Clinical trial NCT03251183: Validation of CMR Against Invasive Haemodynamics in Patients With HFpEF
Official title: Validation of Cardiovascular Magnetic Resonance Against Invasive Haemodynamics in Patients With Heart Failure With Preserved Ejection Fraction (DECIPHER HFpEF)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Failure With Normal Ejection Fraction
Lead sponsor: Goethe University
Sponsor class: OTHER
Collaborators: name: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
First posted: 2017-08-16
Enrollment: 185
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with diagnostic criteria for HFpEF, age/gender matched controls and healty volunteers

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Significant influence of MR Imaging Parameters on a multivariate model to describe the invasive pressure volume relations (EDPVR).
timeFrame: up to 4 weeks. No follow up is planned.
Secondary outcomes:
measure: Association between CMR T1-mapping and biopsy results.
timeFrame: up to 4 weeks. No follow up is planned.
measure: Association between CMR flow echocardiographic flow
timeFrame: up to 4 weeks. No follow up is planned.
measure: Association between a model for diastolic function based on CMR with a model of diastolic function based on echocardiography
timeFrame: up to 4 weeks. No follow up is planned.
measure: Association between CMR function and echocardiographic function
timeFrame: up to 4 weeks. No follow up is planned.
measure: Discriminatory capacity of a multivariate model of invasive and a multivariate model of non-invasive variables.
timeFrame: up to 4 weeks. No follow up is planned.
measure: Reproducibility at one site.
timeFrame: up to 4 weeks. No follow up is planned.
measure: Variability between the different sites.
timeFrame: up to 4 weeks. No follow up is planned.
Other outcomes:
Locations:
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt
state: Hesse
city: Bad Nauheim
country: Germany
facility: Kerckhoff Klinik
city: Berlin
country: Germany
facility: Charite Centrum Herz-, Kreislauf- und Gefäßmedizin
city: Göttingen
country: Germany
facility: University Hospital Göttingen
city: Heidelberg
country: Germany
facility: University Hospital
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig
city: Mainz
country: Germany
facility: Uniersity Hospital Mainz
Study officials:
affiliation: Goethe University Frankfurt
name: Eike C Nagel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: