Abstract
Objective
The aim of this study is to examine the probability of de-novo fQRS in patients with mild COVID-19 disease, as an indicator of cardiac injury.
Methods
Data of 256 patients with normal admission electrocardiography and no comorbidities between 1.12.2020–31.12.2021, were examined retrospectively 6-month after mild COVID-19 disease. Patients were divided into two groups: fQRS+ group (n = 102) and non-fQRS group (n = 154). Relation between fQRS and other electrocardiography, echocardiographic and laboratory findings were investigated.
Results
No significant difference was found between the groups among age and gender. Troponin-I and creatine kinase myocardial band values (retrospectively 9.10 ± 1.76 vs 0.74 ± 1.43, 34.05 ± 82.20 vs. 14.68 ± 4.42), COVID-19 IgG levels (45.78 ± 14.82 vs. 36.49 ± 17.68), diastolic dysfunction (39.21% vs. 15.07%), EF value (58.02 ± 1.95 vs. 64.27 ± 3.07), dyspnea (41.17% vs. 6.84%), post-COVID-19 tachycardia syndrome (19.6% vs. 2.74) were more frequent in fQRS+ group compared to non-fQRS group. The EF value was lower in the presence of fQRS in the high lateral leads (57.12 ± 1.99, 58.47 ± 1.79, p:0.018). There was a positive correlation between IgG value and endsystolic diameter, septum thickness and left atrium diameter. In multivariate analysis de-novo fQRS, dyspnea, high troponin and IgG values, diastolic dysfunction, low EF value and left atrial diameter were determined as independent risk factors for post-COVID-19 tachycardia syndrome in follow-up.
Conclusion
In COVID-19 disease de-novo fQRS, dyspnea, high IgG and troponin value, left atrial diameter, lower EF value, diastolic dysfunction were associated with post-COVID-19 tachycardia syndrome. The de-novo fQRS in SARS-COV-2 may be a predictor of future more important adverse cardiovascular outcomes and this should alert clinicians.
Keywords: Cardiac injury, COVID-19, Ejection fraction, Fragmented QRS (fQRS), Post-COVID-19 tachycardia syndrome
Introduction
Coronavirus disease 2019 (COVID-19) is an important health problem since 2019. Angiotensin converting enzyme 2 (ACE2) has a strong binding affinity to the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) [1]. ACE2 is found in the heart and vessels as well as in the lung tissue. It is assumed that the virus causes heart damage through ACE2 [1]. Acute cardiac injury, defined as serum troponin elevation is detected extensively among patients hospitalized due to COVID-19 in Wuhan and is linked with higher mortality rates in hospitalized patients [2]. Cardiac injury occurs in approximately 8–12% of all hospitalized patients [3]. Direct myocardial injury and systemic inflammation due to viral involvement of cardiomyocytes are the most common mechanisms responsible for cardiac injury [1,4,5]. As we know, no study published so far has examined the development of de-novo fragmented QRS (fQRS) in follow-up in COVID-19 patients. Our study will be the first study in the literature. QRS fragmentation is defined as: the presence of an additional wave like RSR’ pattern in <120 ms duration of QRS complex, or the existence of notched S or R waves without any bundle branch block [6]. fQRS is an electrocardiographic sign of myocardial scar tissue, that explain the nonhomogeneous ventricular conduction delay of injured and/or ischemic ventricular myocardium [7]. fQRS has been associated with coronary artery disease severity, mortality, development of heart failure and arrhythmias.[8,9] fQRS development in COVID-19 patients was taken as an indicator of cardiac injury. In our study, the possibility of occurrence of de-novo fQRS in outpatients without any comorbidities, the relationship between fQRS and SARS-CoV-2 immunoglobulin G (IgG) and other laboratory, electrocardiography and echocardiographic findings were investigated. The aim of this study is to examine the probability of de-novo fQRS in patients with mild COVID-19 disease, as an indicator of cardiac injury.
Method
The data of 256 patients who were admitted to the outpatient clinic of our hospital between December 1, 2020 and December 31, 2021 and had SARS-CoV-2 real-time RT-PCR method (PCR) positive with mild symptoms, not hospitalized, with normal admission electrocardiography (ECG) and no comorbidities were examined retrospectively six months after COVID-19 disease. The history and physical examination information of the patients were recorded. Patients symptoms: cough, fever, dyspnea, chest pain, weakness, loss of taste, loss of smell were recorded. All patients were screened consecutively for post-COVID-19 tachycardia sendrom. Inclusion criteria for the study: Outpatient treatment with COVID-19 PCR positive test results, between the ages of 18–60, without any comorbidity, no previous drug use, without any pathology in admission ECG. Patients laboratory, ECG and echocardiographic data were examined six months after the diagnosis of COVID-19 disease. Exclusion criteria for the study: patients who were hospitalized with a diagnosis of moderate-to-severe viral pneumonia with COVID-19 PCR positive test results, patients with any comorbidities, patients with fQRS or any pathological findings in their admission ECG.
The study complies with the Declaration of Helsinki. We confirm that all methods were carried out in accordance with relevant guidelines and regulations. This retrospective study was approved by Ministry of Health (No. 2021–01-14T12_55_03) as well as Non-Interventional Clinical Research Ethics Committee (No. 2021/47–03).
Laboratory processes
2 ml of venous blood from patients were collected between December 1, 2020 and December 31, 2021. We used an immunofluorescence assay (IFA), using COVID-19 IgG antibody IFA fast test kits (IF2084 for Getein 1600, Getein Biotech, Inc. Nanjing, China), to evaluate the presence of serum IgG antibody against SARS-CoV-2. The test result is displayed numerically in terms of cut-off index (COI) value. Test result is negative if COI is <1.0 and positive if COI is ≥1.0.
Electrocardiographic evaluation
A 12 lead admission ECG was obtained from each patient before any treatment was started. Also six months later ECGs were obtained. ECGs were analyzed by two independent cardiologists according to the modified Minnesota criteria [8]. Presence of fQRS, length of QTc, QT dispersion and PR dispersion were measured. Myocardial regions on ECG was named as; anterioseptum (V1–4), anterolateral (V4–6), high lateral (DI, aVL), inferior (DII, DIII, aVF).
Echocardiographic data
Left ventricular ejection fraction (EF) determined with Simpson's method, diastolic dysfunction, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left atrial diameter, back wall and septum thickness were measured.
Definitions
Post-COVID-19 tachycardia syndrome include postural orthostatic tachycardia syndrome or inappropriate sinus tachycardia. A 30 bpm increase in heart rate within the first ten minutes of head-up TILT test or active standing test, without concomitant blood pressure drop and with aggravation of symptoms, is defined as postural orthostatic tachycardia syndrome [9]. Inappropriate sinus tachycardia is defined as on 24-h ECG monitoring average heart rate exceeding 90 bpm or resting heart rate > 100 bpm [9]. The presence of additional wave like RSR’ pattern in <120 ms duration of fQRS complex, or the existence of notched S or R waves without any bundle branch block (Figure 1 .) has been defined as QRS fragmentation [6]. According to WHO interim guidance, the definitive diagnosis of COVID-19 is based on real-time RT-PCR test.
Fig. 1.
Fragmented QRS morphology.
Statistical analysis
Kolmogorov–Smirnov method was used to analyze all data and fit to a normal distribution.
Chi-square test method was used to analyze categorical variables that are presented as percentages. t-test method was used to analyze continues variables in two-way groups, presented as mean ± standard deviation. Pearson's correlation was used for the numerical data. Statistically significant variables were selected into the multivariate logistic regression analysis using the stepwise method. The results of multivariate regression analyses were presented as odd ratio (OR) with 95% confidence interval (CI). SPSS 20.0 (SPSS, Chicago, IL, USA) software was used, and p < 0.05 were considered as statistically significant.
Results
Table 1. shows the demographic characteristics and symptom findings of our study. There was no significant difference in mean age between groups with and without fQRS (respectively 36.47 ± 8.72, 33.64 ± 9.22, p: 0.085). Also, there was no statistical difference between the groups in terms of gender (p:0.583). Smoking rate was higher in the fQRS+ group (p: 0.006). When we looked at the symptoms of COVID-19 disease, it was found that the possibility of occurrence of fQRS was statistically higher in patients with dyspnea and fatigue (respectively p < 0.001 and p: 0.033). There was no statistical significance between the two groups in terms of other disease symptoms. When we look at the localization of fQRS in ECG, it was observed that it most frequently occurs in inferior leads. Possibility of occurrence of fQRS in the anterior leads is 29.4% p < 0.001, in the anterolateral leads is 2% p:0.398, in the high lateral leads is 33.3% p < 0.001, in inferior leads is 54.9% p < 0.001.
Table 1.
Relation between demographic characteristics, symptoms and de-novo fQRS of the study population.
| Demographic characteristics and symptoms | All patients (n: 248, %) | fQRS (+) (n: 102, %) | non - fQRS (n: 146, %) | P |
|---|---|---|---|---|
| Age (years) | 35.05 ± 8.97 | 36.47 ± 8.72 | 33.64 ± 9.22 | 0.085 |
| Gender (female) | 154 (62.09) | 58 (56.86) | 96 (65.75) | 0.583 |
| Smoking | 62 (25) | 38 (37.3) | 24 (16.43) | 0.006 |
| Cough | 18 (7.25) | 4 (3.92) | 14 (9.58) | 0.315 |
| Fever | 46 (19.35) | 16 (15.68) | 30 (20.54) | 0.645 |
| Joint Pain | 76 (30.64) | 28 (27.45) | 48 (32.87) | 0.697 |
| Fatigue | 78 (31.45) | 20 (19.6) | 58 (39.72) | 0.033 |
| Chest pain | 24 (9.67) | 14 (13.72) | 10 (6.8) | 0.219 |
| Dyspnea | 52 (20.96) | 42 (41.17) | 10 (6.84) | <0.001 |
| Taste abnormalities | 74 (29.83) | 36 (35.29) | 38 (26.02) | 0.234 |
| Smell abnormalities | 66 (26.61) | 36 (35.29) | 30 (20.54) | 0.063 |
The sixth month laboratory values are summarized in Table 2 . The troponin and creatine kinase myocardial band (CK-MB) value was found to be significantly higher in the fQRS+ group (respectively 9.10 ± 1.76 vs. 0.74 ± 1.43, p:0.001, 34.05 ± 82.20 vs. 14.68 ± 4.42, p:0.041). In addition, as an indicator of disease severity, it was observed that COVID-19 IgG antibody level was statistically significant higher in the fQRS+ group (respectively 45.78 ± 14.82, 36.49 ± 17.68, p:0.004). D-dimer value was higher in fQRS+ group, but it was not statistically significant. There was no significant difference between the two groups in terms of other laboratory data.
Table 2.
Relationship between sixth month laboratory values and de-novo fQRS.
| Laboratory values | fQRS (+) | non - fQRS | P |
|---|---|---|---|
| Troponin (pg/mL) | 9.10 ± 1.76 | 0.74 ± 1.43 | 0.001 |
| CK⁎ (U/L) | 222.57 ± 668.64 | 89.96 ± 121.48 | 0.091 |
| CK-MB# (U/L) | 34.05 ± 82.20 | 14.68 ± 4.42 | 0.041 |
| Covid-19 IgG antibody† (CO/I) | 45.78 ± 14.82 | 36.49 ± 17.68 | 0.004 |
| CRP‡ (mg/L) | 2.24 ± 0.905 | 2.21 ± 0.57 | 0.843 |
| Ferritin (ng/mL) | 76.25 ± 58.16 | 67.34 ± 159.55 | 0.367 |
| Urea (ng/dL) | 24.25 ± 9.53 | 23.17 ± 5.60 | 0.400 |
| Creatinine (mg/dL) | 0.72 ± 0.09 | 0.73 ± 0.11 | 0.409 |
| AST§ (U/L) | 19.94 ± 11.19 | 20.34 ± 8.16 | 0.818 |
| ALT⁎⁎ (U/L) | 23.57 ± 15.38 | 22.43 ± 13.29 | 0.656 |
| LDH## (U/L) | 170.65 ± 37.06 | 168.92 ± 28.84 | 0.768 |
| Leukocyte (K/uL) | 35.25 ± 9.32 | 36.68 ± 7.88 | 0.351 |
| Neutrophil (%) | 53.60 ± 10.84 | 52.02 ± 8.48 | 0.368 |
| Haematocrite (%) | 49.38 ± 58.92 | 41.85 ± 2.88 | 0.264 |
| Haemoglobin (g/dL) | 16.09 ± 14.60 | 13.55 ± 1.20 | 0.131 |
| D-dimer (ng/mL) | 95.77 ± 125.03 | 65.69 ± 97.54 | 0.130 |
Abbreviations: ⁎CK: creatine kinase; #CK-MB: creatine kinase myocardial band; †Covid-19 IgG antibody: Covid-19 immunoglobulin G antibody; ‡CRP: C-reactive protein; §AST: aspartate aminotransferase; ⁎⁎ALT: alanine aminotransferase; ##LDH: lactate dehydrogenase.
Table 3. shows the echocardiographic and electrocardiographic findings among the groups in the sixth month. The EF value was statistically significant lower in the fQRS+ group compared to the non-fQRS group (respectively 58.02 ± 1.95, 64.27 ± 3.07, p < 0.001). Also the diastolic dysfunction was more frequent in fQRS+ group (39.21% vs. 15.07%, p:0.01). Presence of fQRS was related also with wider: end-diastolic diameter (46.21 ± 3.73, 44.13 ± 3.18, p:0.039), end-systolic diameter (31.32 ± 3.32, 29.39 ± 2.70, p:0.03), septum thickness (9.82 ± 0.863, 9.04 ± 1.26, 0.012), and left atrium diameter (35.07 ± 2.61 vs 32.22 ± 2.64, p < 0.001). The prevalence of post-COVID-19 tachycardia syndrome in the sixth month was 9.67% (in fQRS+ group 19.6%, in non-fQRS group 2.74%, p < 0.001). There was no significant difference between the groups for other parameters.
Table 3.
Echocardiographic and electrocardiographic findings in the sixth month.
| fQRS (+) | non - fQRS | P | |
|---|---|---|---|
| Ejection fraction (EF) (%) | 58.02 ± 1.95 | 64.27 ± 3.07 | <0.001 |
| Diastolic Dysfunction (n, %) | 40 (39.21%) | 22 (15.07%) | 0.01 |
| End-diastolic diameter (mm) | 46.21 ± 3.73 | 44.13 ± 3.18 | 0.039 |
| End-systolic diameter (mm) | 31.32 ± 3.32 | 29.39 ± 2.70 | 0.03 |
| Septum thickness (mm) | 9.82 ± 0.863 | 9.04 ± 1.26 | 0.012 |
| Back wall thickness (mm) | 9.31 ± 1.06 | 9.36 ± 0.97 | 0.785 |
| Left atrium diameter (mm) | 35.07 ± 2.61 | 32.22 ± 2.64 | <0.001 |
| Post-COVID-19 tachycardia syndrome (n, %) | 20 (19.6%) | 4 (2.74%) | <0.001 |
| QTc (s) | 0.406 ± 0.023 | 0.402 ± 0.023 | 0.309 |
| QT dispersion (s) | 0.369 ± 0.027 | 0.360 ± 0.029 | 0.094 |
| PR dispersion (s) | 0.159 ± 0.144 | 0.142 ± 0.018 | 0.332 |
When we look at the fQRS localization, the EF value was found to be significantly lower in the presence of fQRS in the high lateral ECG leads (57.12 ± 1.99, 58.47 ± 1.79, p: 0.018). There was no significant relationship between the presence of fQRS in other derivations and the EF value.
There was a positive correlation between IgG value and end-systolic diameter, septum thickness and left atrium diameter (respectively r: 0.337 and p < 0.001, r: 0.227 and p:0.013, r: 0.248 and p:0.007).
Predictors of post-COVID-19 tachycardia syndrome were analyzed by logistic regression analysis (Table 4 ). In multivariate analysis de-novo fQRS, dyspnea, high troponin and IgG values, high diastolic dysfunction, low EF value and left atrial diameter were determined as independent risk factors for post-COVID-19 tachycardia syndrome in follow-up.
Table 4.
Multivariate logistic regression analysis on risk factors associated with post-COVID-19 tachycardia syndrome.
| OR | 95% C·I for OR |
p | ||
|---|---|---|---|---|
| Lower | Upper | |||
| De-novo fQRS | 0.999 | 0.998 | 1.000 | 0.007 |
| Dyspnea | 2.244 | 1.192 | 4.234 | 0.048 |
| Troponin | 1.041 | 1.009 | 1.074 | 0.022 |
| COVID-19 IgG levels | 1.957 | 1.122 | 4.525 | 0.001 |
| Diastolic Dysfunction | 1.766 | 1.109 | 2.917 | 0.009 |
| Ejection Fraction | 0.831 | 0.754 | 0.914 | 0.003 |
| Left atrial diameter | 1.875 | 1.099 | 2.657 | 0.023 |
Abbreviations: C·I: Confidence interval.
Discussion
It has been found that ACE-2 receptors in human cells have a strong binding affinity to the spike protein of SARS-CoV-2 [6]. It is assumed that the cardiac injury associated with SARS-CoV-2 is caused by the high rate of ACE-2 receptors in the heart [1]. It is reasonable to assume that the heart injury caused by COVID-19 could be mediated by ACE-2. Infection of the secretory cell population in the bronchial branches is not only affected by ACE-2 expression; potential cofactors such as proteases, TMPRSS2 and furin are also known to affect this process [5]. However, it is not known how these proteases and SARS-Cov-2 affect heart cells and what kind of damage they cause.
In many studies, the high level of “high sensitivity troponin” or the occurrence of new abnormalities in electrocardiography or echocardiography have been defined as indicators of cardiac injury. Acute myocardial injury due to COVID-19 infection contributes to the development of cardiovascular complications such as acute coronary syndrome, myocarditis, cardiomyopathy, arrhythmia, cardiogenic shock or cardiac arrest. Six month after mild COVID-19 disease we examined the probability of occurrence of de-novo fQRS, as an indicator of cardiac injury, also its relationship with laboratory, electrocardiography and echocardiography data. ECG is usually used as noninvasive test for cardiovascular system disease in which fQRS can be easily detected. We observed that among the laboratory data examined six month later, patients with high troponin, CK-MB and IgG values were found to be more likely to develop fQRS. High troponin and CK-MB value shows cardiac injury. There was a positive correlation between IgG value and end-systolic diameter, septum thickness and left atrium diameter. When we scan the literature information, the relationship between IgG and fQRS is emphasized for the first time in our study. In our study, the presence of fQRS, which is an indicator of myocardial fibrosis, and enlargement in the heart cavities, besides high troponin and CK-MB values was determined as an indicator of cardiac injury in patients with high IgG values, which is an indicator that the COVID-19 disease was more severe. To detecting myocardial fibrosis, we can use expensive methods such as biochemical, echocardiographic and radiological [10]. A recent study showed that fQRS was useful in predicting scar areas detected by magnetic resonance imaging [11]. fQRS can be easily detected from routine ECG recordings and shows myocardial fibrosis. In coronary artery disease and acute coronary syndromes, fQRS was found to be associated with high mortality and arrhythmic events [12]. In fQRS group mortality rate was related with larger infarcts areas and left ventricular dysfunction [12]. In another study with COVID-19 patients, fQRS was found to be more frequently in sever group, especially in inferior leads [13]. The presence of fQRS was found to be more frequently in patients with myocardial injury [13].
There was no significant difference found between the groups with and without fQRS between age and gender in our study. When we look at the symptoms, the possibility of occurrence of fQRS was found to be higher in patients with dyspnea and fatigue. Similar to our study the presence of narrow fQRS was associated with worsening New York Heart Association (NYHA) symptom status [14]. Also the relation between fQRS and NYHA symptom status was examined in mitral stenosis, and fQRS was found to be correlated with poor functional NYHA symptom status [15].
In our study, diastolic dysfunction, lower EF value, enlargement in heart cavity was found to be significant in fQRS+ group. LVEF was slightly lower in fQRS group but still in normal range. It was thouth to be due to the low scar burden. But percentage of scar tissue in patients with tachicardia coud not be determined clearly, since we did not have any patients who accepted to have cardiac MRI. As we know fQRS is an electrocardiographic sign of myocardial scar tissue, that explain the nonhomogeneous ventricular conduction delay [7]. In ischemic heard disease (IHD), the presence of fQRS was found to be an independent predictor of left ventricular (LV) dilatation, decreased ejection fraction and myocardial perfusion [[16], [17], [18]]. In patients with non-ischemic or ischemic cardiomyopathy fQRS was also able to predict arrhythmic events [19,20]. In patients with ischemic cardiomyopathy (ICM) fQRS was demonstrated to be an independent predictor of sudden cardiac death (SCD) risk [21]. In another study, fQRS was found to have a predictive value for ventricular arrhythmias and all-cause mortality in patients with dilated cardiomyopathy (DCM) (EF ≤40%) [22].
We found that in COVID-19 patients the probability of occurrence of de-novo fQRS was higher in inferior leads. Especially the presence of fQRS in the high lateral leads was associated with lower EF. In other study, presence of fQRS in inferior leads was found to be an independent predictor for SCD in patients with ischemic and dilated cardiomyopathy [21].
Patients with post-acute COVID-19 syndrome have a wide variety of symptoms such as fatigue, chest pain, decreased exercise tolerance, cognitive impairment, shortness of breath, fever, headache, loss of smell and taste, but rapid heartbeat and palpitations are typical and common complaints [23]. The persistence of these symptoms 4–12 or more then 12 weeks is defined as post-acute COVID-19 syndrome [24]. Approximately 25–50% of post-acute COVID-19 syndrome patients report tachycardia and/or palpitations 12 weeks or longer. In post-acute COVID-19 syndrome, tachycardia may occur as postural orthostatic tachycardia syndrome or inappropriate sinus tachycardia. The authors suggest labeling this condition as “Post-COVID-19 tachycardia syndrome” [25]. In our study we observed that post-COVID-19 tachycardia syndrome occurs 9.67% after 6 months, mostly in fQRS+ group (19.6%). Similar to out study, systematic studies show that 9% of patients with post-acute COVID-19 syndrome report palpitations at six months [23]. Postural orthostatic tachycardia syndrome is characterized by autonomic dysfunction that causes various symptoms such as tachycardia following postural change [9]. It has been previously documented that viral infections can trigger postural orthostatic tachycardia syndrome [26]. The pathophysiological mechanism in postural orthostatic tachycardia syndrome remains unclear. However, evidence of autoimmunity, i.e. the presence of autoantibodies that activate adrenergic and muscarinic receptors [27], hyperadrenergic state [28], similar to loss of taste and smell, peripheral denervation [29] and deconditioning, causing blood pooling in the lower extremities and reflex tachycardia [9] can cause postural orthostatic tachycardia syndrome. It has not been established whether the same mechanisms are responsible for the postural orthostatic tachycardia syndrome and to what extent they contribute to the post-acute COVID-19 syndrome. Inappropriate sinus tachycardia is defined as on 24-hour ECG monitoring mean heart rate exceeding 90 bpm or resting heart rate > 100 bpm [9]. It includes a gain-of-function mutation in the hyperpolarization-activated and cyclic nucleotide-gated (HCN4) channel [30] of the cardiac pacemaker, heart intrinsic sinus node abnormality, autoimmunity, excessive sympathetic activation or vagal retraction [31] In addition to the direct and indirect damage caused by viral infection, there may be other mechanisms contributing to the post-COVID-19 tachycardia syndrome. For example: (i) Persistent lung injury or exacerbation of underlying lung disease that causes desaturation and reflex tachycardia [32], (ii) persistent or intermittent fever that may increase heart rate [33], (iii) pain, (iv) anxiety and depression [33], (v) neuroinflammation and (vi) hypovolemia [33]. We also observed that de-novo fQRS, dyspnea, high troponin and IgG values, high diastolic dysfunction, low EF value and left atrial diameter were determined as independent risk factors for post-COVID-19 tachycardia syndrome in follow-up. Given the novelty of the disease and the lack of basic and clinical data, several unknown mechanisms may also play a role in the post-COVID-19 tachycardia syndrome. Tachycardia can be considered as universal and readily available quantitative marker of severity for post-acute COVID-19 syndrome.
Limitations of our study
Since this is a retrospective and single-center study, the number of our patients is low and there is no long-term follow-up, the possibility of more serious morbidity in patients who develop de-novo fQRS and its relation with other mortalities is not known clearly. If the number of patients had been higher, we might have seen a higher tachycardia rates perhaps in non-fQRS group. Therefore, large studies are required.
Conclusion
De-novo fQRS in the sixth month was found to be an independent risk factor to determine post-COVID-19 tachycardia syndrome. The de-novo fQRS in SARS-COV-2 may be a predictor of future more important adverse cardiovascular outcomes and this should alert clinicians.
Acknowledgments
We would like to thank Gülşah Özel for entering the data.
References
- 1.Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Shi S., Qin M., Shen B., Cai Y., Liu T., Yang F., et al. Association of Cardiac Injury with Mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020 Jul 1;5(7):802–810. doi: 10.1001/jamacardio.2020.0950. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Bansal M. Cardiovascular disease and COVID-19. Diabetes Metab Syndr. 2020 May-Jun;14(3):247–250. doi: 10.1016/j.dsx.2020.03.013. Epub 2020 Mar 25. PMID: 32247212; PMCID: PMC7102662. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Chen C., Chen C., Yan J.T., Zhou N., Zhao J.P. Wang DW. Analysis of myocardial injury in patients with COVID-19 and association between concomitant cardiovascular diseases and severity of COVID-19. Zhonghua Xin Xue Guan Bing Za Zhi. 2020 Jul 24;48(7):567–571. doi: 10.3760/cma.j.cn112148-20200225-00123. Chinese. PMID: 32141280. [DOI] [PubMed] [Google Scholar]
- 5.Lukassen S., Chua R.L., Trefzer T., Kahn N.C., Schneider M.A., Muley T., et al. SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J. 2020 May 18;39(10) doi: 10.15252/embj.20105114. Epub 2020 Apr 14. PMID: 32246845; PMCID: PMC7232010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Das M.K., Khan B., Jacob S., Kumar A., Mahenthiran J. Significance of a fragmented QRS complex versus a Q wave in patients with coronary artery disease. Circulation. 2006 May 30;113(21):2495–2501. doi: 10.1161/CIRCULATIONAHA.105.595892. Epub 2006 May 22. PMID: 16717150. [DOI] [PubMed] [Google Scholar]
- 7.Guo R., Li Y., Xu Y., Tang K., Li W. Significance of fragmented QRS complexes for identifying culprit lesions in patients with non-ST-elevation myocardial infarction: a single-center, retrospective analysis of 183 cases. BMC Cardiovasc Disord. 2012 Jun 19;12:44. doi: 10.1186/1471-2261-12-44. PMID: 22712769; PMCID: PMC3467167. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Prineas R.J., Crow R.S., Zhang Z.-M. Springer Science & Business Media; 2009. The Minnesota code manual of electrocardiographic findings. [Google Scholar]
- 9.Fedorowski A. Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management. J Intern Med. 2019;285(4):352–366. doi: 10.1111/joim.12852. [DOI] [PubMed] [Google Scholar]
- 10.Homsi M., Alsayed L., Das M.K., Mahenthiran J. Fragmented QRS complexes on a 12-lead ECG is a marker of greater myocardial scarring related to coronary artery disease by magnetic resonance imaging. J Am Coll Cardiol. 2008;51:A31. [Google Scholar]
- 11.Das M.K., Maskoun W., Shen C., Michael M.A., Suradi H., Desai M., et al. Fragmented QRS on twelve-lead electrocardiogram predicts arrhythmic events in patients with ischemic and nonischemic cardiomyopathy. Heart Rhythm. 2010 Jan;7(1):74–80. doi: 10.1016/j.hrthm.2009.09.065. Epub 2009 Oct 2. PMID: 20129288. [DOI] [PubMed] [Google Scholar]
- 12.Stavileci B., Cimci M., Ikitimur B., Barman H.A., Ozcan S., Ataoglu E., et al. Significance and usefulness of narrow fragmented QRS complex on 12-lead electrocardiogram in acute ST-segment elevation myocardial infarction for prediction of early mortality and morbidity. Ann Noninvasive Electrocardiol. 2014 Jul;19(4):338–344. doi: 10.1111/anec.12133. Epub 2014 Feb 12. PMID: 24517503; PMCID: PMC6932680. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Barman H.A., Atici A., Alici G., Sit O., Tugrul S., Gungor B., et al. The effect of the severity COVID-19 infection on electrocardiography. Am J Emerg Med. 2020 Oct 7 doi: 10.1016/j.ajem.2020.10.005. S0735-6757(20)30889-5. Epub ahead of print. PMID: 33059987; PMCID: PMC75. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Ozcan S., Cakmak H.A., Ikitimur B., Yurtseven E., Stavileci B., Tufekcioglu E.Y., et al. The prognostic significance of narrow fragmented QRS on admission electrocardiogram in patients hospitalized for decompensated systolic heart failure. Clin Cardiol. 2013 Sep;36(9):560–564. doi: 10.1002/clc.22158. Epub 2013 Jun 10. PMID: 23754185; PMCID: PMC6649522. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Yuce M., Davutoglu V., Ozbala B., Ercan S., Kizilkan N., Akcay M., et al. Fragmented QRS is predictive of myocardial dysfunction, pulmonary hypertension and severity in mitral stenosis. Tohoku J Exp Med. 2010 Apr;220(4):279–283. doi: 10.1620/tjem.220.279. PMID: 20383039. [DOI] [PubMed] [Google Scholar]
- 16.Michael M.A., El Masry H., Khan B.R., Das M.K. Electrocardiographic signs of remote myocardial infarction. Prog Cardiovasc Dis. 2007 Nov-Dec;50(3):198–208. doi: 10.1016/j.pcad.2007.05.003. PMID: 17976504. [DOI] [PubMed] [Google Scholar]
- 17.Mahenthiran J., Khan B.R., Sawada S.G., Das M.K. Fragmented QRS complexes not typical of a bundle branch block: a marker of greater myocardial perfusion tomography abnormalities in coronary artery disease. J Nucl Cardiol. 2007 May-Jun;14(3):347–353. doi: 10.1016/j.nuclcard.2007.02.003. Epub 2007 Apr 16. PMID: 17556169. [DOI] [PubMed] [Google Scholar]
- 18.Flowers N.C., Horan L.G., Thomas J.R., Tolleson W.J. The anatomic basis for high-frequency components in the electrocardiogram. Circulation. 1969 Apr;39(4):531–539. doi: 10.1161/01.cir.39.4.531. PMID: 5778254. [DOI] [PubMed] [Google Scholar]
- 19.Jose F., Krishman M. Fragmanted QRS electrocardiogram-the hidden talisman? Indian Pacing Electrophysiol J. 2009;5:238–240. [PMC free article] [PubMed] [Google Scholar]
- 20.Das M.K., Zipes D.P. Role of the fragmented QRS complexes on a routine 12-lead ECG in predicting mortality and sudden cardiac death. Rev Argent Cardiol. 2010:5–10. [Google Scholar]
- 21.Pei J., Li N., Gao Y., Wang Z., Li X., Zhang Y., et al. The J wave and fragmented QRS complexes in inferior leads associated with sudden cardiac death in patients with chronic heart failure. Europace. 2012 Aug;14(8):1180–1187. doi: 10.1093/europace/eur437. Epub 2012 Feb 2. PMID: 22308082. [DOI] [PubMed] [Google Scholar]
- 22.Sha J., Zhang S., Tang M., Chen K., Zhao X., Wang F. Fragmented QRS is associated with all-cause mortality and ventricular arrhythmias in patient with idiopathic dilated cardiomyopathy. Ann Noninvasive Electrocardiol. 2011 Jul;16(3):270–275. doi: 10.1111/j.1542-474X.2011.00442.x. PMID: 21762255; PMCID: PMC6932517. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Huang C., Huang L., Wang Y., Li X., Ren L., Gu X., et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397(10270):220–232. doi: 10.1016/S0140-6736(20)32656-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Nalbandian A., Sehgal K., Gupta A., Madhavan M.V., McGroder C., Stevens J.S., et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27:601–615. doi: 10.1038/s41591-021-01283-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Stahlberg Marcus, Reistam Ulrika, Fedorowski Artur, Villacorta Humberto, et al. 2022. Post-Covid-19 tachycardia syndrome: a distinct phenotype of post-acute Covid-19 syndrome. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Vernino S., Stiles L.E. Autoimmunity in postural orthostatic tachycardia syndrome: current understanding. Auton Neurosci. 2018;215:78–82. doi: 10.1016/j.autneu.2018.04.005. [DOI] [PubMed] [Google Scholar]
- 27.Kharraziha I., Axelsson J., Ricci F., Di Martino G., Persson M., Sutton R., et al. Serum activity against G protein-coupled receptors and severity of orthostatic symptoms in postural orthostatic tachycardia syndrome. J Am Heart Assoc. 2020;9(15) doi: 10.1161/JAHA.120.015989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Schondorf R., Low P.A. Idiopathic postural orthostatic tachycardia syndrome: an attenuated form of acute pandysautonomia? Neurology. 1993;43(1):132–137. doi: 10.1212/wnl.43.1_part_1.132. [DOI] [PubMed] [Google Scholar]
- 29.Jacob G., Costa F., Shannon J.R., Robertson R.M., Wathen M., Stein M., et al. The neuropathic postural tachycardia syndrome. N Engl J Med. 2000;343(14):1008. doi: 10.1056/NEJM200010053431404. [DOI] [PubMed] [Google Scholar]
- 30.Baruscotti M., Bucchi A., Milanesi R., Paina M., Barbuti A., Gnecchi-Ruscone T., et al. A gain-of-function mutation in the cardiac pacemaker HCN4 channel increasing cAMP sensitivity is associated with familial inappropriate sinus tachycardia. Eur Heart J. 2017;38(4):280–288. doi: 10.1093/eurheartj/ehv582. [DOI] [PubMed] [Google Scholar]
- 31.Olshansky B., Sullivan R.M. Inappropriate sinus tachycardia. Europace. 2019;21(2):194–207. doi: 10.1093/europace/euy128. [DOI] [PubMed] [Google Scholar]
- 32.Zhao Y.M., Shang Y.M., Song W.B., Li Q.Q., Xie H., Xu Q.F., et al. Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine. 2020;25 doi: 10.1016/j.eclinm.2020.100463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Puntmann V.O., Carerj M.L., Wieters I., Fahim M., Arendt C., Hoffmann J., et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19) JAMA Cardiol. 2020;5(11):1265–1273. doi: 10.1001/jamacardio.2020.3557. [DOI] [PMC free article] [PubMed] [Google Scholar]