SAVI-AoS: Stress Aortic Valve Index for Assessing Risk in Aortic Valve Stenosis Patients

Sponsor
Catharina Ziekenhuis Eindhoven (Other)
Overall Status
Recruiting
CT.gov ID
NCT04514250
Collaborator
(none)
100
7
72
14.3
0.2

Study Details

Study Description

Brief Summary

Discrepancies exist among aortic stenosis severity classification, patient symptom burden, and - in some cases - even survival. The new Stress Aortic Valve Index (SAVI) metric correlates better with transvalvular flow and might be a better predictor of symptoms and prognosis.

The current study will demonstrate the value of SAVI (both non-invasive and invasive) in patients with moderate aortic stenosis.

The population will consist of subjects at least 50 years old with moderate aortic stenosis (defined as aortic valve area >1.0 cm2 plus either maximal velocity 2.5-3.9 m/s or mean gradient 15-39 mmHg). Subjects with severe concomitant valve disease or severe unrevascularized coronary artery disease will be excluded, so that the isolated prognosis of aortic stenosis can be investigated.

All subjects will undergo invasive SAVI measurements during catheterization. Furthermore patients will receive non-invasive testing with an exercise echocardiogram and computed tomography (CT) scan for non-invasive SAVI measurements.

The short-term objective will compare SAVI with standard resting indexes for symptom burden, functional capacity, and biomarkers. The long-term objective will associate SAVI and standard resting indexes with clinical outcomes related to valvular disease. The investigators hypothesize that low SAVI (more marked AS during stress) will track with more symptoms and a worse prognosis.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The patients will have several study visits. The index visit will be planned to obtain informed consent and baseline parameters. The measurement visit(s) will consist of the invasive SAVI measurement, echocardiogram, stress echo imaging, 6-minute walk test, quality of life questionnaire, and the cardiac CT. During the final visit after 12 months, subjects will undergo a CT valvular calcium scan, quality of life questionnaire, and 6-minute walk test. Every subject will have an echocardiogram yearly as suggested by guideline criteria and could possibly be contacted until five years after enrollment. Blood samples will be drawn at baseline and the 1-year follow-up. Potentially the new SAVI metric could identify patients at higher risk among those with moderate gradient AS. However, since no outcome data currently exists regarding SAVI and prognosis, no conclusions could be derived from these measurements until study completion.

Condition or Disease Intervention/Treatment Phase

    Study Design

    Study Type:
    Observational [Patient Registry]
    Anticipated Enrollment :
    100 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Stress Aortic Valve Index for Assessing Risk in Aortic Valve Stenosis Patients
    Actual Study Start Date :
    Apr 14, 2021
    Anticipated Primary Completion Date :
    Apr 14, 2027
    Anticipated Study Completion Date :
    Apr 14, 2027

    Outcome Measures

    Primary Outcome Measures

    1. Evaluation of the valve metrics vs baseline clinical parameters (KCCQ) [1 to 5 years]

      A primary endpoint is the comparison of baseline clinical parameters (quality of life survey (Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) (score 1-100), between SAVI (dimensionless) and each of mean aortic gradient (mmHg), aortic valve area (cm2), and maximal aortic valve velocity (m/s)

    2. Evaluation of the valve metrics vs baseline clinical parameters (6MWT) [1 to 5 years]

      A primary endpoint is the comparison of baseline clinical parameters (6 minute walking test (6MWT) (meters), between SAVI (dimensionless) and each of mean aortic gradient (mmHg), aortic valve area (cm2), and maximal aortic valve velocity (m/s)

    3. Evaluation of the valve metrics vs baseline clinical parameters (biomarkers) [1 to 5 years]

      A primary endpoint is the comparison of baseline clinical parameters (biomarkers (NT-proBNP (pg/ml); troponin (ng/L))), between SAVI (dimensionless) and each of mean aortic gradient (mmHg), aortic valve area (cm2), and maximal aortic valve velocity (m/s)

    Secondary Outcome Measures

    1. Correlation between invasive (cardiac catherization) and non-invasive (stress echocardiography; computational fluid dynamics obtained from CT scan data) SAVI measurements [1 year]

      Secondary endpoints will include correlations between invasive (with pressures (mmHg) obtained during cardiac catheterization) and noninvasive (calculated based on pressures (mmHg) achieved during echocardiographic/computional fluid dynamics) SAVI (dimensionless) measurements to explore if stress assessment of the aortic valve can be imaged non-invasively or if it requires invasive hemodynamic measurement for acceptable precision. The same will be done with the cardiac CT scans that will be analyzed to see if computational fluid dynamics can simulate invasive SAVI (dimensionless).

    2. SAVI vs. clinical outcome (number of hospitalizations (hear failure/angina/syncope/rhythm disturbances/valvular intervention/any death/cardiac death) [1 to 5 years]

      Compare SAVI (dimensionless) against standard indexes of aortic stenosis for a composite clinical endpoint of hospital admission for heart failure, angina or syncope, arrhythmia (atrial fibrillation, ventricular tachycardia), valvular intervention (SAVR, TAVI, balloon valvuloplasty), death of any cause, and cardiac death

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years and Older
    Sexes Eligible for Study:
    All
    Inclusion Criteria:
    • Age ≥ 50 years

    • Moderate aortic stenosis confirmed in the past 3 months by standard echocardiographic evaluation: aortic valve area >1.0 cm2 plus either maximal velocity 2.5-3.9 m/s or mean gradient 15-39 mmHg

    • Ability to undergo exercise stress testing

    • Ability to understand and the willingness to provide written informed consent

    Exclusion Criteria:

    A potential subject who meets any of the following criteria will be excluded from participation in this study

    • Any hemodynamic criterion for severe AS: maximal velocity >= 4 m/s, mean gradient >= 40mmHg, aortic valve area =< 1 cm2

    • Percutaneous coronary intervention or coronary artery bypass grafting in the past three months, or have revascularization planned in the near future

    • Known, unrevascularized, and severe coronary artery disease (for example a 90% diameter stenosis or FFR<0.7 in the proximal left anterior descending artery)

    • Impaired left ventricular function (ejection fraction <50%)

    • Unicuspid, bicuspid, or non-calcified aortic valve observed during echocardiography (note that later cusp fusion noted during study-related cardiac imaging will not exclude a subject)

    • Severe aortic regurgitation, mitral valve disease, tricuspid regurgitation, or a significant intracardiac shunt

    • Co-existing hypertrophic cardiomyopathy or severe septal hypertrophy >15mm

    • Persistent atrial fibrillation with uncontrolled ventricular response

    • Recent (within 6 weeks) acute coronary syndrome

    • Estimated glomerular filtration rate ≤30 mL/min or end-stage renal disease on replacement therapy (dialysis)

    • Severe COPD GOLD stage 3 or 4, home oxygen dependence, or ≥2 pulmonary inhalers (note that well-treated and stable asthma and GOLD stage 1 or 2 COPD is permitted)

    • Severe comorbid condition with life expectancy <2 years

    • Prior adverse reaction to dobutamine

    • Severe iodine contrast allergy

    • Pregnancy

    • Severe pulmonary hypertension with systolic pulmonary artery pressure greater than 50mmHg or isolated and symptomatic right ventricular failure

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UMass Medical Memorial Center Worcester Massachusetts United States 01655
    2 UTHealth Houston, McGovern Medical School Houston Texas United States 77030
    3 Fiona Stanley Hospital Perth Australia
    4 Aalborg University Hospital Aalborg Denmark
    5 Asan Medical Center Seoul Korea, Republic of
    6 Catharina Hospital Eindhoven Eindhoven Netherlands 5623EJ
    7 Erasmus University Medical Center Rotterdam Netherlands

    Sponsors and Collaborators

    • Catharina Ziekenhuis Eindhoven

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    dr Pim A.L. Tonino, dr., Catharina Ziekenhuis Eindhoven
    ClinicalTrials.gov Identifier:
    NCT04514250
    Other Study ID Numbers:
    • SAVI-AoS NL74875.100.20
    First Posted:
    Aug 14, 2020
    Last Update Posted:
    Jul 20, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 20, 2022