Efficacy and Safety of a Single-Pill Triple Combination of Olmesartan, Amlodipine, and Rosuvastatin in Hypertensive Patients with Low-to-Moderate Cardiovascular Risk: A Multicenter, Randomized, Open-Label, Active-Control, Phase IV Clinical Trial.

INTRODUCTION: This study evaluated the efficacy and safety of a single-pill triple-combination of olmesartan/amlodipine/rosuvastatin (Olme/Amlo/Rosu) in comparison with a single-pill dual-combination of olmesartan/amlodipine (Olme/Amlo) in hypertensive patients with low-to-moderate cardiovascular risk. METHODS: This multicenter, active-control, randomized study included 106 hypertensive patients at low-to-moderate cardiovascular risk who were randomly assigned to receive either Olme/Amlo/Rosu 20/5/5 mg (Treatment 1), Olme/Amlo/Rosu 20/5/10 mg (Treatment 2), or Amlo/Olme 20/5 mg (Control) once daily for 8 weeks. The primary endpoint was the difference of the percent change in low-density lipoprotein cholesterol (LDL-C) level at 8 weeks from baseline in the 3 groups. RESULTS: The difference in the least square mean percent change (standard deviation) of LDL-C in the Treatment 1 and 2 groups compared with the Control group at 8 weeks was -32.6 (3.7) % and -45.9 (3.3) %, respectively (P < .001). The achievement rates of LDL-C level <100 mg/dL at 8 weeks were significantly different between the 3 groups (65.8%, 86.7%, and 6.3% for Treatment 1, 2, and Control groups, respectively, P < .001). The results of total cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein B, and apolipoprotein B/apolipoprotein A1 were superior in the Treatment 1 and 2 groups compared with the Control group. Serious adverse drug reaction did not occur in the 3 groups. Medication adherence rates were excellent in the 3 groups (98.0% for Treatment 1 group, 99.7% for Treatment 2 group, and 96.3% for the Control group, P > .05). CONCLUSION: Single-pill triple-combination of olmesartan/amlodipine/rosuvastatin was superior to the single-pill dual-combination of amlodipine/olmesartan in LDLC-lowering effects, with excellent safety profiles and adherence rates, in hypertensive patients at low-to-moderate cardiovascular risk.Trial Registration: CLinicalTrials.gov identifier NCT04120753.

The association between metabolic syndrome and heart failure in middle-aged male and female: Korean population-based study of 2 million individuals.

OBJECTIVES: Although an association is known to exist between metabolic syndrome (MetS) and heart failure (HF) risk, large longitudinal studies are limited. We investigated metabolic status as a risk factor for HF in middle-aged male and female and considered sex differences in various risk factors for HF using nationwide real-world data. METHODS: Data obtained from the Korean National Health Insurance Service from 2009 to 2016 were analyzed. A total of 2,151,597 middle-aged subjects (between 50 and 59 years old) were enrolled. Subjects were divided into 3 groups (normal, pre- MetS, and MetS). Cox proportional hazard models were used to estimate the association between MetS and incident HF after adjusting for clinical risk factors. RESULTS: At baseline, MetS existed in 23.77% of male and 10.58% of female. Pre-MetS and MetS increased the risk of HF: the hazard ratios of pre-MetS for incident HF were 1.508 (95% confidence interval [CI], 1.287 to 1.767) in male and 1.395 (95% CI, 1.158 to 1.681) in female, and those of MetS were 1.711 (95% CI, 1.433 to 2.044) in male and 2.144 (95% CI, 1.674 to 2.747) in female. Current smoking, a low hemoglobin level, underweight (body mass index < 18.5 kg/m2), a high creatinine level, and acute myocardial infarction were also predictors of HF in both sexes. CONCLUSIONS: Pre-MetS and MetS were identified as risk factors for HF in middle-aged male and female. The effect of MetS on the occurrence of HF was stronger in female than in male. Pre-MetS was also a predictor of HF, but was associated with a lower risk than MetS.

Associations between the triglyceride-glucose index and cardiovascular disease in over 150,000 cancer survivors: a population-based cohort study.

BACKGROUND: The prevention of subsequent cardiovascular disease (CVD) is an essential part of cancer survivorship care. We conducted the present study to investigate the association between the TyG index (a surrogate marker of insulin resistance) and the risk of cardiovascular disease (CVD) events in cancer survivors. METHODS: Adult cancer patients, who underwent routine health examinations during 2009-2010 and were survived for more than 5 years as of January 1, 2011, were followed for hospitalization of CVD (either ischemic heart disease, stroke, or heart failure) until December 2020. Cox model was used to calculate hazard ratios associated with baseline TyG index (loge [fasting triglyceride (mg) × fasting glucose (mg)/2]) for the CVD hospitalization. RESULTS: A total of 155,167 cancer survivors (mean age 59.9 ± 12.0 years, female 59.1%) were included in this study. A graded positive association was observed between TyG and CVD hospitalization. An 8% elevated risk for CVD hospitalization was observed for a TyG index of 8-8.4 (aHR 1.08 [95% CI 1.01-1.14]); 10% elevated risk for a TyG index of 8.5-8.9 (aHR 1.10 [95% CI 1.03-1.17]); 23% elevated risk for a TyG index of 9.0-9.4 (aHR 1.23 [95% CI 1.15-1.31]); 34% elevated risk for a TyG index of 9.5-9.9 (aHR 1.34 [95% CI 1.23-1.47]); and 55% elevated risk for a TyG index ≥ 10 compared to the reference group (TyG index < 8). Per 1-unit increase in the TyG index, a 16% increase in CVD hospitalization and a 45% increase in acute myocardial infarction hospitalization were demonstrated. Graded positive associations were evident for atherosclerotic CVD subtypes, such as ischemic heart disease, acute myocardial infarction, and ischemic stroke, but not for hemorrhagic stroke or heart failure. CONCLUSIONS: The TyG index may serve as a simple surrogate marker for the risk stratification of future CVD events, particularly atherosclerotic subtypes, in cancer survivors.

Association of Physical Activity and Lower Respiratory Tract Infection Outcomes in Patients With Cardiovascular Disease.

Background To investigate the dose-response association between physical activity and lower respiratory tract infection (LoRI) outcomes in patients with cardiovascular disease. Methods and Results Using the Korean National Health Insurance data, we identified individuals aged 18 to 99 years (mean age, 62.6±11.3 years; women, 49.6%) with cardiovascular disease who participated in health screening from January 1, 2009, to December 31, 2012 (n=1 048 502), and were followed up until 2018 for mortality and until 2019 for hospitalization. Amount of physical activity was assessed using self-reported questionnaires and categorized into 5 groups: 0 (completely sedentary), <500, 500 to 999, 1000 to 1499, and ≥1500 metabolic equivalents of task min/wk. After controlling for various confounders, adjusted hazard ratios (95% CIs) were 1.00 (reference), 0.74 (0.70-0.78), 0.66 (0.62-0.70), 0.52 (0.47-0.57), and 0.54 (0.49-0.60) for LoRI mortality, and 1.00 (reference), 0.84 (0.83-0.85), 0.77 (0.76-0.79), 0.72 (0.70-0.73), and 0.71 (0.69-0.73) for LoRI hospitalization among those engaging in physical activity of 0, <500, 500 to 999, 1000 to 1499, and ≥1500 metabolic equivalents of task min/wk, respectively. Assuming linear association between 0 and 2000 metabolic equivalents of task min/wk, each 500-metabolic equivalents of task min/wk increase of physical activity was associated with reduced LoRI mortality and hospitalization by 22% and 13%, respectively. The negative association was stronger in the older population than in the younger population (P for interaction <0.01). Conclusions In patients with cardiovascular disease, engaging in even a low level of physical activity was associated with a decreased risk of mortality and hospitalization from LoRI than being completely sedentary, and incremental risk reduction was observed with increased physical activity.

Current status of cardiac rehabilitation among representative hospitals treating acute myocardial infarction in South Korea.

Cardiac rehabilitation services are mostly underutilized despite the documentation of substantial morbidity and mortality benefits of cardiac rehabilitation post-acute myocardial infarction. To assess the implementation rate and barriers to cardiac rehabilitation in hospitals dealing with acute myocardial infarction in South Korea, between May and July 2016, questionnaires were emailed to cardiology directors of 93 hospitals in South Korea; all hospitals were certified institutes for coronary interventions. The questionnaires included 16 questions on the hospital type, cardiology practice, and implementation of cardiac rehabilitation. The obtained data were categorized into two groups based on the type of the hospital (secondary or tertiary) and statistically analysed. Of the 72 hospitals that responded (response rate of 77%), 39 (54%) were tertiary medical centers and 33 (46%) were secondary medical centers. All hospitals treated acute myocardial infarction patients and performed emergency percutaneous coronary intervention; 79% (57/72) of the hospitals performed coronary artery bypass grafting. However, the rate of implementation of cardiac rehabilitation was low overall (28%, 20/72 hospitals) and even lower in secondary medical centers (12%, 4/33 hospitals) than in tertiary centers (41%, 16/39 hospitals, p = 0.002). The major barriers to cardiac rehabilitation included the lack of staff (59%) and lack of space (33%). In contrast to the wide availability of acute-phase invasive treatment for AMI, the overall implementation of cardiac rehabilitation is extremely poor in South Korea. Considering the established benefits of cardiac rehabilitation in patients with acute myocardial infarction, more administrative support, such as increasing the fee for cardiac rehabilitation services by an appropriate level of health insurance coverage should be warranted.

Efficacy and Safety of Fenofibrate-Statin Combination Therapy in Patients With Inadequately Controlled Triglyceride Levels Despite Previous Statin Monotherapy: A Multicenter, Randomized, Double-blind, Phase IV Study.

PURPOSE: Residual cardiovascular risk reduction by fenofibrate in patients with high serum triglyceride (TG) levels despite previous statin monotherapy is not well characterized. The purpose of this study was to evaluate the efficacy and safety of a combination of choline fenofibrate and statin in patients with inadequately controlled TG levels despite previous statin monotherapy. METHODS: This prospective, multicenter, randomized, double-blind study was conducted in Korea. A total of 133 patients with controlled LDL-C but elevated TG levels, already receiving statin monotherapy, were enrolled in the study, which was conducted from July 2018 to December 2019. Patients were randomly assigned to receive combination therapy with choline fenofibrate and statin or statin monotherapy in a 1:1 ratio. After 8 weeks of treatment, the lipid profiles and safety parameters of the patients in the 2 groups were compared. FINDINGS: The study included 127 patients (64 in the combination group and 63 in the control group) older than 19 years. After 8 weeks of therapy, mean serum TG levels significantly decreased from 269.8 to 145.5 mg/dL (P < 0.0001) in the combination therapy group, whereas no significant changes occurred in the statin monotherapy group (from 271.1 to 280.5 mg/dL). Contrarily, the mean serum HDLC levels significantly increased from 45.0 to 50.4 mg/dL (P = 0.0004) in the combination therapy group, whereas there were no significant changes in the monotherapy group (from 44.3 to 44.7 mg/dL). There were no additional serious adverse events in the combination therapy group compared with the statin monotherapy group. IMPLICATIONS: The combination therapy using choline fenofibrate and statin was found to be effective in serum TG control and likely tolerable in patients with high TG levels despite statin monotherapy. A larger study, conducted for a longer duration, is needed to evaluate the effectiveness of this combination in reducing cardiovascular risk. ClinicalTrials.gov identifier: NCT03874260.

Development and Validation of a Risk Score Model for Predicting the Cardiovascular Outcomes After Breast Cancer Therapy: The CHEMO-RADIAT Score.

Background Cardiovascular disease is an important cause of mortality among survivors of breast cancer (BC). We developed a prediction model for major adverse cardiovascular events after BC therapy, which is based on conventional and BC treatment-related cardiovascular risk factors. Methods and Results The cohort of the study consisted of 1256 Asian female patients with BC from 4 medical centers in Korea and was randomized in a 1:1 ratio into the derivation and validation cohorts. The outcome measures comprised cardiovascular mortality, myocardial infarction, congestive heart failure, and transient ischemic attack/stroke. To correct overfitting, a penalized Cox proportional hazards regression was performed with a cross-validation approach. Number of cardiovascular diseases (myocardial infarction, peripheral artery disease, heart failure, and transient ischemic attack/stroke), number of baseline cardiovascular risk factors (hypertension, age ≥60, body mass index ≥30 kg/m2, estimated glomerular filtration rate <60 mL/min per 1.73 m2, dyslipidemia, and diabetes mellitus), radiation to the left breast, and anthracycline dose per 100 mg/m2 were included in the risk prediction model. The time-dependent C-indices at 3 and 7 years after BC diagnosis were 0.876 and 0.842, respectively, in the validation cohort. Conclusions A prediction score model, including BC treatment-related risk factors and conventional risk factors, was developed and validated to predict major adverse cardiovascular events in patients with BC. The CHEMO-RADIAT (congestive heart failure, hypertension, elderly, myocardial infarction/peripheral artery occlusive disease, obesity, renal failure, abnormal lipid profile, diabetes mellitus, irradiation of the left breast, anthracycline dose, and transient ischemic attack/stroke) score may provide overall cardiovascular risk stratification in survivors of BC and can assist physicians in multidisciplinary decision-making regarding the BC treatment.

Sex-specific associations of obesity with exercise capacity and diastolic function in Koreans.

BACKGROUND AND AIMS: Women with obesity are highly predominant among patients with heart failure with preserved ejection fraction (HFpEF). We aimed to elucidate sex-specific associations of obesity with exercise capacity and diastolic function. METHODS AND RESULTS: Healthy individuals without known cardiovascular diseases undergoing cardiopulmonary exercise test and echocardiography (n = 736) were included and categorized into 4 groups according to their sex and obesity. Exercise capacity was lower in women than men. Obesity was associated with a lower exercise capacity in women (23.5 ± 7.3 vs. 21.3 ± 5.4 ml/kg/min, p < 0.05) but not in men (28.2 ± 7.8 vs. 28.0 ± 6.6 ml/kg/min, p > 0.10). Overall, women had a higher E/e' than men. Women without obesity had a similar E/e' to men with obesity (8.2 ± 1.8 vs. 8.4 ± 2.1, p > 0.10), and women with obesity had the highest E/e'. Among 5 risk factors (aging, obesity, elevated blood pressure, elevated heart rate, and elevated fasting glucose), obesity was a significant determinant of exercise intolerance in women but not men. Furthermore, obesity was associated with a greater risk of diastolic dysfunction in women than men (women, adjusted odds ratio 4.35 [95% confidence interval 2.44-7.74]; men, adjusted odds ratio 2.91 [95% confidence interval 1.42-5.95]). CONCLUSION: Obesity had a more deleterious effect on exercise capacity and diastolic function in women than men, even in a healthy cohort. These subclinical changes might contribute to the development of a female predominance among HFpEF patients, particularly among individuals with obesity.

The effect of beta-blockers in acute heart failure according to heart rate.

BACKGROUND/AIMS: Beta-blockers (BBs) have been shown to improve clinical outcomes in heart failure (HF) patients. We evaluated the prescribing status of BBs in patients with HF with reduced ejection fraction (HFrEF) at discharge according to the presence or not of bradycardia, and its effect on prognosis. METHODS: Study data were obtained from a multicenter cohort of 3,200 patients hospitalized for HF. Patients were classified into four groups according to the presence of bradycardia and use of BBs at discharge. The primary outcome was the incidence of all-cause death during follow-up. RESULTS: Of 1,584 patients with HFrEF, 281 patients died during follow-up (median 523 days, mean 578.5 ± 429.7 days). In patients with bradycardia, the all-cause death rate did not significantly differ according to the use of BBs, but in those patients without bradycardia, the incidence of all-cause death was significantly lower in the BBs group than the no BBs group. Among these four groups, patients with heart rate (HR) ≥ 60 beats/min with no BBs group had the lowest cumulative death-free survival rate. In addition, HR ≥ 60 beats/min with BBs use was independently associated with a 31% reduced risk of all-cause death in patients with HFrEF. CONCLUSION: BBs had a beneficial effect on clinical prognosis only in those HFrEF patients without bradycardia. Therefore, BBs should be given by clinicians to HF patients without bradycardia to improve their clinical outcomes.

Effect of Prescribing Patterns of Renin-Angiotensin System Blockers and Beta-Blockers on Prognosis of Heart Failure.

INTRODUCTION: Use of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) only, beta-blockers (BB) only, or both has been rarely compared in patients with heart failure (HF). We evaluated the prescribing patterns of ACEi/ARB and BB on prognosis in HF according to left ventricular function. METHODS: Study data were obtained from a national multicenter cohort that included patients hospitalized for HF. Patients were classified into four groups according to the prescription pattern at discharge: all ACEi/ARB and BB treatment group, only ACEi or ARB treatment group, only BB treatment group, and neither ACEi/ARB nor BB group. RESULTS: Use of both ACEi/ARB and BB had significantly lowest all-cause death rates among the four groups in all types of HF. Cox regression analysis showed that use of both drugs was independently associated with 51% reduced risk of all-cause death in patients with HF with preserved ejection fraction (HFpEF) and HF with mid-range ejection fraction (HFmrEF). Treatment with only ACEi/ARB also showed an independent association with a 52% reduction in this group. However, only BB treatment was not associated with reducing long-term mortality in patients with HFpEF and HFmrEF. In patients with HF with reduced ejection fraction, use of ACEi/ARB and/or BB revealed an independent association with a reduced risk of all-cause death regardless of prescribing patterns. CONCLUSIONS: Prescribing patterns were diverse in HF and there was a difference in the degree of risk reduction in all-cause death. In particular, clinicians should consider ACEi/ARB first for patients with HFpEF and HFmrEF prior to BB.

The Impact of Body Mass Index on the Prognostic Value of N-Terminal proB-Type Natriuretic Peptide in Patients with Heart Failure: an Analysis from the Korean Heart Failure (KorHF) Registry.

Background and Objectives: Although an inverse correlation between the level of amino (N)-terminal pro-brain natriuretic peptide (NT-proBNP) and body mass index (BMI) has been reported, the impact of BMI on the prognostic value of NT-proBNP has not been well addressed. Methods: A total of 1,877 patients (67-year-old and 49.9% females) hospitalized for acute heart failure (HF) with documented NT-proBNP levels at baseline were included. Patients were classified into 2 groups by BMI (nonobese: BMI<23 kg/m2 and overweight or obese: BMI≥23 kg/m2). Clinical events during the follow-up including all-cause mortality and HF readmission were assessed. Results: During the median follow-up of 828 days (interquartile range, 111-1,514 days), there were 595 cases of total mortality (31.7%), 600 cases of HF readmission (32.0%), and 934 cases of composite events (49.8%). In unadjusted analyses, higher NT-proBNP level was associated with all-cause mortality and composite events (all-cause mortality and HF readmission) in both patients with BMI<23 kg/m2 and those with BMI≥23 kg/m2. In adjusted analyses controlling for potential confounders, however, a higher NT-proBNP level was associated with all-cause mortality and composite events in patients with BMI<23 kg/m2, but not in those with BMI≥23 kg/m2. Conclusions: The prognostic value of NT-proBNP was more significant in nonobese patients than in overweight and obese patients in this HF population. BMI should be considered when NT-proBNP is used for risk estimation in HF patients.

Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blockers in Heart Failure With Chronic Kidney Disease　- Propensity Score Matching Analysis.

BACKGROUND: Whether angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) exert beneficial effects in patients with concomitant heart failure (HF) and chronic kidney disease (CKD) remains uncertain. In this study, the effects of ACEI and ARB on long-term clinical outcomes in such patients were investigated.Methods and Results:Study data were obtained from a multicenter cohort that included patients hospitalized for HF. A total of 1,601 patients with both HF and CKD were classified according to prescription of ACEI or ARB at discharge. The mortality rate was 19.0% in the ACEI/ARB treatment group (n=943) and 33.6% in the no ACEI/ARB treatment group (n=658) during follow-up. The ACEI/ARB treatment group had a significantly higher cumulative death-free survival rate than the no ACEI/ARB treatment group. Cox regression analysis showed that using ACEI or ARB was independently associated with reduced risk of all-cause death after adjusting for confounding factors. The beneficial effects of ACEI or ARB were retained after propensity score matching. CONCLUSIONS: Prescription of an ACEI or ARB at discharge was associated with reduction in all-cause mortality in patients with acute HF and CKD. Clinicians need to be aware of the prognostic value and consider prescribing ACEI or ARB to high-risk patients.

Increased frequency of CD4+CD57+ senescent T cells in patients with newly diagnosed acute heart failure: exploring new pathogenic mechanisms with clinical relevance.

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.

Tachycardia induced Cardiomyopathy.

Recent studies on radiofrequency catheter ablation (RFCA) in atrial fibrillation show its effectiveness in heart failure (HF) patients; hence, tachycardia-induced cardiomyopathy (T-CMP) is gaining attention. Tachycardia-mediated cardiomyopathy is a reversible left ventricular (LV) dysfunction, which can be induced by any tachyarrhythmia. Early recognition of T-CMP with appropriate treatment of the arrhythmia culprit will lead to the recovery of LV function. Patients with tachycardia and LV dysfunction should be suspected of having T-CMP, with or without established etiology of HF, because T-CMP may present by itself or contribute as a co-existent component. Therapeutic options include rate control, anti-arrhythmic drugs, or catheter ablation. Unlike in animal models, clinical data on human T-CMP is limited. Hence, future research should be more focused on tachyarrhythmia-induced cardiomyopathy as its burden is increasing.

The Impact of Metabolic Syndrome on the Incidence of Atrial Fibrillation: A Nationwide Longitudinal Cohort Study in South Korea.

AIMS: To evaluate the impact of metabolic syndrome (MetS) status on the incidence of atrial fibrillation (AF) in Koreans. METHODS AND RESULTS: Data obtained from the Korean National Health Insurance Service from 2009 to 2016 were analyzed. In total, 7,830,602 men and women (between 30 and 69 years of age) without baseline AF who underwent a national health examination between January 2009 and December 2009 were enrolled. Patients were evaluated to determine the impact of MetS status on their risk of developing AF until December 2016. Using the National Cholesterol Education Program Adult Treatment Panel III criteria, patients were placed into one of three groups depending on MetS component numbers: 0 (normal), 1-2 (Pre-MetS) or 3-5 (MetS). During a mean follow-up of 7.3 years, 20,708 subjects (0.26%) were diagnosed with AF. After multivariable adjustment, the risk of AF was significantly and positively correlated with MetS status (hazard ratios (HR) 1.391, 95% confidence interval (CI) 1.322-1.464 in Pre-MetS and HR 1.722, 95% CI 1.621-1.829 in MetS). When subgroup analyses were conducted according to MetS components, abdominal obesity (HR 1.316, p < 0.001), elevated blood pressure (HR 1.451, p < 0.001), and elevated fasting glucose (HR 1.163, p < 0.001) were associated with an increased risk of AF. CONCLUSION: MetS and pre-MetS are significantly associated with an increased risk of AF in Korean adults. Of the MetS components, abdominal obesity, elevated blood pressure, and elevated fasting glucose are potent risk factors for the risk of AF in this population.

Sex Differences in Long-Term Clinical Outcomes in Patients Hospitalized for Acute Heart Failure: A Report from the Korean Heart Failure Registry.

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.

Cardiovascular outcome of breast cancer patients with concomitant radiotherapy and chemotherapy: A 10-year multicenter cohort study.

BACKGROUND: Cancer treatment increases the risk of cardiovascular (CV) events. However, the long-term CV outcome of breast cancer patients who undergo radiotherapy and chemotherapy concomitantly is unknown. This study aimed to determine the incidence and risk factors of CV events among these patients. METHODS: Six hundred sixty consecutive breast cancer patients older than 50 years from November 2005 to September 2015, were enrolled in four university hospitals. The primary endpoint was CV events including CV mortality, myocardial infarction, heart failure, and stroke. CV events occurred in 14 (2.1%) patients during the follow-up period (median, 47.1 months). RESULTS: Left-side irradiation was associated with increased risk of CV events in patients with doxorubicin dose ≥250mg/m2 but not in patients with doxorubicin dose <250mg/m2. On multivariable analysis, concomitant left-side irradiation with doxorubicin dose ≥250mg/m2 and hypertension were independent risk factors for CV events. CONCLUSION: The risk of CV events was further increased with concomitant left-side irradiation and doxorubicin ≥250mg/m2 in breast cancer patients.

Impact of Heart Rate Reduction with Maximal Tolerable Dose of Bisoprolol on Left Ventricular Reverse Remodeling.

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

Incidence, Risk Factors, and Clinical Characteristics of Peripartum Cardiomyopathy in South Korea.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare disorder associated with pregnancy that can lead to life-threatening conditions. The incidence and clinical characteristics of this condition remain poorly understood. METHODS AND RESULTS: We aimed to perform the first population-based study of PPCM in South Korea, using the Korea National Health Insurance Claims Database of the Health Insurance Review and Assessment Service. Patients who fulfilled predefined diagnostic criteria for PPCM from January 1, 2010, to December 31, 2012, were identified from International Classification of Diseases, Tenth Revision, Clinical Modification codes. To discriminate PPCM from other causes of heart failure, we excluded subjects who already had heart failure-related International Classification of Diseases, Tenth Revision, Clinical Modification codes at least 1 year before delivery. During the study period, there were 1 404 551 deliveries in South Korea, and we excluded 20 159 patients who already had heart failure. In those, a total of 795 cases were identified as PPCM. Patients with PPCM were older, had a higher prevalence of preeclampsia and gestational diabetes mellitus, and were more likely to be primiparous and have multiple pregnancies. Moreover, cesarean section and pregnancy-related complications and in-hospital death were also more common in patients with PPCM. Intriguingly, a considerable number of heart failure cases (n=64; 8.1% of total PPCM) were noted between 5 and 12 months after delivery. CONCLUSIONS: The incidence of PPCM was 1 in 1741 deliveries in South Korea. Patients with PPCM were older, were more associated with primiparity and multiple pregnancy, had more pregnancy-related complications, and revealed higher in-hospital mortality than controls. The number of cases diagnosed as PPCM were decreased over time after delivery; however, a large number of patients were still noted through 12 months after delivery.