HRP at follow-up CCTA, the residential PM2.5 concentration of which was significantly higher than those without HRP at follow-up (25.8 ± 2.0 vs. 25.0 ± 1.7 μg/m3 for patients with newly developed HRP vs. patients without HRP at follow-up; P  = 0.047). An increase in PM2.5 concentration was associated with increased incidence of HRP at follow-up [adjusted hazard ratio (aHR) 1.62, 95% confidence interval (CI) 1.22–2.15, P  < 0.001]. In a secondary analysis, the PM2.5 concentration was associated with an increased risk of the formation of either fibrofatty or necrotic core component in newly developed plaques (aHR 1.41, 95% CI 1.23–1.61, P  < 0.001), and with a higher risk of total plaque volume progression in the pre-existing plaques (aHR 1.14, 95% CI 1.05–1.23, P  = 0.002). Conclusion Exposure to higher concentration of PM2.5 in the ambient air is significantly associated with the development of high-risk coronary plaques. [ABSTRACT FROM AUTHOR]

Objectives: Hyponatraemia is a well-known predictor of clinical outcomes in heart failure (HF). However, the mechanism remains poorly understood. Previous reports suggest that hyponatraemia is related to right HF. We sought to evaluate the association between right ventricular (RV) dysfunction and hyponatraemia, and the impact of this relationship on the prognosis of patients with acute heart failure (AHF).Methods: This is a nested case-control study of the Korean Acute Heart Failure registry. Among 2935 AHF patients enrolled prospectively and consecutively at four tertiary hospitals in Korea from 2011 to 2014, 116 patients with severe persistent hyponatraemia, defined as serum sodium level <130 mmol/L at admission and <135 mmol/L before discharge, were matched with 232 controls, based on propensity scores for hyponatraemia. RV function was assessed with fractional area change (FAC) by echocardiography.Results: RV dysfunction (FAC <35%) was more prevalent in patients with severe persistent hyponatraemia than in those without (81.0% vs 33.6%, p<0.001). Hyponatraemia was strongly associated with RV dysfunction (adjusted OR 8.00, 95% CI 4.50 to 14.22, p<0.001), but not with left ventricular dysfunction (adjusted OR 1.21, 95% CI 0.74 to 1.50, p=0.308). RV dysfunction was an independent predictor of all-cause mortality, after adjustment for hyponatraemia (adjusted HR 2.20, 95% CI 1.53 to 3.15, p<0.001), while hyponatraemia was not (adjusted HR 1.33, 95% CI 0.94 to 1.87, p=0.108).Conclusions: In patients with AHF, hyponatraemia was more common with RV dysfunction. RV dysfunction, rather than hyponatraemia, was more significantly related with patients' prognosis. Thus, the utility of RV dysfunction instead of hyponatraemia per se should be considered in HF risk models.Trial Registration Number: Korean Acute Heart Failure registry NCT01389843; Results. [ABSTRACT FROM AUTHOR]

Previous studies have shown that the clinical expression of hypertrophic cardiomyopathy (HCM) can be determined by obesity and metabolic syndrome. The present study aimed to investigate the association between triglyceride and high-density lipoprotein cholesterol (HDL C) level, the two dyslipidemia-related components of metabolic syndrome, and the incidence of HCM. We also explored an age-dependent association between them. Individuals without previous HCM diagnosis who underwent a designated national health examination in 2009 were recruited. Individuals who used lipid-lowering medications within 1-year of the baseline were excluded. The outcome of interest was a newly diagnosed HCM. Our cohort consisted of 8,652,709 individuals (mean 46 years, 55.6% men). During the median 9.3 years of follow-up, 5932 (0.07%) individuals were newly diagnosed with HCM. There was a gradual increase in the incidence of HCM towards higher triglyceride and lower HDL-C levels (log-rank p < 0.001). When stratified by age, the incidence of HCM was highest in individuals aged ≥65 years, followed by those aged 40–64 and 20–39 years (0.22% vs. 0.07% vs. 0.03%, log-rank p < 0.001). In individuals aged 20–39 years, a higher triglyceride level was associated with a higher incidence of HCM (i.e., ≥200 vs. <100 mg/dL: adjusted hazard ratio 2.28, 95% confidence interval 1.89–2.75), whereas there was no significant association in older groups (p -for-interaction<0.001). Similarly, a lower HDL-C level was associated with a higher incidence of HCM, particularly in individuals aged 20–39 years (p -for-interaction = 0.001). High triglyceride and low HDL-C levels are associated with a higher incidence of HCM, particularly in young individuals. Age-dependent association of triglyceride and HDL-C levels with the incidence of clinical HCM. (a) In the entire cohort (n = 8,652,709), there was a gradual increase in the incidence of clinical HCM towards higher triglyceride and lower HDL-C levels. (b) When stratified by age subgroup, higher triglyceride and lower HDL-C level were significantly associated with a higher incidence of clinical HCM in individuals aged 20–39 years, which was not observed in older individuals. *Indicates statistical significance (p < 0.05). CI, confidence interval; HCM, hypertrophic cardiomyopathy; HDL C, high-density lipoprotein cholesterol; HR, hazard ratio. [Display omitted] • High triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels are associated with a higher incidence of HCM. • Notably, the association between triglyceride or HDL-C levels and incident HCM is particularly strong in young individuals. • Further research is needed to examine whether managing metabolic dyslipidemia can influence the clinical presentation of HCM. [ABSTRACT FROM AUTHOR]

Heart diseases are a growing concern for the spinal cord injury (SCI) population. This study aims to compare the incidence of heart diseases between SCI survivors and the general non-SCI population. We identified 5,083 SCI survivors and 1:3 age- and sex-matched non-SCI controls. Study outcomes were myocardial infarction (MI), heart failure (HF), and atrial fibrillation (AF). The cohort was followed up from the index date (diagnosis date for SCI or corresponding date for matched controls) until 2019. SCI survivors showed a higher risk for MI (adjusted HR [aHR]: 2.41; 95% CI: 1.93-3.00), HF (aHR: 2.24; 95% CI: 1.95-2.56), and AF (aHR: 1.84; 95% CI: 1.49-2.28) compared to controls. The risks were further increased for those who were registered in the National Disability Registry within 1 year from the index date (SCI survivors with disability): SCI survivors with severe disability had the highest risks of MI (aHR: 3.74; 95% CI: 2.43-5.76), HF (aHR: 3.96; 95% CI: 3.05-5.14), and AF (aHR: 3.32; 95% CI: 2.18-5.05). Cervical and lumbar SCI survivors had an increased risk of heart disease regardless of disability compared to matched controls; these risks were slightly higher in those with disability. Thoracic SCI survivors with disability had significantly increased risk of heart disease compared to matched controls. SCI survivors at all levels were at significantly greater risk for heart disease than non-SCI controls, particularly those with severe disability. Clinicians must be aware of the importance of heart disease in SCI survivors. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Limited data are available on the long-term outcomes in patients with hypertrophic cardiomyopathy (HCM) patients with significant coronary artery disease (CAD) requiring revascularization. We investigated the risk of cardiovascular outcomes in HCM patients who underwent coronary revascularization compared to the control group without HCM. HCM patients aged ≥ 20 years were enrolled from the Korean National Health Insurance Database. Information on the diagnosis and previous medical history was obtained from the claims data. Cardiovascular outcomes were identified during 8-year after coronary revascularization in HCM patients (HCM group) and matched controls without HCM (non-HCM control group). A total of 431 patients in the HCM group and 1968 in the non-HCM control group were analyzed. The risk of all-cause death, cardiovascular death, sudden cardiac death (SCD), ischemic stroke, and hospitalization due to heart failure was significantly higher in the HCM group than in the non-HCM group, with prominent risk increase of cardiovascular death (adjusted hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.63–3.15, P < 0.001) and ischemic stroke (adjusted HR 2.38, 95% CI 1.55–3.64, P < 0.001). Beyond 1-year after revascularization, the HCM group still had a significantly higher risk of cardiovascular death, SCD, and ventricular fibrillation/tachycardia compared to the non-HCM group. Mortality and major cardiovascular outcomes occurred more frequently in HCM patients with significant CAD requiring revascularization, compared to the matched non-HCM control group. Active and regular surveillance for concomitant risk factors and relevant intervention are warranted in HCM patients at increased risk for CAD. [ABSTRACT FROM AUTHOR]

Background : To assess the association between the reproductive factors of age at menarche, age at menopause, and reproductive span and the incidence of myocardial infarction (MI) and ischemic stroke (IS). Methods: We used a population-based retrospective cohort study from the National Health Insurance Service database of Korea including a total of 1,224,547 postmenopausal women. Associations between age at menarche (≤ 12, 13–14 [reference], 15, 16, and ≥ 17 years), age at menopause (< 40, 40–45, 46–50, 51–54 [reference], and ≥ 55 years), and reproductive span (< 30, 30–33, 34–36, 37–40 [reference], and ≥ 41 years) and the incidence of MI and IS were assessed by Cox proportional hazard models with adjustment for traditional cardiovascular risk factors and various reproductive factors. Results: During a median follow-up of 8.4 years, 25,181 MI and 38,996 IS cases were identified. Late menarche (≥ 16 years), early menopause (≤ 50 years), and short reproductive span (≤ 36 years) were linearly associated with a 6%, 12–40%, and 12–32% higher risk of MI, respectively. Meanwhile, a U-shaped association between age at menarche and risk of IS was found, with a 16% higher risk in early menarche (≤ 12 years) and a 7–9% higher risk in late menarche (≥ 16 years). Short reproductive span was linearly associated with an increased risk of MI, whereas both shorter and longer reproductive spans were associated with an increased risk of IS. Conclusions: This study demonstrated different patterns of association between age at menarche and incidence of MI and IS: a linear association for MI versus a U-shaped association for IS. Female reproductive factors in addition to traditional cardiovascular risk factors should be considered when assessing overall cardiovascular risk in postmenopausal women. [ABSTRACT FROM AUTHOR]

Anti-tuberculosis treatment can cause significant drug-drug interaction and interfere with effective anticoagulation. However, there is a lack of evidence and conflicting data on the optimal oral anticoagulation in patients treated for tuberculosis. We investigated the safety and effectiveness of anticoagulation with non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in patients on anti-tuberculosis treatment. Patients on concomitant oral anticoagulation and anti-tuberculosis treatment including rifampin were identified from the Korean nationwide healthcare database. Subjects were censored at discontinuation of either anticoagulation or rifampin. The outcomes of interest were major bleeding, death, and ischemic stroke. A total 2090 patients (1153 on warfarin, 937 on NOAC) were included. NOAC users, compared to warfarin users, were older, had a lower prevalence of hypertension, heart failure, ischemic stroke, and aspirin use and a higher prevalence of cancer, with no significant differences in CHA2DS2-VASc or HAS-BLED scores. There were 18 major bleeding events, 106 deaths, and 50 stroke events during a mean follow-up of 2.9 months. After multivariable adjustment, the use of NOAC was associated with a lower risk of incident ischemic stroke (HR 0.51, 95% CI 0.27–0.94), while there was no significant difference in risk for major bleeding or death compared with warfarin. These results suggest that NOACs have better effectiveness for stroke prevention and similar safety compared with warfarin in patients on concomitant anti-tuberculosis treatment. This is the first study assessing the safety and effectiveness of NOACs compared to warfarin in this clinical scenario. [ABSTRACT FROM AUTHOR]

Although atrial fibrillation (AF) is a well-established risk factor for ischemic stroke (IS) in hypertrophic cardiomyopathy (HCM), the risk of IS in HCM patients without documented AF is less recognized. This nationwide population-based cohort study using Korean National Health Insurance database included 8,328 HCM patients without documented AF and 1:2 propensity score-matched 16,656 non-HCM controls between 2010 and 2016. The primary outcome was an incident IS. During a mean follow-up of 6.1 years, IS occurred in 328/8,328 (3.9%) patients with HCM and 443/16,656 (2.7%) controls. The overall incidence of IS was 0.72/100 person-years in the HCM group, which was significantly higher than that in the control group (0.44/100 person-years) (HR 1.64; 95% CI 1.424–1.895; P < 0.001). The overall incidence of IS was 1.36/100 person-years in HCM patients aged ≥ 65 and 2.32/100 person-years years in those with heart failure, respectively. In the HCM group, age ≥ 65 years (adjusted HR 2.74; 95% CI 2.156–3.486; P < 0.001) and chronic heart failure (adjusted HR 1.75; 95% CI 1.101–2.745; P = 0.018) were independent risk factors for IS. HCM patients without documented AF are at a greater risk of IS, especially in those 65 years of age or older or those with chronic heart failure. [ABSTRACT FROM AUTHOR]

Arterial stiffness, a known cardiovascular risk factor, is associated with increasing age and arteriosclerosis. This study examines age-related annual changes in arterial stiffness in a large cohort of healthy individuals without cardiovascular disease, hypertension, or diabetes mellitus. The study included 195,405 Korean adults aged 30–79 years who attended a health check-up between 2006 and 2019. Arterial stiffness was assessed using brachial-ankle pulse wave velocity (baPWV), and the final cohort for the baPWV annual change analysis comprised 147,313 participants. The study found that baPWV values increase progressively with age in both sexes, with the most notable changes occurring in the 70–79 age group. The spread in baPWV measurements, as indicated by the interquartile ranges, generally increases with age but was particularly pronounced in women in the 50s and 60s age groups, with men showing a greater spread in the 70–79 age group. The average annual change in baPWV (ΔbaPWV) values increased from 1.48 cm/s (95 % CI: 0.80–2.16) in the 30–39 age group to 23.72 cm/s (95 % CI: 16.25–31.19) in the 70–79 age group in men. Similarly, for women, the average ΔbaPWV values increased from 1.80 cm/s (95 % CI: 0.93–2.68) to 18.51 cm/s (95 % CI: 7.18–29.85) in the 30–39 and 70–79 age groups, respectively. The study observed that arterial stiffness in men consistently increases across all age groups, whereas in women, it does not significantly increase annually before age 50 but shows a steeper rise after this age. This study emphasizes the progressive nature of arterial stiffness with aging in a healthy population. It highlights notable differences in the rate of progression and the distribution of baPWV between men and women, with men exhibiting a greater spread in the oldest age group. [Display omitted] • The study contributes to understand the progression of arterial stiffness in a healthy Korean adult population. • The findings reveal that arterial stiffness tends to increase with age, especially in older age groups. • The study reveals gender-specific differences in the progression of arterial stiffness. • The findings emphasize the importance of early detection and intervention strategies to mitigate cardiovascular risks. [ABSTRACT FROM AUTHOR]

Alcohol consumption has complex effects on myocardial infarction (MI) and ischemic stroke. We investigated the difference in associations according to drinking patterns (drinking frequency vs. amount per occasion) and sex. This population-based retrospective study included 11,595,191 subjects participating in national health examinations between 2009 and 2010. Using Cox regression analyses, we calculated MI and ischemic stroke risk according to weekly alcohol consumption, drinking frequency, and amount per occasion. For MI, all weekly alcohol consumption amounts showed lower risk compared to non-drinkers: mild (adjusted hazard ratio [aHR], 0.78; 95% confidence intervals [CI], 0.77–0.79), moderate (aHR, 0.71; 95% CI, 0.70–0.73), and heavy (aHR, 0.74; 95% CI, 0.72–0.76). Drinking frequency and amount per occasion did not differ in MI risk. However, women showed increased risk with heavy drinking and ≥8 drinks per occasion. For ischemic stroke, a J-shaped association was observed for weekly alcohol consumption: mild (aHR, 0.91; 95% CI, 0.90–0.92), moderate (aHR, 0.94; 95% CI, 0.93–0.96), and heavy (aHR, 1.04; 95% CI, 1.02–1.06). Among women, ischemic stroke risk began to increase with moderate drinking. Given similar weekly alcohol consumption levels, ischemic stroke risk increased with higher frequency of drinking, not with amount per occasion. Drinking frequency may be a more important risk factor for ischemic stroke than amount per occasion. Among women, the protective effect of alcohol against MI was not evident in heavy amounts, and the risk of ischemic stroke began to increase at lower levels compared to men. [Display omitted] • We investigated drinking patterns and risk of MI and ischemic stroke. • Drinking patterns were drinking frequency vs. amount per occasion, and weekly consumption. • Overall, drinking frequency and amount per occasion did not differ in myocardial infarction (MI) risk. • For women, heavy drinking and ≥8 drinks per occasion showed increased MI risk. • For ischemic stroke, risk increased with higher frequency of drinking, not with amount. [ABSTRACT FROM AUTHOR]

Despite the increasing burden of hypertrophic cardiomyopathy (HCM) on healthcare resources, data on emergency department (ED) utilization in HCM are lacking. This nationwide population-based study extracted 14,542 HCM patients from the National Health Insurance Service database between 2015–2016, and investigated their ED utilization during a one-year period. The reason for ED utilization was defined as the primary diagnosis upon discharge from EDs. The clinical outcome was defined as hospitalization or all-cause mortality within 90 days after the ED visits. A total of 3209 (22.1%) HCM patients visited EDs within a one-year period (mean age, 66.8 ± 13.8 years; male, 57.4%). The majority (71.1%) of HCM patients who visited the EDs were aged ≥ 60 years. The ED utilization rate was higher in women than in men (26.3% versus 19.7%, P < 0.001). Cardiovascular diseases were the most common reason for ED visits (n = 1333, 41.5%). Among HCM patients who visited EDs, 1195 (37.2%) were hospitalized, and 231 (7.2%) died within 90 days. ED visits for cardiovascular disease was associated with a higher 90-day all-cause mortality (adjusted odds ratio, 2.72; 95% confidence interval 1.79–4.12). These findings would serve as a basis for future research to establish medical policies on ED utilization in HCM. [ABSTRACT FROM AUTHOR]

Aims: Diabetes mellitus (DM) often coexists in elderly hypertrophic cardiomyopathy (HCM) patients; however, its impact on clinical outcomes is unclear.Methods: We compared clinical outcomes according to the presence of DM in a nationwide HCM cohort.Results: In 9,883 HCM subjects (mean age 58.5 ± 13.1, men 71.7%), 1,327 (13.4%) had DM. During follow-up (mean 5.9 ± 2.5 years), end-stage renal disease (ESRD) progression, coronary events (myocardial infarction, coronary revascularization), heart failure (HF), cardiovascular mortality, and all-cause mortality occurred in 80 (0.8%), 365 (3.7%), 1,558 (15.8%), 354 (3.6%), and 877 (8.9%) subjects, respectively. DM HCM subjects had significantly higher risks of ESRD progression (HR 3.49, 95% CI 2.20-5.54) and HF (HR 1.15, 95% CI 1.01-1.32) compared to non-DM HCM subjects, independent of age, sex, ischemic heart disease, atrial fibrillation, and other comorbidities. There was a tendency for greater risk of ESRD progression, HF, and all-cause death in subjects with more advanced stage of DM (p-for-trend < 0.05 for all). Insulin-treated DM was associated with the highest risk.Conclusions: DM HCM subjects have higher risk of ESRD progression and HF. Considering the extended life expectancy of HCM and increasing number of elderly HCM subjects, active surveillance and management of DM-related outcomes should be highlighted. [ABSTRACT FROM AUTHOR]

Background: Whether genetic susceptibility to cardiovascular diseases (CVDs) enhances the vulnerability to adverse cardiovascular outcomes by air pollution is unknown. We assessed the combined effect of air pollution and genetic predispositions on CVD risk., Methods and Results: From the UK Biobank cohort, we selected genetically unrelated White British participants without CVD. Levels of ambient particulate matter with a diameter of <2.5 μm (PM 2.5 ) and <10 μm were estimated using land use regression models. An individual's genetic predisposition to CVDs was determined by polygenic risk scores for coronary artery disease, myocardial infarction, stroke, ischemic stroke, heart failure, and atrial fibrillation. We stratified mortality and CVD risk by PM 2.5 exposure across high and low genetic risk groups. A total of 249 082 participants (aged 56.9±8.0 years, 46.8% men) were followed for a median of 10.8 years. The combined effect of PM 2.5 exposure and the genetic predisposition of CVD demonstrated the highest risk of cardiovascular death in the high genetic risk group with the greatest PM 2.5 exposure (adjusted hazard ratios ranging from 1.73 to 2.12 across the polygenic risk score of each CVD). The combination of higher exposure to ambient PM 2.5 and high genetic risk was associated with higher incidence of all CVDs, although no significant interactions were observed between genetic risk and PM 2.5 exposure on cardiovascular death or CVD events., Conclusions: A combination of greater PM 2.5 exposure and higher genetic predisposition to particular CVDs was modestly associated with elevated risks of cardiovascular death and CVDs. Not only alleviating PM 2.5 exposure in the general population but also implementing individualized preventive approach for those at high genetic risk might be beneficial.

Background: The antihypertensive efficacy of fimasartan was assessed based on the transition rate from a combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) to three-drug combination therapy, as compared to other ARBs., Methods: This nationwide cohort study used data obtained from the Korean National Health Insurance Service database. Patients who had received national health checkups within 2 years prior to January 1, 2017, and were concurrently prescribed ARBs and CCBs for > 30 days during the 6 months from January 1, 2017, to June 30, 2017 were included in the study. Patients were categorized into the 'fimasartan group' (those prescribed fimasartan) and the 'non-fimasartan group' (those prescribed ARBs other than fimasartan). The index date was set as the last day of a 30-day prescription period for ARBs and CCBs, with a subsequent 2.5-year follow-up to observe the potential addition of a third drug, such as beta-blockers or diuretics., Results: The study included 34,422 patients with a mean age of 60.3 years and 58.3% being male. The fimasartan group constituted 2.7% (n = 928) of the total, and the non-fimasartan group, 97.3% (n = 33,494). During the follow-up period, 38 patients in the fimasartan group (14.3 per 1,000 person-years) and 3,557 patients in the non-fimasartan group (42.8 per 1,000 person-years) required additional antihypertensive medications. After multivariate adjustment for age, sex, diabetes mellitus, dyslipidemia, cancer, heart failure, systolic blood pressure, and diastolic blood pressure, the fimasartan group showed a significantly lower rate of adding a third medication (hazard ratio 2.68, 95% confidence interval 1.95-3.69) compared to that of the non-fimasartan group., Conclusions: Fimasartan is associated with a lower need for additional antihypertensive drugs compared to other ARBs. This implies its greater effectiveness in hypertension management, potentially enhancing cardiovascular outcomes, and minimizing polypharmacy., (© 2024. The Author(s).)

Background: Sacubitril acts to inhibit neprilysin and as neprilysin is involved in amyloid-beta degradation in the central nervous system, and there is concern that sacubitril/valsartan may increase the risk of dementia. We aimed to compare the risk of incident dementia associated with sacubitril/valsartan and angiotensin II receptor blockers (ARBs)., Methods: Patients with heart failure with reduced ejection fraction treated with either sacubitril/valsartan or ARB, identified from the Korean National Health Insurance Service database, were matched in a 1:2 ratio using propensity scores (6789 on sacubitril/valsartan and 13,578 on ARBs) and followed up for incident dementia., Results: During a mean follow-up of 2.5 years, 526 (2.6%) patients were newly diagnosed with dementia: Alzheimer dementia in 282, vascular dementia in 8, and other dementia in 236. There was no significant difference in the risk of overall dementia (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.70-1.01), Alzheimer dementia (HR 0.85, 95% CI 0.67-1.10), vascular dementia (HR 0.98, 95% CI 0.23-4.11), and all other dementias (HR 0.81, 95% CI 0.62-1.07) between sacubitril/valsartan users and ARB users. These results were consistent regardless of initial sacubitril/valsartan dose and subgroups including old age, previous mild cognitive impairment, previous stroke, and concomitant antiplatelet or anticoagulation. Sensitivity analysis with a 1-year lag period for dementia assessment confirmed the main analysis. Meanwhile, risk of incident stroke was lower in sacubitril/valsartan users compared to ARBs users., Conclusions: In a nationwide propensity-matched cohort of patients with heart failure, sacubitril/valsartan was not associated with an increased risk of incident dementia compared to ARBs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Aims: Recently, deep learning artificial intelligence (AI) models have been trained to detect cardiovascular conditions, including hypertrophic cardiomyopathy (HCM), from the 12-lead electrocardiogram (ECG). In this external validation study, we sought to assess the performance of an AI-ECG algorithm for detecting HCM in diverse international cohorts., Methods and Results: A convolutional neural network-based AI-ECG algorithm was developed previously in a single-centre North American HCM cohort (Mayo Clinic). This algorithm was applied to the raw 12-lead ECG data of patients with HCM and non-HCM controls from three external cohorts (Bern, Switzerland; Oxford, UK; and Seoul, South Korea). The algorithm's ability to distinguish HCM vs. non-HCM status from the ECG alone was examined. A total of 773 patients with HCM and 3867 non-HCM controls were included across three sites in the merged external validation cohort. The HCM study sample comprised 54.6% East Asian, 43.2% White, and 2.2% Black patients. Median AI-ECG probabilities of HCM were 85% for patients with HCM and 0.3% for controls ( P < 0.001). Overall, the AI-ECG algorithm had an area under the receiver operating characteristic curve (AUC) of 0.922 [95% confidence interval (CI) 0.910-0.934], with diagnostic accuracy 86.9%, sensitivity 82.8%, and specificity 87.7% for HCM detection. In age- and sex-matched analysis (case-control ratio 1:2), the AUC was 0.921 (95% CI 0.909-0.934) with accuracy 88.5%, sensitivity 82.8%, and specificity 90.4%., Conclusion: The AI-ECG algorithm determined HCM status from the 12-lead ECG with high accuracy in diverse international cohorts, providing evidence for external validity. The value of this algorithm in improving HCM detection in clinical practice and screening settings requires prospective evaluation., Competing Interests: Conflict of interest: P.A.F., Z.I.A., P.A.N., M.J.A., and K.C.S. are co-inventors of the HCM AI-ECG algorithm. Mayo Clinic has licensed the algorithm to Anumana, Inc., with potential for commercialization. K.C.S. has received research funding from Anumana, Inc., for work related to the HCM AI-ECG algorithm (via the institution). M.J.A. is also a consultant for Abbott, Boston Scientific, Bristol Myers Squibb, Daiichi Sankyo, Invitae, LQT Therapeutics, and Medtronic. M.J.A. and Mayo Clinic also have licensing agreements with AliveCor, ARMGO Pharma, Pfizer, and UpToDate. S.W. reports research, travel, or educational grants to the institution from Abbott, Abiomed, Amgen, Astra Zeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo, Vifor, and V-Wave. He serves as advisory board member and/or member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, Astra Zeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis with payments to the institution but no personal payments. He is also a member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. B.R. is funded by the BHF Oxford Centre of Research Excellence (RE/18/3/34214). S.N. acknowledges support from the Oxford NIHR Biomedical Research Centre and the Oxford British Heart Foundation Centre of Research Excellence., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Little is known about the determinants and outcomes of significant atrial functional tricuspid regurgitation (AFTR)., Objectives: The authors aimed to identify risk factors for significant TR in relation to atrial fibrillation-flutter (AF-AFL) and assess its prognostic implications., Methods: The authors retrospectively studied patients with mild TR with follow-up echocardiography examinations. Significant TR was defined as greater than or equal to moderate TR. AFTR was defined as TR, attributed to right atrial (RA) remodeling or isolated tricuspid annular dilatation, without other primary or secondary etiology, except for AF-AFL. The Mantel-Byar test was used to compare clinical outcomes by progression of AFTR., Results: Of 833 patients with mild TR, 291 (34.9%) had AF-AFL. During the median 4.6 years, significant TR developed in 35 patients, including 33 AFTRs. Significant AFTR occurred in patients with AF-AFL more predominantly than in those patients without AF-AFL (10.3% vs 0.6%; P < 0.001). In Cox analysis, AF-AFL was a strong risk factor for AFTR (adjusted HR: 8.33 [95% CI: 2.34-29.69]; P = 0.001). Among patients with AF-AFL, those who developed significant AFTR had larger baseline RA areas (23.8 vs 19.4 cm 2 ; P < 0.001) and RA area-to-right ventricle end-systolic area ratio (3.0 vs 2.3; P < 0.001) than those who did not. These parameters were independent predictors of AFTR progression. The 10-year major adverse cardiovascular event was significantly higher after progression of AFTR than before or without progression (79.8% vs 8.6%; Mantel-Byar P < 0.001)., Conclusions: In patients with mild TR, significant AFTR developed predominantly in patients with AF-AFL, conferring poor prognosis. RA enlargement, especially with increased RA area-to-right ventricle end-systolic area ratio, was a strong risk factor for progression of AFTR., Competing Interests: Funding Support and Author Disclosures This work was supported by the National Research Foundation of Korea of the Ministry of Science and ICT (NRF-2020R1C1C1010890). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Aims: We aimed to investigate the association between metabolic syndrome (MetS) and coronary artery calcium (CAC) progression in statin-naïve young adults., Methods: From the KOrea Initiatives on Coronary Artery calcification registry, we included asymptomatic young adults aged 20-45 years who underwent serial CAC scans for routine health check-ups. The primary endpoint was CAC progression. We estimated the risk of CAC progression based on the presence and burden of MetS. Among participants with MetS, the temporal relationship between changes in metabolic burden and CAC progression was evaluated., Results: Of 2151 young adults (mean age 41.3 ± 3.8 years; male 85.4%), 488 (22.7%) had MetS. The mean CAC score was 10.8 and 81.3% of them had a CAC score of zero at baseline. During follow-up (median, 2.1 years), CAC progression was observed in 325 (15.1%) adults. MetS was associated with an approximately 1.8-fold increased risk of CAC progression (adjusted hazard ratio [aHR] 1.83, p &lt; 0.001). The risk of CAC progression was directly proportional to the metabolic burden. Elevated blood pressure and elevated triglyceride levels were independent components related to CAC progression, with the strongest contribution being made by elevated blood pressure (aHR 2.00, p &lt; 0.001). A reduction in at least two metabolic burdens was associated with a halved risk of CAC progression in young adults having MetS (odds ratio 0.41, p = 0.018)., Conclusions: In statin-naïve young adults, the metabolic burden was associated with a risk of CAC progression in a dose-dependent manner. Improvement in metabolic imbalance may have a preventive effect on CAC progression., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: We investigated the change of coronary atherosclerosis with long-term exposure to fine particulate matter of aerodynamic diameter <2.5 ​μm (PM 2.5 ) using coronary computed tomography angiography (CCTA)., Methods: Subjects undergoing serial CCTAs between January 2007 and December 2017 (n ​= ​3,127) were analyzed. Each individual's cumulative amount of PM 2.5 exposure between the two CCTAs was evaluated by Kriging interpolation and zonal analysis, considering the time interval between the two CCTAs. The main outcome was progression of coronary artery calcium (CAC) with additional semiquantitative analysis on the changes in the severity and composition of atherosclerotic plaques., Results: The CAC scores increased by 30.8 Agatston units per-year under a median PM 2.5 concentration 24.9 ​μg/m 3 and tended to increase with the cumulative amount of PM 2.5 exposure (r ​= ​0.321, p ​<0.001). The CAC progressed in 1,361 (43.5%) subjects during a median 53 months follow-up. The cumulative amount of PM 2.5 exposure was independently associated with CAC progression (adjusted OR 1.09, p ​<0.001). By random forest analysis, the relative impact of cumulative amount of PM 2.5 exposure on CAC progression was higher than that of traditional cardiovascular risk factors and the average concentration of PM 2.5 . The extent of coronary atherosclerosis and newly developed calcified plaque on follow-up were also significantly associated with the cumulative amount of PM 2.5 exposure., Conclusions: Cumulative exposure to air pollution is associated with the progression of diffuse coronary calcification, the importance of which may be more significant than other traditional cardiovascular risk factors. Further investigations into the causality between PM 2.5 and coronary atherosclerosis are warranted to improve global cardiovascular health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Insufficient evidence is available comparing mortality and cause of death between general hypertrophic cardiomyopathy (HCM) and general non-HCM populations. We aimed to investigate how causes of death and mortality differ in subjects with and without HCM. Using the National Health Insurance Service database from 2009 to 2016, individuals who underwent health check-up(s) with or without a history of HCM were identified. Participants in the HCM group were matched at a 1:1 ratio with those in the non-HCM group using propensity scores calculated from the baseline covariates. Mortality rates and risks were compared between the groups. In total, 14,858 participants (7,429 each in the HCM and non-HCM groups) were followed up over a mean 4.4 ± 2.2 years (mean age, 61.0 years; male proportion, 66.8%). Compared to the non-HCM group, the HCM group showed a higher risk of all-cause and HCM-related mortality and a similar risk for non-cardiovascular mortality (hazard ratio [95% confidence interval] 1.57 [1.38-1.78], 2.71 [1.92-3.83], and 1.04 [0.88-1.23], respectively). The sensitivity analyses consistently showed that the HCM group showed higher risks of all-cause and HCM-related mortality than the non-HCM group. The female participants with HCM were associated with an increasing trend of the risks of all-cause mortality but not HCM-related mortality compared to their male counterparts (p for interaction < 0.001 and 0.185, respectively). In conclusion, compared to the non-HCM population, the general HCM population showed higher risks of both all-cause and HCM-related mortality, but had a similar risk of non-cardiovascular mortality., (© 2022. The Author(s).)

Background: Heart failure (HF) and cancer are currently two leading causes of mortality, and sometimes coexist. However, the relationship between them is not completely elucidated. We aimed to investigate whether patients with HF are predisposed to cancer development using the large Korean National Health Insurance claims database., Methods: This study included 128,441 HF patients without a history of cancer and 642,205 age- and sex-matched individuals with no history of cancer and HF between 1 January 2010 and 31 December 2015., Results: During a median follow-up of 4.06 years, 11,808 patients from the HF group and 40,805 participants from the control were newly diagnosed with cancer (cumulative incidence, 9.2% vs. 6.4%, p < 0.0001). Patients with HF presented a higher risk for cancer development compared to controls in multivariable Cox analysis [hazard ratio (HR) 1.64, 95% confidence interval (CI) 1.61-1.68]. The increased risk was consistent for all site-specific cancers. To minimize potential surveillance bias, additional analysis was performed by eliminating participants who developed cancer within the initial 2 years of HF diagnosis (i.e. 2-year lag analysis). In the 2-year lag analysis, the higher risk of overall cancer remained significant in patients with HF (HR 1.09, 95% CI 1.05-1.13), although the association was weaker. Among the site-specific cancers, three types of cancer (lung, liver/biliary/pancreas, and hematologic malignancy) were consistently at higher risk in patients with HF. An exploratory analysis showed that patients with repeated HF hospitalization had a higher risk of cancer development compared to those without, in a pattern of stepwise increases across the three groups [controls vs. HF without re-hospitalization vs. HF with re-hospitalization ≥1; HR (95% CI), 1.00 (reference) vs. 1.55 (1.51-1.59) vs. 1.96 (1.89-2.03), respectively]., Conclusions: Cancer incidence is higher in patients with HF than the general population. Active surveillance of coexisting malignancy needs to be considered in these patients., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Excessive alcohol consumption is related to atrial fibrillation (AF) development in the general population., Objective: The purpose of this study was to investigate the effect of alcohol consumption on new-onset AF development in asymptomatic healthy individuals., Methods: Asymptomatic healthy adults (age <75 years; body mass index <30 kg/m 2 ) undergoing routine health examinations from 2007 to 2015 were screened. Those with sinus rhythm and without any previously diagnosed medical or surgical illness were recruited for analysis. The primary outcome was new-onset AF. Secondary outcomes were a composite of non-AF cardiac events, including clinically significant tachy- or bradyarrhythmias, acute myocardial infarction, heart failure, or cardiac death., Results: Among 19,634 individuals (50% male; age 19-74 years), 199 cardiac events were recorded, including new-onset AF (n = 160), acute myocardial infarction (n = 30), and clinically significant tachy- or bradyarrhythmia (n =19), during mean follow-up of 7.0 ± 2.8 years. The incidence of new-onset AF was higher in drinkers (hazard ratio [HR] 2.21; 95% confidence interval [CI] 1.55-3.14; P <.001), whereas composite non-AF cardiac events were not correlated to alcohol. There was a dose-dependent increase in the risk of AF according to the amount of alcohol consumed, and the risk increased more abruptly in men than in women. The risk of AF was highest in frequent binge drinkers (HR 3.15; 95% CI 1.98-4.99; P <.001), compared to infrequent light drinkers., Conclusion: In the asymptomatic healthy population, drinking increases the risk of new-onset AF in a dose-dependent manner, regardless of sex. Frequent binge drinking should be avoided., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate the relationship between extracellular volume fraction (ECV), a noninvasive parameter that quantifies the degree of diffuse myocardial fibrosis on cardiac magnetic resonance (CMR), and left ventricular diastolic dysfunction (LVDD) in patients with aortic stenosis (AS)., Background: Myocardial fibrosis on invasive myocardial biopsy is associated with LVDD. However, there is a paucity of data on the association between noninvasively quantified diffuse myocardial fibrosis and the degree of LVDD and how these are related to symptoms and long-term prognosis in patients with AS., Methods: Patients with moderate or severe AS (n = 191; mean age 68.4 years) and 30 control subjects without cardiovascular risk factors underwent CMR. LVDD grade was evaluated using echocardiography according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Clinical outcomes were defined as a composite of all-cause mortality or hospitalization for heart failure aggravation., Results: Patients in higher ECV quintiles had a significantly higher prevalence of LVDD. Higher ECV was particularly associated with decreased myocardial relaxation (septal e' <7 cm/s) and increased LV filling pressure (E/e' ratio ≥15). Although both impaired diastolic function and higher ECV were significantly associated with a worse degree of dyspnea, patients with higher ECV showed greater dyspnea within the same grade of LVDD. During a median follow-up period of 5.6 years, 37 clinical events occurred. Increased ECV, as well as lower septal e' and higher E/septal e' ratio, were independent predictors of clinical events, irrespective of age, AS severity, aortic valve replacement, and left ventricular (LV) ejection fraction. ECV provided incremental prognostic value on top of clinical factors and LV systolic and diastolic function., Conclusions: Diffuse myocardial fibrosis, assessed using ECV on CMR, was associated with LVDD in patients with AS, but both ECV and LV diastolic function parameters provided a complementary explanation for dyspnea and clinical outcomes. Concomitant assessment of both LVDD and diffuse myocardial fibrosis may further identify patients with AS with greater symptoms and worse prognosis., Competing Interests: Author Disclosures This work was supported by a National Research Foundation grant funded by the government of Korea (Ministry of Science and ICT; 2019R1A2C2084099) and a fund from ChongKunDang Pharmaceutical (0620121110). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: We aimed to investigate whether long-term exposure to particulate matter with an aerodynamic diameter <2.5 μm (PM2.5) in the ambient air is related to the development or growth of coronary plaques., Methods and Results: This study involved 364 residents of Seoul, Korea, who underwent serial coronary computed tomographic angiography (CCTA) at an interval of ≥2 years. Each participant's average concentration of residential PM2.5 between the two CCTAs was calculated. Primary endpoint was the development of high-risk plaque (HRP), defined as a plaque with low attenuation, spotty calcium, and positive remodelling. Secondary endpoints were the volume increase of total plaque and its component volume. Among those without HRP at baseline (n = 341), 20 patients developed HRP at follow-up CCTA, the residential PM2.5 concentration of which was significantly higher than those without HRP at follow-up (25.8 ± 2.0 vs. 25.0 ± 1.7 μg/m3 for patients with newly developed HRP vs. patients without HRP at follow-up; P = 0.047). An increase in PM2.5 concentration was associated with increased incidence of HRP at follow-up [adjusted hazard ratio (aHR) 1.62, 95% confidence interval (CI) 1.22-2.15, P < 0.001]. In a secondary analysis, the PM2.5 concentration was associated with an increased risk of the formation of either fibrofatty or necrotic core component in newly developed plaques (aHR 1.41, 95% CI 1.23-1.61, P < 0.001), and with a higher risk of total plaque volume progression in the pre-existing plaques (aHR 1.14, 95% CI 1.05-1.23, P = 0.002)., Conclusion: Exposure to higher concentration of PM2.5 in the ambient air is significantly associated with the development of high-risk coronary plaques., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Despite the advances in the diagnosis and treatment of heart failure (HF), the current hospital-oriented framework for HF management does not appear to be sufficient to maintain the stability of HF patients in the long term. The importance of self-care management is increasingly being emphasized as a promising long-term treatment strategy for patients with chronic HF., Objective: The objective of this study was to evaluate whether a new information communication technology (ICT)-based telehealth program with voice recognition technology could improve clinical or laboratory outcomes in HF patients., Methods: In this prospective single-arm pilot study, we recruited 31 consecutive patients with chronic HF who were referred to our institute. An ICT-based telehealth program with voice recognition technology was developed and used by patients with HF for 12 weeks. Patients were educated on the use of this program via mobile phone, landline, or the Internet for the purpose of improving communication and data collection. Using these systems, we collected comprehensive data elements related to the risk of HF self-care management such as weight, diet, exercise, medication adherence, overall symptom change, and home blood pressure. The study endpoints were the changes observed in urine sodium concentration (uNa), Minnesota Living with Heart Failure (MLHFQ) scores, 6-min walk test, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) as surrogate markers for appropriate HF management., Results: Among the 31 enrolled patients, 27 (87%) patients completed the study, and 10 (10/27, 37%) showed good adherence to ICT-based telehealth program with voice recognition technology, which was defined as the use of the program for 100 times or more during the study period. Nearly three-fourths of the patients had been hospitalized at least once because of HF before the enrollment (20/27, 74%); 14 patients had 1, 2 patients had 2, and 4 patients had 3 or more previous HF hospitalizations. In the total study population, there was no significant interval change in laboratory and functional outcome variables after 12 weeks of ICT-based telehealth program. In patients with good adherence to ICT-based telehealth program, there was a significant improvement in the mean uNa (103.1 to 78.1; P=.01) but not in those without (85.4 to 96.9; P=.49). Similarly, a marginal improvement in MLHFQ scores was only observed in patients with good adherence (27.5 to 21.4; P=.08) but not in their counterparts (19.0 to 19.7; P=.73). The mean 6-min walk distance and NT-proBNP were not significantly increased in patients regardless of their adherence., Conclusions: Short-term application of ICT-based telehealth program with voice recognition technology showed the potential to improve uNa values and MLHFQ scores in HF patients, suggesting that better control of sodium intake and greater quality of life can be achieved by this program., (©Heesun Lee, Jun-Bean Park, Sae Won Choi, Yeonyee E Yoon, Hyo Eun Park, Sang Eun Lee, Seung-Pyo Lee, Hyung-Kwan Kim, Hyun-Jai Cho, Su-Yeon Choi, Hae-Young Lee, Jonghyuk Choi, Young-Joon Lee, Yong-Jin Kim, Goo-Yeong Cho, Jinwook Choi, Dae-Won Sohn. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 02.10.2017.)