Association between Smoking Habit Changes and the Risk of Myocardial Infarction in Ischemic Stroke Patients: A Nationwide Cohort Study.

BACKGROUND: Smoking is a well-known risk factor for cardiovascular diseases, including myocardial infarction (MI) and ischemic stroke (IS). While the relationship between smoking and the risk of cardiovascular diseases is established, the impact of changing smoking habits post-IS on the risk of subsequent MI remains unclear. This study aims to elucidate the effects of alterations in smoking behavior following an IS diagnosis on the likelihood of experiencing an MI. METHODS: Utilizing data from the Korean National Health Insurance Services Database, this nationwide population-based cohort study included 199,051 participants diagnosed with IS between January 2010 and December 2016. Smoking status was categorized based on changes in smoking habits before and after IS diagnosis. The association between changes in smoking behavior and the risk of subsequent MI was analyzed using multivariable Cox proportional hazard regression models. RESULTS: During a median follow-up of 4.17 person-years, a total of 5,734 (2.88%) patients were diagnosed with MI after IS. Smoking quitters (2.93%) or former smokers (2.47%) have a similar or lower rate of MI than the average, even if they have smoked cigarettes, while sustained smokers (3.46%) or new smokers (3.81%) have much higher rates of MI. Among sustained and new smokers, the risk of incident MI was significantly higher than never smokers (new smoker adjusted HR [aHR]: 1.496, 95% CI: 1.262-1.774; sustained smoker aHR: 1.494, 95% CI: 1.361-1.641). Also, among the study participants, approximately two-thirds continued smoking after their IS diagnosis. CONCLUSION: Changing smoking habits after an IS diagnosis significantly influences the risk of subsequent MI. Specifically, continuing or starting to smoke after an IS diagnosis is associated with a higher risk of MI. These results underscore the importance of targeted smoking cessation interventions for stroke patients to reduce the risk of subsequent MI.

Rationale, Design, and Interim Observations of the Steady Movement With Innovating Leadership for Heart Failure (SMILE HF) Registry: A Multicenter Prospective Cohort Registry for Patients With Acute Heart Failure.

Background and Objectives: Heart failure (HF) is a leading cause of hospitalization and death worldwide. The Steady Movement with Innovating Leadership for Heart Failure (SMILE HF) aims to evaluate the clinical characteristics, management, hospital course, and long-term outcomes of patients hospitalized for acute HF in South Korea. Methods: This prospective, observational multicenter cohort study was conducted on consecutive patients hospitalized for acute HF in nine university hospitals since September 2019. Enrolment of 2000 patients should be completed in 2024, and follow-up is planned through 2025. Results: Interim analysis of 1,052 consecutive patients was performed to understand the baseline characteristics. The mean age was 69±15 years; 57.6% were male. The mean left ventricular ejection fraction was 39±15%. The prevalences of HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction were 50.9%, 15.3%, and 29.2%. Ischemic cardiomyopathy (CMP) was the most common etiology (32%), followed by tachycardia-induced CMP (12.8%) and idiopathic dilated CMP (9.5%). The prescription rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers/angiotensin receptor/neprilysin inhibitor, beta-blockers, spironolactone, and sodium-glucose cotransporter-2 inhibitors at discharge were 76.8%, 66.5%, 50.0%, and 17.5%, respectively. The post-discharge 90-day mortality and readmission rates due to HF aggravation were 2.0% and 6.4%, respectively. Our analysis reveals the current state of acute HF in South Korea. Conclusions: Our interim analysis provides valuable insights into the clinical characteristics, management, and early outcomes of acute HF patients in South Korea, highlighting the current state and treatment patterns in this population.

Association between physical activity changes and incident myocardial infarction after ischemic stroke: a nationwide population-based study.

BACKGROUND: The impact of changes in physical activity after ischemic stroke (IS) on the subsequent myocardial infarction (MI) risk is not fully understood. We aimed to investigate the effects of changes in physical activity on the risk of MI after acute IS using data from the Korean National Health Insurance Services Database. METHODS: 224,764 patients newly diagnosed with IS between 2010 and 2016 who underwent two serial biannual health checkups were included. The participants were divided into four categories according to changes in their physical activity: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. The primary outcome was a new diagnosis of incident MI. Multivariable Cox proportional models were used to assess the effects of changes in exercise habits on the risk of MI. RESULTS: After a median of 4.25 years of follow-up, 6,611 (2.94%) MI cases were observed. After adjusting for confounders, new exercisers and exercise maintainers were significantly associated with a lower risk of incident MI than persistent non-exercisers (aHR, 0.849; 95% CI, 0.792-0.911; P-value < 0.001; and aHR, 0.746; 95% CI, 0.696-0.801; P-value < 0.001, respectively). Effects were consistent across sexes, more pronounced in those > 65 years. Notably, any level of physical activity after stroke was associated with a reduced MI risk compared to no exercise. CONCLUSIONS: In this nationwide cohort study, commencing or sustaining physical activity after an IS corresponded to a diminished likelihood of subsequent MI development. Advocating physical activity in ambulatory stroke survivors could potentially attenuate the prospective risk of MI.

Gender Difference of Blood Pressure Control Rate and Clinical Prognosis in Patients With Resistant Hypertension: Real-World Observation Study.

BACKGROUND: There are several differences in the clinical course of hypertension due to the biological and social differences between men and women. Resistant hypertension is an advanced disease state, and significant gender difference could be expected, but much has not been revealed yet. The purpose of this study was to compare gender differences on the current status of blood pressure (BP) control and clinical prognosis in patients with resistant hypertension. METHODS: This is a multicenter, retrospective cohort study using common data model databases of 3 tertiary hospitals in Korea. Total 4,926 patients with resistant hypertension were selected from January 2017 to December 2018. Occurrence of dialysis, heart failure (HF) hospitalization, myocardial infarction, stroke, dementia or all-cause mortality was followed up for 3 years. RESULTS: Male patients with resistant hypertension were younger but had a higher cardiovascular risk than female patients. Prevalence of left ventricular hypertrophy and proteinuria was higher in men than in women. On-treatment diastolic BP was lower in women than in men and target BP achievement rate was higher in women than in men. During 3 years, the incidence of dialysis and myocardial infarction was higher in men, and the incidence of stroke and dementia was higher in women. After adjustment, male sex was an independent risk factor for HF hospitalization, myocardial infarction, and all-cause death. CONCLUSION: In resistant hypertension, men were younger than women, but end-organ damage was more common and the risk of cardiovascular event was higher. More intensive cardiovascular prevention strategies may be required in male patients with resistant hypertension.

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.

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.

Prognostic Value of Leg Muscle Strength in Acute Heart Failure Syndrome.

INTRODUCTION: Leg muscle strength (LMS) may be useful as a frailty index in patients with heart failure. However, LMS, until recently, has been indirectly estimated, and its prognostic value in acute heart failure syndrome (AHFS) is unclear. Therefore, we evaluated the prognostic value of direct LMS assessment and its relationship with proinflammatory mediators in patients with AHFS. METHODS: We directly measured LMS at predischarge using a dynamometer in 110 prospectively and consecutively enrolled patients with AHFS (75 male; 60 ± 14 yr; mean ejection fraction, 29.9% ± 14.6%). The primary end point was cardiovascular (CV) events, defined as CV mortality, cardiac transplantation, or rehospitalization due to heart failure aggravation. Patients were divided into impaired and preserved LMS groups according to Contal and O'Quigley's method. RESULTS: CV events occurred in 28 patients (25.5%) (including 5 CV deaths and 6 cardiac transplantations) during follow-up (median, 246 d; range = 11-888 d). Impaired LMS was associated with significantly higher levels of serum monokine induced by gamma interferon and poor clinical outcomes (P < 0.001). Multivariable Cox proportional hazard analysis (controlling for age, sex, body mass index, heart failure type, hemoglobin level, N-terminal pro-b-type natriuretic peptide level, and beta-blocker use) revealed LMS as an independent predictor of CV events (P = 0.017). CONCLUSION: Impaired LMS, which might be used as a marker of frailty, is associated with increased levels of a proinflammatory chemokine and independently predicts clinical outcomes in patients with AHFS. The direct measurement of LMS is simple and feasible and might have important implications for the risk stratification of patients with AHFS.

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

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

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.

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.

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.

Analysis of cytomegalovirus-specific T-cell responses in patients with hypertension: comparison of assay methods and antigens.

BACKGROUND: Recent studies suggest an association between cytomegalovirus (CMV) infection and hypertension. In the present study, we used a variety of antigens and different assay methods to investigate the relationship between CMV-specific T-cell responses and arterial stiffness in patients with hypertension. METHODS: To evaluate arterial stiffness, pulse wave velocity (PWV) was measured in 207 hypertensive patients (average age, 63 ± 8 years). To measure CMV pp65 and IE-1-specific T-cell responses, we performed intracellular cytokine staining (ICS) and enzyme-linked immunospot (ELISPOT) assays. We also analyzed CMV-specific T-cell responses against 10 different CMV antigens using ELISPOT assays. RESULTS: In patients with hypertension, senescent CD8+ T-cell frequencies were significantly correlated with arterial stiffness. Moreover, arterial stiffness was independently associated with CMV pp65-specific CD8+ T-cell responses as measured by ICS. CMV-specific CD8+ T-cell responses measured by ICS and ELISPOT assays showed good agreement and significant correlation with each other. ELISPOT analyses against 10 different CMV antigens revealed a consistent response pattern irrespective of age, gender, and diabetes. CONCLUSIONS: CMV pp65-specific CD8+ T-cell responses were independently correlated with arterial stiffness in patients with hypertension. Additionally, the results of ICS and ELISPOT assays showed a significant correlation and good agreement with each other. These findings are important for guiding choices regarding the broad clinical application of CMV-specific T-cell response assays in this patient population.

Temporal Trends of De Novo Malignancy Development After Heart Transplantation.

BACKGROUND: Malignancy is a concern in cardiac transplant recipients, but the temporal trends of de novo malignancy development are unknown. OBJECTIVES: The goal of this study was to describe the temporal trends of the incidence, types, and predictors of de novo malignancy in cardiac transplant recipients. METHODS: The authors analyzed the temporal trends of post-transplant incidence, types, and predictors of malignancy using 17,587 primary adult heart-only transplant recipients from the International Society for Heart and Lung Transplantation registry. The main study outcomes included the incidence of, types of, and time to de novo malignancy. RESULTS: The risk of any de novo solid malignancy between years 1 and 5 after transplantation was 10.7%. The cumulative incidence by malignancy type was: skin cancer (7.0%), non-skin solid cancer (4.0%), and lymphoproliferative disorders (0.9%). There was no temporal difference in the time to development according to malignancy type. However, the cumulative incidence of de novo solid malignancy increased from 2000 to 2005 vs. 2006 to 2011 (10.0% vs. 12.4%; p < 0.0001). Survival in patients after de novo malignancy was markedly lower than in patients without malignancy (p < 0.0001). Older recipients and patients who underwent transplantation in the recent era had a higher risk of de novo malignancy. CONCLUSIONS: More than 10% of adult heart transplant recipients developed de novo malignancy between years 1 and 5 after transplantation, and this outcome was associated with increased mortality. The incidence of post-transplant de novo solid malignancy increased temporally, with the largest increase in skin cancer. Individualized immunosuppression strategies and enhanced cancer screening should be studied to determine whether they can reduce the adverse outcomes of post-transplantation malignancy.

The limited prognostic role of echocardiograms in short-term follow-up after acute decompensated heart failure: An analysis of the Korean Heart Failure (KorHF) Registry.

BACKGROUND: The prognostic values of the left ventricular ejection fraction (LVEF) and end-diastolic dimension (LVEDD) have primarily been shown among patients with chronic heart failure (HF), with little representation of patients with acute HF (AHF). Therefore, we investigated the value of these echocardiographic parameters in predicting clinical outcomes among patients in the Korean Heart Failure (KorHF) Registry. METHODS: The KorHF Registry consists of 3,200 patients who were hospitalized with AHF from 2005 to 2009. The Kaplan-Meier method was used to estimate survival and readmission, and differences were assessed using the log-rank test. Predictors of survival were identified using univariate and multivariate Cox proportional hazards regression analyses. RESULTS: Echocardiograms from 2,910 of the 3,200 patients (90.9%) were evaluated. The median LVEF and LVEDD (37% and 56 mm, respectively) were used as cut-offs for the binary transformation of each parameter. The cumulative death-free survival rates for all patients did not significantly differ based on LVEF or LVEDD quartiles; however, an LVEF greater than the median was associated with a better prognosis in ischemic HF patients (log-rank test; p = 0.039). Among ischemic HF patients, LVEF (dichotomized) was a significant predictor of death in a Cox model after adjusting for a history of HF, age, systolic blood pressure (SBP), serum sodium, sex, diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), acute myocardial infarction (AMI), atrial fibrillation (Af) and anemia (hazard ratio (HR) 1.475, 95% confidence interval (CI) 1.099-1.979, p = 0.010). The cumulative readmission-free survival rates significantly differed among ischemic HF patients only when based on LVEDD quartiles (log-rank test; p = 0.001). In multivariate Cox proportional hazards regression analyses, LVEDD (dichotomized) remained a significant variable only among patients with ischemic HF after adjusting for sex, age, AMI, DM, COPD, serum sodium, SBP, blood urea nitrogen (BUN) and anemia (HR 1.401, 95% CI 1.067-1.841, p = 0.015). CONCLUSIONS: Among ischemic AHF patients in the KorHF Registry, LVEF is associated with mortality, whereas LVEDD is only associated with readmission in a binary transformed form.