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.

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.

Simultaneous Occurrence of Immune-Mediated Thrombocytopenia and Myocarditis After mRNA-1273 COVID-19 Vaccination: A Case Report.

With the global spread of severe acute respiratory syndrome coronavirus 2, several vaccines were developed; messenger RNA (mRNA) vaccines have recently been widely used worldwide. However, the incidence of myocarditis following mRNA vaccination is increasing; although the cause of myocarditis has not yet been clearly identified, it is presumed to be caused by a problem in the innate immune system. Immune-mediated thrombocytopenia (ITP) after vaccination is rare but has been reported and is also assumed to occur by the same mechanism. We report the first case of simultaneous myocarditis and ITP after mRNA vaccination. A 38-year-old woman presented with chest pain, mild dyspnea, and sweating after vaccination with mRNA-1273 vaccine (Moderna) 4 days prior to admission. Upon admission to the emergency department, cardiac enzymes were elevated; blood test performed 5 months ago showed normal platelet count, but severe thrombocytopenia was observed upon admission. After administration of intravenous immunoglobulin, the platelet count improved; subsequently, myocarditis was observed on endomyocardial biopsy. Thus, myocarditis and ITP were judged to have occurred simultaneously due to the expression of the innate immune system markers after mRNA vaccination. The patient was discharged on day 6 of admission.

Clinical Implication of 'Obesity Paradox' in Elderly Patients With Acute Myocardial Infarction.

BACKGROUND: The clinical impact of body mass index (BMI), especially in the elderly with acute myocardial infarction (AMI), has not been sufficiently evaluated. The purpose of this study was to elucidate the clinical impact of BMI in very old patients (≥80 years) with AMI. METHODS: The study analysed 2,489 AMI patients aged ≥80 years from the Korea Acute Myocardial Infarction Registry and the Korea Working Group on Myocardial Infarction (KAMIR/KorMI) registries between November 2005 and March 2012. The study population was categorised into four groups based on their BMI: underweight (n=301), normal weight (n=1,150), overweight (n=890), and obese (n=148). The primary endpoint was major adverse cardiovascular event (MACE), a composite of cardiac death, myocardial infarction, target lesion revascularisation, and target vessel revascularisation. RESULTS: Baseline characteristics among the four groups were similar, except for hypertension (45.1 vs 58.4 vs 66.2 vs 69.9%, respectively; p<0.001) and diabetes (16.6 vs 23.6 vs 30.7 vs 35.1%, respectively; p<0.001). Coronary care unit length of stay was significantly different among the four groups during hospitalisation (5.3±5.9 vs 4.8±6.8 vs 4.2±4.0 vs 3.5±2.1 days; p=0.007). MACE (16.9 vs 14.9 vs 13.7 vs 8.8%; p=0.115) and cardiac death (10.3 vs 8.4 vs 7.9 vs 4.1%; p=0.043) less frequently occurred in the obese group than in other groups during the 1-year follow-up. A multivariate regression model showed obese status (BMI ≥27.5 kg/m2) as an independent predictor of reduced MACE (hazard ratio [HR], 0.20; 95% confidence interval [CI], 0.06-0.69; p=0.010) along with reduced left ventricular ejection fraction (≤40%) as a predictor of increased MACE (HR,1.87; 95% CI, 1.31-2.68; p=0.001). CONCLUSION: Body mass index in elderly patients with acute myocardial infarction was significantly associated with coronary care unit stay and clinical cardiovascular outcomes.

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.

Long-Term Comparison of Platinum Chromium Everolimus-Eluting Stent vs. Cobalt Chromium Zotarolimus-Eluting Stent　- 3-Year Outcomes From the HOST-ASSURE Randomized Clinical Trial.

BACKGROUND: There are limited data on the long-term outcome of platinum chromium-based everolimus-eluting stents (PtCr-EES) vs. cobalt chromium-based zotarolimus-eluting stents (CoCr-ZES).Methods and Results:A total of 3,755 patients undergoing percutaneous coronary intervention (PCI) were randomized 2:1 to PtCr-EES or CoCr-ZES, and 96.0% of patients completed the 3-year clinical follow-up. The primary outcome was target lesion failure (TLF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI), and clinically-driven target lesion revascularization (TLR). At 3 years, TLF occurred in 5.3% and in 5.4% of the PtCr-EES and CoCr-ZES groups, respectively (hazard ratio 0.978; 95% confidence interval 0.730-1.310, P=0.919). There were no significant differences in the individual components of TLF. Routine angiographic follow-up was performed in 38.9% of the total patients. In a landmark analysis of the subgroup that had follow-up angiography, the clinically-driven TLR rate of CoCr-ZES was significantly higher than PtCr-EES group during the angiography follow-up period (P=0.009). Overall definite and probable stent thrombosis rates were very low in both groups (0.5% vs. 0.6%, P=0.677). CONCLUSIONS: PtCr-EES and CoCr-ZES had similar and excellent long-term outcomes in both efficacy and safety after PCI in an all-comer population.

Fate of Acute Heart Failure Patients With Mid-Range Ejection Fraction.

BACKGROUND: The outcomes of heart failure (HF) with mid-range ejection fraction (HFmrEF) have been rarely studied, and follow-up data on left ventricular ejection fraction (LVEF) are scarse.Methods and Results:Patients were selected from a prospective multicenter registry of patients hospitalized for acute HF and then classified in the improved group if they exhibited %LVEF change ≥5 with follow-up LVEF ≥50%. Follow-up LVEF reported at least 90 days after discharge was used for classification. Of the 3,085 patients with acute HF, 454 were classified in the HFmrEF, and 276 had follow-up data. Of these 276 patients, 34.1% were classified in the improved group. Multivariate analysis revealed that hypertension, higher heart rate, lower serum sodium level, and maintenance therapy with ß-blocker were associated with improved LVEF. The survival rate was significantly higher in the improved group than in the other groups. Young age and maintenance therapy with renin-angiotensin system blockers or aldosterone antagonists were significantly associated with better survival in HFmrEF. CONCLUSIONS: One-third of HFmrEF patients showed improved LVEF; moreover, the survival rate in the improved group was higher than the other groups. Renin-angiotensin system blockers and aldosterone antagonists could improve the survival of HFmrEF patients.

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 registry at www.ClinicalTrials.gov, NCT00749034.

Atrial Fibrillation on Admission Is Related With Higher Mortality in ST-Segment Elevation Myocardial Infarction Patients.

The prognostic significance of atrial fibrillation (AF) on mortality in ST-segment elevation myocardial infarction (STEMI) patients is not clearly understood. To elucidate the clinical significance of AF on mortality for 1 year in STEMI patients, we retrospectively analyzed the Korea Acute Myocardial Infarction Registry (KAMIR) database, which spans January 2008 to September 2010 and includes 14,329 patients with acute myocardial infarction. We selected 5,556 patients with marked ECG rhythm (NSR, normal sinus rhythm or AF) on emergency room arrival, < 12 hours of symptom onset, and who underwent primary percutaneous coronary intervention (PCI) within 90 minutes of arriving at the hospital. Patients who had been followed-up for at least for 1 year were analyzed (2,636 of NSR, 119 of AF). At enrollment, AF patients were older (70.7 versus 65.5 years, P < 0.001) and had lower systolic blood pressure (120.6 versus 125.9 mmHg, P = 0.050), a higher heart rate (80.4 versus 75.6/minute, P = 0.009), and a higher rate of Killip III, IV (25.0 versus 14.2%, P = 0.002). Patients with AF showed clearly higher all-cause mortality (22.7 versus 9.5%, HR 2.51, 95%CI 1.68~3.76, P < 0.001) and cardiac death rate (17.7 versus 7.5%, HR 2.49, 95%CI 1.59~3.90, P < 0.001) at 1 year after admission compared patients with NSR. AF induced significantly higher all-cause mortality and cardiac mortality rate in STEMI patients who were appropriately revascularized with primary PCI compared to NSR at 1 year.

Impact of low high-density lipoprotein-cholesterol level on 2-year clinical outcomes after acute myocardial infarction in patients with diabetes mellitus.

BACKGROUND: It is still unclear whether low high-density lipoprotein cholesterol (HDL-C) affects cardiovascular outcomes after acute myocardial infarction (AMI), especially in patients with diabetes mellitus. METHODS: A total of 984 AMI patients with diabetes mellitus from the DIabetic Acute Myocardial InfarctiON Disease (DIAMOND) Korean multicenter registry were divided into two groups based on HDL-C level on admission: normal HDL-C group (HDL-C ≥ 40 mg/dL, n = 519) and low HDL-C group (HDL-C < 40 mg/dL, n = 465). The primary endpoint was 2-year major adverse cardiovascular events (MACE), defined as a composite of cardiac death, non-fatal myocardial infarction (MI), and target vessel revascularization (TVR). RESULTS: The median follow-up duration was 730 days. The 2-year MACE rates were significantly higher in the low HDL-C group than in the normal HDL-C group (MACE, 7.44% vs. 3.49%, p = 0.006; cardiac death, 3.72% vs. 0.97%, p = 0.004; non-fatal MI, 1.75% vs. 1.55%, p = 0.806; TVR, 3.50% vs. 0.97%, p = 0.007). Kaplan-Meier analysis revealed that the low HDL-C group had a significantly higher incidence of MACE compared to the normal HDL-C group (log-rank p = 0.013). After adjusting for conventional risk factors, Cox proportional hazards analysis suggested that low HDL-C was an independent risk predictor for MACE (hazard ratio [HR] 3.075, 95% confidence interval [CI] 1.034-9.144, p = 0.043). CONCLUSIONS: In patients with diabetes mellitus, low HDL-C remained an independent risk predictor for MACE after adjusting for multiple risk factors during 2-year follow-up of AMI. TRIAL REGISTRATION: This study was the sub-analysis of the prospective multi-center registry of DIAMOND (Diabetic acute myocardial infarction Disease) in Korea. This is the observational study supported by Bayer HealthCare, Korea. Study number is 15614. First patient first visit was 02 April 2010 and last patient last visit was 09 December 2013.

Comparison of 2-year mortality according to obesity in stabilized patients with type 2 diabetes mellitus after acute myocardial infarction: results from the DIAMOND prospective cohort registry.

BACKGROUND: After acute myocardial infarction (AMI), the replicated phenomenon of obesity paradox, i.e., obesity appearing to be associated with increased survival, has not been evaluated in stabilized (i.e., without clinical events within 1 month post AMI) Asian patients with diabetes mellitus (DM). METHODS: Among 1192 patients in the DIabetic Acute Myocardial InfarctiON Disease (DIAMOND) Korean multicenter registry between April 2010 and June 2012, 2-year cardiac and all-cause death were compared according to obesity (body mass index ≥25 kg/m(2)) in 1125 stabilized DM patients. RESULTS: Compared with non-obese DM patients (62% of AMI patients), obese DM patients had: higher incidence of dyslipidemia (31 vs. 24%, P < 0.01); lower incidence of chronic kidney disease (26 vs. 33%) (P < 0.01); higher left ventricular ejection fraction after AMI (53 ± 11 vs. 50 ± 12%, P < 0.001); and lower 2-year cardiac and all-cause death occurrence (0.7 vs. 3.6% and 1.9 vs. 5.2%, both P < 0.01) and cumulative incidence in Kaplan-Meier analysis (P < 0.005, respectively). Likewise, both univariate and multivariate Cox hazard regression analyses adjusted for the respective confounders showed that obesity was associated with decreased risk of both cardiac [HR, 0.18 (95% CI 0.06-0.60), P = 0.005; and 0.24 (0.07-0.78), P = 0.018, respectively] and all-cause death [0.34 (0.16-0.73), P = 0.005; and 0.44 (0.20-0.95), P = 0.038]. CONCLUSIONS: In a Korean population of stabilized DM patients after AMI, non-obese patients appear to have higher cardiac and all-cause mortality compared with obese patients after adjusting for confounding factors.

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

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

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

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

Association between body mass index and three-year outcome of acute myocardial infarction.

Body mass index (BMI), as an important risk factor related to metabolic disease. However, in some studies higher BMI was emphasized as a beneficial factor in the clinical course of patients after acute myocardial infarction (AMI) in a concept known as the "BMI paradox." The purpose of this study was to investigate how clinical outcomes of patients treated for AMI differed according to BMI levels. A total of 10,566 patients in the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) from May 2010 to June 2015 were divided into three BMI groups (group 1: BMI < 22 kg/m2, group 2: ≥ 22 and < 26 kg/m2, and group 3: ≥ 26 kg/m2). The primary outcome was major adverse cardiac and cerebrovascular event (MACCE) at 3 years of follow-up. At 1 year of follow-up, the incidence of MACCE in group 1 was 10.1% of that in group 3, with a hazard ratio (HR) of 2.27, and 6.5% in group 2, with an HR of 1.415. This tendency continued up to 3 years of follow-up. The study demonstrated that lower incidence of MACCE in the high BMI group of Asians during the 3-year follow-up period compared to the low BMI group. The results implied higher BMI could exert a positive effect on the long-term clinical outcomes of patients with AMI undergoing percutaneous coronary intervention (PCI).

Changes in alcohol consumption habits and risk of atrial fibrillation: a nationwide population-based study.

AIMS: Heavy alcohol consumption is an established risk factor for atrial fibrillation (AF). However, the association between habitual changes in heavy habitual drinkers and incident AF remains unclear. The aim of this study was to evaluate whether absolute abstinence or reduced drinking decreases incident AF in heavy habitual drinkers. METHODS AND RESULTS: Atrial fibrillation-free participants with heavy alcohol consumption registered in the Korean National Health Insurance Service database between 2005 and 2008 were enrolled. Habitual changes in alcohol consumption between 2009 and 2012 were classified as sustained heavy drinking, reduced drinking, and absolute abstinence. The primary outcome measure was new-onset AF during the follow-up. To minimize the effect of confounding variables on outcome events, inverse probability of treatment weighting (IPTW) analysis was performed. Overall, 19 425 participants were evaluated. The absolute abstinence group showed a 63% lower incidence of AF (IPTW hazard ratio: 0.379, 95% confidence interval: 0.169-0.853) than did the sustained heavy drinking group. Subgroup analysis identified that abstinence significantly reduced incident AF in participants with normal body mass index and without hypertension, diabetes, dyslipidaemia, heart failure, stroke, chronic kidney disease, or coronary artery disease (all P-value <0.05). There was no statistical difference in incident AF in participants with reduced drinking compared with sustained heavy alcohol group. CONCLUSION: Absolute abstinence could reduce the incidence of AF in heavy alcohol drinkers. Comprehensive clinical measures and public health policies are warranted to motivate alcohol abstinence in heavy drinkers.

In this study of 19 425 participants, we investigated whether alcohol consumption reduction was associated with lower risk of incident atrial fibrillation (AF) in individuals with chronic heavy alcohol consumption. The absolute abstinence significantly reduced incident AF, but reducing alcohol consumption was not associated with a lower incident AF. The benefit of absolute abstinence for incidence of AF was significantly identified in participants with normal body mass index and without hypertension, diabetes, dyslipidaemia, heart failure, stroke, chronic kidney disease, or coronary artery disease.

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.

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.

Cardiac osteosarcoma: a case report and literature review.

Background: Primary cardiac tumors are rare, and malignant primary cardiac tumors are even rarer. Cardiac osteosarcoma is a very rare type of malignant primary cardiac tumor with limited reported cases. We present a case report of cardiac osteosarcoma and review its characteristics and the related literature. Case summary: A 44-year-old female patient without a specific medical history presented with intermittent dyspnea that started 1 month prior to presentation. A heterogeneous mass was observed in the left atrium on echocardiography and a large mass was observed in the left atrium on computed tomography. Surgery was performed under the suspicion of atypical cardiac myxoma, and the tumor was successfully removed. However, postoperative histopathological examination revealed cardiac osteosarcoma. The patient underwent chemotherapy and has been well maintained without recurrence for 10 years. Conclusion: We present a case report of the echocardiographic features and treatment strategies for cardiac osteosarcoma, an extremely rare cardiac tumor. Multimodal imaging can be helpful; however, a histological diagnosis through surgical resection is essential. Appropriate treatment and follow-up based on histological findings are necessary.

Absence of SOCS3 in the cardiomyocyte increases mortality in a gp130-dependent manner accompanied by contractile dysfunction and ventricular arrhythmias.

BACKGROUND: Suppressor of cytokine signaling-3 (SOCS3) is a key negative-feedback regulator of the gp130 receptor that provides crucial signaling for cardiac hypertrophy and survival; however, an in vivo role of SOCS3 regulation on cardiac gp130 signaling remains obscure. METHODS AND RESULTS: We generated cardiac-specific SOCS3 knockout (SOCS3 cKO) mice. These mice showed increased activation of gp130 downstream signaling targets (STAT3, ERK1/2, AKT, and p38) from 15 weeks of age and developed cardiac dysfunction from approximately 25 weeks of age with signs of heart failure. Surprisingly, SOCS3 cKO failing hearts had minimal histological abnormalities with intact myofibril ultrastructure. In addition, Ca(2+) transients were significantly increased in SOCS3 cKO failing hearts compared with wild-type hearts. We also found that Ser23/24 residues of troponin I were hypophosphorylated in SOCS3 cKO hearts before the manifestation of cardiac dysfunction. These data suggested the presence of abnormalities in myofilament Ca(2+) sensitivity in SOCS3 cKO mice. In addition to the contractile dysfunction, we found various ventricular arrhythmias in SOCS3 cKO nonfailing hearts accompanied by a sarcoplasmic reticulum Ca(2+) overload. To determine the contribution of gp130 signaling to the cardiac phenotype that occurs with SOCS3 deficiency, we generated cardiac-specific gp130 and SOCS3 double KO mice. Double KO mice lived significantly longer and had different histological abnormalities when compared with SOCS3 cKO mice, thus demonstrating the importance of gp130 signaling in the SOCS3 cKO cardiac phenotype. CONCLUSIONS: Our results demonstrate an important role of SOCS3 regulation on cardiac gp130 signaling in the pathogenesis of contractile dysfunction and ventricular arrhythmias.