Association of cumulative health status with subsequent mortality in patients with acute heart failure.

OBJECTIVE:We aim to examine the association between long-term cumulative health status and subsequent mortality among patients with acute heart failure (HF).METHODS:Based on a national prospective cohort study of patients hospitalized for HF, we measured health status by Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 at 4 time points, i.e. admission, 1-,6- and 12-month after discharge. Cumulative health status was interpreted by cumulative KCCQ-12 score and cumulative times of good health status. Outcomes included subsequent all-cause and cardiovascular mortality. Multivariable Cox proportional hazard models were performed to examine the association between cumulative health status and subsequent mortality.RESULTS:Totally, 2328 patients (36.7% women and median age 66 [IQR: 56-75] years) were included, the median follow-up was 4.34 (IQR: 3.93-4.96) years. Compared with Quartile 4, the lowest Quartile 1 had the highest HR for all-cause mortality (2.96; 95% CI: 2.26-3.87), followed by Quartile 2 (1.79; 95% CI: 1.37-2.34) and Quartile 3 (1.62; 95% CI: 1.23-2.12). Patients with 0-time of good health status had the highest risk of all-cause mortality (HR: 2.41, 95% CI: 1.69-3.46) compared with patients with 4-times of good health status. Similar associations persisted for cardiovascular mortality.CONCLUSIONS:A greater burden of cumulative health status indicated worse survival among patients hospitalized for HF. Repeated KCCQ measurements could be helpful to monitor long-term health status and identify patients vulnerable to death. Clinical Trial Registration: www.clinicaltrials.gov (NCT02878811).

Age-Related Trends in the Predictive Value of Carotid Intima-Media Thickness for Cardiovascular Death: A Prospective Population-Based Cohort Study.

Background The age-related trends in the predictive ability of carotid intima-media thickness (CIMT) for cardiovascular risk remain unclear. We aimed to identify the age-related trends in the predictive value of CIMT for cardiovascular death. Methods and Results In a prospective cohort of adults aged 35 to 75 years without history of cardiovascular disease who were enrolled between 2014 and 2020, we measured CIMT at baseline and collected the vital status and cause of death. We divided the study population into 4 age groups (35-44, 45-54, 55-64, and 65-75 years). Competing risk models were fitted to estimate the associations between CIMT and cardiovascular death. The added values of CIMT in prediction were assessed by the differences of the Harrell's concordance index and the net reclassification improvement index. We included 369 478 adults and followed them for a median of 4.7 years. A total of 4723 (1.28%) cardiovascular deaths occurred. After adjusting for the traditional risk factors, the hazard ratios for CIMTmean per SD decreased with age, from 1.27 (95% CI, 1.17-1.37) in the 35 to 44 years age group to 1.14 (95% CI, 1.10-1.19) in the 65 to 75 years age group (P for interaction <0.01). Meanwhile, the net reclassification improvement indexes for CIMTmean were attenuated with age, from 22.60% (95% CI, 15.56%-29.64%) in the 35 to 44 years age group to 7.00% (95% CI, -6.82% to 20.83%) in the 65 to 75 years age group. Similar results were found for maximum CIMT in all age groups. Conclusions CIMT may improve cardiovascular risk prediction in the young and middle-aged populations, rather than those aged ≥55 years.

A novel polygenic risk score improves prognostic prediction of heart failure with preserved ejection fraction in the Chinese Han population.

AIMS:Mortality risk assessment in patients with heart failure (HF) with preserved ejection fraction (HFpEF) presents a major challenge. We sought to construct a polygenic risk score (PRS) to accurately predict the mortality risk of HFpEF.METHODS AND RESULTS:We first carried out a microarray analysis of 50 HFpEF patients who died and 50 matched controls who survived during 1-year follow-up for candidate gene selection. The HF-PRS was developed using the independent common (MAF > 0.05) genetic variants that showed significant associations with 1-year all-cause death (P < 0.05) in 1442 HFpEF patients. Internal cross-validation and subgroup analyses were performed to evaluate the discrimination ability of the HF-PRS. In 209 genes identified by microarray analysis, 69 independent variants (r < 0.1) were selected to develop the HF-PRS model. This model yielded the best discrimination capability for 1-year all-cause mortality with an area under the curve (AUC) of 0.852 (95% CI 0.827-0.877), which outperformed the clinical risk score consisting of 10 significant traditional risk factors for 1-year all-cause mortality (AUC 0.696, 95% CI 0.658-0.734, P = 4 × 10-11), with net reclassification improvement (NRI) of 0.741 (95% CI 0.605-0.877; P < 0.001) and integrated discrimination improvement (IDI) of 0.181 (95% CI 0.145-0.218; P < 0.001). Individuals in the medium and the highest tertile of the HF-PRS had nearly a five-fold (HR = 5.3, 95% CI 2.4-11.9; P = 5.6 × 10-5) and 30-fold (HR = 29.8, 95% CI 14.0-63.5; P = 1.4 × 10-18) increased risk of mortality compared to those in the lowest tertile, respectively. The discrimination ability of the HF-PRS was excellent in cross validation and throughout the subgroups regardless of comorbidities, gender, and patients with or without a history of heart failure.CONCLUSION:The HF-PRS comprising 69 genetic variants provided an improvement of prognostic power over the contemporary risk scores and NT-proBNP in HFpEF patients.

Individual Trajectories of Health Status During the First Year of Discharge From Hospitalization for Heart Failure and Their Associations With Death in the Following Years.

Background Improving health status is one of the major goals in the management of heart failure (HF). However, little is known about the long-term individual trajectories of health status in patients with acute HF after discharge. Methods and Results We enrolled 2328 patients hospitalized for HF from 51 hospitals prospectively and measured their health status via the Kansas City Cardiomyopathy Questionnaire-12 at admission and 1, 6, and 12 months after discharge, respectively. The median age of the patients included was 66 years, and 63.3% were men. Six patterns of Kansas City Cardiomyopathy Questionnaire-12 trajectories were identified by a latent class trajectory model: persistently good (34.0%), rapidly improving (35.5%), slowly improving (10.4%), moderately regressing (7.4%), severely regressing (7.5%), and persistently poor (5.3%). Advanced age, decompensated chronic HF, HF with mildly reduced ejection fraction, HF with preserved ejection fraction, depression symptoms, cognitive impairment, and each additional HF rehospitalization within 1 year of discharge were associated with unfavorable health status (moderately regressing, severely regressing, and persistently poor) (P<0.05). Compared with the pattern of persistently good, slowly improving (hazard ratio [HR], 1.50 [95% CI, 1.06-2.12]), moderately regressing (HR, 1.92 [1.43-2.58]), severely regressing (HR, 2.26 [1.54-3.31]), and persistently poor (HR, 2.34 [1.55-3.53]) were associated with increased risks of all-cause death. Conclusions One-fifth of 1-year survivors after hospitalization for HF experienced unfavorable health status trajectories and had a substantially increased risk of death during the following years. Our findings help inform the understanding of disease progression from a patient perception perspective and its relationship with long-term survival. Registration URL: https://www.clinicaltrials.gov; unique identifier: NCT02878811.

β-blocker and 1-year outcomes among patients hospitalized for heart failure with mid-range ejection fraction.

AIMS:The beneficial effect of β-blocker on heart failure with reduced ejection fraction is well established. However, its effect on the 1-year outcome of heart failure with mid-range ejection fraction (HFmrEF) remains unclear.METHODS AND RESULTS:We analysed the data of the patients with left ventricular ejection fraction (LVEF) between 40% and 49% in China Patient-centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (China PEACE 5p-HF Study), in which patients hospitalized for heart failure from 52 Chinese hospitals were recruited from 2016 to 2018. Two primary outcomes were all-cause death and all-cause hospitalization. The associations between β-blocker use at discharge and outcomes were assessed by inverse probability of treatment weighting (IPTW)-weighted Cox regression analyses. To assess consistency, IPTW adjusting medications analyses, multivariable analyses and dose-effect analyses were performed. A total of 1035 HFmrEF patients were included in the analysis. The mean age was 65.5 ± 12.7 years and 377 (36.4%) were female. The median (interquartile range) of LVEF was 44% (42-47%). Six hundred and sixty-one (63.8%) were treated with β-blocker. Patients using β-blocker were younger with better cardiac function, and more likely to use renin-angiotensin system inhibitor and mineralocorticoid receptor antagonist. During the 1-year follow-up, death occurred in 84 (12.7%) treated and 85 (22.7%) untreated patients (P < 0.0001); all-cause hospitalization occurred in 298 (45.1%) treated and 188 (50.3%) untreated patients (P = 0.04). After IPTW-weighted adjustment, β-blocker use was significantly associated with lower risk of all-cause death [hazard ratio (HR): 0.70; 95% confidence interval (CI): 0.51-0.96, P = 0.03], but not with lower all-cause hospitalization (HR, 0.92, 95% CI, 0.76-1.10, P = 0.36). Consistency analyses showed consistent favourable effect of β-blocker on all-cause death, but not on all-cause hospitalization.CONCLUSIONS:Among patients with HFmrEF, β-blocker use was associated with lower risk of all-cause death, but not with lower risk of all-cause hospitalization.

Change in Depressive Symptoms During the First Month of Discharge and 1-Year Clinical Outcomes in Patients Hospitalized for Heart Failure.

Background The patterns of depressive symptom change during the first month after discharge, as well as their prognostic implications, and predictors of persistent or new-onset depressive symptoms are not well characterized. Methods and Results We included patients hospitalized for heart failure undergoing Patient Health Questionnaire-2 before discharge and at 1 month after discharge in a multicenter prospective cohort. We characterized 4 patterns of change in depressive symptoms-persistent, new-onset, remitted depressive symptoms, and no depressive symptom-and examined the associations between the 4 patterns and 1-year clinical outcomes. We analyzed the factors associated with persistent or new-onset depressive symptoms. A total of 4130 patients were included. Among 1175 (28.5%) symptomatic patients and 2955 (71.5%) symptom-free patients before discharge, 817 (69.5%) had remission, and 366 (12.2%) had new-onset depressive symptoms, respectively. Compared with no depressive symptom, persistent depressive symptoms were associated with an increased risk of cardiovascular death (hazard ratio [HR], 2.10 [95% CI, 1.59-2.79]) and heart failure rehospitalization (HR, 1.56 [95% CI, 1.30-1.87]); new-onset depressive symptoms were associated with an increased risk of cardiovascular death (HR, 1.78 [95%CI, 1.32-2.40]) and heart failure rehospitalization (HR, 1.54 [95% CI, 1.29-1.83]). Remitted depressive symptoms were associated with a slightly increased risk of cardiovascular death but had no significant association with heart failure rehospitalization. Patients who were female or had poor socioeconomic status, stroke history, renal dysfunction, or poor health status had a higher risk of persistent or new-onset depressive symptoms. Conclusions Sex, socioeconomic status, clinical characteristics, and health status help identify patients with high risks of depressive symptoms at 1 month after discharge. Dynamic capture of depressive symptom change during this period informs long-term risk stratifications and targets patients who require psychological interventions and social support to improve clinical outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier (NCT02878811).

Traditional Chinese Medicine in Treating Hypertension.

Hospital Variation of Spironolactone Use in Patients Hospitalized for Heart Failure in China-The China PEACE Retrospective Heart Failure Study.

Background Although aldosterone antagonists improve outcomes in select individuals with heart failure and reduced ejection fraction, studies in the United States have raised concerns about underuse and overuse. Variations in the prescription of aldosterone antagonist in China are unknown. Methods and Results In the multicenter, hospital-based, retrospective China PEACE (China Patient-Centered Evaluative Assessment of Cardiac Events) study, we identified a nationally representative cohort of admissions for heart failure in a nationally representative sample of Chinese hospitals in 2015. Patients were classified into 1 of 3 groups according to their eligibility for spironolactone-"ideal" (left ventricular ejection fraction <40% and without contraindications), "contraindicated" (a documented contraindication, irrespective of left ventricular ejection fraction), and "uncertain-benefit" (all others). We measured hospital variation of spironolactone prescriptions at discharge in the "ideal" and "contraindicated" group and calculated the median odds ratio (MOR), a measure of institution-level variation for 2 individuals with similar characteristics discharged at 2 randomly selected hospitals. Hospital characteristics associated with spironolactone use were identified using multivariable linear regression model. Among 1222 ideal patients from 97 hospitals, the median rate of spironolactone prescription was 78.6% (interquartile range [IQR], 42.8%-89.6% [range, 0%-100%], MOR, 3.4 [95% CI, 2.7-4.0]) at discharge. Among 900 contraindicated patients from 83 hospitals, the median rate of spironolactone prescription was 30.0% (IQR, 9.1%-50.0% [range, 0%-100%], MOR, 3.1 [95% CI, 2.4-3.9]) at discharge. Hospitals with independent departments of cardiology and located in Eastern China were associated with a 38.0% (95% CI, 18.7-57.3; P<0.001) and a 14.6% (95% CI, 2.3%-26.9%; P=0.020) higher rate of spironolactone use for ideal patients. Conclusions In this national study of hospitals in China, the use of spironolactone among ideal patients and the inappropriate use of spironolactone among patients with contraindications was substantial, with rates that varied markedly by institution. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02877914.

Effects of omecamtiv mecarbil in heart failure with reduced ejection fraction according to blood pressure: the GALACTIC-HF trial.

AIM:Patients with heart failure with reduced ejection fraction and low systolic blood pressure (SBP) have high mortality, hospitalizations, and poorly tolerate evidence-based medical treatment. Omecamtiv mecarbil may be particularly helpful in such patients. This study examined its efficacy and tolerability in patients with SBP ≤100 mmHg enrolled in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF).METHODS AND RESULTS:The GALACTIC-HF enrolled patients with baseline SBP ≥85 mmHg with a primary outcome of time to cardiovascular death or first heart failure event. In this analysis, patients were divided according to their baseline SBP (≤100 vs. >100 mmHg). Among the 8232 analysed patients, 1473 (17.9%) had baseline SBP ≤100 mmHg and 6759 (82.1%) had SBP >100 mmHg. The primary outcome occurred in 715 (48.5%) and 2415 (35.7%) patients with SBP ≤100 and >100 mmHg, respectively. Patients with lower SBP were at higher risk of adverse outcomes. Omecamtiv mecarbil, compared with placebo, appeared to be more effective in reducing the primary composite endpoint in patients with SBP ≤100 mmHg [hazard ratio (HR), 0.81; 95% confidence interval (CI), 0.70-0.94] compared with those with SBP >100 mmHg (HR, 0.95; 95% CI, 0.88-1.03; P-value for interaction = 0.051). In both groups, omecamtiv mecarbil did not change SBP values over time and did not increase the risk of adverse events, when compared with placebo.CONCLUSION:In GALACTIC-HF, risk reduction of heart failure outcomes with omecamtiv mecarbil compared with placebo was large and significant in patients with low SBP. Omecamtiv mecarbil did not affect SBP and was well tolerated independent of SBP values.

Development and validation of a risk prediction model for in-hospital major cardiovascular events in patients hospitalised for acute myocardial infarction.

OBJECTIVES:Patients admitted to hospital with acute myocardial infarction (AMI) have considerable variability in in-hospital risks, resulting in higher demands on healthcare resources. Simple risk-assessment tools are important for the identification of patients with higher risk to inform clinical decisions. However, few risk assessment tools have been built that are suitable for populations with AMI in China. We aim to develop and validate a risk prediction model, and further build a risk scoring system.DESIGN:Data from a nationally representative retrospective study was used to develop the model. Patients from a prospective study and another nationally representative retrospective study were both used for external validation.SETTING:161 nationally representative hospitals, and 53 and 157 other hospitals were involved in the above three studies, respectively.PARTICIPANTS:8010 patients hospitalised for AMI were included as development sample, and 4485 and 11 223 other patients were included as validation samples in their corresponding studies.PRIMARY AND SECONDARY OUTCOME MEASURES:The in-hospital major adverse cardiovascular events (MACE) was defined as death from any cause, recurrent AMI, or ischaemic stroke.RESULTS:The proportion of in-hospital MACE was 11.7%, 8.8% and 11.4% among the development sample and two external-validation samples, respectively. Nine predictors (ie, age, sex, left ventricular ejection fraction, Killip class, systolic blood pressure, creatinine, white blood cell count, heart rate and blood glucose) were independently associated with in-hospital MACE. The model performed well on both discrimination and calibration capability, with areas under the Receiver Operating Characteristic Curve (ROC) curve of 0.85, 0.74 and 0.80, and calibration slopes of 0.98, 0.84 and 0.97 in the development sample and two external validation samples, respectively. A point-based risk scoring system was built with good discrimination and reclassification ability.CONCLUSIONS:A prediction model using readily available clinical parameters was developed and externally validated to estimate risks of in-hospital MACE among patients with AMI, thereby better informing decision-making in improving clinical care.

Association of cumulative health status with subsequent mortality in patients with acute heart failure.

OBJECTIVE:We aim to examine the association between long-term cumulative health status and subsequent mortality among patients with acute heart failure (HF).METHODS:Based on a national prospective cohort study of patients hospitalized for HF, we measured health status by Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 at 4 time points, i.e. admission, 1-,6- and 12-month after discharge. Cumulative health status was interpreted by cumulative KCCQ-12 score and cumulative times of good health status. Outcomes included subsequent all-cause and cardiovascular mortality. Multivariable Cox proportional hazard models were performed to examine the association between cumulative health status and subsequent mortality.RESULTS:Totally, 2328 patients (36.7% women and median age 66 [IQR: 56-75] years) were included, the median follow-up was 4.34 (IQR: 3.93-4.96) years. Compared with Quartile 4, the lowest Quartile 1 had the highest HR for all-cause mortality (2.96; 95% CI: 2.26-3.87), followed by Quartile 2 (1.79; 95% CI: 1.37-2.34) and Quartile 3 (1.62; 95% CI: 1.23-2.12). Patients with 0-time of good health status had the highest risk of all-cause mortality (HR: 2.41, 95% CI: 1.69-3.46) compared with patients with 4-times of good health status. Similar associations persisted for cardiovascular mortality.CONCLUSIONS:A greater burden of cumulative health status indicated worse survival among patients hospitalized for HF. Repeated KCCQ measurements could be helpful to monitor long-term health status and identify patients vulnerable to death. Clinical Trial Registration: www.clinicaltrials.gov (NCT02878811).

Age-Related Trends in the Predictive Value of Carotid Intima-Media Thickness for Cardiovascular Death: A Prospective Population-Based Cohort Study.

Background The age-related trends in the predictive ability of carotid intima-media thickness (CIMT) for cardiovascular risk remain unclear. We aimed to identify the age-related trends in the predictive value of CIMT for cardiovascular death. Methods and Results In a prospective cohort of adults aged 35 to 75 years without history of cardiovascular disease who were enrolled between 2014 and 2020, we measured CIMT at baseline and collected the vital status and cause of death. We divided the study population into 4 age groups (35-44, 45-54, 55-64, and 65-75 years). Competing risk models were fitted to estimate the associations between CIMT and cardiovascular death. The added values of CIMT in prediction were assessed by the differences of the Harrell's concordance index and the net reclassification improvement index. We included 369 478 adults and followed them for a median of 4.7 years. A total of 4723 (1.28%) cardiovascular deaths occurred. After adjusting for the traditional risk factors, the hazard ratios for CIMTmean per SD decreased with age, from 1.27 (95% CI, 1.17-1.37) in the 35 to 44 years age group to 1.14 (95% CI, 1.10-1.19) in the 65 to 75 years age group (P for interaction <0.01). Meanwhile, the net reclassification improvement indexes for CIMTmean were attenuated with age, from 22.60% (95% CI, 15.56%-29.64%) in the 35 to 44 years age group to 7.00% (95% CI, -6.82% to 20.83%) in the 65 to 75 years age group. Similar results were found for maximum CIMT in all age groups. Conclusions CIMT may improve cardiovascular risk prediction in the young and middle-aged populations, rather than those aged ≥55 years.

A novel polygenic risk score improves prognostic prediction of heart failure with preserved ejection fraction in the Chinese Han population.

AIMS:Mortality risk assessment in patients with heart failure (HF) with preserved ejection fraction (HFpEF) presents a major challenge. We sought to construct a polygenic risk score (PRS) to accurately predict the mortality risk of HFpEF.METHODS AND RESULTS:We first carried out a microarray analysis of 50 HFpEF patients who died and 50 matched controls who survived during 1-year follow-up for candidate gene selection. The HF-PRS was developed using the independent common (MAF > 0.05) genetic variants that showed significant associations with 1-year all-cause death (P < 0.05) in 1442 HFpEF patients. Internal cross-validation and subgroup analyses were performed to evaluate the discrimination ability of the HF-PRS. In 209 genes identified by microarray analysis, 69 independent variants (r < 0.1) were selected to develop the HF-PRS model. This model yielded the best discrimination capability for 1-year all-cause mortality with an area under the curve (AUC) of 0.852 (95% CI 0.827-0.877), which outperformed the clinical risk score consisting of 10 significant traditional risk factors for 1-year all-cause mortality (AUC 0.696, 95% CI 0.658-0.734, P = 4 × 10-11), with net reclassification improvement (NRI) of 0.741 (95% CI 0.605-0.877; P < 0.001) and integrated discrimination improvement (IDI) of 0.181 (95% CI 0.145-0.218; P < 0.001). Individuals in the medium and the highest tertile of the HF-PRS had nearly a five-fold (HR = 5.3, 95% CI 2.4-11.9; P = 5.6 × 10-5) and 30-fold (HR = 29.8, 95% CI 14.0-63.5; P = 1.4 × 10-18) increased risk of mortality compared to those in the lowest tertile, respectively. The discrimination ability of the HF-PRS was excellent in cross validation and throughout the subgroups regardless of comorbidities, gender, and patients with or without a history of heart failure.CONCLUSION:The HF-PRS comprising 69 genetic variants provided an improvement of prognostic power over the contemporary risk scores and NT-proBNP in HFpEF patients.

Individual Trajectories of Health Status During the First Year of Discharge From Hospitalization for Heart Failure and Their Associations With Death in the Following Years.

Background Improving health status is one of the major goals in the management of heart failure (HF). However, little is known about the long-term individual trajectories of health status in patients with acute HF after discharge. Methods and Results We enrolled 2328 patients hospitalized for HF from 51 hospitals prospectively and measured their health status via the Kansas City Cardiomyopathy Questionnaire-12 at admission and 1, 6, and 12 months after discharge, respectively. The median age of the patients included was 66 years, and 63.3% were men. Six patterns of Kansas City Cardiomyopathy Questionnaire-12 trajectories were identified by a latent class trajectory model: persistently good (34.0%), rapidly improving (35.5%), slowly improving (10.4%), moderately regressing (7.4%), severely regressing (7.5%), and persistently poor (5.3%). Advanced age, decompensated chronic HF, HF with mildly reduced ejection fraction, HF with preserved ejection fraction, depression symptoms, cognitive impairment, and each additional HF rehospitalization within 1 year of discharge were associated with unfavorable health status (moderately regressing, severely regressing, and persistently poor) (P<0.05). Compared with the pattern of persistently good, slowly improving (hazard ratio [HR], 1.50 [95% CI, 1.06-2.12]), moderately regressing (HR, 1.92 [1.43-2.58]), severely regressing (HR, 2.26 [1.54-3.31]), and persistently poor (HR, 2.34 [1.55-3.53]) were associated with increased risks of all-cause death. Conclusions One-fifth of 1-year survivors after hospitalization for HF experienced unfavorable health status trajectories and had a substantially increased risk of death during the following years. Our findings help inform the understanding of disease progression from a patient perception perspective and its relationship with long-term survival. Registration URL: https://www.clinicaltrials.gov; unique identifier: NCT02878811.

β-blocker and 1-year outcomes among patients hospitalized for heart failure with mid-range ejection fraction.

AIMS:The beneficial effect of β-blocker on heart failure with reduced ejection fraction is well established. However, its effect on the 1-year outcome of heart failure with mid-range ejection fraction (HFmrEF) remains unclear.METHODS AND RESULTS:We analysed the data of the patients with left ventricular ejection fraction (LVEF) between 40% and 49% in China Patient-centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (China PEACE 5p-HF Study), in which patients hospitalized for heart failure from 52 Chinese hospitals were recruited from 2016 to 2018. Two primary outcomes were all-cause death and all-cause hospitalization. The associations between β-blocker use at discharge and outcomes were assessed by inverse probability of treatment weighting (IPTW)-weighted Cox regression analyses. To assess consistency, IPTW adjusting medications analyses, multivariable analyses and dose-effect analyses were performed. A total of 1035 HFmrEF patients were included in the analysis. The mean age was 65.5 ± 12.7 years and 377 (36.4%) were female. The median (interquartile range) of LVEF was 44% (42-47%). Six hundred and sixty-one (63.8%) were treated with β-blocker. Patients using β-blocker were younger with better cardiac function, and more likely to use renin-angiotensin system inhibitor and mineralocorticoid receptor antagonist. During the 1-year follow-up, death occurred in 84 (12.7%) treated and 85 (22.7%) untreated patients (P < 0.0001); all-cause hospitalization occurred in 298 (45.1%) treated and 188 (50.3%) untreated patients (P = 0.04). After IPTW-weighted adjustment, β-blocker use was significantly associated with lower risk of all-cause death [hazard ratio (HR): 0.70; 95% confidence interval (CI): 0.51-0.96, P = 0.03], but not with lower all-cause hospitalization (HR, 0.92, 95% CI, 0.76-1.10, P = 0.36). Consistency analyses showed consistent favourable effect of β-blocker on all-cause death, but not on all-cause hospitalization.CONCLUSIONS:Among patients with HFmrEF, β-blocker use was associated with lower risk of all-cause death, but not with lower risk of all-cause hospitalization.

Change in Depressive Symptoms During the First Month of Discharge and 1-Year Clinical Outcomes in Patients Hospitalized for Heart Failure.

Background The patterns of depressive symptom change during the first month after discharge, as well as their prognostic implications, and predictors of persistent or new-onset depressive symptoms are not well characterized. Methods and Results We included patients hospitalized for heart failure undergoing Patient Health Questionnaire-2 before discharge and at 1 month after discharge in a multicenter prospective cohort. We characterized 4 patterns of change in depressive symptoms-persistent, new-onset, remitted depressive symptoms, and no depressive symptom-and examined the associations between the 4 patterns and 1-year clinical outcomes. We analyzed the factors associated with persistent or new-onset depressive symptoms. A total of 4130 patients were included. Among 1175 (28.5%) symptomatic patients and 2955 (71.5%) symptom-free patients before discharge, 817 (69.5%) had remission, and 366 (12.2%) had new-onset depressive symptoms, respectively. Compared with no depressive symptom, persistent depressive symptoms were associated with an increased risk of cardiovascular death (hazard ratio [HR], 2.10 [95% CI, 1.59-2.79]) and heart failure rehospitalization (HR, 1.56 [95% CI, 1.30-1.87]); new-onset depressive symptoms were associated with an increased risk of cardiovascular death (HR, 1.78 [95%CI, 1.32-2.40]) and heart failure rehospitalization (HR, 1.54 [95% CI, 1.29-1.83]). Remitted depressive symptoms were associated with a slightly increased risk of cardiovascular death but had no significant association with heart failure rehospitalization. Patients who were female or had poor socioeconomic status, stroke history, renal dysfunction, or poor health status had a higher risk of persistent or new-onset depressive symptoms. Conclusions Sex, socioeconomic status, clinical characteristics, and health status help identify patients with high risks of depressive symptoms at 1 month after discharge. Dynamic capture of depressive symptom change during this period informs long-term risk stratifications and targets patients who require psychological interventions and social support to improve clinical outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier (NCT02878811).

Traditional Chinese Medicine in Treating Hypertension.

Hospital Variation of Spironolactone Use in Patients Hospitalized for Heart Failure in China-The China PEACE Retrospective Heart Failure Study.

Background Although aldosterone antagonists improve outcomes in select individuals with heart failure and reduced ejection fraction, studies in the United States have raised concerns about underuse and overuse. Variations in the prescription of aldosterone antagonist in China are unknown. Methods and Results In the multicenter, hospital-based, retrospective China PEACE (China Patient-Centered Evaluative Assessment of Cardiac Events) study, we identified a nationally representative cohort of admissions for heart failure in a nationally representative sample of Chinese hospitals in 2015. Patients were classified into 1 of 3 groups according to their eligibility for spironolactone-"ideal" (left ventricular ejection fraction <40% and without contraindications), "contraindicated" (a documented contraindication, irrespective of left ventricular ejection fraction), and "uncertain-benefit" (all others). We measured hospital variation of spironolactone prescriptions at discharge in the "ideal" and "contraindicated" group and calculated the median odds ratio (MOR), a measure of institution-level variation for 2 individuals with similar characteristics discharged at 2 randomly selected hospitals. Hospital characteristics associated with spironolactone use were identified using multivariable linear regression model. Among 1222 ideal patients from 97 hospitals, the median rate of spironolactone prescription was 78.6% (interquartile range [IQR], 42.8%-89.6% [range, 0%-100%], MOR, 3.4 [95% CI, 2.7-4.0]) at discharge. Among 900 contraindicated patients from 83 hospitals, the median rate of spironolactone prescription was 30.0% (IQR, 9.1%-50.0% [range, 0%-100%], MOR, 3.1 [95% CI, 2.4-3.9]) at discharge. Hospitals with independent departments of cardiology and located in Eastern China were associated with a 38.0% (95% CI, 18.7-57.3; P<0.001) and a 14.6% (95% CI, 2.3%-26.9%; P=0.020) higher rate of spironolactone use for ideal patients. Conclusions In this national study of hospitals in China, the use of spironolactone among ideal patients and the inappropriate use of spironolactone among patients with contraindications was substantial, with rates that varied markedly by institution. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02877914.

Effects of omecamtiv mecarbil in heart failure with reduced ejection fraction according to blood pressure: the GALACTIC-HF trial.

AIM:Patients with heart failure with reduced ejection fraction and low systolic blood pressure (SBP) have high mortality, hospitalizations, and poorly tolerate evidence-based medical treatment. Omecamtiv mecarbil may be particularly helpful in such patients. This study examined its efficacy and tolerability in patients with SBP ≤100 mmHg enrolled in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF).METHODS AND RESULTS:The GALACTIC-HF enrolled patients with baseline SBP ≥85 mmHg with a primary outcome of time to cardiovascular death or first heart failure event. In this analysis, patients were divided according to their baseline SBP (≤100 vs. >100 mmHg). Among the 8232 analysed patients, 1473 (17.9%) had baseline SBP ≤100 mmHg and 6759 (82.1%) had SBP >100 mmHg. The primary outcome occurred in 715 (48.5%) and 2415 (35.7%) patients with SBP ≤100 and >100 mmHg, respectively. Patients with lower SBP were at higher risk of adverse outcomes. Omecamtiv mecarbil, compared with placebo, appeared to be more effective in reducing the primary composite endpoint in patients with SBP ≤100 mmHg [hazard ratio (HR), 0.81; 95% confidence interval (CI), 0.70-0.94] compared with those with SBP >100 mmHg (HR, 0.95; 95% CI, 0.88-1.03; P-value for interaction = 0.051). In both groups, omecamtiv mecarbil did not change SBP values over time and did not increase the risk of adverse events, when compared with placebo.CONCLUSION:In GALACTIC-HF, risk reduction of heart failure outcomes with omecamtiv mecarbil compared with placebo was large and significant in patients with low SBP. Omecamtiv mecarbil did not affect SBP and was well tolerated independent of SBP values.

Development and validation of a risk prediction model for in-hospital major cardiovascular events in patients hospitalised for acute myocardial infarction.

OBJECTIVES:Patients admitted to hospital with acute myocardial infarction (AMI) have considerable variability in in-hospital risks, resulting in higher demands on healthcare resources. Simple risk-assessment tools are important for the identification of patients with higher risk to inform clinical decisions. However, few risk assessment tools have been built that are suitable for populations with AMI in China. We aim to develop and validate a risk prediction model, and further build a risk scoring system.DESIGN:Data from a nationally representative retrospective study was used to develop the model. Patients from a prospective study and another nationally representative retrospective study were both used for external validation.SETTING:161 nationally representative hospitals, and 53 and 157 other hospitals were involved in the above three studies, respectively.PARTICIPANTS:8010 patients hospitalised for AMI were included as development sample, and 4485 and 11 223 other patients were included as validation samples in their corresponding studies.PRIMARY AND SECONDARY OUTCOME MEASURES:The in-hospital major adverse cardiovascular events (MACE) was defined as death from any cause, recurrent AMI, or ischaemic stroke.RESULTS:The proportion of in-hospital MACE was 11.7%, 8.8% and 11.4% among the development sample and two external-validation samples, respectively. Nine predictors (ie, age, sex, left ventricular ejection fraction, Killip class, systolic blood pressure, creatinine, white blood cell count, heart rate and blood glucose) were independently associated with in-hospital MACE. The model performed well on both discrimination and calibration capability, with areas under the Receiver Operating Characteristic Curve (ROC) curve of 0.85, 0.74 and 0.80, and calibration slopes of 0.98, 0.84 and 0.97 in the development sample and two external validation samples, respectively. A point-based risk scoring system was built with good discrimination and reclassification ability.CONCLUSIONS:A prediction model using readily available clinical parameters was developed and externally validated to estimate risks of in-hospital MACE among patients with AMI, thereby better informing decision-making in improving clinical care.