Pulse Wave Velocity as a Predictor for Postoperative Cardiovascular Events
Condition: Post-Op Complication; Arterial Stiffness
MeSH terms: Postoperative Complications
Study type: Observational

Summary: 
      Vascular stiffness increases as a person ages, due to the repetitive stress that is put on
      the vascular system which causes changes in the elasticity of the vessel walls. The increased
      stiffness of the arteries puts added stress on the circulatory system. This rise in stiffness
      has been shown to be associated with an increased risk of cardiovascular events, in both
      presumably healthy patients, as well as elderly patients The current method for assessing
      perioperative cardiac risk is the Goldman's Revised Cardiac Risk Index (RCRI). This method,
      however, does not include a direct measurement of arterial stiffness. Applanation tonometry
      is a non-invasive technique that has been shown to reliably provide indices of arterial
      stiffness While the use of applanation tonometry has been widely studied in general medicine,
      it is has not been studied for pre-operative risk assessment in surgical patients.

      The purpose of this investigation is to examine whether aortic stiffness is an independent
      risk factor for developing cardiovascular related adverse events in patients who are having
      major surgery under general anesthesia.

      Applanation tonometry will be performed on the right carotid and femoral arteries to assess
      carotid-femoral pulse wave velocity, a surrogate for aortic stiffness. (SphygmoCor system,
      AtCor Medical, Sydney, Australia). The measurement will be obtained before induction of
      general anesthesia in the presurgical area. Patients' medical history, intraoperative
      hemodynamics, and any postoperative complications will be recorded to determine significant
      correlations and relationships. This information will potentially help identify future
      patients that might be at greater risk of developing an adverse cardiovascular event
      following their surgical procedure.
    

Detailed description: 
      Background: In 1894 William Osler, MD, said: "You are as old as your arteries." A number of
      recent studies have confirmed this prescient proclamation. Vascular rather than chronological
      age is the best predictor of adverse cardiovascular events and mortality from coronary
      insufficiency, ischemia, myocardial infarction, heart failure, cerebrovascular insufficiency
      or stroke, and renal insufficiency or failure. We believe it is likely this also applies to
      perioperative risk of cardiovascular complications from the numerous stress factors
      associated with major surgery.

      Vascular aging leads to central aortic dilation, arterial wall thickening of the media and
      adventitia with sclerotic changes and increased vascular stiffness. These changes lead to
      central blood pressure (BP) augmentation, elevated systolic and pulse pressure, along with
      lowered diastolic BP. (1) Central more elastic vessels cushion and dampen pressure
      oscillations with left ventricular (LV) ejection and transfer this stored energy into
      continuing antegrade pulse waves along the arterial tree during diastole. (2) the pulse wave
      is also reflected back centrally when it meets higher flow resistance at major artery branch
      points and muscular arteries resulting in central aortic combination wave. In a younger
      compliant central aorta the reflected waves arrive after aortic valve closure, augmenting
      early diastolic perfusion pressure an coronary blood flow. Elderly stiff aorta and major
      arteries vessels transfer both antegrade and retrograde pulse waves faster. If heart rate is
      slow enough an asystole long enough, this combination wave will arrive at the central aorta
      during late systole. This elevates LV workload, resulting in compensatory left ventricular
      hypertrophy (LVH). In addition, disappearance of the diastolic combination wave lowers
      coronary perfusion pressure, increasing the risk of coronary insufficiency for the
      hypertrophied LV wall.

      Unfortunately, high blood flow coronary, and renal arteries are not so muscular that they can
      reduce the impact of high combination systolic pressure waveforms. This induces chronic
      kinetic injury to these high blood flow vessels and organs. Increased pulsatility leads to
      arterial remodeling and microcirculation damage in brain and kidney, small lacunare infarcts,
      white matter lesions associated with cognitive dysfunction and dementia, while endothelial
      dysfunction compromises cerebral blood flow, the blood-brain barrier and renal perfusion.
      Again, LVH from elevated combination waveform pressure leads to diastolic dysfunction and
      heart failure. Thus, elevated pulse wave velocity (PWV)and central aortic pulse augmentation
      indices are independent predictors of CAD, stroke, renal dysfunction, and all-cause
      mortality. (1) It is responsible for the rising risk of myocardial insufficiency, ischemia,
      LVH, and heart failure, cerebrovascular insufficiency or injury as well as renal injury and
      impairment with vascular aging.

      The rate of vascular aging is multifactorial, including genetic susceptibilities as well as
      acceleration from vascular disease such as hypertension, atherosclerosis and diabetes. Recent
      trials have shown ACE inhibitors, angiotensin II blocks (ARBs) and Ca++ channel blockers have
      favorable effects on central aortic compliance, reducing LVH and reducing the risk of heart
      failure, stroke and renal impairment. In contrast, Beta blockers enhance central aortic BP
      augmentation by lengthening LV ejection time. Thus the reflected pulse waves arrive during
      late systole, augmenting the combined central aortic wave amplitude and LV workload.

      Pulse wave velocity (PWV)has become a very good measure of aortic stiffness. PWV rises from
      6m/sec in a young person to 10m/sec in a 65 y/o. It increases 2-fold from 20-80 y/o, due to a
      4-fold reduction in aortic distensibility. (3) The CAFE study showed significant reduction in
      central artic BP and adverse cardiovascular events as well as renal impairment with Ca++
      channel blockers, but not with atenolol plus thiazide Rx. (4) The REASON study showed ARBs
      reduced vascular stiffness, wave reflections, central aortic pulse pressure, vascular
      resistance, remodeling and thickness of resistance vessels. (5) Method/Design: The study will
      be human subject non-randomized observational study. This study will enroll approximately 500
      patients. This was determined by a preliminary analysis of 140 patients, of which 19 had
      adverse cardiovascular events, within a week after surgery. The results of this preliminary
      study found average PWV was significantly higher in patients who developed postoperative
      cardiovascular events compared with patients who had uneventful postoperative course.
      (p-value 0.024). Therefore it was determined that 500 patients should be sufficient to see a
      statistically significant difference if there is one. This study will be conducted at day of
      surgery administration area and main operation room at University of Iowa Hospitals and
      clinics. Arterial stiffness will be measured at day of surgery administration area prior to
      the surgery. Carotid-Femoral Pulse Wave Velocity (Aortic Stiffness).

      Carotid-femoral pulse wave velocity (cfPWV) will be determined by applanation tonometry using
      the Sphygmocor system by sequentially recording ECG-gated carotid and femoral artery
      waveforms. Pulse wave signals will be recorded by tonometers positioned at the base of the
      right common carotid artery and over the right femoral artery. The time (t) between the feet
      of simultaneously recorded waves will be determined as the mean of 10 consecutive cardiac
      cycles. PWV is calculated by the system software from the distance between measurement points
      (D) and the measured time delay (t) as follows: cfPWV = D/Δt (m/ s) where D is distance in
      meters and t is the time interval in seconds.

      After consent, the subject will be taken to a private exam room where a noninvasive study of
      PWV and central aortic BP will be performed in supine position using the SphygmoCor sensor
      positioned over the carotid and femoral or radial artery pulse waveform, along with 3-lead
      EKG for QRS timing of the onset of systole. The SphygmoCor pulse wave sensor will be
      calibrated with an upper arm sphygmomanometer cuff BP. The vascular aging measurements will
      not be used to guide or alter medical decision making in the study. The study will take
      approximately 30 min. They will also not be repeated for this protocol either during or after
      surgery.

      Pre and intraoperative data collection will include: ASA status, history of peripheral
      vascular disease, history of ischemic vascular disease, history of congestive heart failure,
      and history of cerebrovascular disease, intraop: all of the routine vital signs, anesthetic
      drug details, fluids, blood loss, and urine output data relevant to the surgical procedure.
      Any significant clinical AEs such as brady- or tachycardia (HR <50 or >100 for >10 min),
      hyper- or hypotension (BP >30% above or > 30% below awake), EKG rhythm or ST segment
      abnormality, abnormal BIS (anesthetic depth) or other EEG issue during anesthesia or surgery,
      and wake up difficulty will be documented in the clinical anesthesia electronic record. All
      other relevant monitoring data such as hypoxemia (pulse oximeter), hypo-or hyperventilation
      (capnography or arterial blood gas values) will be recorded in a clinical data file for each
      subject.

      Postoperative data collection will include vital signs and any clinical cardiac, neurological
      or renal adverse events or other complications especially for the first 30 days, and any
      later events including all-cause mortality up to one year after surgery. Postoperative
      outcome information will be primarily collected via the medical record review. We do not plan
      to visit study subjects at bedside while recovering from surgery as inpatients, and will not
      schedule additional outpatient research follow up visits. However we also plan to call
      enrolled subjects at 1, 6, and 12 months after surgery to ask them whether they have
      experienced postoperative complications such as a a stroke, myocardial infarction,
      dysrhythmia such as atrial fibrillation, heart failure, respiratory failure, kidney function
      problem, renal failure or death.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients who are undergoing surgery and aged 40 and above
      
Keywords: Pulse wave velocity; anesthesia