Comparison of Three-dimensional and Two-dimensional Left Ventricle Strain With Speckle-tracking Echocardiography in Heart Failure With Reduced and Mildly Reduced Ejection Fraction (3V2-STEM-HF)

August 18, 2026 updated by: Istituti Clinici Scientifici Maugeri SpA

Left Ventricular Myocardial Strain Assessed by Three-dimensional Speckle-tracking Echocardiography in Heart Failure With Reduced and Mildly Reduced Ejection Fraction. A Comparison With Two-dimensional Evaluation in a Prospective Study

This study will compare two ultrasound techniques, 2D and 3D speckle-tracking echocardiography, for measuring how well the heart muscle contracts in patients with heart failure and reduced pumping function. While 2D global longitudinal strain (GLS) is widely used and has proven value in predicting outcomes, 3D GLS may provide a more complete assessment of heart function. Researchers will enroll 419 patients from seven cardiac rehabilitation hospitals in Italy and analyze heart ultrasound images using standardized equipment and software. The study will assess how closely 2D and 3D GLS measurements agree, identify factors that influence any differences, and determine whether 3D GLS better predicts the risk of death than 2D GLS.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Left Ventricular Myocardial Strain Assessed by Three-Dimensional Speckle-Tracking Echocardiography in Heart Failure with Reduced or Mildly Reduced Ejection Fraction: Comparison with Two-Dimensional Assessment in a Prospective Observational Study

Background

Global longitudinal strain (GLS) derived from speckle-tracking echocardiography (STE) is a robust, well-validated, and reproducible technique for assessing left ventricular (LV) longitudinal deformation and is available on most modern echocardiography systems. GLS appears to provide superior prognostic value compared with ejection fraction (EF) for predicting major adverse cardiac events across various clinical settings, including chronic heart failure (CHF).

Three-dimensional (3D) STE represents a further advancement in myocardial deformation imaging, enabling rapid and comprehensive assessment of all LV segments and measurement of global 3D GLS from a single dataset. However, in healthy individuals, reference values for 3D and 2D GLS differ significantly, likely because 3D GLS more accurately captures the complex mechanics of LV contraction, whereas 2D GLS provides higher spatial and temporal resolution.

Although 3D STE is increasingly being used to evaluate LV systolic function in patients with CHF, data regarding the agreement and differences between 2D and 3D measurements in this clinical setting remain limited. This issue is particularly relevant in patients with systolic heart failure, as reduced EF appears to weaken the correlation between 2D and 3D GLS measurements, according to available studies with relatively small sample sizes.

Objectives

This prospective multicenter study aims to evaluate the agreement between 2D and 3D GLS measurements obtained using single-vendor ultrasound systems and analysis software in patients with heart failure with reduced ejection fraction (HFrEF) or mildly reduced ejection fraction (HFmrEF).

Secondary objectives are to identify factors associated with differences between 2D and 3D GLS measurements and to determine whether 3D GLS is a stronger independent predictor of all-cause mortality than 2D GLS.

Methods Study Population

This multicenter prospective observational study will enroll patients with HFrEF and HFmrEF, defined as a left ventricular ejection fraction (LVEF) ≤40% and 41-49%, respectively, from the echocardiography laboratories of the Cardiovascular Department of Istituti Clinici Scientifici (ICS) Maugeri across seven tertiary cardiac rehabilitation hospitals in Italy.

The study protocol has been approved to the local Ethics Committee. Written informed consent will be obtained from all participants before eligibility screening.

Image Acquisition and Analysis

Echocardiographic datasets will be acquired using Vivid E95 ultrasound systems (GE Vingmed Ultrasound AS, Horten, Norway) equipped with M5S and 4V probes for 2D and 3D imaging, respectively, or a 4VC probe for both 2D and 3D acquisitions.

The acquisition protocol will include 2-, 3-, and 4-chamber apical views, as well as parasternal short-axis views at the mid-papillary level for 2D imaging, together with 3D LV datasets for the assessment of myocardial strain parameters using 2D and 3D STE. If necessary, two- to six-beat full-volume 3D acquisitions will be performed to ensure complete LV coverage with a frame rate of at least 37 volumes/s.

Two-dimensional and three-dimensional datasets will be analyzed offline using the Q-Analysis and 4D AutoLVQ software packages (EchoPAC BT12 and BT13; GE Vingmed Ultrasound AS) by investigators with at least three years of experience.

Peak global 2D longitudinal strain (2DLε) will be calculated from the three apical views, whereas peak global 2D circumferential strain (2DCε) will be derived from the parasternal short-axis view. Three 3D strain parameters will be obtained from the 3D LV dataset: longitudinal strain (3DLε), circumferential strain (3DCε), radial strain (3DRε), and area strain (3DAε).

Datasets will be excluded from analysis under the following conditions:

  1. poor image quality of either the 2D or 3D datasets, defined using a 4-point scale (poor = 1, fair = 2, good = 3, excellent = 4) because of inadequate signal-to-noise ratio, poor blood-tissue contrast, stitching artifacts or incomplete visualization of the LV wall;
  2. inadequate tracking of more than two LV segments in a single apical 2D view for global 2DLε analysis or in the parasternal short-axis view for 2DCε and 2DRε analysis;
  3. inadequate tracking of more than three LV segments during 3D dataset analysis.

Sample Size

Agreement between 2D and 3D GLS measurements will be assessed using Bland-Altman analysis. Based on published data reporting a mean difference of 0.1% and a standard deviation of differences of 2.9%, the required sample size was calculated to be 419 participants, assuming a maximum acceptable difference between methods of ±6.5%, a type I error (α) of 5%, and a type II error (β) of 20%.

Statistical Analysis

Normally distributed continuous variables will be summarized as mean ± standard deviation (SD), whereas non-normally distributed continuous variables will be reported as median and interquartile range (IQR). Categorical variables will be expressed as counts and percentages.

All LV strain parameters will be analyzed as absolute values, with lower values indicating worse myocardial deformation and higher values indicating better deformation.

Differences between groups will be assessed using unpaired t-tests for normally distributed variables and Mann-Whitney U tests for non-normally distributed variables. Agreement between 2D and 3D LV strain measurements will be evaluated using Bland-Altman analysis. Differences between paired 2D and 3D strain measurements within predefined subgroups will be assessed using paired statistical tests, as appropriate.

Pearson correlation analysis will be used to evaluate associations between the differences in 2D and 3D GLS measurements and demographic, cardiac, and technical variables. Stepwise multivariable linear regression analysis will be performed to identify independent predictors of the differences between 2D and 3D GLS measurements, including age, sex, weight, height, blood pressure, body surface area (BSA), LV volumes, LV mass, temporal resolution, and 3D image quality.

The area under the receiver operating characteristic curve (AUC-ROC) will be used to assess the predictive performance of 2D and 3D GLS for all-cause mortality. The DeLong test will be used to compare the AUCs of the two methods.

All hypothesis tests will be two-sided, and a p-value <0.05 will be considered statistically significant. Statistical analyses will be performed using SPSS software (IBM, Armonk, NY, USA).

Study Type

Observational

Enrollment (Estimated)

419

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with a diagnosis of heart failure and a reduced or mildly reduced ejection fration of left ventricle

Description

Inclusion Criteria:

  • Left ventricular ejection fraction (LVEF) ≤ 49%;
  • Echocardiographic image quality judged to be at least adequate according to a four-point visual image quality scale (good, adequate, poor, or inadequate)

Exclusion Criteria:

  • Inability to maintain the correct position for acquiring echocardiographic images;
  • Arrhythmias that make multi-beat acquisition impossible (if required), such as frequent extrasystoles (supraventricular or ventricular) and atrial fibrillation;
  • Failure to visualize more than 2 segments of the left ventricle (LV), or inability to assess more than 3 segments during 3D GLS analysis;
  • Failure to sign the informed consent form and inability of the participant to understand the objectives of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Heart failure with reduced ejection fraction (HFrEF) or mildly reduced ejection fraction (HFmrEF)
Patients with HFrEF or EFmrEF will be assessed with 2D and 3D echocardiography to evaluate the agreement between 2D and 3D global longitudinal strain measurements

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bland-Altman mean difference (bias) and the limits of agreement (LOA) in comparison with a clinically acceptable range (±6.5%)
Time Frame: At baseline
Bias and the LOA will be compared with a clinically acceptable range (±6.5%)
At baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Covariates and Confounders
Time Frame: At baseline
The factors associated with differences between 2D and 3D GLS measurements
At baseline
Comparison of all-cause mortality by 2D and 3D global longitudinal strain
Time Frame: From enrollment to the end of follow-up (1 year)
The area under the receiver operating characteristic curve (AUC-ROC) will be used to assess the predictive performance of 2D and 3D GLS for all-cause mortality. The DeLong test will be used to compare the AUCs of the two methods.
From enrollment to the end of follow-up (1 year)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituti Clinici Scientifici Maugeri SpA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 8, 2026

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

July 28, 2026

First Submitted That Met QC Criteria

July 28, 2026

First Posted (Actual)

August 3, 2026

Study Record Updates

Last Update Posted (Actual)

August 19, 2026

Last Update Submitted That Met QC Criteria

August 18, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTSM165-25

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All data (anonymized)

IPD Sharing Time Frame

Start date: 6 months after publication of the primary study results. End date: 5 years after publication of the primary study results.

IPD Sharing Access Criteria

De-identified individual participant data underlying the published results, together with the study protocol and statistical analysis plan, will be available to qualified researchers upon reasonable request to the principal investigator. Access will be granted following review and approval of a research proposal and completion of a data-sharing agreement. Data will be provided electronically in a secure manner

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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