Clinical trial NCT03585933: Prognostic Value of Myocardial Fibrosis in Severe Aortic Valve Stenosis
Official title: Prognostic Value of Myocardial Fibrosis in Severe Aortic Valve Stenosis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Aortic Stenosis, Calcific
Keywords: Myocardial fibrosis
Severe aortic stenosis
Cardiovascular magnetic resonance
Scintigraphy
SAVR/TAVI
Lead sponsor: Vilnius University
Sponsor class: OTHER
First posted: 2018-07-13
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with severe aortic stenosis without significant coronary artery disease (CAD), eligible for aortic valve intervention (SAVR or TAVI).

Brief summary: Degenerative aortic valve stenosis (AS) is the most common valve heart disease in the developed Western countries. The hemodynamic progression of AS occurs over time and leads to LV hypertrophy (LVH) as a compensation mechanism of the heart. Morphological changes such as increasing muscle fibre thickness, collagen volume, and interstitial fibrosis occur in AS patients. These changes result in left ventricular (LV) diastolic and systolic dysfunction and, consequently, to with AS related symptoms. When symptoms associated with AS appear, patients' prognosis is poor if surgical aortic valve replacement (SAVR) or a trans-catheter aortic valve implantation (TAVI) is not performed.

Primary hypothesis of the research: fibrotic changes in the myocardium are related to immediate (in hospital) or long-term complications (MACE and all-cause mortality) in patients with severe AS.

The goal of the study is to determine the prognostic implications of focal as well as diffuse myocardial fibrosis in patients with severe aortic valve stenosis.

Detailed description: AS is the most common valvular heart condition in the Western world. In response to increased afterload imposed by AS adaptive left ventricular (LV) remodelling occurs which in a course of a disease transitions from LV hypertrophy to maladaptive changes in the myocardium leading to cardiac decompensation and symptoms development. This transition is predominantly driven by myocardial fibrosis and myocyte cell death. Increasing evidence have demonstrated that presence of myocardial fibrosis, detected by cardiovascular magnetic resonance (CMR), could serve as an early marker of LV decompensation and predict adverse outcomes in patients with aortic stenosis. Currently, the indications for valvular replacement are based on the stenosis severity evaluated by echocardiography and the presence of symptoms.

The objective of the project is to identify parameters of non-invasive imaging modalities (two-dimensional echocardiography with an extended myocardial deformation analysis, 1.5 T CMR with T1 parametric map and late gadolinium enhancement (LGE) predictive of cardiac decompensation and to evaluate the prognostic significance of myocardial fibrotic changes in patients with severe degenerative AS. In patients with suspicion of cardiac amyloidosis, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy will be performed.

Study design: a prospective, open, case-driven, multicentre study (Lithuania, Denmark).

Investigators will assess LV structural and functional alterations before and 12 months after aortic valve intervention. Cardiac imaging data will be aligned with histopathological data from myocardial tissue samples collected at the time of aortic valve replacement in SAVR group. In patients with suspicion of cardiac amyloidosis, DPD scintigraphy and further evaluation regarding amyloidosis will be performed.

Eligibility criteria: Inclusion Criteria:

* Severe aortic stenosis (aortic valve area \<1.0cm2 or aortic valve area index \<0.6 cm2/m2
* Age ≥18 years.
* Signed informed patient consent form.

Exclusion Criteria:

* Severe valvular disease other than AS.
* Significant coronary heart disease requiring revascularisation.
* History of myocardial infarction.
* Previous cardiac surgery.
* Severe renal impairment eGFR \<30ml/min/1.73m2.
* Any absolute contraindication to CMR.
* Inherited or acquired cardiomyopathy.
* Other medical conditions that limits life expectancy or precludes SAVR or TAVI.
* Pregnant or nursing women
* Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study or to follow the protocol
* Patients in permanent atrial fibrillation.
* Significant chronic obstructive pulmonary disease (FEV1 \<70% of predicted value)
* Patient with implanted devices (pacemaker, ICD)

Primary outcomes:
measure: A composite of all-cause mortality and MACE (Acute myocardial infarction, stroke, heart failure requiring hospitalisation)
timeFrame: 2 years
Secondary outcomes:
measure: Cardiovascular mortality
timeFrame: 2 years
measure: Short term mortality
timeFrame: 30 days
measure: Lengh of hospital stay
timeFrame: 30 days
measure: Time to the event ( deathe of MACE)
timeFrame: 2 years
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros clinics
Study officials:
affiliation: Aalborg University
name: Peter Sogaard, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Balciunaite G, Palionis D, Zurauskas E, Skorniakov V, Janusauskas V, Zorinas A, Zaremba T, Valeviciene N, Aidietis A, Serpytis P, Rucinskas K, Sogaard P, Glaveckaite S. Prognostic value of myocardial fibrosis in severe aortic stenosis: study protocol for a prospective observational multi-center study (FIB-AS). BMC Cardiovasc Disord. 2020 Jun 8;20(1):275. doi: 10.1186/s12872-020-01552-8.