Cardiac Output, Cerebral Perfusion and Cognition in Patients Undergoing TAVI (CAPITA)

Cardiac Output, Cerebral Perfusion and Cognition in Patients With Severe Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Implantation

Rationale: Cardiovascular disease and cognitive diseases are closely related. Cognitive impairment is common (21-39%) among patients with severe aortic valve stenosis. The proof-of-concept CP-TAVI study showed that increased cardiac output following transcatheter aortic valve implantation (TAVI) was associated with increased cerebral blood flow. It is hypothesized that increased cerebral blood flow (CBF) subsequently leads to improved cognitive functioning. Additionally, silent micro emboli caused by crushing of the calcified native valve during TAVI may cause cognitive deterioration. If it could be predicted which patients are at risk for TAVI induced cerebral micro emboli, these patients could benefit from cerebral protection devices, preventing cognitive decline.

Objective: The objectives of the CAPITA study are 1A) to identify whether an increase in cardiac output after TAVI is associated with an increase of global CBF; 1B) explore regional differences in CBF after TAVI; 1C) determine whether (global or regional) increased CBF is associated with improved cognitive functioning; 1D) identify patient and procedural characteristics associated with increased cardiac output, CBF and cognitive functioning; 2A) identify the incidence and volume of new white matter hyperintensities after TAVI; 2B) evaluate patient and procedural predictors for the increase in white matter hyperintensities volume, including baseline aortic valve calcification volume, measured with computed tomography; 2C) if aortic valve calcification volume predicts new white matter hyperintensities, define a cut-off value for high-risk patients; 2D) assess whether the increase in white matter hyperintensity volume is associated with deterioration of cognitive scores.

Study design: Prospective observational study, measuring cardiac output (echocardiography), cerebral blood flow (arterial spin labelling magnetic resonance imaging) and cognitive functioning (neuropsychological test battery) prior to TAVI (<24 hours to <one week) and at 3 months follow-up. At one year follow-up, cardiac output and cognitive function will be assessed.

Study population: Patients with severe aortic valve stenosis eligible for transfemoral TAVI (n=142).

Main study parameters/endpoints: Cardiac output (L/min), cerebral blood flow (mL/100g/min, change in %, relative to baseline) and cognitive functioning (extensive neuropsychological testing 60-90 minutes).

Study Overview

• Status: Recruiting
• Conditions: Cognitive Impairment; Aortic Valve Stenosis; Cognitive Change
• Intervention / Treatment: Device: transcatheter aortic valve implantation

• Study Type: Observational
• Enrollment (Anticipated): 142

Contacts and Locations

• Study Contact: Name: Astrid van Nieuwkerk, MD; Phone Number: 0031205666603; Email: a.vannieuwkerk@amsterdamumc.nl

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands
      • Recruiting
      • Amsterdam Universitair Medisch Centrum (AUMC) - Locatie AMC
      • Contact: Astrid van Nieuwkerk, MD; Email: a.vannieuwkerk@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

N=142 patients with symptomatic severe aortic valve stenosis selected for transcatheter aortic valve implantation

Description

Inclusion Criteria:

• Severe aortic valve stenosis (aortic valve area <1cm2 and/or mean aortic valve gradient exceeds 50 mmHg) of a native valve
• Eligible for TAVI
• Able and willing to give informed consent
• Age > 18 years

Exclusion Criteria:

• Presence of MRI contra-indication; inability to lay flat for 30 minutes
• Weight > 130 kg
• Neurological disease
• Active malignant disease;
• Insufficient mastery of the Dutch language
• Inability to withdraw from alcohol use for 24 hours
• Non-atherosclerotic vascular disease (eg vasculitis)
• Planned surgery with general anesthesia within three months after TAVI.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Potential positive cerebral effects generated by an increase in cerebral blood flow after TAVI	Cerebral blood flow (mL/100g/min, change in %, relative to baseline) as measured on arterial spin labelling magnetic resonance imaging)	Change from baseline (pre-tavi) to 3 months
Potential negative cerebral outcomes as a consequence of TAVI induced cerebral embolization	New white matter hyperintensities (number and volume [mL]) and (micro) bleeds	Change from baseline (pre-tavi) to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive functioning	Cognitive functioning on various domains. As measured by a standardized extensive neuropsychological test battery (60-90 minutes) performed by a trained neuropsychologist.	Change from baseline (pre-tavi) to 3 months
Cognitive functioning	Cognitive functioning on various domains. As measured by a standardized extensive neuropsychological test battery (60-90 minutes) performed by a trained neuropsychologist.	1 year
Cardiac output	Cardiac output (L/min) as measured on echocardiography (LVOT VTI)	Change from baseline (pre-tavi) to 3 months
Cardiac output	Cardiac output (L/min) as measured on echocardiography (LVOT VTI)	1 year

Collaborators and Investigators

• Sponsor: Ronak Delewi

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2020
• Primary Completion (Anticipated): November 1, 2022
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: April 11, 2022
• First Submitted That Met QC Criteria: July 28, 2022
• First Posted (Actual): July 29, 2022

Study Record Updates

• Last Update Posted (Actual): July 29, 2022
• Last Update Submitted That Met QC Criteria: July 28, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Cognition; Cognitive impairment; Aortic valve stenosis; Transcatheter aortic valve implantation; Cerebral perfusion; Cerebral blood flow
• Additional Relevant MeSH Terms: Mental Disorders; Heart Diseases; Cardiovascular Diseases; Neurocognitive Disorders; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Cognition Disorders; Aortic Valve Stenosis; Cognitive Dysfunction; Constriction, Pathologic
• Other Study ID Numbers: NL72247.018.19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No