1353724 - Risk Stratification using Heart Rate Response to Breathing Maneuvers in Patients with Suspected Coronary Artery Disease

Vasoactive breathing maneuvers with hyperventilation (HV) and breath-holds (BH), combined with Oxygenation-Sensitive Cardiovascular Magnetic Resonance (OS-CMR) imaging, have been shown to reflect coronary vascular function (1, 2). A retrospective study of heart rate (HR) response to HV showed the potential of blunted HR to differentiate between healthy individuals and patients with cardiovascular disease (3). The present study aimed to assess the predictive value of the HR response to breathing maneuvers for the presence of significant coronary artery disease (CAD).

Methods:

We enrolled patients with suspected or known CAD (age ≥ 35 years) and healthy controls. Using a pulse sensor (EKG-Flex/Pro sensor-SA9306M, Thought Technology Ltd.; Montreal, Canada), beat-to-beat HR was recorded while performing a 4-min breathing maneuver, including 2 minutes of normal breathing (NB), followed by 1 min of deep, paced HV (30 breaths/min), and a subsequent maximal voluntary BH. On the same day, patients underwent clinically indicated adenosine first-pass myocardial perfusion imaging. A significant inducible perfusion deficit, as clinically reported, served as the reference standard. Raw HR data was analyzed using a MATLAB-based automated analysis tool. Heart rate increase was calculated during the HV (HRR-HV), defined as the percentage change in the HR increase during HV relative to average HR during NB [(Mean HR-NB) – (MAX HR-HV)/ (Mean HR-NB) *100] (Fig. 1A).

Results:

We studied 70 patients and 14 control subjects. A diagnosis of inducible myocardial ischemia was made in 43 patients (51% male; 63±10 years). Patients with CAD diagnosis had a significantly lower HR increase (HRR-HV; 20.1%±11.09) than the healthy control group (39.1%±17; p< .001) and the non-CAD group (33.8%±24.1; p=.002) (Fig. 1B). The area under the receiver operating characteristic (ROC) curve for HRR-HV was 0.71 (95%; CI 0.58-0.84) (Fig. 2). An HRR-HV of ≥38% had a sensitivity of 97.6%, specificity of 33.3%, a negative predictive value of 90%, and a positive predictive value (PPV) of 70% for the presence of significant CAD. In patients with intermediate (10%) and high (28%) pre-test probability of CAD, a normal HRR-HV ( >39%) decreased the post-test probability to ≤ 3% (Fig. 3)

Conclusion:

In patients undergoing diagnostic workup for chest pain, the heart rate increase in response to hyperventilation has a moderate diagnostic accuracy, but with a suitable threshold, a high negative predictive value for ruling out significant coronary artery disease. By correctly reclassifying patients with normal HR response from high or intermediate-risk to low-risk, this fast and completely non-invasive approach can reduce risks associated with cardiac testing, and may help reduce costs from unnecessary investigations and procedures.