Cardiometabolic evalUation REgistry of Heart Failure (CURE-HF)

Cardiometabolic Risk Factors and Clinical Outcomes in Heart Failure: An Observational Cohort Study

This is a combined retrospective-prospective observational cohort study investigating the role of systemic and local cardiometabolic risk factors in cardiac structural/functional remodeling and clinical outcomes among heart failure (HF) patients. The study integrates retrospective clinical data (from the past 10 years) and prospective longitudinal follow-up (5 years) of HF patients across HF with reduced (HFrEF), mildly-reduced (HFmrEF), preserved (HFpEF) and improved ejection fraction (HFimpEF) phenotypes. Systemic metabolic factors (e.g., blood lipid profiles, glycemic levels, insulin resistance) and local factors (e.g., epicardial adipose tissue [EAT], perivascular adipose tissue [PVAT]) will be analyzed for their associations with changes in cardiac geometrics and function, dynamic transitions between HF phenotypes, as well as the occurrence of major adverse cardiovascular events (MACEs). The study seeks to advance risk stratification by integrated evaluation of cardiometabolic profiles so as to refine personalized cures in HF management.

Study Overview

• Status: Recruiting
• Conditions: Metabolic Diseases; Heart Failure; Metabolic Cardiovascular Syndrome

Detailed Description

This is a combined retrospective-prospective observational cohort study aiming to elucidate the interplay between systemic/localized cardiometabolic risk factors and their impact on myocardial remodeling, cardiac function, and clinical trajectories in heart failure (HF) patients. By harmonizing retrospective clinical data spanning the past decade with a 5-year prospective longitudinal follow-up, the study encompasses all HF phenotypes, including reduced (HFrEF), mildly reduced (HFmrEF), preserved (HFpEF), and improved ejection fraction (HFimpEF), to capture the full spectrum of disease heterogeneity. Systemic metabolic dysregulation, such as dyslipidemia, impaired glucose metabolism, obesity and other metabolites assessed by mass spectrometry (MS), will be evaluated alongside localized factors, such as epicardial adipose tissue (EAT), perivascular adipose tissue (PVAT) quantified by advanced imaging modalities (cardiac MRI or CT). These factors will be correlated with changes in cardiac geometry (e.g., left ventricular mass, chamber dimensions, wall thickness) and function (e.g., ejection fraction, strain imaging, diastolic parameters), dynamic transitions between HF phenotypes (e.g., HFrEF to HFimpEF), as well as the occurrence of major adverse cardiovascular events (MACEs), defined as a composite of HF re-hospitalization and cardiovascular death. The prospective cohort will undergo standardized baseline assessments (blood biomarkers, echocardiography, cardiac CT or MRI) followed by routine clinical, biochemical and imaging evaluations at least 3-month intervals. Retrospective data will be extracted from electronic health records, including historical imaging studies, laboratory results, and event documentation, ensuring a robust sample size (target n≈3500 retrospective; n≈1200 prospective) for stratified analyses by HF phenotype, sex, and metabolic risk tertiles. Advanced statistical approaches, including multivariable regression analysis, multivariable Cox proportional hazards models and machine learning algorithms, will identify independent predictors for cardiac remodeling, functional alterations, HF phenotype transitions and MACEs. Ethical approval and informed consent are obtained for prospective participants, with retrospective data anonymized to ensure privacy. This study is expected to refine risk stratification tools by integrating metabolic imaging biomarkers and biochemical profiles, ultimately guiding personalized therapeutic cures for HF patients.

• Study Type: Observational
• Enrollment (Estimated): 5000

Contacts and Locations

• Study Contact: Name: Chendie Yang, M.D., Ph.D.; Phone Number: 0086-21-64370045-671503; Email: yangcd1029@163.com
• Study Contact Backup: Name: Xiaoqun Wang, M.D., Ph.D.; Phone Number: 0086-21-64370045-671605; Email: wangxq@shsmu.edu.cn

Study Locations

• China
  • Shanghai, China, 200025
    • Recruiting
    • Ruijin Hospital, Shanghai JiaoTong University School of Medicine
    • Principal Investigator: Xiaoqun Wang, M.D., Ph.D.
    • Sub-Investigator: Shuo Feng, M.D., Ph.D.
    • Contact: Chendie Yang, M.D., Ph.D.; Phone Number: 0086-21-64370045-671503; Email: yangcd1029@163.com
    • Sub-Investigator: Chendie Yang, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

This is a combination of retrospective and prospective cohort. Ambulatory and hospitalized patients with chronic HF (NYHA II-IV) across all ejection fraction phenotypes are consecutively enrolled.

Description

Inclusion Criteria:

1. Age ≥ 18 years

2. Chronic HF (NYHA II~IV), including:

   • HFrEF (HF with reduced ejection fraction): ① HF symptoms±signs ; ② LVEF≤40%.
   • HFimpEF (HF with improved ejection fraction): ① HF symptoms±signs; ② previous LVEF ≤ 40% and a follow-up measurement of LVEF >40%.
   • HFmrEF (HF with mildly reduced ejection fraction): ① HF symptoms±signs; ② LVEF 41%~49%.
   • HFpEF (HF with preserved ejection fraction): ① HF symptoms±signs; ② LVEF ≥50%; ③ objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of LV diastolic dysfunction/raised LV filling pressures, including raised natriuretic peptide.

Exclusion Criteria:

1. Estimated survival ≤ 1 year.
2. Pregnant or lactation, or have the intention to give birth within one year.
3. Poor compliance, unable to follow-up.
4. Mental or physical status not allowing written informed consent.
5. Unwillingness to give informed consent.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in cardiac function	Changes in ejection fraction (EF) measured by echocardiography or cardiac MRI at baseline and during follow-up.	12 months
Major cardiovascular events (MACEs)	A composite endpoint of HF re-hospitalizaion and cardiovascular death during follow-up	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HF re-hospitalization	The occurrence of protocol-adjudicated, unplanned hospitalization (≥24 hours requiring intravenous therapy for worsening HF, validated by symptomatic/hemodynamic criteria and biomarker/imaging evidence) during follow-up.	5 years
Cardiovascular death	The occurrence of cardiovascular death during follow-up.	5 years
All-cause mortality	The occurrence of death during follow-up	5 years
Dynamic transition among HF phenotypes	The occurrence of transition among HF phenotypes (HFrEF, HFimpEF, HFmrEF, HFpEF) measured by echocardiography or cardiac MRI at baseline and during follow-up	12 months
Changes in cardiac diastolic function	Changes in diastolic function (E/e' and E/A), measured by echocardiography at baseline an follow-up	12 months
Changes in cardiac regional myocardial contractile function	Changes in wall motion score index (WMSI) measured by echocardiography at baseline and follow-up	12 months
Changes in left ventricular strain	Changes in left ventricular strain measured by echocardiography or cardiac MR at baseline and during follow-up.	12 months
Changes in left atrial strain	Changes in left atrial strain measured by echocardiography or cardiac MR at baseline and during follow-up.	12 months
Changes in chamber dimensions	The changes in chamber dimensions analyzed by echocardiography or cardiac MRI at baseline and during follow-up	12 months
Changes in left ventricular mass	The changes in cardiac left ventricular mass analyzed by echocardiography or cardiac MRI at baseline and during follow-up.	12 months
Cardiac wall thickness	The changes in wall thickness analyzed by echocardiography or cardiac MRI at baseline and during follow-up.	12 months
Changes in epicardial adipose tissue (EAT) volume	Changes in the volume of EAT measured by cardiac CT or MRI and quantification analysis at baseline and during follow-up.	12 months
Changes in epicardial adipose tissue (EAT) density	Changes in the density of EAT measured by cardiac CT or MRI and quantification analysis at baseline and during follow-up.	12 months
Changes in epicardial adipose tissue (EAT) distribution	Changes in the distribution of EAT measured by cardiac CT or MRI and quantification analysis at baseline and during follow-up.	12 months
Changes in perivascular adipose tissue (PVAT) volume	Changes in the volume of PVAT measured by coronary CT angiography and quantification analysis at baseline and during follow-up.	12 months
Changes in perivascular adipose tissue (PVAT) density	Changes in the density of PVAT measured by coronary CT angiography and quantification analysis at baseline and during follow-up.	12 months
Changes in perivascular adipose tissue (PVAT) distribution	Changes in the distribution of PVAT measured by coronary CT angiography and quantification analysis at baseline and during follow-up.	12 months

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Investigators: Principal Investigator: Ruiyan Zhang, M.D., Ph.D., Ruijin Hospital; Study Chair: Xiaoqun Wang, M.D., Ph.D., Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2030

Study Registration Dates

• First Submitted: April 8, 2025
• First Submitted That Met QC Criteria: April 18, 2025
• First Posted (Actual): April 23, 2025

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 18, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: heart failure; cardiac remodeling; epicardial adipose tissue; major adverse cardiovascular events; cardiometabolic risk factors; heart failure phenotypes
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Glucose Metabolism Disorders; Insulin Resistance; Hyperinsulinism; Heart Failure; Metabolic Syndrome; Metabolic Diseases
• Other Study ID Numbers: RJH-CUREHF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No