The CARE-PREOP3-AAI Study Ankle-arm index in preoperative assessment of postoperative cardiovascular risk
a multinational e-mail/web-based study
Copyright ©2004, CARE-PREOP3

1. Each participating investigator should take responsibility for finding out and adhering to their local policy for the ethics approval of this study. Formal ethics approval varies by site. In the rare (we hope!) case in which ethics approval is required only for examining normal patients, participants are encouraged to enter 'known' and 'suspected' patients while awaiting approval for the 'normal' group.
2. This study began February 2004 and will be completed by January 2007.

In patients seen for risk and medical assessment prior to undergoing operations that do not involve cardiac surgery or peripheral arterial revascularization:

1. Are Ankle to arm Index (AAI) values of 0.9 or less independently associated with a significantly increased incidence of post-operative cardiovascular complications (4% or more)?
2. Do AAI values of 0.9 or less add predictive value when incorporated into the revised Cardiac risk index?
3. Are the differences in the predictive power for post-operative cardiovascular complications when using either palpated or auscultated derived AAI values, compared to Doppler derived AAI values, sufficiently small to obviate the need for Doppler measurements?

Despite improvements in surgical and anesthesiology techniques, cardiovascular complications in the perioperative period remain an important issue, with an incidence of about 2% in patients undergoing non-emergent non-cardiac surgery. Existing prediction rules have poor sensitivity and involve acquisition and assessment of a minimum of 4 to 6 variables.⁽¹⁾ It is well recognized that patients undergoing lower limb arterial disease surgery are at particularly high risk, and severe peripheral arterial disease appears to be a reliable marker for significant and often occult underlying coronary heart disease.^(2,3) Additionally, observational studies of older persons have also determined that lower limb arterial disease is independently associated with increased mortality and cardiovascular morbidity as well as clinically manifest cardiovascular disease, and its risk factors.^(4-6)

History taking for detection of peripheral arterial disease appears to be insufficiently sensitive, especially in the geriatric population. The prevalence of intermittent claudication (IC) in older adults by validated questionnaires such as the Rose questionnaire is less than 5% while the prevalence of peripheral arterial disease (PAD) by non-invasive testing is 2-4-fold higher. Co morbid conditions that cause leg pain may result in under-reporting intermittent claudication.⁽⁶⁾

The ankle to arm blood pressure index (AAI) is defined as the ratio of the systolic blood pressure values from either or both dorsalis pedis and posterior tibial (ankle) arteries divided by the brachial artery value. It is normally greater than one. It may be measured by hand-held Doppler device, stethoscope auscultation, or palpation. Doppler derived AAI is best studied and appears to be a more sensitive method of detecting otherwise “sub-clinical” peripheral arterial disease. Palpated values may correlate well and are a more practical technique for the preoperative assessment setting. A model including assessment of grade of palpated pulse, the number of Doppler-auscultated arterial components, and history of myocardial infarction, also has diagnostic value.⁽⁷⁾

We hypothesize that reduced preoperative AAI values, derived by palpation, auscultation or Doppler methods are independent, sensitive, and specific markers for post-operative cardiovascular complications, or add predictive value to the existing revised cardiac risk index.

An initial pilot project was conducted over May-July 2002, yielding the following observations:

• As seen in the literature, claudication history taking using validated scores such as the Rose score is insensitive and does not predict an AAI of 0.9 or less.
• There is close agreement between auscultated, palpated and Doppler derived measurements of systolic BP in the arms.
• Lower limb systolic blood pressure measurements are more reliably done on posterior tibial arteries (concordant with literature), and the measurement of either the right or left PT is equivalent in sensitivity and specificity to measuring both (using palpated, auscultated or Doppler measurements).
• Ankle to arm Index (AAI) values of 0.9 or less, measured by palpation or the inability to palpate any of the four ankle pulses, are associated with a significantly increased incidence of post-operative cardiovascular complications. AAI values of 0.9 or less, measured by Doppler method, was also predictive, but less so than by the palpation method.

• AAI values of 0.9 or less, measured by palpation, appear to add predictive value when incorporated into the revised Cardiac risk index.

Goals of the study:

To further examine the above findings of the pilot study: In patients undergoing non-cardiac, non-peripheral arterial revascularization surgery:

• If AAI values of 0.9 or less are independently associated with a significantly increased incidence of post-operative complications (4% or more).
• If AAI values of 0.9 or less add predictive value when incorporated into the revised Cardiac risk index.
• If differences in palpated or auscultated, and Doppler-derived AAI predictive power are sufficiently small to obviate the need for Doppler measurements.

References

1. Investigators will join the study as teams of at least 2 to enable the independent, blind comparison of the clinical findings with post-operative outcomes. However, solo clinicians can enroll in the study if they can arrange for someone to perform independent blinded review of post-operative outcomes.
2. Investigators may include clinicians working in any practice setting, as long as they see patients before the scheduled operation.
3. Investigators will enroll at least 12 patients per participating team.
4. Investigators will use email and the Internet for recruitment, data submission, presentation and discussion of study results and generation of manuscripts.
5. If available, hand-held 5 MHz (flat probe head) Doppler devices will be used in addition to auscultation and palpation measurement techniques.

Initially, we plan to enrol 350-400 subjects in order to identify and significant positive correlation between the AAI and Lee scoring system. Given the cardiovascular event rates currently reported in the literature, we may require twice that number to determine any significant differences in predictive power for outcomes between reduced AAI values and the Lee score.

Consenting patients presenting for assessment prior to non-cardiac and non-peripheral arterial revascularization surgery will be consecutively enrolled. This may include patients who have already had a formal preoperative consult.

A sample patient consent form is available by clicking here.

Inclusion criteria:

• Age 50 years or older
• Presenting for any medical assessment prior to proposed surgery (full pre-operative assessment, or non-surgery related assessments, etc)
• Planned surgery to be performed soon after the assessment
  • Includes emergency or urgent surgery, such as orthopaedic fracture surgery

Exclusion criteria:

• Age < 50 years
• Patients scheduled for cardiac surgery or peripheral arterial revascularization procedures
• Patients refusing to participate or unable to consent
• Previous enrolment in this study
• Patients with significant language barriers
• Patients with other significant medical problems preoperatively that preclude their participation (such as emergency or life threatening situations, cognitive impairment or aphasia)
• Patients residing in institutions

This study will collect history data that includes revised Cardiac risk index criteria, and any prior revascularization or amputation for treatment of peripheral vascular disease. Most clinicians examine supine patients from the right side. Aside from weight, the physical examination will include auscultated systolic and diastolic right arm Blood Pressure measurements (supine position), and palpated, Doppler (if available) and or auscultation systolic Blood Pressure measurements in the ankle (supine position), preferentially using the right posterior tibial artery. The AAI will be calculated by: AAI = Ankle systolic BP/Arm systolic BP. Where Doppler is used; the number of auscultated components will also be recorded.

During the preoperative clinic assessment interview the following will be collected

1. History:
1. Age
2. Gender
3. Emergency or non-emergency surgery
4. High risk surgical procedure
• These include: Intraperitoneal (inside the abdominal cavity), intrathoracic (inside the chest), or suprainguinal vascular procedures (above the inguinal ligament in the groin)
5. History of stroke or Transient ischemic attack (ever)
• Ask: Have you ever had or been told you have had a stroke or a "mini-stroke" or a "TIA" (transient ischemic attack).
• Stroke will be defined as an abrupt onset of localized (focal) central nervous system signs or symptoms of dysfunction, caused by a blockage or rupture of a blood vessel to the brain (ischemic, or intracerebral or subarachnoid hemorrhage. The duration of deficit lasts greater than 24 hours.
• A transient ischemic attack will be defined as the abrupt onset of localized (focal) central nervous system signs or symptoms of dysfunction (including amaurosis fugax), which fade over minutes to hours and is associated with full recovery within 24 hours.
6. History of coronary heart disease. This may include:
   1. Myocardial infarction (ever) (may include 12-lead ECG consistent with prior myocardial infarct), or
   2. History of a positive stress test (ever), or
   3. Current complaints of chest pain considered to be secondary to myocardial ischemia
      • Ask "have you ever had a heart attack, or been told that that you had blocked coronary (heart) arteries with damage to your heart muscle, or a myocardial infarction?"
      • Ask "Have you ever done an exercise stress test on a treadmill or bicycle to assess or check out your heart? Was the test abnormal?: Did the result show that you had problems with angina, coronary artery disease, or lack of blood supply to the heart?"
      • Ask: "Do you have angina? Do you get chest pain or discomfort when you exert yourself or get emotionally excited or get exposed to cold temperatures or cold wind?"
      • History of coronary artery revascularization (percutaneous transluminal angioplasty or coronary artery bypass grafting) (ever)
7. History of congestive heart failure, or (cardiogenic) pulmonary edema, or paroxysmal nocturnal dyspnea (ever)
   • Ask "Have you ever had or been told that you have (congestive) heart failure or pulmonary edema or been told that you had water on the lung/or lung congestion or problems from heart failure?"
   • Ask: "Do you get sudden shortness of breath, or dry coughing or wheezing that wakes you up suddenly at night, and makes you have to sit up or get up to get relief?"
8. Serum creatinine value in mmol/L or mg/dl.
9. Prior amputation or re-vascularization procedures for Peripheral arterial disease.
   • Prior Revascularization for peripheral arterial disease can include lower limb (infrainguinal) arterial bypass, graft insertion, or angioplastic procedures.
10. Diabetes, and if so, treated with insulin or oral hypoglycemics.
11. Any current B-blocker use.
2. Physical examination:
1. Body weight
2. Arm auscultated blood pressure (in supine position):
   1. If possible the right arm will be used following standard guidelines for blood pressure determination
   2. Cuff bladder should be >= 0.8 of upper arm circumference
3. Lower leg right posterior tibial systolic blood pressure (supine)

The right posterior tibial (PT) artery will be preferentially used and 2-3 measurements taken (one by palpation, one by auscultation technique, and if available, one by hand-held Doppler device. If the right PT is not available, due to amputation, a cast, fracture, acute trauma or other impediment to measurement in that leg, then alternate arteries will be used in the following order of preference:

• Right dorsalis pedis
• Left posterior tibial
• Left dorsalis pedis

If all 4 pulses cannot be felt the observation is recorded, and auscultation and Doppler determinations are attempted on accessible arteries in the same order of preference: (Right posterior tibial, Right dorsalis pedis, Left posterior tibial, Left dorsalis pedis).

The diagrams below illustrate the location and recommended technique for posterior tibial artery palpation, and BP cuff placement is appended. The blood pressure cuff should be applied so that the lower edge of the cuff is 2-3 cm above the point of arterial measurement, with the center of the cuff bladder positioned above the artery being measured. Palpation and the placement of the bell or diaphragm of a stethoscope, or Doppler probe, should be over the course of the artery in the flat area near the lower, posterior edge of the medial malleolus (arrow in figure).



The dorsalis pedis artery is usually felt on the mid-dorsum of the foot just lateral to the extensor hallucis longus tendon of the great toe.

Pulses should be used for measuring BP by palpation only if they are clearly felt; otherwise record palpation as either "R" (reduced) or "ND" (not detected) and then attempt measurement with auscultation and then, if available, handheld Doppler ultrasound. If a Doppler signal is detected, record the number of arterial components that are heard in each cardiac cycle, on the non-compressed artery, (i.e. do it before inflating the BP cuff). The normal 3-component signal sounds like "WHAAAA-duh-duh" (click to hear example). Record what you hear as 1, 2 or 3.

The Ankle to arm index = Ankle Supine systolic BP / Arm supine systolic BP

It will be recorded separately for each modality of measurement (with recorded calculations to second decimal place.)



Doppler probes

In prior AAI studies, both 5 and 8 MHz hand-held Doppler devices have been used to determine systolic blood pressures. The 8 MHz probe requires maintaining a particular angle of the probe to the interrogated vessel for optimal results and is therefore more operator-dependent. The 5 MHZ devices are preferred. They are easier to use, only require the probe to be placed flat against the skin, and have been successfully used in other studies of peripheral vascular disease detection. If a hand-held Doppler device is used, the type and MHz of the device should be recorded. Sufficient Ultrasound transmission gel should be used to coat the face of the probe and skin, ensuring proper contact and best results.

Postoperatively and post discharge the following data will be collected by a study participant who is blinded to the preoperative data:

1. Operative Factors
• Emergency or non-emergency surgery
• Type of operation (checks that intended operation did occur):
1. Intrathoracic
2. Intraperitoneal (lower or upper abdominal)
3. Suprainguinal vascular
4. Other
2. Investigations (Tests results may not have been available at time of preoperative evaluation)
• Preoperative ECG done: Pathological Qs present?
• Preoperative CXR (optional): If done, pulmonary vascular redistribution?
• Preoperative Serum Creatinine (optional): If done, the value in mmol/L or mg/dl?

Length of hospital stay (days)

Record ALL Clinically significant postoperative cardiovascular complications that occur prior to discharge or post-operative day 7 (which ever comes first).

Record dates of their occurrence:

• Death (Cardiac or non-cardiac)

Cardiac death is defined as any death with a cardiac cause and including those deaths following a cardiovascular procedure such as percutaneous transluminal coronary angioplasty or deaths due to an unknown cause. Non-cardiac is defined as deaths due to a clearly documented non-cardiac cause (e.g. trauma, infection, malignancy).

• Non-fatal Acute myocardial infarction

The diagnosis nonfatal MI requires any two of the following^*

1. Characteristic ischemic chest pain lasting longer than 20 minutes
2. ECG changes including acute ST elevation followed by appearance of Q waves, or new left bundle branch block, or new persistent T wave inversion for at least 24 hours, or new ST segment depression which persists for at least 24 hours
3. Peak CK-MB or troponin I or troponin T greater than the reference limits

^*This definition includes criteria used in Lee et al study, as well as WHO revised criteria as outlined in Meier, MA et al Arch Intern Med 2002: 162; 1585-1589

• Unstable angina requiring intervention

This includes transfer to intensive or coronary care unit, or coronary angiography, coronary angioplasty or revascularization procedures

• Cardiogenic Pulmonary edema

Defined as new onset vascular redistribution, interstitial pulmonary edema, or frank alveolar pulmonary edema confirmed by formal reading of chest radiograph by radiologist) considered to be secondary to heart failure

• Primary cardiac arrest

Defined as a successful resuscitation from either documented or presumed ventricular fibrillation or sustained ventricular tachycardia or asystole.

• Ventricular fibrillation
• Complete Heart block
• Stroke or Transient Ischemic attack

Use the same definitions listed above, in preoperative history section.

This process will be streamlined and simple, with tick-boxes for as many items as possible. The form can be downloaded as an Adobe PDF file by clicking (here). Please keep a copy of your completed data forms in case the journal to which we submit the publication would like random checks done on them.

Data submission will be by an Internet data collection system. Patient identify will be anonymous. Each investigator should have their own method of assigning patient ID numbers that should also be entered on the data collection sheets. To qualify for the study, each patient should have both a clinical exam data collection sheet and a post-operative outcomes sheet.

Simple analyses will follow the approaches outlined in the JAMA 'Primer' (JAMA 1992; 267:2638-44).

Patient demographic characteristics, percentage of patients in each category of calculated Lee cardiac risk score and proportion of patients experiencing postoperative complications of interest will be analysed to determine comparability to cohorts reported in Lee study.

The relationship between AAI values less than or equal to 0.9 and post-operative cardiovascular complications will be assessed using Chi-Square testing, (with t-testing for length of stay).

If statistically significant relationships exist, sensitivity, specificity and likelihood ratios will be calculated, for AAI values derived from palpated, auscultated and Doppler blood pressure measurements.

The relationship between combined AAI values less than or equal to 0.9 and Lee scores, and the incidence of post-operative cardiovascular complications will be assessed using Chi-square testing (with t-testing for length of stay).

The relationship between AAI values of less than or equal to 0.9 and a PAD diagnostic model that uses history of myocardial infarction, grade of palpated pulses, and the number of Doppler arterial components heard per cardiac cycle, will also be assessed.

1. First analyses and draft reports will be sent only to participating investigators.
2. After the investigators are satisfied with the analyses and reports, the manuscript will be submitted to an appropriate journal.
3. Abstracts will be proposed and submitted to national and international meetings by mutual agreement with authorship that includes the phrase 'on behalf of the CARE-Study Group'.
4. Manuscripts will be submitted by mutual agreement with authorship that includes the phrase 'on behalf of the CARE-Study Group'.
5. Publications will include a list of all participants, who submitted useable data on 12 or more patients (in descending order based on the number of patients enrolled) and all methodologists involved with the study.

* Any comments or concerns about this protocol, please email carestudy@rogers.com.