Validation of CMR Against Invasive Haemodynamics in Patients With HFpEF (DECIPHER-HFpEF)

March 8, 2023 updated by: Prof. Eike Nagel, Goethe University

Validation of Cardiovascular Magnetic Resonance Against Invasive Haemodynamics in Patients With Heart Failure With Preserved Ejection Fraction (DECIPHER HFpEF)

Heart failure (HF) currently affects app. 2% of the western population and app. 10% of people >75 years. In about 50% of patients with symptomatic HF ejection fraction (EF) is preserved (HF-PEF). Once patients develop symptoms, the prognosis is poor with 25% mortality at 1 year and 50% mortality at 5 years. HFpEF is one of the major unresolved areas in clinical cardiology. The diagnosis of HFpEF remains a diagnosis of exclusion and currently no non-invasive measure provides a clear diagnosis.

Cardiovascular magnetic resonance (CMR) provides non invasive and radiation free evaluation of heart structure and function. New CMR parameters offer the possibility to describe the underlying pathological and physiological changes associated with HFpEF.

The investigators propose to undertake the first systematic comparison between a CMR protocol and invasive haemodynamics as the best possible gold standard, as well as define the histopathological drivers in myocardial biopsies. The investigators will also examine the relations with tissue and serological biomarkers implicated in HFpEF and the role with standard and novel parameters by echocardiography. If successful, this study will provide tools for a reliable and accurate non-invasive characterization of patients with HFpEF, supporting the diagnosis and grading the severity of disease. This study will provide a reference basis for future diagnostic algorithms in HFpEF, both, for CMR and echocardiography, but also for their relative value in comparison to blood markers or invasive testing. In addition to a new pathway to acess the effects of current and novel therapeutic interventions, the investigators see the greatest potential in identifying a disease stage where the myocardial injury may be reversible.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
185

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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Valentina O Puentmann, MD
  • Phone Number: 004969630186760

Study Locations

  • Germany
      • Bad Nauheim, Germany
        • Kerckhoff Klinik
      • Berlin, Germany
        • Charite Centrum Herz-, Kreislauf- und Gefäßmedizin
      • Göttingen, Germany
        • University Hospital Göttingen
      • Heidelberg, Germany
        • University Hospital
      • Leipzig, Germany
        • Herzzentrum Leipzig
      • Mainz, Germany
        • Uniersity Hospital Mainz
    • Hesse
      • Frankfurt, Hesse, Germany, 60590
        • University Hospital Frankfurt

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with diagnostic criteria for HFpEF, age/gender matched controls and healty volunteers

Description

Main/reproducibility group:

Inclusion Criteria:

  1. Ability to provide informed consent
  2. Typical HF symptoms (NYHA stage II-III) within the last 6 months
  3. EF > 45 % with absence of structural heart disease on echocardiography (except left ventricular hypertrophy or left atrial enlargement)

  4. Echocardiographic evidence of increased left ventricular filling pressures

    1. E/E'sep >15 OR E/E'lat >12 OR Av E/E' >13 OR
    2. E/E' >9 AND left atrial (LA) volume >34 ml/m2 OR systolic pulmonary artery pressure (PAsys): >35 mmHg;
  5. Indication for invasive hemodynamic work-up
  6. Unclear aetiology of heart failure
  7. Adults: age >18 years

Exclusion Criteria:

  1. Patients unable or unwilling to provide informed consent
  2. High likelihood of non-diagnostic PV loops of MR imaging (e.g. atrial fibrillation or high rate of premature ventricular contraction (PVC) (> 10 ventricular Extrasystole (VES)/minute), > 150 kg body weight, inability to lie flat or still)
  3. Contraindication for invasive work-up (allergy to contrast agent, severe renal insufficiency with estimated glomerular filtration rate (eGRF) <30 ml/min)
  4. Contraindications for a contrast enhanced CMR study (allergy to contrast agent, incompatible devices or implants (e.g. non-MR conditional pacemaker), severe claustrophobia)
  5. Previous medical history of EF <45%
  6. Imaging findings confirming a specific diagnosis of myocardial impairment (e.g. amyloid, ischaemic heart disease, valvular disease)

Age-gender matched controls:

Inclusion Criteria:

  1. Ability to provide informed consent
  2. No current or history of symptoms, signs or therapy for heart disease
  3. EF > 45 % with absence of structural heart disease on echocardiography (except left ventricular hypertrophy or left atrial enlargement)
  4. Adults: age >18 years

Exclusion Criteria:

  1. Patients unable or unwilling to provide informed consent
  2. High likelihood of non-diagnostic MR imaging (e.g. atrial fibrillation or high rate of PVC (> 10 VES/minute), > 150 kg body weight, inability to lie flat or still)
  3. Contraindications for a contrast enhanced CMR study (allergy to contrast agent, incompatible devices or implants (e.g. non-MR conditional pacemaker), severe claustrophobia, severe renal insufficiency with eGRF <30 ml/min))
  4. Previous medical history of EF <45%
  5. Imaging findings confirming a specific diagnosis of myocardial impairment (e.g. amyloid, ischaemic heart disease, valvular disease)

Healthy volunteers:

Inclusion Criteria:

  1. Ability to provide informed consent
  2. No current or history of symptoms, signs or therapy for heart disease
  3. EF ≥ 50 % with absence of structural heart disease on echocardiography

Exclusion Criteria:

  1. Contraindications for an MR study
  2. High likelihood of non-diagnostic MR imaging (e.g. atrial fibrillation or high rate of PVC (> 10 VES/minute), > 150 kg body weight, inability to lie flat or still)
  3. Subjects unable or unwilling to provide informed consent
  4. EF <50% in patient history
  5. Imaging findings confirming a specific diagnosis of myocardial impairment (e.g. amyloid, ischaemic heart disease, valvular disease)

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Main group
Blood sampling Comprehensive Cardiovascular magnetic resonance (CMR) Transthoracic echocardiography (TTE) (EchoErgo) Invasive pressure-volume (PV) Loops Left ventricular (LV) biopsy
Diagnostic test: Comprehensive Cardiovascular magnetic resonance (CMR)
Cardiovascular magnetic resonance (CMR) provides non-invasive, radiation-free and in-depth evaluation of myocardial structure and function. In addition to established tools for assessment of cardiac volume, mass, function and regional myocardial scar with late Gadolinium enhancement (LGE), several novel quantitative CMR parameters will be assessed including T1-mapping or fully quantitative perfusion Imaging.
Diagnostic test: Blood sampling
Blood samples will eventually be analysed for markers related to heart failure (BNP/NT)-pro-BNP, myocardial inflammation and fibrosis (cytokine profiling, Galectin-3, Procollagen Type I and III, hsCRP). Whole blood will be frozen for DNA isolation and genome analysis. Peripheral blood mononuclear cells will be isolated by Ficoll in a subset of patients and will be used for RNA isolation allowing RNA-seq or reverse transcription (RT) - polymerase chain reaction (PCR) analysis.
Diagnostic test: TTE (EchoErgo)
Measurements will include cavity dimensions, flow velocities, myocardial motion velocity and strain as well as for change of parameters during ergometric stress.
Diagnostic test: Invasive pressure-volume (PV) Loops
Multiple parameters (including EDPVR, ESPVR, dp/dt min, Tau, Ea) will be derived from the various PV loop assessments and additional relevant parameters will be calculated. Right ventricular and pulmonary pressures including pulmonary vascular resistance will be measured with Swan-Ganz catheters using right venous femoral approach.
Diagnostic test: Left ventricular (LV) biopsy

A set of myocardial biopsies for each patient will be stained with Masson Trichrome for qualitative and quantitative assessment of the collagen volume fraction; fat droplets will be identified by red oil staining, Congo Red for amyloid immunohistology will be used to determine total leukocytes (CD45), T-cells (CD3) and monocytes/macrophages (CD68).

A second set of biopsies will be frozen immediately and stored at -80°. Western blot analysis will be performed to determine alterations at the myofilament level including titin isoform composition and phosphorylation status.
Reproducibility group
Stress-perfusion Cardiovascular magnetic resonance (CMR)
Diagnostic test: Comprehensive Cardiovascular magnetic resonance (CMR)
Cardiovascular magnetic resonance (CMR) provides non-invasive, radiation-free and in-depth evaluation of myocardial structure and function. In addition to established tools for assessment of cardiac volume, mass, function and regional myocardial scar with late Gadolinium enhancement (LGE), several novel quantitative CMR parameters will be assessed including T1-mapping or fully quantitative perfusion Imaging.
Diagnostic test: Blood sampling
Blood samples will eventually be analysed for markers related to heart failure (BNP/NT)-pro-BNP, myocardial inflammation and fibrosis (cytokine profiling, Galectin-3, Procollagen Type I and III, hsCRP). Whole blood will be frozen for DNA isolation and genome analysis. Peripheral blood mononuclear cells will be isolated by Ficoll in a subset of patients and will be used for RNA isolation allowing RNA-seq or reverse transcription (RT) - polymerase chain reaction (PCR) analysis.
Age/gender matched control group
Blood sampling Stress-perfusion Cardiovascular magnetic resonance (CMR) TTE (EchoErgo)
Diagnostic test: Comprehensive Cardiovascular magnetic resonance (CMR)
Cardiovascular magnetic resonance (CMR) provides non-invasive, radiation-free and in-depth evaluation of myocardial structure and function. In addition to established tools for assessment of cardiac volume, mass, function and regional myocardial scar with late Gadolinium enhancement (LGE), several novel quantitative CMR parameters will be assessed including T1-mapping or fully quantitative perfusion Imaging.
Diagnostic test: Blood sampling
Blood samples will eventually be analysed for markers related to heart failure (BNP/NT)-pro-BNP, myocardial inflammation and fibrosis (cytokine profiling, Galectin-3, Procollagen Type I and III, hsCRP). Whole blood will be frozen for DNA isolation and genome analysis. Peripheral blood mononuclear cells will be isolated by Ficoll in a subset of patients and will be used for RNA isolation allowing RNA-seq or reverse transcription (RT) - polymerase chain reaction (PCR) analysis.
Diagnostic test: TTE (EchoErgo)
Measurements will include cavity dimensions, flow velocities, myocardial motion velocity and strain as well as for change of parameters during ergometric stress.
Healthy volunteers
Blood sampling Stress-perfusion Cardiovascular magnetic resonance (CMR) TTE (EchoErgo)
Diagnostic test: Comprehensive Cardiovascular magnetic resonance (CMR)
Cardiovascular magnetic resonance (CMR) provides non-invasive, radiation-free and in-depth evaluation of myocardial structure and function. In addition to established tools for assessment of cardiac volume, mass, function and regional myocardial scar with late Gadolinium enhancement (LGE), several novel quantitative CMR parameters will be assessed including T1-mapping or fully quantitative perfusion Imaging.
Diagnostic test: Blood sampling
Blood samples will eventually be analysed for markers related to heart failure (BNP/NT)-pro-BNP, myocardial inflammation and fibrosis (cytokine profiling, Galectin-3, Procollagen Type I and III, hsCRP). Whole blood will be frozen for DNA isolation and genome analysis. Peripheral blood mononuclear cells will be isolated by Ficoll in a subset of patients and will be used for RNA isolation allowing RNA-seq or reverse transcription (RT) - polymerase chain reaction (PCR) analysis.
Diagnostic test: TTE (EchoErgo)
Measurements will include cavity dimensions, flow velocities, myocardial motion velocity and strain as well as for change of parameters during ergometric stress.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Significant influence of MR Imaging Parameters on a multivariate model to describe the invasive pressure volume relations (EDPVR).
Time Frame: up to 4 weeks. No follow up is planned.
Using a multivariable regression analysis and a respective F test.
up to 4 weeks. No follow up is planned.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Association between CMR T1-mapping and biopsy results.
Time Frame: up to 4 weeks. No follow up is planned.
Using suitable regression and correlation Analysis.
up to 4 weeks. No follow up is planned.
Association between CMR flow echocardiographic flow
Time Frame: up to 4 weeks. No follow up is planned.
Using suitable regression and correlation Analysis.
up to 4 weeks. No follow up is planned.
Association between a model for diastolic function based on CMR with a model of diastolic function based on echocardiography
Time Frame: up to 4 weeks. No follow up is planned.
Using suitable regression and correlation Analysis.
up to 4 weeks. No follow up is planned.
Association between CMR function and echocardiographic function
Time Frame: up to 4 weeks. No follow up is planned.
Using suitable regression and correlation Analysis.
up to 4 weeks. No follow up is planned.
Discriminatory capacity of a multivariate model of invasive and a multivariate model of non-invasive variables.
Time Frame: up to 4 weeks. No follow up is planned.
Using the patient and control groups with comparative ROC analysis and DeLong tests.
up to 4 weeks. No follow up is planned.
Reproducibility at one site.
Time Frame: up to 4 weeks. No follow up is planned.
Using respective intra-class correlations in the groups with multiple measurements.
up to 4 weeks. No follow up is planned.
Variability between the different sites.
Time Frame: up to 4 weeks. No follow up is planned.
Using respective intra-class correlations in the groups with multiple measurements.
up to 4 weeks. No follow up is planned.

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Goethe University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Eike C Nagel, MD, PhD, Goethe University Frankfurt

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 14, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 14, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 12, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 16, 2017

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 10, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 8, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Protocol_ Version 1 20170225

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All data will be shared with other researchers within the German Centre for Cardiovascular Research (DZHK) via the Use and Access Rules

IPD Sharing Time Frame

1 year after finalization of primary analysis

IPD Sharing Access Criteria

Via Use and Access Policy of DZHK

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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