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.

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.

Prediction of longitudinal clinical outcomes after acute myocardial infarction using a dynamic machine learning algorithm.

Several regression-based models for predicting outcomes after acute myocardial infarction (AMI) have been developed. However, prediction models that encompass diverse patient-related factors over time are limited. This study aimed to develop a machine learning-based model to predict longitudinal outcomes after AMI. This study was based on a nationwide prospective registry of AMI in Korea (n = 13,104). Seventy-seven predictor candidates from prehospitalization to 1 year of follow-up were included, and six machine learning approaches were analyzed. Primary outcome was defined as 1-year all-cause death. Secondary outcomes included all-cause deaths, cardiovascular deaths, and major adverse cardiovascular event (MACE) at the 1-year and 3-year follow-ups. Random forest resulted best performance in predicting the primary outcome, exhibiting a 99.6% accuracy along with an area under the receiver-operating characteristic curve of 0.874. Top 10 predictors for the primary outcome included peak troponin-I (variable importance value = 0.048), in-hospital duration (0.047), total cholesterol (0.047), maintenance of antiplatelet at 1 year (0.045), coronary lesion classification (0.043), N-terminal pro-brain natriuretic peptide levels (0.039), body mass index (BMI) (0.037), door-to-balloon time (0.035), vascular approach (0.033), and use of glycoprotein IIb/IIIa inhibitor (0.032). Notably, BMI was identified as one of the most important predictors of major outcomes after AMI. BMI revealed distinct effects on each outcome, highlighting a U-shaped influence on 1-year and 3-year MACE and 3-year all-cause death. Diverse time-dependent variables from prehospitalization to the postdischarge period influenced the major outcomes after AMI. Understanding the complexity and dynamic associations of risk factors may facilitate clinical interventions in patients with AMI.

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.

Metformin treatment is associated with improved survival in diabetic patients hospitalized with acute heart failure: A prospective observational study using the Korean acute heart failure registry data.

AIMS: Although the hypothesis that metformin is beneficial for patients with diabetes and heart failure (HF) has been steadily raised, there is limited data on metformin use in patients with acute HF. We analyzed the association of metformin on all-cause mortality in hospitalized patients with type 2 diabetes and acute HF. METHODS: The Korean Acute Heart Failure registry prospectively enrolled patients hospitalized for acute HF from 2011 to 2014. Among this cohort, we analyzed patients with diabetes with baseline estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73 m2 or more. We analyzed the all-cause mortality and re-hospitalization for HF within 1 year after discharge. Inverse probability treatment weighting method was used to adjust baseline differences on metformin treatment. RESULTS: The study analyzed data from 1,309 patients with HF and diabetes (mean age 69 years, 56 % male). Among them, 613 (47 %) patients were on metformin at admission. During the median follow-up period of 11 months, 132 (19 %) and 74 (12 %) patients not receiving and receiving metformin treatment died, respectively. The mortality rate was lower in metformin users than in non-users (hazard ratio 0.616 [0.464-0.819] P<0.001). After adjustment, metformin was significantly associated with a lower risk for the mortality (hazard ratio 0.677 [0.495-0.928] P=0.015). In subgroup analyses, this association remains significant irrespective of baseline kidney function (eGFR <60 or ≥60 ml/min/1.73 m2, P-for-interaction=0.176) or left ventricular ejection fraction (<40 %, 40-49 %, or ≥50 %, P-for-interaction=0.224). CONCLUSIONS: Metformin treatment at the time of admission was associated with a lower risk for 1-year mortality in patients with diabetes, hospitalized for acute HF.

Korean guidelines for the management of gout.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Korean guidelines for the management of gout.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Prognosis after discontinuing renin angiotensin aldosterone system inhibitor for heart failure with restored ejection fraction after acute myocardial infarction.

Prognostic effect of discontinuing renin-angiotensin-aldosterone-system-inhibitor (RAASi) for patients with heart failure (HF) after acute myocardial infarction (AMI) whose left ventricular (LV) systolic function was restored during follow-up is unknown. To investigate the outcome after discontinuing RAASi in post-AMI HF patients with restored LV ejection fraction (EF). Of 13,104 consecutive patients from the nationwide, multicenter, and prospective Korea Acute Myocardial Infarction-National Institutes of Health (KAMIR-NIH) registry, HF patients with baseline LVEF < 50% that was restored to ≥ 50% at 12-month follow-up were selected. Primary outcome was a composite of all-cause death, spontaneous MI, or rehospitalization for HF at 36-month after index procedure. Of 726 post-AMI HF patients with restored LVEF, 544 maintained RAASi (Maintain-RAASi) beyond 12-month, 108 stopped RAASi (Stop-RAASi), and 74 did not use RAASi (RAASi-Not-Used) at baseline and follow-up. Systemic hemodynamics and cardiac workloads were similar among groups at baseline and during follow-up. Stop-RAASi group showed elevated NT-proBNP than Maintain-RAASi group at 36-month. Stop-RAASi group showed significantly higher risk of primary outcome than Maintain-RAASi group (11.4% vs. 5.4%; adjusted hazard ratio [HRadjust] 2.20, 95% confidence interval [CI] 1.09-4.46, P = 0.028), mainly driven by increased risk of all-cause death. The rate of primary outcome was similar between Stop-RAASi and RAASi-Not-Used group (11.4% vs. 12.1%; HRadjust 1.18 [0.47-2.99], P = 0.725). In post-AMI HF patients with restored LV systolic function, RAASi discontinuation was associated with significantly increased risk of all-cause death, MI, or rehospitalization for HF. Maintaining RAASi will be necessary for post-AMI HF patients, even after LVEF is restored.

Preoperative cardiac troponin I as a predictor of postoperative cardiac events in patients with end stage renal disease undergoing non-cardiac surgery.

We investigated if elevated cardiac troponin I (cTnI) serum levels before non-cardiac surgery were predictors of postoperative cardiac events in patients with end stage renal disease (ESRD) undergoing dialysis. In total, 703 consecutive patients with ESRD undergoing dialysis who underwent non-cardiac surgery were enrolled. Preoperative cTnI serum levels were measured at least once in all patients. The primary endpoint was defined as a composite of cardiac death, myocardial infarction (MI), and pulmonary edema during hospitalization or within 30 days after surgery in patients with a hospitalization longer than 30 days after surgery. Postoperative cardiac events occurred in 48 (6.8%) out of 703 patients (cardiac death 1, MI 18, and pulmonary edema 33). Diabetes mellitus (DM), previous ischemic heart disease, and congestive heart failure were more common in patients with postoperative cardiac events. Peak cTnI serum levels were higher in patients with postoperative cardiac event (180 ± 420 ng/L vs. 80 ± 190 ng/L, p = 0.008), and also elevated peak cTnI levels > 45 ng/L were more common in patients with postoperative cardiac events (66.8% vs. 30.5%, p < 0.001). Multivariate logistic regression analysis showed that DM (odds ratio [OR] 2.509, 95% confidence interval [CI] 1.178-5.345, p = 0.017) and serum peak cTnI levels ≥ 45 ng/L (OR 3.167, 95% CI 1.557-6.444, p = 0.001) were independent predictors for the primary outcome of cardiac death/MI/pulmonary edema. Moreover, cTnI levels ≥ 45 ng/L had an incremental prognostic value to the revised cardiac risk index (RCRI) (Chi-square = 23, p < 0.001), and to the combined RCRI and left ventricular ejection fraction (Chi-square = 12, p = 0.001). Elevated preoperative cTnI levels are predictors of postoperative cardiac events including cardiac death, MI, and pulmonary edema in patients with ESRD undergoing non-cardiac surgery.

In-hospital glycemic variability and all-cause mortality among patients hospitalized for acute heart failure.

BACKGROUND: High glycemic variability (GV) is a poor prognostic marker in cardiovascular diseases. We aimed to investigate the association of GV with all-cause mortality in patients with acute heart failure (HF). METHODS: The Korean Acute Heart Failure registry enrolled patients hospitalized for acute HF from 2011 to 2014. Blood glucose levels were measured at the time of admission, during hospitalization, and at discharge. We included those who had 3 or more blood glucose measurements in this study. Patients were divided into two groups based on the coefficient of variation (CoV) as an indicator of GV. Among survivors of the index hospitalization, we investigated all-cause mortality at 1 year after discharge. RESULTS: The study analyzed 2,617 patients (median age, 72 years; median left-ventricular ejection fraction, 36%; 53% male). During the median follow-up period of 11 months, 583 patients died. Kaplan-Meier curve analysis revealed that high GV (CoV > 21%) was associated with lower cumulative survival (log-rank P < 0.001). Multivariate Cox proportional analysis showed that high GV was associated with an increased risk of 1-year (HR 1.56, 95% CI 1.26-1.92) mortality. High GV significantly increased the risk of 1-year mortality in non-diabetic patients (HR 1.93, 95% CI 1.47-2.54) but not in diabetic patients (HR 1.19, 95% CI 0.86-1.65, P for interaction = 0.021). CONCLUSIONS: High in-hospital GV before discharge was associated with all-cause mortality within 1 year, especially in non-diabetic patients with acute HF.

Modified reverse shock index predicts early outcomes of heart failure with reduced ejection fraction.

AIMS: Increased blood pressure (BP) and decreased heart rate (HR) are signs of stabilization in patients admitted for acute HF. Changes in BP and HR during admission and their correlation with outcomes were assessed in hospitalized patients with heart failure (HF) with reduced ejection fraction (HFrEF). METHODS: A novel modified reverse shock index (mRSI), defined as the ratio between changes in systolic BP and HR during admission, was devised, and its prognostic value in the early outcomes of acute HF was assessed using the Korean Acute HF registry. RESULTS: Among 2697 patients with HFrEF (mean age 65.8 ± 14.9 years, 60.6% males), patients with mRSI ≥1.25 at discharge were significantly younger and were more likely to have de novo HF. An mRSI ≥1.25 was associated with a significantly lower incidence of 60-day and 180-day all-cause mortality [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.31-0.77; HR 0.62, 95% CI 0.45-0.85, respectively], compared with 1 ≤ mRSI < 1.25 (all P < 0.001). Conversely, an mRSI <0.75 was associated with a significantly higher incidence of 60-day and 180-day all-cause mortality (adjusted HR 2.08, 95% CI 1.19-3.62; HR 2.24, 95% CI 1.53-3.27; all P < 0.001). The benefit associated with mRSI ≥1.25 was consistent in sub-group analyses. The correlation of mRSI and outcomes were also consistent regardless of admission SBP, presence of atrial fibrillation, or use of beta blockers at discharge. CONCLUSIONS: In patients hospitalized for HFrEF, the mRSI was a significant predictor of early outcomes. The mRSI could be used as a tool to assess patient status and guide physicians in treating patients with HFrEF.

Prognostic Value of Baseline Neutrophil-to-Lymphocyte Ratio Combined With Anemia in Patients With ST-Segment Elevation Myocardial Infarction: A Nationwide Prospective Cohort Study.

Objective: Data pertaining to the prognostic value of the combination of high neutrophil-to-lymphocyte ratio (NLR) and anemia on admission in patients with ST-segment elevation myocardial infarction (STEMI) are limited. The objective of this study was to investigate the clinical value of baseline NLR in combination with anemia in predicting clinical outcomes after STEMI. Methods: A total of 5,194 consecutive patients with STEMI within 12 hours of symptom onset from the Korea Acute Myocardial Infarction Registry-National Institute of Health database between 2011 and 2015 were categorized into 4 groups according to their NLR and hemoglobin levels: low NLR (<4) without anemia (n=2,722; reference group); high NLR (≥4) without anemia (n=1,527); low NLR with anemia (n=508); and high NLR with anemia (n=437). The co-primary outcomes were 180-day and 3-year all-cause mortality. Results: Mortality rates significantly increased at the 3-year follow-up across the groups (3.3% vs. 5.4% vs. 16.5% vs. 21.7% for 180-day mortality and 5.3% vs. 9.0% vs. 23.8% vs. 33.4% for 3-year mortality; all p-trends <0.001). After adjusting for baseline covariates, the combination of high NLR and anemia was a significant predictor of 180-day mortality after STEMI with low NLR and no anemia as the reference (adjusted hazard ratio, 2.16; 95% confidence interval, 1.58-2.95; p<0.001). Similar findings were observed for the 3-year mortality. Conclusions: This nationwide prospective cohort study showed that the combination of high NLR (≥4) and anemia is a strong predictor of all-cause mortality after STEMI.

Impact of Cardiac Troponin Elevation on Mortality of Patients with Acute Heart Failure: Insights from the Korea Acute Heart Failure (KorAHF) Registry.

We aimed to conduct the largest study evaluating the impact of cardiac troponin (TnI) status on mid- and long-term mortality in patients admitted for acute heart failure (AHF) as compared between patients with ischemic (IHF) vs. non-ischemic heart failure (non-IHF). Among 5625 patients from the Korea Acute Heart Failure (KorAHF) registry, 4396 eligible patients with TnI measurement were analyzed. The patients were included on admission with the diagnosis of AHF, and TnI level was measured on the day of admission. A TnI value of <0.05 ng/mL was considered normal. The patients were divided into four groups according to the etiology of heart failure and the status of TnI: non-IHF with normal TnI (n = 1009) vs. non-IHF with elevated TnI (n = 1665) vs. IHF with normal TnI (n = 258) vs. IHF with elevated TnI (n = 1464). The primary outcome was death from all causes according to the etiology (non-IHF vs. IHF) and TnI elevation during the entire follow-up period of 784 days (IQR 446−1116). Elevation of TnI was observed in 71.2% of all patients with AHF. Patients with IHF had higher all-cause mortality compared to those with non-IHF. Elevated TnI was associated with higher 90-day and post-90-day mortality in the non-IHF group. IHF as compared to non-IHF and elevation of TnI were independent predictors of mortality also in the adjustment analysis. In the IHF group, however, elevated TnI had a higher mortality with only 90-day follow-up (18.6% vs. 25.9%, log-rank p < 0.001), not in the post-90-day follow-up (31.1% vs. 32.5%, log-rank p = 0.799). In conclusion, elevated TnI in patients with heart failure is associated with increased all-cause mortality regardless of the etiology of HF. Elevation of TnI was associated to a higher post-90 day mortality in patients with non-IHF but not in patients with IHF.

Prognostic Impact and Predictors of New-Onset Atrial Fibrillation in Heart Failure.

Background: The prognostic impact and predictors of NOAF in HF patients are not fully elucidated. This study aims to determine whether new-onset atrial fibrillation (NOAF) affects patient outcome and investigate predictors of atrial fibrillation (AF) in acute heart failure (HF) patients using real-world data. Methods: The factors associated with NOAF in 2894 patients with sinus rhythm (SR) enrolled in the Korean Acute Heart Failure (KorAHF) registry were investigated. Survival was analyzed using AF as a time-dependent covariate. Relevant predictors of NOAF were analyzed using multivariate proportional hazards models. Results: Over 27.4 months, 187 patients developed AF. The median overall survival time was over 48 and 9.9 months for the SR and NOAF groups, respectively. Cox regression analysis with NOAF as a time-dependent covariate showed a higher risk of death among patients with NOAF. Multivariate Cox modeling showed that age, worsening HF, valvular heart disease (VHD), loop diuretics, lower heart rate, larger left atrium (LA) diameter, and elevated creatinine levels were independently associated with NOAF. Risk score indicated the number of independent predictors. The incidence of NOAF was 2.9%, 9.4%, and 21.8% in the low-risk, moderate-risk, and high-risk groups, respectively (p < 0.001). Conditional inference tree analysis identified worsening HF, heart rate, age, LA diameter, and VHD as discriminators. Conclusions: NOAF was associated with decreased survival in acute HF patients with SR. Age, worsening HF, VHD, loop diuretics, lower heart rate, larger LA diameter, and elevated creatinine could independently predict NOAF. This may be useful to risk-stratify HF patients at risk for AF.

Corrigendum: The Prescription Characteristics, Efficacy and Safety of Spironolactone in Real-World Patients With Acute Heart Failure Syndrome: A Prospective Nationwide Cohort Study.

[This corrects the article DOI: 10.3389/fcvm.2022.791446.].

The Prescription Characteristics, Efficacy and Safety of Spironolactone in Real-World Patients With Acute Heart Failure Syndrome: A Prospective Nationwide Cohort Study.

Background: Randomized clinical trials of spironolactone showed significant mortality reduction in patients with heart failure with reduced ejection fraction. However, its role in acute heart failure syndrome (AHFS) is largely unknown. Aim: To investigate the prescription characteristics, efficacy and safety of spironolactone in real-world patients with AHFS. Methods: 5,136 AHFS patients who survived to hospital discharge using a nationwide prospective registry in Korea were analyzed. The primary efficacy outcome was 3-year all-cause mortality. Results: Spironolactone was prescribed in 2,402 (46.8%) at discharge: <25 mg in 890 patients (37.1%), ≥25 mg, and <50 mg in 1,154 patients (48.0%), and ≥50 mg in 358 patients (14.9%). Patients treated with spironolactone had a lower proportion of chronic renal failure and renal replacement therapy during hospitalization and had lower serum creatinine level than those who did not. In overall patients, 3-year mortality was not different in both groups (35.9 vs. 34.5%, P = 0.279). The incidence of renal injury and hyperkalemia was 2.2% and 4.3%, respectively, at the first follow-up visit. The treatment effect of spironolactone on mortality was different across subpopulations according to LVEF. The use of spironolactone was associated with a significant reduction in 3-year morality in patients with LVEF ≤ 26% (33.8 vs. 44.3%, P < 0.001; adjusted HR 0.79, 95% CI 0.64-0.97, P = 0.023), but not in patients with LVEF > 26%. Conclusions: Although spironolactone was frequently used at lower doses in real-world practice, use of spironolactone significantly reduced 3-year mortality in patients with severely reduced LVEF with acceptable safety profile. However, our findings remain prone to various biases and further prospective randomized controlled studies are needed to confirm these findings.

Real-world eligibility for vericiguat in decompensated heart failure with reduced ejection fraction.

Aims In 2021, vericiguat was approved by the US Food and Drug Administration (FDA) and the European Commission (EC) for reducing cardiovascular mortality and heart failure (HF) hospitalizations in patients with HF with reduced ejection fraction (HFrEF) based on the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial. However, there has been no report for characterizing the generalizability of vericiguat to real-world clinical practice. Methods and results The Korean Acute Heart Failure (KorAHF) registry is a multicentre prospective cohort study. A total of 5625 patients who were admitted for HF decompensation were consecutively enrolled. We excluded the patients without left ventricular ejection fraction (LVEF) quantification, patients with LVEF > 45%, patients with in-hospital death or urgent heart transplantation, and patients without natriuretic peptide measurement. Among a total of 3014 enrolled patients, there were 21.9% patients with lower systolic blood pressure (SBP) (<100 mmHg) and 20.1% patients without elevated natriuretic peptide. Regarding chronic kidney disease (CKD) status, 5.1% patients had CKD Stage V [estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 ] and 11.8% patients had CKD Stage IV (15 ≤ eGFR < 30 mL/min/1.73 m2 ). When we analysed these criteria sequentially, 21.9% were excluded from lower SBP, 15.9% were excluded from elevated natriuretic peptide, and 4.2% were excluded from advanced CKD Stage V (9.6% for CKD Stages IV and V). Among the KorAHF registry patients, we found two main reasons for not meeting the inclusion criteria of the VICTORIA trial such as low SBP and non-elevated natriuretic peptide. Conclusions Among the Korean hospitalized HFrEF patients, 94.9% met the FDA/EC label criteria, while 58% met the inclusion criteria of the VICTORIA trial. Our findings suggest the need for better strategies to integrate up-to-date HF treatment in a real-world HF population, especially decompensated HF patients with low SBP and non-elevated natriuretic peptide.

A dose-response relationship of renin-angiotensin system blockers and beta-blockers in patients with acute heart failure syndrome: a nationwide prospective cohort study.

AIMS: It remains unclear if patients with acute heart failure syndrome (AHFS) need to reach the maximally tolerated doses of renin-angiotensin system blockers (RASBs) or beta-blockers (BBs) to obtain a survival benefit. This study evaluated the dose-response relationship between RASBs or BBs and survival in AHFS patients. METHODS AND RESULTS: In total, 5331 patients in the Korean Acute Heart Failure registry were analysed based on the doses of RASBs and BBs at discharge. In AHFS patients, RASB use at discharge was associated with a significant reduction in all-cause mortality risk. This effect was dose-dependent for heart failure with reduced ejection fraction (HFrEF) but did not attain statistical significance for heart failure with preserved ejection fraction (HFpEF). BB use at discharge was associated with reduced all-cause mortality in HFrEF patients but not in HFpEF patients. In an additional analysis of 4613 patients with dosage information at the first post-discharge follow-up visit, a significantly higher mortality risk was associated with the maintenance or withdrawal of RASBs compared with up-titrating the dose in HFrEF patients. CONCLUSION: Using RASBs or BBs at discharge was associated with improved survival. A dose-response relationship between RASBs and all-cause mortality was evident in AHFS patients with a reduced ejection fraction but not BBs. It is important to initiate and up-titrate RASBs to the maximally tolerated dose in AHFS patients during the transition period, especially for patients with a reduced ejection fraction.

The current status and outcomes of in-hospital P2Y12 receptor inhibitor switching in Korean patients with acute myocardial infarction.

BACKGROUND/AIMS: While switching strategies of P2Y12 receptor inhibitors (RIs) have sometimes been used in acute myocardial infarction (AMI) patients, the current status of in-hospital P2Y12RI switching remains unknown. METHODS: Overall, 8,476 AMI patients who underwent successful revascularization from Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) were divided according to in-hospital P2Y12RI strategies, and net adverse cardiovascular events (NACEs), defined as a composite of cardiac death, non-fatal myocardial infarction (MI), stroke, or thrombolysis in myocardial infarction (TIMI) major bleeding during hospitalization were compared. RESULTS: Patients with in-hospital P2Y12RI switching accounted for 16.5%, of which 867 patients were switched from clopidogrel to potent P2Y12RI (C-P) and 532 patients from potent P2Y12RI to clopidogrel (P-C). There were no differences in NACEs among the unchanged clopidogrel, the unchanged potent P2Y12RIs, and the P2Y12RI switching groups. However, compared to the unchanged clopidogrel group, the C-P group had a higher incidence of non-fatal MI, and the P-C group had a higher incidence of TIMI major bleeding. In clinical events of in-hospital P2Y12RI switching, 90.9% of non-fatal MI occurred during pre-switching clopidogrel administration, 60.7% of TIMI major bleeding was related to pre-switching P2Y12RIs, and 71.4% of TIMI major bleeding was related to potent P2Y12RIs. Only 21.6% of the P2Y12RI switching group switched to P2Y12RIs after a loading dose (LD); however, there were no differences in clinical events between patients with and without LD. CONCLUSION: In-hospital P2Y12RI switching occurred occasionally, but had relatively similar clinical outcomes compared to unchanged P2Y12RIs in Korean AMI patients. Non-fatal MI and bleeding appeared to be mainly related to pre-switching P2Y12RIs.