Long-term cost-effectiveness of transcatheter mitral valve repair in HF patients with secondary mitral regurgitation.

AIMS: The long-term cost-effectiveness of MitraClip in heart failure patients with secondary mitral regurgitation is still unclear. This study aimed to evaluate the long-term cost-effectiveness of MitraClip added to guideline-directed medical therapy vs. guideline-directed medical therapy alone in heart failure patients with secondary mitral regurgitation from the perspective of the healthcare systems of mainland China, the United Kingdom, Germany, and the United States. METHODS AND RESULTS: A two-stage (decision + Markov) model was built. Health utilities were defined by the New York Heart Association class, heart failure re-hospitalization, and death and were calculated based on the 5 year follow-up results of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation trial. Direct healthcare costs were derived from the nationally representative data. Future utilities and costs were discounted at country-specific rates. The primary outcome was the lifetime incremental cost-effectiveness ratio. The mean age of the base case in our model was 72.2 years. Over a lifetime horizon, treatment with MitraClip was associated with 829 fewer heart failure re-hospitalizations per 1000 treated patients. The MitraClip treatment was associated with incremental quality-adjusted life-year gains of 0.71, 0.76, 0.78, and 0.78, as well as incremental cost-effectiveness ratios of ¥468 462, £28 910, €26 045, and $71 199 per quality-adjusted life-year for a lifetime horizon in mainland China, the United Kingdom, Germany, and the United States, respectively. In probabilistic sensitivity analysis, 0.2%, 59.4%, 99.6%, and 84.7% of patients were cost-effective in mainland China, the United Kingdom, Germany, and the United States at the country-specific willingness-to-pay thresholds. CONCLUSIONS: MitraClip + guideline-directed medical therapy was cost-effective in heart failure patients with secondary mitral regurgitation in the United Kingdom, Germany, and the United States, but not in mainland China from the perspective of the national healthcare system.

The association between TyG and all-cause/non-cardiovascular mortality in general patients with type 2 diabetes mellitus is modified by age: results from the cohort study of NHANES 1999-2018.

BACKGROUND: The prognostic value of triglyceride-glucose (TyG) index in general type 2 diabetes mellitus (T2DM) patients is still unclear. Therefore, we aimed to determine the associations between TyG and all-cause/cause-specific death in a T2DM cohort and explore whether such associations would be modified by age. METHODS: A total of 3,376 patients with T2DM from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were selected and divided into the younger group (< 65 yrs) and the older group (≥ 65 yrs). Baseline TyG was calculated and cause-specific mortality status [cardiovascular (CV), cancer, and non-CV] was determined by the NHANES Public-Use Linked Mortality Files through 31 December 2019. Multivariate Cox and restricted cubic spline (RCS) regression models were used to evaluate the association between TyG and all-cause/cause-specific mortality. Interaction between TyG and age to mortality was also evaluated. Sensitivity analyses were performed in patients without cardiovascular disease, chronic kidney disease, or insulin treatment. RESULTS: During a median follow-up of 107 months, 805 all-cause deaths occurred, of which 250 and 144 were attributed to CV and cancer deaths. There was a significant age interaction to the association between TyG and all-cause/non-CV mortality. After fully adjusting for potential confounding factors, higher TyG was associated with an increased risk of all-cause [TyG per unit increase Hazard Ratio (HR) 1.33, 95% Confidence Interval (CI) 1.06-1.66, p = 0.014] and non-CV mortality (TyG per unit increase HR 1.54, 95% CI 1.18-2.01, p = 0.002) only in the younger group, but not in the older group. There was no significant association between TyG and CV/cancer death in the total cohort and two age subgroups. Similar results were found in RCS and sensitivity analyses. CONCLUSION: In a national sample of patients with T2DM in the United States, we found that the association between TyG and all-cause/non-CV death was modified by age. Higher TyG was only associated with an increased risk of all-cause/non-CV only in T2DM patients younger than 65 years old, but not in older patients.

ASSESS-IE: a Novel Risk Score for Patients with Infective Endocarditis.

Mortality in patients with infective endocarditis (IE) remains high. The existing risk scores are relatively complex with limited clinical application. This study was conducted to establish a new risk model to predict in-hospital and 6-month mortality in IE patients. A total of 1549 adult patients with definite IE admitted to Guangdong Provincial People's Hospital (n=1354) or Xiamen Cardiovascular Hospital (n=195) were included. The derivation cohort consisted of 1141 patients. The score was developed using the multivariate stepwise logistic regression analysis for in-hospital death. Bootstrap analysis was used for validation. Discrimination and calibration were evaluated by the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test. Six risk factors were used as score parameters (1 point for each): aortic valve affected, previous valve replacement surgery, severe heart failure, elevated serum direct bilirubin, moderate-severe anemia and acute stage. The predictive value and calibration of the ASSESS-IE score for in-hospital death were excellent in the derivation (area under the curve [AUC]=0.781, p<0.001; Hosmer-Lemeshow p=0.948) and validation (AUC=0.779, p<0.001; Hosmer-Lemeshow p=0.520) cohorts. The score remained excellent in bootstrap validation (AUC=0.783). The discriminatory ability of the ASSESS-IE score for in-hospital (AUC: 0.781 vs. 0.799, p=0.398) and 6-month mortality (AUC: 0.778 vs. 0.814, p=0.040) were similar with that of Park's score which comprised 14 variables. The ASSESS-IE risk score is a new and robust risk-stratified tool for patients with IE, which might further facilitate clinical decision-making.

Five-year mortality of heart failure with preserved, mildly reduced, and reduced ejection fraction in a 4880 Chinese cohort.

AIMS: Available evidence is incomplete and inconsistent in the outcomes of heart failure (HF) patients with preserved ejection fraction (HFpEF), mildly reduced ejection fraction (HFmrEF), and reduced ejection fraction (HFrEF). There are also limited data on the proportions and long-term prognosis among the three HF phenotypes in China. We aimed to characterize the 5 year prognosis in three HF phenotypes according to EF in a cohort of hospitalized HF patients undergoing coronary angiography in southern China. METHODS AND RESULTS: Hospitalized patients with HF were enrolled from the Cardiorenal ImprovemeNt registry (CIN; ClinicalTrials.gov NCT04407936) between January 2007 and December 2014. HF phenotypes were defined as HFpEF (EF ≥ 50%), HFmrEF (EF 41-49%), and HFrEF (EF ≤ 40%). Kaplan-Meier and Cox proportional hazards models were constructed to examine differences in 5 year outcomes in HF patients with different phenotypes. A total of 4880 HF patients [mean age: 61.8 ± 10.3, male: 3156 (64.7%)] were included: 2768 (57%) had HFpEF, 1015 (21%) had HFmrEF, and 1097 (22%) had HFrEF. Patients with HFrEF were older than those with HFpEF (62.5 ± 10.6 vs. 61.3 ± 10.1, P < 0.001) and more likely to be male (78.0% vs. 55.9%, P < 0.001). With 5 year follow-up through the end of December 2019, 1624 (27.6%) patients died. Controlling confounding variables, declined EF category was independently associated with increased 5 year mortality {HFrEF 25.2% vs. HFpEF 13.4%, adjusted hazard ratio [aHR]: 1.85 [95% confidence interval (CI): 1.45 to 2.35]; HFmrEF 18.1% vs. HFpEF 13.4%, aHR: 1.40 [95% CI: 1.08 to 1.81]; HFrEF 25.2% vs. HFmrEF 18.1%, aHR: 1.32 [95% CI: 1.02 to 1.71]}. CONCLUSIONS: In this Chinese cohort, patients with HFrEF account for less than a fourth of HF patients. One-sixth individuals with HF died in 5 years. HFrEF was associated with a nearly two-fold increased risk of 5 year mortality than HFpEF. Further studies are needed to prospectively evaluate the efficacy of improving treatment on outcomes in all three HF phenotypes.

Prevalence and Prognosis of HFimpEF Developed From Patients With Heart Failure With Reduced Ejection Fraction: Systematic Review and Meta-Analysis.

Background: Heart failure with improved ejection fraction (HFimpEF) is classified as a new type of heart failure, and its prevalence and prognosis are not consistent in previous studies. There is no systematic review and meta-analysis regarding the prevalence and prognosis of the HFimpEF. Method: A systematic search was performed in MEDLINE, EMBASE, and Cochrane Library from inception to May 22, 2021 (PROSPERO registration: CRD42021260422). Studies were included for analysis if the prognosis of mortality or hospitalization were reported in HFimpEF or in patients with heart failure with recovered ejection fraction (HFrecEF). The primary outcome was all-cause mortality. Cardiac hospitalization, all-cause hospitalization, and composite events of mortality and hospitalization were considered as secondary outcomes. Result: Nine studies consisting of 9,491 heart failure patients were eventually included. During an average follow-up of 3.8 years, the pooled prevalence of HFimpEF was 22.64%. HFimpEF had a lower risk of mortality compared with heart failure patients with reduced ejection fraction (HFrEF) (adjusted HR: 0.44, 95% CI: 0.33-0.60). HFimpEF was also associated with a lower risk of cardiac hospitalization (HR: 0.40, 95% CI: 0.20-0.82) and the composite endpoint of mortality and hospitalization (HR: 0.56, 95% CI: 0.44-0.73). Compared with patients with preserved ejection fraction (HFpEF), HFimpEF was associated with a moderately lower risk of mortality (HR: 0.42, 95% CI: 0.32-0.55) and hospitalization (HR: 0.73, 95% CI: 0.58-0.92). Conclusion: Around 22.64% of patients with HFrEF would be treated to become HFimpEF, who would then obtain a 56% decrease in mortality risk. Meanwhile, HFimpEF is associated with lower heart failure hospitalization. Further studies are required to explore how to promote left ventricular ejection fraction improvement and improve the prognosis of persistent HFrEF in patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021260422, identifier: CRD42021260422.

Combined use of low T3 syndrome and NT-proBNP as predictors for death in patients with acute decompensated heart failure.

BACKGROUND: In patients with established HF, low triiodothyronine syndrome (LT3S) is commonly present, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful marker for predicting death. This study was aimed to evaluate the prognostic value of LT3S in combination with NT-proBNP for risk of death in patients with heart failure (HF). METHODS: A total of 594 euthyroid patients hospitalized with acute decompensated HF were enrolled by design. Of these patients, 27 patients died during hospitalization and 100 deaths were identified in patients discharged alive during one year follow-up. Patients were divided into 2 groups on the base of the reference ranges of free T3 (FT3) levels: LT3S group (FT3 < 2.3pg/mL, n = 168) and non-LT3S group (FT3 ≥ 2.3pg/mL, n = 426). RESULTS: In multivariable Cox regression, LT3S was significantly associated with 1 year all-cause mortality (adjusted hazard ratio, 1.85; 95 % confidence interval [CI], 1.21 to 2.82; P = 0.005), but not significant for in-hospital mortality (adjusted hazard ratio, 1.58; 95 % CI, 1.58 to 2.82; P = 0.290) after adjustment for clinical variables and NT-proBNP. Addition of LT3S and NT-proBNP to the prediction model with clinical variables significantly improved the C statistic for predicting 1 year all-cause mortality. CONCLUSIONS: In patients with acute decompensated HF, the combination of LT3S and NT-proBNP improved prediction for 1 year all-cause mortality beyond established risk factors, but was not strong enough for in-hospital mortality.

Baseline Low-Density-Lipoprotein Cholesterol Modifies the Risk of All-Cause Death Associated With Elevated Lipoprotein(a) in Coronary Artery Disease Patients.

Background: The prognostic value of elevated lipoprotein(a) [Lp(a)] in coronary artery disease (CAD) patients is inconsistent in previous studies, and whether such value changes at different low-density-lipoprotein cholesterol (LDL-C) levels is unclear. Methods and Findings: CAD patients treated with statin therapy from January 2007 to December 2018 in the Guangdong Provincial People's Hospital (NCT04407936) were consecutively enrolled. Individuals were categorized according to the baseline LDL-C at cut-off of 70 and 100 mg/dL. The primary outcome was 5-year all-cause death. Multivariate Cox proportional models and penalized spline analyses were used to evaluate the association between Lp(a) and all-cause mortality. Among 30,908 patients, the mean age was 63.1 ± 10.7 years, and 76.7% were men. A total of 2,383 (7.7%) patients died at 5-year follow-up. Compared with Lp(a) <50 mg/dL, Lp(a) ≥ 50 mg/dL predicted higher all-cause mortality (multivariable adjusted HR = 1.19, 95% CI 1.07-1.31) in the total cohort. However, when analyzed within each LDL-C category, there was no significant association between Lp(a) ≥ 50 mg/dL and higher all-cause mortality unless the baseline LDL-C was ≥ 100 mg/dL (HR = 1.19, 95% CI 1.04-1.36). The results from penalized spline analyses were robust. Conclusions: In statin-treated CAD patients, elevated Lp(a) was associated with increased risks of all-cause death, and such an association was modified by the baseline LDL-C levels. Patients with Lp(a) ≥ 50 mg/dL had higher long-term risks of all-cause death compared with those with Lp(a) <50 mg/dL only when their baseline LDL-C was ≥ 100 mg/dL.

Does higher SBP at discharge explain better outcomes in non-heart failure with reduced ejection fraction patients? Insights from Fuwai Hospital.

OBJECTIVE: We hypothesized that discharge SBP had different associations with outcomes in non-HFrEF (left ventricular ejection fraction ≥40%) patients with or without high blood pressure (HBP) at admission. METHODS: Non-HFrEF patients hospitalized for decompensated heart failure were consecutively recruited and were categorized into HBP (admission SBP ≥130 mmHg) group and non-HBP group. The primary outcome was a composite of cardiovascular death and heart transplantation. Multivariate Cox and penalized spline analyses were used to assess the relationships between discharge SBP and outcomes. RESULTS: Nine hundred and sixty-four non-HFrEF patients were enrolled with a median follow-up of 71.8 months. Three hundred and sixty-five (37.9%) patients had HBP. In multivariate Cox analyses, non-HBP patients with higher discharge SBP were associated with a better outcome (per 10 mmHg increased, hazard ratio = 0.788, P = 0.001). However, an opposite relationship between discharge SBP and the primary outcome was observed in HBP group (per 10 mmHg increased, hazard ratio = 1.312, P = 0.002). Results of penalized spline regression models showed that there was a U-shaped association between discharge SBP and outcomes in the total cohort. Compared with 120 mmHg, the risk of the primary outcome increased when discharge SBP was below 99 mmHg in non-HBP group; in HBP group, a worse outcome was observed when discharged SBP was above 145 mmHg. CONCLUSION: Non-HFrEF had a U-shaped association between discharge SBP and adverse events. Such an association was modified by admission HBP. Higher discharge SBP correlated with a worse outcome in non-HFrEF patients with admission HBP, as opposed to patients admitted without HBP.

Cost-effectiveness of adding dapagliflozin to standard treatment for heart failure with reduced ejection fraction patients in China.

AIMS: This study was to determine the cost-effectiveness of dapagliflozin in heart failure with reduced ejection fraction (HFrEF) patients in China from a perspective of health care payers. METHODS AND RESULTS: We built a Markov model to perform a cost-effectiveness analysis comparing standard treatment + dapagliflozin (10 mg, q.d.) with standard treatment for HFrEF. The base case in our simulation was a 65-year-old HFrEF patient and was modelled over 15 years. Inputs of the model were derived from the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial and other relevant data from China. Costs, quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER) were estimated for adding dapagliflozin relative to standard treatment. Costs and QALY were discounted at a 4.2% rate annually. All costs are presented in 2017 US dollars. Dapagliflozin would be considered very cost-effective if the ICER was lower than a willingness-to-pay (WTP) threshold of $8573.4. Uncertainty was assessed in our model using one-way, two-way, and probabilistic sensitivity analysis (PSA). In our base case, compared with standard treatment, adding dapagliflozin was more expensive ($5829.4 vs. $4377.1) but more effective (4.82 vs. 4.44 QALYs). The respondent ICER was $3827.6 per QALY gained at 15-year follow-up. When the simulated horizon was longer than 3.5 years, the respondent ICER became lower than the WTP threshold. The inputs with the largest impact on ICER were the cost of dapagliflozin, the cardiovascular mortality in both groups, and the cost of hospitalization for heart failure. Most results of sensitivity analysis were robust. PSA showed a similar result as the base case (ICER = $4412.5 per QALY gained). In Monte Carlo simulation, at a WTP threshold of $8573.4 per QALY, dapagliflozin was considered very cost-effective in 53.10% of the simulations. CONCLUSIONS: Dapagliflozin was a very cost-effective treatment option for HFrEF patients in China according to the result of our model. Our findings will help doctors and health care payers to make decisions in clinical practice. Future real-world studies of cost-effectiveness of dapagliflozin based on Chinese population were also needed.

Different prognostic association of systolic blood pressure at different time points with postdischarge events in patients hospitalized for decompensated heart failure.

BACKGROUND: The association of systolic blood pressure (SBP) with mortality in heart failure (HF) patients is paradoxical, and the time points of baseline SBP are also different across prior studies. We hypothesized that the levels of SBP at admission and at discharge had different associations with postdischarge events. METHODS: The study population included patients hospitalized for decompensated HF in the Heart Failure Center of Fuwai Hospital from January 1, 2009 to December 31, 2014. The primary outcome was a composite of cardiovascular (CV) death and heart transplantation. Multivariate Cox proportional-hazards and restricted cubic spline analyses were used to assess the relationships between SBP at different time points and outcomes. RESULTS: In total, 2005 patients were included with a median follow-up of 48.4 months. The median age was 59 years, and 69.9% were male. Multivariate Cox analyses showed that compared with SBP < 105 mmHg, higher SBP at admission was associated with better long-term primary outcome (105-119 mmHg, HR = 0.764, P = 0.005; 120-134 mmHg, HR = 0.658, P < 0.001; ≥ 135 mmHg, HR = 0.657, P = 0.001). Patients whose discharge SBP was higher than 135 mmHg had a similar primary outcome as those with SBP < 105 mmHg (HR = 0.969, P = 0.867), and the results remained unchanged even after adjusting for admission SBP (HR = 1.235, P = 0.291). The results of restricted cubic spline analysis indicated similar associations. CONCLUSIONS: Lower but not higher SBP at admission is associated with more CV deaths/heart transplantations (a reverse J-shaped curve). In contrast, there is a U-shaped association between discharge SBP and CV mortality/heart transplantation.

Can Torsemide and Combination of Loop Diuretics Improve Mortality in Patients with Chronic Heart Failure After Discharge?

The aim of this study was to investigate the effect on mortality of torsemide and a combination of loop diuretics (furosemide + torsemide) in contemporary practice in patients with chronic heart failure (HF).We investigated patients with HF in the Heart Failure Center of Fuwai Hospital from 2009 to 2013 who were discharged on furosemide, torsemide, or a combination of the 2 drugs. Using inverse probability weighting (IPW) to account for nonrandom selection of diuretic strategies, we assessed the association between different diuretic strategies and mortality.Among 956 patients, 19.7% (n = 188) received furosemide, 36.6% (n = 350) torsemide, and 43.7% (n = 418) the combination therapy. The torsemide-treated and combination-treated patients had worse heart function and higher furosemide equivalent. Univariable Cox proportional hazards models showed that the combination group had worse outcomes (all-cause HR = 2.044, P = 0.008; CV HR = 1.988, P = 0.011), while torsemide was associated with an outcome (all-cause HR = 1.640, P = 0.078; CV HR = 1.509, P = 0.147) similar to that of furosemide. After IPW, torsemide was associated with a nominally lower mortality compared with furosemide (all-cause HR = 0.738, P = 0.222; CV HR = 0.667, P = 0.110), and the association between the combination treatment and increased mortality was no longer statistically significant (all-cause HR = 1.207, P = 0.470;CV HR = 1.174, P = 0.540).We found that torsemide and the combination strategy had similar outcomes when compared with furosemide. However, considering the lack of diuretic randomized clinical trials (RCTs) conducted with the aim of exploring the effect on mortality of different diuretic treatments, prospective trials are needed to investigate the effect of different diuretic strategies in chronic HF.