The exercise ECG cardiac stress test with or without imaging has become a mainstay in the noninvasive assessment of coronary artery disease (CAD). In fact, the primary value of stress testing is commonly thought to be in diagnosing and managing CAD, but researchers have established that stress testing can provide critical and otherwise unobtainable information for other cardiac diseases, particularly heart failure (HF).
Heart Failure and Exercise Testing
Exercise intolerance and reduction in functional aerobic capacity are among the key manifestations of HF. The preferred measure of an HF patient's functional aerobic capacity or cardiorespiratory fitness is maximum consumption of oxygen (VO2 max), which is most accurately measured with a cardiopulmonary exercise test (CPET). The CPET requires specialized equipment that enables measurement of the oxygen consumed and carbon dioxide produced during exercise.
Despite its importance, CPET is not widely available, especially in cardiac rehab settings. However, more easily obtainable parameters from the cardiac ECG stress test that assess autonomic tone can provide equally useful information.
Impaired Autonomic Function Parameters in LV Systolic Dysfunction Patients
Patients with HF with reduced ejection fraction (HFrEF) exhibit impaired autonomic function, which is believed to be due to impaired vagal tone and enhanced sympathetic function. These autonomic changes lead to reduced responsiveness to β adrenergic stimulation due to reduced adrenergic receptors and reduced downstream signaling. In response to these changes, the heart rate fails to increase normally during exercise (chronotropic incompetence) in patients with HF, which likely contributes to observed limitations in exercise.
Heart Rate Recovery as a Prognosticator in Heart Failure
Heart rate recovery (HRR) after exercise stress is the result of an early increase in parasympathetic tone with a more gradual reduction in sympathetic tone. It is a powerful predictor of mortality in normal subjects and patients with CAD.
A study in the Journal of Cardiac Failure demonstrated that HRR one minute after exercise was an independent predictor of mortality in patients with HFrEF. They studied 202 patients with HFrEF and found that HRR was independently associated with mortality or a need for urgent transplantation over 624 days of follow up. The association persisted after adjusting for max VO2 and the HF Survival Score. HF patients with HRR ≥30 beats/min had a low risk of events, irrespective of the risk predicted by the survival scores.
The authors found an association between reduced HRR and biomarkers of inflammation, and they hypothesized that "pathophysiologic links between autonomic function and inflammation may be mediators of this association."
In a subgroup of 15 subjects, reduced post-exercise HRR was associated with increased serum markers of inflammation (interleukin-6 r=0.58, p=0.024, high sensitivity C-reactive protein r=0.66, p=0.007).
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Heart Rate Reduction vs. Cardiopulmonary Exercise Test in Heart Failure Assessment
Researchers publishing in the American Heart Journal studied 87 patients with compensated HFrEF using CPET and found that HRR at 1 minute (HRRR1) correlated well with max VO2 and provided independent ability to predict a patient's 1-year death/hospitalization end point.
They concluded that HRR1 "appears to outperform peak VO2, LVEF, and HF etiology in predicting risk of death or hospitalization" and that "given the independent prognostic value of HRR, this variable alone may provide valuable clinical information when ventilatory expired gas analysis is not available."
Heart Rate Reduction in Heart Failure with Preserved Ejection Fraction
Abnormal HR response during exercise testing has also been observed in HF patients with preserved ejection fraction (HFpEF). A study published in Circulation: Heart Failure found that patients with HFpEF had lower peak HR response during maximal exercise than control patients, with 34% exhibiting chronotropic incompetence. Abnormal HRR was noted in 23% of HFpEF patients versus only 2% of controls.
Looking Beyond Coronary Artery Disease
Although the cardiac stress test has a firmly established role in diagnosis and management of CAD, these studies show that the technique has wider applications in the cardiology sphere. Through analysis of heart rate response during and after exercise, the cardiac stress ECG modality provides insights into the status of the patient's autonomic nervous system. In particular, HRR has emerged as a simple yet powerful tool for assessing the autonomic nervous system in HF patients with normal or reduced ejection fraction.
HRR is associated with the most sophisticated measure of cardiopulmonary fitness and has been shown to be a critical prognostic tool. It should be noted that to date, no studies have clearly demonstrated that modifying HRR through exercise or medication results in improved outcomes.