Despite some limitations of our study, to the best of our knowledge, this is the first reported cohort study on the comparisons of five key CDRs for syncope patients in an older Chinese population. Since the number of patients suffering from syncope-related adverse outcomes increases sharply after 60 years , older patients mostly have multiple comorbid conditions, and risk stratification is based on probable short-term adverse outcomes, it is crucial to distinguish non-low-risk patients for further timely precise therapies. We conducted this study to compare our clinical applications of the CDRs for the assessment of older adults with syncope. A total of 171 enrolled patients were followed up for one month and practical adverse outcomes were compared against the ROSE, SFSR, FAINT, CSRS, and BSC CDRs.
Overall, 33.92% of our study cohort had an adverse outcome at one month. The sex was roughly the same (males 83 vs. females 88), but the women were significantly older than the men (p<0.05). Women live longer and pay much more attention to their health care than men . In our exploration, the adverse incidences were affected by the comorbidities of hypertension, CHF, and COPD, as well as the levels of SpO2, BNP, and TnT. In addition, our study also suggested that the levels of haemoglobin and creatinine have potential influences on adverse incidences. SpO2, BNP and haemoglobin are three variables in the ROSE rule, CHF is a variable in the SFSR, FAINT, and BSC rules, and BNP and TnT are two variables in the FAINT rule. In addition, the SFSR, CSRS and BSC rules all emphasize the measurement of blood pressure . However, creatinine has not been involved in any CDRs until now, while the level of creatinine is relevant to inner body fluid metabolism and may affect the body’s circulatory perfusion before syncope.
For the four diagnostic categories for syncope, the number of patients and the adverse incidences were greater in cardiac syncope patients than other patients, which is in accordance with previous studies on advanced age . It seemed that NMS patients had sex-specific and age-related differences in the incidence of adverse events, but CS patients suggested no similar results. Compared with CS, NMS is a kind of benign syncope, and neural regulation has differences between sexes and ages, while CS is a serious symptom with high mortality, so the syncope type itself has its own characteristics and clinical prognosis [23–25]. In the research, more than half of the adverse incidences in one month were relevant to AMI and arrhythmia. Cardiac syncope is associated with higher mortality, irrespective of age and sex. Thus, the five CDRs in our investigation all included cardiac elements in their assessments and highlighted the significance of cardiogenic parameters, which reflects the importance of cardiac syncope in the elderly population.
The ROSE and SFSR rules showed higher specificities and NPVs, and AUC areas were greater than 0.8, which meant that they had significance in identifying and screening non-high-risk syncope patients, which was roughly consistent with the previous clinical studies of each CDR [9–10]. In addition, the kappa coefficients for the concordance of these two CDRs with short-term adverse events were greater than 0.7, which suggests more reliable consistency. The AUC areas of the FAINT, FAINT2, CSRS, and BSC rules were all greater than or approximately 0.7. The FAINT and BSC rules had higher sensitivities and NPVs than the other rules, while the CSRS rule had moderate results in our clinical applications. It seemed that the FAINT and BSC rules had advantages in identifying high-risk syncope patients. The BSC rule has included the most comprehensive elements for syncope assessment until now, indicating high risk if any one item is positive. The kappa coefficient of the BSC rule was greater than 0.6, which suggests substantial consistency. The CSRS rule assigns various points to each of the factors based on the relative magnitude of the coefficient, and its external validation in an Australian cohort of 283 patients was completed in 2020, so larger and more widespread clinical applications are needed in the future. The kappa coefficient of the CSRS rule was close to 0.5, which suggests moderate consistency.
The FAINT rule was set up for elderly patients in 2020, and the preliminary results of the recent multicentre external validation in Europe and the US suggest that it is safe to evaluate elderly patients with scores of 0 or 1 . The cut-off value of "1" was used in the original study for patient evaluation analysis, which means that 24 patients were “misjudged” as positive in our study if the cut-off score was 1, which may cause a higher proportion of low-risk patients to spend more money on further clinical examinations. Therefore, we additionally set “2” as another cut-off score for evaluation by the FAINT rule (FAINT2) to make the comparison with short-term prediction for elderly patients. Our FAINT results indicated that the sensitivity and NPV were higher and the specificity was lower, which was consistent with the original studies by Probst . On the other hand, the results of the FAINT2 rule indicated that the specificity and PLR were higher and the sensitivity was lower. The areas of both AUCs were higher than 0.6, while the area and accuracy of the FAINT2 rule were slightly higher. The kappa coefficients of the FAINT and FAINT2 rules were both greater than 0.5, indicating moderate consistency. In that case, what is the significance of original research on the FAINT rule to improve the evaluation sensitivity at the expense of specificity? Considering that the proportion of cardiac syncope in elderly patients is higher, its complications are more dangerous when it occurs. The higher sensitivity of the FAINT rule may avoid the possibility of missing adverse events at best, but it requires more relevant medical resources, so the FAINT rule may be much more valuable for elderly people who have any history of cardiovascular diseases under the condition of sufficient medical resources. Probst gave a deep explanation of the original exploration: The FAINT rule sets no serious adverse cardiac events’ omission as the main point, so its high sensitivity and low NLR were the original intentions of the study. However, this rule is not suitable for screening low-risk patients at present since international multicentre validation has not been completed. As we know, the FAINT rule has been evaluated in a clinical study of elderly syncope patients with the largest sample size until now, but the population included patients aged 60 years and above with syncope or near syncope (the sensation of the impending loss of consciousness without the actual loss of it), and the patient refusal rate was as high as 53.2% when the study was implemented, which could be a kind of sample bias. The FAINT rule includes two biochemical elements relevant to cardiac function and myocardial damage. Compared with the ROSE rule, which includes only BNP levels, and the SFSR rule without biochemical elements, the FAINT rule certainly improves the laboratory work and medical cost, but it is helpful to reduce the diagnosis rate of "unexplained syncope" in clinics, so its net effect analysis in health economics is worth further exploration in the future. At the same time, the FAINT rule is much simpler than the CSRS and BSC rules to use in assessments. These five rules all showed the assessment values for elderly syncope patients in practice. To date, there is still no syncope risk stratification rule that can be used independently of physician judgement, and it only plays a role in assisting judgement and decreasing the cognitive load for physicians when making clinical decisions.
Overall, the proportion of one-month adverse incidences in our study was 33.92%. It was higher than that reported in the original studies of the ROSE, SFSR, FAINT, CSRS and BSC rules, but similar to that reported in other studies [26–27]. The discrepancy between the proportion of short-term adverse events was relevant to the different levels of public health services and disease preventive abilities in the cohort population. Additionally, it was related to the characteristics of the enrolled patients: the median age of the elderly patients in this study was 75 years, and 69.59% of them were over 70 years, whose incidence of adverse events was higher than that of patients aged 60-69 years (38.66% vs. 23.08%). The incidence of syncope in the elderly population generally increases with age, but the body is in a declining stage as it ages, so the physiological stress response after syncope may be partly damaged, and the complications could be more complex, which leads to the risks of adverse events being much higher [6, 28–31]. Moreover, the original FAINT study included "near syncope" patients whose clinical risk status was relatively low.
Our study was conducted at a single centre with limited resources. First, the international multicentre external validation of the FAINT and CSRS rules is still in progress. Larger sample sizes and multicentre data will certainly result in better assessments of the current risk rules. Second, the well-designed prospective study will be worthy of further exploration of its clinical significance based on previous retrospective work. Third, the confounders used in the risk stratification may not have been inclusive of all causes or influencing factors of syncope. For example, creatinine could possibly have influenced the adverse incidences in our study, which needs further investigation in the future. Fourth, we did not collect information regarding secondary diagnoses when syncope patients arrived at the emergency department, and these data may be useful in further clarifying outcomes among patients. These limitations are expected to be improved in future research.