Journal of Nuclear Cardiology

, Volume 25, Issue 2, pp 521–525 | Cite as

Are the differences clinically relevant? The European Perspective

Editorial
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Due to the variable and multifaceted clinical presentation, the prevalence of stable coronary artery disease (CAD) is difficult to determine. Population-based studies have reported an estimated prevalence of 4-7% among 45-64 year olds and 10-15% among 65-84 year olds.1 Despite trends that suggest a decreasing mortality,2 the prevalence of stable CAD does not appear to have decreased. The accurate and timely diagnosis of CAD remains challenging. Clinical history and physical examination may be misleading or unyielding, and the traditional stress electrocardiogram (ECG) may lack sensitivity thereby missing out on a substantial proportion of patients with clinically significant CAD. Sekhri and colleagues reported that every third patient suffering CAD death or myocardial infarction having had clinical work-up for CAD in the preceding 5 years had been erroneously cleared from a suspected CAD diagnosis.3 On the other hand, the prognosis of stable CAD may vary from excellent to very poor based on the severity of disease and extent of jeopardized myocardium. Over the years, randomized trials have demonstrated that medical therapy, including platelet inhibitors, cholesterol-lowering drugs, and inhibitors of the renin-angiotensin-aldosterone system and lifestyle changes are the most effective treatments to affect long-term outcomes while revascularization should be reserved for patients at immediate high risk of cardiovascular events or refractory to medical treatment.4-6

The global importance of appropriate CAD diagnosis and treatment has prompted international cardiological societies, such as the European Society of Cardiology (ESC), the American College of Cardiology (ACC), and the American Heart Association (AHA) to issue recommendations and update them periodically based on new evidence. This issue of the Journal of Nuclear Cardiology features a comparison between the most recent European (EU)4 and US7,8 guidelines dealing with stable CAD. Both guidelines have emphasized over the last years the increasing role that imaging technologies play in (i) the initial work-up of suspected CAD, (ii) the prognostic assessment of established CAD and its impact on treatment strategies, and (iii) the follow-up of CAD patients after treatment. While both EU and US guidelines agree on the majority of issues, minor differences of opinion may still be observed and are most likely related to differences between EU and US local practice, medico-legal and socio-economic systems, and different weighing of the published evidence. Furthermore, in the field of medical imaging, evidence from large randomized trials is scarce, therefore, the appropriate use of technologies is largely based on interpretation and comparison of diagnostic studies and longitudinal cohorts. Moreover, it should be mentioned, that both guideline documents date back to 2013 and 2012, respectively. The field of medical imaging is rapidly growing and several new studies have been published in the meantime which are expected to modify the recommendations in future issues of these documents. The purpose of the present editorial is to work out the most important differences in recommendations and to highlight those with potential relevance for clinical practice.

Diagnostic approach to CAD

In the initial diagnostic work-up of patients with suspected CAD, both EU and US guidelines base their recommendations on traditional Bayesian probabilistic concepts, which describe the effect of the pretest probability (PTP) on the post-test disease likelihood after a positive or negative test result. PTP can be readily estimated from published charts based on the typicality of symptoms and the gender and age of the patients (Table 1).9 Both guidelines recognize the best discriminatory ability of imaging technologies in patients with intermediate PTP (a concept recently challenged by the updated United Kingdom National Institute of Clinical Excellence (NICE) recommendations10) which is arbitrarily defined as 15-85% in the ESC document. In low PTP patients (i.e., PTP < 15%), the European guidelines discourage any further testing (since the likelihood of a false positive result would actually exceed the likelihood of a true positive test result) and instead recommend testing for alternative diagnoses. According to the ESC guidelines, a low PTP patient would be a women of 30-49 years with atypical chest pain or any men < 30 years. In contrast, US guidelines give a class IIa recommendation for exercise ECG (if rest ECG is interpretable and the patient is able to exercise) or alternatively for cardiac CT (CCT) and stress echocardiography in low PTP patients. Although there are little data indicating clinical usefulness of imaging techniques in low PTP patients, the US guidelines acknowledge that nonetheless in certain cases the level of uncertainty acceptable to physicians and patients may prompt further testing, and that the precise boundaries for low PTP are ill-defined and vary from < 10% to < 30% across different studies.
Table 1

Pretest probability from age, gender, and symptoms

Adapted from Genders TS, et al.9

Green: low; Yellow–Orange: intermediate; Red: high

Traditionally, stress ECG is the most frequently used stress test for CAD detection applied by cardiologists and general physicians due to their wide availability, simple set-up, and low cost. In the previous 2006 issue of the ESC guidelines, stress ECG was the central initial CAD test and stress imaging was only considered for patients with uninterpretable ECG (e.g., digitalis, left bundle branch block, pre-excitation ECG, or paced rhythm) or patients unable to exercise. Both EU and US guidelines have evolved by acknowledging the superior diagnostic accuracy of stress imaging tests compared to stress ECG (Table 2) and exploiting these advantages in diagnostic algorithms. However, the approach to the patient is quite different between EU and US guidelines: In the US guidelines, the choice of diagnostic test is primarily governed by the patient’s ability to exercise. In a patient who is able to exercise, stress ECG remains the initial test with additional imaging (stress myocardial perfusion imaging (MPI) or echocardiography) only added if the ECG is uninterpretable or PTP is high. The rationale to favor physical stress testing over pharmacological stress is to provide a more physiological correlation to the patient’s daily symptom burden and physical work capacity (the latter being an important prognostic indicator). Pharmacological stress imaging is reserved for patients who are unable to exercise.
Table 2

Comparison of diagnostic accuracy of CAD tests

 

Sens (%)

Spec (%)

Exercise ECGa

45-50

85-90

Exercise stress echocardiography

80-85

80-88

Exercise stress SPECT

73-92

63-87

Dobutamine stress echocardiography

79-83

82-86

Dobutamine stress MRIb

79-88

81-91

Vasodilator stress echocardiography

72-79

92-95

Vasodilator stress SPECT

90-91

75-84

Vasodilator stress MRIb

67-94

61-85

Coronary CTAc

95-99

64-83

Vasodilator stress PET

81-97

74-91

aResults without/with minimal referral bias

bResults obtained in populations with medium-to-high prevalence of disease without compensation for referral bias

cResults obtained in populations with low-to-medium prevalence of disease

Adapted from 2013 ESC guidelines for stable CAD4

The EU guidelines take a more radical approach and differ from the US document in two points: (1) Traditional stress ECG is no longer recommended as the only CAD test if more advanced imaging modalities are available, (2) the choice of stress imaging test is not primarily governed by the patient’s ability to exercise but rather by PTP taking also into account additional factors like availability, local expertise, radiation exposure, and patient suitability for any given imaging test (Figure 1). In patients in the higher spectrum of intermediate likelihood (66-85%), the EU guidelines discourage the use of stress ECG alone altogether due to the lower sensitivity of the technique compared to imaging and the risk of missing out on a significant number of CAD diagnoses. Evidence for favoring stress imaging over stress ECG alone is weak and is largely based upon the higher comparative diagnostic accuracy of imaging. The WOMEN study did not document any prognostic advantages of stress MPI over stress ECG in very low-risk women.11
Figure 1

Diagnostic algorithm for CAD detection in patients at intermediate pretest probability as proposed by the ESC guidelines for stable CAD4

Coronary computed tomography angiography (CCTA) has emerged over the last 10 years as an excellent diagnostic CAD imaging test with a very high sensitivity and particularly a high negative predictive value. Due to this high negative predictive value, the test is currently used in patients with low-to-intermediate PTP when the main goal is to exclude CAD. In the presence of significant coronary stenoses on CT, the positive predictive value of CT is usually lower, due to the inability of CT to determine the hemodynamic significance of coronary lesions (unless newer techniques such as CT-FFR or CT perfusion are added). Both US and EU guidelines acknowledge the increasing role of CCTA in the diagnostic work-up of suspected CAD with a class IIa recommendation for patients with low-to-intermediate PTP (which in the EU guidelines is arbitrarily defined as 15-50%). This recommendation is based on the particular high negative predictive value of CCTA and the high discriminatory capacity in this range of PTP.12 Moreover, both guidelines propose CCTA as an alternative technique in patients with failed or inconclusive findings on stress testing.

It is likely that future issues of guidelines in both EU and US will further upgrade the recommendations for CCTA in stable CAD patients: In the meantime, several important studies have been published which demonstrate at least equipoise in diagnostic certainty and patient outcomes for CCTA compared to stress testing. The PROMISE trial randomized 10,000 patients with suspected CAD to an initial diagnostic testing strategy with CCTA versus stress testing (in 67% stress radionuclide imaging) and revealed no difference in clinical outcomes over 2-year follow-up. CCTA resulted in a slightly lower number of coronary angiograms with non-obstructive coronary arteries while it also doubled the number of revascularizations.13 The SCOT-HEART trial randomized more than 4,000 patients to a conventional testing strategy including clinical history and stress ECG (imaging only performed in 10% of patients) versus CCTA on top of conventional testing strategy. The primary endpoint of this study was diagnostic certainty which was significantly enhanced in the CCTA group. Moreover, CCTA resulted in more cancelations of diagnostic tests and more changes in medical therapy. On clinical follow-up over 3 years, CCTA was even associated with a borderline significant 38% reduction in cardiac death and myocardial infarction rates.14

Risk stratification of CAD

Besides its diagnostic value, the information contained in diagnostic imaging is often exploited for risk stratification. In simple words: the more severe the findings on imaging, the worse the cardiac prognosis of the patients, and the more aggressive treatment strategies should be to reverse patients’ risk. Cardiac radionuclide imaging has always been at the forefront of imaging modalities to demonstrate its potent ability to predict cardiac events independently of other clinical factors. Both guidelines acknowledge the prognostic value of cardiac radionuclide imaging in patients suspected or known CAD and refer to the large body of evidence accumulated over several decades.15

Similarly, to the chapter on diagnostic assessment, the recommendations for the use of CCTA for risk stratification of the patients are a little shyer in both the US and EU guidelines (class IIa). Likewise, this recommendation is likely to be upgraded in the future since several large longitudinal studies with CCTA have been published in the meantime with several ten thousands of patients.16,17

Follow-up of patients with established CAD

The role of imaging in the follow-up of patients with established coronary artery disease who are either under pharmacological treatment or after revascularization procedures remains a debated issue. Both guideline documents recommend the use of stress testing (ideally in combination with imaging) for the follow-up of patients with new or recurrent symptoms, in which recurrence of myocardial ischemia either in the coronary artery territory previously treated by revascularization or in a remote territory is sought. Interestingly, the guidelines somewhat disagree in their recommendations for CCTA: While the EU guidelines abstain from giving any particular recommendation for CCTA in the follow-up of patients with established CAD, the US guidelines acknowledge the potential value of cardiac CT for assessing patients with coronary artery bypass grafts and/or intracoronary stents with a diameter of 3 mm or more (class IIb recommendation). Indeed, the diagnostic accuracy of CCTA for bypass grafts (particularly saphenous vein grafts) is very high (due to their large diameter and low extent of cardiac motion compared to native coronary arteries).18 However, in bypass graft patients, the native coronary arteries tend to calcify at faster pace, and therefore become often non-evaluable with CCTA. Stented segments can be assessed with regard to stent patency in large diameter stents with modern image reconstruction algorithms provided the patient has low heart rate, no cardiac motion artifacts, and no excessive calcifications.

In asymptomatic patients, recommendations for routine follow-up with imaging are even more controversial. While routine periodic clinical reassessment is commonly recommended including assessment of symptoms, cardiovascular risk factor control, and adherence to medical therapy, the role of routine imaging follow-up is not recommended due to the lack of evidence suggesting any benefit. On the other hand, the increased risk of radiation from repeat imaging studies should be considered. Exceptions to this rule are mentioned in the US guidelines and are patients with a history of silent ischemia or who are at very high risk of rapid CAD progression. In such patients, repeat routine imaging testing can be considered after the warranty period for the individual test selected has expired, e.g., every 2-3 years for stress radionuclide perfusion imaging. The EU guidelines are more restrictive in their recommendations giving only a class IIb recommendation and highlighting thereby the lack of randomized evidence for routine testing.

Notes

Disclosure

OG reports no conflict of interest related to the content of this article

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Copyright information

© American Society of Nuclear Cardiology 2017

Authors and Affiliations

  1. 1.University Heart Center ZurichZurichSwitzerland

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