Kyung Kuk Hwang

A multicentre cohort study of acute heart failure syndromes in Korea: Rationale, design, and interim observations of the Korean Acute Heart Failure (KorAHF) registry

The Korean Acute Heart Failure registry (KorAHF) aims to evaluate the clinical characteristics, management, hospital course, and long‐term outcomes of patients hospitalized for acute heart failure syndrome (AHFS) in Korea.

Inhibition of Coxsackievirus-associated dystrophin cleavage prevents cardiomyopathy

Heart failure in children and adults is often the consequence of myocarditis associated with Coxsackievirus (CV) infection. Upon CV infection, enteroviral protease 2A cleaves a small number of host proteins including dystrophin, which links actin filaments to the plasma membrane of muscle fiber cells (sarcolemma). It is unknown whether protease 2A-mediated cleavage of dystrophin and subsequent disruption of the sarcolemma play a role in CV-mediated myocarditis. We generated knockin mice harboring a mutation at the protease 2A cleavage site of the dystrophin gene, which prevents dystrophin cleavage following CV infection. Compared with wild-type mice, we found that mice expressing cleavage-resistant dystrophin had a decrease in sarcolemmal disruption and cardiac virus titer following CV infection. In addition, cleavage-resistant dystrophin inhibited the cardiomyopathy induced by cardiomyocyte-restricted expression of the CV protease 2A transgene. These findings indicate that protease 2A-mediated cleavage of dystrophin is critical for viral propagation, enteroviral-mediated cytopathic effects, and the development of cardiomyopathy.

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.

Comparison of short-term clinical outcomes between ticagrelor versus clopidogrel in patients with acute myocardial infarction undergoing successful revascularization; from Korea Acute Myocardial Infarction Registry—National Institute of Health

BACKGROUND Although ticagrelor has been well-known to improve clinical outcomes in patients with acute myocardial infarction (AMI) without increased bleeding risk, its clinical impacts have not been well established in East Asian patients. METHODS Between November 2011 and June 2015, a total of 8010 patients (1377 patients were prescribed ticagrelor and 6633 patients clopidogrel) undergoing successful revascularization were analyzed from Korea Acute Myocardial Infarction Registry-National Institute of Health. The patients who discontinued or occurred in-hospital switching between two antiplatelet agents were excluded. RESULTS After propensity score matching (1377 pairs), no difference in the composite of cardiac death, MI, stroke, or target vessel revascularization at 6months was observed between two groups (4.2% vs. 4.9%, p=0.499). However, the incidences of in-hospital Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding were higher in ticagrelor than clopidogrel (2.6% vs. 1.2%, p=0.008; 3.8% vs. 2.5%, p=0.051). The in-hospital mortality was higher in patients with than those without TIMI major bleeding (11.3% vs. 0.9%, p<0.001). In a subgroup analysis, a higher risk for in-hospital TIMI major bleeding with ticagrelor was observed in patients≥75years or with body weight<60kg (odd ratio [OR]=3.209; 95% confidence interval [CI]=1.356-7.592) and in those received trans-femoral intervention (OR=1.996; 95% CI=1.061-3.754). CONCLUSIONS Our study shows that ticagrelor did not reduce ischemic events yet, however, was associated with increased risk of bleeding complications compared with clopidogrel. Further large-scale, long-term, randomized trials should be required to assess the outcomes of ticagrelor for East Asian patients with AMI.

Comparison of clinical outcomes between culprit vessel only and multivessel percutaneous coronary intervention for ST-segment elevation myocardial infarction patients with multivessel coronary diseases

Background The clinical significance of complete revascularization for ST segment elevation myocardial infarction (STEMI) patients during admission is still debatable. Methods A total of 1406 STEMI patients from the Korean Myocardial Infarction Registry with multivessel diseases without cardiogenic shock who underwent primary percutaneous coronary intervention (PPCI) were analyzed. We used propensity score matching (PSM) to control differences of baseline characteristics between culprit only intervention (CP) and multivessel percutaneous coronary interventions (MP), and between double vessel disease (DVD) and triple vessel disease (TVD). The major adverse cardiac event (MACE) was analyzed for one year after discharge. Results TVD patients showed higher incidence of MACE (14.2% vs. 8.6%, P = 0.01), any cause of revascularization (10.6% vs. 5.9%, P = 0.01), and repeated PCI (9.5% vs. 5.7%, P = 0.02), as compared to DVD patients during one year after discharge. MP reduced MACE effectively (7.3% vs. 13.8%, P = 0.03), as compared to CP for one year, but all cause of death (1.6% vs. 3.2%, P = 0.38), MI (0.4% vs. 0.8%, P = 1.00), and any cause of revascularization (5.3% vs. 9.7%, P = 0.09) were comparable in the two treatment groups. Conclusions STEMI patients with TVD showed higher rate of MACE, as compared to DVD. MP performed during PPCI or ad hoc during admission for STEMI patients without cardiogenic shock showed lower rate of MACE in this large scaled database. Therefore, MP could be considered as an effective treatment option for STEMI patients without cardiogenic shock.

Clinical impact of admission hyperglycemia on in-hospital mortality in acute myocardial infarction patients

BACKGROUND Acute hyperglycemia on admission is common in acute myocardial infarction (AMI) patients regardless of diabetic status, and is known as one of prognostic factors. However, the effect of hyperglycemia on non-diabetic patients is still on debate. METHODS A total of 12,625 AMI patients (64.0±12.6years, 26.1% female) who were enrolled in Korea Acute Myocardial Infarction Registry-National Institute of Health between November 2011 and December 2015, were classified into 4367 diabetes (65.4±11.6years, 30.4% female) and 8228 non-diabetes (63.3±13years, 23.9% female). Patients were analyzed for in-hospital clinical outcome according to admission hyperglycemic status. RESULTS In diabetic patients, independent predictors of in-hospital mortality were old age, high HbA1C, pre-Thrombolysis In Myocardial Infarction (TIMI) flow 0, left ventricle ejection fraction<40%, cardiogenic shock and ventricular tachycardia. In non-diabetic patients, independent predictors of in-hospital mortality were old age, high admission glucose (≥200mg/dL), pre TIMI flow 0, failed percutaneous coronary intervention, low left ventricle ejection fraction<40%, cardiogenic shock, stent thrombosis and decreased Hb≥5g/dL. In hospital mortality was significantly higher in diabetic patients compared to non-diabetic patients (5.0% vs. 3.4%, p<0.001). However, non-diabetic patients with hyperglycemia have significantly higher mortality compared to diabetic patients (17.4% vs. 7.2%, p<0.001). Comorbidity including cardiogenic shock (p<0.001), cerebral hemorrhage (p=0.012), decreased Hb≥5g/dL (p=0.013), atrioventricular block (p<0.001) and ventricular tachycardia (p=0.007) was higher in non-diabetic with hyperglycemia than in diabetic patients. CONCLUSIONS These findings underscore clinical significance of admission hyperglycemia on in-hospital mortality in non-diabetic AMI patients.

Comparison of prasugrel versus clopidogrel in Korean patients with acute myocardial infarction undergoing successful revascularization

BACKGROUND Although there have been several reports that prasugrel can improve clinical outcomes, the efficacy and safety of prasugrel is unknown in Korean patients with acute myocardial infarction (AMI) undergoing successful revascularization. METHODS A total of 4421 patients [637 patients were prescribed prasugrel (60/10 or 5mg, loading/maintenance dose) and 3784 patients clopidogrel (600 or 300/75mg)] with AMI undergoing successful revascularization were enrolled from the core clinical cohort of Korea Acute Myocardial Infarction Registry-National Institute of Health. RESULTS After propensity score matching (637 pairs), there were no significant differences in baseline clinical and procedural characteristics and in-hospital medications between the two groups. The primary efficacy endpoint, defined as the composite of cardiac death, MI, stroke, or target vessel revascularization at 6 months showed no significant difference between prasugrel and clopidogrel (2.4% vs. 2.9%, p=0.593). Also, no difference was observed in the composite of cardiac death, MI, or stroke during hospitalization between two groups (0.8% vs. 0.9%, p=0.762). However, the incidence of in-hospital Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding was significantly higher in prasugrel compared with clopidogrel (5.3% vs. 2.7%, p=0.015). In multivariate linear regression analysis, trans-femoral intervention, use of glycoprotein IIb/IIIa inhibitors, use of calcium channel blocker, and use of prasugrel were independent predictors of in-hospital TIMI major or minor bleeding [odds ratio (OR)=6.918; 95% confidence interval (CI)=2.453-19.510, OR=2.577; 95% CI=1.406-4.724, OR=4.016; 95% CI=1.382-11.668, OR=2.022; 95% CI=1.101-3.714]. CONCLUSIONS Our study shows that the recommended dose of prasugrel had significantly higher in-hospital bleeding complications without reducing ischemic events compared with clopidogrel. However, further large-scale, long-term, randomized clinical trials are required to accurately assess the efficacy and safety of prasgurel and to find out the optimal dose for Korean AMI patients.

Outcomes of de novo and acute decompensated heart failure patients according to ejection fraction

Objective There are conflicting results among previous studies regarding the prognosis of heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF). This study aimed to compare the outcomes of patients with de novo acute heart failure (AHF) or acute decompensated HF (ADHF) according to HFpEF (EF≥50%), or HFrEF (EF<40%) and to define the prognosis of patients with HF with mid-range EF (HFmrEF, 40≤EF<50%). Methods Between March 2011 and February 2014, 5625 consecutive patients with AHF were recruited from 10 university hospitals. A total of 5414 (96.2%) patients with EF data were enrolled, which consisted of 2867 (53.0%) patients with de novo and 2547 (47.0%) with ADHF. Each of the enrolled group was stratified by EF. Results In de novo, all-cause death rates were not significantly different between HFpEF and HFrEF (HFpEF vs HFrEF, 206/744 (27.7%) vs 438/1631 (26.9%), HRadj 1.15, 95% CI 0.96 to 1.38, p=0.14). However, among patients with ADHF, HFrEF had a significantly higher mortality rate compared with HFpEF (HFpEF vs HFrEF, 245/613 (40.0%) vs 694/1551 (44.7%), HRadj 1.25, 95% CI 1.06 to 1.47, p=0.007). Also, in ADHF, HFmrEF was associated with a significantly lower mortality rate within 1 year compared with HFrEF (HFmrEF vs HFrEF, 88/383 (23.0%) vs 430/1551 (27.7%), HRadj 1.31, 95% CI 1.03 to 1.65, p=0.03), but a significantly higher mortality rate after 1 year compared with HFpEF (HFmrEF vs HFpEF, 83/295 (28.1%) vs 101/469 (21.5%), HRadj 0.70, 95% CI 0.52 to 0.96, p=0.02). Conclusions HFpEF may indicate a better prognosis compared with HFrEF in ADHF, but not in de novo AHF. For patients with ADHF, the prognosis associated with HFmrEF was similar to that of HFpEF within the first year following hospitalisation and similar to HFrEF 1  year after hospitalisation.

Clinic and home blood pressure lowering effect of an angiotensin receptor blocker, fimasartan, in postmenopausal women with hypertension

AbstractAngiotensin receptor blockers may be an appropriate first-line agent for postmenopausal women with hypertension because the activation of renin–angiotensin–aldosterone system is suggested as one possible mechanism of postmenopausal hypertension. However, there are few studies substantiating this effect. This study aimed to investigate clinic and home blood pressure (BP) lowering effect of fimasartan, a new angiotensin receptor blocker, in postmenopausal women with hypertension.Among patients with hypertension enrolled in K-Mets Study, 1373 women with fimasartan as a first antihypertensive drug and 3-months follow-up data were selected. They were divided into 2 groups; premenopausal women (pre-MPW; n = 382, 45.3 ± 4.6 years) and postmenopausal women (post-MPW; n = 991, 60.9 ± 8.2 years).Baseline clinic systolic BP was not different (pre-MPW; 152.9 ± 15.2 vs. post-MPW; 152.8 ± 13.5 mm Hg), but diastolic BP was lower in post-MPW (pre-MPW; 95.7 ± 9.4 vs. post-MPW; 91.9 ± 9.4 mm Hg, P <0.001). After 3-month treatment, clinic BP declined effectively without significant differences between 2 groups (&Dgr;systolic/diastolic BP: pre-MPW; −25.7 ± 17.7/−14.2 ± 11.3 vs. post-MPW; −25.7 ± 16.3/−13.1 ± 10.9 mm Hg). Home morning and evening systolic BP decreased similarly in both groups (&Dgr;morning/evening systolic BP: pre-MPW; −21.3 ± 17.9/−23.1 ± 15.8 vs. post-MPW; −20.4 ± 17.3/−20.2 ± 19.2 mm Hg). Fimasartan also significantly decreased the standard deviations of home morning and evening systolic BP of pre-MPW and post-MPW.Fimasartan was a similarly effective BP lowering agent in both post-MPW and pre-MPW with hypertension, and it also decreased day-to-day BP variability.

Impact of heart rate reduction with maximal tolerable dose of bisoprolol on left ventricular reverse remodeling

Background We aimed to evaluate effect of heart rate (HR) reduction on left ventricular reverse remodeling (LVRR) in Korean patients with heart failure with reduced ejection fraction (HFrEF). Methods Ambulatory patients with HFrEF, who had paired echocardiograms, N-terminal prohormone brain natriuretic peptide (NT-proBNP), and global assessment score (GAS) at baseline and 6-month (n = 157), were followed up on preset treatment schedule with bisoprolol. Results The LVRR occurred in 49 patients (32%) at 6-month. In multivariable analysis, independent predictors associated with LVRR were use of anti-aldosterone agent (odds ratio [OR], 4.18; 95% confidence interval [CI], 1.80–9.71), young age (OR, 0.96; 95% CI, 0.92–0.99), high baseline HR (OR, 3.76; 95% CI, 1.40–10.10), and favorable baseline GAS (OR, 1.73; 95% CI, 1.06–2.81). Beneficial effect of bisoprolol, in terms of LVRR, NT-proBNP, and GAS, was remarkable in the high HR group (baseline HR ≥ 75 beats per minute [bpm]), which showed a large HR reduction. Conclusion High baseline HR (≥ 75 bpm) showed an association with LVRR and improvement of NT-proBNP and GAS in patients with HFrEF. This seems to be due to a large HR reduction after treatments with bisoprolol. Trial Registration ClinicalTrials.gov Identifier: NCT00749034