Staging Heart Failure With Preserved Ejection Fraction (StageHFpEF)

Staging Heart Failure With Preserved Ejection Fraction by Assessing Cardiac Chamber Involvement With Echocardiography

Heart failure with preserved ejection fraction (HFpEF) is considered a systemic condition in which the prevalence of cardiovascular, metabolic, pulmonary and renal conditions determine the extent of cardiac involvement. Numerous attempts have been made to phenotype HFpEF, but patients still lack a clinically and/or prognostically relevant approach.

Progressive cardiac deterioration in HFpEF appears to be associated with a worse prognosis. However, no attempt has been made to classify the extent of cardiac involvement in HFpEF. Investigators proposed the concept of HFpEF staging according to the extent of cardiac involvement identified by transthoracic echocardiography: Stage 1: isolated left ventricular involvement; Stage 2: left atrial myopathy; Stage 3: pulmonary vasculature involvement; and Stage 4: right chambers involvement.

The study aims to investigate the associations between the proposed stages and clinical outcomes in HFpEF patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiovascular Diseases; Heart Failure; Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Other: No interventions

Detailed Description

HFpEF is a major global public health concern due to increasing incidence and prevalence, poor prognosis and limited availability of disease-modifying therapy. The management of HFpEF and the development of novel treatments are complicated due to the heterogeneous nature of the disease, which presents multiple clinical phenotypes. Each is characterised by a unique combination of cardiac and non-cardiac comorbidities such as hypertension, obesity, type 2 diabetes, chronic kidney disease, chronic obstructive pulmonary disease and others. Numerous attempts have been made to phenotype HFpEF, but patients still lack a clinically and/or prognostically relevant approach.

Looking beyond the phenotypes, HFpEF is considered a systemic condition in which the prevalence of cardiovascular, metabolic, pulmonary and renal conditions determine the extent of cardiac involvement. Progressive cardiac deterioration in HFpEF appears to be associated with a worse prognosis. However, no attempt has been made to classify the extent of cardiac involvement in HFpEF.

Investigators proposed the concept of HFpEF staging according to the extent of cardiac involvement identified by transthoracic echocardiography (TTE), which includes four stages: Stage 1: isolated left ventricular involvement; Stage 2: left atrial myopathy; Stage 3: pulmonary vasculature involvement; and Stage 4: right chambers involvement. Emerging data suggest that every subsequent cardiac chamber deterioration could be of prognostic value.

The study aims to investigate the associations between the proposed stages and clinical outcomes in HFpEF patients.

• Study Type: Observational
• Enrollment (Estimated): 700

Contacts and Locations

• Study Contact: Name: Anastasia Shchendrygina; Phone Number: +79262309207; Email: a.shchendrygina@gmail.com
• Study Contact Backup: Name: Svetlana Rachina; Email: rachina_s_a@staff.sechenov.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 119415
    • A Shchendrygina
    • Contact: Anastasia Shchendrygina; Phone Number: 89262309207; Email: a.shchendrygina@gmail.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with HFpEF, male and female, 40 years old and over who meet eligibility criteria.

Description

Inclusion Criteria:

1. ≥ 40 years of age, male and female
2. Heart failure symptoms, New York Heart Association (NYHA) II- III
3. Left ventricular ejection fraction (LVEF) > 50% documented by echocardiography at screening

4. One of the following scenarios:

   A) At screening, N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥300 pg/mL (sinus rhythm) or ≥600 pg/mL (if AF) and echocardiographic criteria see #5

   B) Previously confirmed HFpEF in combination with a history of hospitalization for HFpEF decompensation >30 days before screening defined as the presence of dyspnea and 2 of the following:

   • Rales on chest auscultation or sings of congestion on X-ray/CT scan
   • Peripheral Oedema
   • Elevated NT-proBNP ≥300 pg/mL (sinus rhythm) or ≥600 pg/mL (if AF)

5. Structural and/or functional abnormalities of heart, at least one of the following:

   • Left atrial volume index (LAVI) >34 mL/m2 (if AF >40 mL/m2)
   • Left ventricular mass index (LVMI) =115 g/m2 for males and =95 g/m2 for females
   • Relative wall thickness > 0.42
   • E/e' ratio at rest >9
6. Stable doses of oral loop diuretics, if prescribed
7. Ability to provide informed consent

Exclusion Criteria:

• Any prior measurements of LVEF <50%
• Established diagnosis of infiltrative (amyloidosis etc.), hypertrophic cardiomyopathy, muscular dystrophies, complex congenital heart disease, active myocarditis or pericardial constriction
• Planned interventions, including major cardiac surgery, percutaneous coronary intervention (PCI), transcatheter aortic valve implantation (TAVI), or implantation of cardiac resynchronization therapy
• Elective PCI or atrial fibrillation ablation within 30 days before visit
• Moderate and severe valve stenosis and more than mild primary valve regurgitation
• Acute myocardial infarction in the last 3 months, cardiac surgery, pulmonary embolism or cerebrovascular accident within the last six months
• Candidates for heart transplantation
• Secondary hypertension
• Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease
• Any active cancer
• Infective endocarditis
• Alcoholic cirrhosis
• End-stage kidney disease
• Any other condition judged by the investigator that could account for heart failure symptoms and signs (e.g., anaemia, hypothyroidism).

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HFpEF Stage 1: Isolated left ventricle involvement; Established if patients meet the criteria of Stage 1, according to the proposed classification, which are: LVMI >115 g/m2 in men/ and >95 g/m2 in women or; Relative wall thickness (RWT) >0.42 or; Elevated LV filling pressures at rest (E/e' >9) doi.org/10.15420/ecr.2024.31	Other: No interventions; No interventions
HFpEF Stage 2: Left atrial myopathy; Stage 1 criteria, plus: LAVI >34 ml/m2, if sinus rhythm or; AF	Other: No interventions; No interventions
HFpEF Stage 3: Pulmonary vasculature involvement; Stage 1-2 criteria, plus: Pulmonary artery systolic pressure (PASP) >35 mmHg and/or; Tricuspid regurgitation (TR) velocity >2.8 m/s	Other: No interventions; No interventions
HFpEF Stage 4: Right chambers involvement; Stage 1-3 criteria, plus: Fractional area change (FAC) <35% or; S' <9.5 cm/s and/or; Tricuspid annular plane systolic excursion (TAPSE) <17 mm and/or; Right atria (RA) volume index (>39 ml/m2 in men/ >33 ml/m2 for women)	Other: No interventions; No interventions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first occurrence of composite endpoint of all-cause death or HF hospitalisation	Measured in months	From randomisation to end of 12 months follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of all-cause deaths, Cardiovascular (CV) deaths, HF hospitalisations or urgent HF visits	Measured as count of event	From randomisation to end of 12 months follow-up
Time to occurrence of all-cause death	Measured in months	From randomisation to end of 12 months follow-up
Time to occurrence of CV death	Measured in months	From randomisation to end of 12 months follow-up
Time to first HF hospitalisation or urgent HF Visit	Measured in months	From randomisation to end of 12 months follow-up

Collaborators and Investigators

• Sponsor: I.M. Sechenov First Moscow State Medical University
• Investigators: Principal Investigator: Anastasia Shchendrygina, Sechenov University

Publications and helpful links

Helpful Links

• The publication which define the concept of Staging Heart Failure with Preserved Ejection Fraction by Assessing Cardiac Chamber Involvement

Study record dates

Study Major Dates

• Study Start (Estimated): April 20, 2025
• Primary Completion (Estimated): April 13, 2028
• Study Completion (Estimated): December 13, 2028

Study Registration Dates

• First Submitted: April 9, 2025
• First Submitted That Met QC Criteria: April 9, 2025
• First Posted (Actual): April 16, 2025

Study Record Updates

• Last Update Posted (Actual): April 20, 2025
• Last Update Submitted That Met QC Criteria: April 16, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Echocardiography; Staging; Classification; HFpEF
• Additional Relevant MeSH Terms: Heart Diseases; Heart Failure; Cardiovascular Diseases
• Other Study ID Numbers: 05-22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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