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.

Implantable Cardioverter-defibrillator Utilization and Its Outcomes in Korea:Data from Korean Acute Heart Failure Registry

Background@#There are sparse data on the utilization rate of implantable cardioverterdefibrillator (ICD) and its beneficial effects in Korean patients with heart failure with reduced left ventricular ejection fraction (LVEF). @*Methods@#Among 5,625 acute heart failure (AHF) patients from 10 tertiary university hospitals across Korea, 485 patients with reassessed LVEF ≤ 35% at least 3 months after the index admission were enrolled in this study. The ICD implantation during the follow-up was evaluated. Mortality was compared between patients with ICDs and age-, sex-, and follow-up duration matched control patients. @*Results@#Among 485 patients potentially indicated for an ICD for primary prevention, only 56 patients (11.5%) underwent ICD implantation during the follow-up. Patients with ICD showed a significantly lower all-cause mortality compared with their matched control population: adjusted hazard ratio (HR) (95% confidence interval [CI]) = 0.39 (0.16–0.92), P = 0.032. The mortality rate was still lower in the ICD group after excluding patients with cardiac resynchronization therapy (adjusted HR [95% CI] = 0.09 [0.01–0.63], P = 0.015).According to the subgroup analysis for ischemic heart failure, there was a significantly lower all-cause mortality in the ICD group than in the no-ICD group (HR [95% CI] = 0.20 [0.06– 0.72], P = 0.013), with a borderline statistical significance (interaction P = 0.069). @*Conclusion@#Follow-up data of this large, multicenter registry suggests a significant underutilization of ICD in Korean heart failure patients with reduced LVEF. Survival analysis implies that previously proven survival benefit of ICD in clinical trials could be extrapolated to Korean patients.

J-curve relationship between corrected QT interval and mortality in acute heart failure patients

Background/Aims@#This study investigated the prognostic power of corrected QT (QTc) interval in patients with acute heart failure (AHF) according to sex. @*Methods@#We analyzed multicenter Korean Acute Heart Failure registry with patients with AHF admitted from 2011 to 2014. Among them, we analyzed 4,990 patients who were followed up to 5 years. Regarding QTc interval based on 12 lead electrocardiogram, patients were classified into quartiles according to sex. @*Results@#During follow-up with median 43.7 months, 2,243 (44.9%) patients died. The relationship between corrected QT interval and all-cause mortality followed a J-curve relationship. In Kaplan-Meier analysis, both sex had lowest mortality in the second QTc quartile. There were significant prognostic differences between the second and the fourth quartiles in male (log-rank p = 0.002), but not in female (log-rank p = 0.338). After adjusting covariates, the third (hazard ratio [HR], 1.185; 95% confidence interval [CI], 1.001 to 1.404; p = 0.049) and the fourth (HR, 1.404; 95% CI, 1.091 to 1.535; p = 0.003) quartiles demonstrated increased risk of mortality compared to the second quartile in male. In female, however, there was no significant difference across quartiles. QTc interval was associated with 5-year all-cause mortality in J-shape with nadir of 440 to 450 ms in male and 470 to 480 ms in female. @*Conclusions@#QTc interval was an independent predictor of overall death in male, but its significance decreased in female. The relationship between QTc interval and all-cause mortality was J-shaped in both sex.

High Incidence and Mortality of Out-of-Hospital Cardiac Arrest on Traditional Holiday in South Korea

BACKGROUND AND OBJECTIVES: This study aimed to confirm the effects of traditional holidays on the incidence and outcomes of out-of-hospital cardiac arrest (OHCA) in South Korea. METHODS: We studied 95,066 OHCAs of cardiac cause from a nationwide, prospective study from the Korea OHCA Registry from January 2012 to December 2016. We compared the incidence of OHCA, in-hospital mortality, and neurologic outcomes between traditional holidays, Seollal (Lunar New Year's Day) and Chuseok (Korean Thanksgiving Day), and other day types (weekday, weekend, and public holiday). RESULTS: OHCA occurred more frequently on traditional holidays than on the other days. The median OHCA incidence were 51.0 (interquartile range [IQR], 44.0–58.0), 53.0 (IQR, 46.0–60.5), 52.5 (IQR, 45.3–59.8), and 60.0 (IQR, 52.0–69.0) cases/day on weekday, weekend, public holiday, and traditional holiday, respectively (p<0.001). The OHCA occurred more often at home rather than in public place, lesser bystander cardiopulmonary resuscitation (CPR) was performed, and the rate of cessation of CPR within 20 minutes without recovery of spontaneous circulation was higher on traditional holiday. After multivariable adjustment, traditional holiday was associated with higher in-hospital mortality (adjusted hazard ratio [HR], 1.339; 95% confidence interval [CI], 1.058–1.704; p=0.016) but better neurologic outcomes (adjusted HR, 0.503; 95% CI, 0.281–0.894; p=0.020) than weekdays. CONCLUSIONS: The incidence of OHCAs was associated with day types in a year. It occurred more frequently on traditional holidays than on other day types. It was associated with higher in-hospital mortality and favorable neurologic outcomes than weekday.

Development and Validation of Deep-Learning Algorithm for Electrocardiography-Based Heart Failure Identification

BACKGROUND AND OBJECTIVES: Screening and early diagnosis for heart failure (HF) are critical. However, conventional screening diagnostic methods have limitations, and electrocardiography (ECG)-based HF identification may be helpful. This study aimed to develop and validate a deep-learning algorithm for ECG-based HF identification (DEHF). METHODS: The study involved 2 hospitals and 55,163 ECGs of 22,765 patients who performed echocardiography within 4 weeks were study subjects. ECGs were divided into derivation and validation data. Demographic and ECG features were used as predictive variables. The primary endpoint was detection of HF with reduced ejection fraction (HFrEF; ejection fraction [EF]≤40%), and the secondary endpoint was HF with mid-range to reduced EF (≤50%). We developed the DEHF using derivation data and the algorithm representing the risk of HF between 0 and 1. We confirmed accuracy and compared logistic regression (LR) and random forest (RF) analyses using validation data. RESULTS: The area under the receiver operating characteristic curves (AUROCs) of DEHF for identification of HFrEF were 0.843 (95% confidence interval, 0.840–0.845) and 0.889 (0.887–0.891) for internal and external validation, respectively, and these results significantly outperformed those of LR (0.800 [0.797–0.803], 0.847 [0.844–0.850]) and RF (0.807 [0.804–0.810], 0.853 [0.850–0.855]) analyses. The AUROCs of deep learning for identification of the secondary endpoint was 0.821 (0.819–0.823) and 0.850 (0.848–0.852) for internal and external validation, respectively, and these results significantly outperformed those of LR and RF. CONCLUSIONS: The deep-learning algorithm accurately identified HF using ECG features and outperformed other machine-learning methods.

Development and Validation of Deep-Learning Algorithm for Electrocardiography-Based Heart Failure Identification

BACKGROUND AND OBJECTIVES@#Screening and early diagnosis for heart failure (HF) are critical. However, conventional screening diagnostic methods have limitations, and electrocardiography (ECG)-based HF identification may be helpful. This study aimed to develop and validate a deep-learning algorithm for ECG-based HF identification (DEHF).@*METHODS@#The study involved 2 hospitals and 55,163 ECGs of 22,765 patients who performed echocardiography within 4 weeks were study subjects. ECGs were divided into derivation and validation data. Demographic and ECG features were used as predictive variables. The primary endpoint was detection of HF with reduced ejection fraction (HFrEF; ejection fraction [EF]≤40%), and the secondary endpoint was HF with mid-range to reduced EF (≤50%). We developed the DEHF using derivation data and the algorithm representing the risk of HF between 0 and 1. We confirmed accuracy and compared logistic regression (LR) and random forest (RF) analyses using validation data.@*RESULTS@#The area under the receiver operating characteristic curves (AUROCs) of DEHF for identification of HFrEF were 0.843 (95% confidence interval, 0.840–0.845) and 0.889 (0.887–0.891) for internal and external validation, respectively, and these results significantly outperformed those of LR (0.800 [0.797–0.803], 0.847 [0.844–0.850]) and RF (0.807 [0.804–0.810], 0.853 [0.850–0.855]) analyses. The AUROCs of deep learning for identification of the secondary endpoint was 0.821 (0.819–0.823) and 0.850 (0.848–0.852) for internal and external validation, respectively, and these results significantly outperformed those of LR and RF.@*CONCLUSIONS@#The deep-learning algorithm accurately identified HF using ECG features and outperformed other machine-learning methods.

High Incidence and Mortality of Out-of-Hospital Cardiac Arrest on Traditional Holiday in South Korea

BACKGROUND AND OBJECTIVES@#This study aimed to confirm the effects of traditional holidays on the incidence and outcomes of out-of-hospital cardiac arrest (OHCA) in South Korea.@*METHODS@#We studied 95,066 OHCAs of cardiac cause from a nationwide, prospective study from the Korea OHCA Registry from January 2012 to December 2016. We compared the incidence of OHCA, in-hospital mortality, and neurologic outcomes between traditional holidays, Seollal (Lunar New Year's Day) and Chuseok (Korean Thanksgiving Day), and other day types (weekday, weekend, and public holiday).@*RESULTS@#OHCA occurred more frequently on traditional holidays than on the other days. The median OHCA incidence were 51.0 (interquartile range [IQR], 44.0–58.0), 53.0 (IQR, 46.0–60.5), 52.5 (IQR, 45.3–59.8), and 60.0 (IQR, 52.0–69.0) cases/day on weekday, weekend, public holiday, and traditional holiday, respectively (p<0.001). The OHCA occurred more often at home rather than in public place, lesser bystander cardiopulmonary resuscitation (CPR) was performed, and the rate of cessation of CPR within 20 minutes without recovery of spontaneous circulation was higher on traditional holiday. After multivariable adjustment, traditional holiday was associated with higher in-hospital mortality (adjusted hazard ratio [HR], 1.339; 95% confidence interval [CI], 1.058–1.704; p=0.016) but better neurologic outcomes (adjusted HR, 0.503; 95% CI, 0.281–0.894; p=0.020) than weekdays.@*CONCLUSIONS@#The incidence of OHCAs was associated with day types in a year. It occurred more frequently on traditional holidays than on other day types. It was associated with higher in-hospital mortality and favorable neurologic outcomes than weekday.

Prognostic Implication of Ventricular Conduction Disturbance Pattern in Hospitalized Patients with Acute Heart Failure Syndrome

BACKGROUND AND OBJECTIVES@#Conflicting data exist regarding the prognostic implication of ventricular conduction disturbance pattern in patients with heart failure (HF). This study investigated the prognostic impact of ventricular conduction pattern in hospitalized patients with acute HF.@*METHODS@#Data from the Korean Acute Heart Failure registry were used. Patients were categorized into four groups: narrow QRS (<120 ms), right bundle branch block (RBBB), left bundle branch block (LBBB), and nonspecific intraventricular conduction delay (NICD). The NICD was defined as prolonged QRS (≥120 ms) without typical features of LBBB or RBBB. The primary endpoint was the composite of all-cause mortality or rehospitalization for HF aggravation within 1 year after discharge.@*RESULTS@#This study included 5,157 patients. The primary endpoint occurred in 39.7% of study population. The LBBB group showed the highest incidence of primary endpoint followed by NICD, RBBB, and narrow QRS groups (52.5% vs. 49.7% vs. 44.4% vs. 37.5%, p<0.001). In a multivariable Cox-proportional hazards regression analysis, LBBB and NICD were associated with 39% and 28% increased risk for primary endpoint (LBBB hazard ratio [HR], 1.392; 95% confidence interval [CI], 1.152–1.681; NICD HR, 1.278; 95% CI, 1.074–1.520) compared with narrow QRS group. The HR of RBBB for the primary endpoint was 1.103 (95% CI, 0.915–1.329).@*CONCLUSIONS@#LBBB and NICD were independently associated with an increased risk of 1-year adverse event in hospitalized patients with HF, whereas the prognostic impacts of RBBB were limited.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843

Beta-Blockers in Patients with Heart Failure with Preserved Ejection Fraction: Results from The Korea Acute Heart Failure (KorAHF) Registry

BACKGROUND AND OBJECTIVES@#Beta-blockers are indicated in patients with heart failure (HF) with reduced ejection fraction. However, their efficacy in patients with HF with preserved ejection fraction (HFpEF) is uncertain. We investigated the hypothesis that beta-blockers are associated with reduced adverse events in patients with HFpEF.@*METHODS@#The Korea Acute Heart Failure (KorAHF) is a prospective observational multicentre cohort study. The 5,625 patients hospitalized for acute HF syndrome in 10 tertiary university hospitals across the country have been consecutively enrolled between March 2011 and February 2014. Of these patients, 2,152 patients with HFpEF (ejection fraction ≥40%) were investigated. The primary outcome was all-cause mortality according to beta-blocker use.@*RESULTS@#During a median follow-up duration of 807 days, 702 patients died. In Cox proportional hazards model beta-blocker use was associated with a 14% reduced all-cause death (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75–0.98), but not with reduce rehospitalization (HR, 1.03; 95% CI, 0.85–1.27). In the propensity-score matched population, beta-blockers were also associated with reduced all-cause death (HR, 0.80; 95% CI, 0.69–0.94) but not with reduced rehospitalization (HR, 1.08; 95% CI, 0.87–1.33).@*CONCLUSIONS@#In Korean patients with HFpEF, use of beta-blockers is associated with reduced all-cause death but not with reduced rehospitalization.

Beta-Blockers in Patients with Heart Failure with Preserved Ejection Fraction: Results from The Korea Acute Heart Failure (KorAHF) Registry

BACKGROUND AND OBJECTIVES: Beta-blockers are indicated in patients with heart failure (HF) with reduced ejection fraction. However, their efficacy in patients with HF with preserved ejection fraction (HFpEF) is uncertain. We investigated the hypothesis that beta-blockers are associated with reduced adverse events in patients with HFpEF. METHODS: The Korea Acute Heart Failure (KorAHF) is a prospective observational multicentre cohort study. The 5,625 patients hospitalized for acute HF syndrome in 10 tertiary university hospitals across the country have been consecutively enrolled between March 2011 and February 2014. Of these patients, 2,152 patients with HFpEF (ejection fraction ≥40%) were investigated. The primary outcome was all-cause mortality according to beta-blocker use. RESULTS: During a median follow-up duration of 807 days, 702 patients died. In Cox proportional hazards model beta-blocker use was associated with a 14% reduced all-cause death (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75–0.98), but not with reduce rehospitalization (HR, 1.03; 95% CI, 0.85–1.27). In the propensity-score matched population, beta-blockers were also associated with reduced all-cause death (HR, 0.80; 95% CI, 0.69–0.94) but not with reduced rehospitalization (HR, 1.08; 95% CI, 0.87–1.33). CONCLUSIONS: In Korean patients with HFpEF, use of beta-blockers is associated with reduced all-cause death but not with reduced rehospitalization.

Prognostic Implication of Ventricular Conduction Disturbance Pattern in Hospitalized Patients with Acute Heart Failure Syndrome

BACKGROUND AND OBJECTIVES: Conflicting data exist regarding the prognostic implication of ventricular conduction disturbance pattern in patients with heart failure (HF). This study investigated the prognostic impact of ventricular conduction pattern in hospitalized patients with acute HF. METHODS: Data from the Korean Acute Heart Failure registry were used. Patients were categorized into four groups: narrow QRS (<120 ms), right bundle branch block (RBBB), left bundle branch block (LBBB), and nonspecific intraventricular conduction delay (NICD). The NICD was defined as prolonged QRS (≥120 ms) without typical features of LBBB or RBBB. The primary endpoint was the composite of all-cause mortality or rehospitalization for HF aggravation within 1 year after discharge. RESULTS: This study included 5,157 patients. The primary endpoint occurred in 39.7% of study population. The LBBB group showed the highest incidence of primary endpoint followed by NICD, RBBB, and narrow QRS groups (52.5% vs. 49.7% vs. 44.4% vs. 37.5%, p<0.001). In a multivariable Cox-proportional hazards regression analysis, LBBB and NICD were associated with 39% and 28% increased risk for primary endpoint (LBBB hazard ratio [HR], 1.392; 95% confidence interval [CI], 1.152–1.681; NICD HR, 1.278; 95% CI, 1.074–1.520) compared with narrow QRS group. The HR of RBBB for the primary endpoint was 1.103 (95% CI, 0.915–1.329). CONCLUSIONS: LBBB and NICD were independently associated with an increased risk of 1-year adverse event in hospitalized patients with HF, whereas the prognostic impacts of RBBB were limited. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843

The mortality benefit of carvedilol versus bisoprolol in patients with heart failure with reduced ejection fraction

BACKGROUND/AIMS@#It is unknown whether different β-blockers (BBs) have variable effects on long-term survival of patients with heart failure with reduced ejection fraction (HFrEF). This study compares the effects of two BBs, carvedilol and bisoprolol, on survival in patients with HFrEF.@*METHODS@#The Korean Acute Heart Failure (KorAHF) registry is a prospective multicenter cohort that includes 5,625 patients who were hospitalized for acute heart failure (AHF). We selected 3,016 patients with HFrEF and divided this study population into two groups: BB at discharge (n = 1,707) or no BB at discharge (n = 1,309). Among patients with BB at discharge, subgroups were formed based on carvedilol prescription (n = 831), or bisoprolol prescription (n = 553). Propensity score matching analysis was performed.@*RESULTS@#Among patients who were prescribed a BB at discharge, 60.5% received carvedilol and 32.7% received bisoprolol. There was a significant reduction in all-cause mortality in those patients with HFrEF prescribed a BB at discharge compared to those who were not (BB vs. no BB, 26.1% vs. 40.8%; hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.52 to 0.67; p < 0.001). However, there was no significant difference in the rate of all-cause mortality between those receiving different types of BB (carvedilol vs. bisoprolol, 27.5% vs. 23.5%; HR, 1.21; 95% CI, 0.99 to 1.47; p = 0.07). Similar results were observed after propensity score matching analysis (508 pairs, 26.2% vs. 23.8%; HR, 1.10; 95% CI, 0.86 to 1.40; p = 0.47).@*CONCLUSIONS@#In the treatment of AHF with reduced EF after hospitalization, mortality benefits of carvedilol and bisoprolol were comparable.

Body fluid status assessment by bio-impedance analysis in patients presenting to the emergency department with dyspnea

BACKGROUND/AIMS: Fluid retention occurs in patients with heart failure, accounting for dyspnea. We investigated the diagnostic implication of body fluid status, assessed by bio-impedance analysis (BIA), in acute heart failure (AHF) among patients who presented with dyspnea. METHODS: A total of 100 patients who presented with dyspnea and suspected with AHF were analyzed in this study. We enrolled 50 AHF and 50 non-AHF patients discriminated through echocardiographic analysis and Framingham criteria and were matched by age and sex. Body composition was analyzed using a multifrequency BIA. RESULTS: AHF patients demonstrated higher extracellular water (ECW)/total body water (TBW) compared with non-AHF patients (0.412 ± 0.017 vs. 0.388 ± 0.023, p 0.412 at lower extremities with sensitivity and specificity of 0.780 and 0.960. The ECW/TBW of the lower extremities (ECW/TBWL) was correlated with log B-type natriuretic peptide (BNP) levels (r = 0.603, p 0.412 had an independent association with AHF patients (p = 0.011). CONCLUSIONS: The ECW/TBWL was higher in patients with dyspnea caused by AHF than their counterparts and demonstrated an independent diagnostic implication. It may be a promising marker to diagnose AHF at bedside.

Prognostic Significance of Left Axis Deviation in Acute Heart Failure Patients with Left Bundle branch block: an Analysis from the Korean Acute Heart Failure (KorAHF) Registry

BACKGROUND AND OBJECTIVES@#The prognostic impact of left axis deviation (LAD) on clinical outcomes in acute heart failure syndrome (AHFS) with left bundle branch block (LBBB) is unknown. The aim of this study was to determine the prognostic significance of axis deviation in acute heart failure patients with LBBB.@*METHODS@#Between March 2011 and February 2014, 292 consecutive AHFS patients with LBBB were recruited from 10 tertiary university hospitals. They were divided into groups with no LAD (n=189) or with LAD (n=103) groups according to QRS axis <−30 degree. The primary outcome was all-cause mortality.@*RESULTS@#The median follow-up duration was 24 months. On multivariate analysis, the rate of all-cause death did not significantly differ between the normal axis and LAD groups (39.7% vs. 46.6%, adjusted hazard ratio, 1.01; 95% confidence interval, 0.66, 1.53; p=0.97). However, on the multiple linear regression analysis to evaluate the predictors of the left ventricular ejection fraction (LVEF), presence of LAD significantly predicted a worse LVEF (adjusted beta, −3.25; 95% confidence interval, −5.82, −0.67; p=0.01). Right ventricle (RV) dilatation was defined as at least 2 of 3 electrocardiographic criteria (late R in lead aVR, low voltages in limb leads, and R/S ratio < 1 in lead V5) and was more frequent in the LAD group than in the normal axis group (p < 0.001).@*CONCLUSIONS@#Among the AHFS with LBBB patients, LAD did not predict mortality, but it could be used as a significant predictor of worse LVEF and RV dilatation (Trial registry at KorAHF registry, ClinicalTrial.gov, NCT01389843).

Prognostic Significance of Left Axis Deviation in Acute Heart Failure Patients with Left Bundle branch block: an Analysis from the Korean Acute Heart Failure (KorAHF) Registry

BACKGROUND AND OBJECTIVES: The prognostic impact of left axis deviation (LAD) on clinical outcomes in acute heart failure syndrome (AHFS) with left bundle branch block (LBBB) is unknown. The aim of this study was to determine the prognostic significance of axis deviation in acute heart failure patients with LBBB. METHODS: Between March 2011 and February 2014, 292 consecutive AHFS patients with LBBB were recruited from 10 tertiary university hospitals. They were divided into groups with no LAD (n=189) or with LAD (n=103) groups according to QRS axis < −30 degree. The primary outcome was all-cause mortality. RESULTS: The median follow-up duration was 24 months. On multivariate analysis, the rate of all-cause death did not significantly differ between the normal axis and LAD groups (39.7% vs. 46.6%, adjusted hazard ratio, 1.01; 95% confidence interval, 0.66, 1.53; p=0.97). However, on the multiple linear regression analysis to evaluate the predictors of the left ventricular ejection fraction (LVEF), presence of LAD significantly predicted a worse LVEF (adjusted beta, −3.25; 95% confidence interval, −5.82, −0.67; p=0.01). Right ventricle (RV) dilatation was defined as at least 2 of 3 electrocardiographic criteria (late R in lead aVR, low voltages in limb leads, and R/S ratio < 1 in lead V5) and was more frequent in the LAD group than in the normal axis group (p < 0.001). CONCLUSIONS: Among the AHFS with LBBB patients, LAD did not predict mortality, but it could be used as a significant predictor of worse LVEF and RV dilatation (Trial registry at KorAHF registry, ClinicalTrial.gov, NCT01389843).

24-Hour blood pressure response to lower dose (30 mg) fimasartan in Korean patients with mild to moderate essential hypertension

BACKGROUND/AIMS: Fimasartan is an angiotensin type 1 receptor blocker (ARB) which has comparable efficacy and tolerability with other ARBs. The aim of this study was to evaluate 24-hour blood pressure (BP) lowering efficacy and the tolerability of the low dose fimasartan compared with valsartan in patients with mild to moderate hypertension. METHODS: This study was a phase II, prospective, multicenter, randomized, double-blind, parallel-grouped trial. A total of 75 hypertensive patients, whose mean ambulatory BP monitoring values were ≥ 135/85 mmHg, were randomized to either fimasartan 30 mg or valsartan 80 mg daily. The primary efficacy endpoint was the change in the mean 24-hour systolic BP (SBP) values from the baseline and at the week 8. Secondary endpoints included the change in the mean 24-hour diastolic BP values, the daytime and the nighttime mean BP values at week 8, the trough-to-peak (T/P) ratio and the smoothness index. RESULTS: At week 8, the mean 24-hour SBP values significantly decreased in both groups; –10.5 ± 11.9 mmHg (p < 0.0001) in the fimasartan group and –5.5 ± 11.6 mmHg (p = 0.0307) in the valsartan group. The difference between two groups was 4.3 ± 2.9 mmHg but there was no statistical significance (p = 0.1392). The global T/P ratio in the fimasartan 30 mg groups were 0.48 and 0.40 in the valsartan 80 mg group, respectively (p = 0.3411). The most frequent adverse events (AEs) were acute pharyngitis and there were no cases of severe AEs. CONCLUSIONS: In mild-to-moderate hypertensive patients, low dose (30 mg) fimasartan showed comparable 24-hour BP lowering efficacy compared with valsartan (80 mg). There was no difference in tolerability between two groups.

Clinical Characteristics and Outcome of Acute Heart Failure in Korea: Results from the Korean Acute Heart Failure Registry (KorAHF)

BACKGROUND AND OBJECTIVES: The burden of heart failure has increased in Korea. This registry aims to evaluate demographics, clinical characteristics, management, and long-term outcomes in patients hospitalized for acute heart failure (AHF). SUBJECTS AND METHODS: We prospectively enrolled a total of 5625 consecutive subjects hospitalized for AHF in one of 10 tertiary university hospitals from March 2011 to February 2014. Descriptive statistics were used to determine the baseline characteristics of the study population and to compare them with those from other registries. RESULTS: The mean age was 68.5±14.5 years, 53.2% were male, and 52.2% had de novo heart failure. The mean systolic and diastolic blood pressures were 131.2±30.3 mmHg and 78.6±18.8 mmHg at admission, respectively. The left ventricular ejection fraction was ≤40% in 60.5% of patients. Ischemia was the most frequent etiology (37.6%) and aggravating factor (26.3%). Angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and aldosterone antagonists were prescribed in 68.8%, 52.2%, and 46.6% of the patients at discharge, respectively. Compared with the previous registry performed in Korea a decade ago, extracorporeal membrane oxygenation (ECMO) and heart transplantation have been performed more frequently (ECMO 0.8% vs. 2.8%, heart transplantation 0.3% vs. 1.2%), and in-hospital mortality decreased from 7.6% to 4.8%. However, the total cost of hospital care increased by 40%, and one-year follow-up mortality remained high. CONCLUSION: While the quality of acute clinical care and AHF-related outcomes have improved over the last decade, the long-term prognosis of heart failure is still poor in Korea. Therefore, additional research is needed to improve long-term outcomes and implement cost-effective care.

Relation of Renal Function with Left Ventricular Systolic Function and NT-proBNP Level and Its Prognostic Implication in Heart Failure with Preserved versus Reduced Ejection Fraction: an analysis from the Korean Heart Failure (KorHF) Registry

BACKGROUND AND OBJECTIVES: The relationship between ejection fraction (EF), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and renal function is unknown as stratified by heart failure (HF) type. We investigated their relation and the prognostic value of renal function in heart failure with preserved ejection fraction (HFpEF) vs. reduced ejection fraction (HFrEF). MATERIALS AND METHODS: NT-proBNP, glomerular filtration rate (GFR), and EF were obtained in 1,932 acute heart failure (AHF) patients. HFrEF was defined as EF<50%, and renal dysfunction as GFR<60 mL/min/1.73 m² (mild renal dysfunction: 30≤GFR<60 mL/min/1.73 m²; severe renal dysfunction: GFR<30 mL/min/1.73 m²). The primary outcome was 12-month all-cause death. RESULTS: There was an inverse correlation between GFR and log NT-proBNP level (r=−0.298, p<0.001), and between EF and log NT-proBNP (r=−0.238, p<0.001), but no correlation between EF and GFR (r=0.017, p=0.458). Interestingly, the prevalence of renal dysfunction did not differ between HFpEF and HFrEF (49% vs. 52%, p=0.210). Patients with renal dysfunction had higher 12-month mortality in both HFpEF (7.9% vs. 15.2%, log-rank p=0.008) and HFrEF (8.6% vs. 16.8%, log-rank p<0.001). Multivariate analysis showed severe renal dysfunction was an independent predictor of 12-month mortality (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.40–3.11). When stratified according to EF: the prognostic value of severe renal dysfunction was attenuated in HFpEF patients (HR, 1.46; 95% CI, 0.66–3.21) contrary to HFrEF patients (HR, 2.43; 95% CI, 1.52–3.89). CONCLUSION: In AHF patients, the prevalence of renal dysfunction did not differ between HFpEF and HFrEF patients. However, the prognostic value of renal dysfunction was attenuated in HFpEF patients.

Trends in Hospitalized Acute Myocardial Infarction Patients with Heart Failure in Korea at 1998 and 2008

Heart failure (HF) complicating acute myocardial infarction (AMI) is common and is associated with poor clinical outcome. Limited data exist regarding the incidence and in-hospital mortality of AMI with HF (AMI-HF). We retrospectively analyzed 1,427 consecutive patients with AMI in the five major university hospitals in Korea at two time points, 1998 (n = 608) and 2008 (n = 819). Two hundred twenty eight patients (37.5%) in 1998 and 324 patients (39.5%) in 2008 of AMI patients complicated with HF (P = 0.429). AMI-HF patients in 2008 were older, had more hypertension, previous AMI, and lower systolic blood pressure than those in 1998. Regarding treatments, AMI-HF patients in 2008 received more revascularization procedures, more evidence based medical treatment and adjuvant therapy, such as mechanical ventilators, intra-aortic balloon pulsation compared to those in 1998. However, overall in-hospital mortality rates (6.4% vs 11.1%, P = 0.071) of AMI-HF patients were unchanged and still high even after propensity score matching analysis, irrespective of types of AMI and revascularization methods. In conclusion, more evidence-based medical and advanced procedural managements were applied for patients with AMI-HF in 2008 than in 1998. However the incidence and in-hospital mortality of AMI-HF patients were not significantly changed between the two time points.

PPARgamma modulates vascular smooth muscle cell phenotype via a protein kinase G-dependent pathway and reduces neointimal hyperplasia after vascular injury

Vascular smooth muscle cells (VSMCs) undergo phenotypic changes in response to vascular injury such as angioplasty. Protein kinase G (PKG) has an important role in the process of VSMC phenotype switching. In this study, we examined whether rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, could modulate VSMC phenotype through the PKG pathway to reduce neointimal hyperplasia after angioplasty. In vitro experiments showed that rosiglitazone inhibited the phenotype change of VSMCs from a contractile to a synthetic form. The platelet-derived growth factor (PDGF)-induced reduction of PKG level was reversed by rosiglitazone treatment, resulting in increased PKG activity. This increased activity of PKG resulted in phosphorylation of vasodilator-stimulated phosphoprotein at serine 239, leading to inhibited proliferation of VSMCs. Interestingly, rosiglitazone did not change the level of nitric oxide (NO) or cyclic guanosine monophosphate (cGMP), which are upstream of PKG, suggesting that rosiglitazone influences PKG itself. Chromatin immunoprecipitation assays for the PKG promoter showed that the activation of PKG by rosiglitazone was mediated by the increased binding of Sp1 on the promoter region of PKG. In vivo experiments showed that rosiglitazone significantly inhibited neointimal formation after balloon injury. Immunohistochemistry staining for calponin and thrombospondin showed that this effect of rosiglitazone was mediated by modulating VSMC phenotype. Our findings demonstrate that rosiglitazone is a potent modulator of VSMC phenotype, which is regulated by PKG. This activation of PKG by rosiglitazone results in reduced neointimal hyperplasia after angioplasty. These results provide important mechanistic insight into the cardiovascular-protective effect of PPARgamma.