Validation of CMR Against Invasive Haemodynamics in Patients With HFpEF

Completed

• Conditions: Heart Failure With Normal Ejection Fraction
• Interventions: Diagnostic Test: Comprehensive Cardiovascular magnetic resonance (CMR); Diagnostic Test: Blood sampling; Diagnostic Test: TTE (EchoErgo); Diagnostic Test: Invasive pressure-volume (PV) Loops; Diagnostic Test: Left ventricular (LV) biopsy

• Registration Number: NCT03251183
• Lead Sponsor: Goethe University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-05-14
• Study First Submitted QC: 2017-08-12
• Study First Posted: 2017-08-16
• Study Start: 2018-01-14
• Primary Completion: 2022-12-31
• Study Completion: 2022-12-31
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-08
• Last Update Posted: 2023-03-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 185

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Age/gender matched control group	Comprehensive Cardiovascular magnetic resonance (CMR)	Blood sampling Stress-perfusion Cardiovascular magnetic resonance (CMR) TTE (EchoErgo)
Main group	Blood sampling	Blood sampling Comprehensive Cardiovascular magnetic resonance (CMR) Transthoracic echocardiography (TTE) (EchoErgo) Invasive pressure-volume (PV) Loops Left ventricular (LV) biopsy
Main group	Left ventricular (LV) biopsy	Blood sampling Comprehensive Cardiovascular magnetic resonance (CMR) Transthoracic echocardiography (TTE) (EchoErgo) Invasive pressure-volume (PV) Loops Left ventricular (LV) biopsy
Main group	Comprehensive Cardiovascular magnetic resonance (CMR)	Blood sampling Comprehensive Cardiovascular magnetic resonance (CMR) Transthoracic echocardiography (TTE) (EchoErgo) Invasive pressure-volume (PV) Loops Left ventricular (LV) biopsy
Main group	TTE (EchoErgo)	Blood sampling Comprehensive Cardiovascular magnetic resonance (CMR) Transthoracic echocardiography (TTE) (EchoErgo) Invasive pressure-volume (PV) Loops Left ventricular (LV) biopsy
Reproducibility group	Comprehensive Cardiovascular magnetic resonance (CMR)	Stress-perfusion Cardiovascular magnetic resonance (CMR)
Healthy volunteers	TTE (EchoErgo)	Blood sampling Stress-perfusion Cardiovascular magnetic resonance (CMR) TTE (EchoErgo)
Age/gender matched control group	TTE (EchoErgo)	Blood sampling Stress-perfusion Cardiovascular magnetic resonance (CMR) TTE (EchoErgo)
Healthy volunteers	Comprehensive Cardiovascular magnetic resonance (CMR)	Blood sampling Stress-perfusion Cardiovascular magnetic resonance (CMR) TTE (EchoErgo)
Main group	Invasive pressure-volume (PV) Loops	Blood sampling Comprehensive Cardiovascular magnetic resonance (CMR) Transthoracic echocardiography (TTE) (EchoErgo) Invasive pressure-volume (PV) Loops Left ventricular (LV) biopsy
Reproducibility group	Blood sampling	Stress-perfusion Cardiovascular magnetic resonance (CMR)
Healthy volunteers	Blood sampling	Blood sampling Stress-perfusion Cardiovascular magnetic resonance (CMR) TTE (EchoErgo)
Age/gender matched control group	Blood sampling	Blood sampling Stress-perfusion Cardiovascular magnetic resonance (CMR) TTE (EchoErgo)

Primary Outcome Measures

Name	Time	Method
Significant influence of MR Imaging Parameters on a multivariate model to describe the invasive pressure volume relations (EDPVR).	up to 4 weeks. No follow up is planned.	Using a multivariable regression analysis and a respective F test.

Secondary Outcome Measures

Name	Time	Method
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.	Using suitable regression and correlation Analysis.
Association between CMR flow echocardiographic flow	up to 4 weeks. No follow up is planned.	Using suitable regression and correlation Analysis.
Reproducibility at one site.	up to 4 weeks. No follow up is planned.	Using respective intra-class correlations in the groups with multiple measurements.
Association between CMR T1-mapping and biopsy results.	up to 4 weeks. No follow up is planned.	Using suitable regression and correlation Analysis.
Variability between the different sites.	up to 4 weeks. No follow up is planned.	Using respective intra-class correlations in the groups with multiple measurements.
Association between CMR function and echocardiographic function	up to 4 weeks. No follow up is planned.	Using suitable regression and correlation Analysis.
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.	Using the patient and control groups with comparative ROC analysis and DeLong tests.

Trial Locations

Locations (7)

Uniersity Hospital Mainz; 🇩🇪 Mainz, Germany

University Hospital Frankfurt; 🇩🇪 Frankfurt, Hesse, Germany

University Hospital; 🇩🇪 Heidelberg, Germany

Kerckhoff Klinik; 🇩🇪 Bad Nauheim, Germany

Charite Centrum Herz-, Kreislauf- und Gefäßmedizin; 🇩🇪 Berlin, Germany

University Hospital Göttingen; 🇩🇪 Göttingen, Germany

Herzzentrum Leipzig; 🇩🇪 Leipzig, Germany