In-hospital glycemic variability and all-cause mortality among patients hospitalized for acute heart failure.

BACKGROUND: High glycemic variability (GV) is a poor prognostic marker in cardiovascular diseases. We aimed to investigate the association of GV with all-cause mortality in patients with acute heart failure (HF). METHODS: The Korean Acute Heart Failure registry enrolled patients hospitalized for acute HF from 2011 to 2014. Blood glucose levels were measured at the time of admission, during hospitalization, and at discharge. We included those who had 3 or more blood glucose measurements in this study. Patients were divided into two groups based on the coefficient of variation (CoV) as an indicator of GV. Among survivors of the index hospitalization, we investigated all-cause mortality at 1 year after discharge. RESULTS: The study analyzed 2,617 patients (median age, 72 years; median left-ventricular ejection fraction, 36%; 53% male). During the median follow-up period of 11 months, 583 patients died. Kaplan-Meier curve analysis revealed that high GV (CoV > 21%) was associated with lower cumulative survival (log-rank P < 0.001). Multivariate Cox proportional analysis showed that high GV was associated with an increased risk of 1-year (HR 1.56, 95% CI 1.26-1.92) mortality. High GV significantly increased the risk of 1-year mortality in non-diabetic patients (HR 1.93, 95% CI 1.47-2.54) but not in diabetic patients (HR 1.19, 95% CI 0.86-1.65, P for interaction = 0.021). CONCLUSIONS: High in-hospital GV before discharge was associated with all-cause mortality within 1 year, especially in non-diabetic patients with acute HF.

Incidence, Predictors, and Clinical Outcomes of New-Onset Diabetes Mellitus after Percutaneous Coronary Intervention with Drug-Eluting Stent.

We investigated the incidence, predictors, and long-term clinical outcomes of new-onset diabetes mellitus (DM) after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). A total of 6,048 patients treated with DES were retrospectively reviewed and divided into three groups: 1) known DM (n = 2,365; fasting glucose > 126 mg/dL, glycated hemoglobin > 6.5%, already receiving DM treatment, or previous history of DM at the time of PCI); 2) non-DM (n = 3,247; no history of DM, no laboratory findings suggestive of DM at PCI, and no occurrence of DM during follow-up); and 3) new-onset DM (n = 436; non-DM features at PCI and occurrence of DM during follow-up). Among 3,683 non-DM patients, 436 (11.8%) patients were diagnosed with new-onset DM at 3.4 ± 1.9 years after PCI. Independent predictors for new-onset DM were high-intensity statin therapy, high body mass index (BMI), and high level of fasting glucose and triglycerides. The 8-year cumulative rate of major adverse cardiac events (a composite of cardiovascular death, myocardial infarction, stent thrombosis, or any revascularization) in the new-onset DM group was 19.5%, which was similar to 20.5% in the non-DM group (P = 0.467), but lower than 25.0% in the known DM group (P = 0.003). In conclusion, the incidence of new-onset DM after PCI with DES was not low. High-intensity statin therapy, high BMI, and high level of fasting glucose and triglycerides were independent predictors for new-onset DM. Long-term clinical outcomes of patients with new-onset DM after PCI were similar to those of patients without DM.

Trends in receiving chemotherapy for advanced cancer patients at the end of life.

BACKGROUND: The use of chemotherapy in advanced cancer patients has increased with the development of novel, high-efficacy anticancer therapeutic agents. In the current study, we analyzed the 10-year trends in patients receiving chemotherapy at the end of life. METHOD: We retrospectively reviewed mortality data for advanced cancer patients who died in 2000, 2005, and 2010 at a single institution. The trends of receiving palliative chemotherapy at the end of life were assessed for each year. In addition, logistic regression analysis was performed to determine the factors associated with receiving chemotherapy. RESULTS: We analyzed the records of 2,345 patients who died of cancer. Patients with less responsive tumors were less likely to receive chemotherapy than patients with responsive tumors at the time of death. Patients who were ≥ 65 years were less likely to receive chemotherapy compared with patients who were < 65 years at the end of life. However, the proportion of older patients receiving chemotherapy in the last month of life increased in 2010 (44.2%) compared with 2005 (32.7%) and 2000 (25.7%). Compared with the year 2000, the likelihood of receiving chemotherapy during the last 1 month of life increased in 2005 (odds ratio [OR], 2.05; 95% confidence interval [CI], 1.60-2.62) and 2010 (OR, 4.42; 95% CI, 3.51-5.57). CONCLUSIONS: The proportion of patients receiving chemotherapy at the end of life increased successively from 2000 to 2005 to 2010. Physicians should consider whether to continue chemotherapy at the end of life.

Blood pressure and heart failure: focused on treatment.

Heart failure (HF) remains a significant global health burden, and hypertension is known to be the primary contributor to its development. Although aggressive hypertension treatment can prevent heart changes in at-risk patients, determining the optimal blood pressure (BP) targets in cases diagnosed with HF is challenging owing to insufficient evidence. Notably, hypertension is more strongly associated with HF with preserved ejection fraction than with HF with reduced ejection fraction. Patients with acute hypertensive HF exhibit sudden symptoms of acute HF, especially those manifested with severely high BP; however, no specific vasodilator therapy has proven beneficial for this type of acute HF. Since the majority of medications used to treat HF contribute to lowering BP, and BP remains one of the most important hemodynamic markers, targeted BP management is very concerned in treatment strategies. However, no concrete guidelines exist, prompting a trend towards optimizing therapies to within tolerable ranges, rather than setting explicit BP goals. This review discusses the connection between BP and HF, explores its pathophysiology through clinical studies, and addresses its clinical significance and treatment targets.

Nocturnal systolic blood pressure dipping and progression of chronic kidney disease.

The relationship between declining nocturnal blood pressure (BP) and adverse cardiovascular outcomes is well-recognized. However, the relationship between diurnal BP profile and the risk of chronic kidney disease (CKD) progression is unclear. Herein, we examined the association between nocturnal systolic SBP (SBP) dipping and CKD progression in 1061 participants at the Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (CMERC-HI). The main exposure was diurnal systolic BP (SBP) profile and diurnal SBP difference ([nighttime SBP-daytime SBP] × 100/daytime SBP). The primary outcome was CKD progression, defined as a composite of ≥ a 50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy. During 4749 person-years of follow-up (median, 4.8 years), the composite outcome occurred in 380 (35.8%) participants. Compared to dippers, the hazard ratios (HRs) for the risk of adverse kidney outcomes were 1.02 (95% confidence interval [CI], 0.64-1.62), 1.30 (95% CI, 1.02-1.66), and 1.40 (95% CI, 1.03-1.90) for extreme dipper, non-dipper, and reverse dipper, respectively. In a continuous modeling, a 10% increase in diurnal SBP difference was associated with a 1.21-fold (95% CI, 1.07-1.37) higher risk of CKD progression. Thus, decreased nocturnal SBP decline was associated with adverse kidney outcomes in patients with CKD. Particularly, patients with non-dipping and reverse dipping patterns were at higher risk for CKD progression than those with a dipping pattern.

Heart Failure Statistics 2024 Update: A Report From the Korean Society of Heart Failure.

Background and Objectives: The number of people with heart failure (HF) is increasing worldwide, and the social burden is increasing as HF has high mortality and morbidity. We aimed to provide updated trends on the epidemiology of HF in Korea to shape future social measures against HF. Methods: We used the National Health Information Database of the National Health Insurance Service to determine the prevalence, incidence, hospitalization rate, mortality rate, comorbidities, in-hospital mortality, and healthcare cost of patients with HF from 2002 to 2020 in Korea. Results: The prevalence of HF in the total Korean population rose from 0.77% in 2002 to 2.58% (1,326,886 people) in 2020. Although the age-standardized incidence of HF decreased over the past 18 years, the age-standardized prevalence increased. In 2020, the hospitalization rate for any cause in patients with HF was 1,166 per 100,000 persons, with a steady increase from 2002. In 2002, the HF mortality was 3.0 per 100,000 persons, which rose to 15.6 per 100,000 persons in 2020. While hospitalization rates and in-hospital mortality for patients with HF increased, the mortality rate for patients with HF did not (5.8% in 2020), and the one-year survival rate from the first diagnosis of HF improved. The total healthcare costs for patients with HF were approximately $2.4 billion in 2020, a 16-fold increase over the $0.15 billion in 2002. Conclusions: The study's results underscore the growing socioeconomic burden of HF in Korea, driven by an aging population and increasing HF prevalence.

Metformin treatment is associated with improved survival in diabetic patients hospitalized with acute heart failure: A prospective observational study using the Korean acute heart failure registry data.

AIMS: Although the hypothesis that metformin is beneficial for patients with diabetes and heart failure (HF) has been steadily raised, there is limited data on metformin use in patients with acute HF. We analyzed the association of metformin on all-cause mortality in hospitalized patients with type 2 diabetes and acute HF. METHODS: The Korean Acute Heart Failure registry prospectively enrolled patients hospitalized for acute HF from 2011 to 2014. Among this cohort, we analyzed patients with diabetes with baseline estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73 m2 or more. We analyzed the all-cause mortality and re-hospitalization for HF within 1 year after discharge. Inverse probability treatment weighting method was used to adjust baseline differences on metformin treatment. RESULTS: The study analyzed data from 1,309 patients with HF and diabetes (mean age 69 years, 56 % male). Among them, 613 (47 %) patients were on metformin at admission. During the median follow-up period of 11 months, 132 (19 %) and 74 (12 %) patients not receiving and receiving metformin treatment died, respectively. The mortality rate was lower in metformin users than in non-users (hazard ratio 0.616 [0.464-0.819] P<0.001). After adjustment, metformin was significantly associated with a lower risk for the mortality (hazard ratio 0.677 [0.495-0.928] P=0.015). In subgroup analyses, this association remains significant irrespective of baseline kidney function (eGFR <60 or ≥60 ml/min/1.73 m2, P-for-interaction=0.176) or left ventricular ejection fraction (<40 %, 40-49 %, or ≥50 %, P-for-interaction=0.224). CONCLUSIONS: Metformin treatment at the time of admission was associated with a lower risk for 1-year mortality in patients with diabetes, hospitalized for acute HF.

Advanced heart failure: a contemporary approach.

Advanced heart failure (HF) is defined as the persistence of severe symptoms despite the use of optimized medical, surgical, and device therapies. These patients require timely advanced treatments, such as heart transplantation or long-term mechanical circulatory support (MCS). Inotropic agents are often used to reduce congestion and increase cardiac output, while renal replacement therapy may be beneficial if necessary. Cardiac resynchronization therapy has clear benefits in patients with HF with reduced ejection fraction, particularly with left bundle branch block (QRS duration > 130 ms). The role of implantable cardioverter-defibrillators in advanced HF patients requires further investigation considering the introduction of novel HF medications. In selected patients with significant secondary mitral regurgitation, transcatheter edge-to-edge repair can help delay heart transplantation or long-term MCS. In later stages, the appropriateness of heart transplantation should be evaluated, and the use of short- or long-term MCS may be considered. A multidisciplinary HF management program is crucial for patients with advanced HF. Recent treatment advances, including drugs, devices, and MCS, have broadened the options available to patients with advanced HF and this trend is expected to continue.

The characteristic large-scale annual analysis by gender and age in heart failure patients: cohort for 10 years in Korea.

AIMS: The prevalence and incidence rate of heart failure (HF) continues to increase along with the aging of the population and the increase of ischaemic heart disease. The morbidity and mortality of HF are also on the rise in the industrialized countries; it can be a great public health problem. A detailed and accurate analysis of the demographical incidence and prevalence of HF is an important first step in predicting the occurrence of the disease in the future and proper preparing for prevention. Here, we aimed to analyse the annual prevalence and incidence of HF by gender and age using long-term national health insurance service data in the Republic of Korea. METHODS AND RESULTS: A total of 47 243 patients newly diagnosed with HF between 2006 and 2015 among nationally representative random subjects of 1 000 000 were included. The data of age and gender were analysed by year, and the total population information of the Ministry of Land, Infrastructure, and Transport of Korea was referred to compare the data of HF patients with the total population (2008-15). Over the decade from 2006 to 2015, the prevalence of HF patients showed tendency of increase (P < 0.001). The overall incidence rate was also gradually increasing (P < 0.001), but in women, it tended to decrease gradually. Women significantly accounted higher than the male group in incidence of HF over the period (54.6% vs. 45.4%, P < 0.001). The mean age at the time of diagnosis gradually increased (P = 0.002 for total, P = 0.001 for each gender). Total incidence was highest in 70s (27.22%), but males were the most in their 60s and females were in their 70s. Analysis of annual trend by age and gender distribution of HF incidence in men presented highest in the 50s-70s with a similar pattern annually, and the incidence is increasing more recently. Different from that of men, in the case of women, the incidence gradually increased with age in a similar annual pattern, peaking in their 70s and gradually decreasing in recent years. CONCLUSIONS: The prevalence and incidence of HF are gradually increasing. It increased rapidly in their 50s and older. It showed an increased incidence of HF especially in men between their 50s and 70s, and more observation and caution for the management of the risk factors may be needed to prevent HF in the male group.

Delayed blood pressure recovery after exercise stress test is associated with autonomic dysfunction and pulse pressure in a middle-aged healthy group.

BACKGROUND: Delayed heart rate (HR) and blood pressure recovery after exercise test is known as the reliable indexes of autonomic dysfunction. Here we tried to evaluate the serial changes in various indicators during exercise test and correlations with recovery of HR and blood pressure in a normotensive healthy middle-aged group. METHODS: A total of 122 patients without hypertension or diabetes was enrolled (mean age, 55.6 ± 11.0; male, 56.6%; mean blood pressure, 124.8 ± 16.6 / 81.5 ± 9.6 mmHg). Treadmill test was performed for evaluation of chest pain. Patients with coronary artery disease, positive treadmill test result, left ventricular dysfunction or renal failure were excluded. Heart rate recovery was calculated by subtracting the HR in the first or second minute of recovery period from the HR of peak exercise (HRR1 or HRR2). Systolic blood pressure in the 4th minute of recovery stage (SBPR4) was used to show delayed blood pressure recovery. RESULTS: Metabolic equivalents (METs) and HR in stage 2 to 4 were significantly correlated with both HRR1 and HRR2. Multiple regression analysis of HRR revealed significant correlation of METs and SBPR4. SBPR4 was significantly correlated with both HRR1 and HRR2 (HRR1, r = -0.376, p<0.001; HRR2, r = -0.244, p = 0.008) as well as SBP in the baseline to stage 3 and pulse pressure (r = 0.406, p<0.001). CONCLUSIONS: Delayed BP recovery after peak exercise test revealed significant association with autonomic dysfunction and increased pulse pressure in normotensive middle-aged healthy group. It can be a simple and useful marker of autonomic dysfunction and arterial stiffness.

Human induced pluripotent stem cell line YCMi007-A generated from a dilated cardiomyopathy patient with a heterozygous dominant c.613C > T (p. Arg205Trp) variant of the TNNT2 gene.

Cardiac muscle troponin T protein binds to tropomyosin and regulates the calcium-dependent actin-myosin interaction on thin filaments in cardiomyocytes. Recent genetic studies have revealed that TNNT2 mutations are strongly linked to dilated cardiomyopathy (DCM). In this study, we generated YCMi007-A, a human induced pluripotent stem cell (hiPSC) line from a DCM patient with a p. Arg205Trp mutation in the TNNT2 gene. The YCMi007-A cells show high expression of pluripotent markers, normal karyotype, and differentiation into three germ layers. Thus, YCMi007-A-an established iPSC-could be useful for the investigation of DCM.

Clinical Implications of Device-Detected Atrial Fibrillation in Cardiac Resynchronization Therapy.

BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) is associated with decreased cardiac resynchronization therapy (CRT) benefits compared to sinus rhythm (SR). Effective biventricular (BiV) pacing is a determinant of CRT success, but AF can interfere with adequate BiV pacing and affect clinical outcomes. We investigated the effect of device-detected AF on clinical outcomes and optimal BiV pacing in patients with heart failure (HF) treated with CRT. METHODS: We retrospectively analyzed 174 patients who underwent CRT implantation between 2012 and 2019 at a tertiary center. The optimal BiV pacing percentage was defined as ≥98%. Device-detected AF was defined as an atrial high-rate episode ≥180 beats per minute lasting more than 6 minutes during the follow-up period. We stratified the patients without preexisting AF at pre-implantation into device-detected AF and no-AF groups. RESULTS: A total of 120 patients did not show preexisting AF at pre-implantation, and 54 had AF. Among these 120 patients, 19 (15.8%) showed device-detected AF during a median follow-up of 25.1 months. The proportion of optimal BiV pacing was significantly lower in the device-detected AF group than in the no-AF group (42.1% vs. 75.2%, p=0.009). The device-detected AF group had a higher incidence of HF hospitalization, cardiovascular death, and all-cause death than the no-AF group. The device-detected AF and previous AF groups showed no significant differences regarding the percentage of BiV pacing and clinical outcomes. CONCLUSIONS: For HF patients implanted with CRT, device-detected AF was associated with lower optimal BiV pacing and worse clinical outcomes than no-AF.

Statin Therapy in HIGH-Risk Individuals with NORMal Coronary Arteries: The HIGH-NORM Study.

AIMS: Mismatches between the risk status of a patient and coronary imaging data can lead to conflicting strategies to prevent a cardiovascular event. We evaluated whether statin use was associated with cardiovascular benefit in high-risk individuals whose coronary computed tomography angiography (CCTA) results showed normal coronary arteries. METHODS: Among asymptomatic individuals whose CCTA showed normal or near normal coronary arteries, 3,389 persons with high- or very-high-risk status were included in this retrospective study. After 1:2 propensity score matching, 906 individuals (302 new statin users and 604 controls; mean age 61 years; male 58%) were analysed. The primary outcome variable was major adverse cardiovascular and cerebrovascular events (MACCEs) that consisted of cardiovascular death, nonfatal myocardial infarction, coronary revascularisation, and nonfatal ischemic stroke. RESULTS: At a median follow-up of 5.8 years, 20 statin users and 17 controls (7.4 and 5.6 events/1,000 person-year, respectively; hazard ratio [HR) 1.04; p=0.92) experienced MACCE. Kaplan-Meier curves showed similar MACCE rates in both groups (p=0.91). In separate analyses for persons with normal (p=0.29) or near normal coronary arteries (p=0.67), MACCE rates did not differ between the groups. Age (HR 1.04; p=0.044), male sex (HR 3.06, p=0.018), and smoking (HR 2.87, p=0.019) were independently associated with MACCEs. In subgroup analyses, no significant factors affected the relationship between statin use and MACCEs. CONCLUSIONS: Statin use was not associated with cardiovascular risk reduction in high-risk persons with normal or near normal coronary arteries. More individualised lipid-lowering therapy may benefit this population.

Prognostic Cardiac Magnetic Resonance Markers of Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy for Predicting Heart Failure Outcomes.

Background Left ventricular (LV) involvement is frequently observed in arrhythmogenic cardiomyopathy (ACM). We investigated the association of LV myocardial assessment using cardiac magnetic resonance (CMR) with clinical outcomes including heart failure (HF)-related events in ACM. Methods and Results We retrospectively analyzed 60 patients with ACM between 2005 and 2020 according to the 2010 Task Force Criteria and assessed HF-related events (HF hospitalization, heart transplantation, and cardiac death) and ventricular tachycardia events. We analyzed CMR findings including late gadolinium enhancement (LGE) in all subjects and obtained mapping values (native T1, extracellular volume, and T2) on 30 (50%) patients out of them. Among the study population (mean age 49 years, 77% male), 41 (68%) patients had LV LGE. During a median follow-up of 34 months, there were 13 (22%) HF-related events, and 20 (30%) ventricular tachycardia events. Kaplan-Meier survival analysis revealed that HF-related events occurred only in patients with LV LGE (+) (versus LV LGE (-), log-rank P=0.006), and the events were not significantly different regarding right ventricular LGE (log-rank P>0.999). When categorized by median value for each mapping parameter, HF-related events occurred more in patients with higher native T1 (versus lower native T1, log-rank P=0.002), and higher T2 (versus lower T2, log-rank P=0.002), higher extracellular volume (versus lower extracellular volume, log-rank P=0.002). However, regarding ventricular tachycardia events, there were no significant differences according to these CMR markers. Conclusions LV myocardial assessment using CMR with LGE imaging and native T1, T2, and extracellular volume markers were significantly associated with HF-related event risk in patients with ACM.

Cardiac Rehabilitation in Heart Failure.

Heart failure (HF) is a complex clinical syndrome caused by a structural and/or functional cardiac abnormality, resulting in reduced organ perfusion. The goals of treatment in patients with HF are to improve functional capacity and quality of life, and to reduce mortality. Cardiac rehabilitation (CR) including exercise training is one of the treatment options, and current guidelines recommend CR as safe and effective for patients with HF. CR has been known to improve exercise capacity and quality of life, minimize HF progression, and lower mortality in patients with HF. Improvement of vascular endothelial function, activation of the neurohormonal system, increase of mitochondrial oxygen utilization in peripheral muscles, and increase of chronotropic responses are possible mechanisms of the beneficial effects of exercise-based CR in HF. Although CR has been shown to decrease morbidity and mortality, it is underutilized in clinical practice. Despite the existence of concrete evidence of clinical benefits, the CR participation rates of patients with HF range from only 14% to 43% worldwide, with high dropout rates after enrollment. These low participation rates have been attributed to several barriers, including patient factors, professional factors, and service factors. The motivation for participating in CR and for overcoming the patients' barriers for CR before discharge should be provided to each patient. Current guidelines strongly recommend applying a CR program to all eligible patients with HF.

Post-transplant absolute lymphocyte count predicts early cytomegalovirus infection after heart transplantation.

Immunosuppressive therapy can decrease rejection episodes and increase the risk of severe and fatal infections in heart transplantation (HT) recipients. Immunosuppressive therapy can also decrease the absolute lymphocyte count (ALC), but the relationship between early post-transplant ALC and early cytomegalovirus (CMV) infection is largely unknown, especially in HT. We retrospectively analyzed 58 HT recipients who tested positive for CMV IgG antibody and received basiliximab induction therapy. We collected preoperative and 2-month postoperative data on ALC and CMV load. The CMV load > 1200 IU/mL was used as the cutoff value to define early CMV infection. Post-transplant lymphopenia was defined as an ALC of < 500 cells/µL at postoperative day (POD) #7. On POD #7, 29 (50.0%) patients had post-transplant lymphopenia and 29 (50.0%) patients did not. The incidence of CMV infection within 1 or 2 months of HT was higher in the post-transplant lymphopenia group than in the non-lymphopenia group (82.8% vs. 48.3%, P = 0.013; 89.7% vs. 65.5%, P = 0.028, respectively). ALC < 500 cells/µL on POD #7 was an independent risk factor for early CMV infection within 1 month of HT (odds ratio, 4.14; 95% confidence interval, 1.16-14.77; P = 0.029). A low ALC after HT was associated with a high risk of early CMV infection. Post-transplant ALC monitoring is simple and inexpensive and can help identify patients at high risk of early CMV infection.

Association of muscular fitness with rehospitalization for heart failure with reduced ejection fraction.

BACKGROUND: Limited information is available regarding the prognostic potential of muscular fitness parameters in heart failure (HF) with reduced ejection fraction (HFrEF). HYPOTHESIS: We aimed to investigate the predictive potential of knee extensor muscle strength and power on rehospitalization and evaluate the correlation between exercise capacity and muscular fitness in patients newly diagnosed with HFrEF. METHODS: Ninety nine patients hospitalized with a new diagnosis of HF were recruited (64 men; aged 58.7 years [standard deviation (SD), 13.2 years]; 32.3% ischemic; ejection fraction, 28% [SD, 8%]). The inclusion criteria were left ventricular ejection fraction <40% and sufficient clinical stability to undergo exercise testing. Aerobic exercise capacity was measured with cardiopulmonary exercise testing. Knee extensor maximal voluntary isometric contraction (MVIC) and muscle power (MP) were measured using the Baltimore therapeutic equipment system. The clinical outcome was HF rehospitalization. RESULTS: Over a mean follow-up period of 1709 ± 502 days, 39 patients were rehospitalized due to HF exacerbation. HF rehospitalization was more probable for patients with diabetes and lower oxygen uptake at peak exercise (peak VO2 ), knee extensor MVIC, and MP. The Kaplan-Meier survival analysis revealed significantly different cumulative HF rehospitalization rates according to the tertiles of peak VO2 (P = 0.005) and MP (P = 0.002). Multivariable Cox proportional hazard model showed that the lowest tertiles of peak VO2 (hazard ratio (HR), 6.26; 95% confidence interval (CI), 1.93-20.27); and MP (HR, 5.29; 95% CI, 1.05-26.53) were associated with HF rehospitalization. Knee extensor muscle power was an independent predictor for rehospitalization in patients with HFrEF. CONCLUSION: Knee extensor muscle power was an independent predictor for rehospitalization in patients with HFrEF.

Risk of Cardiac Disease in Patients With Breast Cancer: Impact of Patient-Specific Factors and Individual Heart Dose From Three-Dimensional Radiation Therapy Planning.

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.

Clinical evidence of initiating a very low dose of sacubitril/valsartan: a prospective observational analysis.

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.

Prevalence and prognosis of the 2018 vs 2008 AHA definitions of apparent treatment-resistant hypertension in high-risk hypertension patients.

Resistant hypertension was defined according to the 2008 scientific statement as office blood pressure ≥ 140/90 mm Hg and the 2018 scientific statement as office blood pressure ≥ 130/80 mm Hg. We investigated the prognostic significance of lowered blood pressure threshold for defining resistant hypertension in the 2018 American Heart Association scientific statement compared with that in the 2008 scientific statement. The participants of this prospective cohort were enrolled from December 2013 to November 2018. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and heart failure hospitalization. Renal event was defined as a ≥ 50% decline in estimated glomerular filtration rate or progression to end-stage renal disease. A total of 206 patients among 2018 (10.2%) were diagnosed with resistant hypertension by the previous definition (≥140/90 mm Hg), and 276 patients among 2011 (13.7%) were diagnosed with resistant hypertension by the updated definition (≥130/80 mm Hg). During a median follow-up of 4.5 years, 33 MACEs (3.7 per 1000 patient-years) and 164 renal events (19.9 per 1000 patient-years) occurred in the study population. Treatment-resistant hypertension groups had a higher incidence rate of MACEs and renal events than the control groups. In multivariate Cox proportional hazards regression analysis, resistant hypertension by both definitions was significantly associated with increased risk of MACE and renal event. Both the previous and updated definitions of resistant hypertension were significant predictors of MACEs and renal events. This finding supports the adoption of the updated criteria for resistant hypertension in clinical practice.