Cognitive Outcome After Surgical and Transcatheter Aortic Valve Replacement (COSTA)

Aortic valve stenosis is one of the most common types of heart disease in the aging Western population. While surgical cardiac valve replacement (SAVR) is a standard therapy for patients with aortic stenosis, catheter-assisted aortic valve implantation (TAVI) has developed as an alternative to open-heart surgery, especially for high-risk patients. Recently, increased surgeon experience and improved transcatheter valve systems have led to a global trend to use TAVI in patients with low or intermediate risk. Although cognitive impairment after cardiac surgery is well known, the effect of TAVI on cognitive function has not yet been adequately investigated. The aim of this study is to compare the occurrence and progression of delirium, postoperative cognitive decline (POCD), cerebral infarction, and health-related quality of life (QOL) in patients with intermediate risk for catheter-assisted (TAVI) and surgical (SAVR) aortic valve replacement.

Study Overview

• Status: Completed
• Conditions: Postoperative Delirium; Postoperative Cognitive Dysfunction; Transcatheter Aortic Valve Replacement; Surgical Aortic Valve Replacement
• Intervention / Treatment: Procedure: Transcatheter Aortic Valve Implantation; Procedure: Surgical Aortic Valve Replacement

Detailed Description

The present project is a substudy of the DEDICATE Trial (ID: NCT03112980). It is a randomized intervention study taking place at the Kerckhoff-Klink Bad Nauheim Germany (Campus Justus Liebig University Giessen) involving 100 patients undergoing aortic valve replacement (TAVI vs. SAVR) with a focus on cognitive outcome. A detailed assessment of psychological and health-related functions will be performed before intervention, during hospitalization and 3 months after intervention. During hospitalization, the occurrence and progression of delirium will be assessed with the Intensive Care Delirium Screening Checklist (ICDSC). Other cognitive data will be collected before and 3 months after surgery with a selected and comprehensive neuropsychological test battery, including the evaluation of attention, word fluency, executive functions and various functional areas of memory. In addition, parameters of health-related QOL will be collected before and 3 months after the intervention using the SF-36, and information on anxiety and depression will be collected using the Hospital Anxiety and Depression Scale (HADS). A few days after the intervention, magnetic resonance images of the brain will be acquired to assess cerebral infarction.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marius Butz, Dipl.-Psych.; Phone Number: +496032 996 5812; Email: m.butz@kerckhoff-klinik.de
• Study Contact Backup: Name: Martin Jünemann, Dr.med.M.Sc.; Phone Number: +49641 98545301; Email: Martin.Juenemann@neuro.med.uni-giessen.de

Study Locations

• Germany
  • Bad Nauheim, Germany, 61231
    • Department of Cardiac Surgery, Kerckhoff-Klinik GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 63 years to 83 years (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Heart team decision that both TAVI and SAVR are medically justified based on

   • Degenerative aortic valve stenosis:

     • Mean gradient > 40 mmHg or
     • Jet velocity > 40 m/s or
     • Surface of aortic valve < 1.0 cm²

   • Patient shows symptoms of aortic stenosis

     • NYHA functional class ≥ II or
     • Angina pectoris or
     • Syncope
   • Low to intermediate surgical risk (STS: 2-6%)
   • A transfemoral or alternative access for TAVI can be implemented
2. Patient has agreed in writing to participate in the study
3. Patient is able to understand the patient information and sign it personally
4. Patient agrees to undergo SAVR if randomization into the control group occurs
5. Readiness for MRT examination and neuropsychological testing after 3 months
6. Patients aged 65 to 85 years.
7. Native German speaker (since a neuropsychological test is language dependent)

Exclusion Criteria:

1. Congenital aortic valve defects
2. Untreated clinically significant coronary artery disease or severe mitral or tricuspid insufficiency or mitral stenosis
3. Previous heart surgery
4. Percutaneous coronary intervention performed within one month prior to the study
5. Hemodynamic instability requiring inotropic support or mechanical circulatory support
6. Ischemic stroke or intracranial bleeding within the month before the start of the study
7. Severe ventricular dysfunction with left ventricular ejection fraction < 20% as measured by echocardiogram
8. Hypertrophic obstructive cardiomyopathy or severe basal septum hypertrophy
9. Echocardiographic detection of intracardiac mass, thrombus, vegetation, or endocarditis
10. Any other atherosclerotic disease that is considered as a contraindication for isolated aortic valve surgery
11. Symptomatic carotid or vertebral artery disease
12. Existing neurological or psychiatric disease (particularly cerebral infarction, cranio- cerebral trauma, manifest depression or dementia) that may interfere with neuropsychological testing.
13. Contraindications for MRI examination (e.g. cardiac pacemaker, vena cava filter, claustrophobia)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transcatheter Aortic Valve Implantation	Procedure: Transcatheter Aortic Valve Implantation; Transcatheter Aortic Valve Implantation
Active Comparator: Surgical Aortic Valve Replacement	Procedure: Surgical Aortic Valve Replacement; Surgical Aortic Valve Replacement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with postoperative cognitive decline at 3 months after surgery, defined as a decrease between pre- and postoperative examinations of one standard deviation in at least 20% of all objective neuropsychological parameters	The objective neuropsychological parameters measure cognitive domains like immediate memory span, free recall, recognition memory, selective attention, working memory, inhibition and word fluency. These cognitive domains will be measured with the following instruments: "Verbaler Lern- und Merkfähigkeitstest" (VLMT), "Trail Making Test A/B" (TMT), "Letter Number Span Test" (LNS), Block Tapping Test (BTT), "Regensburger Wortflüssigkeits-Test" (RWT), and "Syndrom-Kurz Test" (SKT).	Immediately pre-surgery to 3 months post-surgery
Number of participants with postoperative cognitive decline at the time of discharge from the acute clinic, defined as a decrease between the pre- and postoperative examinations of one standard deviation measured with the "Montreal Cognitive Assessment"	The "Montreal Cognitive Assessment" (MOCA) is a screening procedure for general cognitive function.	Immediately pre-surgery to approximately 1 week post-surgery
Number of participants with postoperative delirium during the stay in the intensive care unit as assessed by the "Intensive Care Delirium Screening Checklist" (ICDSC)	Postoperative delirium is defined as the occurrence of at least one delirious episode during a stay in the intensive care unit. The "Intensive Care Delirium Screening Checklist" (ICDSC) record the clinical symptoms of consciousness, attention, orientation, hallucinations, psychomotor retardation or agitation, speech, and changing symptoms by observing behavior and asking concrete questions to the patient.	Immediately post-surgery to approximately 7 days post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline cognitive failures in everyday life at 3 months after surgery as assessed by the "Cognitive Failures Questionnaire" (CFQ)	The "Cognitive Failures Questionnaire" (CFQ) measure the frequency of failures in daily living in terms of memory, attention, action, and perception. It comprises 29 questions, which are answered on a 5-step Likert scale. Higher scores mean a worse outcome.	Immediately pre-surgery to 3 months post-surgery
Change from baseline health-related quality of life at 3 months after surgery as assessed by the "36-Item Short Form Health Survey" (SF36)	The "36-Item Short Form Health Survey" (SF36) includes 36 questions covering 8 health-related factors: vitality, physical functioning, bodily pain, general health perception, physical role function, emotional role function, social role functioning, and mental health. An aggregated percentage score is calculated for each of the eight factors. The percentage scores range from 0% to 100%. Higher scores mean a better outcome.	Immediately pre-surgery to 3 months post-surgery
Change from baseline anxiety at 3 months after surgery as assessed by the "Hospital Anxiety and Depression Scale" (HADS).	With the "Hospital Anxiety and Depression Scale" (HADS), an instrument will be used that refers to the psychological core aspects of depression and anxiety. Each scale contains 7 questions to be answered on a 4-step Likert scale by the patients themselves. After inverting negative questions, higher scores mean a worse outcome.	Immediately pre-surgery to 3 months post-surgery
Change from baseline depression at 3 months after surgery as assessed by the "Hospital Anxiety and Depression Scale" (HADS).	With the "Hospital Anxiety and Depression Scale" (HADS), an instrument will be used that refers to the psychological core aspects of depression and anxiety. Each scale contains 7 questions to be answered on a 4-step Likert scale by the patients themselves. After inverting negative questions, higher scores mean a worse outcome.	Immediately pre-surgery to 3 months post-surgery
Number of participants with postoperative acute ischemic lesions at the time of discharge from the acute clinic as assessed by magnetic resonance images (MRI).	Cranial MRI will be performed using a 3-T scanner (Skyra; Siemens, Erlangen, Germany). The protocol of imaging will include a T2-weighted turbo spin-echo sequence, a T2-weighted turbo spin-echo sequence for dark fluid, a T1-weighted FLASH sequence and a diffusion-weighted echo-planar imaging sequence.	Once within the 6th-10th day immediately post-surgery
Number of participants with postoperative microemboli at the time of discharge from the acute clinic as assessed by magnetic resonance images (MRI).	Cranial MRI will be performed using a 3-T scanner (Skyra; Siemens, Erlangen, Germany). The protocol of imaging will include a T2-weighted turbo spin-echo sequence, a T2-weighted turbo spin-echo sequence for dark fluid, a T1-weighted FLASH sequence and a diffusion-weighted echo-planar imaging sequence.	Once within the 6th-10th day immediately post-surgery

Collaborators and Investigators

• Sponsor: Heart and Brain Research Group, Germany
• Investigators: Principal Investigator: Marius Butz, Dipl.-Psych., Department of Cardiac Surgery, Kerckhoff Clinic Bad Nauheim; Principal Investigator: Tibo Gerriets, Prof.Dr.med., Department of Neurology, Gesundheitszentrum Wetterau; Principal Investigator: Markus Schönburg, Prof.Dr.med., Department of Cardiac Surgery, Kerckhoff Clinic Bad Nauheim; Principal Investigator: Martin Jünemann, Dr.med.M.Sc., Clinic for Neurology, University Hospital Gießen; Principal Investigator: Won-Keun Kim, Dr.med., Department of Cardiac Surgery, Kerckhoff Clinic Bad Nauheim

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2019
• Primary Completion (Actual): December 19, 2022
• Study Completion (Actual): December 19, 2022

Study Registration Dates

• First Submitted: August 27, 2020
• First Submitted That Met QC Criteria: August 27, 2020
• First Posted (Actual): September 1, 2020

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Cognition Disorders; Delirium; Cognitive Dysfunction; Postoperative Cognitive Complications; Emergence Delirium
• Other Study ID Numbers: MC 68/2017

Drug and device information, study documents

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