The primary objective of this study is to assess wall shear stress in the left ventricle outflow tract using 4D flow CMR in healthy controls, asymptomatic HCM and before and after surgical myectomy in patients with HOCM,
ID
Source
Brief title
Condition
- Myocardial disorders
- Cardiac and vascular disorders congenital
- Cardiac therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome: wall shear stress in HOCM patients (preoperative and at 6
months follow-up), HCM patients and controls.
Secondary outcome
First secondary outcome: Omics in HOCM patients
Omics (Tomo-seq and/or nanopore and/or other omics technique) will yield gene
expression information for approximately 10.000 genes, for ±200 positions along
±2 cm tissue samples of patients with HCM. The raw output thus is a 10.000 x
200 gene expression table (genes x position) for each sample for each patient.
Second secondary outcome: Hemodynamic parameters in HOCM patients, HCM patients
and controls.
Kinetics (kinetic energy, energy loss, LV myocardial deformation (by myocardial
strain analysis)) and blood flow (helicity and vorticity of blood flow will be
obtained to characterize LV flow).
Background summary
Hypertrophic Cardiomyopathy (HCM) is an inherited myocardial disease
characterised by left ventricular hypertrophy (LVH), which carries an increased
risk of life-threatening arrhythmias and sudden cardiac death. Presentation and
phenotype of HCM also varies during lifetime, with specific differences between
children and adults with HCM. HCM is associated with left ventricular outflow
tract obstruction (LVOTO) due to interventricular septum hypertrophy, so called
hypertrophic obstructive cardiomyopathy (HOCM). Currently, echocardiography is
the gold standard for the assessment of HCM and most often used to guide
surgical intervention for HOCM, but is hampered with reduced acoustic window.
Meanwhile, cardiac magnetic resonance (CMR) is a comprehensive and non-invasive
imaging modality capable of providing information on cardiac morphology,
function, flow, perfusion and tissue characterization of patients with HCM.
Despite the use of both imaging modalities for preoperative planning of
surgical myectomy, it can still be challenging for the surgeon to correctly
identify the extent and location of LVOT tissue that needs to be surgically
removed in case of symptomatic LVOTO. Too conservative excision may lead to
recurrence of LVOTO, whereas too aggressive excision may negatively affect
cardiac function after surgery.
Recently, four-dimensional (4D) flow CMR has been shown to provide reliable
qualitative and quantitative evaluation of the blood flow within the entire
heart. Several 4D flow CMR studies demonstrated abnormal blood flow patterns
and disturbed kinetics in the LV of HCM patients, specifically in the LVOT. 4D
flow CMR may therefore be of additive value to characterize the location and
extent of LVOT obstruction in HOCM, and thereby be of additive value for
planning of surgical myectomy, in a complementary role to routine CMR and
echocardiography.
Secondly, it is currently unknown whether or which molecular mechanisms
underlie the local remodelling in the LVOT observed in HOCM patients, in
response to local wall tension. In other words, it is unclear to which extent
local gene expression in HCM patients may be related to (abnormalities in)
local flow dynamics, myocardial deformation, and myocardial tissue
characteristics of the LVOT. Based on recent advancements in RNA sequencing it
is possible to obtain local HCM gene expression profiles with a high spatial
resolution. Determination of the relationship between local flow patterns,
myocardial deformation and myocardial tissue characterization in the LVOT, and
how this influences HCM gene expression, could help to improve our
understanding of HCM pathogenesis.
All parameters gained from the CRYSTAL study will add valuable non-invasive
hemodynamic diagnostic parameters for the evaluation of HCM patients (children
and adults), specifically for timing and planning of myectomy, and
post-operative evaluation.
Study objective
The primary objective of this study is to assess wall shear stress in the left
ventricle outflow tract using 4D flow CMR in healthy controls, asymptomatic HCM
and before and after surgical myectomy in patients with HOCM,
Study design
Descriptive study and explorarory
Study burden and risks
HOCM patients undergoing surgical myectomy
o Participating in this study places minimal burden on the participants, as all
clinical investigations are non-invasive and do not involve radiation exposure,
which aligns with standard clinical practice.
o We will reassess the examinations, if any variables are missing from the
examinations report. This process does not add any extra burden since the
examinations have already been conducted. Additionally, the evaluation will be
performed using approved products from UMC Utrecht, thereby introducing minimal
additional risks.
Adults with HCM not undergoing surgical myectomy
o All patients will undergo standard of care examinations according to the UMC
Utrecht hospital, including routine CMR and non-invasive 4D flow imaging,
echocardiography, cardiopulmonary exercise testing and ECG.
o We will reassess the examinations, if any variables are missing from the
examinations report. This process does not add any extra burden since the
examinations have already been conducted. Additionally, the evaluation will be
performed using approved products from UMC Utrecht, thereby introducing minimal
additional risks.
Healthy adults without HCM
o Participation in this study has limited burden and risks for patients as it
entails, questions for baseline characteristic, CMR with additional 4D flow
measurements. A total of 60 minutes of CMR scan time will be the maximum.
o Participating in this study places minimal burden on the participants, as all
clinical investigations are non-invasive and do not involve radiation exposure.
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
HOCM patients undergoing surgical myectomy
o HOCM diagnosis according to the 2020 AHA/ACC Guideline for the Diagnosis and
Treatment of patients With Hypertrophic Cardiomyopathy (2). Patients with
resting or provoked gradients > 50 mm Hg generally considered to be the
threshold for surgical myectomy in those patients with drug-refractory symptoms
(2).
o Patients undergoing surgical myectomy in UMC Utrecht. Heart team (consisting
of one cardiologist and one cardiothoracic surgeon) determine if surgical
myectomy is required.
o Basal and midventricular HCM.
o No concomitant surgery. The following procedures are not considered as
concomitant surgery: MAZE procedure, Left Atrial Appendage (LAA) resection,
device implementation (Pacemaker or ICD).
o Patients > 18 years at the moment of the myectomy procedure
o Participation in UNRAVEL Biobank.
o Willing to comply with the study procedures and written informed consent.
Adults with HCM
o HCM diagnosis according to the 2020 AHA/ACC Guideline for the Diagnosis and
Treatment of patients With Hypertrophic Cardiomyopathy (2). Imaging (2D
echocardiography or CMR) showing a maximal end-diastolic wall thickness of > 15
mm basal or midventricular, in the absence of another cause of hypertrophy.
Limited hypertrophy (13-14 mm) can be diagnostic when present in family members
of a patient with HCM or in conjunction with a positive genetic test.
o Patients > 18 years, if possible aged matched HCM control subjects with
respect to surgical myectomy patients.
o Participation in UNRAVEL Biobank.
o Willing to comply with the study procedures and written informed consent.
Healthy adult controls
o Patients > 18 years.
o Willing to comply with the study procedures and written informed consent.
Exclusion criteria
o General contra-indications to CMR.
o Aortic valve stenosis grade > 2.
o Intrinsic mitral valve (rheumatic, degenerative, infective, and mitral
annulus calcification).
o Apical HCM.
o The coexistence of other forms of congenital heart disease.
o Prior cardiac surgery, stroke, percutaneous coronary intervention or previous
alcohol septal ablation therapy.
o Concomitant surgery in group undergoing surgical myectomy. The following
procedures are not considered as concomitant surgery: MAZE procedure, Left
Atrial Appendage (LAA) resection, device implementation (Pacemaker or ICD).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL84587.041.23 |