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).

Eligibility and Cost-Utility Analysis of Dapagliflozin in Patients with Heart Failure Across the Whole Spectrum of Ejection Fraction in South Korea.

BACKGROUND: The DAPA-HF and DELIVER trials demonstrated the clinical benefits of dapagliflozin in heart failure (HF) patients across the entire ejection fraction (EF) spectrum. However, further investigation is needed for the real-world application of dapagliflozin in HF patients. This study examines the proportion of real-world HF patients eligible for dapagliflozin and evaluates the cost-effectiveness of adding dapagliflozin to current HF therapy. METHODS: Data from the nationwide prospective registry, the Korean Acute Heart Failure (KorAHF) registry, were used to determine dapagliflozin eligibility based on the enrollment criteria of the DAPA-HF/DELIVER trials. A cost-utility analysis was conducted using a Markov model to assess the cost-effectiveness of dapagliflozin by comparing it to the standard of care. RESULTS: Out of 5178 KorAHF patients, 48.7% met the enrollment criteria of the DAPA-HF/DELIVER trials, while 89.5% met the label criteria (US Food and Drug Administration, European Medicines Agency, and Korean Ministry of Food and Drug Safety). Eligibility was highest among HF patients with preserved EF (55.3% vs. HF with mildly reduced EF and HF with reduced EF 46.4%). Dapagliflozin proved to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 4557 US dollar (US$) per quality-adjusted life year, which falls below the US$18,182 willingness-to-pay threshold. The cost-effectiveness benefit was more pronounced in patients with a left ventricular EF (LVEF) ≤ 40% (ICER US$3279 for LVEF ≤ 40% vs. US$8383 for LVEF > 40%). CONCLUSIONS: Discrepancies in dapagliflozin eligibility were observed between real-world data and clinical trial results. The addition of dapagliflozin to HF therapy proved to be highly cost-effective across the entire EF spectrum.

Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea.

BACKGROUND: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. METHODS: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). RESULTS: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). CONCLUSION: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843.

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.

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.

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.

Secular trends and determinants of influenza vaccination uptake among patients with cardiovascular disease in Korea: Analysis using a nationwide database.

Background: Influenza vaccination reduces cardiovascular events in patients with cardiovascular disease (CVD). Identifying the factors that affect influenza vaccination uptake can help improve the prognosis in patients with CVD. This study aimed to evaluate the secular trends of influenza vaccination uptake and factors associated with lack of vaccination in individuals with CVD. Materials and methods: We analyzed the annual trends and factors associated with influenza vaccination among 3,264 patients with CVD, included from the Korea National Health and Nutrition Examination Survey which reflect the health and nutritional status of the nationwide population of Korea conducted between 2007/2008 and 2018/2019. We used a stratified, multistage sampling method. Results: The influenza vaccination rate was greater in patients with CVD (53-74%) than in those without CVD (28-40%). Multivariable logistic regression analysis showed that age <50 years [odds ratio (OR), 16.22; 95% confidence interval (CI), 7.72-34.07], 50-64 years (OR, 6.71; 95% CI, 4.37-10.28), male sex (OR, 1.45; 95% CI, 1.14-1.65), and asthma (OR, 0.45; 95% CI, 0.22-0.92) were independently associated with a lack of influenza vaccination. Among patients aged <65 years, smoking (OR, 2.30; 95% CI, 1.31-4.04), college graduation status (OR, 1.81; 95% CI, 1.16-2.82), and hypertension (OR, 0.70; 95% CI, 0.51-0.95) were independently associated with influenza vaccination. For individuals aged 65years, there was no significant determinant of lack of vaccination. Conclusion: In patients with CVD, a continuous increase in the secular trend of influenza vaccination was demonstrated in Korea. Young age, male sex, and non-asthma status were independently associated with lack of influenza vaccination uptake.

End-of-Life Care for End-stage Heart Failure Patients.

Efforts to improve end-of-life (EOL) care have generally been focused on cancer patients, but high-quality EOL care is also important for patients with other serious medical illnesses including heart failure (HF). Recent HF guidelines offer more clinical considerations for palliative care including EOL care than ever before. Because HF patients can experience rapid, unexpected clinical deterioration or sudden death throughout the disease trajectory, choosing an appropriate time to discuss issues such as advance directives or hospice can be challenging in real clinical situations. Therefore, EOL issues should be discussed early. Conversations are important for understanding patient and family expectations and developing mutually agreed goals of care. In particular, high-quality communication with patient and family through a multidisciplinary team is necessary to define patient-centered goals of care and establish treatment based on goals. Control of symptoms such as dyspnea, pain, anxiety/depression, fatigue, nausea, anorexia, and altered mental status throughout the dying process is an important issue that is often overlooked. When quality-of-life outweighs expanding quantity-of-life, the transition to EOL care should be considered. Advanced care planning including resuscitation (i.e., do-not resuscitate order), device deactivation, site for last days and bereavement support for the family should focus on ensuring a good death and be reviewed regularly. It is essential to ensure that treatment for all HF patients incorporates discussions about the overall goals of care and individual patient preferences at both the EOL and sudden changes in health status. In this review, we focus on EOL care for end-stage HF patients.

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

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

Impact of multivessel versus single-vessel disease on the association between low diastolic blood pressure and mortality after acute myocardial infarction with revascularization.

BACKGROUND: Previous studies demonstrated a J-shaped relationship between low diastolic blood pressure (DBP) and adverse clinical outcomes in patients with acute myocardial infarction (AMI) that was sensitive to revascularization. Hypothesized herein, was that this relationship differs between patients with multivessel disease (MVD) and those with single-vessel disease due to differing degrees of myocardial ischemic burden. METHODS: Among 9,983 AMI patients from the Korea Acute Myocardial Infarction Registry database who underwent percutaneous coronary intervention and were followed up for a median duration of 3.2 years, average on-treatment DBP was calculated at admission, discharge, and every scheduled visit and divided into these parameters: < 70 mmHg, 70-74 mmHg, 75-79 mmHg, and ≥ 80 mmHg. The relationship between average on-treatment DBP and clinical outcomes including all-cause death, cardiovascular (CV) death, non-CV death, and hospitalization for heart failure was analyzed using the Cox regression models adjusted for clinical covariates. RESULTS: In patients with MVD, all-cause death (hazard ratio [HR]: 1.47; 95% confidence interval [CI]: 1.06-2.04, p = 0.012) and CV death (HR: 1.59; 95% CI: 1.02-2.46, p = 0.027) were significantly increased in patients with a DBP < 70 mmHg, showing a J-shaped relationship. However, these findings were not significant for single-vessel disease. On a sensitivity analysis excluding subjects with a baseline SBP < 120 mmHg, an increased risk of a low DBP < 70 mmHg remained in MVD. CONCLUSIONS: The J-shaped relationship between low DBP and adverse clinical outcomes in AMI patients who underwent revascularization persisted in MVD, which has a high ischemic burden. These high-risk patients require cautious treatment.

Positive Effect of Air Purifier Intervention on Baroreflex Sensitivity and Biomarkers of Oxidative Stress in Patients with Coronary Artery Disease: A Randomized Crossover Intervention Trial.

Exposure to fine particulate matter increases the risk of cardiovascular morbidity and mortality. Few studies have tested the beneficial effect of indoor air filtration intervention in patients with cardiovascular disease. The aim of this study is to investigate the effect of air filtration on mitigating cardiovascular health in patients with coronary artery disease. This randomized, double-blind, crossover study is conducted with 38 coronary artery disease patients. The intervention consists of the following three periods: two-week active and sham air filtration interventions, with a two-week washout period. The indoor PM2.5 concentration is continuously monitored during the entire study period. We measure the blood pressure, heart rate variability, baroreflex sensitivity, autonomic function test results, and endothelial function. The two-week active air filtration intervention for two weeks reduces the average indoor concentration of PM2.5 by 33.9%. The indoor PM2.5 concentration is significantly correlated to cross-correlation baroreflex sensitivity. Active air filtration is significantly associated with a decrease in the indicator of oxidative stress represented as 8-hydroxy-2'-deoxyguanosine. This study shows that a short-term air filtration intervention improved baroreflex sensitivity and might reduce oxidative stress in coronary artery disease patients. These findings suggest that the use of an air purifier could mitigate the recurrence of cardiovascular disease events in patients with coronary artery disease.

Successful extracorporeal membrane oxygenation treatment of catecholamine-induced cardiomyopathy-associated pheochromocytoma.

The main mechanism of Takotsubo cardiomyopathy (TCM) is catecholamine-induced acute myocardial stunning. Pheochromocytoma, a catecholamine-secreting tumor, can cause several cardiovascular complications, including hypertensive crisis, myocardial infarction, toxic myocarditis, and TCM. A 29-year-old woman presented to our hospital with general weakness, vomiting, dyspnea, and chest pain. The patient was nullipara, 28 weeks' gestation, and had a cachexic morphology. Her cardiac enzyme levels were elevated and bedside echocardiography showed apical akinesia, suggesting TCM. The next day, she could not feel the fetal movement, and an emergency cesarean section was performed. After delivery, the patient experienced cardiac arrest and was transferred to the intensive care unit for cardiopulmonary resuscitation (CPR). Spontaneous circulation returned after 28 minutes of CPR, but cardiogenic shock continued, and extracorporeal membrane oxygenation (ECMO) was initiated. On the third day of ECMO maintenance, left ventricular ejection fraction improved and blood pressure stabilized. On the eighth day after ECMO insertion, it was removed. However, complications of the left leg vessels occurred, and several surgeries and interventions were performed. A left adrenal gland mass was found on computed tomography and was removed while repairing the leg vessels. Pheochromocytoma was diagnosed and left adrenalectomy was performed.

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.

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

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

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

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

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

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