The Role of Cardiac Mechanics, Biomarkers and Frailty in Aortic Stenosis

Recruiting

• Conditions: Heart Failure; Aortic Stenosis
• Interventions: Other: Observational only

• Registration Number: NCT02856620
• Lead Sponsor: Christine Henri

Brief Summary

The role of cardiac mechanics, circulating biomarkers and frailty in predicting outcomes in patients with aortic stenosis after aortic valve replacement (SCRABLES -The 2-Parts Study) Part I: Observational study to characterize phenotypes, structural alterations and biomarkers profiles in a broad spectrum of patients with aortic stenosis and heart failure with preserved ejection fraction (HFpEF).

Part II: Prospective cohort study to characterize patients' phenotypes, cardiac structural alterations, circulating biomarkers and frailty in order to optimize risk stratification and patient selection for aortic valve intervention.

Detailed Description

Part I: This part will be an observational exploratory analysis to collate available data from Treatment of preserved cardiac function heart failure with an aldosterone antagonist trial (TOPCAT) cohort regarding the potential role of clinical phenotype, structural alterations and biomarkers profiles that can help determine symptom severity in a AS and HFpEF, and offer insights into which patients with AS may suffer from HFpEF after aortic valve replacement (AVR).

Part II: This part will be a prospective cohort study to create an AS functional capacity score that will include phenotypic classification, structural alterations using novel echocardiographic parameters such as cardiac mechanics, biomarkers profiles and frailty evaluation in order to more accurately predict functional capacity before (Segment A) and after aortic valve intervention (Segment B) and to compare with healthy control group (Segment C).

Study Timeline

• Study Start: 2016-07
• Study First Submitted: 2016-07-26
• Study First Submitted QC: 2016-08-02
• Study First Posted: 2016-08-05
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-20
• Last Update Posted: 2024-11-22
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

Part I - Patients part of the TOPCAT cohort from Americas fulfilling inclusion criteria of Part II-Group 3 (see below) and/or patients enrolled in the Part II study

Part II - Segment A and B Age ≥ 18 years old AS classified according to aortic valve area measured by Doppler echocardiography Group 1: Moderate AS (1.0-1.5cm2) Group 2: Severe AS (1cm2) Group 3: HF with preserved left ventricular ejection fraction (LVEF ≥45%) without significant AS

Part II - Segment C (Control Group) Age ≥ 18 years old Healthy subject taking into account exclusions parameters at the time of screening Able to sign the consent form

Exclusion Criteria

Part I and II - Segment A and B Prior AVR either by surgery or trans-aortic valve implantation; Severe mitral valve disease or aortic regurgitation; LVEF < 45% Myocardial infarction within the previous 3 months; Angina limiting the 6MWTD and thought to be the result of severe coronary artery disease; Cerebrovascular transient ischemic attack or stroke within the previous 6 months; Known active infection or cancer; renal insufficiency (glomerular filtration rate <30 mL/min/1.73m2) or end-stage renal disease; Significant anemia (haemoglobin <90 g/L) or thrombocytopenia (platelet count <50), history of bleeding diathesis or coagulopathy; Life expectancy <12 months due to non-cardiac co-morbid conditions; Chronic obstructive pulmonary disease with Global initiative for chronic obstructive lung disease (GOLD) stages 3-4; musculoskeletal disease limiting the ability to perform the 6MWTD.

Part II - Segment C (Control Group) History of cardiovascular disease Risk factors associated with cardiovascular (treated diabetes, hypertension, body mass index >30kg/m2) Pregnancy or breastfeeding All other cause from Segment A and B

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Moderate AS without HF	Observational only	-
HFpEF without AS	Observational only	-
Normal age-matched controls	Observational only	-
Severe AS without HF	Observational only	-
Moderate AS with HF	Observational only	-
Severe AS with HF	Observational only	-

Primary Outcome Measures

Name	Time	Method
6-Minutes Walk Test Distance (6MWTD)	12 to 18 months

Secondary Outcome Measures

Name	Time	Method
Kansas City Cardiomyopathy Questionnaire (KCCQ)	12 to 18 months
The Physical Ability Score (PAS)	12 to 18 months
Occurrence of major adverse events defined as stroke, myocardial infarction, pacemaker implantation, prolonged (>14 days) or re-hospitalization, lack of reduction in doses of diuretics, new onset of heart failure and mortality	12 to 18 months

Trial Locations

Locations (1)

Montreal Heart Institute; 🇨🇦 Montreal, Quebec, Canada