Non-invasive work-up of suspected obstructive CAD in Romania – quo vadis?

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Ali Yilmaz1

1 Department of Cardiology and Angiology University Hospital Münster, Germany

Editorial comment to
Miftode et al., „SPECT versus ECG/echocardiography in the evaluation of ischemic heart disease – preliminary results in northeastern Romania“

Cardiovascular disease (CVD) – including coronary artery disease (CAD) – is the leading cause of death (not only) in Europe: According to the latest available European data1, 45% of all deaths are caused by CVD – with an even higher percentage in „middle income“ European countries compared to „high income“ ones. Hence, prevention, early diagnosis and successful the-rapy of CAD are of paramount importance – particu-larly in countries with a promising future, however, middle income such as Romania.
Hemodynamically relevant coronary artery steno-ses may cause chest pain and/or dyspnea, but also be present without any symptoms. And vice versa, angina pectoris may also occur in patients without obstruc-tive CAD due to different other reasons2. Therefore, a physician taking care of patients with cardiovascular risk factors and/or presence of chest pain symptoms is in need of appropriate diagnostic tools in order to safely rule-in or rule-out obstructive CAD in such patients3. The chosen diagnostic approach should be straightforward and minimise use of both personal and fi nancial resources while allowing a conclusive and cli-nically helpful diagnosis.
Current European guidelines suggest to first assess the individual pre-test probability (PTP) of CAD and thereafter, to choose the appropriate non-invasive di-agnostic modality based on the respective PTP value4. Possible non-invasive methods for further work-up of suspected CAD comprise exercise-ECG, stress-echocardiography, single-photon emission computed tomography (SPECT), cardiovascular magnetic reso-nance (CMR), positron emission tomography (PET) and coronary computed tomography angiography (CCTA). Each method has its individual strengths and limitations, and one has to consider both patient spe-cific as well as technical/local factors before choosing the most appropriate non-invasive imaging modality3.
In this context, Miftode et al. performed a small-si-zed study in northeastern Romania comprising 17 sta-ble patients who underwent (exercise) ECG, echocar-diography and exercise-SPECT for non-invasive work-up of suspected or known CAD5. Due to the fact that this study was performed in a Romanian hospital without a cath lab and that the authors are presenting their preliminary results, data from invasive coronary angiography were unfortunately not available (or not yet included into their analyses). Rather broad (and somewhat imprecise) inclusion criteria defined as pre-sence of either symptoms, resting ECG abnormaliti-es or known CAD were used. In 13 out of 17 (76%) patients, exercise-SPECT demonstrated the presence of ischemic perfusion defects whereas ischemic ECG changes were only observed in 9 out of 17 (53%) pa-tients. Noteworthy, there were two female patients with ischemic ECG changes but without any perfusion defects at SPECT. Moreover, there were some cor-relations detected between scintigraphic fi ndings and echocardiographic parameters such as left ventricular wall thickness or end-diastolic diameter. Unfortuna-tely, study limitations such as the small sample size, the authors‘ approach in patient selection and the missing gold- or reference-standard regarding the presence of obstructive CAD (e.g. data from invasive coronary an-giography) do not really allow to draw any substantial conclusions. Nevertheless, the additional use of non-invasive SPECT imaging will hopefully allow to better identify those patients that suffer from relevant myo-cardial ischemia (and will therefore benefit from subsequent invasive coronary angiography) while sparing patients without obstructive CAD unnecessary car-diac catheterizations. Considering available data that implicates the number of interventional cardiologists (only 4.4 per million people in Romania compared to e.g. 31.0 per million in Austria) are so far rather low in Romania1, accurate non-invasive work-up of suspec-ted obstructive CAD is of paramount importance.
There is no doubt that exercise-SPECT will impro-ve the diagnostic yield regarding non-invasive detecti-on of obstructive CAD when compared to (exercise) ECG or resting echocardiography – as was done in the study of Miftode et al. From a clinical point-of-view, it will be more appropriate to compare the diagnos-tic accuracy of exercise-SPECT to other non-invasive stress methods – that are also available in northeastern Romania – such as stress-echocardiography. Which of those methods (at least of those that are locally availa-ble) shows the best diagnostic performance to rule-in and rule-out obstructive CAD? While the aforemen-tioned European guidelines clearly state that exercise-ECG should only be performed in patients with a PTP of 15-65% whereas stress-echocardiography, SPECT, CMR and PET can be performed in those with a PTP of 15-85%4, these guidelines do not suggest any algori-thm regarding the appropriate or individual choice of the respective non-invasive method.
Fortunately, Knuuti et al. as well as Danad et al. re-cently addressed exactly this question and performed well reasoned and comprehensive meta-analyses6, 7. When looking only at those studies that used invasive fractional fl ow reserve (FFR) measurements for the diagnosis of obstructive CAD, Knuuti et al. detected some important findings7: In total, 4.131 patients from 23 studies were included into this analysis; the best performance in ruling-in obstructive CAD was docu-mented for stress-CMR, followed by PET and SPECT whereas the best performance for ruling-out obstruc-tive CAD was documented for stress-CMR, PET and CCTA (with similar likelihood ratios). In general, both stress-CMR and PET demonstrated the best perfor-mance within a broad range of PTP values whereas stress-echocardiography and SPECT showed a poorer performance, and exercise-ECG the poorest perfor-mance (being actually without a relevant additional va-lue in ruling-in or -out obstructive CAD). It will not be a surprise if the present recommendation to perform exercise-ECG in patients with a PTP of 15-65% will completely be removed in the upcoming revision of the respective European guidelines.
Taken together, the efforts of Miftode et al. to use SPECT imaging in northeastern Romania in order to improve the non-invasive diagnosis of obstructive CAD deserve attention and will certainly increase the diagnostic accuracy in identifying those patients that will benefit from subsequent cardiac catheterization. Moreover, including SPECT (similar to stress-CMR) into the diagnostic algorithm of CAD work-up may also be cost-effective from a general point-of-view8. However, in consideration of local resources and expertise, not only SPECT imaging but also novel methods such as stress-CMR that promises an even higher diagnostic yield without any radiation burden should also be pursued in Romania – in the interest of the Romanian people.

Conflict of interest: none declared.

1. Timmis A, Townsend N, Gale C, Grobbee R, Maniadakis N, Flather M, Wilkins E, Wright L, Vos R, Bax J, Blum M, Pinto F, Vardas P. European Society of Cardiology: Cardiovascular Disease Statistics 2017. Eur Heart J 2018 February 14;39(7):508-79.
2. Yilmaz A, Sechtem U. Angina pectoris in patients with normal coro-nary angiograms: current pathophysiological concepts and therapeu-tic options. Heart 2012 July;98(13):1020-9.
3. Yilmaz A, Sechtem U. Ischaemia testing in patients with stable angina: which test for whom? Heart 2014 December;100(23):1886-96.
4. Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Bu-daj A, Bugiardini R, Crea F, Cuisset T, Di MC, Ferreira JR, Gersh BJ, Gitt AK, Hulot JS, Marx N, Opie LH, Pfisterer M, Prescott E, Rus-chitzka F, Sabate M, Senior R, Taggart DP, van der Wall EE, Vrints CJ, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopou-los P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Knuuti J, Valgimigli M, Bueno H, Claeys MJ, Donner-Banzhoff N, Erol C, Frank H, Funck-Brentano C, Gaemperli O, Gonzalez-Juanatey JR, Hamilos M, Hasdai D, Husted S, James SK, Kervinen K, Kolh P, Kristensen SD, Lancellotti P, Maggioni AP, Piepoli MF, Pries AR, Romeo F, Ryden L, Simoons ML, Sirnes PA, Steg PG, Timmis A, Wijns W, Windecker S, Yildirir A, Zamorano JL. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary ar-tery disease of the European Society of Cardiology. Eur Heart J 2013 October;34(38):2949-3003.
5. Miftode R. SPECT versus ECG/Echocardiography in the evaluation of ischemic heart disease – preliminary results in northeastern Roma-nia. 2019.
6. Danad I, Szymonifka J, Twisk JWR, Norgaard BL, Zarins CK, Knaap-en P, Min JK. Diagnostic performance of cardiac imaging methods to diagnose ischaemia-causing coronary artery disease when directly compared with fractional fl ow reserve as a reference standard: a meta-analysis. Eur Heart J 2017 April 1;38(13):991-8.
7. Knuuti J, Ballo H, Juarez-Orozco LE, Saraste A, Kolh P, Rutjes AWS, Juni P, Windecker S, Bax JJ, Wijns W. The performance of non-inva-sive tests to rule-in and rule-out signifi cant coronary artery stenosis in patients with stable angina: a meta-analysis focused on post-test disease probability. Eur Heart J 2018 September 14;39(35):3322-30.
8. Greenwood JP, Ripley DP, Berry C, McCann GP, Plein S, Bucciarelli-Ducci C, Dall‘Armellina E, Prasad A, Bijsterveld P, Foley JR, Man-gion K, Sculpher M, Walker S, Everett CC, Cairns DA, Sharples LD, Brown JM. Effect of Care Guided by Cardiovascular Magnetic Res-onance, Myocardial Perfusion Scintigraphy, or NICE Guidelines on Subsequent Unnecessary Angiography Rates: The CE-MARC 2 Ran-domized Clinical Trial. JAMA 2016 September 13;316(10):1051-60.

ISSN – online: 2734 – 6382
ISSN-L 1220-658X
ISSN – print: 1220-658X
The Romanian Journal of Cardiology is indexed by:
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CODE: 379
CME Credits: 10 (Romanian College of Physicians)
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