Abstract
Background
Exercise prescription for patients with cardiovascular disease remains a challenge. The concept of exercising at an intensity equivalent to one's anaerobic threshold has been well studied and highly recommended in the fitness industry for other populations. For this concept to be applicable to patients with cardiovascular disease, the level and intensity of activity must not trigger myocardial ischemia.
Hypothesis
We hypothesized that the heart rate at ventilatory anaerobic threshold (HRVAT) will not exceed heart rate at ischemic threshold (HRIT) (ie, HRVAT ≤ HRIT in a majority [>50%] of patients).
Methods
In this retrospective pilot study, 19 patients, mean age at baseline of 45.0 ± 15.6 years, who had positive cardiopulmonary exercise stress testing were included. Heart rate at ventilatory anaerobic threshold (VAT) was derived from a computer‐analyzed V‐slope method. The ischemic threshold (IT) was determined from electrocardiogram. The exercise test parameters at VAT in relation to IT were examined.
Results
Heart rate at VAT preceded heart rate at IT in 89.5% of patients. On average, achievement of VAT preceded IT relative to workload (119.5 ± 49.6 vs 132.6 ± 47.5; P < 0.01), heart rate (121.2 ± 15.9 vs 133.3 ± 17.5; P < 0.01), oxygen consumption (19.3 ± 4.9 vs 20.8 ± 3.7; P < 0.01), and respiratory exchange ratio (0.96 ± 0.10 vs 1.01 ± 0.07; P < 0.01).
Conclusions
Greater than 50% of patients met the criteria of HRVAT ≤ HRIT; therefore, we propose that anaerobic threshold is a suitable target aerobic exercise heart rate for all patients with cardiovascular diseases indicated for cardiopulmonary rehabilitation.
Keywords: Cardiac Rehabilitation, Exercise Testing, Ventilatory Anaerobic Threshold
1. INTRODUCTION
It is universally recognized that exercise training or rehabilitation is a cornerstone in managing patients with cardiovascular diseases.1, 2 Besides the direct positive impact on cardiovascular health, exercise training has been found to confer benefit indirectly through modification of cardiovascular risk factors—hypertension,3 insulin resistance and glucose tolerance,4 and lipid profile.5
Given the overwhelming evidence in support of exercise training on patients with cardiovascular diseases, international guidelines have been drawn to aid physicians in exercise prescription. Current guidelines recommend specific training modalities for each individual subpopulation of patients with cardiovascular diseases and its risk factors separately.6 Although this allows for targeted exercise prescription, an important limitation in its application lies in the fact that patients with cardiovascular diseases typically present with the risk factors and other comorbidities. As such, healthcare professionals encounter difficulty in selecting appropriate training modalities. A review of literature also reveals that substantial inconsistencies remain in recommendations of exercise prescriptions, rendering the field ambiguous and inconclusive, and revealing an inherent difficulty faced by physicians regarding exercise prescription. Selecting an appropriate training modality is a delicate task; sufficient intensity is required to allow for adequate training stimulus7, 8 while avoiding precipitation of unnecessary adverse cardiac events.9, 10
The concept of anaerobic threshold has been well established in the fitness industry. It has been defined as the highest level of oxygen consumption without a sustained elevation in serum lactate and metabolic acidosis,11 also known as the point of lowest metabolic strain12 and maximum fuel efficiency. In the last decade, the use of anaerobic threshold as a target exercise training intensity has been well studied on different populations such as elite athletes,13 apparently healthy population,14 the elderly,15 and patients with chronic kidney disease,16 multiple sclerosis,17 and polio.18 The consensus reached from these studies was that anaerobic threshold is an appropriate exercise training target. Within the last decade, Meyer et al. also proposed anaerobic threshold for the population with chronic heart failure.12 Despite the widespread study of anaerobic threshold and its established beneficial and measurable clinical benefits in different populations, it has not been established whether this is applicable for all cardiac patients suitable for cardiopulmonary rehabilitation.
For any cardiovascular rehabilitation, safety is always a concern. Therefore, for a recommendation to be feasible, it is paramount that the corresponding intensity does not elicit myocardial ischemia as it can set the stage for cardiac arrhythmias,19 or even myocardial infarction. In this article, the anaerobic threshold will be determined using ventilatory parameters and therefore referred to as the ventilatory anaerobic threshold (VAT). The aim of this pilot study was to retrospectively evaluate whether heart rate at VAT precedes heart rate equivalent at ischemic threshold (IT) using ST depression as a marker for myocardial ischemia. We hypothesized that the heart rate at ventilatory anaerobic threshold (HRVAT) will not exceed heart rate at ischemic threshold (HRIT) (ie, HRVAT ≤ HRIT, in a majority [>50%] of patients).
2. METHODS
2.1. Study subjects
The records of all 393 patients who underwent cardiopulmonary exercise stress testing (CPET) at the National Heart Centre Singapore (NHCS) from January 2011 to August 2015 were retrospectively reviewed. Of the 393 patients, 37 were excluded from the study as they had incomplete data on VAT and electrocardiogram (ECG) recordings during exercise, and another 14 failed to achieve their VAT during the CPET. The remaining 342 (87%) with positive CPET (n = 22) and negative CPET (n = 320) were considered. Of the 22 patients with positive CPET, only 19 were included in the final study population; 3 were excluded due to signs of left ventricular hypertrophy on ECG. The inclusion criteria were patients (1) indicated for cardiopulmonary rehabilitation at NHCS, and (2) achieved their VAT during the submaximal exercise stress testing. Patients were excluded if their electrocardiography shows signs of left ventricular hypertrophy according to Cornell voltage criteria or any baseline arrhythmias. The other main exclusion criteria were: unstable angina, uncontrolled cardiac dysrhythmias causing symptoms or hemodynamic compromise, recent myocardial infarction (within 2 days), symptomatic severe aortic stenosis, uncontrolled symptomatic heart failure, uncontrolled hypertension, locomotion disability, and an inability to exercise. Of the group with negative CPET, 97 served as the control group for this study. The patients in this group were referred for atypical chest pain, exertional dyspnea, or exercise‐induced arrhythmia, and had negative findings. Patients with any active cardiac lesions, congenital heart diseases, or structural heart diseases were not included. The study was approved by the institutional review board of SingHealth.
Traditional modifiable and nonmodifiable cardiac risk factors of hypertension, diabetes, dyslipidemia, smoking, and family history of cardiac diseases were also recorded. Smoking status was based on the evidence in the medical record. Both former and current smokers constituted a positive smoking history.
2.2. Cardiopulmonary exercise stress testing
Exercise stress testing was performed on a Schiller STM 1500 model treadmill with a Ramp protocol (Schiller, Baar, Switzerland). The exercise protocol was individualized to each subjects' exercise capacity. The speed of the treadmill belt was fixed between 1.5 mph and 3.3 mph based on the physician's perspective of patients' exercise capacity gained through history taking, physical examination, and relevant investigations. The initial slope of the treadmill was 0, with increments of 1% to 2% every minute. The patients were verbally encouraged to exercise to volitional fatigue, regardless the maximal heart rate achieved. No medications were stopped before the CPET. The criteria for termination of test were: fatigue, dyspnea, excessive hypertensive response (≥230/130 mm Hg), ≥2 mm ST depression in at least 2 adjacent leads, and/or angina. A CPET is considered as positive when the ST segment is depressed, either horizontal or downsloping at ≥1 mm for at least 2 consecutive beats.
Heart rate via 12‐4 lead ECG and exhaled gases via a face mask were continuously monitored with Schiller CARDIOVIT CS‐200 Ergo Spiro (Schiller). Blood pressure and transcutaneous oxygen saturation at the index finger were monitored with Schiller BP‐200 plus with Masimo SET 2000 (Schiller). Baseline ECG was recorded, and subsequent readings were recorded at each 60 seconds, and expired ventilator data were analyzed and expressed at each 20 seconds. The following parameters were determined using a Ganshorn (Niederlauer, Germany) Power‐Cube gas analyzer: oxygen pulse in milliliters per beat, oxygen uptake (VO2) in liters per minure, breath‐by‐breath minute ventilation, and respiratory exchange ratio (RER). The heart rate at VAT was computer determined using the V‐slope method. The age‐predicted maximum heart rate was calculated by the equation (220 − age). The age predicted maximum VO2 was also calculated according to standard equation. O2 pulse was calculated by dividing VO2 by heart rate.
2.3. Statistical analysis and calculations
Data were analyzed using SAS 9.3 (SAS Institute Inc., Cary, NC). Continuous data are summarized as mean ± standard deviation, whereas categorical variables are reported as percentages. Significant differences in baseline clinical and CPET variables between the positive and control populations were analyzed using a 2‐sample t test. Comparisons of exercise test parameters at VAT and IT taken on the same patient were analyzed with a paired t test. The 90% confidence interval (CI) on the proportion of patients with HRVAT ≤ HRIT was calculated using EpiTools (Ausvet, Canberra, Australia) online calculator for a CI on a single proportion. Proportions were expressed as percentages. The significance level was set at P < 0.05, and all tests were 2‐sided.
3. RESULTS
3.1. Patient characteristics
The baseline demographic and clinical characteristics of the study group are documented in Table 1, and the selected cardiopulmonary exercise test variables are presented in Table 2. The resting heart rate, resting diastolic blood pressure (DBP), peak DBP, peak VO2 (% predicted), and O2 pulse showed significant difference between patients with positive CPET and the control. The exercise data at VAT and IT for all subjects with positive CPET are presented in Table 3. In the 19 patients with positive CPET, 17 (89.5%) patients had a heart rate at VAT equal or preceding that of their IT. An exact 2‐sided 90% CI using the Clopper‐Pearson method is 0.704‐0.981 (P = 0.0006). Therefore, it can be stated with 95% confidence that HRVAT ≤ HRIT in at least 70.4% of the target population.
Table 1.
Clinical characteristics of the study cohort
| Positive CPET, n = 19a | Control, n = 97 | P Value | |
|---|---|---|---|
| Age, years | 45.0 ± 15.6 | 43.2 ± 15.1 | 0 . 487 |
| Gender (% male) | 52 . 6 | 61 . 9 | 0 . 456 |
| BMI (kg/m 2 ) | 23 . 6 ± 4.6 | 25 . 1 ± 5.8 | 0 . 294 |
| NYHA I b | 68 . 4 | 95 . 9 | 0 . 0012 c |
| Cardiac risk factors (%) | |||
| Diabetes mellitus | 21 . 1 | 4 . 1 | 0 . 855 |
| Hypertension | 26 . 3 | 15 . 5 | 0 . 317 |
| Hyperlipidemia | 52 . 6 | 26 . 8 | 0 . 269 |
| Family history of cardiac diseases | 15 . 8 | 7 . 2 | 0 . 210 |
| Smoking history | 10 . 5 | 13 . 4 | 1 . 000 |
Abbreviations: BMI, body mass index; CPET, cardiopulmonary exercise testing; NYHA, New York Heart Association.
Clinical diagnosis: hypertrophic cardiomyopathy, 2; ischemic heart disease, 7; dilated cardiomyopathy, 3; valvular pathology, 3; congenital heart disease, 4; pulmonary hypertension, 1; atypical chest pain, 1; repaired ascending aortic aneurysm, 1.
All of the patients were either NYHA I or II.
P < 0.05.
Table 2.
Selected CPET variables of study cohort
| Parameters | Positive CPET, n = 19 | Control, n = 97 | Adjusted P Values |
|---|---|---|---|
| Resting HR (bpm) | 71.3 ± 7.7 | 81.1 ± 18.1 | 0 . 0197 a |
| Peak HR (bpm) | 147.2 ± 18.1 | 159.5 ± 22.7 | 0 . 0733 |
| Age‐predicted peak HR (%) | 85.0 ± 10.9 | 90.4 ± 14.8 | 0 . 8294 |
| HR at VAT (bpm) | 121.2 ± 15.9 | 126.0 ± 23.6 | 0 . 5915 |
| Resting SBP (mm Hg) | 123.1 ± 17.7 | 130.2 ± 16.0 | 0 . 1756 |
| Resting DBP (mm Hg) | 75.2 ± 8.3 | 83.5 ± 10.6 | 0 . 0099 a |
| Peak SBP (mm Hg) | 194.4 ± 28.9 | 193.5 ± 24.3 | 0 . 5448 |
| Peak DBP (mm Hg) | 91.5 ± 30.2 | 84.8 ± 18.3 | 0 . 0266 a |
| Peak VO 2 (mL/kg ‐1 /min ‐1 ) b | 23.5 ± 5.9 | 28.8 ± 8.9 | 0 . 0502 |
| Peak VO 2 (% predicted) b | 82.8 ± 17.2 | 100.0 ± 25.3 | 0 . 0008 a |
| Max VE (L/min) | 49.9 ± 16.6 | 62.9 ± 24.1 | 0 . 0646 |
| O 2 pulse (mL/beat) | 10.2 ± 3.7 | 13.1 ± 4.8 | 0 . 0376 a |
| HRR (bpm) | 28.3 ± 19.3 | 17.6 ± 20.6 | 0 . 0632 |
| RER (VAT) b | 0.94 ± 0.12 | 0.88 ± 0.14 | 0 . 2628 |
| RER (peak) b | 1.08 ± 0.09 | 1.09 ± 0.08 | 0 . 7431 |
Abbreviations: CPET, cardiopulmonary exercise testing; DBP, diastolic blood pressure; HR, heart rate; HRR, heart rate reserve; RER, respiratory exchange ratio; SBP, systolic blood pressure; VAT, ventilatory anaerobic threshold; VE, minute ventilation; VO 2, oxygen consumption.
P < 0.05.
Two patients with positive CPET did not have data for peak VO 2 and RER available.
Table 3.
Exercise data at VAT and IT for patients with positive CPET
| Subject | Workload (W) | HR (bpm) | HR Max (% Pred) | VO2 (mL/kg/min) | RER | HR, VAT ≤ IT | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| VAT | IT | VAT | IT | VAT | IT | VAT | IT | VAT | IT | ||
| 1 | 65 | 65 | 121 | 121 | 63 . 0 | 63 . 0 | 16 . 6 | 16 . 6 | 1 . 06 | 1 . 06 | √ |
| 2 | 68 | 72 | 143 | 149 | 88 . 8 | 92 . 5 | 20 . 4 | 22 . 0 | 0 . 94 | 1 . 04 | √ |
| 3 | 119 | 129 | 114 | 119 | 66 . 3 | 69 . 2 | 13 . 0 | 16 . 7 | 0 . 78 | 0 . 87 | √ |
| 4 | — | — | 119 | 160 | 67 . 2 | 90 . 4 | — | — | — | — | √ |
| 5 | 81 | 100 | 116 | 131 | 68 . 2 | 77 . 1 | 16 . 5 | 21 . 1 | 0 . 88 | 0 . 99 | √ |
| 6 | 88 | 93 | 103 | 116 | 52 . 0 | 58 . 6 | 13 . 5 | 17 . 2 | 0 . 96 | 0 . 94 | √ |
| 7 | 73 | 89 | 123 | 151 | 65 . 4 | 80 . 3 | 17 . 8 | 20 . 2 | 0 . 84 | 0 . 97 | √ |
| 8 | — | — | 107 | 127 | 68 . 2 | 80 . 9 | — | — | — | — | √ |
| 9 | 126 | 137 | 137 | 154 | 75 . 7 | 85 . 1 | 18 . 2 | 18 . 7 | 1 . 08 | 1 . 15 | √ |
| 10 | 157 | 157 | 120 | 123 | 80 . 0 | 82 . 0 | 20 . 7 | 21 . 1 | 1 . 01 | 1 . 04 | √ |
| 11 | 148 | 148 | 111 | 109 | 68 . 9 | 67 . 7 | 22 . 0 | 20 . 3 | 1 . 00 | 0 . 95 | — |
| 12 | 63 | 92 | 135 | 145 | 82 . 3 | 88 . 4 | 23 . 3 | 26 . 3 | 0 . 98 | 1 . 05 | √ |
| 13 | 227 | 247 | 133 | 149 | 79 . 4 | 87 . 6 | 28 . 7 | 29 . 1 | 1 . 00 | 1 . 02 | √ |
| 14 | 136 | 136 | 118 | 118 | 59 . 6 | 59 . 6 | 24 . 6 | 24 . 6 | 0 . 99 | 0 . 99 | √ |
| 15 | 51.2 | 113 | 97 | 115 | 57 . 1 | 67 . 6 | 10 . 7 | 14 . 6 | 0 . 72 | 0 . 98 | √ |
| 16 | 162 | 191 | 99 | 144 | 67 . 3 | 98 . 0 | 16 . 6 | 20 . 3 | 1 | 1 . 08 | √ |
| 17 | 186 | 186 | 111 | 111 | 59 . 7 | 59 . 7 | 19 . 8 | 19 . 8 | 1 | 1 | √ |
| 18 | 144 | 133 | 137 | 129 | 69 . 9 | 65 . 8 | 27 . 0 | 24 . 4 | 1 . 01 | 0 . 99 | — |
| 19 | 137 | 166 | 157 | 162 | 93 . 5 | 96 . 4 | 18 . 4 | 21 . 2 | 0 . 99 | 1 . 11 | √ |
| Total | 17/19 (89.5%) | ||||||||||
Abbreviations: HR, heart rate; IT, ischemic threshold; RER, respiratory exchange ratio; VAT, ventilatory anaerobic threshold; VO 2, oxygen consumption.
In Table 4, the selected exercise test variables at VAT and IT are presented. On average, the VAT was significantly lower than the IT in relation to workload, heart rate, percent of heart rate maximum, VO2, and RER.
Table 4.
Comparison of exercise test parameters at VAT and IT
| Parameters | VAT | IT | P |
|---|---|---|---|
| Workload (W) a | 119.5 ± 49.6 | 132.6 ± 47.5 | 0 . 0034 b |
| HR (bpm) | 121.2 ± 15.9 | 133.3 ± 17.5 | 0 . 0007 b |
| % HR max | 70.1 ± 10.8 | 77.4 ± 13.1 | 0 . 0009 b |
| VO 2 (mL/min) a | 19.3 ± 4.9 | 20.8 ± 3.7 | 0 . 0040 b |
| RER a | 0.96 ± 0.10 | 1.01 ± 0.07 | 0 . 0030 b |
Abbreviations: HR, heart rate; IT, ischemic threshold; RER, respiratory exchange ratio; VAT, ventilatory anaerobic threshold; VO2, oxygen consumption.
Two patients did not have the data for workload, VO2, and RER.
P < 0.05.
4. DISCUSSION
The main finding of this study was that the heart rate at VAT equaled or preceded that of IT in a majority (89.5%) of our study population. This finding is consistent with a study performed by Meyer et al20 on 27 patients with angiographically documented coronary artery disease (CAD). Out of 27 patients, 16 (59.3%) had onset of VAT preceding the onset of IT, whereas 6 (22.2%) patients had VAT occurring at IT, for a total of 22/27 (81.5%) patients having a heart rate at VAT occurring at or preceding IT.
Exercise prescription should always remain prudent to minimize any unnecessary risk of cardiac events. Anaerobic threshold was previously studied and recommended in patients with recent myocardial ischemia21, 22 and heart failure.12 However, it was unclear if the recommendation could also apply to patients with mixed cardiac lesions. IT was used as a safety benchmark in evaluating the suitability of using anaerobic threshold as a target exercise heart rate based on well‐entrenched knowledge that exercise training intensity should stay below the threshold capable of eliciting myocardial ischemia. The results of our study suggest that exercising at anaerobic threshold is safe, and this preliminary finding is clinically significant for cardiac rehabilitation. It could potentially ease physicians' dilemma in exercise prescription. Currently, cardiac rehabilitation guidelines only exist for individuals with cardiac diseases and specific risk factors. One study reported that existing exercise prescription for patients with CAD may trigger myocardial ischemia as assessed by scintigraphy during rehabilitation.23 Therefore, rather than a 1‐size‐fits‐all approach, there is a need for emphasis toward individualization of exercise training.24
Another interesting finding from our study was that the difference in heart rate at VAT between patients with positive CPET and the controls did not reach significance. In contrast, a previous study has reported heart rate at VAT in the positive stress testing group to be significantly lower than that of the control subjects (P < 0.001).25 The reason for this may be due to difference in the clinical characteristics of both the study and control group. Anaerobic threshold reflects the functional capacity of the cardiovascular system. Although CPET is a sensitive tool for identifying decreased heart function,26 the finding from this study implies that having a positive CPET does not dictate a lower anaerobic threshold, and thus functional impairment of the cardiovascular system.
4.1. Limitations
Our study involves a small cohort of subjects; therefore, the results obtained cannot be considered definitive. The limitations of the present study also include its retrospective nature; thus, retesting of data is not allowed. There is a definite trend that the heart rate at VAT precedes that of IT, indicating that it can be used as a safe exercise target heart rate for exercise in patients with cardiovascular disease. It would be premature to generalize the results obtained to the broader population of cardiac patients at this point of time. Future validation is definitely warranted. Future direction of this study would include using stress echocardiogram to evaluate for any regional wall motion abnormalities when one is exercising at anaerobic threshold. This would improve accuracy in determining the presence of myocardial ischemic at an intensity equivalent to anaerobic threshold.
5. CONCLUSION
This study is the first to demonstrate that VAT heart rates precede IT heart rate in a substantial majority of nonhomogenous patients referred for cardiopulmonary rehabilitation. The implication is that an individual's anaerobic exercise heart rate can possibly be used as an exercise target heart rate during a cardiopulmonary rehabilitation program, with minimal risk of triggering myocardial events, yet achieving the desired outcome. This study provides a framework for studying the use of anaerobic threshold in patients with cardiac diseases.
Conflicts of interest
The authors declare no potential conflicts of interest.
Tan S. J. J., Allen J. C., and Tan S. Y.. Determination of ideal target exercise heart rate for cardiac patients suitable for rehabilitation. Clin Cardiol. 2017;40:1008–1012. 10.1002/clc.22758
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