Methods

The study population consisted of consecutive patients undergoing myocardial perfusion scintigraphy for clinical reasons who managed to complete ≥9 minutes of exercise on the treadmill, reaching the end of stage 3 of the Bruce protocol. From January 1, 2003 to December 31, 2004 there were 3,269 MPS studies performed in our department. Treadmill exercise was used as the stress method in 2,197 patients (67%). Of these, 516 (24%) managed ≥9 minutes of the Bruce protocol. For patients who underwent >1 study during this period, only the first was included in the analysis.

Symptom-limited exercise testing was performed according to the Bruce protocol, with patients encouraged to exercise for as long as possible. Patients were required to omit any β-blockers for 48 hours before the test. Target heart rate was calculated as 220 beats/min minus a patient’s age, with adequate heart rate response being ≥85% of the target, although the test was not terminated on achievement of target heart rate alone. After exercise, a patient was monitored for symptoms or electrocardiographic (ECG) changes for at least a further 3 minutes.

Myocardial perfusion scintigraphy was performed using technetium-99m tetrofosmin (Myoview, GE Healthcare, Ltd., Amersham, Bucks, United Kingdom) predominantly using a 1-day stress/rest protocol, with a small number of 1-day rest/stress and 2-day protocols. For the stress/rest protocol, technetium-99m tetrofosmin approximately 250 MBq was injected intravenously at peak stress. The study at rest was performed a minimum of 3 hours after stress, with injection of technetium-99m tetrofosmin 750 MBq before acquisition. Single-photon emission computed tomographic acquisition was carried out on Philips CardioMD or Forte dual-headed γ cameras (Philips Healthcare, Best, The Netherlands); 32 projections were acquired over a 180° contoured orbit with 45 to 60 seconds per projection. Wherever possible, images at rest were gated with 16 frames per cardiac cycle. Iterative reconstruction was used for static perfusion images, with filtered back projection of gated images.

Analysis of single-photon emission computed tomographic data was performed by an experienced nuclear cardiologist using a Philips Pegasys workstation (Philips Healthcare, Best, The Netherlands) with Cedars-Sinai (Los Angeles, California) AutoQuant software. Static tomographic perfusion images during stress and at rest were displayed as short-axis, horizontal and vertical long-axis slices, with the 2 sets of images side by side. The study interpreter had access to clinical and exercise test (including 12-lead ECG) data. Perfusion defects were scored semiquantitatively on a 9-segment model. A defect present only on the stress images was considered reversible. One seen on stress and at-rest images, with associated wall motion/thickening abnormality on the gated study, was considered fixed. If a defect was present on the 2 sets of images but wall motion appeared normal on the gated study, the possibility of attenuation by soft tissue or the diaphragm was excluded before reporting it as a genuine fixed perfusion defect.

Guidelines from the Drivers Vehicle Licensing Authority in the United Kingdom state that, to maintain a vocational license, patients with known or suspected cardiovascular disease must complete 9 minutes of the Bruce protocol, off antianginal medication, without chest pain or ECG evidence of ischemia. To qualify on MPS grounds, left ventricular ejection fraction must be ≥40% and ≤10% of total myocardium should show reversible ischemia.

Drivers Vehicle Licensing Authority criteria were retrospectively applied to the exercise test and MPS components of each study to categorize these individually as “qualifying” (low risk) or “disqualifying” (high risk). An exercise test was deemed to be high risk if there was ≥1-mm ST-segment elevation or ≥2-mm planar/downsloping ST-segment depression, or if the patient described limiting anginal chest pain. Myocardial perfusion scintigram was deemed to be high risk if there was reversible hypoperfusion amounting to ≥1 myocardial segment or left ventricular ejection fraction was <40% on gated single-photon emission computed tomogram.

Follow-up data collection was performed by contacting each patient by telephone or in writing. If further information was required, a patient’s general practitioner was contacted, together with review of hospital records, where necessary. Documented adverse events comprised all-cause mortality, cardiac death (sudden arrhythmic death, known or suspected acute myocardial infarction [MI], refractory heart failure, or unexpected death with no obvious noncardiac cause) and nonfatal MI. Myocardial revascularization procedures—percutaneous coronary intervention (PCI) and coronary artery bypass grafting—were also recorded. Hard cardiac events were cardiac death and nonfatal MI only. If a patient reported having an MI, clinical records were reviewed to verify that the diagnosis conformed to necessary criteria (including a requirement for increased troponin I or T levels).

For statistical analysis, continuous data are expressed as mean ± SD, categorical data as proportions. Student’s t test was used to analyze normally distributed continuous data, with Mann-Whitney U test for nonparametric data. Categorical variables were analyzed using chi-square or Fisher’s exact tests. A p value <0.05 was considered statistically significant.

Results

Baseline characteristics of the study population are listed in Table 1 . In the 516 patients, median age was 53 years (range 28 to 79), and almost 3/4 (73%) were men. In contrast to the traditional patient population referred for treadmill exercise testing as a first-line investigation, a substantial proportion of study patients had proved CAD (35%), previous MI (13%), or previous revascularization (23%). There were important differences between male and female patients. Compared to men, women were less likely to have a background of coronary disease (9% vs 45%, p <0.001) and were more likely to have chest pain (82% vs 55%, p <0.001).

By design, all patients completed ≥9 minutes of the Bruce protocol during treadmill exercise testing. Total exercise time was 9 to 15 minutes. One hundred forty-nine patients (29%) had a disqualifying/high-risk exercise test because of significant ECG changes and/or limiting chest pain. Of the 170 patients with abnormal MPS appearances, 69 had a reversible perfusion defect amounting to ≥10% total left ventricular myocardium and/or left ventricular ejection fraction <40%. These 69 studies (13% total) would therefore have been considered high risk according to the criteria described earlier. The proportion with high-risk exercise test results was comparable for men and women (31% vs 23%, p = 0.12), but men were more likely to have high-risk MPS findings (19% vs 0%, p <0.001).

Table 2 presents a comparison of findings on exercise testing and myocardial perfusion scintigram according to vocational licensing eligibility. Of 367 patients with a qualifying exercise test, 38 (10%) had high-risk MPS findings. Of 149 patients with a disqualifying exercise test, 118 (79%) had reassuring MPS findings. Thirty-one patients (6%) had disqualifying abnormalities on exercise testing and myocardial perfusion scintigram. Overall level of agreement between the 2 investigations was poor (kappa 0.13, 95% confidence interval 0.05 to 0.20).

Of the original 516 patients, 498 (97%) were successfully followed up at a median of 49 months after myocardial perfusion scintigraphy (range 12 to 61). Of the remaining 18 patients, most were known to have moved house or general practitioner practice, leaving no valid contact details. During the follow-up period there were 8 hard cardiac events (1.6%) and a further 8 noncardiac deaths. Cardiac events comprised 2 sudden deaths, 1 cardiac arrest due to ventricular fibrillation, and 5 nonfatal MIs ( Table 3 ). Of these, 3 were classified as non–ST-elevation MI and 2 as ST-elevation MI (1 related to acute stent thrombosis a week after elective PCI). Only 2 of the 147 (1.4%) with a disqualifying exercise test and 1 of the 67 (1.5%) with disqualifying myocardial perfusion scintigram had a cardiac event. Most events occurred in the group with reassuring exercise test and MPS findings, although there was no statistically significant difference in rates between subgroups (p = 0.62). Annual cardiac event rate was <0.5% per year.

Table 3

Clinical and investigation findings for patients with cardiac events

	Exercise Test Findings		MPS Findings
Patient Age (years)/Sex	Chest Pain	ECG Changes	Ischemia	EF (%)	Nature of Cardiac Event	Time After Testing
41/M	0	0	0	50	Sudden death	23 months
42/M	0	0	0	>72	STEMI (subsequent 2-vessel PCI)	2 months
45/F	0	0	0	71	NSTEMI (CA: no obstruction)	55 months
47/M	0	0	0	N/A	NSTEMI (subsequent PCI)	2 months
48/M	0	0	0	55	NSTEMI (CA: no obstruction)	33 months
52/M	+	+	0	65	STEMI (after PCI stent thrombosis)	22 months
57/M	0	+	>10%	32	VF arrest (subsequent elective PCI)	10 months
60/M	0	0	<10%	55	Sudden death	8 months

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