J-shaped relationship between serum creatinine and mortality in Korean patients with acute heart failure.

BACKGROUND: Cachexia and sarcopenia are common among heart failure (HF) patients and are linked to poor outcomes. As serum creatinine levels are influenced by both renal function and muscle mass, our study aimed to investigate the relationship between serum creatinine levels and mortality in acute HF patients. METHODS: We enrolled 5198 consecutive acute HF patients from the Korea Acute Heart Failure (KorAHF) registry, excluding those on renal replacement therapy. Patients were categorized into five groups based on their discharge serum creatinine levels: low (< 0.6 mg/dL), reference (0.6-0.89 mg/dL), upper normal (0.9-1.19 mg/dL), high (1.2-1.49 mg/dL), and very high (≥ 1.5 mg/dL). The primary endpoint was post-discharge all-cause mortality. RESULTS: The mean creatinine level was 1.20 ± 0.88 mg/dL. Notably, 335 (6.4%) patients had serum creatinine levels < 0.6 mg/dL. These patients were younger (mean age, 67 years) and more likely to have a low BMI (< 18.5 kg/m2) compared to the reference group (15.3% vs. 6.4%). Over a median follow-up of 975 days, 1743 (34.8%) patients died. We observed a J-shaped relationship between serum creatinine levels and mortality, with both low and high levels associated with increased mortality. After adjusting for covariates, including age, sex, body mass index, diabetes, hypertension, smoking, malignancy, atrial fibrillation on electrocardiography, levels of C-reactive protein, sodium, hemoglobin, albumin, brain natriuretic peptide, de novo heart failure, use of beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists, patients with serum creatinine levels < 0.6 mg/dL had a 33% higher risk of all-cause mortality (HR, 1.33; 95% CI, 1.06 to 1.66) compared to those with levels of 0.6-0.89 mg/dL. However, BUN, which is not affected by muscle metabolism, exhibited a linear relationship with mortality. CONCLUSIONS: Among acute HF patients, there exists a J-shaped relationship between discharge serum creatinine levels and mortality, highlighting the increased mortality risk in individuals with very low serum creatinine levels.

Differences in the Effects of Beta-Blockers Depending on Heart Rate at Discharge in Patients With Heart Failure With Preserved Ejection Fraction and Atrial Fibrillation.

Background and Objectives: Beta-blockers (BBs) improve prognosis in heart failure (HF), which is mediated by lowering heart rate (HR). However, HR has no prognostic implication in atrial fibrillation (AF) and also BBs have not been shown to improve prognosis in heart failure with preserved ejection fraction (HFpEF) with AF. This study assessed the prognostic implication of BB in HFpEF with AF according to discharge HR. Methods: From the Korean Acute Heart Failure Registry, 687 patients with HFpEF and AF were selected. Study subjects were divided into 4 groups based on 75 beats per minute (bpm) of HR at discharge and whether or not they were treated with BB at discharge. Results: Of the 687 patients with HFpEF and AF, 128 (36.1%) were in low HR group and 121 (36.4%) were in high HR group among those treated with BB at discharge. In high HR group, HR at discharge was significantly faster in BB non-users (85.5±9.1 bpm vs. 89.2±12.5 bpm, p=0.005). In the Cox model, BB did not improve 60-day rehospitalization (hazard ratio, 0.93; 95% confidence interval [95% CI], 0.35-2.47) or mortality (hazard ratio, 0.77; 95% CI, 0.22-2.74) in low HR group. However, in high HR group, BB treatment at discharge was associated with 82% reduced 60-day HF rehospitalization (hazard ratio, 0.18; 95% CI, 0.04-0.81), but not with mortality (hazard ratio, 0.77; 95% CI, 0.20-2.98). Conclusions: In HFpEF with AF, in patients with HR over 75 bpm at discharge, BB treatment at discharge was associated with a reduced 60-day rehospitalization rate.

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.

Effect of hemoglobin A1c change on 24-month clinical outcomes in patients with diabetes after acute myocardial infarction.

BACKGROUND: The average glycated hemoglobin (HbA1c) may not accurately reflect glycemic control status during the mid-term after acute myocardial infarction (AMI). We aimed to evaluate changes in HbA1c and their effect on mid-term clinical outcomes in patients with diabetes and AMI. METHODS: We enrolled patients with diabetes ( n  = 967) who underwent HbA1c measurement in the Korean nationwide registry. These patients were categorized into three groups based on changes in HbA1c from index admission to the 1-year follow-up visit: a decrease in HbA1c > 1%, changes in HbA1c within 1%, and an increase in HbA1c > 1%. Clinical outcomes at 24 months were examined. RESULTS: The baseline HbA1c levels were 8.55 ±â€…0.85, 7.00 ±â€…0.98 and 7.07 ±â€…1.05 ( P  = 0.001) and HbA1c levels after 1 year were 6.62 ±â€…0.73, 7.05 ±â€…0.98 and 9.26 ±â€…1.59 ( P  = 0.001) for patients with 3 groups, respectively. Patients with a 1% decrease in HbA1c had significantly lower incidence of major adverse cardiovascular events (MACE), cardiac death, and rehospitalization after 24 months than those with a 1% increase in HbA1c. However, in the Cox regression analysis, a >1% decrease in HbA1c change was not an independent factor for MACE, cardiac death, and rehospitalization. CONCLUSIONS: Our analysis indicates that an HbA1c decrease of >1% within the first 12 months was not an independent prognostic factor until the 24-month mark. Therefore, standard diabetic control is recommended for patients with diabetes and AMI for up to 2 years.

Lower Atrial Fibrillation Risk With Sodium-Glucose Cotransporter 2 Inhibitors Than With Dipeptidyl Peptidase-4 Inhibitors in Individuals With Type 2 Diabetes: A Nationwide Cohort Study.

BACKGROUND AND OBJECTIVES: Accumulating evidence shows that sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce adverse cardiovascular outcomes. However, whether SGLT2i, compared with other antidiabetic drugs, reduce the new development of atrial fibrillation (AF) is unclear. In this study, we compared SGLT2i with dipeptidyl peptidase-4 inhibitors (DPP-4is) in terms of reduction in the risk of AF in individuals with type 2 diabetes. METHODS: We included 42,786 propensity score-matched pairs of SGLT2i and DPP-4i users without previous AF diagnosis using the Korean National Health Insurance Service database between May 1, 2016, and December 31, 2018. RESULTS: During a median follow-up of 1.3 years, SGLT2i users had a lower incidence of AF than DPP-4i users (1.95 vs. 2.65 per 1,000 person-years; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.97; p=0.028]). In individuals without heart failure, SGLT2i users was associated with a decreased risk of AF incidence (HR, 0.70; 95% CI, 0.52-0.94; p=0.019) compared to DPP-4i users. However, individuals with heart failure, SGLT2i users was not significantly associated with a change in risk (HR, 1.04; 95% CI, 0.44-2.44; p=0.936). CONCLUSIONS: In this nationwide cohort study of individuals with type 2 diabetes, treatment with SGLT2i was associated with a lower risk of AF compared with treatment with DPP-4i.

SCORE and SCORE2 in East Asian Population: A Performance Comparison.

Background: Systematic COronary Risk Evaluation 2 (SCORE2) and SCORE2-Older Persons (OP) models have been proposed as new cardiovascular risk evaluation tools. Objectives: This study evaluated the performance of SCORE/SCORE-OP and SCORE2/SCORE2-OP in the East Asian population by using population-based cohort data from the National Health Insurance Service (NHIS) Health Screening Cohort of Korea. Methods: A total of 324,384 NHIS examinees from 2004 to 2005 were divided into 5 age groups: 40-49 years, 50-59 years, 60-69 years,70-79 years, and more than 80 years. The examinees had their predicted cardiovascular disease risks calculated by using SCORE, SCORE2, SCORE-OP, and SCORE2-OP models. The low-risk model was applied on the basis of the cohort's observed event rates. The observed and predicted cardiovascular risks were compared. Results: A total of 324,384 subjects were included (mean age 51.4 ± 7.3 years; women, 37.9% for the SCORE/SCORE2 group and mean age 73.0 ± 2.8 years; women, 47.5% for the SCORE/SCORE2-OP group). Over a median follow-up of 9 years, cardiovascular events occurred in 15.0% and 28.9% in SCORE/SCORE2 and SCORE/SCORE2-OP groups, respectively. The SCORE/SCORE-OP model underestimated cardiovascular disease risk in young men (aged 40-49 years) and women (aged 40-59 years) and overestimated it in older age groups. In contrast, SCORE2/SCORE2-OP invariably overestimated the risk in all age groups and sexes. SCORE2/SCORE2-OP showed no improvement in Harrell's concordance index (C-index) compared with SCORE/SCORE-OP. Calibration plots favored SCORE2 over SCORE but not SCORE2-OP over SCORE-OP. Conclusions: Both SCORE2/SCORE2-OP and SCORE/SCORE-OP overestimated cardiovascular disease risk with low performance. SCORE2/SCORE2-OP showed slight improvement over older versions, but modifications are necessary for the East Asian population.

Association Between Orthostatic Hypertension and Frailty Among Older Patients With Hypertension.

BACKGROUND: Frailty frequently coexists with hypertension in older patients. We aimed to evaluate the association between frailty and positional change in blood pressure, especially orthostatic hypertension. METHODS: Participants were recruited from 12 University hospitals in South Korea. Using a digital device, trained research nurses measured blood pressure in the supine and standing positions. Physical frailty was evaluated using the Korean version of the FRAIL questionnaire, gait speed, and handgrip strength. Orthostatic hypertension was defined as a ≥20-mm Hg increase in systolic blood pressure within 3 minutes of standing and upright systolic blood pressure of ≥140 mm Hg. RESULTS: We analyzed the data of 2065 participants who had been enrolled until December 31, 2022. The mean age was 73.2±5.6 years, and 52.0% were female. The mean blood pressure was 137.1±14.9/75.1±9.7 mm Hg. Among the participants, 1886 (91.3%) showed normal response after standing, but 94 (4.6%) had orthostatic hypertension, and 85 (4.1%) had orthostatic hypotension. Orthostatic hypertension was associated with female sex, obesity, cognitive function, physical frailty, and lower quality of life. In the multivariable analysis, body mass index and frailty status were independently associated with orthostatic hypertension. CONCLUSIONS: Orthostatic hypertension is associated with physical frailty, cognitive impairment, and low quality of life in older patients with hypertension. Therefore, evaluation of orthostatic blood pressure changes to confirm orthostatic hypertension or hypotension in frail older adults will serve as an important diagnostic procedure in vulnerable patients. Further studies are required to identify the underlying mechanisms of this association.

Characteristics According to Frailty Status Among Older Korean Patients With Hypertension.

BACKGROUND: As the prevalence of hypertension increases with age and the proportion of the older population is also on the rise, research on the characteristics of older hypertensive patients and the importance of frailty is necessary. This study aimed to identify clinical characteristics of older hypertension in Korea and to investigate these characteristics based on frailty status. METHODS: The HOW to Optimize eLDerly systolic BP (HOWOLD-BP) is a prospective, multicenter, open-label, randomized clinical trial that aims to compare intensive (target systolic blood pressure [SBP] ≤ 130 mmHg) with standard (target SBP ≤ 140 mmHg) treatment to reduce cardiovascular events in older hypertensive Korean patients aged ≥ 65 years. Data were analyzed through a screening assessment of 2,085 patients recruited from 11 university hospitals. Demographic, functional (physical and cognitive), medical history, laboratory data, quality of life, and medication history of antihypertensive drugs were assessed. RESULTS: The mean age was 73.2 years (standard deviation ± 5.60), and 48.0% (n = 1,001) were male. Prevalent conditions included dyslipidemia (66.5%), obesity (body mass index ≥ 25 kg/m², 53.6%), and diabetes (28.9%). Dizziness and orthostatic hypotension were self-reported by 1.6% (n = 33) and 1.2% (n = 24), respectively. The majority of patients were on two antihypertensive drugs (48.4%), while 27.5% (n = 574) and 20.8% (n = 433) were on 1 and 3 antihypertensive medications, respectively. Frail to pre-frail patients were older and also tended to have dependent instrumental activities of daily living, slower gait speed, weaker grip strength, lower quality of life, and lower cognitive function. The frail to pre-frail group reported more dizziness (2.6% vs. 1.2%, P < 0.001) and had concerning clinical factors, including lower glomerular filtration rate, more comorbidities such as diabetes, stroke, and a history of admission. Frail to pre-frail older hypertensive patients used slightly more antihypertensive medications than robust older hypertensive patients (1.95 vs. 2.06, P = 0.003). Pre-frail to frail patients often chose beta-blockers as a third medication over diuretics. CONCLUSION: This study described the general clinical characteristics of older hypertensive patients in Korea. Frail hypertensive patients face challenges in achieving positive clinical outcomes because of multifactorial causes: they are older, have more morbidities, decreased function, lower quality of life and cognitive function, and take more antihypertensive medications. Therefore, it is essential to comprehensively evaluate and monitor disease-related or drug-related adverse events more frequently during regular check-ups, which is necessary for pre-frail to frail older patients with hypertension. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003787.

Eligibility and Cost-Utility Analysis of Dapagliflozin in Patients with Heart Failure Across the Whole Spectrum of Ejection Fraction in South Korea.

BACKGROUND: The DAPA-HF and DELIVER trials demonstrated the clinical benefits of dapagliflozin in heart failure (HF) patients across the entire ejection fraction (EF) spectrum. However, further investigation is needed for the real-world application of dapagliflozin in HF patients. This study examines the proportion of real-world HF patients eligible for dapagliflozin and evaluates the cost-effectiveness of adding dapagliflozin to current HF therapy. METHODS: Data from the nationwide prospective registry, the Korean Acute Heart Failure (KorAHF) registry, were used to determine dapagliflozin eligibility based on the enrollment criteria of the DAPA-HF/DELIVER trials. A cost-utility analysis was conducted using a Markov model to assess the cost-effectiveness of dapagliflozin by comparing it to the standard of care. RESULTS: Out of 5178 KorAHF patients, 48.7% met the enrollment criteria of the DAPA-HF/DELIVER trials, while 89.5% met the label criteria (US Food and Drug Administration, European Medicines Agency, and Korean Ministry of Food and Drug Safety). Eligibility was highest among HF patients with preserved EF (55.3% vs. HF with mildly reduced EF and HF with reduced EF 46.4%). Dapagliflozin proved to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 4557 US dollar (US$) per quality-adjusted life year, which falls below the US$18,182 willingness-to-pay threshold. The cost-effectiveness benefit was more pronounced in patients with a left ventricular EF (LVEF) ≤ 40% (ICER US$3279 for LVEF ≤ 40% vs. US$8383 for LVEF > 40%). CONCLUSIONS: Discrepancies in dapagliflozin eligibility were observed between real-world data and clinical trial results. The addition of dapagliflozin to HF therapy proved to be highly cost-effective across the entire EF spectrum.

Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea.

BACKGROUND: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. METHODS: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). RESULTS: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). CONCLUSION: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843.