HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shetler, K. Articles by Myers, J. Search for Related Content PubMed PubMed Citation Articles by Shetler, K. Articles by Myers, J.

CLINICAL STUDY: STRESS TESTING

Heart rate recovery: validation and methodologic issues

^a Division of Cardiovascular Medicine, Stanford University Medical Center and the Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA

Manuscript received March 22, 2001; revised manuscript received August 15, 2001, accepted August 29, 2001.

^* Reprint requests and correspondence: Dr. Victor Froelicher, Cardiology Division (111C), Veterans Affairs Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304 USA.
vicmd{at}aol.com

	Abstract

Top Abstract Methods Results Discussion References

 
OBJECTIVES: The goal of this study was to validate the prognostic value of the drop in heart rate (HR) after exercise, compare it to other test responses, evaluate its diagnostic value and clarify some of the methodologic issues surrounding its use.

BACKGROUND: Studies have highlighted the value of a new prognostic feature of the treadmill test—rate of recovery of HR after exercise. These studies have had differing as well as controversial results and did not consider diagnostic test characteristics.

METHODS: All patients were referred for evaluation of chest pain at two university-affiliated Veterans Affairs Medical Centers who underwent treadmill tests and coronary angiography between 1987 and 1999 as predicted after a mean seven years of follow-up. All-cause mortality was the end point for follow-up, and coronary angiography was the diagnostic gold standard.

RESULTS: There were 2,193 male patients who had treadmill tests and coronary angiography. Heart rate recovery at 2 min after exercise outperformed other time points in prediction of death; a decrease of <22 beats/min had a hazard ratio of 2.6 (2.4 to 2.8 95% confidence interval). This new measurement was ranked similarly to traditional variables including age and metabolic equivalents but failed to have diagnostic power for discriminating those who had angiographic disease.

CONCLUSIONS: Heart rate at 1 or 2 min of recovery has been validated as a prognostic measurement and should be recorded as part of all treadmill tests. This new measurement does not replace, but is supplemental to, established scores.

Abbreviations and Acronyms   CABG   coronary artery bypass grafting   CAD   coronary artery disease   HR   heart rate   METS   metabolic equivalents   MI   myocardial infarction   PTCA   percutaneous transluminal coronary angioplasty   RAS   renin-angiotensin-sympathetic nervous system   ROC   receiver operating characteristic

As with any new finding, it is essential to validate its reproducibility and applicability in other populations as well as to demonstrate what methodology is required to obtain similar results. Heart rate recovery has been shown to be prognostic usually at 1 or 2 min after exercise in populations referred for standard exercise testing (1), referred for nuclear testing (2) and with the use of submaximal protocols (3), but the threshold value for an abnormal test (cut-point) has varied. In one previous study, the protocol used was staged with a cool-down walk, yet current guidelines suggest that ramp-testing and rapid supine patient placement after the exercise test offer advantages over other methods and should be considered (4). The effect of beta-blockers, the optimal time point in recovery to measure HR drop, as well as the appropriate cut-point to assess the magnitude of the decrease in HR remain unresolved. Moreover, while the prognostic value of HR recovery has been highlighted, its relative value compared with other treadmill responses and its diagnostic value remain uncertain.

The purpose of this study was to validate this measurement, compare it with other test responses, evaluate its diagnostic value and clarify some of the methodologic issues surrounding its use.

	Methods

Top Abstract Methods Results Discussion References

 
Population.   A total of 8,000 male patients underwent treadmill testing at two Veterans Affairs Medical Centers between 1987 and 1998. Of these, 3,454 were evaluated for chest pain with coronary angiography within three months of treadmill testing. Patients with previous cardiac surgery or angiography, valvular heart disease, left bundle branch block, paced rhythms or Wolff-Parkinson-White on their resting electrocardiogram were excluded from the study. Remaining were 2,193 patients for survival analysis; after excluding those with previous myocardial infarction (MI) by history or by Q waves, there was a subgroup of 1,282. While the total remaining patients are appropriate for prognostic assessment, the evaluation of the diagnostic properties of a test should be performed in the subgroup without MI (4).

Exercise testing
Patients underwent symptom-limited treadmill testing using the U.S. Air Force School of Aerospace Medicine (5) or an individualized ramp treadmill protocol (6). The physiologic distinction of these protocols is that the patient is subjected to small, frequent increments in workload rather than uneven increases every 3 min. Information gathered from a questionnaire enabled maximal exercise to be reached at approximately 10 min (7). Patients did not perform a cool-down walk but were placed supine as soon as possible after exercise. The reasons for termination were angina, >2 mm of abnormal ST depression, drop in systolic blood pressure or ominous arrhythmias. Visual ST-segment depression was measured at the J junction and corrected for pre-exercise ST-segment depression. An abnormal response was defined as 1 mm or more of horizontal or downsloping ST-segment depression. Blood pressure was taken manually, and metabolic equivalents (METS) were estimated from treadmill speed and grade. Heart rate was measured supine, standing, during each minute of exercise, at maximum exercise and in recovery at 1, 2, 3 and 5 min. Heart rate recovery was defined as (maximum HR—HR at specified time period after exercise) and represented the drop in HR during that time interval. No test was classified as indeterminate (8); medications were not withheld, and maximal HR target was not used as an end point. The exercise tests were performed, analyzed and reported with a standard protocol utilizing a computerized database.

Coronary angiography
Coronary artery narrowing was visually estimated and expressed as percent lumen diameter stenosis. Patients with a 50% narrowing of the left main, left anterior descending, left circumflex or right coronary arteries or their major branches were considered to have significant angiographic coronary artery disease (CAD). Severe disease was considered to be two-vessel disease if the proximal left anterior descending was involved; otherwise, three-vessel or left main disease were considered severe. The 50% criterion was chosen to be consistent with definitions used by the Coronary Artery Bypass Graft Surgery Trialists’ Collaboration (9). In addition, the Duke coronary artery jeopardy score was calculated (10). Ejection fraction was estimated from biplane left ventricular angiograms. Decisions for cardiac catheterization were consistent with clinical practice.

Follow-up
The social security death index was used to match all of the patients’ names to their social security numbers. The index was updated weekly, and the most current records were used. Death status was determined as of July 2000 and was 100% complete. No other information regarding hospitalizations, cardiac interventions or cause of death during the follow-up was known.

Statistical methods
All-cause mortality was used as the end point for follow-up, and coronary angiography was utilized for diagnostic gold standard.

Survival analysis was performed using Kaplan-Meier curves to compare variables and cut-points, and the Cox hazard function was used to demonstrate which variables were independently and significantly associated with death. Automatic selection of variables was performed with a Z value cutoff of 2 and 20 iterations. Hazard ratios were calculated along with their 95% confidence intervals.

Logistic regression was used to separate subjects into those with and without significant angiographic disease, based on clinical and measured exercise variables in the diagnostic subpopulation. Forward selection was used with entry at a significance level <0.05. The general linear logistic regression model used took the following form:

where a is the intercept, b and c are coefficients and x and y are variable values.

How well the models separated patients with and without a given outcome (abnormal angiogram or death) was assessed by means of the area under a receiver operating characteristic (ROC) curve, which ranged from 0 to 1, with 0.5 corresponding to no discrimination (i.e., random performance) and 1.0 to perfect discrimination.

Number Crunching System Software (Salt Lake City, Utah) was used for all statistical analyses.

	Results

Top Abstract Methods Results Discussion References

 
Patient characteristics.   This male study population had a mean height of 69.6 in. (±2.9 in.), a mean weight of 191 lbs (±34 lbs) and a mean body mass index of 28 ± 9. Average resting HR was 76 ± 14 beats/min, with a corresponding mean systolic blood pressure of 125 ± 20 mm Hg. Regarding medications, 4.4% reported taking digoxin, and 34% were taking beta-blockers. No significant differences in these parameters were noted between those who survived and those who died. Other relevant variables for the entire population, for those who survived and the 413 patients who died over the mean seven-year (median six) follow-up are presented with significance levels in Table 1. There was an average annual mortality of 2%.

View larger version (12K): [in this window] [in a new window]   Figure 1 Kaplan-Meier survival curves for the three published criteria for heart rate recovery: (Top) 1 min post/12 beats/min drop, (Middle) 1 min post/18 beats/min drop and (Bottom) 2 min post/42 beats/min drop.

View larger version (16K): [in this window] [in a new window]   Figure 2 Kaplan-Meier survival curve for the 2 min post/22 beats/min drop criterion found to be optimal in our study.

View larger version (20K): [in this window] [in a new window]   Figure 3 Kaplan-Meier survival curves for 2 min post/22 beats/min drop according to beta-blocker status.

Prognostic score
Because the ischemic components of the Duke treadmill score were not predictive of all-cause mortality, we elected to consider the combined use of METS and HR recovery. Figure 4 presents a Kaplan-Meier plot using a METS criterion of 5 and HR recovery criterion of 22 beats/min as well as for abnormal by both criteria.

View larger version (22K): [in this window] [in a new window]   Figure 4 Kaplan-Meier survival curves for the criteria of 2 min post/22 beats/min drop or <5 metabolic equivalents (METS) exercise capacity and for patients who fulfilled both criteria. HRR = heart rate drop at 2 min post exercise.

We chose cut-points in this prognostic score by which to stratify patients into high-, intermediate- and low-risk as illustrated in Figure 5. The high-risk group had a hazards ratio of greater than five times. The score was entered along with data from cardiac catheterization into a proportional hazards regression model with automatic selection. The above score was chosen first with a Z value of 13.3 (p < 0.001) followed by ejection fraction with a Z value of 3 (p < 0.002) and, finally, the Duke jeopardy score with a Z value of 2.6 (p = 0.01). When cardiac catheterization variables were added to the Cox hazard model, they were superceded by the score variables.

View larger version (18K): [in this window] [in a new window]   Figure 5 Kaplan-Meier survival curves for the three levels of risk stratification according to the score.

	Discussion

Top Abstract Methods Results Discussion References

 
Heightened activation of the renin-angiotensin-sympathetic nervous system (RAS) at rest is associated with adverse outcomes in cardiovascular disease (13). The RAS hyperactivity has been shown to predict death in congestive heart failure, as demonstrated by studies of neurohormonal mediators, HR variability and baroreflex sensitivity (14). Recent attention has been paid to manifestations of the RAS and the balance between the sympathetic and parasympathetic nervous system during exercise testing (15). During exercise there is activation of the sympathetic nervous system and withdrawal of parasympathetic activity; the reverse occurs during recovery.

Previous studies.   Recently, consideration has been given to the role of HR in recovery as a predictor of mortality. Heart rate recovery is mediated by vagal reactivation, and the rate at which HR declines appears to be a reflection of a faster recovery from the sympathetic drive necessary during exercise (16). Increased vagal activity associated with a faster HR recovery has been shown to be associated with a decrease in risk of death (17). For this reason, several recent studies have looked at HR recovery after exercise as a prognostic tool. These studies are summarized in Table 3. In the first study, Cole et al. (2) looked at 2,428 adults who had been referred for exercise scintigraphy over six years. They found that, using a drop of 12 beats/min at 1 min after exercise as the definition of an abnormal response, a relative risk of 4.0 for death was observed. The group with a value <12 had a mortality of 19%, while the group with an HR decrease >12 had a mortality of 5% over the six-year period. The study employed the symptom-limited Bruce protocol with a 2-min cool-down walk. Patients on beta-blockers were included in the study, and no difference was seen in the ability of the test to discriminate between low- and high-risk patients in those patients on beta-blockers. The investigators used all-cause mortality and performed survival analysis with and without censoring of interventions (coronary artery bypass grafting [CABG] and percutaneous transluminal coronary angioplasty [PTCA]) and found no difference in results.

To further elucidate the power of HR recovery in distinct populations, these investigators then published another study using patients referred for standard exercise treadmill testing (1). Using the same methods as the original study, the investigators found similar results, although, notably, the cut-off value for an abnormal test was different. Patients with an abnormal HR recovery had 8% mortality at 5.2 years, whereas patients with a normal HR recovery had only 2% mortality. Neither this nor the previous study censored for CABG or PTCA, and this study had 8% patients with CABG enrolled along with 75% asymptomatic individuals. The investigators also compared the prognostic ability of HR recovery to that of the Duke treadmill score. While the individual components of the Duke score (except exercise capacity) did not have prognostic power, the score produced similar survival curves to HR recovery and, in patients with abnormal scores on both tests, survival was even further compromised.

This study
In our study, we attempted again to validate the use of HR recovery for prognosis in a male veteran population. The mortality rate in our study was higher than it was in previous studies of HR recovery. Using similar statistical analyses, we found that a decrease of HR in recovery of <22 beats/min at 2 min after exercise identified a high-risk group of patients. While these data confirm the utility of HR recovery, it is important to note that several studies have employed different cut-points for defining an abnormal test, even when the testing protocol (e.g., presence or absence of cool-down, minute of recovery when measurements are made) are the same. Therefore, it is difficult to know which value is most applicable to the general population.

Beta-blockade
We also found that the clinical administration of beta-blockers had no significant impact on the prognostic value of HR recovery. Given the impact of beta-blockers on the ability to achieve maximum HR, it would not be unreasonable to imagine that the medication might have an impact on HR recovery. However, the same results were found in those who reached target HR and those who did not. Further analysis of this issue would be warranted to better understand the true impact of this medication and maximal HR.

Multivariable analysis
Through multivariate analysis, we evaluated the power of several other clinical and treadmill variables to see how they compared with HR recovery in their ability to predict outcome. Similar to Cole et al. (2), we found that a low METS capacity was the most powerful variable associated with outcome. This finding was not shared by Nishime et al. (1), in which the strongest predictor of death was resting tachycardia. It is important to note that in our study and those of Nishime et al. (1) and Cole et al. (3), ischemic ST responses on the treadmill did not predict death. Exercise-induced angina was also not a significant variable in the study by Nishime et al. (1) nor in our study. The Duke treadmill score (18) includes both of these variables, and they have been predictors of cardiovascular outcome in several other studies.

This raises the question as to why ischemic variables included in the Duke score that clearly have diagnostic power do not predict all-cause mortality. While all-cause mortality has advantages over cardiovascular mortality as an end point (19), the Duke score was generated using the end points of infarction and cardiovascular death (18). Furthermore, cardiology interventions such as bypass surgery or catheter interventions were censored in the Duke study (i.e., subjects were removed from the survival analysis when these events occurred). Such censoring should increase the association of ischemic variables with outcome by removing patients whose disease has been alleviated and, thereby, would not be as likely to experience the outcome. We did not censor patients in this study on the basis of whether or not they had a cardiovascular procedure during follow-up because we do not have that information. From a previous study using a similar patient population, our group found that 75% of deaths were cardiovascular deaths, and 20% of patients were censored in follow-up due to bypass surgery (20). If the proportions of these statistics are similar in our current population, it would not be unreasonable to expect a bias against the predictive power of these variables. However, this hypothesis would need to be proven since censoring had no impact on HR recovery findings in the study that did censor (2) nor in the Duke score. In fact, exercise-induced ST depression predicted all-cause mortality with and without censoring in an earlier study (21). These contradictory results could potentially be due to the more effective methods of treatment currently available for coronary disease.

Diagnostic characteristics
A distinct advantage over previous studies is that we selected a group who underwent coronary angiography. This made it possible to evaluate the diagnostic ability of HR recovery. Surprisingly, HR recovery was not selected among the standard variables to be included in a logistic model, and the ROC curve did not indicate any discriminatory value. Thus, while HR recovery has been validated as an important prognostic variable, it did not help the diagnosis of coronary disease in this study.

Study limitations
While our study was unique in its strict adherence to guidelines in the performance of exercise testing and its inclusion of angiographic data, there were some limitations. The use of a ramp protocol differed from previous studies using the Bruce protocol, but, rather than being a limitation, this extends earlier findings to another protocol. The lack of inclusion of women is quite important, especially given the different characteristics of treadmill testing between women and men that have previously been shown. Additionally, we were unable to provide information on cause of death and did not have information about cardiovascular procedures during the follow-up period, so we could not censor on them. As mentioned earlier, the inability to censor may skew results. Without censoring, we are predicting prognosis in spite of, or in addition to, modern therapy rather than predicting who should have interventions. The pathophysiology of an inadequate HR decrease in recovery has not been explained by our study. Finally, as mentioned previously, our angiographic subset was subject to work-up bias.

Conclusions
We found that, among male patients with or without prior MI but without prior bypass surgery referred for clinical exercise testing done without cool-down walk but with prompt supine placement, an HR drop of 22 beats/min at 2 min recovery had prognostic, but not diagnostic, value. Heart rate at 1 or 2 min of recovery has been validated as a prognostic treadmill measurement and should be recorded as part of all treadmill tests. The prognostic power of this measurement does not appear to be affected by beta-blockade, but its cut-point is most likely affected by population selection and protocol. A score including HR recovery, METS, age and history of typical angina pectoris was superior to cardiac catheterization data for predicting prognosis. To date, this measurement has not been evaluated as a diagnostic indicator, and we found that it was not diagnostic of angiographic CAD. The drop of HR in recovery or its score should supplement, but not replace, the Duke treadmill score that has been validated as a predictor of infarct-free survival and diagnostic of angiographic CAD. Though our analysis has not explained the pathophysiology of an inadequate decline of HR after exercise, it may well represent a marker of habitual physical activity level (16).

	References

Top Abstract Methods Results Discussion References

 

1. Nishime EO, Cole CR, Blackstone EH, et al. Heart rate recovery and treadmill exercise score as predictors of mortality in patients referred for exercise ECG. JAMA. 2000;284:1392–1398[Abstract/Free Full Text]
2. Cole CR, Blackstone EH, Pashkow FJ, et al. Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med. 1999;341:1351–1357[Abstract/Free Full Text]
3. Cole CR, Foody JM, Blackstone EH, et al. Heart rate recovery after submaximal exercise testing as a predictor of mortality in a cardiovascular healthy cohort. Ann Intern Med. 2000;132:552–555[Abstract/Free Full Text]
4. Gibbons RJ, Balady GJ, Beasley JW, et al. ACC/AHA guidelines for exercise testing: A report of the american college of cardiology/american heart association task force on practice guidelines. J Am Coll Cardiol. 1997;30:260–311[CrossRef][Medline]
5. Am J Cardiol. 1977;39(5):
6. Chest. 1992;101(5 (Suppl)):
7. Myers J, Do D, Herbert W, Ribisl P, Froelicher VF. A nomogram to predict exercise capacity from a specific activity questionnaire and clinical data. Am J Cardiol. 1994;73:591–596[CrossRef][Medline]
8. Reid MC, Lachs MS, Feinstein AR. Use of methodological standards in diagnostic test research: Getting better but still not good. JAMA. 1995;274:645–651[Abstract]
9. Yusuf S, Zucker D, Peduzzi P, et al. Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. [published erratum appears in Lancet 1994 Nov 19;344(8934):1446]Lancet. 1994;344(8922):563–570[CrossRef][Medline]
10. Califf RM, Phillips HR, Hindman MC, et al. Prognostic value of a coronary artery jeopardy score. J Am Coll Cardiol. 1985;5:1055–1063[Abstract]
11. Do D, West JA, Morise A, Froelicher V. A consensus approach to diagnosing coronary artery disease based on clinical and exercise test data. Chest. 1997;111:1742–1749[Abstract/Free Full Text]
12. Yamada H, Do D, Morise A, et al. Review of studies using multivariable analysis of clinical and exercise test data to predict angiographic coronary artery disease. Prog Cardiovasc Dis. 1997;39:457–481[CrossRef][Medline]
13. Eur Heart J. 1998;19(Suppl F):
14. Clin Cardiol. 1995;18(Suppl I):
15. Lauer MS, Francis GS, Okin PM, et al. Impaired chronotropic response to exercise stress testing as a predictor of mortality. JAMA. 1999;281:524–529[Abstract/Free Full Text]
16. Imai K, Sato H, Hori M, Kusuoka H, et al. Vagally mediated heart rate recovery after exercise is accelerated in athletes but blunted in patients with chronic heart failure. J Am Coll Cardiol. 1994;24:1529–1535[Abstract]
17. Hull SS, Vanoli E, Adamson PB, et al. Do increases in markers of vagal activity imply protection from sudden death?: The case of scopolamine. Circulation. 1995;91:2516–2519[Abstract/Free Full Text]
18. Mark DB, Shaw L, Harrell FE Jr., et al. Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease. N Engl J Med. 1991;325:849–853[Abstract]
19. Lauer MS, Blackstone EH, Young JB, et al. Cause of death in clinical research: Time for a reassessment? J Am Coll Cardiol. 1999;34:618–620[Free Full Text]
20. Froelicher VF, Morrow K, Brown M, et al. Prediction of atherosclerotic cardiovascular death in men using a prognostic score. Am J Cardiol. 1994;73:133–138[CrossRef][Medline]
21. Morrow K, Morris CK, Froelicher VF, et al. Prediction of cardiovascular death in men undergoing noninvasive evaluation for coronary artery disease. Ann Intern Med. 1993;118:689–695[Abstract/Free Full Text]

This article has been cited by other articles:

				P. N. Peterson, D. J. Magid, C. Ross, P. M. Ho, J. S. Rumsfeld, M. S. Lauer, E. E. Lyons, S. S. Smith, and F. A. Masoudi Association of Exercise Capacity on Treadmill With Future Cardiac Events in Patients Referred for Exercise Testing Arch Intern Med, January 28, 2008; 168(2): 174 - 179. [Abstract] [Full Text] [PDF]

				S. Sundaram, M. Carnethon, K. Polito, A. H. Kadish, and J. J. Goldberger Autonomic effects on QT-RR interval dynamics after exercise Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H490 - H497. [Abstract] [Full Text] [PDF]

				T. A. Dewland, A. S. Androne, F. A. Lee, R. J. Lampert, and S. D. Katz Effect of acetylcholinesterase inhibition with pyridostigmine on cardiac parasympathetic function in sedentary adults and trained athletes Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H86 - H92. [Abstract] [Full Text] [PDF]

				W. Shu, W. Lei, and S. Peng Recent development of ischaemic heart disease in sex difference Postgrad. Med. J., April 1, 2007; 83(978): 240 - 243. [Abstract] [Full Text] [PDF]

				N. J. Leeper, F. E. Dewey, E. A. Ashley, M. Sandri, S. Y. Tan, D. Hadley, J. Myers, and V. Froelicher Prognostic Value of Heart Rate Increase at Onset of Exercise Testing Circulation, January 30, 2007; 115(4): 468 - 474. [Abstract] [Full Text] [PDF]

				P. Kligfield and M. S. Lauer Exercise Electrocardiogram Testing: Beyond the ST Segment Circulation, November 7, 2006; 114(19): 2070 - 2082. [Full Text] [PDF]

				H. Schubiner, B. Hassunizadeh, and R. Kaczynski A controlled study of autonomic nervous system function in adults with attention-deficit/hyperactivity disorder treated with stimulant medications: results of a pilot study. J Atten Disord, November 1, 2006; 10(2): 205 - 211. [Abstract] [PDF]

				J. J. Goldberger, F. K. Le, M. Lahiri, P. J. Kannankeril, J. Ng, and A. H. Kadish Assessment of parasympathetic reactivation after exercise Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2446 - H2452. [Abstract] [Full Text] [PDF]

				L. J. Shaw, C. N. Bairey Merz, C. J. Pepine, S. E. Reis, V. Bittner, S. F. Kelsey, M. Olson, B. D. Johnson, S. Mankad, B. L. Sharaf, et al. Insights From the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part I: Gender Differences in Traditional and Novel Risk Factors, Symptom Evaluation, and Gender-Optimized Diagnostic Strategies J. Am. Coll. Cardiol., February 7, 2006; 47(3_Suppl_S): S4 - S20. [Abstract] [Full Text] [PDF]

				C. Falcone, M. P. Buzzi, C. Klersy, and P. J. Schwartz Rapid Heart Rate Increase at Onset of Exercise Predicts Adverse Cardiac Events in Patients With Coronary Artery Disease Circulation, September 27, 2005; 112(13): 1959 - 1964. [Abstract] [Full Text] [PDF]

				S. Mora, R. F. Redberg, A. R. Sharrett, and R. S. Blumenthal Enhanced Risk Assessment in Asymptomatic Individuals With Exercise Testing and Framingham Risk Scores Circulation, September 13, 2005; 112(11): 1566 - 1572. [Abstract] [Full Text] [PDF]

				M. Lauer, E. S. Froelicher, M. Williams, and P. Kligfield Exercise Testing in Asymptomatic Adults: A Statement for Professionals From the American Heart Association Council on Clinical Cardiology, Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention Circulation, August 2, 2005; 112(5): 771 - 776. [Abstract] [Full Text] [PDF]

				L. L. Smith, M. Kukielka, and G. E. Billman Heart rate recovery after exercise: a predictor of ventricular fibrillation susceptibility after myocardial infarction Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1763 - H1769. [Abstract] [Full Text] [PDF]

				J. H. Mieres, L. J. Shaw, A. Arai, M. J. Budoff, S. D. Flamm, W. G. Hundley, T. H. Marwick, L. Mosca, A. R. Patel, M. A. Quinones, et al. Role of Noninvasive Testing in the Clinical Evaluation of Women With Suspected Coronary Artery Disease: Consensus Statement From the Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and Intervention, American Heart Association Circulation, February 8, 2005; 111(5): 682 - 696. [Abstract] [Full Text] [PDF]

				D. R. Ricardo, M. B. de Almeida, B. A. Franklin, and C. G. S. Araujo Initial and Final Exercise Heart Rate Transients: Influence of Gender, Aerobic Fitness, and Clinical Status Chest, January 1, 2005; 127(1): 318 - 327. [Abstract] [Full Text] [PDF]

				A. P. Morise Heart Rate Recovery: Predictor of Risk Today and Target of Therapy Tomorrow? Circulation, November 2, 2004; 110(18): 2778 - 2780. [Full Text] [PDF]

				M P Frenneaux Autonomic changes in patients with heart failure and in post-myocardial infarction patients Heart, November 1, 2004; 90(11): 1248 - 1255. [Abstract] [Full Text] [PDF]

				K. Nasir, R. F. Redberg, M. J. Budoff, E. Hui, W. S. Post, and R. S. Blumenthal Utility of Stress Testing and Coronary Calcification Measurement for Detection of Coronary Artery Disease in Women Arch Intern Med, August 9, 2004; 164(15): 1610 - 1620. [Abstract] [Full Text] [PDF]

				M. S. Lauer Chronotropic incompetence: Ready for prime time J. Am. Coll. Cardiol., July 21, 2004; 44(2): 431 - 432. [Full Text] [PDF]

				L. W. Raymond Vagal Pas de Deux: Heart-Lung Interplay in Postexercise Heart Rate Recovery Chest, April 1, 2004; 125(4): 1186 - 1190. [Full Text] [PDF]

				N. Seshadri, T. R. Gildea, K. McCarthy, C. Pothier, M. S. Kavuru, and M. S. Lauer Association of an Abnormal Exercise Heart Rate Recovery With Pulmonary Function Abnormalities Chest, April 1, 2004; 125(4): 1286 - 1291. [Abstract] [Full Text] [PDF]

				I. G. Poornima, T. D. Miller, T. F. Christian, D. O. Hodge, K. R. Bailey, and R. J. Gibbons Utility of myocardial perfusion imaging in patients with low-risk treadmill scores J. Am. Coll. Cardiol., January 21, 2004; 43(2): 194 - 199. [Abstract] [Full Text] [PDF]

				B. P. Yawn, K. A. Ammar, R. Thomas, and P. C. Wollan Test-Retest Reproducibility of Heart Rate Recovery After Treadmill Exercise Ann. Fam. Med, November 1, 2003; 1(4): 236 - 241. [Abstract] [Full Text] [PDF]

				S. Mora, R. F. Redberg, Y. Cui, M. K. Whiteman, J. A. Flaws, A. R. Sharrett, and R. S. Blumenthal Ability of Exercise Testing to Predict Cardiovascular and All-Cause Death in Asymptomatic Women: A 20-Year Follow-up of the Lipid Research Clinics Prevalence Study JAMA, September 24, 2003; 290(12): 1600 - 1607. [Abstract] [Full Text] [PDF]

				D. P. Vivekananthan, E. H. Blackstone, C. E. Pothier, and M. S. Lauer Heart rate recovery after exercise is apredictor of mortality, independent of the angiographic severity of coronary disease J. Am. Coll. Cardiol., September 3, 2003; 42(5): 831 - 838. [Abstract] [Full Text] [PDF]

				B. R. Chaitman Abnormal heart rateresponses to exercise predict increased long-term mortality regardless of coronary disease extent: The question is why? J. Am. Coll. Cardiol., September 3, 2003; 42(5): 839 - 841. [Full Text] [PDF]

				A S Androne, K Hryniewicz, R Goldsmith, A Arwady, and S D Katz Acetylcholinesterase inhibition with pyridostigmine improves heart rate recovery after maximal exercise in patients with chronic heart failure Heart, August 1, 2003; 89(8): 854 - 858. [Abstract] [Full Text] [PDF]

				Y. J. Cheng, M. S. Lauer, C. P. Earnest, T. S. Church, J. B. Kampert, L. W. Gibbons, and S. N. Blair Heart Rate Recovery Following Maximal Exercise Testing as a Predictor of Cardiovascular Disease and All-Cause Mortality in Men With Diabetes Diabetes Care, July 1, 2003; 26(7): 2052 - 2057. [Abstract] [Full Text] [PDF]

				J. P. Frolkis, C. E. Pothier, E. H. Blackstone, and M. S. Lauer Frequent Ventricular Ectopy after Exercise as a Predictor of Death N. Engl. J. Med., February 27, 2003; 348(9): 781 - 790. [Abstract] [Full Text] [PDF]

				P. Palatini, D. T. Ko, P. R. Hebert, H. M. Krumholz, D. H. Perlo, J. Myers, V. Froelicher, and G. J. Balady Exercise Capacity and Mortality N. Engl. J. Med., July 25, 2002; 347(4): 288 - 290. [Full Text] [PDF]

M. S.