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Abnormal Heart Rate Recovery Immediately After Treadmill Testing : Correlation with Clinical, Exercise Testing, and Myocardial Perfusion Parameters

Introduction
The heart is under influence of both divisions of the autonomic nervous system. The sympathetic system has positive chronotropic action whereas the parasympathetic system has negative chronotropic action. Previous studies have shown that imbalance between sympathetic and parasympathetic tone and excessive stimulation of the sympathetic nervous system are fundamental risk factors for cardiac death (Barron et al., 1996, Sandvik et al., 1996, and Schwartz et al., 1992).
The rise in heart rate during exercise is considered to be a direct consequence of sympathetic activation combined with parasympathetic withdrawal, whereas the decline in heart rate immediately after exercise is thought to be a function of reactivation of the parasympathetic (Schwartz 1992, Arai et al., 1989, and Imai et al., 1994).
The heart rate recovery, defined as the decrease in heart rate from peak exercise to one minute after cessation of exercise, has important prognostic significance. The purpose of this study was to evaluate heart rate recovery as an index of myocardial ischemia assessed by myocardial perfusion single photon emission computed tomography (SPECT) imaging which is a reliable method for assessing myocardial perfusion (Georgoulias et al., 1996, and Rigo et al., 1994).

2
Aim of the work

The aim of this study was to evaluate the degree of heart rate recovery after treadmill testing as an index of myocardial ischemia, by focusing on the correlation between heart rate recovery and clinical, exercise testing and myocardial perfusion scanning parameters related to ischemia.
Patients and methods

This study included 50 patients (30 males and 20 females) who were referred to the Nuclear Cardiology Laboratory at Ain Shams University Hospital for evaluation of the presence or absence of ischemic heart disease during the period from June 2004 to June 2005.
Exclusion Criteria:
We excluded patients with history of:
•     Heart failure.
•     Left bundle branch block.
•     Pre-excitation syndrome.
•     Atrioventricular block.
•     Known sick sinus syndrome with tachyarrhythmia or bradycardia.
•     Prior myocardial infarction or an irreversible defect on their scintigrams.
•     Previous cardiac surgery (bypass grafting or angiography), congenital or valvular heart disease.
•     Cardiomyopathy.
•     Those with implanted pacemaker.
•     Diabetic patients.
•     Patients receiving digoxin or amiodarone.
•     Patients with a contraindication to or inability to perform or to achieve a satisfactory exercise level because of noncardiac condition.

Medications:
Medications that could possibly influence patient's performance on exercise testing were temporarily withdrawn. β-Blockers and calcium channel antagonist were discontinued 48 hours before and during the study. Nitrates were discontinued 24 hours before and during the study, other Antiarrythmic medications were also discontinued (at least 48 hours before and during the study).

All patients were subjected to the following:

1. History taking:
Before testing, brief interviews with all patients were done from which data were obtained on:
o     Age.
o     Sex.
o     Symptoms.
o     Medications.
o     Coronary risk factors.
o     Previous cardiac events.
o     Family history.
Hypertension was defined as a systolic blood pressure of 140 mmHg or greater at rest and/or a diastolic blood pressure of 90 mmHg or greater at rest, or treatment with antihypertension medication. Diagnosis of diabetes mellitus and lipid disorder were derived from the interview with the patients and the use of corresponding medications.

2. Physical examination:
A proper physical examination was done to all patients with particular attention to the following:
o     Signs denoting the presence of heart failure such as the presence of an S3 gallop, increased JVP, hepatomegaly, pulmonary rales, and lower limb edema.
o     The presence of any pulse irregularities that may suggest the presence of underlying arrhythmia.
o     The presence of any murmur.
o     The presence of any sign of other system affection.
After that an intravenous cannula was inserted before the test was started.
3. Exercise ECG:
After a 6 to 12 hours fasting, all patients underwent a maximal treadmill exercise testing using an automated programmable treadmill (Cardio PC/E, Innobase program). Bruce protocol was used in all patients.

A. ECG recording:
A 12-lead electrocardiogram was obtained at baseline, during each stage of exercise, at peak workload and at 1-minute intervals for 8 minutes after exercise.

B. Blood pressure measurement:
The blood pressure was measured by arm-cuff method with a mercurial sphygmomanometer and a stethoscope for auscultation before testing, at peak exercise, and during recovery period at each minute.

C. Symptoms:
Data on symptoms were recorded throughout the test and during the recovery period, the heart rate, arrhythmias, and ST-segment changes were continuously monitored.

D. ST-segment response:
As a criterion of ischemic ST-segment response, we considered ≥ 1 mm horizontal or downsloping ST-segment depression 80 milliseconds after the J point or more than 1 mm of additional ST-segment rise in leads without pathologic Q waves.

E. Termination of the test:
Predetermined criteria for stopping the test were: target heart rate (85 % of age predicted maximal heart rate) achieved, excessive fatigue, onset of severe chest pain, the occurrence of significant ST-segment depression, hypotensive blood pressure response (decrease in blood pressure or failure of blood pressure to rise ≥ 10 mmHg), serious cardiac arrhythmia, onset of neurologic symptoms (e.g. ataxia) or abnormalities, or the patients request to stop. The duration of exercise and the reason for stopping were also recorded.     

After achieving peak workload, the treadmill stopped (no "cool-down" period was allowed) and the patients immediately laid on a bed, situated next to the treadmill.
The patients remained in the supine position for 8 minutes, which was considered the recovery period (this period was prolonged in case the symptoms or electrocardiographic changes were persistent).

F. Heart rate recovery:
The reduction in the heart rate from its value at peak exercise to the rate 1 minute later was determined as heart rate recovery.

G. Chronotropic response:
Chronotropic response was defined as the percentage of maximal age-predicted heart rate achieved at peak exercise and it was calculated by the following formula: 100 peak heart rate / 220- age, a value of 85% or greater was considered to be normal.

H. Heart rate reserve:
Heart rate reserve (percentage) was calculated by the following formula: 100 (peak heart rate – resting heart rate) / ([220 – age] – resting heart rate).

4. SPECT Myocardial Perfusion Imaging:
Myocardial perfusion studies were performed to all patients using Technetium 99m sestamibi.

A. Image acquisition:
Tomographic images were obtained using a rotating circular head gamma camera (GE / Starcam 4000 I) with a low energy general purpose collimator interfaced to a computer. An arc of 180 degree was used, spanning from the 45-degree right anterior oblique projection to the 45-degree left posterior oblique projection. A total of 32 images were obtained, of 20 seconds each, using a 64 × 64 acquisition matrix with photon energy limits set at 20 % window around the 140 KeV Tc-99 m peaks.
Transaxial reconstruction was done using a standard back projection technique with a Ramp-Hanning filter. The reconstructed tomographic slices were 6 mm thick and were reoriented along in the short, horizontal long, and vertical long axes for interpretation.

B. Protocol used:
Rest- stress Technetium 99m sestamibi SPECT studies were done using the separate-day protocol, rest imaging performed after intravenous injection of 20 to 25 mCi of Technetium 99m sestamibi, and half to one hour later SPECT myocardial perfusion imaging obtained.
On another day, stress imaging was performed after intravenous injection of 15 to 20 mCi of Technetium 99m sestamibi 1 minute before cessation of exercise, and then half to one hour later SPECT myocardial perfusion imaging obtained.

C. Interpretation of the images:
For SPECT interpretation, the left ventricle was divided into 20 segments:

1-basal anterior wall 7-mid anterior wall 13-apical anterior wall
2-basal anteroseptal 8-mid anteroseptal 14-apical anteroseptal
3-basal inferoseptal 9-mid inferoseptal 15-apical inferoseptal
4-basal inferior 10-mid inferior 16-apical inferior
5-basal inferolateral 11-mid inferolateral 17-apical inferolateral
6-basal anterolateral 12-mid anterolateral 18-apical anterolateral
19-anteroapical
20-inferoapical

The 20 segment scoring system is based on 3 short-axis slices (distal [apical], mid, and basal) to represent the entire left ventricle, with the apex represented by 2 segments visualized in a mid-vertical long-axis image. Each of the 20 segments has a distinct name and number (Berman et al., 1991).
Then the images were evaluated (both stress and rest) by scoring uptake in each of the 20 segments, using a 5-point scoring system (0, normal uptake; 1, mildly reduced uptake; 2, moderately reduced uptake; 3, severely reduced uptake; 4, no uptake) (Berman et al., 1991).
Ischemia was considered with an uptake more than 0 on stress images and an improvement of the score by at least one unit at rest.
Finally, the "summed score" of the segments in stress and rest was calculated to obtain the "summed stress score" and "summed rest score", and then a "summed difference score" was estimated by subtracting the "summed rest score" from the "summed stress score" to assess extent and severity of ischemia.

Data management:
Data were collected, verified, revised, and then edited on personal computer.
The data were then analyzed statistically using SPSS statistical program version (12), the following tests were done:
1)     X = mean
2)     SD = standard deviation
3)     T test for independent samples
4)     ANOVA = analysis of variance
5)     Chi-square test
6)     Pearson correlation coefficient (r)
The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated using the following equation, respectively:
Sensitivity = No. of true positive / No. of true positive + No. of false negative
Specificity = No. of true negative / No. of true negative + No. of false positive
Accuracy = No. of true positive + No. of true negative / No. of true positive + No. of true negative + No. of false positive + No. of false negative
Positive predictive value = No. of true positive / No. of true positive + No. of false positive
Negative predictive value = No. of true negative / No. of true negative + No. of false negative

Results

This study included 50 patients (30 males and 20 females) who were referred to the Nuclear Cardiology Laboratory at Ain Shams University Hospital for evaluation of the presence or absence of ischemic heart disease during the period from June 2004 to June 2005.
There were 30 males and 20 females with a male to female ratio of 1.5: 1. Their ages ranged from 30 to 75 years with a mean of 50.32 9.89 years.

I. Clinical characteristics of all patients:
The study population included 30 males (60 %) and 20 females (40 %) with a male to female ratio of 1.5:1. Twenty-five patients (50 %) were hypertensive, 9 patients (18 %) were smokers, and 11 patients (22 %) had a positive family history of ischemic heart disease and from the 50 patients, 38 patients had a documented cholesterol level in which 15 patients (39.5 %) had a high cholesterol level (≥ 200 mg/dl). The clinical characteristics of all patients are shown in table 3.

Table 3: The clinical characteristics of all patients
Variables      Values
No. of patients     50
Age (years)     Mean 50.32 9.89
Sex (male)     30 (60 %)
Sex (female)     20 (40 %)
Smokers     9 (18 %)
Non smokers     33 (66 %)
Ex-smokers     8 (16 %)
Hypertension     25 (50 %)
High cholesterol level (≥200) (Total No. 38 patients)     15 (39.5 %)
Positive Family History     11 (22 %)

II. According to the exercise test result patients were divided into two groups as regard to their heart rate recovery value; we considered 21 beats/ min as the cut point between normal and abnormal.
* Group I: included thirty-three patients (sixty-six percent, 66%) with a normal heart rate recovery (≥ 21 beats/min).
* Group II: included seventeen patients (thirty-four percent, 34 %) with an abnormal heart rate recovery (< 21 beats/min).

A. The clinical characteristics of both groups:
1. Age:
Patients in group II had a mean age of 53.7 ± 9 years while patients in group I had a mean age of 48.5 ± 10, so patients in group II tend to be older than patients in group I without significant difference (P > 0.05).
2. Sex:
There were 20 male patients (60.6 %) and 13 female patients (39.4 %) in group I, while group II included 10 male patients (58.8 %) and 7 female patients (41.2 %), there was no statistically significant difference between both groups (P > 0.05).

3. Smoking:
The percentage of smokers was comparatively higher in group II (5 patients, 29.4 %), compared with 4 patients (12.1 %) in group I, without significant difference, (P > 0.05).
4. Hypertension:
Nine patients were hypertensive (52.9 %) in group II, which was slightly higher than the number of hypertensive patients in group I (16 patients, 48.5 %), but without significant difference (P > 0.05).

5. Cholesterol level:
Cholesterol levels were reported in 38 patients, 26 of them in group I and 12 patients in group II.
In group I, 10 patients (38.5 %) had a high cholesterol level (≥ 200 mg/dl), while in group II, 5 patients (41.7 %) had a high cholesterol level, but there was no statistically significant difference (P > 0.05).
6. Family history of ischemic heart disease:
A positive family history of ischemic heart disease was found in 9 patients (27.3 %) in group I, compared to 2 patients (11.8 %) in group II. Although the number was higher in group I but it yielded no statistically significant difference (P > 0.05).
The clinical characteristics and comparison between both groups are shown in table 4, and figures 1to 6.

Table 4: The clinical characteristics of both groups
Variables     Group I
No. 33     Group II
No. 17     P value     Significance
Age (years)     48.5 ± 10     53.7± 9     > 0.05     N. S.
Sex (male)     20 (60.6%)     10 (58.8 %)     > 0.05     N. S
Sex (female)     13 (39.4 %)     7 (41.2 %)     > 0.05     N. S
Smokers     4 (12.1 %)     5 (29.4 %)     > 0.05     N. S
Hypertension     16 (48.5 %)     9 (52.9 %)     > 0.05     N. S
High cholesterol level (≥200) (Total No. 38 patients)     10 (38.5 %)
(No. 26)     5 (41.7 %)
(No. 12)     > 0.05     N. S
Positive Family History     9 (27.3 %)     2 (11.8 %)     > 0.05     N. S

Fig. 1: showing the mean age of patients in both groups

Group I = mean age 48.5 ± 10 years, Group II = mean age 53.7 ± 9, (P > 0.05).

Fig. 2: showing the male: female ratio in both groups

Group I= 20 (60.6%) males and 13 (39.4%) females,
Group II= 10 (58.8%) males and 7 (41.2%), (P > 0.05).
Fig. 3: comparison between the numbers of smokers in both groups

Group I (No.33) = 4 (12.1%) smokers, Group II (No.17) = 5 (29.4%) smokers, (P > 0.05).

Fig. 4: showing the prevalence of hypertension among the patients in both groups

Group I= 16 (48.5%) hypertensive, Group II= 9 (52.9%) hypertensive, (P > 0.05).


Fig. 5: showing patients with high cholesterol level in both groups

Group I = 10 (38.5%) patients with a high cholesterol level (≥200), and Group II = 5 (41.7%) patients with a high cholesterol level (≥200), (P > 0.05).

Fig. 6: showing the prevalence of a positive family history of ischemic heart disease in both groups

Group I (No.33) = 9 (27.3%) patients, and Group II (No.17) = 2 (11.8%) patients with a positive family history of ischemic heart disease, (P > 0.05).

B. The exercises parameters of both groups:
1. Resting and peak exercise heart rate:
Patients in group I had a mean resting heart rate of 88 ± 17 beats/min, and it reached 153 ± 15 beats/ min at peak exercise, while in group II the mean resting heart rate was 86 ± 17 beats/ min, and it reached 146 ± 16 beats/ min at peak exercise. There was no statistically significant difference between the two groups (P > 0.05), (Table 5, fig.7).
2. Peak systolic and diastolic blood pressure:
The mean systolic blood pressure at peak exercise was 168 ± 25 mmHg, and the mean diastolic blood pressure at peak exercise was 85 ± 14 mmHg in group I, while in group II the mean systolic blood pressure at peak exercise was 162 ± 29 mmHg, and the mean diastolic blood pressure at peak exercise was 89 ± 14 mmHg. There was no statistically significant difference between the two groups (P > 0.05), (Table 6, fig. 8).

Table 5: Resting and peak exercise heart rate
Exercise parameters     Group I
No. = 33     Group II
No. = 17     P value     
Significance
Resting heart rate (beats/min)     88 ± 17     86 ± 17     > 0.05     
N. S.
Peak heart rate (beats/min)     153 ± 15     146 ± 16     > 0.05     
N. S.


Fig. 7: Resting and peak exercise heart rate of both groups

(P > 0.05)
Table 6: Peak systolic and diastolic blood pressure
Exercise parameters     Group I
No. = 33     Group II
No. = 17     P value     
Significance
Maximum systolic blood pressure (mmHg)     168 ± 25     162 ± 29     > 0.05     
N. S.


Maximum diastolic blood pressure (mmHg)     85 ± 14     89 14     > 0.05     
N. S.

Fig. 8: showing peak systolic and diastolic blood pressure in both groups

(P > 0.05)
3. Exercise duration and peak work load:
In group I the mean exercise duration was 8.7 2.6 minutes with a peak work load of 9.8 ± 2.2 METs, and in group II, the mean exercise duration was 8.5 ± 2.2 minutes with a peak work load of 9.5 ± 2.3 METs. There was no statistically significant difference between the two groups (P > 0.05), (Table 7, figures 9 and 10).


Table 7: Exercise duration and peak work load
Exercise parameters     Group I
No. = 33     Group II
No. = 17     P value     
Significance
Exercise duration (minutes)     8.7 ± 2.6     8.5 ± 2.2     > 0.05     
N. S

Peak work load (METs)     9.8 ± 2.2     9.5 ± 2.3     > 0.05     
N. S.


Fig. 9: showing exercise duration in both groups

Mean exercise duration in Group I=8.7±2.6 minutes, and in Group II= 8.5±2.2 minutes, (P > 0.05).
Fig. 10: showing peak work load in both groups

P > 0.05
4. Chronotropic response and heart rate reserve:
The mean chronotropic response achieved by patients in group I was 89.1 ± 6.7 %, and the mean heart rate reserve was 76.9 ± 15.6 %, while in group II, the mean chronotropic response achieved was 87.6 ± 8.7 %, and the mean heart rate reserve was 75.5 ± 17.3 %. There was no statistically significant difference between the two groups (P > 0.05), (Table 8, and figure 11).

Table 8: Chronotropic response and heart rate reserve
Exercise parameters     Group I
No. = 33     Group II
No. = 17     P value     
Significance
Chronotropic response (%)     89.1 6.7     87.6 ± 8.7     > 0.05     
N. S.

Heart rate reserve (%)     76.9 ± 15.6     75.5± 17.3     > 0.05     
N. S.

Fig. 11: showing mean chronotropic response and heart rate reserve in both groups

P> 0.05
5. Mean heart rate recovery value:
Patients in group I had a mean heart rate recovery value of 31 ± 7 beats/ min, while patients in group II had a mean heart rate recovery value of 15 ± 4 beats/min, so group II had a much lower mean heart rate recovery value than group I, with a high statistically significant difference (P < 0.001), (Table 9, fig. 12).

Table 9: Mean heart rate recovery value
Exercise parameters     Group I
No. = 33     Group II
No. = 17     P value     
Significance
Heart rate recovery value (beats/min)     31 ± 7     15 ± 4     < 0.001     
H. S.



Fig. 12: showing mean heart rate recovery in both groups

6. Angina and ST-depression during exercise:
Three patients (17.6 %) developed angina during the test while ST-segment depression occurred in four patients (23.5 %) in group II. On the other hand, in group I, five patients (15.2 %) developed angina during the test while ST-segment depression occurred in three patients (9.1 %). There was no statistically significant difference between the two groups (P > 0.05), (Table 10, figures 13 and 14).





Table 10: Angina and ST-depression during exercise
Exercise parameters     Group I
No. = 33     Group II
No. = 17     P value     
Significance
Angina     5 (15.2 %)     3 (17.6 %)     > 0.05     N. S.
ST-depression     3 (9.1 %)     4 (23.5 %)     > 0.05     N. S.
Fig. 13: showing the percent of patients who developed angina during exercise test in both groups

Group I= 5 (15.2%) patients, and Group II= 3 (17.6%) patients with angina, (P > 0.05).
Fig. 14: showing the percent of patients with an ST-depression

Group I =3 (9.1%) patients, and Group II= 4 (23.5%) patients with an ST-depression, (P > 0.05).
C. SPECT imaging results of both groups:
1. SPECT imaging results:
In group I, 13 patients (39.4 %) had an abnormal SPECT imaging result, and in group II 12 patients (70.6 %) had an abnormal SPECT imaging result.
The percentage of patients with an abnormal myocardial perfusion result was higher in group II, compared to group I results and the difference was statistically significant (70.6 % vs 39.4 %, P < 0.05), (Table 11, fig. 15).

Tabl3 11: SPECT imaging results of both groups


SPECT results     Group I
No. = 33     Group II
No. = 17
     No.     %     No.     %
Normal     20     60.6     5     29.4
Abnormal     13     39.4     12     70.6
P value     < 0.05
significance     significant

2. The summed difference score:
The summed difference score (SDS) was derived by subtracting the summed rest score from the summed stress score and this represented the extent and severity of stress-induced ischemia.
Patients in group I had a mean SDS of 2.51 ± 3.18, while the mean SDS for patients in group II was 5.17 ± 5.35.
A significant difference was found between patients in group I and patients in group II with respect to "summed difference score" (SDS), (P < 0.05), (Table 12, fig. 16).
Therefore, patients in group II had a mean SDS that was significantly higher than group I, which indicated that patients in group II had a stress-induced ischemia (both in extent and severity) reflected by the higher SDS, more than patients in patients group I, (5.17 5.35 vs 2.51 ± 3.18, P < 0.05).
Table 12: The summed difference score of the tow groups

SDS     Group I
No. = 33     Group II
No. = 17
Mean     2.51     5.17
SD     ± 3.18     ± 5.35
P     < 0.05
Significance      Significant


Fig. 15: showing SPECT imaging results of both groups

Group I (No.33) = 13 (39.4%) patients, and Group II (No.17) = 12 (70.6%) patients with an abnormal SPECT imaging result, (P < 0.05) (Significant).

Fig. 16: showing the mean summed difference score (SDS) of the two groups

3. Territory of ischemia:
Ischemia involving the territory of Left Anterior Descending artery (LAD), Right Coronary Artery (RCA), or Left Circumflex Artery (LCX) was recorded in each group.
Ischemia involving LAD territory was reported in 4 patients (30.8 %) in group I and 2 patients (16.7 %) in group II.
RCA territory was involved in 3 patients (23.1 %) in group I and 6 patients (50 %) in group II.
While only 2 patients (15.4 %) in group I had ischemia in LCX territory, the remaining patients had a multi vessels disease; 4 patients (30.8 %) in group I and 4 patients (33.3 %) in group II.
There was no statistically significant difference between the two groups (P > 0.05), (Table 13, fig. 17).
Table 13: The territory involved by ischemia


Territory
     Group I
No. = 33     Group II
No. = 17
     No.     %     No.     %
LAD     4     30.8     2     16.7
RCA     3     23.1     6     50
LCX     2     15.4     ---     ---
MVD     4     30.8     4     33.3
P value     > 0.05
Significance     Not significant
Fig. 17: showing the territory involved by ischemia in both groups

LAD=Left Anterior Descending, RCA=Right Coronary Artery, LCX=Left Circumflex Artery, MVD= Multi Vessels Disease.
D. Correlation between heart rate recovery and chronotropic variables:
A statistically non significant positive correlation was found between heart rate recovery and chronotropic response (r = 0.134, P > 0.05), heart rate recovery and heart rate reserve (r = 0.089, P > 0.05), and heart rate recovery and peak heart rate (r = 0.19, P > 0.05).
By considering the calculation of heart rate recovery 1-minute after exercise as a test or an index of myocardial ischemia and considering SPECT myocardial perfusion imaging as the standard test for assessing myocardial perfusion, the following results were obtained:
Specificity = 80%, sensitivity = 48%, accuracy = 64%, positive predictive value = 70.58%, and negative predictive value = 60.6%.

Peak hear rate=163 beats/min, 1-minuta hear rate=130 beats/min, hear rate recovery=33 beats/ min.
Fig 18: Exercise ECG 1-minute after cessation of exercise in a patient with normal hear rate recovery [patient No. 4]

Fig 19: Normal Tc-99m sestamibi SPECT scan in a patient with normal heart rate recovery [patient No. 4]

Peak hear rate=169 beats/min, 1-minuta hear rate=154 beats/min, hear rate recovery=15 beats/ min.
Fig 20: Exercise ECG 1-minute after cessation of exercise in a patient with abnormal hear rate recovery [patient No. 16]

Fig 21: Abnormal Tc-99m sestamibi myocardial perfusion SPECT study in a patient with abnormal heart rate recovery showing partially reversible defect involving the inferior regions (territory of RCA) and another defect involving the anteroseptal regions (territory of LAD) [patient No. 16]

Discussion
A significant number of reports have studied the pathophysiology of the increase in heart rate during exercise testing and of its decrease at the termination of the test, which are due to change in tone balance between the sympathetic and the parasympathetic nervous system (Imai et al 1994., and Ellestad et al., 1996).
The prognostic importance of the chronotropic response to exercise stress testing and heart rate recovery after exercise has been established. Delayed decrease in the heart rate during the first minute after treadmill testing appears to be an important predictor of overall mortality in dependant of the workload, the presence or absence of myocardial perfusion defects and the change in heart rate during exercise (Lauer et al., 1999, Cole et al., 2000, and Watanabe et al., 2001).
A heart rate decrease of more than 12 beat/min, 1 minute after the cessation of peak exercise, has been proposed in previous studies to be normal (Cole et al., 1999 and Desai et al., 2001).
In the early 1990s, 2,428 patients were referred for exercise nuclear testing at the Cleveland Clinic for evaluation of known or suspected coronary disease. All of the subjects were potential first-time candidates for coronary angiography. Heart rate recovery was defined as the difference in heart rate at peak exercise and that measured one minute later. It should be noted that all subjects underwent a cool-down period during recovery; that is, after peak exercise had been achieved, they walked slowly at a shallow grade for two minutes before stopping exercise altogether. Patients with an abnormal heart rate recovery (≤ 12 bpm) were at markedly increased risk of death compared to those with a normal heart rate recovery (Cole et al., 1999).
We believe that the value of heart rate recovery may be affected even by the small workload during the "cool-down" period. In addition, the implication of the workload during this period different for each patient. Therefore the patients in our study did not undergo a "cool-down" period. After peak exercise, they almost immediately terminated the testing and laid down on a bed. It is likely that this is an important reason why the median value for heart rate recovery in our study group was greater than values found in other studies (26 beats/min vs 17 beats/min in a study by Cole et al), (Cole et al., 1999).
Cole et al (1999), in their study found that a reduction of 12 beats/min or less from peak heart rate to 1-minute after exercise to be abnormal, but in this study they used a 2 minutes “cool-down period”, cardioactive medication was not necessarily discontinued, and diabetic patients were included.
We considered 21 beats/min as the lowest normal value as regard to previous study similar to our study in patients’ selection, exercise protocol used, and the use of a cool-down period after exercise (Georgoulias et al., 2003), they determined the lowest normal value of heart rate recovery by using mean value ±2 SD in a subgroup of subjects without pathologic finding on either treadmill testing or perfusion imaging and without any evidence of coronary artery disease by both medical history and further examination.
Left ventricular systolic dysfunction is one of the most powerful predictors of risk in patients with known or suspected coronary disease (O’Connor et al., 1997). Watanabe and colleagues studied this issue in 5,438 patients who underwent exercise cardiography.
By the nature of the exercise echocardiography protocol, left ventricular systolic function was systematically measured in all subjects. In these patients, heart rate recovery again emerged as an independent predictor of risk, providing prognostic information over and above that provided by left ventricular systolic dysfunction. In fact, an abnormal heart rate recovery was associated with a risk of death that was just as high risk of death as a left ventricular ejection fraction of < 40%. The combination of an abnormal heart rate recovery with left ventricular systolic dysfunction was associated with a particularly high death rate (Watanabe et al., 2001).
Watanabe et al (2001), defined the lowest normal value of heart rate recovery as 19 beats /min and its median value as 30 beats /min, values which are relatively close to our study, they also used variable exercise protocols, and patients with history of previous cardiac surgery (bypass grafting and/or PCI) were not excluded.
Myocardial SPECT imaging is a reliable method for assessing myocardial perfusion (Georgoulias et al., 1996, Aepfelbacher et al., 2001, Rigo et al., 1994, and Brown et al., 1991). In our study we excluded patients whose heart rate recovery or myocardial perfusion imaging might have been affected by factors other than myocardial ischemia. Therefore we believe that the considerable correlation between the value of heart rate recovery and the myocardial perfusion score ("summed difference score") reflects the influence of ischemia on its value.
Lauer et al (1999), also reported the relationship between exercise heart rate response and myocardial perfusion. They found a significantly higher frequency of myocardial perfusion defects among patients who failed to achieve at least 85% of the age-predicted maximum heart rate or who had a low chronotropic index.
In our study the subgroup of patients with abnormal heart rate recovery were of an older age compared to patients with normal heart rate recovery, but without significant difference (53 ± 9 vs 48 ± 10, P > 0.05). These results are similar to the results of other studies such as [Georgoulias et al study [2003] (63 ± 15 vs 52 ± 12, P < 0.05), Cole et al [1999] (61 ± 12 vs 55 12, P < 0.001), and Watanabe et al [2001] (65 ± 10 vs 56 ± 11, P < 0.001)], except that they found the difference to be statistically significant. This is may be due to the larger mean age in their studies compared to our study.
Patients with abnormal heart rate recovery were more likely to be males more than females, but this difference did not reach statistical significant difference (58.8 % vs 41.2 %, P > 0.05). Watanabe et al found similar results (64 % vs 63 %, P > 0.05). However, in Georgoulias et al study, similar results was found but with significant difference (82 % vs 67 %, P < 0.05). This may be due to the percentage of males in the entire population in Georgoulias et al study was higher than in our study (73 % vs 60 %). While in Cole et al study were more likely to be female (39 % vs 37 %, P > 0.05), (Georgoulias et al., 2003, Watanabe et al., 2001, and Cole et al., 1999).
The percentage of patients with hypertension was slightly higher in the subgroup of patients with abnormal heart rate recovery, but this difference was not statistically significant, (52.9 % vs 48.5 %, P > 0.05). This is similar to the results of Georgoulias et al study (59 % vs 44 %, P < 0.05), Cole et al (52 % vs 38 %, P < 0.001), and Watanabe et al (62 % vs 42 %, P < 0.001). However, they found a significant difference which may be attributed to the larger population included in their studies (Georgoulias et al (304 patients), Cole et al (2428 patients), and Watanabe et al (5438 patients)).


The same finding as above was found considering smoking, the percentage of smokers was comparatively higher in the subgroup of patients with abnormal heart rate recovery, without significant difference, (29.4 % vs 12.1 %, P > 0.05), compared to Georgoulias et al study (49 % vs 39 %, P > 0.05), Cole et al (24 % vs 15 %, P < 0.001), and Watanabe et al (18 % vs 15 %, P < 0.05), (Georgoulias et al., 2003, Watanabe et al., 2001, and Cole et al., 1999).
The percentage of patients with high cholesterol level (≥ 200 mg/dl) was slightly higher in the abnormal subgroup compared to those with normal hear rate recovery, without significant difference, (41.7 % vs 38.5 %, P > 0.05), compared to Georgoulias et al study, they found that patients with abnormal heart rate recovery were more likely to be hyperlipidemic than patients with normal heart rate recovery (84 % vs 52 %, P < 0.001), (Georgoulias et al., 2003).
In our study, we found a statistically non significant positive correlation between heart rate recovery and chronotropic response (r = 0.134, P > 0.05), heart rate recovery and heart rate reserve (r = 0.089, P > 0.05), and heart rate recovery and peak heart rate (r = 0.19, P > 0.05). These results are in concordance with the results of Georgoulias et al, except that they found it significant. They found a significant positive correlation between heart rate recovery and chronotropic response (r = 0.55, P < 0.001), between heart rate recovery and heart rate reserve (r = 0.56, P < 0.001), and heart rate recovery and peak heart rate (r = 0.53, P < 0.001). The significant correlation may be attributed to the larger number of patients included in Georgoulias et al study (304 patients vs 50 patients in our study), and the larger median value of heart rate recovery ( 35 beats/min vs 26 beats/min in our study).
The percentage of patients who showed an ischemic ST-segment change was higher in the abnormal subgroup, without significant difference, (23.5 % vs 9.1 %, P > 0.05), Georgoulias et al found the same results but with significant difference (39 % vs 20 %, P < 0.05), while Watanabe found no significant difference (18 % vs 17 %, P > 0.05), (Georgoulias et al., 2003, Watanabe et al., 2001).
We also found, that the percentage of patients who reported angina during the exercise testing was slightly more in the abnormal subgroup but without statistically significant difference, (17.6 % vs 15.2 %, P > 0.05), Georgoulias et al study (26 % vs 8 %, P < 0.001), and Watanabe et al (16 % vs 12 %, P < 0.001), found it significant, while Cole et al found no difference between the groups in the percentage of patients with ischemic ST-segment changes (19 % vs. 21 %, P> 0.05) or angina during treadmill testing (15 % vs. 14%, P > 0.05), (Georgoulias et al., 2003, Watanabe et al., 2001, and Cole et al., 1999).
In addition, the percentage of patients with an abnormal myocardial perfusion result was higher in patients with abnormal heart rate recovery, (70.6 % vs 39.4 %, P < 0.05). Cole et al also reported a higher proportion of patients with perfusion defects on TI-201 scintigrams in the group with abnormal heart rate recovery (23 % vs 19 %, P < 0.05), (Cole et al., 1999).
A significant difference was found between patients with normal heart rate recovery and abnormal heart rate recovery with respect to "summed difference score" (SDS), (2.51 ± 3.18 vs 5.17 ± 5.35, P < 0.05), which is comparable to the results found by Georgoulias et al (0.38 ± 0.09 vs 0.74 ± 0.11, P < 0.001), (Georgoulias et al., 2003).
In our study we considered the heart rate recovery 1-minute after exercise as test to detect ischemia in patient underwent exercise ECG because of their undiagnosed chest pain and it yielded the following: Specificity = 80%, sensitivity = 48%, accuracy = 64%, positive predictive value = 70.58%, and negative predictive value = 60.6%.

Summary

The heart rate recovery, defined as the decrease in heart rate from peak exercise to one minute after cessation of exercise, has important prognostic significance. The purpose of this study was to evaluate the heart rate recovery as an index of myocardial ischemia assessed by myocardial perfusion single photon emission computed tomography (SPECT) imaging.
This study included 50 patients, who were referred for evaluation of the presence or absence of ischemic heart disease.
All patients were subjected to a history taking, and physical examination, then exercise ECG and myocardial perfusion studies were performed to all patients using Technetium 99m sestamibi.
Patients were divided into two groups, group I with a normal heart rate recovery (≥ 21 beats/min), and group II with an abnormal heart rate recovery (< 21 beats/min).
The clinical characteristics of the two groups as regard to sex, age, hypertension, smoking, family history and cholesterol level were compared and showed statistically non significant difference.
Exercise ECG results showed that group II had a much lower mean heart rate recovery value than group I, with a high statistically significant difference.
With respect to SPECT imaging results, we found that the percentage of patients with an abnormal myocardial perfusion result was higher in group II. Also, patients in group II had a mean SDS that was significantly higher than group I.
A statistically non significant positive correlation between heart rate recovery and chronotropic response, heart rate reserve, and peak heart rate was found.
The heart rate recovery as a test to detect ischemia yielded the following:
Specificity = 80%, sensitivity = 48%, accuracy = 64%, positive predictive value = 70.58%, and negative predictive value = 60.6%.

Conclusion and Recommendations

In conclusion, we found that the heart rate recovery value 1 minute after exercise is a useful parameter in detecting myocardial ischemia.
The calculation of the heart rate recovery value during exercise testing will maximize the information it provides for the assessment of the severity and extent of myocardial ischemia.
More studies, with well defined conditions for the calculation of hear rate recovery value, are required for the definition of a generally accepted lowest normal value.
Finally, it may contribute to the selection of the patients who are in need of more expensive and complicated examination methods, such as the myocardial perfusion scintigrams.


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Article By: Dr. Emad Kamel Abou sabt
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Comments On Abnormal Heart Rate Recovery Immediately After Treadmill Testing : Correlation with Clinical, Exercise Testing, and Myocardial Perfusion Parameters  "2 Comment(s)"

Dr. Nael28/1/2014

good effort

Vibash11/12/2012

Great work! Congratulations!

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