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.

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.

Benefit of a staged in-hospital revascularization strategy in hemodynamically stable patients with ST-segment elevation myocardial infarction and multivessel disease: Analyses by risk stratification.

AIMS: The proper timing and indication of revascularization for a non-culprit artery in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) without cardiogenic shock remains controversial. METHODS AND RESULTS: This multicenter study included patients with STEMI and MVD without cardiogenic shock. Data were analyzed at 3 years according to the percutaneous coronary intervention (PCI) strategy: immediate multivessel revascularization (MVR) (n = 351), stepwise MVR (n = 510), and culprit-only PCI (n = 1,142). The primary outcome was all-cause mortality. The stepwise MVR group had a lower risk of all-cause death. The results were consistent after multivariate regression, propensity-score matching, inverse probability weighting, and Bayesian proportional hazards modeling. In subgroup analyses stratified by the Global Registry of Acute Coronary Events score, stepwise MVR also lowered the risk of all-cause death compared to culprit-only PCI and immediate MVR in high risk patients but not in patients at low to intermediate risk. CONCLUSIONS: In patients with STEMI and MVD without cardiogenic shock, in-hospital stepwise MVR was associated with a lower risk of all-cause death than culprit-only PCI or immediate MVR, particularly in the high-risk subgroup.

Effectiveness of a new cardiac risk scoring model reclassified by QRS fragmentation as a predictor of postoperative cardiac event in patients with severe renal dysfunction.

BACKGROUND: It is difficult to evaluate the risk of patients with severe renal dysfunction before surgery due to various limitations despite high postoperative cardiac events. This study aimed to investigate the value of a newly reclassified Revised Cardiac Risk Index (RCRI) that incorporates QRS fragmentation (fQRS) as a predictor of postoperative cardiac events in patients with severe renal dysfunction. METHODS: Among the patients with severe renal dysfunction, 256 consecutive patients who underwent both a nuclear stress test and noncardiac surgery were evaluated. We reclassified RCRI as fragmented RCRI (FRCRI) by integrating fQRS on electrocardiography. We defined postoperative major adverse cardiac event (MACE) as a composite of cardiac death, nonfatal myocardial infarction, and pulmonary edema. RESULTS: Twenty-eight patients (10.9%) developed postoperative MACE, and this was significantly frequent in patients with myocardial perfusion defect (41.4% vs. 28.0%, p = 0.031). fQRS was observed 84 (32.8%) patients, and it was proven to be an independent predictor of postoperative MACE after adjusting for the RCRI (odds ratio 3.279, 95% confidence interval (CI) 1.419-7.580, p = 0.005). Moreover, fQRS had an incremental prognostic value for the RCRI (chi-square = 7.8, p = 0.005), and to the combination of RCRI and age (chi-square = 9.1, p = 0.003). The area under curve for predicting postoperative MACE significantly increased from 0.612 for RCRI to 0.667 for FRCRI (p = 0.027) and 23 patients (32.4%) originally classified as RCRI 2 were reclassified as FRCRI 3. CONCLUSIONS: A newly reclassified FRCRI that incorporates fQRS, is a valuable predictor of postoperative MACE in patients with severe renal dysfunction undergoing noncardiac surgery.

N-terminal pro-brain natriuretic peptide and coronary collateral formation in patients undergoing primary percutaneous coronary intervention.

There is insufficient information on the relationship between the N-terminal pro-brain natriuretic peptide (NT-proBNP) level and collateral circulation (CC) formation after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction. We analyzed 857 patients who underwent primary PCI. The serum NT-proBNP levels were measured on the day of admission, and the CC was scored according to Rentrop's classification. Log-transformed NT-proBNP levels were significantly higher in patients with good CC compared to those with poor CC (6.13 ± 2.01 pg/mL versus 5.48 ± 1.97 pg/mL, p < 0.001). The optimum cutoff value of log NT-proBNP for predicting CC was 6.04 pg/mL. Log NT-proBNP ≥ 6.04 pg/mL (odds ratio 2.23; 95% confidence interval 1.51-3.30; p < 0.001) was an independent predictor of good CC. CC development was higher in patients with a pre-TIMI flow of 0 or 1 than those with a pre-TIMI flow of 2 or 3 (22.6% versus 8.8%, p = 0.001). The incidence of left ventricular (LV) dysfunction (< 50%) was greater in patients with a pre-TIMI flow of 0 or 1 (49.8% versus 35.5%, p < 0.001). The release of NT-proBNP was greater in patients with LV dysfunction (34.3% versus 15.6%, p < 0.001). The incidence of good CC was greater in patients with log NT-proBNP levels ≥ 6.04 pg/ml (16.8% versus 26.2%, p = 0.003). The association between NT-proBNP and collateral formation was not influenced by pre-TIMI flow and LV function. NT-proBNP appears to reflect the degree of collateral formation in the early phase of STEMI and might have a new role as a useful surrogate biomarker for collateral formation in patients undergoing primary PCI.

Effects of Asian dust-derived particulate matter on ST-elevation myocardial infarction: retrospective, time series study.

BACKGROUND: Dust storms affect human health by impairing visibility and promoting interactions with microscopic organisms, such as bacteria and fungi. Although ST-elevation MI (STEMI) and non-ST-elevation MI (NSTEMI) differ mechanistically, few studies have investigated the incidence of cardiovascular diseases according to infarction type; these studies have yielded inconsistent findings. This study aimed to examine whether PM size (< 2.5 µm (PM2.5) and < 10 µm (PM10)) modifies the effect of Asian dust on acute myocardial infarction (AMI), with separate analyses for STEMI and NSTEMI. METHODS: MI-related data from 9934 emergency visits were collected from the Korea AMI Registry from 2005 to 2017. Asian dust events were defined as days with visibility of ≤10 km. Generalized linear models were used to analyze data with natural cubic splines. To examine potential modifiers, analyses were stratified by age, smoking status, and body mass index (BMI). RESULTS: No significant associations were observed between Asian dust and AMI. By adjusting for different lag structures, a significant effect was exclusively observed in STEMI. For moving average lags, the largest value at lag 5 (relative risk [RR] 1.083; 95% confidence interval [CI], 1.007-1.166) for single and lags 0-7 (RR 1.067; 95% CI: 1.002-1.136) was observed for PM2.5; for PM10, the largest significant effect was observed at lag 4 (RR 1.075; 95% CI: 1.010-1.144) for single and lags 0-7 (RR 1.067; 95% CI: 1.002-1.136). RRs were significantly higher in < 65-year-olds than in ≥65-year-olds. Additionally, RRs between the BMI < 25 and BMI ≥ 25 groups were not different; statistically significant effects were observed for concentration at lags 0-5 (RR: 1.073; 95% CI: 1.002-1.150) and lags 0-6 (RR: 1.071; 95% CI: 1.001-1.146) in the BMI < 25 group. A negative exposure-response association was observed between daily average visibility-adjusted PM and STEMI and daily average visibility-adjusted PM in < 65-year-olds. CONCLUSIONS: Reducing PM2.5 and PM10 emissions, particularly during the days of Asian dust, may be crucial and reduce STEMI and AMI incidence among < 65-year-olds. These results indicate that the Asian dust alarm system needs revision to protect vulnerable populations.

Impact of Cardiovascular Risk Factors and Cardiovascular Diseases on Outcomes in Patients Hospitalized with COVID-19 in Daegu Metropolitan City.

BACKGROUND: Data regarding the association between preexisting cardiovascular risk factors (CVRFs) and cardiovascular diseases (CVDs) and the outcomes of patients requiring hospitalization for coronavirus disease 2019 (COVID-19) are limited. Therefore, the aim of this study was to investigate the impact of preexisting CVRFs or CVDs on the outcomes of patients with COVID-19 hospitalized in a Korean healthcare system. METHODS: Patients with COVID-19 admitted to 10 hospitals in Daegu Metropolitan City, Korea, were examined. All sequentially hospitalized patients between February 15, 2020, and April 24, 2020, were enrolled in this study. All patients were confirmed to have COVID-19 based on the positive results on the polymerase chain reaction testing of nasopharyngeal samples. Clinical outcomes during hospitalization, such as requiring intensive care and invasive mechanical ventilation (MV) and death, were evaluated. Moreover, data on baseline comorbidities such as a history of diabetes, hypertension, dyslipidemia, current smoking, heart failure, coronary artery disease, cerebrovascular accidents, and other chronic cardiac diseases were obtained. RESULTS: Of all the patients enrolled, 954 (42.0%) had preexisting CVRFs or CVDs. Among the CVRFs, the most common were hypertension (28.8%) and diabetes mellitus (17.0%). The prevalence rates of preexisting CVRFs or CVDs increased with age (P < 0.001). The number of patients requiring intensive care (P < 0.001) and invasive MV (P < 0.001) increased with age. The in-hospital death rate increased with age (P < 0.001). Patients requiring intensive care (5.3% vs. 1.6%; P < 0.001) and invasive MV (4.3% vs. 1.7%; P < 0.001) were significantly greater in patients with preexisting CVRFs or CVDs. In-hospital mortality (12.9% vs. 3.1%; P < 0.001) was significantly higher in patients with preexisting CVRFs or CVDs. Among the CVRFs, diabetes mellitus and hypertension were associated with increased requirement of intensive care and invasive MV and in-hospital death. Among the known CVDs, coronary artery disease and congestive heart failure were associated with invasive MV and in-hospital death. In multivariate analysis, preexisting CVRFs or CVDs (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.07-3.01; P = 0.027) were independent predictors of in-hospital death after adjusting for confounding variables. Among individual preexisting CVRF or CVD components, diabetes mellitus (OR, 2.43; 95% CI, 1.51-3.90; P < 0.001) and congestive heart failure (OR, 2.43; 95% CI, 1.06-5.87; P = 0.049) were independent predictors of in-hospital death. CONCLUSION: Based on the findings of this study, the patients with confirmed COVID-19 with preexisting CVRFs or CVDs had worse clinical outcomes. Caution is required in dealing with these patients at triage.

Impact of diabetes mellitus on mortality in patients with acute heart failure: a prospective cohort study.

BACKGROUND: Although more than one-third of the patients with acute heart failure (AHF) have diabetes mellitus (DM), it is unclear if DM has an adverse impact on clinical outcomes. This study compared the outcomes in patients hospitalized for AHF stratified by DM and left ventricular ejection fraction (LVEF). METHODS: The Korean Acute Heart Failure registry prospectively enrolled and followed 5625 patients from March 2011 to February 2019. The primary endpoints were in-hospital and overall all-cause mortality. We evaluated the impact of DM on these endpoints according to HF subtypes and glycemic control. RESULTS: During a median follow-up of 3.5 years, there were 235 (4.4%) in-hospital mortalities and 2500 (46.3%) overall mortalities. DM was significantly associated with increased overall mortality after adjusting for potential confounders (adjusted hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.03-1.22). In the subgroup analysis, DM was associated with higher a risk of overall mortality in heart failure with reduced ejection fraction (HFrEF) only (adjusted HR 1.14, 95% CI 1.02-1.27). Inadequate glycemic control (HbA1c ≥ 7.0% within 1 year after discharge) was significantly associated with a higher risk of overall mortality compared with adequate glycemic control (HbA1c < 7.0%) (44.0% vs. 36.8%, log-rank p = 0.016). CONCLUSIONS: DM is associated with a higher risk of overall mortality in AHF, especially HFrEF. Well-controlled diabetes (HbA1c < 7.0%) is associated with a lower risk of overall mortality compared to uncontrolled diabetes. Trial registration ClinicalTrial.gov, NCT01389843. Registered July 6, 2011. https://clinicaltrials.gov/ct2/show/NCT01389843.

Gender difference in the impact of Ischaemic heart disease on heart failure.

BACKGROUND: Although the impact of ischaemic heart disease (IHD) on heart failure (HF) is evolving, there is uncertainty about the role of IHD in determining the risk of clinical outcomes by gender. This study evaluated the gender difference in the impact of IHD on long-term clinical outcomes in patients with heart failure reduced ejection fraction (HFrEF). METHODS: Study data were obtained from a nationwide registry, which is a prospective multicentre cohort that included 3200 patients who were hospitalized for HF. A total of 1638 patients with HFrEF were classified by gender. The primary outcome was all-cause death during follow-up. RESULTS: In total, 133 women (18.9%) died and 168 men (18.0%) died during the follow-up (median, 489 days). Women with HFrEF with IHD had a significantly lower cumulative survival rate than women without IHD at the long-term follow-up (74.8% vs 84.9%, log-rank P = .001). However, the survival rate was not different in men with HFrEF with IHD compared with men without IHD. A Cox regression analysis showed that IHD had a 1.43-fold increased risk for all-cause mortality independently in women after adjusting for confounding factors (odds ratio 1.43, 95% confidence interval 1.058-1.929, P = .020). CONCLUSION: Ischaemic heart disease was an independent risk factor for long-term mortality in women with HFrEF. IHD should be actively evaluated in women with HF for predicting clinical outcomes and initiating appropriate treatment. Women with HF caused by IHD should be treated more meticulously to avoid a poor prognosis.

Intravascular modality-guided versus angiography-guided percutaneous coronary intervention in acute myocardial infarction.

BACKGROUND: Few data are available for current usage patterns of intravascular modalities such as intravascular ultrasound (IVUS), optical coherence tomography (OCT), and fractional flow reserve (FFR) in acute myocardial infarction (AMI). Moreover, patient and procedural-based outcomes related to intravascular modality guidance compared to angiography guidance have not been fully investigated yet. METHODS: We examined 11,731 patients who underwent percutaneous coronary intervention (PCI) from the Korea AMI Registry-National Institute of Health database. Patient-oriented composite endpoint (POCE) was defined as all-cause death, any infarction, and any revascularization. Device-oriented composite endpoint (DOCE) was defined as cardiac death, target-vessel reinfarction, and target-lesion revascularization. RESULTS: Overall, intravascular modalities were utilized in 2,659 (22.7%) patients including 2,333 (19.9%) IVUS, 277 (2.4%) OCT, and 157 (1.3%) FFR. In the unmatched cohort, POCE (5.4 vs. 8.5%; adjusted hazard ratio (HR) 0.75; 95% confidence interval (CI) 0.61-0.93; p = .008) and DOCE (4.6 vs. 7.4%; adjusted HR 0.77; 95% CI 0.61-0.97; p = .028) were significantly lower in intravascular modality-guided PCI compared with angiography-guided PCI. In the propensity-score-matched cohorts, POCE (5.9 vs. 7.7%; HR 0.74; 95% CI 0.60-0.92; p = .006) and DOCE (5.0 vs. 6.8%; HR 0.72; 95% CI 0.57-0.90; p = .004) were significantly lower in intravascular modality guidance compared with angiography guidance. The difference was mainly driven by reduced all-cause mortality (4.4 vs. 7.0%; p < .001) and cardiac mortality (3.3 vs. 5.2%; p < .001). CONCLUSION: In this large-scale AMI registry, intravascular modality guidance was associated with an improving clinical outcome in selected high-risk patients.

Osborn waves during therapeutic hypothermia and recurrence of fatal arrhythmia in patients resuscitated following sudden cardiac arrest.

BACKGROUND: This study investigates the impact of the occurrence of Osborn waves during therapeutic hypothermia (TH) on the recurrence of future fatal arrhythmias in patients resuscitated after sudden cardiac arrest (SCA). METHODS: Of all survivors of out-of-hospital SCA, 100 consecutive patients (mean age, 52 ± 15 years; 80% men) who received TH were included in this study. RESULTS: The most common first documented arrhythmia was ventricular fibrillation (VF) (77%), and ischemic heart disease (44%) and idiopathic VF (22%) were the most common causes of SCA in resuscitated patients. During TH, Osborn waves developed in 29 patients (29%). Osborn waves occurred more frequently in patients with Brugada syndrome. Patients with Osborn waves had lower in-hospital (10.3% vs 26.8%; P = .072) and 1-year death rates (20.7% vs 39.4%; P = .073) and better cerebral function (cerebral performance category scale, 2.0 ± 1.5 vs 2.7 ± 1.8; P = .053) than those without Osborn waves, although there was no statistical significance. Among 78 in-hospital survivors, 31 (40%) underwent implantable cardioverter-defibrillator (ICD) implantation. Appropriate ICD shocks from fatal arrhythmias were more frequent in patients who had Osborn waves than in those without Osborn waves (43% vs 6%; P = .032). CONCLUSIONS: Osborn waves during TH had no significant effect on the survival and cerebral function of patients resuscitated SCA. However, appropriate ICD shocks due to the recurrence of VF were more frequent in patients with Osborn waves during long-term follow-up.

A Case of COVID-19 with Acute Myocardial Infarction and Cardiogenic Shock.

A 60-year-old male patient with coronavirus disease-2019 showed new onset ST-segment elevation in V1-V2 leads on electrocardiogram and cardiac enzyme elevation in intensive care unit. He had a history of type 2 diabetes mellitus, hypertension, and dyslipidemia. He was receiving mechanical ventilation and veno-venous extracorporeal membrane oxygenation treatment for severe hypoxia. Two-D echocardiogram showed regional wall motion abnormalities. We performed primary percutaneous coronary intervention for acute myocardial infarction complicating cardiogenic shock under hemodynamic support. He expired on the 16th day of admission because of cardiogenic shock and multi-organ failure. Active surveillance and intensive treatment strategy are important for saving lives of COVID-19 patients with acute myocardial infarction.

Beta-blocker Therapy at Discharge in Patients with Acute Heart Failure and Atrial Fibrillation.

BACKGROUND: ß-blockers (BBs) are considered primary therapy in stable heart failure (HF) with reduced ejection fraction (HFrEF) without atrial fibrillation (AF); evidence-based benefits of BB on outcome have been documented. However, BBs have not been shown to improve mortality or reduce hospital admissions in HF patients with AF. This study assessed the relationship between BBs at discharge and relevant clinical outcomes in acute heart failure (AHF) patients with AF. METHODS: From the Korean Acute Heart Failure Registry, 936 HFrEF and 639 HF patients with preserved ejection fraction (HFpEF) and AF were selected. Propensity score (PS) matching accounted for BB selection bias when assessing associations. RESULTS: BB-untreated patients in the overall cohort of HFrEF and HFpEF had greater deteriorated clinical and laboratory characteristics. In the 670 PS-matched cohort of HFrEF patients, incidences of all clinical events at 60 days and 1 year were not different according to use of BBs. In the 470 PS-matched cohort of HFpEF, rehospitalization and composite outcome at 6 months and 1 year more frequently occurred in non-users of BBs. After adjusting for covariates in the multivariable Cox model of matched cohorts, BB was not associated with clinical outcomes at 60 days and 1 year in HFrEF with AF patients. In HFpEF patients with AF, BB use was associated with reduced 6-month (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20-0.74) and 1-year rehospitalization (HR, 0.53; 95% CI, 0.34-0.82). CONCLUSION: In the HFrEF with AF PS-matched cohort, the use of BBs at discharge was not associated with clinical outcome. However, in HFpEF with AF, the use of BB was associated with reduced rehospitalization during the 6-month and 1-year follow up.

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 cardioverter-defibrillator (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 under-utilization 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843.

Incremental Predictive Value of Plasma Renin Activity as a Prognostic Biomarker in Patients with Heart Failure.

BACKGROUND: The association of N-terminal pro-B type natriuretic peptide (NT-proBNP) and plasma renin activity (PRA) for the prognosis of the patients with acute heart failure (HF) has not been fully investigated. This study aimed to determine the association between NT-proBNP and PRA and to investigate the incremental value of PRA to NT-proBNP for predicting long term prognosis in patients with acute HF. METHODS: Three hundred and ninety-six patients (mean age, 64.7 ± 15.9 years; 46.5% female) presenting with acute HF were enrolled between December 2004 and July 2013. Patients with newly diagnosed HF as well as patients with acute exacerbated chronic HF were included. The prognosis was assessed with the composite event of all-cause mortality and readmission for HF during a 2-year follow-up period. RESULTS: The etiology of HF was ischemic in 116 (29.3%) patients. In a Cox proportional hazards model, log-transformed PRA (hazard ratio [HR], 1.205; P = 0.007) was an independent predictor of the composite outcome of all-cause mortality and readmission for HF in addition to age (HR, 1.032; P = 0.001), white blood cell (WBC) count (HR, 1.103; P < 0.001), and left ventricular ejection fraction (LVEF) (HR, 0.978; P = 0.013). Adding PRA to age, sex, LVEF, and NT-proBNP significantly improved the prediction for the composite outcome of all-cause mortality and readmission for HF, as shown by the net reclassification improvement (0.47; P < 0.001) and integrated discrimination improvement (0.10; P < 0.001). CONCLUSION: PRA could provide incremental predictive value to NT-proBNP for predicting long term prognosis in patients with acute HF.

Comparison of Characteristics and 3-Year Outcomes in Patients With Acute Heart Failure With Preserved, Mid-Range, and Reduced Ejection Fraction.

BACKGROUND: The clinical characteristics and outcomes of acute heart failure (AHF) according to left ventricular ejection fraction (LVEF) have not been fully elucidated, especially for patients with mid-range LVEF. We performed a comprehensive comparison of the epidemiology, patterns of in-hospital management, and clinical outcomes in AHF patients with different LVEF categories. Methods and Results: The Korean Acute Heart Failure (KorAHF) registry is a prospective multicenter cohort of hospitalized AHF patients in Korea. A total of 5,374 patients enrolled in the KorAHF registry were classified according to LVEF based on the 2016 ESC guidelines. More than half of the HF patients (58%) had reduced EF (HFrEF), 16% had mid-range EF (HFmrEF), and 25% had preserved EF (HFpEF). The HFmrEF patients showed intermediate epidemiological profiles between HFrEF and HFpEF and had a propensity to present as de-novo HF with ischemic etiology. Patients with lower LVEF had worse short-term outcomes, and the all-cause in-hospital mortality, including urgent heart transplantation, of HFrEF, HFmrEF, and HFpEF was 7.1%, 3.6%, and 3.0%, respectively. Overall, discharged AHF patients showed poor 3-year all-cause death up to 38%, which was comparable between LVEF subgroups (P=0.623). CONCLUSIONS: Each LVEF subgroup of AHF patients was a heterogeneous population with diverse characteristics, which have a significant effect on the clinical outcomes. This finding suggested that focused phenotyping of AHF patients could help identify the optimal management strategy and develop novel effective therapies.

Prognostic Impact of ß-Blocker Dose After Acute Myocardial Infarction.

BACKGROUND: The differential prognostic impact of ß-blocker dose after acute myocardial infarction (AMI) has been under debate. The current study sought to compare clinical outcome after AMI according to ß-blocker dose using the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH). Methods and Results: Of the total population of 13,104 consecutive AMI patients enrolled in the KAMIR-NIH, the current study analyzed 11,909 patients. These patients were classified into 3 groups (no ß-blocker; low-dose [<25% of target dose]; and high-dose [≥25% of target dose]). The primary outcome was cardiac death at 1 year. Compared with the no ß-blocker group, both the low-dose and high-dose groups had significantly lower risk of cardiac death (HR, 0.435; 95% CI: 0.363-0.521, P<0.001; HR, 0.519; 95% CI: 0.350-0.772, P=0.001, respectively). The risk of cardiac death, however, was similar between the high- and low-dose groups (HR, 1.194; 95% CI: 0.789-1.808, P=0.402). On multivariable adjustment and inverse probability weighted analysis, the result was the same. CONCLUSIONS: The use of ß-blockers in post-AMI patients had significant survival benefit compared with no use of ß-blockers. There was no significant additional benefit of high-dose ß-blockers compared with low-dose ß-blockers, however, in terms of 1-year risk of cardiac death.

Comparison of Clinical Outcomes Between Ticagrelor and Prasugrel in Patients With ST-Segment Elevation Myocardial Infarction　- Results From the Korea Acute Myocardial Infarction Registry-National Institutes of Health.

BACKGROUND: There is little information regarding comparison of ticagrelor and prasugrel in patients with ST-segment elevation myocardial infarction (STEMI). We sought to compare clinical outcomes between ticagrelor and prasugrel in STEMI.Methods and Results:A total of 1,440 patients with STEMI who underwent successful primary percutaneous coronary intervention were analyzed; the data were obtained from the Korea Acute Myocardial Infarction Registry-National Institutes of Health. Of the patients, 963 received ticagrelor, and 477 received prasugrel. The primary study endpoint was 12-month major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), and target vessel revascularization (TVR). MACE occurred in 91 patients (6.3%) over the 1-year follow-up, and there were no differences in the incidence of MACE (hazard ratio [HR] 1.20, 95% confidence interval [CI] 0.76-1.91, P=0.438) between the 2 groups. Analysis by propensity score matching (429 pairs) did not significantly affect the results. The incidence of in-hospital major bleeding events was still comparable between the 2 groups (2.4% vs. 2.5%, odds ratio 0.75, 95% CI 0.30-1.86, P=0.532), and there was no significant difference in the incidence of MACE (5.4% vs. 5.8%, HR 0.98, 95% CI 0.56-1.74, P=0.951) after matching. CONCLUSIONS: Ticagrelor and prasugrel showed similar efficacy and safety profiles for treating STEMI in this Korean multicenter registry.

Effects of Statin Intensity on Clinical Outcome in Acute Myocardial Infarction Patients.

BACKGROUND: There has been debate regarding the added benefit of high-intensity statins compared with low-moderate-intensity statins, especially in patients with acute myocardial infarction (AMI).Methods and Results:The Korea Acute Myocardial Infarction Registry-National Institutes of Health consecutively enrolled 13,104 AMI patients. Of these, a total of 12,182 patients, who completed 1-year follow-up, were included in this study, and all patients were classified into 3 groups (no statin; low-moderate-intensity statin; and high-intensity statin). The primary outcome was major adverse cardiac event (MACE) including cardiac death, non-fatal MI, and repeat revascularization at 1 year. Both low-moderate-intensity and high-intensity statin significantly reduced low-density lipoprotein cholesterol (LDL-C; all P<0.001). Compared with the no statin group, both statin groups had significantly lower risk of MACE (low-moderate intensity: HR, 0.506; 95% CI: 0.413-0.619, P<0.001; high intensity: HR, 0.464; 95% CI: 0.352-0.611, P<0.001). The risk of MACE, however, was similar between the low-moderate- and high-intensity statin groups (HR, 0.917; 95% CI: 0.760-1.107, P=0.368). Multivariable adjustment, propensity score matching, and inverse probability weighted analysis also produced the same results. CONCLUSIONS: When adequate LDL-C level is achieved, patients on a low-moderate-intensity statin dose have similar cardiovascular outcomes to those on high-intensity statins.