The Predictive Value of the Heart Rate Response to Breathing Maneuvers for Inducible Myocardial Perfusion Deficits

Breathing maneuvers, i.e. hyperventilation followed by breath-holding, have been shown to change coronary dynamics; hyperventilating narrows the coronary arteries, puts "stress" on the heart, and increases the heart rate, whereas breath-hold dilates the coronary arteries and decreases the heart rate," rest". Heart rate response to hyperventilation has been reported to have high diagnostic accuracy to rule out heart disease. The cardiac stress test, the modality of choice for the initial assessment of patients with suspected coronary artery disease(CAD), is routinely overprescribed by physicians, which exerts a financial burden on the healthcare system. Hence, developing an inexpensive, reliable, and available tool-HR response to breathing maneuvers- may avoid unnecessary referrals for cardiac stress tests by an effective differentiation of patients with CAD from healthy people. This study aims to assess the negative predictive value of the HR response to a 4-minute breathing maneuver for inducible myocardial ischemia, avoiding further stress testing as a gatekeeper.

Patients with suspected CAD must have a clinical indication for cardiac stress test based on the clinical judgement of their referring physician and be referred to adenosine stress first-pass perfusion MRI located at the McGill University Health Centre (MUHC). Healthy participants must have no known history of cardiovascular or respiratory diseases. At the time of recruitment, eligible participants will perform the 4-minute breathing maneuver, comprised of 2 minutes of normal breathing and 1-min hyperventilation (rate of 30 breaths or more per minute) followed by a maximal breath-hold. A portable FDA-approved device will be used to record HR and respiration patterns during breathing maneuvers, which enables us to observe the beat-to-beat HR changes during each phase of the breathing maneuvers. On the same day, the participants' socio-demographics, medications, medical history and INTERHEART risk scores will be obtained. Afterwards, patients referred for a stress test will undergo adenosine stress first-pass perfusion MRI as prescribed by their referring physician to validate the findings of the breathing maneuver and detect CAD. Inside the MRI, the participants will also be asked to perform the same 4-min breathing maneuver during Oxygenation Sensitive-Cardiac Magnetic Resonance imaging (OS-CMR) protocol. This imaging technique provides a non-invasive assessment of myocardial oxygenation, relying on the paramagnetic features of deoxygenated hemoglobin as the intrinsic contrast agent.

Eligibility Criteria:
Inclusion Criteria:

* Healthy volunteers:

  1. Aged \> 35
  2. No known current or pre-existing problems that would affect the cardiovascular or respiratory system

Patient population:

1. Aged \> 35
2. Clinically indicated referral for adenosine stress first-pass perfusion MRI in subjects with known or suspected coronary artery disease

Exclusion Criteria:

Healthy Volunteers:

1. MR incompatible devices such as pacemakers, defibrillators, implanted material, or foreign bodies.
2. Consumption of caffeine (coffee, tea, cocoa, chocolate, "energy drink") during the 12 hours prior to the exam
3. Presence of cardiovascular disease.
4. Regular nicotine consumption during the last 6 months

Patient Population:

1. MR incompatible devices such as pacemakers, defibrillators, implanted material, or foreign bodies.
2. Vasoactive medication (e.g. nitrate, beta-blocker, calcium channel blocker) during the 12 hours prior to the exam.
3. Consumption of caffeine (coffee, tea, cocoa, chocolate, "energy drink") during the 12 hours prior to the exam
4. Acute Coronary Syndrome (ACS), or previous Coronary Artery Bypass Surgery
5. Previous myocardial infarction within one month
6. Clinically unstable condition
7. Significant or uncontrolled arrhythmia
8. Patients who are pregnant
9. Active myocarditis, constrictive pericarditis, any cardiomyopathy, cardiac or systemic amyloidosis
10. Left bundle branch block (LBBB)
11. Established valvular regurgitation or stenosis abnormality above moderate severity
12. Patients with a known history of heart failure (Ejection fraction\<40%)