The Prognostic Importance of Abnormal Heart Rate Recovery and Chronotropic Response Among Exercise Treadmill Test Patients

Thomas M. Maddox, MD, MSc, FACC; Colleen Ross, MS; P. Michael Ho, MD, PhD, FACC; Frederick A. Masoudi, MD, MSPH, FACC; David Magid, MD, MPH; Stacie L. Daugherty, MD, MSPH; Pam Peterson, MD, MSPH, FACC; John S. Rumsfeld, MD, PhD, FACC

Disclosures

Am Heart J. 2008;156(4):736-744. 

In This Article

Discussion

In this large community-based cohort study of ETT patients, we found that the combination of abnormal HRR and CR was independently associated with increased all-cause mortality or nonfatal MI. This finding was supported by the similar trends seen among the individual secondary outcomes of all-cause mortality and nonfatal MI and the stepwise increase in risk in proportion to the number of abnormalities in HRR and CR. In addition, HRR and CR provided additional prognostic information to the DTS and identified higher risk patients among those with low-risk DTS.

Although several prior studies have combined various ETT parameters for the diagnosis of CAD,[9] little is known about the best way to integrate the HRR and CR parameters from ETT with regard to prognosis. One recent study among 1,910 US veterans from a single center found a significant association between combined abnormal HRR and CR and cardiovascular mortality.[11] However, the study did not provide information on how to integrate these findings with the DTS. Our study expands on these findings by demonstrating the association with a variety of adverse outcomes in a larger, community-based population. In addition, we provide a clinically useful method for interpreting these findings by stratifying our cohort by DTS.

The results of this study provide important additional insight into the role of HRR and CR for prognosis among ETT outpatients with low-risk DTS. Previously, these patients were deemed to be at low-risk for future mortality and cardiac events.[12] However, our analysis demonstrates that 5.7% of low-risk DTS patients with abnormalities of both HRR and CR died or had a nonfatal MI, in comparison to only 3.0% of intermediate-risk DTS patients with normal HRR and CR. The higher event rate in these "low-risk" patients compared to "intermediate-risk" patients supports the importance of HRR and CR in assessing prognosis and argues for the reclassification of patient risk based on this additional information. In contrast, the presence of abnormalities in either HRR or CR did not provide additional prognostic insight among intermediate-risk DTS patients.

These findings also suggest several future avenues for research to manage this increased risk for events, including the effectiveness of additional testing to evaluate these patients (eg, nuclear perfusion imaging, cardiac catheterization) and the evaluation of interventions to modify their risk profiles (eg, intensive medical therapies, disease management programs, exercise training). This additional prognostic information provided by HRR and CR, which are routinely collected by most noninvasive laboratories, also argues for their consistent inclusion in ETT interpretation. Currently, many laboratories in the United States only report the DTS or its constituent components. Our findings support a recent review calling for more complete inclusion of ETT data into standardized clinical reports.[23]

The pathophysiology of abnormal HRR and CR is not fully understood. Both HRR and CR appear to measure the autonomic response to exercise, abnormalities of which have been demonstrated to independently predict adverse cardiac outcomes.[5,12] Predisposition to fatal arrhythmias, sudden cardiac death, and significant CAD have been postulated as potential mediators of these outcomes.[10,24,25,26]

Heart rate recovery appears to measure the capacity of the cardiovascular system to reverse the vagal withdrawal that occurs during exercise.[11,17,18] Abnormalities in this reversal, as indicated by abnormal HRR, are associated with mortality in asymptomatic patients, patients with undergoing coronary angiography, patients undergoing stress echocardiography, and patients undergoing nuclear perfusion imaging.[23] This association is independent of left ventricular systolic function, functional capacity, and CAD severity.[23] Higher rates of fatal arrhythmias and sudden cardiac death may explain this increased risk-a recent study of asymptomatic patients demonstrated that abnormal HRR was a stronger predictor of sudden cardiac death, as compared to other modes of death.[10]

Chronotropic response appears to assess the autonomic response to exercise. Abnormalities in this response may indicate disruptions in autonomic balance and an inability of the cardiovascular system to appropriately respond to the sympathetic discharge and parasympathetic withdrawal that occurs during exercise.[27] Some studies have suggested that chronotropic incompetence serves as a protective response in the presence of CAD to avoid excessively high heart rates and its associated demands for coronary artery flow.[26,28]

This study has several potential limitations. First, our population was drawn from a single managed care organization in Colorado, which may limit the generalizability of our findings. However, Kaiser Colorado is a large, integrated, health care delivery system, with broad representation of the state's insured population. Second, our population was generally healthy, as indicated by the predominance of low-risk or intermediate-risk DTS. Thus, we cannot generalize our findings to a sicker population undergoing ETT. However, because optimal clinical management is less clear for low-risk or intermediate-risk patients, as compared to high-risk patients, the insights provided by our analysis should have applicability to most patients undergoing ETT. In addition, our findings demonstrated that HRR and CR parameters are especially valuable among low-risk DTS patients. Third, our assessment of hospitalization for nonfatal MI was based on ICD-9 codes data, which could have resulted in misclassification of the diagnosis. However, prior studies have verified this method as a robust method by which to ascertain MI occurrence.[29] Fourth, because of the small number of cardiac-related deaths in our cohort, we were unable to determine the association of HRR and CR with cardiac-related mortality. However, by reporting all-cause mortality and nonfatal MI, we are able to describe important adverse outcomes for patients and clinicians alike. Fifth, we are unable to assess MI outcomes among those 1,902 patients who disenrolled from Kaiser Permanente before the completion of the study period. However, these patients were evenly distributed by HRR and CR category, so any effect of these missing data would likely have biased our findings toward the null. Sixth, as with all observational studies, there is the potential for unmeasured confounders contributing to the associations found. However, our findings are consistent with prior literature regarding abnormal HRR and CR, and we had a wide array of ETT and clinical variables for risk adjustment. In addition, observational studies are the best way to assess "real world" patterns of care and outcomes.

In conclusion, we found that the presence of both abnormal HRR and CR among ETT patients is predictive of all-cause mortality and nonfatal MI. In particular, abnormal HRR and CR provide additional risk stratification among low-risk DTS patients, enabling providers to identify those patients at higher risk for adverse outcomes. These results support the routine incorporation of HRR and CR in ETT interpretation and suggest the need to evaluate whether further testing and/or more intensive treatment of patients found to be at increased risk based on these parameters can improve outcomes.

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