The effect of sustained-release CARvedilol in patients with hypErtension and heart failure with preserved ejection fraction: a study protocol for a pilot randomized controlled trial (CARE-preserved HF).

Background: Although beta-blockers improve clinical outcomes in heart failure with reduced ejection fraction, the benefit of beta-blockers in heart failure with preserved ejection fraction (HFpEF) is uncertain. Global longitudinal strain (GLS) is a robust predictor of heart failure outcomes, and recent studies have shown that beta-blockers are associated with improved survival in those with low GLS (GLS <14%) but not in those with GLS ≥14% among patients with LVEF ≥40%. Therefore, the objective of this trial is to evaluate the effect of sustained-release carvedilol (carvedilol-SR) on the outcome [N-terminal pro-B-natriuretic peptide (NT-proBNP) concentration] in patients with hypertension and HFpEF and will assess the differential effects of these drugs on the outcome, according to the GLS categories. Methods: This prospective randomized double-blind multicenter trial (CARE-preserved HF) will include 100 patients with HFpEF from three tertiary hospitals in South Korea. Patients with HFpEF and hypertension aged ≥20 years who have evidence of functional and structural heart disease on echocardiography and elevated natriuretic peptide will be enrolled. Eligible participants will be randomized 1:1 to either the carvedilol-SR group (n = 50) or the placebo group (n = 50). Patients in the carvedilol-SR group will receive 8, 16, 32, or 64 mg carvedilol-SR once daily for 6 months, and the dose of carvedilol will be up-titrated at the discretion of the treating physicians. The primary efficacy outcome was the time-averaged proportional change in N-terminal pro-B-natriuretic peptide concentration from baseline to months 3 and 6. We will also evaluate the differential effects of carvedilol-SR on primary outcomes according to GLS, using a cut-off of 14% or the median value. Discussion: This randomized controlled trial will investigate the efficacy and safety of carvedilol-SR in patients with HFpEF and hypertension. Clinical Trial Registration: ClinicalTrial.gov, identifier NCT05553314.

The Third Nationwide Korean Heart Failure III Registry (KorHF III): The Study Design Paper.

With advancements in both pharmacologic and non-pharmacologic treatments, significant changes have occurred in heart failure (HF) management. The previous Korean HF registries, namely the Korea Heart Failure Registry (KorHF-registry) and Korean Acute Heart Failure Registry (KorAHF-registry), no longer accurately reflect contemporary acute heart failure (AHF) patients. Our objective is to assess contemporary AHF patients through a nationwide registry encompassing various aspects, such as clinical characteristics, management approaches, hospital course, and long-term outcomes of individuals hospitalized for AHF in Korea. This prospective observational multicenter cohort study (KorHF III) is organized by the Korean Society of Heart Failure. We aim to prospectively enroll 7,000 or more patients hospitalized for AHF at 47 tertiary hospitals in Korea starting from March 2018. Eligible patients exhibit signs and symptoms of HF and demonstrate either lung congestion or objective evidence of structural or functional cardiac abnormalities in echocardiography, or isolated right-sided HF. Patients will be followed up for up to 5 years after enrollment in the registry to evaluate long-term clinical outcomes. KorHF III represents the nationwide AHF registry that will elucidate the clinical characteristics, management strategies, and outcomes of contemporary AHF patients in Korea. Trial Registration: ClinicalTrials.gov Identifier: NCT04329234.

Heart Failure Statistics 2024 Update: A Report From the Korean Society of Heart Failure.

Background and Objectives: The number of people with heart failure (HF) is increasing worldwide, and the social burden is increasing as HF has high mortality and morbidity. We aimed to provide updated trends on the epidemiology of HF in Korea to shape future social measures against HF. Methods: We used the National Health Information Database of the National Health Insurance Service to determine the prevalence, incidence, hospitalization rate, mortality rate, comorbidities, in-hospital mortality, and healthcare cost of patients with HF from 2002 to 2020 in Korea. Results: The prevalence of HF in the total Korean population rose from 0.77% in 2002 to 2.58% (1,326,886 people) in 2020. Although the age-standardized incidence of HF decreased over the past 18 years, the age-standardized prevalence increased. In 2020, the hospitalization rate for any cause in patients with HF was 1,166 per 100,000 persons, with a steady increase from 2002. In 2002, the HF mortality was 3.0 per 100,000 persons, which rose to 15.6 per 100,000 persons in 2020. While hospitalization rates and in-hospital mortality for patients with HF increased, the mortality rate for patients with HF did not (5.8% in 2020), and the one-year survival rate from the first diagnosis of HF improved. The total healthcare costs for patients with HF were approximately $2.4 billion in 2020, a 16-fold increase over the $0.15 billion in 2002. Conclusions: The study's results underscore the growing socioeconomic burden of HF in Korea, driven by an aging population and increasing HF prevalence.

Effectiveness of a Smartphone App-Based Intervention With Bluetooth-Connected Monitoring Devices and a Feedback System in Heart Failure (SMART-HF Trial): Randomized Controlled Trial.

BACKGROUND: Current heart failure (HF) guidelines recommend a multidisciplinary approach, discharge education, and self-management for HF. However, the recommendations are challenging to implement in real-world clinical settings. OBJECTIVE: We developed a mobile health (mHealth) platform for HF self-care to evaluate whether a smartphone app-based intervention with Bluetooth-connected monitoring devices and a feedback system can help improve HF symptoms. METHODS: In this prospective, randomized, multicenter study, we enrolled patients 20 years of age and older, hospitalized for acute HF, and who could use a smartphone from 7 tertiary hospitals in South Korea. In the intervention group (n=39), the apps were automatically paired with Bluetooth-connected monitoring devices. The patients could enter information on vital signs, HF symptoms, diet, medications, and exercise regimen into the app daily and receive feedback or alerts on their input. In the control group (n=38), patients could only enter their blood pressure, heart rate, and weight using conventional, non-Bluetooth devices and could not receive any feedback or alerts from the app. The primary end point was the change in dyspnea symptom scores from baseline to 4 weeks, assessed using a questionnaire. RESULTS: At 4 weeks, the change in dyspnea symptom score from baseline was significantly greater in the intervention group than in the control group (mean -1.3, SD 2.1 vs mean -0.3, SD 2.3; P=.048). A significant reduction was found in body water composition from baseline to the final measurement in the intervention group (baseline level mean 7.4, SD 2.5 vs final level mean 6.6, SD 2.5; P=.003). App adherence, which was assessed based on log-in or the percentage of days when symptoms were first observed, was higher in the intervention group than in the control group. Composite end points, including death, rehospitalization, and urgent HF visits, were not significantly different between the 2 groups. CONCLUSIONS: The mobile-based health platform with Bluetooth-connected monitoring devices and a feedback system demonstrated improvement in dyspnea symptoms in patients with HF. This study provides evidence and rationale for implementing mobile app-based self-care strategies and feedback for patients with HF. TRIAL REGISTRATION: ClinicalTrials.gov NCT05668000; https://clinicaltrials.gov/study/NCT05668000.

Impact of Everolimus Initiation and Corticosteroid Weaning During Acute Phase After Heart Transplantation on Clinical Outcome: Data from the Korean Organ Transplant Registry (KOTRY).

The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56 years (interquartile range [IQR], 45-62), and the median follow-up time was 3.9 years (IQR 2.0-5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09-0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19-0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.

Application and Potential of Artificial Intelligence in Heart Failure: Past, Present, and Future.

The prevalence of heart failure (HF) is increasing, necessitating accurate diagnosis and tailored treatment. The accumulation of clinical information from patients with HF generates big data, which poses challenges for traditional analytical methods. To address this, big data approaches and artificial intelligence (AI) have been developed that can effectively predict future observations and outcomes, enabling precise diagnoses and personalized treatments of patients with HF. Machine learning (ML) is a subfield of AI that allows computers to analyze data, find patterns, and make predictions without explicit instructions. ML can be supervised, unsupervised, or semi-supervised. Deep learning is a branch of ML that uses artificial neural networks with multiple layers to find complex patterns. These AI technologies have shown significant potential in various aspects of HF research, including diagnosis, outcome prediction, classification of HF phenotypes, and optimization of treatment strategies. In addition, integrating multiple data sources, such as electrocardiography, electronic health records, and imaging data, can enhance the diagnostic accuracy of AI algorithms. Currently, wearable devices and remote monitoring aided by AI enable the earlier detection of HF and improved patient care. This review focuses on the rationale behind utilizing AI in HF and explores its various applications.

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

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

Clinical Implications of Device-Detected Atrial Fibrillation in Cardiac Resynchronization Therapy.

BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) is associated with decreased cardiac resynchronization therapy (CRT) benefits compared to sinus rhythm (SR). Effective biventricular (BiV) pacing is a determinant of CRT success, but AF can interfere with adequate BiV pacing and affect clinical outcomes. We investigated the effect of device-detected AF on clinical outcomes and optimal BiV pacing in patients with heart failure (HF) treated with CRT. METHODS: We retrospectively analyzed 174 patients who underwent CRT implantation between 2012 and 2019 at a tertiary center. The optimal BiV pacing percentage was defined as ≥98%. Device-detected AF was defined as an atrial high-rate episode ≥180 beats per minute lasting more than 6 minutes during the follow-up period. We stratified the patients without preexisting AF at pre-implantation into device-detected AF and no-AF groups. RESULTS: A total of 120 patients did not show preexisting AF at pre-implantation, and 54 had AF. Among these 120 patients, 19 (15.8%) showed device-detected AF during a median follow-up of 25.1 months. The proportion of optimal BiV pacing was significantly lower in the device-detected AF group than in the no-AF group (42.1% vs. 75.2%, p=0.009). The device-detected AF group had a higher incidence of HF hospitalization, cardiovascular death, and all-cause death than the no-AF group. The device-detected AF and previous AF groups showed no significant differences regarding the percentage of BiV pacing and clinical outcomes. CONCLUSIONS: For HF patients implanted with CRT, device-detected AF was associated with lower optimal BiV pacing and worse clinical outcomes than no-AF.

Iron Deficiency in Korean Patients With Heart Failure.

BACKGROUND: Although iron deficiency (ID) is an important and treatable risk factor for heart failure (HF), data on ID are scarce in Asian patients with HF. Therefore, we sought to determine the prevalence and clinical characteristics of ID in hospitalized Korean patients with HF. METHODS: In this prospective, multicenter cohort study, 461 patients with acute HF seen at five tertiary centers from January to November 2019 in Korea were enrolled. ID was defined as serum ferritin < 100 µg/L or ferritin 100-299 µg/L in combination with transferrin saturation < 20%. RESULTS: The patients' mean age was 67.6 ± 14.9 years, and 61.8% were male. Among total 461 patients, ID was present in 248 patients (53.8%). The prevalence of ID was significantly higher in women than in men (65.3% vs. 47.3%, P < 0.001). In a multivariable logistic regression analysis, the independent predictors of ID were female sex (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.47-3.30), valvular heart disease (OR, 2.10; 95% CI, 1.10-4.17), higher heart rate (OR, 1.10; 95% CI, 1.01-1.21), anemia (OR, 1.60; 95% CI, 1.07-2.40), and the use of clopidogrel (OR, 1.56; 95% CI, 1.00-2.45). Among women, the prevalence of ID did not significantly differ between younger and older women (< 65 years: 73.7% vs. ≥ 65 years: 63.0%, P = 0.222), those with low and high body mass index (BMI < 25 kg/m²: 66.2% vs. BMI ≥ 25 kg/m²: 69.6%, P = 0.703), or those with low and high natriuretic peptide (NP) levels (NP < median: 69.8% vs. NP ≥ median: 61.1%, P = 0.295). Only 0.2% patients with acute HF received intravenous iron supplementation in Korea. CONCLUSION: The prevalence of ID is high in hospitalized Korean patients with HF. Because ID cannot be diagnosed by clinical parameters, routine laboratory examinations are necessary to identify patients with ID. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04812873.

The ReInforcement of adherence via self-monitoring app orchestrating biosignals and medication of RivaroXaban in patients with atrial fibrillation and co-morbidities: a study protocol for a randomized controlled trial (RIVOX-AF).

Background: Because of the short half-life of non-vitamin K antagonist oral anticoagulants (NOACs), consistent drug adherence is crucial to maintain the effect of anticoagulants for stroke prevention in atrial fibrillation (AF). Considering the low adherence to NOACs in practice, we developed a mobile health platform that provides an alert for drug intake, visual confirmation of drug administration, and a list of medication intake history. This study aims to evaluate whether this smartphone app-based intervention will increase drug adherence compared with usual care in patients with AF requiring NOACs in a large population. Methods: This prospective, randomized, open-label, multicenter trial (RIVOX-AF study) will include a total of 1,042 patients (521 patients in the intervention group and 521 patients in the control group) from 13 tertiary hospitals in South Korea. Patients with AF aged ≥19 years with one or more comorbidities, including heart failure, myocardial infarction, stable angina, hypertension, or diabetes mellitus, will be included in this study. Participants will be randomly assigned to either the intervention group (MEDI-app) or the conventional treatment group in a 1:1 ratio using a web-based randomization service. The intervention group will use a smartphone app that includes an alarm for drug intake, visual confirmation of drug administration through a camera check, and presentation of a list of medication intake history. The primary endpoint is adherence to rivaroxaban by pill count measurements at 12 and 24 weeks. The key secondary endpoints are clinical composite endpoints, including systemic embolic events, stroke, major bleeding requiring transfusion or hospitalization, or death during the 24 weeks of follow-up. Discussion: This randomized controlled trial will investigate the feasibility and efficacy of smartphone apps and mobile health platforms in improving adherence to NOACs. Trial registration: The study design has been registered in ClinicalTrial.gov (NCT05557123).

Statins and Clinical Outcomes in Patients With Low to Moderate Risk but With Non-obstructive Carotid Plaques: The SCOPE-CP Study.

BACKGROUND AND OBJECTIVES: Some individuals exhibit discrepancies between risk classifications assessed using clinical factors and those obtained by vascular imaging. We aimed to evaluate whether statins provide clinical outcome benefits in patients classified as having low to moderate cardiovascular risk but with carotid plaque. METHODS: This was a retrospective propensity score matching study. A total of 12,158 consecutive patients undergoing carotid ultrasound between January 2012 to February 2020 were screened. Individuals with low to moderate cardiovascular risk who were not currently recommended for statin therapy but had carotid plaques were included. Among 1,611 enrolled individuals, 806 (statin group: 403, control group: 403) were analyzed. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCEs: cardiovascular death, myocardial infarction, coronary revascularization, and ischemic stroke or transient ischemic attack) and all-cause mortality. RESULTS: During the median follow-up of 6.0 years, the incidence of MACCEs did not differ between the groups (6.1 and 5.7/1,000 person-years in the control and statin groups, respectively; adjusted hazard ratio [HR], 0.95; p=0.90). The incidence of all-cause mortality did not differ (3.9 and 3.9/1,000 person-years, respectively; adjusted HR, 1.02; p=0.97). Kaplan-Meier curves revealed similar rates of MACCEs (log-rank p=0.72) and all-cause mortality (log-rank p=0.99) in the 2 groups. Age and smoking were independent predictors of MACCEs. Subgroups exhibited no differences in clinical outcomes with statin use. CONCLUSIONS: Benefit of statin therapy was likely to be limited in low to moderate risk patients with carotid plaques. These results could guide physicians in clinical decision-making regarding cardiovascular prevention.

Impact of predicted heart mass-based size matching on survival after heart transplantation in Korea: Analysis of the Korean Organ Transplant Registry.

BACKGROUND: Previous studies regarding donor-recipient size and sex matching in heart transplantation (HTx) mainly included Caucasians with only a small portion of Asians. Even predicted heart mass (PHM) has not yet been elucidated in Asians. We evaluated the association between donor-recipient sex and size matching, including mismatching by PHM, and post-heart transplant survival in Korea. METHODS: We enrolled 660 adult HTx recipients between January 2014 and December 2020 using the Korean Organ Transplant Registry data. Recipients were categorized based on donor-recipient PHM, body weight, and sex matching. The primary outcome was 1-year mortality and retransplantation after HTx and survival analyses were performed using Kaplan-Meier method and Cox proportional hazard models. RESULTS: Among 660 patients, 74 (11.2%), 404 (61.2%), and 182 (27.6%) received undersized (<-15%), matched (-15% to 20%), and oversized (>20%) hearts by PHM, respectively. Size mismatching by PHM was present in a large number of sex-mismatched patients with 85.1% of male donor-female recipients being classified as oversized by PHM and 62.2% of female donor-male recipients being classified as undersized by PHM. Recipients of undersized or oversized hearts by PHM showed an increased 1-year mortality compared with recipients of matched-size hearts (14.8% versus 9.7%; log-rank p = 0.038). The increased mortality persisted after adjusting for other factors affecting mortality (hazard ratio = 1.60, 95% confidence interval: 1.01-2.56). These associations were not shown in obese recipients (body mass index ≥25 kg/m2). Heart size mismatching by body weight (log-rank p = 0.332) or sex mismatching (all, log-rank p > 0.05) did not predict 1-year mortality after HTx. CONCLUSION: Heart size matching by PHM, not by body weight or sex, was associated with increased 1-year mortality after HTx in Korea.

Self-Monitoring of Blood Pressure and Feed-back Using APP in TReatment of UnconTrolled Hypertension (SMART-BP): A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Self-monitoring of blood pressure (SMBP) is a reliable method used to assess BP accurately. However, patients do not often know how to respond to the measured BP value. We developed a mobile application-based feed-back algorithm (SMBP-App) for tailored recommendations. In this study, we aim to evaluate whether SMBP-App is superior to SMBP alone in terms of BP reduction and drug adherence improvement in patients with hypertension. METHODS: Self-Monitoring of blood pressure and Feed-back using APP in TReatment of UnconTrolled Hypertension (SMART-BP) is a prospective, randomized, open-label, multicenter trial to evaluate the efficacy of SMBP-App compared with SMBP alone. Patients with uncomplicated essential hypertension will be randomly assigned to the SMBP-App (90 patients) and SMBP alone (90 patients) groups. In the SMBP group, the patients will perform home BP measurement and receive the standard care, whereas in the SMBP-App group, the patients will receive additional recommendations from the application in response to the obtained BP value. Follow-up visits will be scheduled at 12 and 24 weeks after randomization. The primary endpoint of the study is the mean home systolic BP. The secondary endpoints include the drug adherence, the home diastolic BP, home and office BP. CONCLUSIONS: SMART-BP is a prospective, randomized, open-label, multicenter trial to evaluate the efficacy of SMBP-App. If we can confirm its efficacy, SMBP-App may be scaled-up to improve the treatment of hypertension. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04470284.

2022 Consensus Statement on the Management of Familial Hypercholesterolemia in Korea.

Familial hypercholesterolemia (FH) is the most common monogenic disorder. Due to the marked elevation of cardiovascular risk, the early detection, diagnosis, and proper management of this disorder are critical. Herein, the 2022 Korean guidance on this disease is presented. Clinical features include severely elevated low-density lipoprotein-cholesterol (LDL-C) levels, tendon xanthomas, and premature coronary artery disease. Clinical diagnostic criteria include clinical findings, family history, or pathogenic mutations in the LDLR, APOB, or PCSK9. Proper suspicion of individuals with typical characteristics is essential for screening. Cascade screening is known to be the most efficient diagnostic approach. Early initiation of lipid-lowering therapy and the control of other risk factors are important. The first-line pharmacological treatment is statins, followed by ezetimibe, and PCSK9 inhibitors as required. The ideal treatment targets are 50% reduction and <70 mg/dL or <55 mg/dL (in the presence of vascular disease) of LDL-C, although less strict targets are frequently used. Homozygous FH is characterized by untreated LDL-C >500 mg/dL, xanthoma since childhood, and family history. In children, the diagnosis is made with criteria, including items largely similar to those of adults. In women, lipid-lowering agents need to be discontinued before conception.

2022 Consensus statement on the management of familial hypercholesterolemia in Korea.

Familial hypercholesterolemia (FH) is the most common monogenic disorder. Due to the marked elevation of cardiovascular risk, the early detection, diagnosis, and proper management of this disorder are critical. Herein, the 2022 Korean guidance on this disease is presented. Clinical features include severely elevated low-density lipoprotein cholesterol (LDL-C) levels, tendon xanthomas, and premature coronary artery disease. Clinical diagnostic criteria include clinical findings, family history, or pathogenic mutations in the LDLR, APOB, or PCSK9. Proper suspicion of individuals with typical characteristics is essential for screening. Cascade screening is known to be the most efficient diagnostic approach. Early initiation of lipid-lowering therapy and the control of other risk factors are important. The first-line pharmacological treatment is statins, followed by ezetimibe, and PCSK9 inhibitors as required. The ideal treatment targets are 50% reduction and < 70 or < 55 mg/dL (in the presence of vascular disease) of LDL-C, although less strict targets are frequently used. Homozygous FH is characterized by untreated LDL-C > 500 mg/dL, xanthoma since childhood, and family history. In children, the diagnosis is made with criteria, including items largely similar to those of adults. In women, lipid-lowering agents need to be discontinued before conception.

Prevalence and clinical characteristics of primary aldosteronism in a tertiary-care center in Korea.

Approximately 29% of Korean adults have hypertension; however, the prevalence of primary aldosteronism among the hypertensive population is largely unknown. The aim of our study was to evaluate the prevalence and clinical characteristics of primary aldosteronism in a tertiary-care center in Korea. We retrospectively analyzed 1173 patients with newly diagnosed or preexisting hypertension who were referred to our tertiary-care hospital between January 2013 and December 2018. Patients were screened for primary aldosteronism with the aldosterone-renin ratio and underwent a saline infusion test for diagnostic confirmation. Adrenal computed tomography and adrenal venous sampling were performed for subtype classification for primary aldosteronism. Among the 1173 patients (mean age, 51.8 years; women, 53.2%), 360 (30.7%) had positive screening-test results, of whom 71 (6.1%) were finally diagnosed with primary aldosteronism. Conclusive subtype differentiation was made in 55 patients, of whom 15 (27%) had an aldosterone-producing adenoma, 4 (7%) had unilateral adrenal hyperplasia, and 36 (66%) had bilateral adrenal hyperplasia. Patients with primary aldosteronism had a higher ambulatory blood pressure, left ventricular mass index, and urinary albumin-to-creatinine ratio than those without. Moreover, the primary aldosteronism group had a higher prevalence of left ventricular hypertrophy and albuminuria than the non-primary aldosteronism group. Primary aldosteronism may be more common (6.1%) among Korean patients with hypertension than generally recognized. Primary aldosteronism was associated with a higher degree and prevalence of target organ damage and a higher blood pressure level. Wide application of screening tests for primary aldosteronism may be beneficial in detecting this potentially curable cause of hypertension.

Prevalence and prognosis of refractory hypertension diagnosed using ambulatory blood pressure measurements.

The prognosis of refractory hypertension is largely unknown due to its low prevalence. This study aimed to investigate the prognosis of refractory hypertension and compare it with those of resistant and nonresistant hypertension. We retrospectively analyzed the data of 16,284 participants with hypertension who underwent ambulatory blood pressure (BP) monitoring between 2012 and 2019 at a tertiary center. Uncontrolled BP was defined as a 24-h BP ≥ 130/80 mmHg as assessed by ambulatory BP monitoring. Resistant hypertension was defined as uncontrolled BP despite the use of three antihypertensive medications, including a diuretic or the use of ≥4 drugs regardless of BP control. Refractory hypertension was defined as uncontrolled BP despite the use of ≥5 antihypertensive medications. Among 16,284 patients with hypertension (mean age 59.2 ± 15.5 years, 52.7% men), 1501 (9.2%) and 150 (0.9%) patients had resistant and refractory hypertension, respectively. The prevalence of chronic kidney disease, end-stage renal disease, heart failure, previous stroke, left ventricular hypertrophy, and the riser/nondipper patterns of circadian BP rhythm progressively increased from patients with nonresistant hypertension to patients with resistant hypertension to patients with refractory hypertension. During a median follow-up of 3.9 years, the risk of cardiovascular mortality progressively increased from patients with nonresistant hypertension to patients with resistant hypertension (hazard ratio 1.62, 95% confidence interval 1.16-2.26) to patients with refractory hypertension (hazard ratio 5.22, 95% confidence interval 3.04-8.96). In conclusion, refractory hypertension, defined as uncontrolled ambulatory BP levels, was associated with a higher risk of all-cause and cardiovascular mortality than nonresistant or resistant hypertension.

Generation of a human induced pluripotent stem cell line YCMi004-A from a patient with dilated cardiomyopathy carrying a protein-truncating mutation of the Titin gene and its differentiation towards cardiomyocytes.

Dilated cardiomyopathy (DCM) is a heart muscle disease that causes heart failure and is the leading cause for heart transplantation. It is a heart muscle disease resulted from a variety of genetics, toxic, metabolic, and infectious causes. One of the most prevalent genetic causes of DCM is a protein-truncating variant in the Titin gene (TTNtv). We have generated a human-induced pluripotent stem cell (hiPSC) line from patients who underwent heart transplantation due to DCM carrying a TTNtv mutation (c.70051C > T, p.Arg23351Ter) at the age of 20. The generated hiPSCs showed normal karyotype (46, XY) and expression of pluripotency markers, and were differentiated towards cardiomyocytes successfully.

C-reactive protein and statins in heart failure with reduced and preserved ejection fraction.

Background: High C-reactive protein (CRP) levels are associated with poor outcomes of heart failure (HF), and statins are known to reduce CRP levels. We investigated the prognostic value of CRP and statin in patients with HF with reduced and preserved ejection fraction (EF). Methods: Altogether, 3,831 patients from the Korean Acute Heart Failure registry were included and stratified according to the tertiles of CRP levels (T1: CRP < 0.30 mg/dL, T2: 0.30-1.14 mg/dL, and T3: CRP > 1.14 mg/dL). HF with reduced EF (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF) were defined as left ventricular ejection fraction (LVEF) ≤ 40%, 41-49%, ≥50%, respectively. The primary endpoints were all-cause, in-hospital, and post-discharge mortality. Results: No significant correlation was observed between CRP levels and LVEF (r = 0.02, P = 0.131). The prevalence of risk factors increased gradually from T1 to T3 in both the types of HF. Overall, 139 (3.6%) and 1,269 (34.4%) patients died during the index admission and follow-up (median: 995 days), respectively. After adjustment, each increase in the CRP tertiles was independently associated with in-hospital mortality (HFrEF: OR 1.58 and 95% CI 1.09-2.30, HFmrEF: OR 1.51 and 95% CI 0.72-3.52, and HFpEF: OR 2.98, 95% CI 1.46-6.73) and post-discharge mortality (HFrEF: HR 1.20, 95% CI 1.08-1.33, HFmrEF: HR 1.38 and 95% CI 1.12-1.70, and HFpEF: HR 1.37, 95% CI 1.02-1.85). In only patients with LVEF > 40% with highest CRP tertile, statin-users showed better survival trend than those without statins. Conclusion: CRP is an excellent prognostic marker for HFrEF, HFmrEF, and HFpEF, implying that the neurohumoral and inflammatory pathways might be independent pathways. Statins may be beneficial in HF patients with increased CRP levels. Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT013 89843].

Association of Physical Activity Level With Risk of Dementia in a Nationwide Cohort in Korea.

Importance: Current guidelines recommend 500 to 999 metabolic equivalent (MET)-minutes per week (MET-min/wk) of regular physical activity. However, evidence regarding the association between light-intensity physical activity (LPA) and dementia in older adults is inconsistent. Objective: To assess the association between physical activity and new-onset dementia, focusing on the dose-response association between physical activity and dementia and the association of LPA with the incidence of dementia. Design, Setting, and Participants: For this nationwide retrospective cohort study, we analyzed 62 286 participants aged 65 years or older without preexisting dementia who had available health checkup data from the Korean National Health Insurance Service database from January 2009 to December 2012. Participants were followed up until December 31, 2013, and data analysis was performed from July 2020 to January 2021. Exposures: Physical activity level was assessed using a standardized, self-reported questionnaire at baseline. Physical activity-related energy expenditure (in MET-min/wk) was calculated by summing the product of frequency, intensity, and duration. Main Outcomes and Measures: Incidence of dementia. Incidence rates were calculated by dividing the number of events by the person-time at risk (presented as the incidence per 1000 person-years). Hazard ratios (HRs) and 95% CIs for dementia were analyzed according to physical activity level. Competing risk regression was performed by using the Fine-Gray subdistribution hazard model, with mortality as the competing risk for dementia events. Multivariable regression models were constructed with adjustment for various patient characteristics. Incident dementia occurring 2 years after enrollment was assessed, and separate analyses included all follow-up periods. Restricted cubic spline curves were used to examine the association of continuous values of physical activity with dementia. Results: Among 62 286 participants, 60.4% were women, and the mean (SD) age was 73.2 (5.3) years. During a median follow-up of 42 months, 3757 participants (6.0%) developed dementia, and the overall incidence was 21.6 per 1000 person-years. Compared with inactive individuals (0 MET-min/wk), insufficiently active (1-499 MET-min/wk; mean, 284 MET-min/wk), active (500-999 MET-min/wk; mean, 675 MET-min/wk), and highly active participants (≥1000 MET-min/wk; mean, 1627 MET-min/wk) showed 10% (adjusted hazard ratio [HR], 0.90; 95% CI, 0.81-0.99), 20% (adjusted HR, 0.80; 95% CI, 0.71-0.92), and 28% (adjusted HR, 0.72; 95% CI, 0.60-0.83) reduced dementia risk, respectively. Thus, a progressive decrease in the adjusted HR of dementia was associated with increasing physical activity level, and a restricted cubic spline curve showed that this association started with a low amount of total physical activity. This association was consistent regardless of age, sex, and other comorbidities or after censoring for stroke. Compared with total sedentary behavior, even a low amount of LPA (1-299 MET-min/wk; mean, 189 MET-min/wk) was associated with reduced dementia risk (adjusted HR, 0.86; 95% CI, 0.74-0.99). Conclusions and Relevance: In older adults, an increased physical activity level, including a low amount of LPA, was associated with a reduced risk of dementia. Promotion of LPA might reduce the risk of dementia in older adults.