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Background: Chemotherapy-related cardiotoxicity is a significant concern because it is a major cause of morbidity. This study aimed to provide in-depth information on the symptoms of chemotherapy-related cardiotoxicity (CRCT) by exploring literature that concurrently reports the types and symptoms of CRCT in patients with breast cancer. Methods: A scoping review was performed according to an a priori protocol using the Joanna Briggs Institute's guidelines. The participants were patients with breast cancer. The concept was the literature of specifically reported symptoms directly matched with CRCT and the literature, in English, from 2010, and the context was open. The search strategy included four keywords: "breast cancer," "chemotherapy," "cardiotoxicity," and "symptoms." All types of research designs were included; however, studies involving patients with other cancer types, animal subjects, and symptoms not directly related to CRCT were excluded. Data were extracted and presented including tables and figures. Results: A total of 29 articles were included in the study, consisting of 23 case reports, 4 retrospective studies, and 2 prospective studies. There were no restrictions on the participants' sex; however, all of them were women, except for one case report. The most used chemotherapy regimens were trastuzumab, capecitabine, and doxorubicin or epirubicin. The primary CRCT identified were myocardial dysfunction and heart failure, followed by coronary artery disease, pulmonary hypertension, and other conditions. Major tests used to diagnose CRCT include echocardiography, electrocardiography, serum cardiac enzymes, coronary angiography, computed tomography, and magnetic resonance imaging. In all case reports, CRCT was diagnosed through an incidental checkup according to the patient's symptom presentation; however, only 10 of these studies showed a baseline checkup before chemotherapy. The five most common CRCT symptoms were dyspnea, chest pain, peripheral edema, fatigue, and palpitations, which were assessed by patient-reported symptom presentation rather than using a symptom assessment tool. Dyspnea with trastuzumab treatment and chest pain with capecitabine treatment were particularly characteristic. The time for first symptom onset after chemotherapy ranged from 1 hour to 300 days, with anthracycline-based regimens requiring 3–55 days, trastuzumab requiring 60–300 days, and capecitabine requiring 1–7 days. Conclusions: This scoping review allowed data mapping according to the study design and chemotherapy regimens. Cardiac assessments for CRCT diagnosis were performed according to the patient's symptoms. There were approximately five types of typical CRCT symptoms, and the timing of symptom occurrence varied. Therefore, developing and applying a CRCT-specific and user-friendly symptom assessment tool are expected to help healthcare providers and patients manage CRCT symptoms effectively. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Frailty is an issue in patients with heart failure (HF). A Korean version of the frailty scale (K‐FRAIL) has been developed. Hypothesis: We aimed to analyze the relationship between the K‐FRAIL scale and physical performance in patients with HF. Methods: This study included 142 patients with HF aged ≥65 years from a single center. Muscular fitness was assessed using the handgrip test and knee extensor strength measurement. Aerobic capacity was assessed using the cardiopulmonary exercise test and 6‐min walk test (6MWT). Frailty was assessed using the K‐FRAIL questionnaire. Results: Peak VO2 and 6MWT scores significantly decreased as frailty worsened, but handgrip and knee extensor strength did not. In the multivariate analysis, peak VO2 (β = −.31; p =.002) and 6MWT score (β = −.38; p <.001) showed significant inverse associations with the K‐FRAIL score. Based on the receiver operating characteristic curve analysis, the cut‐off values of peak VO2 (hazard ratio, 5.08; p =.023) and 6MWT (hazard ratio, 3.99; p =.020) were independent predictors of frailty. Conclusion: In older patients with HF, physical performance correlates with the degree of frailty. The K‐FRAIL scale is correlated with the peak VO2 and 6MWT. [ABSTRACT FROM AUTHOR]

Aims: Increased red cell distribution width (RDW) is a poor prognostic factor in patients with heart failure (HF). However, only a few large‐scale studies have identified the clinical utility of RDW after adjusting for covariates affecting RDW. Methods and results: From January 2010 to April 2021, we retrospectively enrolled patients diagnosed with HF from three referral hospitals with available RDW data (taken within 3 months of HF diagnosis) using an integrated clinical data system. Patients with an ejection fraction (EF) < 50% or HFA‐PEFF (Heart Failure Association Pre‐test assessment, Echocardiography and natriuretic peptide, Functional testing, Final aetiology) score ≥ 2 without severe valvular heart disease or coronary revascularization were enrolled. The primary endpoint was all‐cause mortality, and cardiovascular mortality was also collected. Multivariable Cox regression analysis and stabilized inverse probability of treatment weighting (IPTW) were used to identify any association between RDW and all‐cause death by balancing covariates or compounding factors. The global χ2 score was calculated and discrimination analysis was performed to evaluate the incremental value of RDW in predicting prognosis. Among the 6599 participants enrolled in this study, 1256 (19.0%) cases of all‐cause death occurred, and the median duration of follow‐up was 887 (interquartile range 351–1589) days. Elevated RDW at the initial diagnosis was associated with poor prognosis [cumulative incidence: 819 (30.2%) vs. 437 (11.2%), relative risk 1.58, 95% confidence interval (CI) 1.51–1.67, log‐rank P < 0.001]. Multivariable Cox analysis showed that elevated RDW was a poor prognostic factor for the primary endpoint [hazard ratio (HR) 1.11, 95% CI 1.06–1.16, P < 0.001], independent of clinical risk factors, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), and EF, which was concordant with the stabilized IPTW (HR 1.29, 95% CI 1.10–1.49, P < 0.001). Adding RDW to model composed of traditional risk factors, NT‐proBNP, and echocardiographic parameters showed incremental prognostic value for predicting poor prognosis (area under the receiver operating characteristic curve, 0.799–0.826; P < 0.001). Conclusions: Increased RDW at the time of diagnosis is associated with poor prognosis in patients with HF, independent of clinical risk factors, such as NT‐proBNP, and echocardiographic parameters. Therefore, RDW may aid in the management of these patients beyond traditional risk factors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims In 2021, vericiguat was approved by the US Food and Drug Administration (FDA) and the European Commission (EC) for reducing cardiovascular mortality and heart failure (HF) hospitalizations in patients with HF with reduced ejection fraction (HFrEF) based on the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial. However, there has been no report for characterizing the generalizability of vericiguat to real‐world clinical practice. Methods and results The Korean Acute Heart Failure (KorAHF) registry is a multicentre prospective cohort study. A total of 5625 patients who were admitted for HF decompensation were consecutively enrolled. We excluded the patients without left ventricular ejection fraction (LVEF) quantification, patients with LVEF > 45%, patients with in‐hospital death or urgent heart transplantation, and patients without natriuretic peptide measurement. Among a total of 3014 enrolled patients, there were 21.9% patients with lower systolic blood pressure (SBP) (<100 mmHg) and 20.1% patients without elevated natriuretic peptide. Regarding chronic kidney disease (CKD) status, 5.1% patients had CKD Stage V [estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2] and 11.8% patients had CKD Stage IV (15 ≤ eGFR < 30 mL/min/1.73 m2). When we analysed these criteria sequentially, 21.9% were excluded from lower SBP, 15.9% were excluded from elevated natriuretic peptide, and 4.2% were excluded from advanced CKD Stage V (9.6% for CKD Stages IV and V). Among the KorAHF registry patients, we found two main reasons for not meeting the inclusion criteria of the VICTORIA trial such as low SBP and non‐elevated natriuretic peptide. Conclusions Among the Korean hospitalized HFrEF patients, 94.9% met the FDA/EC label criteria, while 58% met the inclusion criteria of the VICTORIA trial. Our findings suggest the need for better strategies to integrate up‐to‐date HF treatment in a real‐world HF population, especially decompensated HF patients with low SBP and non‐elevated natriuretic peptide. [ABSTRACT FROM AUTHOR]

Aims: A waiting period of more than 3 months is recommended for patients before undergoing cardiac resynchronization therapy (CRT). However, due to an anticipated high mortality rate, early implementation of CRT might be beneficial for some patients. We aimed to evaluate the rate and the probability of left ventricular (LV) function improvement and their predictors in patients with heart failure (HF) with indications for CRT. Methods and results: From March 2011 to February 2014, a total of 5625 hospitalized patients for acute HF were consecutively enrolled in 10 tertiary hospitals. Among them, we analysed 1792 patients (mean age 63.96 ± 15.42 years, female 63.1%) with left ventricular ejection fraction (LVEF) ≤ 35% at the baseline echocardiography and divided them into three groups: 144 with left bundle branch block (LBBB), 136 with wide QRS complexes without LBBB, and 1512 not having these findings (control). We compared and analysed these three groups for improvement of LV function at follow‐up echocardiography. In patients who met CRT indications (patients with LBBB or wide QRS complexes without LBBB), logistic regression was performed to identify risk factors for no improvement of LV. No improvement of LV was defined as LVEF ≤ 35% at follow‐up echocardiography or the composite adverse outcomes: death, heart transplantation, extracorporeal membrane oxygenation, or use of a ventricular assist device before follow‐up echocardiography. A classification tree was established using the binary recursive partitioning method to predict the outcome of patients who met CRT indications. In a median follow‐up of 11 months, LVEF improvement was observed in 24.3%, 15.4%, and 40.5% of patients with LBBB, wide QRS complexes without LBBB, and control, respectively. Patients meeting CRT indications had higher 3 month mortality rates than the control (24.6% vs. 17.7%, P = 0.002). Multivariable logistic regression analysis revealed that large LV end‐systolic dimension [odds ratio (OR) 1.10, 95% confidence interval (CI) 1.05–1.15, P < 0.001], low LVEF (OR 0.92, 95% CI 0.87–0.98, P = 0.006), diabetes requiring insulin (OR 6.49, 95% CI 2.53–19.33, P < 0.001), and suboptimal medical therapy (OR 6.85, 95% CI 3.21–15.87, P < 0.001) were significant factors predictive of no improvement. A decision tree analysis was consistent with these results. Conclusions: Patients with CRT indications had higher mortality during their follow‐up compared with control. LV function improvement was rare in this population, especially when they had some risk factors. These results suggest that the uniform waiting period before CRT implantation could be reconsidered and individualized. [ABSTRACT FROM AUTHOR]

Background: Patients with diabetes mellitus (DM) have a higher prevalence of heart failure (HF) than those without it. Approximately 40 % of HF patients have DM and they tend to have poorer outcomes than those without DM. This study evaluated the impact of insulin therapy on mortality among acute HF patients. Methods: A total of 1740 patients from the Korean Acute Heart Failure registry with DM were included in this study. The risk of all-cause mortality according to insulin therapy was assessed using the Cox proportional hazard models with inverse probability of treatment weighting to balance the clinical characteristics (pretreatment covariates) between the groups. Results: DM patients had been treated with either oral hypoglycemic agents (OHAs) alone (n = 620), insulin alone (n = 682), or insulin combined with OHAs (n = 438). The insulin alone group was associated with an increased mortality risk compared with the OHA alone group (HR = 1.41, 95 % CI 1.21–1.66]). Insulin therapy combined with OHAs also showed an increased mortality risk (HR = 1.29, 95 % CI 1.14–1.46) compared with the OHA alone group. Insulin therapy was consistently associated with increased mortality risk, regardless of the left ventricular ejection fraction (LVEF) or HF etiology. A significant increase in mortality was observed in patients with good glycemic control (HbA1c < 7.0 %) receiving insulin, whereas there was no significant association in patients with poor glycemic control (HbA1c ≥ 7.0%). Conclusions: Insulin therapy was found to be associated with increased mortality compared to OHAs. The insulin therapy was harmful especially in patients with low HbA1c levels which may suggest the necessity of specific management strategies and blood sugar targets when using insulin in patients with HF. [ABSTRACT FROM AUTHOR]

Background: To investigate the effect of beta-blockers according to NP levels and HF phenotypes because natriuretic peptide (NP) level can be used to risk-stratify HF patients regardless of left ventricular ejection fraction (LVEF). Methods: Of 5,625 patients in the Korean acute heart failure registry, we included patients with LVEF and NP levels. HF phenotypes were defined as HF with reduced ejection fraction (HFrEF) (EF ≤ 40%), HF with midrange ejection fraction (HFmrEF) (40% < EF < 50%), and HF with preserved EF (HFpEF) (EF ≥ 50%). Patients were further stratified by NP tertiles. Primary outcome was 5-year all-cause mortality according to beta-blocker use at discharge. Results: Both B-type NP (BNP) (r = −0.279, P < 0.001) and N-terminal pro-BNP (r = −0.186, P < 0.001) levels correlated inversely with LVEF. During a median follow-up duration of 961 days, 1560 (35.3%) patients died. In HFrEF, patients taking beta-blockers showed better survival regardless of NP levels. Regarding HFmrEF, there was no mortality difference between those taking and not taking beta-blockers. In HFpEF, beta-blocker use demonstrated lower mortality in those in the 3rd NP tertile (log-rank P = 0.041) but not in those in the 1st and 2nd NP tertiles (log-rank P > 0.05). After adjusting covariates, the use of beta-blockers was associated with a 38%-reduced mortality (hazard ratio: 0.62; 95% confidence interval: 0.39–0.98; P = 0.040) in HFpEF patients in the 3rd NP tertile but not in those in 1st and 2nd tertiles. Conclusions: We confirm that the use of beta-blockers is beneficial in patients with HFrEF. Furthermore, we extend the benefits of beta-blockers to patients with HFpEF and high NP levels. Clinical Trial Registration: ClinicalTrial.gov identifier: NCT01389843 URL: https://clinicaltrials.gov/ct2/show/NCT01389843 [ABSTRACT FROM AUTHOR]

Sacubitril/valsartan is superior to enalapril in reducing the risks of cardiovascular death and preventing hospitalization in patients with heart failure and reduced ejection fraction (HFrEF). However, patients often do not receive sacubitril/valsartan because of concerns about hypotension. We examined the feasibility of initiating sacubitril/valsartan at a very low dose (VLD) in potentially intolerant patients with HFrEF and subsequent dose up-titration, treatment persistence and outcomes. We analyzed 206 patients with HFrEF grouped according to starting sacubitril/valsartan dose. The VLD group (n = 106) commenced 25 mg twice daily, and the standard-dose (SD) group (n = 100) started on ≥ 50 mg twice daily. Baseline systolic blood pressure was 103 ± 12 mmHg vs. 119 ± 14 mmHg in the SD group (P < 0.001). The maximal target dose achievement rate was higher in the SD group (27.0% vs 9.4%, p = 0.001) and the VLD group experienced more dose up-titrations and fewer down-titrations than the SD group. The VLD group had a decrease in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) similar to the SD group and a similar increase in left ventricular ejection fraction. There were no significant differences in symptomatic hypotension, worsening renal function, hyperkalemia, cardiovascular mortality, and rehospitalization due to HF between the two groups during follow-up period. In patients considered by the treating physician likely to be intolerant of sacubitril/valsartan, initiation with 25 mg twice daily was generally possible and patients remained in therapy, with similar decreases in NT-proBNP and increases in left ventricular ejection fraction to those observed in patients receiving SD sacubitril/valsartan. [ABSTRACT FROM AUTHOR]

Objective: Machine learning (ML) algorithm can improve risk prediction because ML can select features and segment continuous variables effectively unbiased. We generated a risk score model for mortality with ML algorithms in East-Asian patients with heart failure (HF). Methods: From the Korean Acute Heart Failure (KorAHF) registry, we used the data of 3683 patients with 27 continuous and 44 categorical variables. Grouped Lasso algorithm was used for the feature selection, and a novel continuous variable segmentation algorithm which is based on change-point analysis was developed for effectively segmenting the ranges of the continuous variables. Then, a risk score was assigned to each feature reflecting nonlinear relationship between features and survival times, and an integer score of maximum 100 was calculated for each patient. Results: During 3-year follow-up time, 32.8% patients died. Using grouped Lasso, we identified 15 highly significant independent clinical features. The calculated risk score of each patient ranged between 1 and 71 points with a median of 36 (interquartile range: 27–45). The 3-year survival differed according to the quintiles of the risk score, being 80% and 17% in the 1st and 5th quintile, respectively. In addition, ML risk score had higher AUCs than MAGGIC-HF score to predict 1-year mortality (0.751 vs. 0.711, P < 0.001). Conclusions: In East-Asian patients with HF, a novel risk score model based on ML and the new continuous variable segmentation algorithm performs better for mortality prediction than conventional prediction models. Clinical Trial Registration: Unique identifier: INCT01389843 https://clinicaltrials.gov/ct2/show/NCT01389843. [ABSTRACT FROM AUTHOR]

Aims: Tachycardia is a reversible event that may cause hemodynamic decompensation but may not necessarily cause direct damages to the myocardium. To evaluate the clinical outcomes of patients with heart failure (HF) and atrial fibrillation (AF), whose acute decompensation was tachycardia mediated. Methods and results: The Korean Acute Heart Failure registry was a prospective registry that consecutively enrolled 5625 patients with acute HF. Patients were classified into three groups according to the rhythm and aggravating factor: (i) 3664 (65.1%) patients with sinus rhythm (SR), (ii) 1033 (18.4%) patients with AF whose decompensation was tachycardia‐mediated, AF‐TM (+), and (iii) N = 928 (16.5%) patients with AF whose decompensation was not tachycardia‐mediated, AF‐TM (−). The primary outcomes were in‐hospital and post‐discharge 1 year all‐cause mortality. At admission, the mean heart rate was 90.8 ± 23.4, 86.8 ± 26.8, and 106.3 ± 29.7 beats per minute for the SR, AF‐TM (−), and AF‐TM (+) groups, respectively. The AF‐TM (+) group had more favourable characteristics such as de novo onset HF, less diabetes, ischaemic heart disease, and higher blood pressure than the AF‐TM (−) group. In‐hospital mortality rates were 5.1%, 6.5%, and 1.7% for SR, AF‐TM (−), and AF‐TM (+) groups, respectively. In logistic regression analysis, the AF‐TM (+) group had lower in‐hospital mortality after adjusting the significant covariates (odds ratio, 0.49; 95% confidence interval, 0.26–0.93). The mortality rate did not differ between SR and AF‐TM (−) groups. During 1 year follow‐up, 990 (18.5%) patients died. In univariate and multivariate Cox proportional regression analyses, there was no difference in 1‐year all‐cause mortality between the three groups. Conclusions: In patients with HF and AF, patients whose acute decompensation is tachycardia‐mediated have better in‐hospital, but similar post‐discharge outcomes compared with those with SR or those with AF whose decompensation is not tachycardia‐mediated. Clinical Trial Registration: ClinicalTrial.gov NCT01389843. [ABSTRACT FROM AUTHOR]

Renal dysfunction is considered as a relative contraindication for heart transplantation (HTx). However, in the real world setting, many patients with advanced heart failure (HF) experience worsening of renal function and some even require renal replacement therapy (RRT) by the time they undergo HTx. We aimed to investigate the prognosis and clinical outcomes of HTx patients who required RRT during the perioperative period. The Korean Organ Transplant Registry (KOTRY) is a nationwide organ transplant registry in Korea. A total of 501 HTx patients had been prospectively enrolled in the KOTRY registry during 2014–2018. Among the 501 patients, 13 underwent combined heart and kidney transplantation (HKTx). The 488 patients who underwent isolated HTx were grouped according to their pre- and postoperative RRT status. The primary outcome was progression to dialysis-dependent end-stage renal disease (ESRD) after HTx. The secondary outcome was all-cause mortality after HTx. The median follow-up was 22 months (9–39 months). Patients who needed preoperative RRT but were free from postoperative RRT showed comparable overall survival and renal outcome to patients who were free from both pre- and postoperative RRT. In multivariable analysis, preoperative RRT was not associated with progression to ESRD or all-cause mortality after HTx; however, postoperative RRT was a significant predictor for both progression to ESRD and all-cause mortality after HTx. Preoperative creatinine or estimated glomerular filtration rate (eGFR) were not predictive of progression to ESRD after HTx. The present analysis suggests that preoperative RRT requirement does not indicate irreversible renal dysfunction in patients waiting for HTx. However, postoperative RRT was associated with progression to ESRD and mortality after HTx. [ABSTRACT FROM AUTHOR]

Background: Self-care behaviours are important to improve health outcomes in patients with heart failure. However, little is known about the factors related to the subdimensions of self-care behaviours in these patients. Aims: To identify the factors associated with the subdimensions of self-care behaviours among South Korean patients with heart failure. Methods: The participants in this cross-sectional descriptive study conducted between October 2016 and January 2017 were 178 patients with heart failure. Self-care behaviours were measured using the EHFScB-9, which has three subdimensions: autonomy-based adherence; provider-directed adherence; and consulting behaviours. Demographic characteristics, experience of heart failure education, physical function, patient health questionnaire-9, Pittsburgh sleep quality index and self-care confidence were also measured. Descriptive statistics and multiple linear regression analysis were conducted. Results: The mean age was 62 ± 12 years, and 37% were women. Younger age (P =0.023), no experience of heart failure education (P =0.039), poor physical function (P =0.003), poor sleep quality (P =0.037) and lower self-care confidence (P =0.001) were significantly associated with poor autonomy-based adherence. Being employed (P =0.042), poor sleep quality (P =0.042) and lower levels of self-care confidence (P =0.001) were associated with poor provider-directed adherence. Younger age (P =0.001) and lower self-care confidence (P =0.001) were associated with lower engagement in consulting behaviours. Conclusion: The three subdimensions of self-care behaviours were associated with different psychosocial factors, necessitating the development of tailored interventions and educational materials based on unique self-care behaviour patterns in patients with heart failure. [ABSTRACT FROM AUTHOR]

Aims: Sacubitril/valsartan (SV) reduced heart failure hospitalization and cardiovascular mortality compared with enalapril in the Prospective Comparison of ARNI with ACE‐I to Determine Impact on Global Mortality and Morbidity in Heart Failure trial. However, this trial excluded patients with end stage of renal disease (ESRD); thus, the efficacy and safety of SV in heart failure with reduced ejection fraction (HFrEF) with ESRD remains uncertain. Methods and results: We retrospectively analysed the clinical and laboratory data of 501 HFrEF patients who administered with SV from March 2017 to April 2019 in a single tertiary university hospital. A total of 23 HFrEF patients with ESRD on dialysis [58.3% non‐ischaemic heart failure; left ventricular ejection fraction (LVEF): 29.7 ± 4.4%] were included in this study. At baseline and follow‐up visit, we evaluated cardiovascular biomarkers such as high‐sensitive troponin T (hsTnT), soluble ST2 (sST2), echocardiographic parameters, and clinical and adverse events. The mean dose of SV was 90 ± 43 mg/day at baseline and 123 ± 62 mg/day at last follow‐up (follow‐up duration: median 132 days). The level of hsTnT was significantly reduced from 236.2 ± 355.3 to 97.0 ± 14.0 pg/mL (P = 0.002), and the sST2 level was significantly reduced from 40.4 ± 44.0 to 19.6 ± 14.1 ng/mL (P = 0.005). LVEF was significantly improved from 29.7 ± 4.4% to 40.8 ± 10.4% (P = 0.002). During the follow‐up, up‐titration, down‐titration, and maintenance of SV dosing were observed in 7 (30%), 5 (21.7%), and 11 patients (47.8%), respectively. SV down‐titration group had adverse events including symptomatic hypotension (systolic blood pressure <100 mmHg) (n = 4) and dizziness (n = 1), but they did not discontinue SV therapy. Conclusions: We found that SV could safely reduce the hsTnT and sST2 levels and improve LVEF in HFrEF patients with ESRD. As far as we know, this is the first study to show the efficacy and safety of SV in HFrEF with ESRD on dialysis. Larger prospective, long‐term follow‐up study should be warranted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Although a better survival rate in women than in men has been reported in heart failure (HF) with reduced ejection fraction (HFrEF), the sex-specific prognosis has scarcely been addressed in HF with preserved EF (HFpEF). Thus, this study investigated the sex difference in clinical outcomes in patients with HFpEF, as well as in those with HFrEF. Materials and Methods: We studied clinical outcomes of 2,572 hospitalized patients due to HF (66.8 ± 14.4 years, 49.7% women) in the Korean Heart Failure Registry. Patients were divided into two groups by left ventricular EF (LVEF): HFpEF (LVEF ≥50%, n = 764) and HFrEF (LVEF <40%, n = 1,808) groups. Results: During a median follow-up of 1,121 days, there were 693 (28.7%) deaths and 1,073 (44.5%) composite events (death and HF readmission). There were no sex differences in the incidence of death or composite events during follow-up in both HFrEF and HFpEF groups (p > 0.05 for each). In 1:1 age-matched population (n = 1,005 in each sex), the long-term mortality was significantly lower in women than men in HFrEF group (p = 0.005), but not in HFpEF group (p = 0.786), while the incidences of composite events were similar between sex irrespective of LVEF (p > 0.05). However, there were no significant associations between sex and clinical outcomes in multivariable analysis (p > 0.05 for each). Conclusions: Sex per se was not the significant factor determining long-term clinical outcomes in HF patients regardless of the LVEF. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to develop and validate deep-learning-based artificial intelligence algorithm for predicting mortality of AHF (DAHF). Methods and results: 12,654 dataset from 2165 patients with AHF in two hospitals were used as train data for DAHF development, and 4759 dataset from 4759 patients with AHF in 10 hospitals enrolled to the Korean AHF registry were used as performance test data. The endpoints were in-hospital, 12-month, and 36-month mortality. We compared the DAHF performance with the Get with the Guidelines–Heart Failure (GWTG-HF) score, Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score, and other machine-learning models by using the test data. Area under the receiver operating characteristic curve of the DAHF were 0.880 (95% confidence interval, 0.876–0.884) for predicting in-hospital mortality; these results significantly outperformed those of the GWTG-HF (0.728 [0.720–0.737]) and other machine-learning models. For predicting 12- and 36-month endpoints, DAHF (0.782 and 0.813) significantly outperformed MAGGIC score (0.718 and 0.729). During the 36-month follow-up, the high-risk group, defined by the DAHF, had a significantly higher mortality rate than the low-risk group(p<0.001). Conclusion: DAHF predicted the in-hospital and long-term mortality of patients with AHF more accurately than the existing risk scores and other machine-learning models. [ABSTRACT FROM AUTHOR]

Background: We investigated the role of nutritional risk index (NRI) in predicting 1-year mortality in patients with acute decompensated heart failure (ADHF). Methods: Among 5,625 cohort patients enrolled in Korean Acute Heart Failure (KorAHF) Registry, a total of 5,265 patients who were possible to calculate NRI [NRI = (1.519 x serum albumin [g/dl]) + (41.7 x weight [kg]/ideal body weight [kg])] were enrolled. The patients were divided into 4 groups according to the NRI quartile; Q1 <89 (n = 1121, 69.9 ± 14.5 years, 632 males), Q2 89–95 (n = 1234, 69.7 ± 14.4 years, 677 males), Q3 95–100 (n = 1199, 68.8 ± 14.0 years, 849 males), Q4 >100 (n = 1711, 65.6 ± 14.5 years, 779 males). Primary end-point was all-cause mortality at 1-year clinical follow-up. Results: The 1-year mortality was significantly increased as the NRI quartile decreased, and the lowest NRI quartile was associated with the highest 1-year mortality (Q1: 27.5% vs. Q2: 20.9% vs. Q3: 12.9% vs. Q4: 8.7%, linear p <0.001). On Kaplan-Meier survival analysis, the significant inter-quartile difference was observed (p <0.001 for all). In multivariate analysis using Cox proportional hazard regression, the lowest NRI quartile was an independent predictor of 1-year mortality in patients with ADHF. Conclusions: Poor nutritional status as assessed by NRI and quartile grading of NRI was associated with 1-year mortality in Korean patients with ADHF. The assessment of nutritional status by NRI may provide additional prognostic information and thus would be useful in the risk stratification of the patients with ADHF. [ABSTRACT FROM AUTHOR]

Background: In clinical practice, a risk prediction model is an effective solitary program to predict prognosis in particular patient groups. B-type natriuretic peptide (BNP)and N-terminal pro-b-type natriuretic peptide (NT-proBNP) are widely recognized outcome-predicting factors for patients with heart failure (HF).This study derived external validation of a risk score to predict 1-year mortality after discharge in hospitalized patients with HF using the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC)program data. We also assessed the effect of adding BNP or NT-proBNP to this risk score model in a Korean HF registry population. Method and results: We included 5625 patients from the Korean acute heart failure registry (KorAHF) and excluded those who died in hospital. The MAGGIC constructed a risk score to predict mortality in patients with HF by using 13 routinely available patient characteristics (age, gender, diabetes, chronic obstructive pulmonary disorder (COPD), HF diagnosed within the last 18 months, current smoker, NYHA class, use of beta blocker, ACEI or ARB, body mass index, systolic blood pressure, creatinine, and EF). We added BNP or NT-proBNP, which are the most important biomarkers, to the MAGGIC risk scoring system in patients with HF. The outcome measure was 1-year mortality. In multivariable analysis, BNP or NT-proBNP independently predicted death. The risk score was significantly varied between alive and dead groups (30.61 ± 6.32 vs. 24.80 ± 6.81, p < 0.001). After the conjoint use of BNP or NT-proBNP and MAGGIC risk score in patients with HF, a significant difference in risk score was noted (31.23 ± 6.46 vs. 25.25 ± 6.96, p < 0.001).The discrimination abilities of the risk score model with and without biomarker showed minimal improvement (C index of 0.734 for MAGGIC risk score and 0.736 for MAGGIC risk score plus BNP or NT-proBNP, p = 0.0502) and the calibration was found good. However, we achieved a significant improvement in net reclassification and integrated discrimination for mortality (NRI of 33.4%,p < 0.0001 and IDI of 0.002, p < 0.0001). Conclusion: In the KorAHF, the MAGGIC project HF risk score performed well in a large nationwide contemporary external validation cohort. Furthermore, the addition of BNP or NT-proBNPto the MAGGIC risk score was beneficial in predicting more death in hospitalized patients with HF. [ABSTRACT FROM AUTHOR]

Background: Depressive symptoms and vitamin D deficiency predict cardiac events in heart failure patients, but whether vitamin D supplements are associated with depressive symptoms and cardiac events in heart failure patients remains unknown. Purpose: The purpose of this study was to compare the association of vitamin D supplement use with depressive symptoms and cardiac events in heart failure patients with mild or moderate to severe depressive symptoms. Methods: A total of 177 heart failure patients with depressive symptoms (Patient Health Questionnaire-9 score ≥5) completed a three-day food diary to determine dietary vitamin D deficiency. Patients were split into four groups by dietary vitamin D adequacy versus deficiency and vitamin D supplement use versus non-use. The Patient Health Questionnaire-9 was used to reassess depressive symptoms at six months. Data on cardiac events for up to one year and vitamin D supplement use were obtained from patient interview and medical record review. Hierarchical linear and Cox regressions were used for data analysis. Results: Sixty-six patients (37.3%) had dietary vitamin D deficiency and 80 (45.2%) used vitamin D supplements. In patients with moderate to severe depressive symptoms, the group with dietary vitamin D deficiency and no supplements had the highest Patient Health Questionnaire-9 score at six months (β=0.542, p<0.001) and shortest cardiac event-free survival (p<0.001) among the four groups, the group with dietary vitamin D deficiency and no supplements didn’t have the highest Patient Health Questionnaire-9 score at six months and shortest cardiac event-free survival in patients with mild depressive symptoms. Conclusions: Vitamin D supplements predicted lower depressive symptoms and reduced cardiac events for patients with moderate to severe depressive symptoms. Vitamin D deficiency was associated with higher risk of shorter cardiac event-free survival in heart failure patients regardless of vitamin D supplementation. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the prognostic role of cardiac magnetic resonance imaging (CMR)-based extracellular volume fraction (ECV) in patients with non-ischemic dilated cardiomyopathy (NIDCM) and compare it with late gadolinium enhancement (LGE) parameters.Methods: This was a single-center, prospective, cohort study of 117 NIDCM patients (71 men, 51.9 ± 16.7 years) who underwent clinical 3.0-T CMR. Myocardial ECV and LGE were quantified on the left ventricular myocardium. The presence of midwall LGE was also detected. Nineteen healthy subjects served as controls. The primary end points were cardiovascular (CV) events defined by CV death, rehospitalization due to heart failure, and heart transplantation.Results: During the follow-up period (median duration, 11.2 months; 25th-75th percentile, 7.8-21.9 months), the primary end points occurred in 19 patients (16.2%). The ECV (per 3% and 1% increase) was associated with a hazard ratio of 1.80 and 1.22 (95% confidence interval [CI], 1.48-2.20 and 1.14-1.30, respectively; p < 0.001) for the CV events. Multivariable analysis also indicated that ECV was an independent prognostic factor and had a higher prognostic value (Harrell's c statistic, 0.88) than LGE quantification values (0.77) or midwall LGE (0.80).Conclusion: CMR-based ECV independently predicts the clinical outcome in NIDCM patients.Key Points: • T1-mapping-based ECV is a useful parameter of risk stratification in NIDCM • ECV has a higher prognostic value than LGE • Contrast-enhanced T1-mapping CMR is a feasible and safe method. [ABSTRACT FROM AUTHOR]

Background: In this study, a new algorithm was developed for estimating the pump outflow of a pneumatic ventricular assist device (p-VAD). The pump outflow estimation algorithm was derived from the ideal gas equation and determined the change in blood-sac volume of a p-VAD using two external pressure sensors.Objectives: Based on in vitro experiments, the algorithm was revised to consider the effects of structural compliance caused by volume changes in an implanted unit, an air driveline, and the pressure difference between the sensors and the implanted unit.Methods: In animal experiments, p-VADs were connected to the left ventricles and the descending aorta of three calves (70-100 kg). Their outflows were estimated using the new algorithm and compared to the results obtained using an ultrasonic blood flow meter (UBF) (TS-410, Transonic Systems Inc., Ithaca, NY, USA).Results: The estimated and measured values had a Pearson's correlation coefficient of 0.864. The pressure sensors were installed at the external controller and connected to the air driveline on the same side as the external actuator, which made the sensors easy to manage. [ABSTRACT FROM AUTHOR]

Background Cardiac resynchronization therapy (CRT) is an important therapy in patients with heart failure (HF) and dyssynchrony. We performed the present study to elucidate clinical factors associated with cardiac vein accessibility. Methods In 255 consecutive patients (age, 48.7 ± 19.4 years; male, 126), cardiac venography was performed during CRT implantation or an electrophysiological study. We measured the diameters and the proximal branching angles of the lateral cardiac and posterior ventricular veins. Easy accessibility of the cardiac vein was defined as a lumen diameter ≥1.6 mm with an angle of ≥90°. We compared baseline characteristics between patients with and without easily accessible cardiac veins. We compared cardiac vein accessibility between patients with and without HF, including ischemic and nonischemic HF, and between males and females. Results In 189 (74.1%) patients, the cardiac veins were easily accessible. The cardiac veins were more easily accessible in patients with HF (n = 75) compared with patients without HF (n = 180; 89.3% and 67.8%, respectively; P < 0.001). The cardiac veins were more easily accessible in patients with nonischemic HF (n = 56) compared with patients with ischemic HF (n = 19; 96.4% and 68.4%, respectively; P = 0.003). The cardiac veins were more easily accessible in females compared with males (79.8% and 68.3%, respectively; P = 0.035). Conclusions Accessing the cardiac veins for CRT implantation was difficult in ∼10% of patients with HF. Cardiac vein accessibility was high in patients with nonischemic HF and in females. [ABSTRACT FROM AUTHOR]

Background: Post-exercise heart rate recovery (HRR) is an index of parasympathetic function associated with clinical outcome in patients with chronic heart failure. However, its relationship with the pro-inflammatory response and prognostic value in consecutive patients with acute decompensated heart failure (ADHF) has not been investigated. Methods: We measured HRR and pro-inflammatory markers in 107 prospectively and consecutively enrolled, recovered ADHF patients (71 male, 59 ± 15 years, mean ejection fraction 28.9 ± 14.2%) during the pre-discharge period. The primary endpoint included cardiovascular (CV) events defined as CV mortality, cardiac transplantation, or rehospitalization due to HF aggravation. Results: The CV events occurred in 30 (28.0%) patients (5 cardiovascular deaths and 7 cardiac transplantations) during the follow-up period (median 214 days, 11–812 days). When the patients with ADHF were grouped by HRR according to the Contal and O’Quigley’s method, low HRR was shown to be associated with significantly higher levels of serum monokine-induced by gamma interferon (MIG) and poor clinical outcome. Multivariate Cox regression analysis revealed that low HRR was an independent predictor of CV events in both enter method and stepwise method. The addition of HRR to a model significantly increased predictability for CV events across the entire follow-up period. Conclusion: Impaired post-exercise HRR is associated with a pro-inflammatory response and independently predicts clinical outcome in patients with ADHF. These findings may explain the relationship between autonomic dysfunction and clinical outcome in terms of the inflammatory response in these patients. [ABSTRACT FROM AUTHOR]

Objective: Plasma level of N-terminal-pro-brain natriuretic peptide (NT-proBNP) is a reliable prognostic factor in patients with heart failure (HF). However, it is unclear how differently the biomarker predicts adverse outcomes in HF with preserved EF (HFpEF) versus HF with reduced EF (HFrEF).Methods: From the Korean Heart Failure registry, a prospective multicentre cohort for consecutive patients who were hospitalised for acute HF syndrome, those with available NT-proBNP and LVEF measurements were extracted. Patients with LVEF ≥50% were categorised as the HFpEF group (N=528) and those with ≤40% as the HFrEF group (N=1142).Results: Patients with HFpEF had significantly lower NT-proBNP level than those with HFrEF (median 2723 vs 5644 ng/L, p<0.001). Event-free survival did not differ between the two groups either in terms of death from any cause (88.4% vs 86.9%; p=0.471) or the composite of death or HF readmission at 1 year (73.8% vs 70.6%; p=0.225). High levels of NT-proBNP were significantly associated with poor outcomes. However, the relationship was not different among the HFpEF and HFrEF groups (interaction p=0.956 for all-cause death; p=0.351 for the composite of all-cause death or HF hospitalisation).Conclusions: Plasma level of NT-proBNP is the most powerful prognostic factor in both HFpEF and HFrEF. Although patients with HFpEF have lower NT-proBNP levels, the prognosis of a patient with HFpEF expected from a given NT-proBNP level is similar with his/her counterpart with HFrEF. [ABSTRACT FROM AUTHOR]

Aims In acute heart failure ( AHF) patients, pulmonary oedema and low tissue perfusion may lead to changes in the acid-base balance, which may be associated with worse outcomes. Methods and results In this prospective nationwide cohort study from 24 academic hospitals, arterial blood gas ( ABG) was measured in 1982 AHF patients at hospital admission. Acidosis was defined as pH <7.36, and alkalosis as pH >7.44. Mortality was stratified according to ABG results. Overall, 19% had acidosis, 37% had normal pH, and 44% had alkalosis. The most common type of acidosis was the mixed type (42%) followed by metabolic acidosis (40%), and the most common type of alkalosis was respiratory alkalosis (58%). At 12 months' follow-up 304 patients (15%) died. Patients with acidosis had higher mortality (acidosis 19.5%, neutral pH 13.7%, alkalosis 14.9%; P = 0.007). In the Cox proportional-hazards regression model, acidosis was a significant predictor of mortality (hazard ratio 1.93; 95% confidence intervals 1.27-2.93) along with N-terminal pro-brain type natriuretic peptide ( NT-proBNP), among others. In contrast, alkalosis was not associated with increased mortality. pH had an incremental prognostic value over NT-proBNP (net reclassification improvement 30%; P < 0.001), and ABG analysis identified extra patients at increased risk for mortality among patients with an NT-proBNP level less than the median (12-month mortality 17.5% vs. 9.9%; P = 0.009). Conclusion In high-risk AHF patients, the most common acid-base imbalance is respiratory alkalosis. Acidosis is observed in every fifth patient and is a significant predictor of mortality. pH provides an additional prognostic value and may be used to optimize risk stratification in high-risk AHF patients. [ABSTRACT FROM AUTHOR]

Aims The Korean Acute Heart Failure registry ( KorAHF) aims to evaluate the clinical characteristics, management, hospital course, and long-term outcomes of patients hospitalized for acute heart failure syndrome ( AHFS) in Korea. Methods and results This is a prospective observational multicentre cohort study funded by the Korea National Institute of Health. Patients hospitalized for AHFS in 10 tertiary university hospitals across the country have been consecutively enrolled since March 2011. The study is expected to complete the scheduled enrolment of 5000 patients some time in 2014, and follow-up is planned through 2016. As of April 2012, the interim analysis of 2066 consecutive subjects was performed to understand the baseline characteristics of the population. The mean age was 69 ± 14 years; 55% were male; and 50% were de novo heart failure. The mean left ventricular ejection fraction ( LVEF) was 40 ± 18%. Ischaemia was both the leading cause (38%) and the most frequent aggravating factor (26%) of AHFS. ACE inhibitors/ ARBs and beta-blockers were prescribed at discharge in 65% and 51% of the patients, respectively. In-hospital mortality was 5.2%, and 0.9% of patients received urgent heart transplantation. Low blood pressure and azotaemia were the most important predictors of in-hospital mortality. The post-discharge 30-day and 180-day all-cause mortality were 1.2% and 9.2%, respectively. Conclusions Our analysis reveals that the prognosis of AHFS in Korea is poor and that there are specific features, including lower blood pressures at admission and lower rates of heart failure related to hypertension, compared with other registries. Adherence to current guidelines should be improved. [ABSTRACT FROM AUTHOR]

Aim Poor health-related quality of life ( HRQOL) in patients with chronic heart failure ( CHF) may be one of the most common predictors of mortality and rehospitalization. This study was conducted to identify factors affecting HRQOL in Korean patients with CHF using two HRQOL measurements. Methods The study included a sample of 114 patients. HRQOL was measured by the Minnesota Living with Heart Failure Questionnaire ( MLHFQ) and the World Health Organization's Quality of Life Instrument - Short Version ( WHOQOL-BREF). Multiple regression analyses were performed to analyze the relationship between the factors and HRQOL. Results Significant correlations were found between MLHFQ and WHOQOL-BREF in total and component scores, with the two exceptions of WHOQOL-BREF psychological and MLHFQ physical or total. The perceived economic status, functional status, and sex were factors identified as having an effect on HRQOL. Conclusion The MLHFQ was better able to differentiate sex, comorbidity, and functional status. Further studies are needed to implement cost-effective nursing interventions for patients with CHF to improve their HRQOL. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hemoconcentration is a surrogate marker of effective decongestion and diuresis therapy. Recently, hemoconcentration has been associated with decreased mortality and rehospitalization in heart failure (HF) patients. However, the prognostic power of hemoconcentration in a large sample-sized HF cohort was limited until now. Methods and results: We analyzed data from hospitalized patients with acute heart failure (AHF) that were enrolled in the Korean Heart Failure Registry(n =2,357). The primary end point was a composite of all-cause mortality and HF rehospitalization during the follow-up period (median=347, interquartile range=78–744days).Hemoconcentration, defined as an increased hemoglobin level between admission and discharge, was presented in 1,016 AHF patients (43.1%). In multivariable logistic regression, hemoglobin, total cholesterol, and serum glucose levels at admission, and ischemic HF, were significant determinants for hemoconcentration occurrence. The Kaplan–Meier curve showed that event-free survival was significantly higher in the hemoconcentration group compared to the non-hemoconcentration group (65.1% vs. 58.1%, log rank p <0.001). In multiple Cox proportional hazard analysis, hemoconcentration was an independent predictor of the primary end point after adjusting for other HF risk factors (hazard ratio=0.671, 95% confidence interval=0.564–0.798, p <0.001). Conclusions: Hemoconcentration during hospitalization was a prognostic marker of fewer clinical events in the AHF cohort. Therefore, this novel surrogate marker will help in the risk stratification of AHF patients. [Copyright &y& Elsevier]

Objectives: A prolonged QRS duration has been associated with an unfavorable prognosis in chronic compensated heart failure (HF). However, its predictive value during an admission for acute HF is limited, even in HF with a preserved ejection fraction (EF). The purpose of this study was to evaluate the prognostic utility of the QRS duration in acute HF. Methods: Analyses were performed using data from 1,489 patients with a 2-year follow-up. The patients were selected from the Korean Acute Heart Failure Registry and were divided into three groups according to QRS duration (≤80, 81-119 or ≥120 ms). The all-cause mortality and readmission for HF were assessed. Results: During the study period, 774 primary events occurred (359 deaths and 415 HF). The event frequencies were higher in patients with a prolonged QRS duration. The increased risk associated with the QRS duration was also demonstrated after adjustment for cardiac outcome variables. The prognostic significance of the QRS duration was demonstrated in patients with reduced EF but not in those with a preserved EF. Conclusions: A prolonged QRS duration could be a significant predictor of the 2-year cardiac outcome in patients with acute HF, particularly in those with a reduced EF. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims and objectives. To assess the learning needs of patients with heart failure in Korea as this information is the cornerstone for developing a programme based on patients' learning needs. Background. Heart failure is a life-threatening event and a significant cause of morbidity and mortality in Korea. Cardiac educational programmes are intended to prevent the recurrence of heart failure and improve patients' quality of life. However, patients' information requests have historically not been well met by physicians and nurses in Korea. Design. A descriptive and exploratory study was designed. Methods. We recruited 121 patients with heart failure between the ages of 19-88 years. Self-report questionnaires, which included general characteristics, disease-related characteristics and the Heart Failure Patients' Learning Needs Inventory patient version, were used to gather data. Results. The only general characteristic that was significantly related to patients' learning needs was their occupation. No disease-related characteristics were related to learning needs. The overall mean learning needs score was 3·78. Conclusion. Patients' learning needs in Korea are lower than those typically seen in Western countries. Korean patients with heart failure had a low level of knowledge about heart failure and did not recognise the importance of being informed about their disease, which is why Korean patients with heart failure tend to depend on their physicians to make decisions related to their health management. These conditions can negatively affect clinical outcomes. Relevance to clinical practice. Although an educational programme for patients with heart failure should be based on the patients' learning needs, heart failure management and education programmes in Korea are not currently developed using a needs-based approach. Therefore, this study will provide a basis for encouraging Korean patients to obtain information about their disease and to guide professionals in developing heart failure management and education programmes. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: We sought to identify metabolic pathways characterizing human heart failure (HF) using 1NMR based urinary metabolomic analysis in conjunction with multivariate statistics. Design and methods: Patients with systolic HF of ischemic origin (n=15) and healthy controls (n=20) participated in this study. Patients with type 2 diabetes mellitus were excluded. Results: The results showed that the urine of the HF patients had higher levels of metabolites for acetate (p<0.05) and acetone (p<0.01) compared to the healthy controls. In addition, there was a perturbation in methylmalonate metabolism as shown by increased urinary levels of methylmalonic acid (p<0.001) in the HF patients. HF patients also had increased urinary levels of cytosine (p<0.01) and phenylacetylglycine (p<0.01) and decreased 1-methylnicotinamide (p<0.05) compared to healthy controls. Conclusions: TCA cycle metabolites and fatty acid metabolism were modified in the HF patients, indicating altered energy metabolism. Moreover, perturbations of metabolism in nucleotide and methylmalonate were observed. [Copyright &y& Elsevier]

Abstract: Myocardial oxidative stress and Ca2+ overload induced by ischemia-reperfusion may be involved in the development and progression of myocardial dysfunction in heart failure. Xanthine oxidase, which is capable of producing reactive oxygen species, is considered as a culprit regarding ischemia-reperfusion injury of cardiomyocytes. Even though inhibition of xanthine oxidase by allopurinol in failing hearts improves cardiac performance, the regulatory mechanisms are not known in detail. We therefore hypothesized that allopurinol may prevent the xanthine oxidase-induced reactive oxygen species production and Ca2+ overload, leading to decreased calcium-responsive signaling in myocardial dysfunction. Allopurinol reversed the increased xanthine oxidase activity in ischemia-reperfusion injury of neonatal rat hearts. Hypoxia-reoxygenation injury, which simulates ischemia-reperfusion injury, of neonatal rat cardiomyocytes resulted in activation of xanthine oxidase relative to that of the control, indicating that intracellular xanthine oxidase exists in neonatal rat cardiomyocytes and that hypoxia-reoxygenation induces xanthine oxidase activity. Allopurinol (10 μM) treatment suppressed xanthine oxidase activity induced by hypoxia-reoxygenation injury and the production of reactive oxygen species. Allopurinol also decreased the concentration of intracellular Ca2+ increased by enhanced xanthine oxidase activity. Enhanced xanthine oxidase activity resulted in decreased expression of protein kinase C and sarcoendoplasmic reticulum calcium ATPase and increased the phosphorylation of extracellular signal-regulated protein kinase and p38 kinase. Xanthine oxidase activity was increased in both ischemia-reperfusion-injured rat hearts and hypoxia-reoxygenation-injured cardiomyocytes, leading to reactive oxygen species production and intracellular Ca2+ overload through mechanisms involving p38 kinase and extracellular signal-regulated protein kinase (ERK) via sarcoendoplasmic reticulum calcium ATPase (SERCA) and protein kinase C (PKC). Xanthine oxidase inhibition with allopurinol modulates reactive oxygen species production and intracellular Ca2+ overload in hypoxia-reoxygenation-injured neonatal rat cardiomyocytes. [Copyright &y& Elsevier]

Delayed-enhanced dual-energy computed tomography (DECT) can evaluate the extent and degree of myocardial fibrosis while coronary CT angiography (CCTA) is a widely accepted coronary artery evaluation method. We sought to describe the role of combined cardiac CT for the evaluation of underlying etiology in patients with newly diagnosed heart failure with reduced ejection fraction (HFrEF). Sixty-three consecutive patients (31 men, 63 ± 16 years) with newly diagnosed HFrEF were enrolled in this prospective study. Coronary artery disease and myocardial fibrosis were evaluated on CCTA and DECT, respectively, and the tentative underlying etiologies of heart failure (HF) were determined with combinations of findings from both CTs. Concordance between tentative etiologies from cardiac CT and final etiologies from clinical decisions within a 2-year follow-up was assessed. Eighteen patients were diagnosed with ischemic HF on initial cardiac CT, and the final diagnosis was not changed. Another 45 patients with nonischemic HF included tentative etiologies of dilated cardiomyopathy (n = 32, 71.1%), sarcoidosis or myocarditis (n = 8, 17.8%), amyloidosis (n = 2, 4.4%), noncompaction (n = 2, 4.4%) and arrhythmogenic right ventricular cardiomyopathy (n = 1, 2.2%). Five nonischemic HF patients showed different etiologies between initial cardiac CT and clinical decisions. The concordance between cardiac CT and clinical decisions was 92.1%. A high degree of concordance was achieved between tentative etiologies from cardiac CT and final diagnoses from clinical decisions. Combined cardiac CT is a feasible, safe and effective imaging tool for the initial evaluation of newly diagnosed HFrEF patients. [ABSTRACT FROM AUTHOR]

The application of a simple blood test to predict prognosis in acute heart failure (AHF) patients is not well established. Neutrophil-lymphocyte ratio (NLR) is inexpensive and easy to obtain in hospitalized patients using a routine blood test. We evaluate the prognostic implications of NLR as an independent predictor of in-hospital and long-term mortality in AHF patients. Among 5625 patients enrolled in the Korean Acute Heart Failure registry, 5580 patients were classified into quartiles by their NLR level, and analyzed for in-hospital and post-discharge three-year mortality. Patients in the highest NLR quartile had the highest in-hospital and post-discharge three-year mortality. The same results were seen by dividing the aggravating factor into the infection or ischemia group and the non-infection or non-ischemia group. For patients aggravated from infection or ischemia, a cut-off NLR value was 7.0 that increase the risk of in-hospital and post-discharge three-year mortality. In subgroups of patients not aggravated from infection or ischemia, a cut-off NLR value was 5.0 that increase the risk of in-hospital and post discharge three-year mortality. Elevated NLR in AHF patients at the index hospitalization is an independent predictor for in-hospital and post-discharge three-year mortality. Taken together, NLR is a marker for risk assessment of AHF patients. [ABSTRACT FROM AUTHOR]

Treatment of heart failure (HF) in the elderly face many difficulties due to lack of robust evidence. We analyzed the outcome of HF in octogenarians using a nationwide HF registry. Among 5625 patients from the Korean Acute Heart Failure (KorAHF) registry, prognosis of octogenarian HF and the association of guideline-directed medical therapy (GDMT) with mortality and readmissions were analyzed. Octogenarian patients (1185, 22.4%) showed a higher mortality, and males were especially at increased risk (HR (hazard ratio) 1.19, 95% CI 1.01–1.40). A J-curve association between blood pressure (BP) and mortality was observed regardless of age, but the nadir value was lower in octogenarians (123.8 vs. 127.9 mmHg for systolic blood pressure (SBP); 67.1 vs. 73.9 mmHg for diastolic blood pressure (DBP), p < 0.001). Use of GDMT in octogenarian patients with HF and reduced ejection fraction (EF) were inadequate (74.3%, 47.1%, and 46.1% in octogenarians vs. 78.4%, 59.8%, and 55.2% in non-elderly for renin-angiotensin system inhibitors, beta-blockers, and aldosterone antagonists, respectively; all p < 0.05). However, those on medications had a significant reduction in 6 month mortality. For octogenarians with HF and preserved EF, angiotensin receptor blocker use reduced hospitalizations for HF in men (HR 0.19, 95% CI 0.04–0.87), but not in women (p-interaction = 0.037). HF in octogenarians were found to have different characteristics compared with the non-elderly. However, adequate use of GDMT was still associated with improved survival, and more attention should be given to prescribing medications with clinical benefits. [ABSTRACT FROM AUTHOR]

Background: To investigate the impact of admission hyperglycemia (HGL) on in-hospital death (IHD) and 1-year mortality in acute heart failure (AHF) patients with or without diabetes mellitus (DM). Methods: Among 5625 AHF patients enrolled in a nationwide registry, 5541 patients were divided into four groups based on the presence of admission HGL and diabetes mellitus (DM). Admission HGL was defined as admission glucose level > 200 mg/dL. IHD and 1-year mortality were compared. Results: IHD developed in 269 patients (4.9%), and 1-year death developed in 1220 patients (22.2%). DM was a significant predictor of 1-year death (24.8% in DM vs. 20.5% in non-DM, p < 0.001), but not for IHD. Interestingly, admission HGL was a significant predictor of both IHD (7.6% vs. 4.2%, p < 0.001) and 1-year death (26.2% vs. 21.3%, p = 0.001). Admission HGL was a significant predictor of IHD in both DM and non-DM group, whereas admission HGL was a significant predictor of 1-year death only in non-DM (27.8% vs. 19.9%, p = 0.003), but not in DM group. In multivariate analysis, admission HGL was an independent predictor of 1-year mortality in non-DM patients (HR 1.32, 95% CI 1.03–1.69, p = 0.030). Conclusion: Admission HGL was a significant predictor of IHD and 1-year death in patients with AHF, whereas DM was only a predictor of 1-year death. Admission HGL was an independent predictor of 1-year mortality in non-DM patients with AHF, but not in DM patients. Careful monitoring and intensive medical therapy should be considered in AHF patients with admission HGL, regardless of DM. [ABSTRACT FROM AUTHOR]

Recent animal studies showed T cells have a direct pathogenic role in the development of heart failure (HF). However, which subsets of T cells contribute to human HF pathogenesis and progression remains unclear. We characterized immunologic properties of various subsets of T cells and their clinical implications in human HF. Thirty-eight consecutive patients with newly diagnosed acute HF (21 males, mean age 66 ± 16 years) and 38 healthy control subjects (21 males, mean age 62 ± 12 years) were enrolled. We found that pro-inflammatory mediators, including CRP, IL-6 and IP-10 and the frequencies of CD57+ T cells in the CD4+ T cell population were significantly elevated in patients with acute HF compared to control subjects. A functional analysis of T cells from patients with acute HF revealed that the CD4+CD57+ T cell population exhibited a higher frequency of IFN-γ- and TNF-α- producing cells compared to the CD4+CD57− T cell population. Furthermore, the frequency of CD4+CD57+ T cells at baseline and its elevation at the six-month follow-up were significantly related with the development of cardiovascular (CV) events, which were defined as CV mortality, cardiac transplantation, or rehospitalization due to HF exacerbation. In conclusion, CD4+CD57+ senescent T cells showed more inflammatory features and polyfunctionality and were associated with clinical outcome in patients with acute HF. More detailed study for senescent T cells might offer new opportunities for the prevention and treatment of human HF. [ABSTRACT FROM AUTHOR]

Introduction: Excessive sodium intake is known to activate the inflammatory process, contributing to a worse prognosis in patients with heart failure (HF). However, there is limited evidence about the effect of reduced sodium intake on inflammatory activation in patients with HF. Aim: To determine whether reduced sodium intake affects serum level of tumor necrosis factor alpha (TNF α) in patients with symptomatic HF. Methods: This is a secondary analysis of 109 HF patients (age 64±9 years, 29% female) enrolled in a randomized controlled trial of dietary sodium reduction. All patients classified as NYHA class III/IV who had a baseline daily sodium intake > 3g were randomly assigned to one of 3 groups: 1) a symptom monitoring and restricted 3 g sodium diet (SMART) group, 2) a telephone monitoring (TM) group, or 3) a usual care control group. The SMART group received a tailored education of self-monitoring for symptom and sodium intake using a daily symptom and high sodium food checklist through biweekly phone calls for 8 weeks. The TM group received biweekly phone calls to engage in restricting sodium intake for 8 weeks. At baseline, 3 and 6 months, daily sodium intake was assessed using a 3-day food diary. Serum level of TNF α was measured at baseline, 3 and 12 months. Linear mixed models were used for data analysis. Results: At 6 months, 46% of the SMART group (n=37) had < 3g of daily sodium intake, while only 17% of the TM group (n=35) and 8% of the control group (n=37) ate < 3g of daily sodium (p <.001). The SMART group and the TM group showed significant reduction in serum level of TNF α (p <.001; p <.001) across the time compared to the usual care control group, after controlling age, gender, body mass index, ejection faction, total comorbidity score, and beta blocker use in the linear mixed model (Figure). Conclusion: Reduced sodium intake is associated with decreased level of TNF α in patients with symptomatic HF. Helping patients with HF engage in self-monitoring for symptom and sodium intake can inhibit activation of inflammation in patients with HF. [ABSTRACT FROM AUTHOR]

Background: Carvedilol is a non-selective, third-generation beta-blocker and is one of the cornerstones for treatment for patients with heart failure and reduced ejection fraction (HFrEF). However, due to its short half-life, immediate-release carvedilol (IR) needs to be prescribed twice a day. Recently, slow-release carvedilol (SR) has been developed. The aim of this study is to evaluate whether carvedilol-SR is non-inferior to standard carvedilol-IR in terms of its clinical efficacy in patients with HFrEF.Methods/design: Patients with stable HFrEF will be randomly assigned in a 1:1 ratio to the carvedilol-SR group (160 patients) and the carvedilol-IR group (160 patients). Patients aged ≥ 20 years, with a left ventricular ejection fraction ≤ 40%, N-terminal pro B-natriuretic peptide (NT-proBNP) ≥ 125 pg/ml or BNP ≥ 35 pg/ml, who are clinically stable and have no evidence of congestion or volume retention, will be eligible. After randomization, patients will be followed up for 6 months. The primary endpoint is the change in NT-proBNP level from baseline to the study end. The secondary endpoints include the proportion of patients with NT-proBNP increment > 10% from baseline, composite of all-cause mortality and readmission, mortality rate, readmission rate, changes in blood pressure, quality of life, and drug compliance.Discussions: The SLOW-HF trial is a prospective, randomized, open-label, phase-IV, multicenter study to evaluate the therapeutic efficacy of carvedilol-SR compared to carvedilol-IR in HFrEF patients. If carvedilol-SR proves to be non-inferior to carvedilol-IR, a once-daily prescription of carvedilol may be recommended for patients with HFrEF.Trial Registration: ClinicalTrials.gov, ID: NCT03209180 . Registered on 6 July 2017. [ABSTRACT FROM AUTHOR]

Backgrounds Retinal vein occlusion (RVO) is one of the major causes of visual impairment in elderly people. Risk factors for RVO are also common risk factors for cardiovascular disease, including heart failure (HF). However, the association between RVO and HF has not been evaluated. Methods and results A retrospective propensity-score matched cohort study was conducted using national representative 1 million samples from the Korea National Health Insurance Service. The RVO group included patients with a first diagnosis of either central or branch RVO (n = 1754) and the comparison group included randomly selected patients (n = 8749) who were matched to sociodemographic factors and the year of RVO diagnosis. In the longitudinal cohort, HF developed in 11.6% and 8.0% of patients in the RVO and comparison groups, respectively, (p < 0.001) during the 11-year follow-up period (median, 7.6 years). RVO was significantly associated with an increased risk of HF after multivariable adjustment (HR = 1.36; 95% CI, 1.16–1.60). In terms of HF subtypes, RVO was associated with the risk of ischemic HF but not with the risk of non-ischemic HF. The effect size (~ HR) for HF by RVO was larger in patients without each comorbidity than in patients with each comorbidity. Conclusions Our observational study on nationwide data suggests that RVO is associated with an increased risk of the incidence of HF, especially ischemic HF. An optimal surveillance strategy and referring from ophthalmologists to cardiologists should be considered in the presence of one or more additional HF risk factors in patients with RVO. [ABSTRACT FROM AUTHOR]

NT-pro B-type natriuretic peptide (NT-proBNP) is a powerful prognostic factor for acute heart failure. We investigated whether NT-proBNP levels differ based on the type of heart failure present. Using the Korean Acute Heart Failure Registry, a prospective, multicenter cohort, we categorized patients into two groups: de novo heart failure (DNHF, n = 1617) and acute decompensated chronic heart failure (ADHF, n = 1212). NT-proBNP levels were measured on admission. The primary outcome was all-cause mortality, and the secondary outcomes were re-hospitalization for heart failure and a composite of all-cause mortality or re-hospitalization for heart failure at 90 days and 1 year. NT-proBNP levels were significantly lower in patients with DNHF than in those with ADHF (median 4213 vs. 5523 ng/L, p < 0.001). Compared to patients with DNHF, patients with ADHF had a significantly worse prognosis for 1-year all-cause mortality (adjusted hazard ratio (HR) = 1.46 [95% confidence interval (CI) = 1.07–1.98], p = 0.017). A higher NT-proBNP level was associated with higher 1-year all-cause mortality for both heart failure types (adjusted HR = 2.00, p = 0.002 in ADHF; adjusted HR = 2.41, p = 0.003 in DNHF). However, all-cause mortality risk was always higher in patients with ADHF than in those with DNHF for any given NT-proBNP level. NT-proBNP levels are an important prognostic factor for both DNHF and ADHF. Notably, patients with ADHF had consistently higher risks than those with DNHF with the same NT-proBNP level for 1-year all-cause mortality. • As time passed, ADHF had poorer outcomes than DNHF. • NT-proBNP had an important role as a prognostic factor in both DNHF and ADHF. • ADHF patients had higher risks than DNHF patients at any level of NT-proBNP. [ABSTRACT FROM AUTHOR]

Abstract: Background: Red blood cell distribution width (RDW) has been shown to predict clinical outcomes in cardiovascular diseases. We studied whether RDW is useful to predict early mortality in patients with acute dyspnea at an emergency department (ED). Methods: We retrospectively analyzed 907 patients with acute dyspnea who visited the ED from January 2009 to May 2009. Primary outcome was 30-day mortality. Results: Acute decompensated heart failure (29.9%) was the most common adjudicated discharge diagnosis followed by cancer (14.8%) and pneumonia (12.5%). There was a stepwise increase of 30-day mortality risk from lowest (RDW<12.9%) to highest (RDW>14.3%) RDW tertiles (1.4% vs. 8.3% vs. 18.3%; log-rank P<0.001). In multivariate Cox hazard analysis, RDW was an independent predictor of 30-day mortality after adjusting for other risk factors (HR 1.23; 95% CI 1.11–1.36; P<0.001). Adding RDW to conventional clinical predictors significantly improved prediction for 30-day mortality as measured by the area under the ROC curve (AUC, from 0.873 to 0.885; P=0.023) and the net reclassification improvement (NRI=14.1%; P<0.001)/integrated discrimination improvement (IDI=0.038; P=0.006). Conclusions: Our findings suggest that RDW measured at ED is an independent and additive predictor of early mortality in patients with acute dyspnea. [Copyright &y& Elsevier]

Purpose: This retrospective cohort study aimed to determine whether adjuvant radiation therapy increases the risk of cardiac toxicity in Asian women with breast cancer, with a focus on patient-specific factors.Methods and Materials: We evaluated women who underwent primary breast surgery for breast cancer with (n = 520) or without (n = 774) adjuvant radiation therapy between January 2005 and May 2013. Patients who underwent breast surgery without radiation therapy were categorized as patients who received 0 Gy to the heart. The primary endpoint was the occurrence of a breast cancer treatment-related heart disease (BCT-HD), defined as a diagnosis of angina pectoris, unstable angina, myocardial infarction, ischemic heart disease, heart failure, or atrial fibrillation.Results: In total, 1294 patients were included. The overall 5- and 10-year BCT-HD rates were 2.4% and 5.7%, respectively. The risk of an BCT-HD significantly increased per 1-Gy increase in the mean heart dose (adjusted hazard ratio: 1.23). Additionally, histories of hypertension (hazard ratio: 1.92), and diabetes (hazard ratio: 2.51) were found to be adverse risk factors, whereas regular physical exercise (hazard ratio: 0.17) was a protective factor. Subgroup analysis according to risk groups showed that the effect of increasing mean heart dose (per Gy) was similar between women without or with minimal risk factors (hazard ratio: 1.23) and women with multiple risk factors (hazard ratio: 1.27).Conclusions: The results indicate a radiation dose-effect relationship for cardiac disease in breast cancer patients, highlighting that there remains a considerable risk of cardiac toxicity even with 3-dimensional radiation therapy planning. Thus, measures to minimize the heart dose in breast cancer patients undergoing adjuvant radiation therapy, even in those without any risk factor for cardiac disease, should be routinely implemented. [ABSTRACT FROM AUTHOR]