Validation of CMR Against Invasive Haemodynamics in Patients With HFpEF
DECIPHER-HFpEF
Validation of Cardiovascular Magnetic Resonance Against Invasive Haemodynamics in Patients With Heart Failure With Preserved Ejection Fraction (DECIPHER HFpEF)
1 other identifier
observational
185
1 country
7
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started Jan 2018
Longer than P75 for all trials
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 14, 2017
CompletedFirst Posted
Study publicly available on registry
August 16, 2017
CompletedStudy Start
First participant enrolled
January 14, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2022
CompletedMarch 10, 2023
March 1, 2023
5 years
May 14, 2017
March 8, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Significant influence of MR Imaging Parameters on a multivariate model to describe the invasive pressure volume relations (EDPVR).
Using a multivariable regression analysis and a respective F test.
up to 4 weeks. No follow up is planned.
Secondary Outcomes (7)
Association between CMR T1-mapping and biopsy results.
up to 4 weeks. No follow up is planned.
Association between CMR flow echocardiographic flow
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
up to 4 weeks. No follow up is planned.
Association between CMR function and echocardiographic function
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.
up to 4 weeks. No follow up is planned.
- +2 more secondary outcomes
Study Arms (4)
Main group
Blood sampling Comprehensive Cardiovascular magnetic resonance (CMR) Transthoracic echocardiography (TTE) (EchoErgo) Invasive pressure-volume (PV) Loops Left ventricular (LV) biopsy
Reproducibility group
Stress-perfusion Cardiovascular magnetic resonance (CMR)
Age/gender matched control group
Blood sampling Stress-perfusion Cardiovascular magnetic resonance (CMR) TTE (EchoErgo)
Healthy volunteers
Blood sampling Stress-perfusion Cardiovascular magnetic resonance (CMR) TTE (EchoErgo)
Interventions
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.
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.
Measurements will include cavity dimensions, flow velocities, myocardial motion velocity and strain as well as for change of parameters during ergometric stress.
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.
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.
Eligibility Criteria
Patients with diagnostic criteria for HFpEF, age/gender matched controls and healty volunteers
You may qualify if:
- Ability to provide informed consent
- Typical HF symptoms (NYHA stage II-III) within the last 6 months
- EF \> 45 % with absence of structural heart disease on echocardiography (except left ventricular hypertrophy or left atrial enlargement)
- Echocardiographic evidence of increased left ventricular filling pressures
- E/E'sep \>15 OR E/E'lat \>12 OR Av E/E' \>13 OR
- E/E' \>9 AND left atrial (LA) volume \>34 ml/m2 OR systolic pulmonary artery pressure (PAsys): \>35 mmHg;
- Indication for invasive hemodynamic work-up
- Unclear aetiology of heart failure
- Adults: age \>18 years
You may not qualify if:
- Patients unable or unwilling to provide informed consent
- 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)
- Contraindication for invasive work-up (allergy to contrast agent, severe renal insufficiency with estimated glomerular filtration rate (eGRF) \<30 ml/min)
- Contraindications for a contrast enhanced CMR study (allergy to contrast agent, incompatible devices or implants (e.g. non-MR conditional pacemaker), severe claustrophobia)
- Previous medical history of EF \<45%
- Imaging findings confirming a specific diagnosis of myocardial impairment (e.g. amyloid, ischaemic heart disease, valvular disease)
- Age-gender matched controls:
- Ability to provide informed consent
- No current or history of symptoms, signs or therapy for heart disease
- EF \> 45 % with absence of structural heart disease on echocardiography (except left ventricular hypertrophy or left atrial enlargement)
- Adults: age \>18 years
- Patients unable or unwilling to provide informed consent
- 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)
- 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))
- Previous medical history of EF \<45%
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
University Hospital Frankfurt
Frankfurt am Main, Hesse, 60590, Germany
Kerckhoff Klinik
Bad Nauheim, Germany
Charite Centrum Herz-, Kreislauf- und Gefäßmedizin
Berlin, Germany
University Hospital Göttingen
Göttingen, Germany
University Hospital
Heidelberg, Germany
Herzzentrum Leipzig
Leipzig, Germany
Uniersity Hospital Mainz
Mainz, Germany
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Eike C Nagel, MD, PhD
Goethe University Frankfurt
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Univ. Prof. Dr. med.
Study Record Dates
First Submitted
May 14, 2017
First Posted
August 16, 2017
Study Start
January 14, 2018
Primary Completion
December 31, 2022
Study Completion
December 31, 2022
Last Updated
March 10, 2023
Record last verified: 2023-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF, CSR, ANALYTIC CODE
- Time Frame
- 1 year after finalization of primary analysis
- Access Criteria
- Via Use and Access Policy of DZHK
All data will be shared with other researchers within the German Centre for Cardiovascular Research (DZHK) via the Use and Access Rules