LVH alters the measurement of cardiac repolarization. Characteristic ECG changes associated with LVH including STE, prominent septal Q waves, T-wave inversion, and ST-segment depression, which may lead to misdiagnosis of acute myocardial infarction 6. The presence of LVH, when associated with STE, has been demonstrated as a risk factor for false-positive ST-segment elevation myocardial infarction diagnoses, commonly leading to unnecessary reperfusion therapy 9–14. Chest pain centers have been built in many countries. Chest pain centers have been shown to shorten the reperfusion therapy time, which is associated with better outcomes for myocardial infarction patients 3. However, in order to shorten the reperfusion time, physicians at chest pain centers often do not have enough time for careful differential diagnosis 12. Previous studies have shown that in the early stages of chest pain center construction, the incidence of false activation of cardiac catheterization laboratory increased, and the occurrence of false activation events was closely related to electrocardiographic LVH 12,14. More seriously, previous publications have shown that LVH with STE is an independent risk factor for misdiagnosing STEMI in patients with aortic dissection 19,20. Aortic dissection is a catastrophic disease with rapid onset, rapid progression, high mortality, and poor natural prognosis 19. Patients with aortic dissection who are misdiagnosed as STEMI will lead to serious consequences 21,22. Therefore, physicians should be keenly aware of the possibility of LVH confounding the ability to recognize true STEMI 6. For patients with STE, physicians need to quickly identify patients with true STEMI for reperfusion treatment, while minimizing misdiagnosis of nonischemic diseases as STEMI to avoid iatrogenic damage. Thus, it is necessary to reduce misdiagnosis by finding a method that can be used to identify STE secondary to LVH and ischemic STE.
However, STEMI guidelines do not define STE diagnostic thresholds for LVH patients. The 2017 ESC Guidelines for the management of acute myocardial infarction indicate that STE is considered suggestive of ongoing coronary artery acute occlusion in the following cases: at least two contiguous leads with STE > 0.1 mV in all leads other than leads V2-V3, where the following cutoff points apply: STE > 0.2 mV in men ≥ 40 years, STE ≥ 0.25 mV in men < 40 years, or STE ≥ 0.15 mV in women [in the absence of LVH or left bundle branch block (LBBB)] 1. The 2013 ACCF/AHA guidelines for the management of STE myocardial infarction define diagnostic STE, in the absence of LVH or left LBBB, as new STE at least 1 mm (0.1 mV) in two or more anatomically contiguous leads (with allowance of up to 1.5 mm (0.15 mV) in leads V2–V3 for women and 2 mm (0.2 mV) in the same leads for men) 23. Interestingly, these guidelines define diagnostic thresholds in the absence of LVH, but the guidelines do not clarify how to diagnose STEMI in the case of LVH, which might result in many unnecessary, potentially dangerous coronary angiographies.
Based on the deficiencies of current clinical guidelines, we need to find more methods to help clinicians make a differential diagnosis. There have been many studies looking for ECG characteristics and clinical features of STEMI patients with LVH to help identify cases of myocardial infarction. For example, a study by Armstrong et al. suggested using a ratio of ST-segment to R-S-wave magnitude ≥ 25% as a diagnostic criteria for STEMI to improve specificity of diagnosis in patients with anterior territory STE 17. However, using these additional ECG diagnostic criteria and clinical features to identify STEMI may reduce the sensitivity of the ECG for STEMI diagnosis. To date, no clinical studies have been performed to identify independent predictors of STE in nonischemic patients with LVH. Therefore, we tried to investigate the risk factors for STE in patients with LVH but without STEMI in order to provide more information for differential diagnosis.
Risk factors for STE After researching the literature, we collected and analyzed common potential risk factors that may affect the ST segment. According to multivariate logistic regression analysis, a value of SV1+RV5 larger than 4.8 mV is an independent risk factor for STE in patients with electrocardiographic LVH. SV1+RV5 is the main indicator of the Sokolow- Lyon standard in diagnosing LVH, which reflects the projection of the largest vector of the left ventricular depolarization on the horizontal plane 6,18. Our study further finds that the value of SV1+RV5 could not only be used to diagnose electrocardiographic LVH, but also that the magnitude of SV1+RV5 is positively correlated with the risk of nonischemic STE. Therefore, LVH patients combined with STE and an elevated SV1+RV5 (larger than 4.8 mV) should be highly suspect for the possibility of secondary nonischemic STE. Conversely, if STE occurs when SV1+RV5 is not significantly elevated (less than 4.8 mV), then STEMI might be considered to avoid misdiagnosis and delaying primary angioplasty. To determine how the SV1+RV5 performs to differentiate between ischemic STE and nonischemic STE secondary to LVH, a threshold of 4.8 mV was chosen by optimizing receiver operating characteristic (ROC) curves. For a patient with an SV1+RV5 larger than 4.8 mV, physicians should be keenly aware of the possibility of nonischemic STE secondary to LVH. Otherwise, STEMI should be considered. The specificity is high (0.8) but the sensitivity is low (0.4) on the ROC curve. Given that missed diagnosis of STEMI could lead to serious consequences, high specificity is needed to minimize the possibility of missed diagnosis. Considering that the magnitude of SV1+RV5 is an additional auxiliary differential diagnosis method, lower sensitivity is acceptable. Therefore, a value of SV1+RV5 greater than 4.8 mV could be used for clinical differential diagnosis and is worth further research.
We also found that stroke is related with the incidence of STE in patients with LVH. Patients with stroke are more likely to have STE, and the incidence of STE is 2.11-fold higher than that without stroke. The mechanism is not clear. We believe this might be related to brain-heart interaction, a group of heart disease secondary to central nervous system disorders, such as stroke 24–26. Previous publications have reported that ECG abnormalities in stroke occur in 70% -80% of cases, and are mainly represented as ST-T abnormalities (including STE) 27–30. In the current study, we found that superimposed stroke based on electrocardiographic LVH results in a significant increase in the incidence of STE.
Previous publications indicate that infection has important effects on the cardiovascular system. That pneumonia is a risk factor for acute cardiac complications has been documented thoroughly in several large cohorts 31,32. Therefore, we included infection as a potential risk factor in the logistic regression analysis. According to the results of the multiple logistic regression analysis, patients combined with infection and electrocardiographic LVH are more prone to STE, and the incidence of STE is increased by 108% compared with non-infected patients. Several mechanisms, related to the systemic response to infection, can account for the ST-T change. Acute inflammation can influence cardiac metabolic supply-to-demand ratio, depress myocardial function and increase left ventricular afterload 32–34.
Given the high incidence of LVH, our findings have important implications. Clinicians need to realize the importance of secondary STE in patients with LVH and exercise appropriate clinical alertness to avoid misdiagnosing non-ischemic STE as ischemic STE. An adequate estimation of the risk of STE secondary to electrocardiographic LVH will require new strategies that adequately weigh clinical factors associated with non-ischemic STE in our study. We found that a value of SV1+RV5 larger than 4.8 mV, stroke, and infectious disease are independent risk factors for STE in patients with LVH. Physicians should be keenly aware of the possibility of nonischemic STE secondly to LVH in patients with an SV1+RV5 larger than 4.8 mV, or combined with infection or stroke to avoid false-positive cardiac catheterization laboratory activation. It should be emphasized that since we have eliminated other factors that may cause ST segment elevation, such as myocardial infarction, the myocardial enzymes in most of the cases we included are normal. Therefore, applying the conclusion of this research to cases with normal myocardial enzymes might have higher specificity.
Limitations First, we analyzed the clinical features of patients with STE caused by LVH to help differential diagnosis. However, we did not explore the clinical features of STEMI with LVH. However, risk factors, such as hypertension, diabetes, hyperlipidemia, and smoking history, have been identified as risk factors for STEMI 1. These risk factors, which have been widely used to identify ischemic STE and STE secondary to LVH in clinical practice, may be important clinical features of STEMI in patients with LVH. Second, we did not collect cardiac ultrasound or magnetic resonance (MR) results from cases of electrocardiographic LVH to verify true LVH on structure 35. However, previous studies have found that electrocardiographic LVH itself, not depending on structural hypertrophy, is a risk factor for misdiagnosis of STEMI 35. Third, there are currently several ECG criteria available for the diagnosis of LVH, including the Sokolow-Lyon standard, Cornell standard, and Gubner-Ungerleider standard. This study only used the Sokolow-Lyon standard to diagnose ECG LVH. However, the Sokolow-Lyon criterion has a higher diagnostic specificity, which is recommended by the guidelines for hypertension 30,36. Fourth, the potential influencing factors we included may not be comprehensive, and there may be other potential influencing factors for ST segment elevation that have not been included and analyzed. However, the factors we analyzed cover common clinical indicators and factors already mentioned in the literature. More importantly, the factors we include in the analysis are easy to obtain, being routine indicators of clinical laboratory tests. Therefore, the potential influencing factors we discussed could be applied to different grades of hospitals, enabling our conclusions to have broader application.