In this small retrospective single-center study we showed that patients with angina and a positive SPECT scan indicating reversible ischemia but no significant epicardial coronary artery disease in coronary angiography have very good long-term prognosis in the following years and very low cardiovascular morbidity and mortality. The particularly long average follow-up time of the study, more than 5.5 years, the evidence of no cardiac deaths and a very low rate of revascularization during follow-up period enhance the value of our results. The fact that the rate of death in the “lost to follow-up” patients was not significantly different could be considered as an indice of similarity between the two groups, at least for major outcomes. The rate of hospitalization for cardiovascular reasons during the follow-up period is quite low and the majority is related to arrhythmic events and conduction disturbances rather than acute coronary syndromes. Symptoms of heart failure are reported by one out of ten patients, but with most of them in NYHA class I and no related hospitalizations. The particularly low number of patients complaining about angina is quite striking, although the questionnaire used is not validated and we cannot exclude the possibility of misinterpretation of angina symptoms or heart failure symptoms.
It is undoubtful that our study lacks sufficient data to identify how many of our patients had true dynamic macro- or microvascular impairment, which could explain the positive SPECT scan results, and how many were just “victims” of artifacts of the study. Yet, the very low overall rate of dismal outcomes in the majority of the patients during a long follow up period probably renders such a quest unnecessary.
Our study had a low total rate of false positive myocardial SPECT scans. Such rates are reported in early studies of MPS performance in the diagnosis of coronary artery disease, with a significant number of gated SPECT scans and supine and prone acquisitions (13). Yet later “real world” series report significantly higher rates of false positive scans above 50%, raising questions on the accuracy of the method in ruling-in patients for coronary artery disease and the subsequent cost of such a strategy. An explanation for our low rate of false positive scans could be the fact that we excluded from analysis all patients that had an LBBB morphology at rest ECG before coronary angiogram. Furthermore, recent literature suggests that this morphology could be a source of increased false positive SPECT scans and subsequently misdiagnosis, leading to unnecessary coronary angiograms (11).
To sum up, our study has numerous limitations. Firstly, the retrospective nature of the study and the lack of clinical information about the patient’s thorough medical history when they underwent the index coronary angiography deprives us of data regarding the etiology of the false positive results of SPECT scans. Secondly a considerable number of patients that could not be contacted is an issue that could raise suspicion of a higher mortality/morbidity and cardiovascular events rate in that group. Yet the fact that the data derived from public social security records did not show statistically significant difference as far as mortality is concerned, (irrespective of the etiology) is partially reassuring. Another limitation is that the follow up is via telephone contact with a non-validated questionnaire and the accuracy of answers could be questioned, particularly when quantitative data like NYHA score are assessed. We also had no data regarding the percentage of exercise stress versus vasodilator stress SPECT scans in our sample, known parameters that affect sensitivity and specificity of CAD diagnosis in MPS. Lastly, the limited SPECT scan data regarding the amount and distribution of area at risk in non-revascularized patients, yet with a diagnosis of “positive SPECT”, may have contributed to the minuscule cardiovascular morbidity and mortality in the years following the index coronary angiography.
Finally, we observed a very low morbidity and mortality rate in women participants during more than 5 years follow up. This result is not in accord with other INOCA studies. For example, the National Heart, Lung, and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation (WISE) study, depicted that the prognosis of patients with INOCA is far from benign. (14) The small number of women in our study, as well as our inability to determine the reason for false positive SPECT scan results (artifacts, INOCA or others) may be the reasons for this discrepancy with previous data.