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Cancer Related Cardiovascular ToxicitySAFE-HEARTNCT07916337

3D Versus 2D Strain Echocardiography for Early Detection of Cardiotoxicity During Cancer Therapy

An observational study of Cancer Related Cardiovascular Toxicity and Anthracycline Related Cardiotoxicity in Breast Cancer, run by Region Skane at 1 site in Sweden.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Some cancer treatments, such as anthracycline chemotherapy and HER2-targeted therapy, can damage the heart (cardiotoxicity). If heart damage is detected early, heart-protective treatment can be started and cancer treatment can often continue without interruption. Read more about this study

Who is it for?
Ages 18 years and older
How many people
130 participants
Where
1 siteSweden
Study dates
3 Feb 2025to 31 Dec 2028
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Consecutive adult patients with breast cancer, lymphoma or sarcoma who are referred for baseline echocardiography before starting anthracycline and/or HER2-targeted therapy at the echocardiography laboratories of Skåne University Hospital in Lund (Department of Cardiology) and Malmö (Department of Clinical Physiology), Sweden. Patients are identified through echocardiography referrals from the oncology and haematology departments and invited to participate at the time of the baseline examination.

Who may be able to join

  • Age 18 years or older
  • Diagnosis of breast cancer, lymphoma or sarcoma
  • Scheduled for treatment with anthracyclines and/or HER2-targeted therapy
  • Referred for baseline echocardiography before start of cancer therapy at Skåne University Hospital, Lund or Malmö
  • Written informed consent

Who cannot join

  • Pregnancy
  • Inability to provide informed consent
  • Insufficient image quality for 3D speckle-tracking analysis at baseline echocardiography

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ashkan Labaf, MD, PhD contact

+4646-171000

ashkan.labaf@med.lu.se

Sweden1 site, 1 recruiting
  • Skåne University Hospital Lund and Malmö

    Lund, Skåne County, 222 42

    Ashkan Labaf, MD, PhD, +46(0)704877662, ashkan.labaf@med.lu.se

    Recruiting

Other trials in Sweden

About this study

Official title: A Prospective Observational Study of 3D Versus 2D Speckle-Tracking Echocardiography for Early Detection of Cardiotoxicity in Patients Treated With Anthracyclines and/or HER2-Targeted Therapy (SAFE-HEART)

Some cancer treatments, such as anthracycline chemotherapy and HER2-targeted therapy, can damage the heart (cardiotoxicity). If heart damage is detected early, heart-protective treatment can be started and cancer treatment can often continue without interruption.

Heart ultrasound (echocardiography) is the standard method for monitoring the heart during cancer treatment. Today, heart function is mainly assessed with two-dimensional (2D) measurements, which may miss early changes. A newer technique, three-dimensional speckle-tracking echocardiography (3D strain), follows the heart muscle's movement in all directions and may detect damage earlier and more accurately.

Read more

The SAFE HEART study will investigate whether 3D strain detects early heart damage better than 2D strain and conventional measures of pumping function (ejection fraction) in adults with breast cancer, lymphoma or sarcoma who are treated with anthracyclines and/or HER2-targeted therapy at Skåne University Hospital in Lund and Malmö, Sweden.

Participants undergo heart ultrasound, ECG and blood tests for cardiac biomarkers (troponin I and NT-proBNP) before, during and after cancer treatment. Blood samples are also stored in a biobank to search for new markers that can predict heart damage. Participants who develop signs of heart damage, and a matched group without heart damage, may be asked to undergo a cardiac magnetic resonance (MRI) scan.

Read the detailed description

Background: Cancer therapy-related cardiac dysfunction (CTRCD) is a major complication of anthracycline and HER2-targeted therapy and may lead to interruption of potentially curative cancer treatment. Left ventricular ejection fraction (LVEF) lacks sensitivity for subclinical myocardial injury. 2D global longitudinal strain (GLS) is recommended in the 2022 ESC Cardio-Oncology Guidelines for early detection of subclinical dysfunction, and the guidelines favour 3D echocardiography, but clinical evidence for 3D speckle-tracking echocardiography (3D-STE) remains limited. 3D-STE allows tracking of speckles in all directions, including out-of-plane motion, and simultaneous assessment of longitudinal, circumferential, radial and area strain from a single volumetric dataset. Right ventricular involvement in cardiotoxicity is also insufficiently studied.

Design: Prospective, observational, two-centre cohort study at Skåne University Hospital (Lund and Malmö), Sweden. Consecutive adult patients referred for baseline echocardiography before anthracycline and/or HER2-targeted therapy for breast cancer, lymphoma or sarcoma are invited to participate.

Study procedures: Echocardiography including 2D and 3D acquisitions is performed according to a standardised protocol. 3D strain (left and right ventricle) and 3D LVEF are analysed using vendor-integrated software. Echocardiography and cardiac biomarkers (high-sensitivity troponin I and NT-proBNP) are obtained at the following time points:

  • Breast cancer: baseline and thereafter according to clinical indication during and after treatment, typically every 3-4 months.
  • Lymphoma and sarcoma: baseline, 6 months and 24 months after treatment start. Clinical risk factors are collected by questionnaire at baseline. 3D parameters are analysed offline and are not used for clinical decision-making; clinical management follows standard care.

Biobank: Blood samples (EDTA and serum) are collected at baseline and approximately 6 months after treatment start and stored in Region Skåne Biobank for future biomarker analyses.

Cardiac MRI sub-study: Approximately 20-25 participants with echocardiographic or biomarker evidence of cardiac injury and 20-25 matched participants without cardiac injury from the same cohort are asked to undergo contrast-enhanced cardiac MRI for tissue characterisation.

Clinical outcomes: Initiation of heart failure medication, heart failure hospitalisation and all-cause mortality are retrieved from Region Skåne health records and national Swedish registers.

Ethics: Approved by the Swedish Ethical Review Authority (Dnr 2024-06788-01; amendment 2025-05980-02).

Keywords
Cardiotoxicity, Cancer therapy-related cardiac dysfunction, CTRCD, Anthracyclines, HER2-targeted therapy, Trastuzumab, 3D speckle-tracking echocardiography, Global longitudinal strain, Cardio-oncology, Biobank
Medical subject headings
Breast Neoplasms, Cardiotoxicity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT07916337
Study groupRoleWhat they receive
Breast cancerAdults with breast cancer scheduled for anthracycline and/or HER2-targeted therapy. 2D and 3D echocardiography and cardiac biomarkers (troponin I, NT-proBNP) at baseline and thereafter according to clinical indication, typically every 3-4 months. Biobank samples at baseline and approximately 6 months.
Lymphoma and sarcomaAdults with lymphoma or sarcoma scheduled for anthracycline-based therapy. 2D and 3D echocardiography and cardiac biomarkers (troponin I, NT-proBNP) at baseline, 6 months and 24 months after treatment start. Biobank samples at baseline and approximately 6 months.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in 3D left ventricular strain parameters compared with 2D global longitudinal strain during follow-up

    Relative change (%) from baseline in left ventricular strain parameters measured by 3D speckle-tracking echocardiography (global longitudinal strain, global circumferential strain, global radial strain and global area strain), compared with the relative change in global longitudinal strain measured by 2D speckle-tracking echocardiography in the same patients at each follow-up examination.

    Measured: From baseline (before start of cancer therapy) through 12 months of follow-up (breast cancer) and 24 months of follow-up (lymphoma and sarcoma)

Secondary outcomes (10)
  1. Change in 3D left ventricular ejection fraction compared with 2D left ventricular ejection fraction

    Relative change (%) from baseline in right ventricular free wall longitudinal strain measured by speckle-tracking echocardiography.

    Measured: From baseline (before start of cancer therapy) through 12 months of follow-up (breast cancer) and 24 months of follow-up (lymphoma and sarcoma)

  2. Change in right ventricular free wall longitudinal strain

    Relative change (%) from baseline in right ventricular strain (free wall and global longitudinal strain) and 3D right ventricular ejection fraction measured by echocardiography.

    Measured: From baseline (before start of cancer therapy) through 12 months of follow-up (breast cancer) and 24 months of follow-up (lymphoma and sarcoma)

  3. Incidence of cancer therapy-related cardiac dysfunction (CTRCD)

    Proportion of participants developing asymptomatic or symptomatic CTRCD according to the 2022 ESC Cardio-Oncology Guidelines definitions, based on LVEF, 2D GLS and cardiac biomarkers.

    Measured: From baseline (before start of cancer therapy) through 12 months of follow-up (breast cancer) and 24 months of follow-up (lymphoma and sarcoma)

  4. Area under the receiver operating characteristic curve of early change in 3D strain parameters for prediction of CTRCD

    Area under the receiver operating characteristic curve (AUC) for early relative change (%) in 3D left ventricular strain parameters measured by 3D speckle-tracking echocardiography, compared with 2D global longitudinal strain and left ventricular ejection fraction, for prediction of subsequent CTRCD according to the 2022 ESC Cardio-Oncology Guidelines.

    Measured: From baseline (before start of cancer therapy) through 12 months of follow-up (breast cancer) and 24 months of follow-up (lymphoma and sarcoma)

  5. Correlation between change in 3D and 2D strain parameters and change in high-sensitivity troponin I

    Spearman correlation coefficient between the relative change (%) from baseline in left ventricular strain parameters measured by 3D speckle-tracking echocardiography (global longitudinal, circumferential, radial and area strain) and 2D global longitudinal strain measured by 2D speckle-tracking echocardiography, and the change from baseline in plasma concentration of high-sensitivity troponin I (ng/L), measured by laboratory immunoassay.

    Measured: From baseline (before start of cancer therapy) through 12 months of follow-up (breast cancer) and 24 months of follow-up (lymphoma and sarcoma)

  6. Proportion of echocardiographic examinations with image quality adequate for 3D strain analysis

    Percentage of echocardiographic examinations in which image quality is adequate for analysis of left ventricular strain by 3D speckle-tracking echocardiography, compared with the percentage adequate for 2D speckle-tracking echocardiography.

    Measured: From baseline (before start of cancer therapy) through 12 months of follow-up (breast cancer) and 24 months of follow-up (lymphoma and sarcoma)

  7. Correlation between 3D strain parameters and cardiac magnetic resonance measures

    Spearman correlation coefficient between left ventricular strain parameters measured by 3D speckle-tracking echocardiography (global longitudinal, circumferential, radial and area strain, %) and cardiac magnetic resonance measures: left ventricular ejection fraction (%), native T1 (ms), T2 (ms), extracellular volume (%) and extent of late gadolinium enhancement (% of left ventricular mass), in participants with and without evidence of cardiac injury.

    Measured: Up to 24 months after start of cancer therapy

  8. Number of participants with initiation of heart failure medication, hospitalisation for heart failure or all-cause death

    Number of participants with at least one of the following events: initiation of heart failure medication, hospitalisation for heart failure or death from any cause, retrieved from Region Skåne health records and national Swedish registers.

    Measured: From baseline (before start of cancer therapy) through 12 months of follow-up (breast cancer) and 24 months of follow-up (lymphoma and sarcoma)

  9. Correlation between change in 3D and 2D strain parameters and change in NT-proBNP

    Spearman correlation coefficient between the relative change (%) from baseline in left ventricular strain parameters measured by 3D speckle-tracking echocardiography (global longitudinal, circumferential, radial and area strain) and 2D global longitudinal strain measured by 2D speckle-tracking echocardiography, and the change from baseline in plasma concentration of NT-proBNP (ng/L), measured by laboratory immunoassay.

    Measured: From baseline (before start of cancer therapy) through 12 months of follow-up (breast cancer) and 24 months of follow-up (lymphoma and sarcoma)

  10. Change in 3D right ventricular ejection fraction

    Absolute change (percentage points) from baseline in right ventricular ejection fraction measured by 3D echocardiography.

    Measured: From baseline (before start of cancer therapy) through 12 months of follow-up (breast cancer) and 24 months of follow-up (lymphoma and sarcoma)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 2026
  2. Study start3 Feb 2025
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
130 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07916337
Sponsor's protocol ID
2024-06788-01
Acronym
SAFE-HEART
Status last verified
Oct 2026
First submitted
22 Oct 2026
Last updated
4 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Individual participant data will not be shared publicly due to Swedish and EU data protection regulations (GDPR) and the conditions of the ethical approval, which do not permit transfer of personal data outside the research group. De-identified data may be made available to qualified researchers upon reasonable request to the principal investigator, subject to approval by the Swedish Ethical Review Authority and a data sharing agreement.

Questions about this trial

What is this clinical trial studying?

An observational study of Cancer Related Cardiovascular Toxicity and Anthracycline Related Cardiotoxicity in Breast Cancer, run by Region Skane at 1 site in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ashkan Labaf, MD, PhD (+4646-171000, ashkan.labaf@med.lu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in 3D left ventricular strain parameters compared with 2D global longitudinal strain during follow-up (time frame: From baseline (before start of cancer therapy) through 12 months of follow-up (breast cancer) and 24 months of follow-up (lymphoma and sarcoma)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.

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