Frailty and Cognitive Function Assessment of TAVI Patients

Quality of Life Clinical Trial

Official title:

Frailty and Cognitive Function Assessment of TAVI Patients (The Hungarian Frailty Score) - Observational, Prospective, Singe Center Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02650388
• Other study ID #: 56174-1/2015/EKU(0470/15)
• Status: Recruiting
• Phase: Phase 4
• First received: December 22, 2015
• Last updated: January 6, 2016
• Start date: November 2015
• Est. completion date: October 2018

Study information

• Verified date: December 2015
• Source: Hungarian Institute of Cardiology
• Contact: Peter Andreka, MD, PhD.
• Phone: 0036703820470
• Email: andreka.peter[@]kardio.hu
• Is FDA regulated: No
• Health authority: Hungary: Scientific and Medical Research Council Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Aortic stenosis (AS) is the most common valve disease among the adult population, in the majority of the cases it only requires treatment in advanced age. Transcatheter aortic valve implantation (TAVI) has become available as an alternative treatment for very high risk or even inoperative patients who are suffering from symptomatic aortic stenosis. Until now it has been learnt that there are group of patients who are in a very bad condition and who are so frail that they do not benefit from TAVI. These patients have worse survival rate and more importantly poor quality of life in spite of a successful procedure. Cardiac surgery risk scores like Society of Thoracic surgery score (STS) and EUROSCORE are less accurate in aging high risk people. In elderly it is principal to make differentiation between utility and futility. On the other hand, beside frailty status the main barrier to TAVI is the risk of neurological impairment. Neurological injury and impairment in TAVI can occur as cerebrovascular event (CVE) and/or neurocognitive dysfunction. The two neurocognitive dysfunctions - post-operative delirium (POD) and post-operative cognitive dysfunction (POCD). Most cases remain undetected although clinically could be apparent or silent. The neurological injury can be observed and/or detected by neuroimaging techniques and cognitive trajectories. A well established and validated frailty score based on relatively simple and feasible tests could help in our everyday practice to evaluate the prognosis of elderly people undergoing TAVI and to determine those patients who really benefit from the procedure.

Description:

Aortic stenosis (AS) is the most common valve disease among the adult population, in the majority of the cases it only requires treatment in advanced age. Surgical aortic valve replacement (SAVR) is very often refused because of advanced age and poor general condition. These patients used to receive only medical treatment which is less favorable compared to SAVR. Nowadays transcatheter aortic valve implantation (TAVI) has become available as an alternative treatment for very high risk or even inoperable patients who are suffering from symptomatic aortic stenosis (1). Between 2012 and 2014 TAVI has been used extensively, accumulating over 100,000 procedures performed worldwide since 2002 (2). TAVI was originally developed for those patients who were considered too frail to undergo SAVR (3). Recently, we are able to perform TAVI in almost all patients with high procedure success rate and achieve good hemodynamic results. Despite these promising results, the one year outcome is not so evident. Until now it has been learnt that there are a group of patients who are in a very bad condition and who are so frail that they do not benefit from TAVI. These patients have worse survival rate and more importantly poor quality of life in spite of a successful procedure. Cardiac surgery risk scores like Society of Thoracic surgery score (STS) and EUROSCORE are less accurate in aging high risk people (4). Advanced age is often accompanied with frail general conditions and, the estimated morbidity and mortality values do not correlate well with the postoperative outcomes. In these risk scores very important relevant factors like frailty and disability are not taken into account. In elderly it is principal to make differentiation between utility and futility. Frailty is a clinical syndrome that reflects impaired physiologic reserve and increased vulnerability to stressors (5). However frailty as a geriatric concept has existed for a long time, its importance has recently gained high priority in the concept of older adults especially who undergo TAVI(1). By today frailty scores have increasing importance and are used more frequently by several investigators. Slow 5m gait speed has evidently proven unfavorable outcomes (6, 7), other frailty assessment tools like handgrip strength test, activities of daily living (ADL), instrumental activities of daily living (iADL), nutritional assessment, mini-mental status, etc. has been being investigated continuously.

On the other hand, beside frailty status the main barrier to TAVI is the risk of neurological impairment. The TAVI candidate patients have specific central nervous system (CNS) issues because of neurobiological changes of aging, e.g. decreased brain weight and volume, decreased neurotransmitter system function, decreased neuronal gene expression and Alzheimer type changes (8). Neurological injury and impairment in TAVI can occur as cerebrovascular event (CVE) and/or neurocognitive dysfunction. Both forms might be clinically apparent and detected, clinically apparent but undetected and clinically silent and undetected. The two neurocognitive dysfunctions - post-operative delirium (POD) and post-operative cognitive dysfunction (POCD) - most cases remain undetected although clinically could be apparent or silent (9). POD is defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). POCD is defined by Kappetein et al., as "deterioration of intellectual function presenting as impaired memory or concentration presenting with temporal association to surgery" (9, 10). The neurological injury can be observed and/or detected by neuroimaging techniques and cognitive trajectories. Some insult caused by TAVI might remain in the clinically silent area and might be observed only as slight neurocognitive dysfunction. Analization of the incidence and underlying etiology of the neurological events may lead to identification of recently non-recognized techniques or neuroprotective strategies, devices. The most elevated incidence of CVEs is within 24 hours of TAVI. This risk of further events might be high for up to two months (11). One fifth of health-related quality of life (HRQOL) is characterized by cognitive functions. Studies and reports on cognitive, psychiatric, and/or neurological events following TAVI have focused on major and well-marked complications, e.g., stroke, TIA, and post-operative delirium (12). Meantime TAVI is associated with a high incidence (73%-84%) of silent cerebral embolism as detected by diffusion-weighted MRI (13).

Chronological age does not always reflect biological age and there is a wide range between fit to frail (14). A well established and validated frailty score based on relatively simple and feasible tests could help in our everyday practice to evaluate the prognosis of elderly people undergoing TAVI and to determine those patients who really benefit from the procedure. Post-Operative Cognitive Dysfunction (POCD) in patients undergoing TAVI (and/or SAVR) was examined in only a few studies published during the last 10 years. Examinations and investigation of finer, long-term and possibly positive post-operative cognitive outcomes following TAVI (and SAVR) are significantly under-represented in the current medical literature (15).

Hypothesis:

There is a significant correlation between the Hungarian Frailty Score (HFS) and post procedure outcomes and quality of life preservation. HFS score would be a useful tool to estimate those who will benefit from TAVI. We also hypothesize that cognitive performance will be preserved, and will improve at the end of 12th month after TAVI due to better cerebral circulation.

Objectives and aims

1. Generate and validate a new risk score system called the Hungarian Frailty Score (HFS), which represents an objective tool for evaluation of the frailty syndrome in patients undergoing TAVI procedure.

2. To determine the changes and to prove that there is no cognitive decline in patients undergoing TAVI if so any (pre and post TAVI cognitive function will be assessed).

Primary aims:

To estimate the correlation between the HFS, and the in-hospital stay, 30 day and 1-year outcomes evaluated according to the VARC 2 Criteria. The benefit of this study is to conclude exact data about quality of life and provide a comprehensive investigation of pre- and post-TAVI cognitive outcomes. We plan to define that apart from the incidence of possible neurological signs and the radiological evidences of neurogical injury and POCD, there is no decline in long term cognitive functions and there is improvement in the long term quality of life (QoL).

Secondary aims:

Find correlation and differences between HFS, QoL, eyeball test, and cognitive outcomes. Additional impact is to assess whether POD and POCD are a part of same condition, spectrum, and what can we do to prevent them.

Expected results:

To generate a simple and useable risk score system adopted to the Hungarian population for evaluating patients who undergo TAVI and collect data about post TAVI QoL and cognitive functions, and to register changes in the pre and post procedure frailty score. Non-diagnosed preoperative cognitive impairments and CVEs of the patient will be detected at baseline.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: October 2018
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Age = 75 years,

• Severe, symptomatic aortic stenosis,

• High risk for cardiac surgery (STS and logistic Euroscore ),

• According multidisciplinary (heart) team decision TAVI is preferable,

• Willing to participate

Exclusion Criteria:

• Died before TAVI

• Not willing to participate

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Heart Valve Disease
• Heart Valve Diseases
• Quality of Life

Intervention

Behavioral:
• Cognitive fuction, quality of life
To test the above score in patients undergoing TAVI

Locations

Country	Name	City	State
Hungary	Hungarian Institute of Cardiology	Budapest

Sponsors (2)

Lead Sponsor	Collaborator
Hungarian Institute of Cardiology	Semmelweis University

Country where clinical trial is conducted

Hungary, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To correlate HFS with mortality at 30 days and 1-year		1 year	No
Secondary	Find correlation and differences between HFS and QoL		1 year	No
Secondary	Find correlation and differences between HFS and eyeball testing		1 year	No
Secondary	Find correlation and differences between HFS and cognitive outcomes.		1 year	No