NCT03251183

Validation of CMR Against Invasive Haemodynamics in Patients With HFpEF

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

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 185 (actual)
• Sponsor: Goethe University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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.

Conditions

• Heart Failure With Normal Ejection Fraction

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2018-01-14
• Primary completion: 2022-12-31
• Completion: 2022-12-31
• First posted: 2017-08-16
• Last updated: 2023-03-10

Locations

7 sites across 1 country: Germany