In Europe, subjects >65 years of age currently constitute 17% of the entire population, with some variations between countries (see Figure 1).1 More importantly, as a consequence of the ageing population, elderly subjects are expected to account for 30% of the European population by 2050. Currently, cardiovascular disease is the major cause of death in Europe (~20% of all causes) and more than two-thirds of cardiovascular deaths are registered in the elderly.2 Despite the need for effective strategies to assess prognosis in elderly patients with known or suspected coronary artery disease (CAD), few data have been collected so far in this specific population with the commonly used diagnostic modalities.3 Regardless of age, American College of Cardiology/American Heart Association practical guidelines recommend exercise electrocardiogram (ECG) testing (EET) as the initial non-invasive method for evaluating CAD in patients with a normal or near-normal resting ECG who can exercise adequately.4 The guidelines acknowledge that the elderly represent a special population in whom EET may be more difficult both to perform and to interpret, but there are insufficient data to recommend stress imaging over standard EET in this group of subjects. In fact, despite the need for individualised prognostic information in the elderly, these patients have not been adequately represented in studies of CAD.5
Single-photon-emission computed tomography (SPECT) myocardial perfusion scintigraphy (MPS) represents a well-established method of collecting both diagnostic and prognostic information in patients with known or suspected CAD, and its feasibility and accuracy have been tested in a variety of different subpopulations.6 To date, few studies have focused on the use of MPS in elderly patients,7 and only recent evidence supports the strong value of MPS for prognostic stratification and selection of optimal therapy in elderly patients evaluated for CAD.8
SPECT MPS versus EET for the Assessment of Myocardial Ischaemia in the Elderly
Owing to its wide availability, simplicity and low cost, EET still represents a convenient first-line test for the evaluation of elderly patients with known or suspected CAD. However, the performance of EET with either treadmill or bicycle may pose some practical difficulties in the elderly. Muscle weakness, deconditioning, neurological/orthopaedic disorders and peripheral vascular disease are frequently responsible for a limited exercise capacity in these subjects.
In many cases, the use of less challenging protocols for the stress test is required in individuals >65 years of age, and the ischaemic threshold may not always be reached. Even the interpretation of EET results in the elderly may differ from that in the young. The elevated prevalence of CAD in this population leads to a high incidence of false-negative results, leading to reduced negative predictive value for CAD detection.4 In addition, ECG abnormalities are significantly more common in the elderly, which complicates test interpretation.
In general terms, SPECT MPS may represent a valuable alternative to EET for accurate assessment of myocardial ischaemia in elderly patients (see Table 1).9,10 Furthermore, in patients unable to complete an exercise test, MPS offers the opportunity to employ an imaging protocol with pharmacological stress. Adenosine or dipyridamole stress MPS imaging in particular has been safely applied for CAD detection even in patients >80 years of age.11 Finally, pharmacological stress showed a better diagnostic performance than exercise stress with SPECT MPS in patients with left bundle branch block, which is a highly frequent ECG abnormality in the elderly population.12
A few studies have evaluated the prognostic utility of EET information in the elderly, and in some cases have indicated a limited ability to predict survival from cardiac events compared with the situation in younger patients.13 A main issue with EET when applied in the elderly for prognostic stratification is the observation that the vast majority of patients end up in the intermediate-risk group.14 This is because the workload that may be achieved by elderly subjects is frequently inadequate to induce ischaemia, but exercise-induced ST depression and angina are both required for a high-risk classification with commonly used scoring systems such as the Duke treadmill score.
SPECT MPS for Prognostic Stratification of Elderly Patients
Despite the increased absolute risk of major cardiac events imposed by age, in the elderly SPECT MPS may still maintain a strong predictive power for adverse prognosis. Table 2 reports data from the major studies evaluating the prognostic value of MPS in the elderly. Overall, MPS showed the ability to identify a low-risk subgroup of elderly patients with normal or mildly abnormal imaging results. In these patients, an annual event rate of about 1% has been reported in the majority of the evaluated studies.
Recently, Hachamovitch et al. examined the role of dual-isotope SPECT MPS for prognostic evaluation in a large group of patients ≥75 years of age.8 Of note, compared with age-matched individuals in the general US population, a higher risk of cardiac death was documented in the overall study cohort (n=5,200 patients), while a significantly lower risk was reported when only patients with normal MPS results were considered (see Figure 2).
Interesting data from the Mayo Clinic nuclear cardiology database documented a better ability to risk-stratify elderly patients using exercise thallium-201 (Tl-201) SPECT imaging than with the EET.15 The percentage of patients classified as intermediate-risk decreased from 68% using the Duke treadmill score to 16% when the summed stress score from MPS was employed (see Figure 3).
SPECT MPS with pharmacological stress may represent a valuable alternative for the consistent proportion of elderly patients with co-morbidities precluding the capacity to perform an adequate stress test (up to 50% of the total population in some reports).16 In this setting, when using dobutamine as the stressor, a higher prevalence of arrhythmias (including supraventricular tachycardia and atrial fibrillation) has been observed in the elderly.17 Thus, vasodilator stressors such as adenosine or dipyridamole may be preferable. In this regard, by applying dipyridamole Tl-201 SPECT in a population of patients with a mean age of 77 years, the strongest MPS-derived prognostic variable was the presence of perfusion defects in more than two coronary vascular supply territories, which was suggestive of multivessel CAD.18 Studies conducted with SPECT MPS demonstrated that elderly patients who performed a pharmacological stress test had higher hard event rates than those undergoing an exercise test.19 To partially explain these findings it should be noted that the non-randomised prescription of a pharmacological stress test in patients unable to exercise may lead to the selection of a subgroup with worse prognosis. In the previously mentioned study from Hachamovitch et al., patients undergoing pharmacological stress testing were older and more frequently presented markers of increased cardiovascular risk (e.g. prior myocardial infarction or revascularisation, diabetes, hypertension, etc.) compared with patients in the exercise stress group.8
Less widely investigated is the value of stress MPS for the prognostic characterisation of very old patients (≥80 years of age) with known or suspected CAD. The use of pharmacological stress testing is particularly frequent in this type of population with common difficulties with exercise. Zafrir et al. studied an octogenarian population (mean age 83 years) evaluated by exercise (29%) or dypiridamole (71%) stress MPS, confirming that event-free survival was significantly lower in patients with an abnormal scan than in those with a normal scan.20 These data indicated that even in very old (>80 years of age) patients, a non-ischaemic MPS was associated with a relatively low risk of cardiac events (3.2% per year). In agreement with this report, Hachamovitch et al. recently confirmed that even in very old patients (>85 years of age), MPS is able to stratify groups with significantly different levels of risk of cardiac death (see Figure 2).8
Gated SPECT provides additional information on ventricular systolic function and may be conveniently applied for prognostic evaluation in combination with data on myocardial perfusion.21 In a group of patients ≥75 years of age with known or suspected CAD evaluated by gated SPECT, De Winter et al. identified the summed rest score and the resting left ventricular end-systolic volume as independent predictors of cardiac death.22 Hachamovitch et al. showed that combining left ventricular ejection fraction and perfusion data enhanced risk stratification, with the lowest level of risk observed when both normal ejection fraction and preserved perfusion were present (see Figure 4).8
In conclusion, SPECT MPS has the ability to successfully stratify risk of adverse cardiac events in elderly (>65 years of age) as well as very elderly (>80 years of age) patients. The finding of a normal MPS study in an elderly patient has been repeatedly associated with a low level of risk (~1% annual event rate). Practical advantages over EET are represented by the possibility of accurately identifying myocardial ischaemia in the large subgroup of elderly subjects with ECG abnormalities and the opportunity of using a pharmacological stress test in subjects unable to exercise. An MPS-guided approach for the referral of elderly patients for revascularisation procedures seems to be feasible, but its clinical efficacy needs to be prospectively verified.