Comprehensive Assessment of Frailty Clinical Trial
Official title:
Frailty In Cardiac Surgery Copenhagen Study
Background:
Over the past decades there have been seen an increase in life expectancy in Denmark. One of
the consequences is that the patients who need heart surgery have a higher average age and
some of these patients have a fragile physique that increases the risks of major surgery.
In cardiac surgery, there are different types of scoring system for assessing the
preoperative risk of death associated with surgery. Among them are EuroSCORE and STS systems
the most used.
This study evaluate the preoperative risk using the frailty score system, CAF (comprehensive
assessment of frailty), based on an assessment of the patient's physical condition. If the
patient has a lower than expected physical condition, the patient is frail. The assessment of
the physical condition generated from questions about the patient's medical history and
physical activity as well as performing less physical tests, consisting of strength, balance
and walking speed.
Purpose:
A prospective observational study, who investigates how many of the patients who must undergo
heart surgery, that is frail. Then compare the patients who are frail with non-frail patients
in terms of complications, mortality and quality of life after the procedure. By use of CAF
score the patients are scored frail or non-frail. There is planned a further study which
compare degree of kidney injury in frail with non-frail patients. Our assumption is that
patients which are frail, have an increased risk of complications and longer hospital stay,
higher consumption of intensive days and more readmissions. Using frailty score in
combination with the existing score systems EuroSCORE and STS score, are believed to be a
better predictor of complications following heart surgery.
Method:
FICS study is a prospective observational study of patients undergoing cardiac surgery in the
cardiothoracic department of Rigshospitalet. Planned to enroll 600 patients over a two year
period. The study consists of various smaller physical test and questions. Which is used to
assess whether the patient is frail and not frail.
Postoperatively follow-up after 30 days with a phone call and after 12 months through danish
data register. At the both follow-up times, data are collected on the somatic readmissions /
diagnoses and vital status through the national register and review of relevant journal
notes. Afterwards comparing complications and mortality.
Who can enter:
One patients can be included if the following criteria are met: Age> 65 years, Elective or
subacute surgery, CABG (coronary artery bypass grafting),valve substitution or combination of
these
If one or more of the following criteria are met, the patient is not included in the study:
Acute surgery, Clinical unstable, Severe neuropsychiatric impairment, Uncooperative
(psychiatric diagnosis) and Re-operations.
Side effects, risks and disadvantages:
Today preoperative risk assessment are assessed by EuroSCORE. Introduction of CAF, frailty
score will not expose patients to the risk or side effect, since the course or treatment does
not change.
Economy:
There are considered that the study are economically justified, since hypothetically this
would lead to fewer readmissions, fewer days in intensive care and shorter hospital.
Acquisition:
The patients will in this trial be over 65 years old and must have completed elective or
subacute cardiac surgery. They will receive participant information and thus the opportunity
to read about the study before the first appearance.
At first appearance they meet our project assistant and get here verbal information about the
study, where also questions can be answered. Subsequently, the patients will be asked to sign
a consent form.
Publication of test results / research ethics statement:
The knowledge and results obtained through the survey will provide essential scientific
information of significance for the future course and treatment of patients undergoing
cardiac surgery with regard to the number of hospital days, intensive days and readmissions.
Thus, the investigator believes that the study is appropriate and ethically
Background:
In general, patients referred to cardiac surgery are aging. An increasing number of patients
are now older than 70 years. [1]This older population of patients undergoing cardiac surgery
often has several comorbidities and has an increased risk of complications and mortality
compared to the younger patients.[1,2] Furthermore, several studies have shown that elderly
patients with cardiovascular diseases may be frail. Frailty is a term used to assess the true
biological status of a patient and defined as a patient's impaired resistance to stressors
due to a decline in physiologic reserve.[3-8] In cardiac surgery there are several risk
scores to assess 30-day mortality exists. The most common are the European system for cardiac
operative risk evaluation (EuroSCORE) I, EuroSCORE II and the Society of Thoracic Surgeons
(STS) score. However, the EuroSCORE seems to have a tendency to overestimate the
perioperative risk in the elderly population and opposite the STS score a tendency to
underestimate the risk. One of the reasons for this may be that none of the risk scores
incorporate the biological status of the patients.[9-11] Within the last 5 years a few
studies evaluating different 'frailty scores' in cardiac patients has been published.
[3-6,8,12-16] None of these frailty risk scores are fully validated and therefore widely
adopted. In a German single center study of 400 patients undergoing elective cardiac surgery
and aged 74 or above frailty was assessed by the comprehensive assessment of frailty (CAF)
score. The CAF scores assess weakness, self-reported exhaustion, slowness of gait speed, low
activity and physical performance. [14,15] The CAF score correlates well with the EuroSCORE
and STS score, but is a very complex and time consuming risk score. In an effort to make the
test more clinical practical a simpler version of the CAF score has been developed. The
'frailty predicts death one year after elective cardiac surgery test' (FORECAST) includes;
chair rise, self-reported weakness, stair climbing, two physicians estimation of frailty and
serum creatinine level. [14,17]
Aim:
In an observational prospective study, we will identify and describe the number of frail
patients undergoing first time cardiac surgery in our department, compare the risk of
short-term and long-term complications and compare quality of life in frail versus non-frail
patients. Frailty will be assessed with the CAF score. In a substudy we will analyze the risk
of renal insufficiency.
Hypothesis:
Patients deemed frail using the CAF score have increased risk of short-term and long-term
complications. With the frailty score in addition to EuroSCORE or STS score, we can better
predict complications compared to EuroSCORE or STS score alone.
Method:
A) Patients/study population:
FICS study is a prospective observational study of elderly patients undergoing cardiac
surgery at the Department of Cardiothoracic Surgery, Rigshospitalet, Copenhagen University
Hospital, Denmark. Expect to include 600 patients during a two years inclusion period. With a
minimum of 12 month inclusion period, but all included in the analysis, with a maximum
follow-up time.
B) Inclusion criteria:
1. All patients aged above 65 years old
2. Patients referred to elective and subacute cardiac surgery
3. All undergoing CABG (coronary artery bypass grafting), valve replacement and CABG with
valve replacement.
C) Exclusions criteria:
1. Emergent surgery
2. Clinically unstable
3. Severe neuropsychiatric impairment
4. No cooperation (psychiatric diagnosis).
5. Reoperations
D) Follow-up:
Patients are followed after discharge by searching The Danish National Registry, which
contains informations an all somatic hospital admissions. From which there will be collected
a copy of the patient record for all hospital admissions. Patient records will be assessed
for pour predefined outcome measures.
Information about vital status will be achieved by searching the Danish Central Civil
Register. The cause of death will be obtained from patients records and death certificates.
After 30 days we will contact the patients through phone to ask about their quality of life
and intake/changes in medicine and again a follow up in Danish Central Civil Register at 12
month.
E) Substudies:
Study 1, Short-term follow-up:
This study describe the proportion of frail patients in our department undergoing cardiac
surgery. We will further compare the number of complications between the two groups.
30-day follow-up comparing frail vs non-frail patients undergoing cardiac surgery:
Primary outcome:
In this study the primary outcome will be 30-day all-cause mortality in frail vs. non-frail
patients (hospital mortality or death within 30 days postoperatively).
Secondary outcomes: MACCE (Major Adverse Cardiac and Cerebrovascular Events) including:
- AMI
- Stroke
- Mortality
Tertiary outcomes:
- Stroke
- Renal failure until discharged:
- Prolonged ventilation (>24 h)
- Days in intensive care unit (ICU)
- Readmission in ICU
- Deep sternal wound infection (need for operative intervention and antibiotic therapy,
with positive culture)
- Need for reoperation (major bleeding)
- Perioperative complications ex gastrointestinal complication (ischemia, gastric ulcer)
- Days of hospitalization
- Discharged to other hospital or nursing home for ongoing medication or rehabilitation
and how many days until discharged to home
Study 2, Long-term follow-up:
This study do a follow up, so the last one included is follow minimum 12 month. And the first
one included is followed up until the last is recruited.
12 month follow-up in frail vs non-frail patients undergoing cardiac surgery:
Primary outcome:
In this study the primary outcome is all-cause of mortality after 12 month in frail vs.
non-frail patients.
Secondary outcomes: MACCE (Major Adverse Cardiac and Cerebrovascular Events) including:
- AMI:
- Stroke
- Mortality
Tertiary outcomes:
- Discharged to other hospital or nursing home for ongoing medication or rehabilitation
and how many days until discharged to home
- Prolonged hospitalization ( > 14 days)
- Number of Re-hospitalization
- New diagnosis and medication ( changes and new)
- Social support (need for more help, both care and tools)
- Other complications.
Study 3,Predicting postoperative Acute Kidney Injury (AKI) in frail vs. non-frail patients
undergoing cardiac surgery:
AKS is a major complication after cardiac surgery and associated with increased mortality and
morbidity. It has been proven that knowing patients renal reserve before surgery is
important, both for predicting mortality and AKI outcomes. Since early detection of these
patients may contribute to improving outcomes. Estimation of the renal reserve by Serum
creatinine, eGFR, Serum cystatin C, Urinary neutrophil gelatinase-associated lipocalin
(NGAL), Cr EDTA Clearance and 24 hr. collection of urine to determine Cr Clearance, protein
and albumin. This samples will be collecte on preoperative day, postoperativly day 5 and 3 a
follow-up 3 months postoperativley.
Primary outcome: In this study the primary outcome is development of AKI and the severity of
AKI in frail vs. non-frail patients, defined as having one of the following:
- Diuresis <0,5ml/kg/hr. for >6 consecutive hours
- Serum creatinine raised by >26umol/L within 48 hours
- serum creatinine rises >1,5 fold from the reference value ( the lowest value recorded
within 3 months)
Secondary outcomes:
- Persistent AKI: Having AKI for 48 hours or longer. Study 4, To examine the correlation
between frailty score and the other two commonly used surgical risk scores, EuroSCORE and STS
and their performance characteristics in patients over the age of 65 undergoing cardiac
surgery. This study compare the commonly used risk estimation systems for patients undergoing
cardio-surgical procedures, as STS in north America and EuroSCORE in Europe with the frailty
score CAF and FORECAST for estimation of mortality and morbidity 30 days and 12 month
mortality.
F) The Frailty scoring scale:
CAF:
Evaluation of frailty by using the comprehensive assessment of frailty (CAF) scoring scale of
S. Sündermann. [14][15]This is based on a combination of different scoring scales. The first
part is based on the Fried criteria: weight loss, self-reported exhaustion, low activity,
slowness of gait speed and weakness. Where CAF includes all except weight loss. Self-reported
exhaustion are two questions by the original CES-D scale, Center for epidemiological study
Depression. Low activity by asking to instrumental activity of daily living (IADL). The IADL
used are, walking, housework, outdoor activity, regular sport and others. Following are
kilocalories per week calculated by formula: Kilo Cal= (w x frequency of activity x duration
of activity)/2. Slowness, speed in meters per second, where the patient walk 4 meters in
normal walking speed and weakness through grip strength by pulling as strong as you can the
grasp of the dynamometer in kilograms (kg).
The second part is physical performance tests. Testing the balance, how long you can stand
still with your feet together, with one feet halfway in front of the other (semi-tandem) and
with one feet completely in front of the other one (tandem). At each position the time is
measured and put in to frailty table to score points. In the last element of balance the
patients is asked to turn around themselves 360 degrees and again the time is obtained. Then
testing the body control, get up and down from a chair three times, put on and remove a
jacket and pick up a pen from the floor.
The last part is Laboratory tests, including level of serum albumin, Creatinine and calculate
Forced expiratory volume in 1 s (FEV1).
At the end two physicians, different from the person observing the CAF test (one cardiac
surgeon and one experienced clinician) estimate the patients frailty after the Clinical
frailty scale score.
The Clinical frailty scale is from the Canadian Study of Health and Aging, Which is based on
a frailty index composed of 70 items, from where you estimate the frailty on a scale 1-7. 1.
Very fit: robust, active, energetic, well motivated and fit; these people commonly exercise
regularly and are in the most fit group for their age. 2. Well: without active disease, but
less fit than people in category 1. 3. Well, with treated comorbid disease: disease symptoms
are well controlled compared with those in category 4. 4. Apparently vulnerable: although not
frankly dependent, these people commonly complain of being "slowed up" or have disease
symptoms. 5. Mildly frail: with limited dependence on others for instrumental activities of
daily living. 6. Moderately frail: help is needed with both instrumental and non-
instrumental activities of daily living. 7. Severely frail: completely dependent on others
for the activities of daily living, or terminally ill.
Finally to get the patients total CAF score, you add each individual test scores together. It
has a maximum score of 35 points. That is divided into not frail 1-10, moderately frail 11-25
and severely frail 26-35.
Out from the CAF score, there is a ability to score and use FORECAST (Frailty predicts death
One year after elective cardiac surgery test) which include only 5 of CAF items: chair rise,
weakness, stair climb, CFS (clinical frailty scale) and Serum creatinine. FORECAST has a
maximum score of 14 points, which also is divided into, not frail 0-4, moderately frail 5-7
and severely frail 8-14.[17]
Statistics:
Sample size calculation. Based on the CAF frailty score patients will categorizes into the
non-frail group (CAF score <11) or the frail group (CAF score 11 or above). In a previous
study Sündermann et al. found that 50% of the patients above 75 years undergoing first time
CABG were deemed frail using the CAF score. Furthermore, they observed that 1 year mortality
was 7% in the non-frail group versus 14% in frail-group[17] . Based on a power of 80% and a
risk of type I error of 5% and the mortality reported above gives an inclusion of at least
300 patients in each group.
Data analysis Categorical data will be presented as numbers and percentages and compared
using chi square test or Fischer exact test, as appropriate. Continuous data will be
described as means with corresponding standard deviations (SD) and compared using students
t-test.
Time to event for the primary and secondary outcomes will be analyzed using a Cox regression
model. Survival curves will be illustrated with Kaplan-Meier plots.
A P-value of less than 0.05 will be considered significant.
Administration:
The preoperative testing for frailty will take place in the Department of Cardiothoracic
Surgery Rigshospitalet, Copenhagen University Hospital, Denmark.
Economy:
This is a non-profit study. The expenses will be covered by the involving departments at
Rigshospitalet. The department of cardiothoracic surgery will cover the costs of a project
nurse during the inclusion period.
Ethics:
Today our department use EuroSCORE as a risk score preoperative. The use of frailty score has
been used in the department of cardiology the last years.
Admission of frailty scoring in our department is humanly justified since the patient takes
no risk and there are no side effects.
We find it financially responsible to introduce, because we hypothetical expect that this
will lead to fewer readmissions, fewer ICU days and hospitalization days.
Appendix Definitions Definition MACCE:[18] Non-fatal cardiac arrest: An absence of cardiac
rhythm or presence of chaotic rhythm requiring any component of basic or advanced cardiac
life support.
Acute myocardial infarction: Increase and gradual decrease in troponin level or a faster
increase and decrease of creatine kinase isoenzyme as markers of myocardial necrosis in the
company of at least one of the following: ischaemic symptoms, abnormal Q waves on the ECG,
ST-segment elevation or depression; or coronary artery intervention (e.g. coronary
angioplasty) or a typical decrease in an elevated troponin level detected at its peak after
surgery in a patient without a documented alternative explanation for the troponin elevation.
Congestive heart failure: New in-hospital signs or symptoms of dyspnoea or fatigue,
orthopnoea, paroxysmal nocturnal dyspnoea, increased jugular venous pressure, pulmonary rales
on physical examination, cardiomegaly, or pulmonary vascular engorgement.
New cardiac arrhythmia: ECG evidence of atrial flutter, atrial fibrillation, or second- or
third-degree atrioventricular conduction block.
Angina: Dull diffuse substernal chest discomfort precipitated by exertion or emotion and
relieved by rest or nitroglycerin.
Stroke: Embolic, thrombotic, or haemorrhagic event lasting at least 30 min with or without
persistent residual motor, sensory, or cognitive dysfunction; if the neurological symptoms
continue for .24 h, a person is diagnosed with stroke, and if lasting ,24 h the event is
defined as a transient ischaemic attack.
Cardiovascular death: Any death, unless an unequivocal non-cardiovascular cause could be
established.
Cerebrovascular death: A death caused by cerebrovascular disease.
Renal Failure: diuresis <0,5ml/kg/hr. for >6 consecutive hours or serum creatinine raised by
>26umol/L (0,3 mg/dl) within 48 hours or serum creatinine rises >1,5 fold from the reference
value at the day 0 to 14.
;