Clinical trial NCT06939985: Cardiometabolic evalUation REgistry of Heart Failure
Official title: Cardiometabolic Risk Factors and Clinical Outcomes in Heart Failure: An Observational Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Heart Failure
Metabolic Cardiovascular Syndrome
Metabolic Diseases
Keywords: heart failure
cardiometabolic risk factors
epicardial adipose tissue
cardiac remodeling
heart failure phenotypes
major adverse cardiovascular events
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2025-04-23
Enrollment: 5000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in cardiac function
timeFrame: 12 months
measure: Major cardiovascular events (MACEs)
timeFrame: 5 years
Secondary outcomes:
measure: HF re-hospitalization
timeFrame: 5 years
measure: Cardiovascular death
timeFrame: 5 years
measure: All-cause mortality
timeFrame: 5 years
measure: Dynamic transition among HF phenotypes
timeFrame: 12 months
measure: Changes in cardiac diastolic function
timeFrame: 12 months
measure: Changes in cardiac regional myocardial contractile function
timeFrame: 12 months
measure: Changes in left ventricular strain
timeFrame: 12 months
measure: Changes in left atrial strain
timeFrame: 12 months
measure: Changes in chamber dimensions
timeFrame: 12 months
measure: Changes in left ventricular mass
timeFrame: 12 months
measure: Cardiac wall thickness
timeFrame: 12 months
measure: Changes in epicardial adipose tissue (EAT) volume
timeFrame: 12 months
measure: Changes in epicardial adipose tissue (EAT) density
timeFrame: 12 months
measure: Changes in epicardial adipose tissue (EAT) distribution
timeFrame: 12 months
measure: Changes in perivascular adipose tissue (PVAT) volume
timeFrame: 12 months
measure: Changes in perivascular adipose tissue (PVAT) density
timeFrame: 12 months
measure: Changes in perivascular adipose tissue (PVAT) distribution
timeFrame: 12 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Study officials:
affiliation: Ruijin Hospital
name: Ruiyan Zhang, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Ruijin Hospital
name: Xiaoqun Wang, M.D., Ph.D.
role: STUDY_CHAIR
References: