Sex differences in the associations between relative fat mass and all-cause and cardiovascular mortality: A population-based prospective cohort study.

BACKGROUND AND AIMS: The novel sex-specific anthropometric equation relative fat mass (RFM) is a new estimator of whole-body fat %. The study aimed to investigate the predictive role of RFM in cardiometabolic abnormalities, cardiovascular disease (CVD), all-cause and cardiovascular mortality, and explored potential sex differences. METHODS AND RESULTS: The study analyzed data from 26,754 adults in NHANES 1999-2010, with a median follow-up of 13.8 years. The correlation between RFM and body composition as well as fat distribution assessed by dual-energy X-ray absorptiometry was investigated. Weighted multivariable generalized linear models, Cox proportional hazards models and restricted cubic spline were applied to investigate the predictive role of RFM in metabolic markers, cardiovascular risk factors, CVD, all-cause and cardiovascular mortality. RFM exhibited a robust correlation with both whole-body fat % and trunk fat %. Higher RFM exhibited a stronger association with impaired glucose homeostasis, serum lipids, the incidence of hypertension, and coronary heart disease in males, while a stronger association with C-reactive protein in females. A U-shaped association between RFM and all-cause mortality was observed only in males. The hazard ratio (HR) of all-cause and cardiovascular mortality in males increased rapidly when RFM exceeded 30. However, in females, the HR of all-cause and cardiovascular mortality fluctuated until RFM exceeded 45, after which it increased rapidly. CONCLUSION: RFM was a sex-specific estimator for both general and central obesity, sex-specific differences in predicting cardiometabolic abnormalities and adverse events using RFM might be partially attributed to differences in body composition and fat distribution between sexes.

Prognostic Value of QRS Duration in Patients with Dilated Cardiomyopathy According to Left Ventricular Ejection Fraction.

Background: The prognostic significance of QRS duration (QRSd) in patients with dilated cardiomyopathy (DCM) and a left ventricular ejection fraction (LVEF) between 30% and 50% is unclear, resulting in questions regarding eligibility for cardiac resynchronisation therapy. This study aimed to explore the prognostic role of QRSd in patients with DCM and a LVEF 30-50% or LVEF < 30. Methods: Patients hospitalised at Fuwai hospital with DCM who had a LVEF ≤ 50% were prospectively included. The primary outcomes were a composite of death, heart transplantation, and rehospitalisation for worsening heart failure. Results: Among the 633 patients included, 302 (47.7%) had a LVEF of 30-50%. The multivariable hazard ratio (HR) for QRSd ≥ 120 ms was 1.65 (95% confidence interval [CI] 1.29-2.11, p < 0.001) for overall DCM patients, 2.8 (95% CI 1.82-4.30, p < 0.001) for patients with LVEF 30-50%, and 1.41 (95% CI 1.02-1.94, p = 0.036) for patients with LVEF < 30%. QRSd ≥ 120 ms tended to be more strongly associated with outcome in patients with LVEF 30-50% than in those with LVEF < 30% despite the non-significant interaction (p = 0.067). DCM patients with QRSd ≥ 120 ms and LVEF 30-50% did not experience a significantly better outcome than those with LVEF < 30% and QRSd < 120 ms after propensity-score matching (HR 0.91, 95% CI 0.61-1.36, p = 0.645). Conclusions: QRSd independently predicts prognosis in DCM patients irrespective of LVEF and identifies a group of high-risk patients who may benefit from device implantation despite the absence of severely reduced LVEF.

Serum Potassium Levels and Mortality in Hospitalized Heart Failure Patients.

Background: To assess the link between serum potassium ( K + ) and all-cause mortality in hospitalized heart failure (HF) patients. Methods: Hospitalized HF patients (n = 3114) were analyzed at the Fuwai Hospital Heart Failure Center. Before discharge, HF patients were divided into four groups according to the K + level quartiles: K + ≤ 3.96 mmol/L (Q1), 3.96 < K + ≤ 4.22 mmol/L (Q2), 4.22 < K + ≤ 4.52 mmol/L (Q3), and K + > 4.52 mmol/L (Q4). At 90 days, 2 years, and maximal follow-up, all-cause mortality was the primary outcome. Results: Patients with HF in the Q4 group had worse cardiac function, higher N-terminal pro-B-type natriuretic peptide levels, lower left ventricular ejection fractions and lower estimated glomerular filtration rates than patients in the Q2 group. In the multivariate-adjusted Cox analysis, the mortality assessed during the 90-day, 2-year, and maximal follow-up examinations increased in the Q4 group of HF patients but not in the Q1 and Q3 groups. The Q4 group had a 28% (hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 1.09-1.49, p = 0.002) higher risk of all-cause mortality at maximum follow-up. Hypokalemia and hyperkalemia were linked to increased HF mortality risk at the 90-day, 2-year, and maximal follow-up periods. Conclusions: Serum K + levels had a J-shaped association with all-cause mortality in HF patients. Both hypokalemia and a K + level of > 4.52 mmol/L were associated with increased all-cause mortality in the short term and long term, suggesting a narrow target K + range in HF patients. Clinical Trial Registration: Unique Identifier: NCT02664818; URL: clinicaltrials.gov.

Prevalence and prognostic importance of malnutrition, as assessed by four different scoring systems, in elder patients with heart failure.

BACKGROUND AND AIMS: The lack of standard diagnostic criteria in elder patients with heart failure (HF) makes it challenging to diagnose and manage malnutrition. We aimed to explore the prevalence of malnutrition, its associations and prognostic significance among elder patients with HF using four different nutritional scoring systems. METHODS AND RESULTS: Consecutively presenting patients aged ⩾65 years, diagnosed with HF, and admitted to HF care unit of Fuwai Hospital CAMS&PUMC (Beijing, China) were assessed for nutritional indices. In total, 1371 patients were enrolled (59.4% men; mean age 72 years; median NT-proBNP 2343 ng/L). Using scores for the prognostic nutritional index (PNI) ≤38, controlling nutritional status (CONUT) score >4, geriatric nutritional risk index (GNRI) ≤91, and triglycerides, total cholesterol, and body weight index (TCBI) ≤1109, 10.4%, 18.3%, 9.2%, and 50.0% of patients had moderate or severe malnutrition, respectively. There was a strong association between worse scores and lower body mass index, more severe symptoms, atrial fibrillation, and anemia. The mortality over a median follow-up of 962 days (interquartile range (IQR): 903-1029 days) was 28.3% (n = 388). For those with moderate or severe condition, 1-year mortality was 35.2% for PNI, 28.3% for CONUT, 28.0% for GNRI, and 19.1% for TCBI. Malnutrition, defined by any of the included indices, showed added prognostic value when incorporated into a model and included preexisting prognostic factors (C-statistic: 0.711). However, defining malnutrition by the CONUT score yielded the most significant improvement in the prognostic predictive value (C-statistic: 0.721; p < 0.001). CONCLUSION: Malnutrition is prevalent among elder patients with HF and confers increased mortality risk. Among the nutritional scores studied, the CONUT score was most effective in predicting the mortality risk. CLINICAL TRIAL REGISTRATION: URL: ClinicalTrials.gov; Unique Identifier: NCT02664818.

Prognostic utility of the prognostic nutritional index combined with serum sodium level in patients with heart failure.

BACKGROUND AND AIMS: Both malnutrition and hyponatremia (serum sodium <135 mmol/L) can be induced by the impaired absorption function of the edematous intestinal wall caused by heart failure (HF) and are prognostic factors of mortality in HF. However, little is known about the interrelationship of nutritional status and hyponatremia in mortality risk prediction in HF. METHODS AND RESULTS: This study enrolled 2882 HF patients admitted to the HF care unit of Fuwai Hospital, Beijing, China from 2008 to 2018; 71.3% were male and the mean age was 56.64 ± 15.96 years. Nutritional status was assessed by prognostic nutritional index (PNI), calculated as serum albumin (g/L) + 5 × total lymphocyte count (109/L). Lower PNI indicates worse nutritional status. Patients were divided into 8 groups based on baseline PNI quartiles (Q1: <43.6, Q2: 43.6-48.55, Q3: 48.55-63.25, Q4: >63.25) and sodium level (normal sodium and hyponatremia). After adjustment, patients in the PNI Q1 associated with hyponatremia had a 2.12-fold higher risk of all-cause death (95% confidence interval [CI]: 1.67-2.70) compared with those in the PNI Q4 with normal sodium. A refinement in risk prediction was observed after adding PNI quartile and serum sodium category to the original model (ΔC-statistic = 0.018, 95% CI: 0.007-0.025; net re-classification index = 0.459, 95% CI: 0.371-0.548; integrated discrimination improvement = 0.025, 95% CI: 0.018-0.032). CONCLUSION: HF patients with both the lowest PNI quartile and hyponatremia are at higher risk of all-cause mortality. The combination of PNI and serum sodium level enhanced the predictive value for all-cause mortality in hospitalized HF patients. CLINICAL TRIAL REGISTRATION: URL: ClinicalTrials.gov; Unique Identifier: NCT02664818.

Association of Sex With Cardiovascular Outcomes in Heart Failure Patients With Obstructive or Central Sleep Apnea.

BACKGROUND: This study investigated the association of sex with cardiovascular outcomes in a prospective cohort of patients with heart failure (HF) with obstructive sleep apnea or central sleep apnea. METHODS AND RESULTS: Patients were screened for sleep apnea on admission using multichannel cardiopulmonary monitoring from May 2015 to July 2018. The primary outcome was a composite of cardiovascular death or unplanned hospitalization for worsening HF. Ultimately, 453 patients with HF with obstructive sleep apnea or central sleep apnea were included; 71 (15.7%) and 382 (84.3%) were women and men, respectively. During a median follow-up of 2.33 years, 248 (54.7%) patients experienced the primary outcome. In the overall population, after adjusting for potential confounders, women had an increased risk of the primary outcome (66.2% versus 52.6%; hazard ratio [HR], 1.47 [95% CI, 1.05-2.04]; P=0.024) and HF rehospitalization (62.0% versus 46.6%; HR, 1.55 [95% CI, 1.10-2.19]; P=0.013) compared with men but a comparable risk of cardiovascular death (21.1% versus 23.3%; HR, 0.78 [95% CI, 0.44-1.37]; P=0.383). Likewise, in patients with HF with obstructive sleep apnea, women had a higher risk of the primary outcome (81.8% versus 46.3%, HR, 2.37 [95% CI, 1.28-4.38]; P=0.006) and HF rehospitalization (81.8% versus 44.7%, HR, 2.46 [95% CI, 1.32-4.56], P=0.004). However, in patients with HF with central sleep apnea, there was no statistically significant difference between women and men. CONCLUSIONS: In hospitalized patients with HF, female sex was associated with an increased risk of the primary outcome and HF rehospitalization, especially in those with obstructive sleep apnea. Screening for sleep apnea should be emphasized to improve the prognosis. REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02664818.

Predictive value of remnant cholesterol level for all-cause mortality in heart failure patients.

Background: Lower cholesterol levels are associated with increased mortality in heart failure (HF) patients. Remnant cholesterol corresponds to all cholesterol not found in high-density lipoprotein (HDL) and low-density lipoprotein (LDL). The prognostic role of remnant cholesterol in HF remains unknown. Objective: To reveal the relationship between the baseline remnant cholesterol level and all-cause mortality in HF patients. Methods: This study enrolled 2,823 patients hospitalized for HF. Kaplan-Meier analysis, Cox regression, C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the prognostic value of remnant cholesterol for all-cause mortality in HF. Results: The mortality rate was lowest in the fourth quartile of remnant cholesterol, which had an adjusted hazard ratio (HR) for death of 0.56 [HR: 0.39, 95% confidence interval (CI): 0.46-0.68, p < 0.001] relative to the first quartile. After adjustment, a one-unit increase in the level of remnant cholesterol was associated with a 41% decrease in the risk of all-cause mortality (HR: 0.59, 95% CI: 0.47-0.73, p < 0.001). A refinement in risk prediction was observed after adding remnant cholesterol quartile to the original model (ΔC-statistic = 0.010, 95% CI: 0.003-0.017; NRI = 0.036, 95% CI: 0.003-0.070; IDI = 0.025, 95% CI: 0.018-0.033; all p < 0.05). Conclusion: Low remnant cholesterol levels are associated with increased all-cause mortality in HF patients. The addition of the remnant cholesterol quartile improved the predictive value over traditional risk factors. Clinical Trial Registration: ClinicalTrials.gov, Unique Identifier: NCT02664818.

Incorporating inflammatory biomarkers into a prognostic risk score in patients with non-ischemic heart failure: a machine learning approach.

Objectives: Inflammation is involved in the mechanisms of non-ischemic heart failure (NIHF). We aimed to investigate the prognostic value of 21 inflammatory biomarkers and construct a biomarker risk score to improve risk prediction for patients with NIHF. Methods: Patients diagnosed with NIHF without infection during hospitalization were included. The primary outcome was defined as all-cause mortality and heart transplantations. We used elastic net Cox regression with cross-validation to select inflammatory biomarkers and construct the best biomarker risk score model. Discrimination, calibration, and reclassification were evaluated to assess the predictive value of the biomarker risk score. Results: Of 1,250 patients included (median age, 53 years, 31.9% women), 436 patients (34.9%) experienced the primary outcome during a median of 2.8 years of follow-up. The final biomarker risk score included high-sensitivity C-reactive protein-to-albumin ratio (CAR) and red blood cell distribution width-standard deviation (RDW-SD), both of which were 100% selected in 1,000 times cross-validation folds. Incorporating the biomarker risk score into the best basic model improved the discrimination (ΔC-index = 0.012, 95% CI 0.003-0.018) and reclassification (IDI, 2.3%, 95% CI 0.7%-4.9%; NRI, 17.3% 95% CI 6.4%-32.3%) in risk identification. In the cross-validation sets, the mean time-dependent AUC ranged from 0.670 to 0.724 for the biomarker risk score and 0.705 to 0.804 for the basic model with a biomarker risk score, from 1 to 8 years. In multivariable Cox regression, the biomarker risk score was independently associated with the outcome in patients with NIHF (HR 1.76, 95% CI 1.49-2.08, p < 0.001, per 1 score increase). Conclusions: An inflammatory biomarker-derived risk score significantly improved prognosis prediction and risk stratification, providing potential individualized therapeutic targets for NIHF patients.

Association of hypoxic burden metrics with cardiovascular outcomes in heart failure and sleep-disordered breathing.

AIMS: Heart failure (HF) and sleep-disordered breathing (SDB) frequently coexist. We aimed to compare the prognostic value of different nocturnal hypoxic burden metrics in hospitalized HF patients. METHODS AND RESULTS: HF patients underwent polygraphy screening for SDB in this prospective cohort. Hypoxic burden metrics assessed using pulse oximetry included time < 90% oxygen saturation (T90), proportion of total recording time < 90% oxygen saturation (TRT90), oxygen desaturation index (ODI), and mean oxygen saturation (meanSO2 ). The prespecified endpoints were the composite of cardiovascular death or admission for worsening HF. This study included 764 hospitalized HF patients, 16.5% and 36.6% of whom had obstructive and central sleep apnoea, respectively. With a median follow-up time of 2.2 years, endpoint events occurred in 410 (53.7%) patients. In univariate and multivariate analyses, T90, TRT90, and meanSO2 were substantially associated with the composite outcome, whereas ODI was not. After multivariate Cox model adjustment, patients with 5.0 ≤ T90 ≤ 52.0 min [hazard ratio (HR) 1.32, 95% confidence interval (CI): 1.02-1.71, P = 0.034] or T90 > 52.0 min (HR 1.56, 95% CI: 1.21-2.02, P = 0.001) had a greater risk of the composite outcome than those with T90 < 5.0 min. The TRT90 and T90 results were similar. Compared with meanSO2  > 95%, meanSO2  < 93% (HR 1.47, 95% CI: 1.16-1.88, P = 0.002) was correlated with adverse outcomes. CONCLUSIONS: The hypoxic burden metrics T90, TRT90, and meanSO2 , but not ODI, were independent predictors of cardiovascular death or readmission for worsening HF. Indicators of duration and severity, not just the frequency of nocturnal hypoxaemia, should be valued and considered for intervention to improve outcomes in HF patients.

Machine Learning for Mortality Prediction in Patients With Heart Failure With Mildly Reduced Ejection Fraction.

Background Machine-learning-based prediction models (MLBPMs) have shown satisfactory performance in predicting clinical outcomes in patients with heart failure with reduced and preserved ejection fraction. However, their usefulness has yet to be fully elucidated in patients with heart failure with mildly reduced ejection fraction. This pilot study aims to evaluate the prediction performance of MLBPMs in a heart failure with mildly reduced ejection fraction cohort with long-term follow-up data. Methods and Results A total of 424 patients with heart failure with mildly reduced ejection fraction were enrolled in our study. The primary outcome was all-cause mortality. Two feature selection strategies were introduced for MLBPM development. The "All-in" (67 features) strategy was based on feature correlation, multicollinearity, and clinical significance. The other strategy was the CoxBoost algorithm with 10-fold cross-validation (17 features), which was based on the selection result of the "All-in" strategy. Six MLBPMs with 5-fold cross-validation based on the "All-in" and the CoxBoost algorithm with 10-fold cross-validation strategy were developed by the eXtreme Gradient Boosting, random forest, and support vector machine algorithms. The logistic regression model with 14 benchmark predictors was used as a reference model. During a median follow-up of 1008 (750, 1937) days, 121 patients met the primary outcome. Overall, MLBPMs outperformed the logistic model. The "All-in" eXtreme Gradient Boosting model had the best performance, with an accuracy of 85.4% and a precision of 70.3%. The area under the receiver-operating characteristic curve was 0.916 (95% CI, 0.887-0.945). The Brier score was 0.12. Conclusions The MLBPMs could significantly improve outcome prediction in patients with heart failure with mildly reduced ejection fraction, which would further optimize the management of these patients.

Big Endothelin-1 as a Predictor of Reverse Remodeling and Prognosis in Dilated Cardiomyopathy.

This study aimed to investigate the predictive value of Big endothelin-1(ET-1) for left ventricular reverse remodeling (LVRR) and prognosis in patients with dilated cardiomyopathy (DCM). Patients with DCM and a left ventricular ejection fraction (LVEF) ≤ 50% from 2008 to 2017 were included. LVRR was defined as the LVEF increased by at least 10% or follow-up LVEF increased to at least 50% with a minimum improvement of 5%; meanwhile, the index of left ventricular end-diastolic diameter (LVEDDi) decreased by at least 10% or LVEDDi decreased to ≤33 mm/m2. The composite outcome for prognostic analysis consisted of death and heart transplantations. Of the 375 patients included (median age 47 years, 21.1% female), 135 patients (36%) had LVRR after a median of 14 months of treatment. An independent association was found between Big ET-1 at baseline and LVRR in the multivariate model (OR 0.70, 95% CI 0.55-0.89, p = 0.003, per log increase). Big ET-1, body mass index, systolic blood pressure, diagnosis of type 2 diabetes mellitus (T2DM) and treatment with ACEI/ARB were significant predictors for LVRR after stepwise selection. Adding Big ET-1 to the model improved the discrimination (∆AUC = 0.037, p = 0.042 and reclassification (IDI, 3.29%; p = 0.002; NRI, 35%; p = 0.002) for identifying patients with LVRR. During a median follow-up of 39 (27-68) months, Big ET-1 was also independently associated with the composite outcome of death and heart transplantations (HR 1.45, 95% CI 1.13-1.85, p = 0.003, per log increase). In conclusion, Big ET-1 was an independent predictor for LVRR and had prognostic implications, which might help to improve the risk stratification of patients with DCM.

Hyponatremia and lower normal serum sodium levels are associated with an increased risk of all-cause death in heart failure patients.

AIM: To explore the relationship between the serum sodium level on admission and all-cause mortality in HF patients. DESIGN: A single-center retrospective cohort study. METHODS: Patients hospitalized with HF at the Heart Failure Center, Fuwai Hospital, from November 2008 to November 2018 were enrolled. RESULTS: A total of 3649 patients were included, and the mean sodium level was 137.19 ± 4.36 mmol/L, with a range from 115.6 to 160.9 mmol/L. During a median follow-up of 1101 days, mortality occurred in 1413 (38.7%) hospital survivors. After adjustment for age, sex, and other potential confounders, patients with sodium levels <135 mmol/L (hazard ratio [HR]: 1.67; 95% confidence interval [CI]: 1.29-2.16) and 135-137 mmol/L (HR: 1.34; 95% CI: 1.01-1.78) had an increased risk of all-cause mortality compared to those with sodium levels of 139-141 mmol/L.

Afterload-related cardiac performance is a powerful hemodynamic predictor of mortality in patients with chronic heart failure.

Background: Afterload-related cardiac performance (ACP), a diagnostic parameter for septic cardiomyopathy, integrates both cardiac performance and vascular effects and could predict prognosis in septic shock. Objectives: We hypothesized that ACP would also correlate with clinical outcomes in patients with chronic heart failure (HF). Design: A retrospective study. Methods: We retrospectively studied consecutive patients with chronic HF who underwent right heart catheterization and established an expected cardiac output-systemic vascular resistance (CO-SVR) curve model in chronic HF for the first time. ACP was calculated as COmeasured/COpredicted × 100%. ACP > 80%, 60% < ACP ⩽ 80%, and ACP ⩽ 60% represented less impaired, mildly impaired, and severely impaired cardiovascular function, respectively. The primary outcome was all-cause mortality, and the secondary outcome was event-free survival. Results: A total of 965 individual measurements from 290 eligible patients were used to establish the expected CO-SVR curve model (COpredicted = 53.468 × SVR -0.799). Patients with ACP ⩽ 60% had higher serum NT-proBNP levels (P < 0.001), lower left ventricular ejection fraction (P = 0.001), and required dopamine more frequently (P < 0.001). Complete follow-up data were available in 263 of 290 patients (90.7%). After multivariate adjustment, ACP remained associated with both primary outcome (hazard ratio (HR) 0.956, 95% confidence interval (CI) 0.927-0.987) and secondary outcome (HR 0.977, 95% CI 0.963-0.992). Patients with ACP ⩽ 60% had the worst prognosis (all P < 0.001). ACP was significantly more discriminating (area under the curve of 0.770) than other conventional hemodynamic parameters in predicting mortality (Delong test, all P < 0.05). Conclusion: ACP is a powerful independent hemodynamic predictor of mortality in patients with chronic HF. ACP and the novel CO-SVR two-dimensional graph could be useful in assessing cardiovascular function and making clinical decisions. Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02664818.

Improved Prognostic Performance of Right Atrial Pressure-Corrected Cardiac Power Output in Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction.

Cardiac power output (CPO) is a powerful predictor of adverse outcomes in heart failure (HF). However, the original formula of CPO included the difference between mean arterial pressure and right atrial pressure (RAP). The prognostic performance of RAP-corrected CPO (CPORAP) remains unknown in heart failure with preserved ejection fraction (HFpEF). We studied 101 HF patients with a left ventricular ejection fraction > 40% who had pulmonary hypertension due to left heart disease. CPORAP was significantly more discriminating than CPO in predicting outcomes (Delong test, P = 0.004). Twenty-five (24.8%) patients presented with dis-concordantly high CPORAP and low CPO when stratified by the identified CPORAP threshold of 0.547 W and the accepted CPO threshold of 0.803 W. These patients had the lowest RAP, and their cumulative incidence was comparable with those with concordantly high CPO and CPORAP (P = 0.313). CPORAP might identify patients with right ventricular involvement, thereby providing better prognostic performance than CPO in HFpEF.

Estimated plasma volume status adds prognostic value to hemodynamic parameters in advanced heart failure.

BACKGROUND: Estimated plasma volume status (ePVS) is a marker of intravascular congestion and has prognostic value in patients with heart failure (HF). The elevation of intracardiac filling pressures is defined as hemodynamic congestion and is also associated with poor prognosis. However, the relationship between intravascular congestion and hemodynamic congestion remains unclear. This study sought to explore the correlation between ePVS and hemodynamic parameters and determine the association between ePVS and clinical outcomes in patients with advanced HF. METHODS: Patients with advanced HF underwent right heart catheterization (RHC) for hemodynamic profiles. The sum of right atrial pressure (RAP) and pulmonary arterial wedge pressure (PAWP) > 30 mmHg was considered to present with hemodynamic congestion. Blood tests were conducted within 24 h of RHC. We calculated ePVS using the Strauss-derived Duarte formula. The primary outcome was all-cause mortality. RESULTS: A total of 195 patients were divided into two groups based on the cut-off value of ePVS (4.08 dL/g) calculated from receiver operating characteristic analysis. Patients with ePVS > 4.08 dL/g were more likely to present with wet rales (21.2% vs. 9.9%, P = 0.032) and had a higher risk of death (HR 4.748, 95% CI 2.385-9.453), regardless of whether RAP + PAWP was normal or elevated (all P < 0.05). Hemodynamic parameters and ePVS were not correlated (all P > 0.05). High ePVS significantly improved the predictive value beyond the clinical plus hemodynamic prognostic model (area under the curve of 0.844, Delong test, P = 0.024). CONCLUSION: ePVS could additionally add prognostic value to hemodynamic parameters in advanced heart failure, although not correlated with hemodynamic parameters.

sST2 and Big ET-1 as Alternatives of Multi-Biomarkers Strategies for Prognosis Evaluation in Patients Hospitalized with Heart Failure.

Objective: To identify biomarkers with independent prognostic value and investigate the prognostic value of multiple biomarkers in combination in patients hospitalized with heart failure. Methods: A total of 884 consecutive patients hospitalized with heart failure from 2015 to 2017 were enrolled. Twelve biomarkers were measured on admission, and the relationships between biomarkers and outcomes were assessed. Results: During the median follow-up of 913 days, 291 patients (32.9%) suffered from primary endpoint events. Soluble suppression of tumorigenicity-2 (sST2) (per log [unit] increase, adjusted HR [95% CI]: 1.39 [1.13,1.72], P = 0.002) and big endothelin-1 (big ET-1) (per log [unit] increase, adjusted HR [95% CI]: 1.56 [1.23,1.97], P < 0.001) remained independent predictors of primary endpoint event after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). Both sST2 (C-statistic: 0.810 vs 0.801, P = 0.005, and 0.832 vs 0.826, P = 0.024, respectively) and big ET-1 (C-statistic: 0.829 vs 0.801, P = 0.001, and 0.843 vs 0.826, P < 0.001, respectively) significantly improved the predictive value for primary endpoint event at 1 year and 3 years. However, only big ET-1 (C-statistic: 0.852 vs 0.846, P = 0.014) significantly improved the predictive value at 3 months when added to clinical predictors and known biomarkers. According to the number of elevated biomarkers (including NT-proBNP, hs-cTnT, sST2, and big ET-1), patients with three or more elevated biomarkers had a higher risk of primary endpoint event compared to those with two elevated biomarkers (P = 0.001), as well as in patients with two elevated biomarkers compared to those with one elevated biomarker (P = 0.004). However, the risk of primary endpoint event was comparable between patients with one elevated biomarker and those with no elevated biomarker (P = 0.582). Conclusion: Multiple biomarkers in combination could provide a better prognostic value than a single biomarker. sST2 and big ET-1 could act as alternatives of multi-biomarkers strategies for prognosis evaluation beyond NT-proBNP and hs-cTnT in patients hospitalized with heart failure.

Clinical characteristics and outcomes of patients hospitalized with heart failure with preserved ejection fraction and low NT-proBNP levels.

The aim of this study was to investigate the clinical characteristics and prognosis of patients hospitalized with heart failure with preserved ejection fraction (HFpEF) and low N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Seven hundred ninety consecutive patients hospitalized with HFpEF from 2006 to 2017 were enrolled. Clinical characteristics and outcomes were compared between low NT-proBNP group (<300 ng/L) and elevated NT-proBNP group (≥300 ng/L). 108 HFpEF patients (13.7%) presented with low NT-proBNP levels. Age, body mass index, atrial fibrillation, New York Heart Association functional class, and albumin were independent predictors of low NT-proBNP levels in HFpEF patients. During the median follow-up duration of 1103 days, 11 patients (10.2%) in low NT-proBNP group suffered from primary endpoint event. Elevated NT-proBNP group had a higher risk of all-cause death or heart transplantation than low NT-proBNP group (adjusted HR [95%CI]: 2.36 [1.24,4.49], P = .009). Stratified analyses showed that the association between NT-proBNP (elevated NT-proBNP group vs low NT-proBNP group) and risk of all-cause death or heart transplantation was stronger in non-atrial fibrillation patients than in atrial fibrillation patients (P value for interaction = .025). Furthermore, the associations between NT-proBNP and risk of all-cause death or heart transplantation were stronger in younger and male patients than in older and female patients. However, both subgroups only reached borderline significant (P values for interaction = .062 and .084, respectively). Our findings suggest that low NT-proBNP levels were common in patients hospitalized with HFpEF. Patients with HFpEF and low NT-proBNP levels had a better prognosis than those with elevated NT-proBNP levels, particularly in younger, male, and non-atrial fibrillation patients.

Combined use of right ventricular coupling and pulmonary arterial elastance as a comprehensive stratification approach for right ventricular function.

Right ventricular (RV)-pulmonary arterial uncoupling is the consequence of increased afterload and/or decreased RV contractility. However, the combination of arterial elastance (Ea) and end-systolic elastance (Ees)/Ea ratio to assess RV function is unclear. We hypothesized that the combination of both could comprehensively assess RV function and refine risk stratification. The median Ees/Ea ratio (0.80) and Ea (0.59 mmHg/mL) were used to classify 124 patients with advanced heart failure into four groups. RV systolic pressure differential was defined as end-systolic pressure (ESP) minus beginning-systolic pressure (BSP). Patients among different subsets showed dissimilar New York Heart Association functional class (V = 0.303, p = 0.010), distinct tricuspid annular plane systolic excursion/ pulmonary artery systolic pressure (mm/mmHg; 0.65 vs. 0.44 vs. 0.32 vs. 0.26, p < 0.001), and diverse prevalence of pulmonary hypertension (33.3% vs. 35% vs. 90% vs. 97.6%, p < 0.001). By multivariate analysis, Ees/Ea ratio (hazard ratio [HR] 0.225, p = 0.004) and Ea (HR 2.194, p = 0.003) were independently associated with event-free survival. Patients with Ees/Ea ratio greater than or equal to 0.80 and Ea less than 0.59 mmHg/mL had better outcomes (p < 0.05). In patients with Ees/Ea ratio greater than or equal to 0.80, those with Ea greater than or equal to 0.59 mmHg/mL had a higher adverse outcome risk (p < 0.05). Ees/Ea ratio less than or equal to 0.80 was associated with adverse outcomes, even when Ea was less than 0.59 mmHg/mL (p < 0.05). Approximately 86% of patients with ESP-BSP greater than 5 mmHg had an Ees/Ea ratio less than or equal to 0.80 and/or an Ea greater than or equal to 0.59 mmHg/mL (V = 0.336, p = 0.001). Combined use of Ees/Ea ratio and Ea could be a comprehensive approach to assessing RV function and predicting outcomes. An exploratory analysis demonstrated that Ees/Ea ratio and Ea might be roughly estimated based on RV systolic pressure differential.

Prognostic value of high-sensitivity cardiac troponin I in patients with non-ischaemic heart failure: insights from China.

AIMS: Evidence of the prognostic value of high-sensitivity troponin in patients with non-ischaemic heart failure (NIHF) is scarce. This study aimed to assess the predictive value of high-sensitivity cardiac troponin I (hs-cTnI) in NIHF patients. METHODS: Hs-cTnI was measured at baseline in 650 NIHF patients admitted to the Heart Failure Center. The prognostic value of hs-cTnI was assessed based on a well-established model (including age, sex, New York Heart Association class, left ventricular ejection fraction, haemoglobin, sodium, estimated glomerular filtration rate, diabetes mellitus, treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, treatment with ß-blockers, and NT-proBNP). RESULTS: During a median follow-up of 1036 days, 163 patients died of various causes. In total, 46.92% of patients had high hs-cTnI (hs-cTnI >0.011 ng/ml). Over a 3-year follow-up, patients with high hs-cTnI (>0.011 ng/ml) had a 1.54 [95% confidence interval (95% CI) 1.11-2.15] fold higher all-cause mortality risk than those without. Increasing concertation of hs-cTnI was also associated with a 23.0% (95% CI 13-33%, per log2 increase) increment risk of all-cause mortality. The inclusion of hs-cTnI significantly improved the risk prediction and stratification of all-cause mortality (integrated discrimination improvement 1.58%, 95% CI 0.38-2.79%, absolute net reclassification improvement 23.41% 95% CI 4.52-44.49%, additive net reclassification improvement 27.8%, 95% CI 9.29-46.3%) of the well-established model. CONCLUSIONS: Hs-cTnI provides significant prognostic value and could further remarkably improve risk stratification and prediction capabilities in NIHF patients.

Prognostic value of RDW alone and in combination with NT-proBNP in patients with heart failure.

BACKGROUND: Red blood cell distribution width (RDW) and N-terminal pro brain natriuretic peptide (NT-proBNP) may predict the prognosis of heart failure (HF). However, the impact of combined RDW and NT-proBNP levels as a prognostic marker of HF remains unclear and the significance of this combination at various time-points has not been sufficiently studied. HYPOTHESIS: RDW can predict prognosis in HF at various time-points and combination with NT-proBNP improves the prognostic value. METHODS: Patients admitted to HF care unit of Fuwai Hospital CAMS&PUMC (Beijing, China) with a diagnosis of HF from November 2008 to November 2018 were analyzed retrospectively. RESULTS: In total, 3231 patients with available RDW data at admission were evaluated (median age 58 years, 71.9% males, 39.7% coronary heart disease, 68.6% New York Heart Association [NYHA] III or IV). Median RDW and NT-proBNP at admission were 13.4% (interquartile range [IQR]: 12.7%-14.5%), and 1723.00 pg/ml (IQR: 754.00-4006.25 pg/ml), respectively. During 2.9-year median follow-up, all-cause death occurred in 1075 (33.27%) patients. Kaplan-Meier survival curve and Cox proportional-hazard models, showed patients in the top quarter RDW had a 32.0% increased mortality compared to the bottom quarter (hazard ratio: 4.39, 95% confidence interval: 3.59-5.38; p <.001). The top quarter RDW retained independent prognostic value across HF with reduced ejection fraction [HFrEF], HF with mid-range ejection fraction [HFmrEF], and HF with preserved ejection fraction [HFpEF] subgroups. Patients were subsequently divided into four groups by median RDW and NT-proBNP. Comparison of Kaplan-Meier survival curves for various groups showed good risk stratification (p < .001). CONCLUSIONS: RDW is an independent predictor of mortality among patients with HF in the short-, medium-, and long-term. Combination of RDW and NT-proBNP improves the prognostic value. This is true across all clinical subtypes of heart failure (HFrEF, HFmrEF, HFpEF), and among most subgroups of patients with various comorbidities (infection, diabetes, hypertension).