Nonspecific ventricular repolarization abnormalities: A wolf in sheep's clothing

Carmona-Puerta, R.; Lorenzo-Martínez, E.

doi:10.1016/j.rceng.2022.03.008

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Carmona-Puerta, E. Lorenzo-Martínez" "autores" => array:2 [ 0 => array:4 [ "nombre" => "R." "apellidos" => "Carmona-Puerta" "email" => array:1 [ 0 => "endotelio1975@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "E." 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ECG: electrocardiogram; NVRA: nonspecific ventricular repolarization abnormalities." ] ] ] "textoCompleto" => "IntroductionNonspecific ventricular repolarization abnormalities (NVRA) have traditionally been considered benign electrocardiographic findings. This had led to difficulties in their clinical interpretation, especially in asymptomatic patients. Some factors, such as the clinical scenario, comorbidities with implicit cardiovascular risk, and medical expertise together with the better knowledge we now have about the clinical significance of NVRA based on epidemiological studies should radically change the way we approach this challenge in echocardiography.DefinitionsNVRA are electrocardiographic modifications of the ST-T wave that are not associated with particular conditions, such as the high, peaked T waves of hypokalemia or the deep T-wave inversion observed with intracranial hemorrhage, acute myocardial ischemia, or apical hypertrophic cardiomyopathy. They are sometimes referred to as minor ventricular repolarization abnormalities (MVRA), a term interchangeable with NVRA.Their presentation includes shallow ST-segment depression or flat, shallowly inverted, or isodiphasic (only negative/positive) T waves without evidence of a specific cause<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). According to Bayes de Luna et al.,<a class="elsevierStyleCrossRef" href="#bib0015">3</a> they are small ST-segment deviations (elevations or depressions <1 mm), small changes in T-wave morphology (more symmetrical appearance and/or subtle voltage changes), and minor changes in the U wave. The abnormalities can be confined to the ST segment or the T wave or both at the same time; be persistent or transitory; and be seen on one or more leads at the same time. Surawicz and Knilans<a class="elsevierStyleCrossRef" href="#bib0020">4</a> propose that the term NVRA can be used when the interpreter is unable to form an opinion given that this entails the risk of being incorrect.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>The current recommendations for electrocardiogram (ECG) standardization and interpretation consider it appropriate to use the terms “slight” or “indeterminate” for minor T-wave abnormalities due to the impossibility of developing a cause-specific classification. They do not mention if the same should be applicable to ST segment abnormalities.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> This document does not mention the term NVRA, but provides quantitative definitions of the T wave that can be applied to the descriptive definition of NVRA.Flat T waves are those whose amplitude is between 0.1 and −0.1 mV on the I, II, aVL (with R wave >0.3 mV), and V2-V6 leads whereas the term “low” should be used when the T-wave amplitude is less than 10% of the R-wave amplitude on the same lead. Inverted T waves are defined as those whose amplitude is between −0.1 and −0.5 mV and, although they are not categorized as shallow, they can be assumed as such based on the document’s definitions of deep inversion (−0.5 to −1.0 mV) and a giant negative T wave (<−1.0 mV).ST/T abnormalities can also be classified as primary and secondary.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> A primary abnormality is produced by direct myocardial injury, which affects the characteristics of the action potential of ventricular myocytes. Secondary abnormalities are the consequence of ventricular depolarization abnormalities which disrupt the normal way ventricular repolarization occurs, as observed in ventricular hypertrophy (strain pattern), ventricular pre-excitation, ventricular stimulation via a pacemaker, bundle branch blocks, and any rhythm of ventricular origin.NVRA should only be diagnosed when the ST/T abnormalities are primary, even if morphologically they meet the requirements of secondary abnormalities in some cases. In the latter case, the cause of ST/T abnormality is evident and thus, it cannot be considered a nonspecific change. One exception would be left ventricular hypertrophy when the principal diagnostic criteria (voltage indices) are not met and the NVRA are the only secondary findings.The Minnesota Code is used specifically to ensure uniformity in ECG descriptions in epidemiological studies (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). MVRA are represented by the codes 4.3 (J-point depression <0.5 mm); 4.4 (J-point depression ≥1 mm with ascending or U-shaped ST segment); 5.3 (flat, biphasic, or inverted T waves <1 mm); and 5.4 (positive T wave of a low amplitude, T:R index <1:20).<a class="elsevierStyleCrossRef" href="#bib0030">6</a> The Novacode classification version 5.8 has also been used for this purpose. Both the Minnesota Code and the Novacode classification are equally useful for predicting fatal cardiac events and overall mortality in epidemiological studies.<a class="elsevierStyleCrossRefs" href="#bib0035">7,8</a><elsevierMultimedia ident="fig0010"></elsevierMultimedia>EpidemiologyThe majority of population studies concur that NVRA are frequent electrical findings, with a prevalence that range from 5.0% to 22.1%.<a class="elsevierStyleCrossRefs" href="#bib0045">9–19</a> One out of every ten middle-aged (45–64 years) and older adults (≥65 years) in the United States presents with minor ST-segment depression.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> The prevalence of NVRA is higher in patients who are older, who are Black, and who have cardiovascular risk factors.<a class="elsevierStyleCrossRefs" href="#bib0065">13,21–25</a>In a minority of works, the prevalence of NVRA is lower than what is indicated above. Among individuals 40−64 years of age without a medical history of coronary disease, Greenland et al.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> found nonspecific T-wave and ST-segment abnormalities in 1.9% and 1.5% of women, respectively, and in 1.6% and 1.2% of men, respectively.Among participants in the MINACOR study, minor ST-segment abnormalities accounted for 1.8% of cases.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> The electrocardiographic data from 24,062 adolescents from secondary schools in Rome, Italy, revealed a low prevalence of NVRA, despite having included persistent juvenile T-wave pattern and early repolarization in the definition of this term.<a class="elsevierStyleCrossRef" href="#bib0135">27</a>In 13,179 Spanish workers (16–74 years) who underwent routine medical examinations, very low prevalences of ST-segment deviation (0.2%) and T-wave abnormalities (0.7%) were found.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> In 16,793 Koreans who consulted in a medical center for routine check-ups, ST/T disorders of any type were observed in 1037 individuals. Of them, at least one MVRA was documented in 95.3%.<a class="elsevierStyleCrossRef" href="#bib0145">29</a>The association of NVRA with female sex has been systematically confirmed.<a class="elsevierStyleCrossRefs" href="#bib0060">12,13,21–24,30,31</a> It is linked to modulating factors such as mitral valve prolapse, hyperdynamic circulation, hyperventilation, and female hormones.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> For this reason, it has even been proposed that different criteria for ST/T abnormalities for men and women should be defined.<a class="elsevierStyleCrossRef" href="#bib0160">32</a> Unlike what has been observed in most works, in the HELIUS study, a smaller proportion of women had any minor ECG abnormality compared to men.<a class="elsevierStyleCrossRef" href="#bib0165">33</a>Nonspecific ST-segment depression has been reported in focal myocarditis and indeed, it may be one of the earliest clinical signs of it.<a class="elsevierStyleCrossRef" href="#bib0170">34</a> In 20 children with acute fulminant myocarditis studied by Lv et al.,<a class="elsevierStyleCrossRef" href="#bib0175">35</a> NVRA were a frequent finding.High prevalences of NVRA were reported in patients with COVID-19, with figures ranging from 29% to 41%, similar values to what is reported in healthy centenarian subjects.<a class="elsevierStyleCrossRefs" href="#bib0180">36–39</a> In women with breast implants without any acute medical conditions, ST-segment depression and a negative T wave are the most common type of electrocardiographic findings.<a class="elsevierStyleCrossRef" href="#bib0200">40</a> NVRA have also been reported in patients with collagen diseases. It is 3.3 times more likely that they will be detected in patients with systemic lupus erythematosus than in those with rheumatoid arthritis, regardless of age and sex.<a class="elsevierStyleCrossRef" href="#bib0205">41</a> ST/T abnormalities are also observed in cases of poisoning with tricyclic antidepressants.<a class="elsevierStyleCrossRef" href="#bib0210">42</a> In patients with sickle cell disease (homozygous S), NVRA are present in up to 53% of cases.<a class="elsevierStyleCrossRef" href="#bib0215">43</a>Clinical significanceMultiple causes of NVRA are recognized in addition to related factors in which it is difficult to establish a direct causal link (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Evidence gathered to date allows for interpreting these electrocardiographic patterns with greater precision.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Cardiovascular morbidity and mortalityThe association between NVRA and the presence of coronary disease, atrial fibrillation, and stimulation devices has been confirmed.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> NVRA were associated with a greater incidence of new-onset atrial fibrillation or flutter in a Korean study with a median follow-up time of 8.5 years.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> However, the data from that research study do not allow for knowing the specific prognostic value of MVRA, as they were analyzed together with major ST/T changes.In adult populations, NVRA predict reduced survival and an increased risk of sudden death.<a class="elsevierStyleCrossRef" href="#bib0220">44</a> In an Israeli study on adults without known cardiovascular disease, it was found that nonspecific T-wave changes appeared to be associated with an increase in long-term all-cause mortality.<a class="elsevierStyleCrossRef" href="#bib0225">45</a> Other results based on follow-up on a Belgian population showed that flat T-wave findings were among the electrical abnormalities most predictive of cardiac mortality.<a class="elsevierStyleCrossRef" href="#bib0230">46</a>In post-menopausal women, the identification of minor ECG abnormalities (analyzed jointly and classified according to the Novacode classification) was associated with the onset of coronary (hazard ratio (HR) = 1.55; 95% confidence interval (CI) = 1.14–2.11) and cardiovascular disease (HR = 1.39; 95% CI = 1.14–1.68).<a class="elsevierStyleCrossRef" href="#bib0235">47</a>A recent investigation corroborated that cardiovascular risk factors are associated with future onset of NVRA.<a class="elsevierStyleCrossRef" href="#bib0240">48</a> NVRA have been associated with an increased risk of mortality due to coronary disease, the occurrence of coronary events, and primary arrhythmias in older adult patients.<a class="elsevierStyleCrossRefs" href="#bib0245">49,50</a> Minor ST/T abnormalities on precordial leads have even been seen in patients with significant left main coronary artery lesions.<a class="elsevierStyleCrossRef" href="#bib0255">51</a> Minimal changes in non-ST-segment elevation acute coronary syndrome can also be observed.<a class="elsevierStyleCrossRef" href="#bib0260">52</a> Persistent NVRA not attributable to physiological disorders are associated with cardiovascular mortality.<a class="elsevierStyleCrossRef" href="#bib0245">49</a>Greenland et al.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> determined the impact of NVRA on cardiovascular mortality and found that minor T-wave abnormalities (in men) and minor ST-segment depression (in women) were associated with an increased risk of death due to cardiovascular and coronary disease. In two cohorts derived from the NHANES-III study, a greater risk of cardiovascular mortality was found when NVRA was identified.<a class="elsevierStyleCrossRefs" href="#bib0075">15,53</a>In a cohort of middle-aged adult men without a medical history of cardiovascular disease who were followed-up on for 29 years, the presence of NVRA was independently associated with mortality due to myocardial infarction, cardiovascular disease, and all causes.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> The risk was greater when NVRA were detected 2 or ≥3 times on annual examinations compared to just one observance in five consecutive years. The presence of flat T waves was associated with a risk of major adverse cardiovascular events on a univariate and multivariate analysis in a low-risk general adult population.<a class="elsevierStyleCrossRef" href="#bib0085">17</a>In a sample of 50-year-old Swedish men, the identification of minor T-wave abnormalities increased the risk of overall and cardiovascular death by 56% and 78%, respectively, after follow-up over two decades.<a class="elsevierStyleCrossRef" href="#bib0270">54</a> The significance of new-onset MVRA was examined by Sawai et al.<a class="elsevierStyleCrossRef" href="#bib0275">55</a> in a prospective Japanese cohort. Its identification was associated with increased risk of overall cardiovascular disease.In the WOSCOPS study (men between 55 and 64 years of age), a univariate analysis showed that MVRA entailed a significant risk for the endpoint of death due to cardiovascular disease/non-fatal myocardial infarction and for all-cause mortality at five years. The risk was even greater than what was observed with other classical risk factors.<a class="elsevierStyleCrossRef" href="#bib0280">56</a>The anatomical localization of T-wave inversion also influences the magnitude of cardiovascular risk. In a representative sample of Finnish subjects, a multivariate analysis showed that T-wave inversion on anterior and lateral leads, but not on inferior leads, was associated with a greater risk of coronary heart disease.<a class="elsevierStyleCrossRef" href="#bib0285">57</a> Only lateral T-wave inversions were associated with a greater risk of mortality in the total study population.Using data from 1393 subjects included in the CHAS study, Vu et al.<a class="elsevierStyleCrossRef" href="#bib0290">58</a> reported new-onset MVRA in 9.4% after 39 years of follow-up. A favorable cardiovascular risk profile at the start of the study or an improvement in the profile during follow-up were not significantly associated with the onset of these electrocardiographic abnormalities compared to other categories of greater cardiovascular risk. However, a low risk profile was associated with a lower rate of developing major ECG abnormalities.The CARDIA study evaluated the possible link between NVRA and subclinical atherosclerosis through their association with coronary artery calcium measurements and common carotid intima-media thickness. A multivariate analysis which included 2175 participants revealed no association with coronary artery calcium measurements (odds ratio (OR) = 0.91; 95% CI = 0.77–1.08), although this was not the case for the common carotid intima-media thickness index (OR = 1.27; 95% CI = 1.07–1.50).<a class="elsevierStyleCrossRef" href="#bib0155">31</a>Hypertension/left ventricular hypertrophyIn a large Chinese study that included 15,038 hypertensive individuals, it was observed that NVRA behaved as independent predictors of poor blood pressure control.<a class="elsevierStyleCrossRef" href="#bib0295">59</a> During follow-up on 1970 hypertensive patients without ischemic heart disease, the occurrence of coronary events was greater in patients with MVRA than in those with normal repolarization after adjusting for the effects of age, sex, diabetes mellitus, serum cholesterol, tobacco use, left ventricular hypertrophy, and pulse pressure.<a class="elsevierStyleCrossRef" href="#bib0300">60</a> NVRA were associated with deterioration in left ventricular relaxation and left ventricular hypertrophy in a cross-sectional study comprising 74,976 Koreans who underwent a comprehensive medical examination.<a class="elsevierStyleCrossRef" href="#bib0305">61</a> The association between NVRA and abnormal left ventricular relaxation was greater in the group at intermediate and high risk of cardiovascular disease.Cerebrovascular diseaseA Japanese study established that men with MVRA had a 2.3 times greater age-adjusted relative risk of both ischemic and hemorrhagic stroke.<a class="elsevierStyleCrossRef" href="#bib0310">62</a> In another study on subjects of the same nationality, MVRA were associated with an increased risk of cerebral infarction in the entire population studied.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>In the REGARDS study cohort, it was demonstrated that the presence of NVRA significantly increased the risk of incident ischemic stroke independently of the existence of traditional or new risk factors or major ECG abnormalities.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> There was an independent nonlinear association between NVRA and mortality in patients with subarachnoid hemorrhage who underwent surgery for aneurysms (OR = 3.1; p = 0.031).<a class="elsevierStyleCrossRef" href="#bib0315">63</a>Diabetes mellitusIn individuals with diabetes, a hypothesis has been proposed that the higher rate of NVRA development could be related to silent myocardial ischemia based on the notion that autonomic neuropathy eliminates the sensation of pain.<a class="elsevierStyleCrossRefs" href="#bib0320">64,65</a>EpilepsyA recent systematic review found that individuals who have epilepsy have a greater probability of having minor ST-segment abnormalities in interictal periods.<a class="elsevierStyleCrossRef" href="#bib0330">66</a> Up to 40% of epileptic seizures could cause ST-segment depression, but troponin T levels remain normal in most patients. This shows that if the change is induced by acute transitory ischemia, the myocardial lesion is not severe.<a class="elsevierStyleCrossRef" href="#bib0335">67</a>In 127 children diagnosed with epilepsy in whom pre-existing heart disease or ion channel diseases were ruled out, the prevalence of nonspecific ST-segment abnormalities was 19% and the prevalence of nonspecific T-wave abnormalities was 30%.<a class="elsevierStyleCrossRef" href="#bib0340">68</a> The duration of epilepsy was an independent risk factor for ECG changes in these children.COVID-19In 31 consecutive COVID-19 cases, the presence of myocardial damage gave rise to T-wave inversions of up to 5 mm, but never greater than 2 mm, in patients without heart involvement.<a class="elsevierStyleCrossRef" href="#bib0345">69</a> NVRA significantly predicted death due to COVID-19 in a retrospective cohort that comprised 756 patients.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> ST/T abnormalities are more probable in severe COVID-19 than in mild forms.<a class="elsevierStyleCrossRef" href="#bib0350">70</a>The presence of NVRA in patients with COVID-19 is associated with myocardial lesion and poor outcomes, including among others: greater need for intensive care unit admission, more frequent mechanical ventilatory support, and greater mortality.<a class="elsevierStyleCrossRefs" href="#bib0190">38,71</a> Recently, Angeli et al.<a class="elsevierStyleCrossRef" href="#bib0360">72</a> concluded in a study that ECG abnormalities during hospitalization due to COVID-19 pneumonia reflect a wide spectrum of cardiovascular complications, have a late onset, do not progress in parallel with lung abnormalities, and can occur after negative swabs.In 82 children with asymptomatic, mild, or moderate COVID-19 who did not require hospitalization, Heching et al.<a class="elsevierStyleCrossRef" href="#bib0365">73</a> demonstrated electrocardiographic changes in 21%, but borderline abnormalities—which included NVRA—were only detected in ten patients (12%). In patients with moderate, severe, and critical COVID-19 who were discharged (n = 594), ST/T changes were identified (without indicating specific or nonspecific abnormalities) at three months in 19.9% of cases; their prevalence was greater among those with moderate disease. In 23.5% of cases, these abnormalities persisted at six months from discharge.<a class="elsevierStyleCrossRef" href="#bib0370">74</a>The prevalence of ST/T changes remained elevated at one year of follow-up (20%, n = 486) and was higher among patients who had moderate and critical COVID-19. The electrocardiographic changes in COVID-19 can be explained by the following factors acting jointly or individually: 1) cytokine storm, 2) hypoxic lesion, 3) electrolyte abnormalities, 4) plaque rupture, 5) coronary artery spasm, and 6) microthrombi or direct endothelial or myocardial lesion.<a class="elsevierStyleCrossRef" href="#bib0375">75</a>Other clinical contextsIn an independent analysis of the CARDIA study, no relationship was found between occasional marijuana use among young adults and the existence of minor ECG changes.<a class="elsevierStyleCrossRef" href="#bib0380">76</a> Recently, Xiao et al.<a class="elsevierStyleCrossRef" href="#bib0385">77</a> reported that non-alcoholic fatty liver disease constituted an independent predictor of NVRA after analyzing data from 32,922 patients (adjusted OR = 1.29; 95% CI = 1.12–1.48).The clinical value of NVRA increases if we take into account that most studies find a much lower prevalence of major ST/T abnormalities, which varies according to age, sex, type of population analyzed, and pre-existing comorbidities.<a class="elsevierStyleCrossRefs" href="#bib0390">78,79</a> At present, it is accepted that NVRA have potential from a preventative point of view.<a class="elsevierStyleCrossRef" href="#bib0270">54</a>The mechanism by which NVRA act as cardiovascular predictors is not known. There has been speculation about the following mechanisms: (1) markers of patent heart disease expressed incompletely on the ECG; (2) subclinical myocardial damage, and (3) systemic disease with cardiac involvement.In a nontrivial number of cases, patients with NVRA present with symptoms that point to ischemic heart disease. The presence of such symptoms is more important as a predictor of risk than the electrocardiographic changes themselves.Negative resultsContrary to the aforementioned findings, in the MINACOR study, which analyzed an initial cohort of 352 hypertensive, non-diabetic patients without associated cardiovascular disease who were followed-up on for 16 years, no significant association between NVRA and cardiovascular morbidity and mortality was found (HR = 0.97; 95% CI = 0.49–1.90).<a class="elsevierStyleCrossRef" href="#bib0095">19</a> Some authors have argued that the cause of this lack of an association could be related to the binary form of the analysis (presence of NVRA or not) and suggest that a dose-response analysis based on the exponential increase in cardiovascular mortality as the number of minor ECG abnormalities increases would be better.<a class="elsevierStyleCrossRef" href="#bib0075">15</a>In patients with peripheral arterial disease, minor ECG abnormalities were not significant predictors of major cardiovascular events.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> After 19 years of follow-up on 1306 patients with type 1 diabetes mellitus (mean age 35.5 ± 6.9 years) who formed part of the EDIC study, it was not found that minor ECG abnormalities were significant predictors of cardiovascular events.<a class="elsevierStyleCrossRef" href="#bib0400">80</a>In the last two studies mentioned, a general classification was used for ECG abnormalities (major and minor abnormalities). Although this simplifies the analysis from a practical point of view, the lack of a separate approach to the different types of changes may have affected their conclusions. The investigators of the EDIC study themselves recognized in the study limitations that if ECG abnormalities had been analyzed separately, different associations with cardiovascular disease may have been drawn. However, they argued that the overall classification had been satisfactorily used before and that statistical power increases with it.A summary of the main prognostic studies can be seen in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>RecommendationsMost available studies demonstrate that the presence of NVRA entails significant cardiovascular risk. As such, we recommend that they should be added to the classical cardiovascular risk factors examined during the clinical evaluation. The variety of contexts in which they may appear means that different approaches should be considered for their analysis. When NVRA occur in acute scenarios, such as precordial pain indicative of acute myocardial ischemia, symptoms that imply electrolyte disorders (diarrhea, chronic kidney disease), the post-seizure period, or active COVID-19, the interpretation should be more causal.The biggest challenge is the case of asymptomatic patients in whom whether there are identifiable cardiovascular risk factors must be taken into account (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). In the event they are present, a possible causal nexus aimed at the heart as the target organ should be searched for. Working with identified risk factors will be the primordial task.Improving blood pressure control, improving glycemic control, reducing body weight in individuals with obesity, stopping smoking and excessive alcohol intake, doing physical activity, and eating a healthy diet should be recommended in these cases. Due to these patients’ increased risk of cardiovascular events, quarterly monitoring in a medical consultation should be planned in all cases.ConclusionsMany clinical studies demonstrate that NVRA should be considered in a cardiovascular risk evaluation. They may represent initial forms of left ventricular hypertrophy or a subtle expression of significant coronary disease or various cardiomyopathies.In other non-cardiovascular contexts, the presence of NVRA indicates a cardiac repercussion. Their appearance in asymptomatic adults should not be taken lightly and this scenario represent the greatest clinical challenge. The cumulative evidence reveals their capacity for predicting cardiovascular morbidity and mortality. Therefore, when present, a diligent analysis must be conducted before concluding that they are a benign finding.NVRA must be included as another risk factor in preventative medicine.FundingThis review has not received specific grants from agencies in the public, commercial, or non-profit sectors.Conflicts of interestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1792882" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1569612" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1792883" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1569611" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Definitions" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Epidemiology" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Clinical significance" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Cardiovascular morbidity and mortality" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Hypertension/left ventricular hypertrophy" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Cerebrovascular disease" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Diabetes mellitus" ] 4 => array:2 [ "identificador" => "sec0045" "titulo" => "Epilepsy" ] 5 => array:2 [ "identificador" => "sec0050" "titulo" => "COVID-19" ] 6 => array:2 [ "identificador" => "sec0055" "titulo" => "Other clinical contexts" ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "Negative results" ] ] ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Recommendations" ] 9 => array:2 [ "identificador" => "sec0070" "titulo" => "Conclusions" ] 10 => array:2 [ "identificador" => "sec0075" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflicts of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-02-21" "fechaAceptado" => "2022-03-16" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1569612" "palabras" => array:4 [ 0 => "Minor nonspecific ST-T abnormalities" 1 => "Electrocardiogram" 2 => "Cardiovascular mortality" 3 => "Nonspecific ventricular repolarization abnormalities" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1569611" "palabras" => array:4 [ 0 => "Alteraciones menores inespecíficas del ST-T" 1 => "Electrocardiograma" 2 => "Mortalidad cardiovascular" 3 => "Trastornos inespecíficos de la repolarización ventricular" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "The term nonspecific ventricular repolarization abnormalities refers to a set of minor alterations of the ST segment and/or the T wave. For a long time, they have been of little clinical interest as they do not translate into specific diagnoses. It has even been asserted that they constitute benign electrocardiographic findings. Their presence has been reported in various cardiovascular and non-cardiovascular diseases. However, it is frequently identified in apparently healthy asymptomatic people. A growing number of studies demonstrate their importance as predictors of cardiovascular morbidity and mortality, expanding their spectrum towards cardiovascular prevention. In light of the body of scientific evidence, it is imperative that the traditional view of nonspecific ventricular repolarization abnormalities changes." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El término trastornos inespecíficos de la repolarización ventricular se refiere a un conjunto de alteraciones menores del segmento ST y/o la onda T. Durante mucho tiempo han sido de escaso interés clínico al no traducir diagnósticos específicos. De forma extrema, se ha aseverado que constituyen hallazgos electrocardiográficos benignos. Su presencia se ha reportado en diversos estados patológicos cardiovasculares y no cardiovasculares. Sin embargo, con frecuencia se identifica en personas asintomáticas aparentemente sanas. Un creciente número de estudios demuestran su importancia como predictores de morbimortalidad cardiovascular, expandiendo su espectro hacia la prevención cardiovascular. A la luz de las evidencias científicas acumuladas se impone un cambio en la visión tradicional que se ha tenido con los trastornos inespecíficos de la repolarización ventricular." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Carmona-Puerta R, Lorenzo-Martínez E. Trastornos inespecíficos de la repolarización ventricular: un lobo con piel de oveja. Rev Clin Esp. 2022;222:549–562." ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1013 "Ancho" => 3008 "Tamanyo" => 843131 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Twelve-lead electrocardiogram that shows nonspecific ventricular repolarization abnormalities in a 43-year-old asymptomatic man. Flat T waves are observed on the I, aVL, V5, and V6 leads. The patient had a diagnosis of controlled hypertension and had a normal echocardiogram." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1903 "Ancho" => 3008 "Tamanyo" => 294923 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Proposed clinical management algorithm for asymptomatic patients with nonspecific ventricular repolarization disorders. *The algorithm may vary depending on clinical progress. ECG: electrocardiogram; NVRA: nonspecific ventricular repolarization abnormalities." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Physiological \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minor T-wave inversion in young adults and women on V2 and inferior leads \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hyperventilation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stress \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">After food intake \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Changes in position \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Changes in sympathetic tone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pathophysiological (directly or indirectly associated) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cardiovascular abnormalities \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypertension \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Heart failure \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cardiac stimulation (cardiac memory in its shallow forms) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ventricular arrhythmias (cardiac memory in its shallow forms) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intermittent left bundle branch block (cardiac memory in its shallow forms) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intermittent ventricular pre-excitation (cardiac memory in its shallow forms) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myocardial ischemia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myocarditis (frequent finding) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pericarditis (stage 3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mitral valve prolapse (frequently on inferior leads) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pericardial effusion \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pericardial abscess \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Infiltrative cardiac diseases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pulmonary embolism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Electrolyte abnormalities \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mild hypokalemia/hypomagnesemia/hypocalcemia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Endocrine abnormalities \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diabetes mellitus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypothyroidism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypopituitarism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Adrenal gland failure \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Connective tissue diseases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Systemic lupus erythematosus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rheumatoid arthritis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neurological diseases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Epilepsy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ischemic and hemorrhagic stroke \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Becker muscular dystrophy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Post-resuscitation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Left pleural effusion \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">COVID-19 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Malignant hyperthermia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Use of certain drugs (antiarrhythmics, psychotropics) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute exposure to ambient particles <2.5 µm in diameter \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Electroconvulsive therapy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gastroenteritis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cholecystitis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sickle cell anemia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Truncal vagotomy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Breast implants \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Causes and/or factors associated with nonspecific ST-segment and T-wave abnormalities." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "MTWA: minor T-wave abnormalities; MSTD: minor ST-segment depression; ECG: electrocardiogram; HR: hazard ratio; HT: hypertension; CI: confidence interval; OR: odds ratio; RR: relative risk; NVRA: nonspecific ventricular repolarization abnormalities." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">References \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Electrocardiographic definitions \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study type \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study population \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Main outcomes related to NVRA \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Istolahti et al.,<a class="elsevierStyleCrossRef" href="#bib0285">57</a> 2021<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inverted T wave if amplitude <0 µVIn isodiphasic T waves, the lowest part of the wave indicated the levelLead groups: lateral (I, aVL, V5, and V6), inferior (II, aVF), and anterior (V2, V3, and V4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational, prospective study with 15 years of follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 6354Age: >30 yearsFinnish \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Risk of coronary heart disease for inverted T waves in anterior (HR = 2.37; 95% CI = 1.20−4.68) and inferior localizations (HR = 1.65; 95% CI = 1.27−2.15)Risk of death with inverted T waves on lateral leads (HR = 1.59; 95% CI = 1.29−1.96) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Shin et al.,<a class="elsevierStyleCrossRef" href="#bib0085">17</a> 2020 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minnesota Code \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational, prospective study with 12 years of follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 8444Age: 40−69 yearsLow-risk Korean population \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Flat T waves, increased risk of major cardiovascular eventsUnivariate: HR = 1.70; 95% CI = 1.27−2.28Multivariate: HR = 1.42; 95% CI = 1.05−1.92 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sjöland et al.,<a class="elsevierStyleCrossRef" href="#bib0270">54</a> 2020 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minnesota Code \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational, prospective study with > 20 years of follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 839Randomly selected 50-year-old Swedish males followed-up on until death \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increased risk in cases of minor T-wave abnormalitiesRisk of overall mortality: HR = 1.56; 95% CI = 1.10−2.21Risk of cardiovascular mortality: HR = 1.78; 95% CI = 1.13−2.79 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sawano et al.,<a class="elsevierStyleCrossRef" href="#bib0065">13</a> 2020 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minnesota Code \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational, prospective study with a mean follow-up of 9.6 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 14,077Average age: 63.4 ± 9.1 yearsWomen: 59.1%Black: 41.4%North Americans living in areas with high prevalences of stroke (50%) and other continental areas (50%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increased risk of ischemic stroke in patients with isolated NVRAMultivariate analysis:HR = 1.32; 95% CI = 1.05−1.67Adjusted for age, sex, race, geographic location, educational level, and age-race interaction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">McCullough et al.,<a class="elsevierStyleCrossRef" href="#bib0180">36</a> 2020 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">According to the judgment of 2 electrocardiographers with more than 100,000 reports/year between them \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational, retrospective cohort study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 756Average age: 63.3 ± 16.0 years37% women, 61% non-white, 57% hypertensivePatients hospitalized in a large university hospital in New York \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The presence of NVRA on the ECG taken upon hospital admission was associated with a greater risk of death due to COVID-19Univariate OR = 1.86; 95% CI = 1.18−2.92 and multivariate OR = 2.31; 95% CI = 1.27−4.21 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hari et al.,<a class="elsevierStyleCrossRef" href="#bib0075">15</a> 2019 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minnesota Code \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational, prospective study with a mean follow-up of 13.9 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 6467Average age: 58.9 years old.Representative sample of noninstitutionalized North American civilians49% non-Hispanic whites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The presence of minor isolated ST/T abnormalities increases the risk of cardiovascular mortalityModel adjusted for age, sex, race, various cardiovascular risk factors, and other minor ECG abnormalities:HR = 1.22; 95% CI = 1.00−1.47 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Goldman et al.,<a class="elsevierStyleCrossRef" href="#bib0225">45</a> 2019 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minnesota Code \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational, prospective study with a mean follow-up of 31 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 2,601, randomized selectionAge: 54.5 ± 8.0 years52% womenNo known cardiovascular diseaseIsraeli population \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nonspecific T-wave changes were associated with overall mortality risk on the multivariate analysisHR = 1.18; 95% CI = 1.05−1.33 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ishikawa et al.,<a class="elsevierStyleCrossRef" href="#bib0060">12</a> 2018 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minnesota Code \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational, prospective study with annual follow-up for 10 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 10,642Average age: 55.4 ± 11.2 years37.6% menGeneral Japanese population \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Association between NVRA and occurrence of cerebral infarctionHR = 2.10; 95% CI = 1.57−2.81NVRA in cases with hyperlipidemia: HR = 1.75; 95% CI = 1.15−2.67 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sawai et al.,<a class="elsevierStyleCrossRef" href="#bib0275">55</a> 2017 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minnesota Code \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational, prospective study with a median follow-up of 23 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 9374 (3545 men/5829 women)Japanese individuals \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minor ST-segment abnormalities: 19% increase in total cardiovascular disease riskMinor T-wave abnormalities: 42% increase in total cardiovascular disease risk \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Badheka et al.,<a class="elsevierStyleCrossRef" href="#bib0265">53</a> 2012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minnesota Code \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational retrospective study with data collected prospectively. Mean follow-up: 13.5 ± 3.8 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 4426 North AmericansAge: 40−90 yearsNo coronary disease or equivalents \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Risk of overall mortality according to presence of NVRA: HR = 1.37; 95% CI = 1.03−1.81. Risk of cardiovascular mortality according to presence of NVRA: HR = 1.71; 95% CI = 1.04−2.83The model was adjusted for age, sex, race, body mass index, smoking habit, hypercholesterolemia, glomerular filtration rate, heart rate, corrected QT interval, and left ventricular mass index \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Macfarlane and Norris,<a class="elsevierStyleCrossRef" href="#bib0280">56</a> 2007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minnesota Code \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational, prospective study.Estimation of risk at 5 years of follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 6,595, Scottish menAge: 55−65 years at the start of the study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Risk of cardiovascular disease/non-fatal myocardial infarction at five years: HR = 1.70; 95% CI = 1.28−2.26Risk of all-cause death at five years: HR = 2.16; 95% CI = 1.53−3.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Schillaci et al.,<a class="elsevierStyleCrossRef" href="#bib0300">60</a> 2004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minnesota Code \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational, prospective study with a mean follow-up of 4.7 years, maximum 9.1 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 1970 hypertensive patients without ischemic heart disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increased risk of coronary events in hypertensive patients with NVRAHR = 2.07; 95% CI = 1.23−3.47 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ohira et al.,<a class="elsevierStyleCrossRef" href="#bib0310">62</a> 2003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minnesota Code \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational, prospective study with follow-up for 15.4 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 10,741Age: 40−69 yearsPopulation of four Japanese communities \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increased risk of ischemic or hemorrhagic stroke in men with NVRA (RR adjusted for age = 2.3)After adjusting for HT, the risk remained significant:RR total stroke = 1.8; 95% IC = 1.3−2.4RR ischemic stroke = 1.9; 95% IC = 1.3−2.8RR hemorrhagic stroke = 1.7; 95% IC = 1.0−3.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Greenland et al.,<a class="elsevierStyleCrossRef" href="#bib0130">26</a> 2003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minnesota Code \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational, prospective study with follow-up for 22 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 17,6157556 Caucasian and 429 African American women9144 Caucasian and 486 African American menAge: 40−64 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MTWA in men: increased risk of mortality due to cardiovascular disease: Age-adjusted HR = 2.24, p<0.001 and coronary disease: Age-adjusted HR = 2.21, p<0.001MSTD in women: increased risk of mortality due to cardiovascular disease: HR = 1.93 and coronary disease: HR = 1.91All HR are adjusted for age \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Daviglus et al.,<a class="elsevierStyleCrossRef" href="#bib0080">16</a> 1999 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minnesota Code \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational, prospective study with follow-up for 29 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 1673Age upon entering the study: 40−55 yearsWithout evidence of coronary disease or major ECG abnormalities in the first five years of follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RR of death adjusted for age since an ECG with minor ST/T abnormalities up to ≥3Due to myocardial infarction: one ECG-RR = 1.66 (95% CI = 1.05−2.62), ≥3 ECG-RR = 2.63 (95% CI = 1.35−5.12)Due to cardiovascular diseases: one ECG-RR = 1.42 (95% CI = 1.01−2.02), ≥3 ECG-RR = 2.88 (95% CI = 1.81−4.56)Due to all causes: one ECG-RR = 1.34 (95% CI = 1.04−1.73), ≥3 ECG-RR = 1.88 (95% CI = 1.25−2.82) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">De Bacquer et al.,<a class="elsevierStyleCrossRef" href="#bib0230">46</a> 1998 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minnesota Code \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational, prospective study with follow-up for at least 10 years regarding cause of death \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 5208 men and 4746 women selected by random sampling stratified based on age and sexAge: 25−74 yearsBelgian populationNo evidence of coronary disease at the start of the study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Flat T waves predicted cardiovascular mortality:RR = 2.47; 95% CI = 1.83−3.32 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "The study did not discriminate between major and minor T-wave inversions, but half of the sample presented with a T wave ≤−50 µV." ] ] ] "descripcion" => array:1 [ "en" => "Main studies which show the prognostic value of nonspecific ventricular repolarization abnormalities." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:80 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Goldberger’s clinical electrocardography: a simplifield approach" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. 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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Nonspecific ventricular repolarization abnormalities &#40;NVRA&#41; have traditionally been considered benign electrocardiographic findings&#46; This had led to difficulties in their clinical interpretation&#44; especially in asymptomatic patients&#46; Some factors&#44; such as the clinical scenario&#44; comorbidities with implicit cardiovascular risk&#44; and medical expertise together with the better knowledge we now have about the clinical significance of NVRA based on epidemiological studies should radically change the way we approach this challenge in echocardiography&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Definitions</span><p id="par0010" class="elsevierStylePara elsevierViewall">NVRA are electrocardiographic modifications of the ST-T wave that are not associated with particular conditions&#44; such as the high&#44; peaked T waves of hypokalemia or the deep T-wave inversion observed with intracranial hemorrhage&#44; acute myocardial ischemia&#44; or apical hypertrophic cardiomyopathy&#46; They are sometimes referred to as minor ventricular repolarization abnormalities &#40;MVRA&#41;&#44; a term interchangeable with NVRA&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Their presentation includes shallow ST-segment depression or flat&#44; shallowly inverted&#44; or isodiphasic &#40;only negative&#47;positive&#41; T waves without evidence of a specific cause<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; According to Bayes de Luna et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> they are small ST-segment deviations &#40;elevations or depressions &#60;1&#8239;mm&#41;&#44; small changes in T-wave morphology &#40;more symmetrical appearance and&#47;or subtle voltage changes&#41;&#44; and minor changes in the U wave&#46; The abnormalities can be confined to the ST segment or the T wave or both at the same time&#59; be persistent or transitory&#59; and be seen on one or more leads at the same time&#46; Surawicz and Knilans<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> propose that the term NVRA can be used when the interpreter is unable to form an opinion given that this entails the risk of being incorrect&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The current recommendations for electrocardiogram &#40;ECG&#41; standardization and interpretation consider it appropriate to use the terms &#8220;slight&#8221; or &#8220;indeterminate&#8221; for minor T-wave abnormalities due to the impossibility of developing a cause-specific classification&#46; They do not mention if the same should be applicable to ST segment abnormalities&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> This document does not mention the term NVRA&#44; but provides quantitative definitions of the T wave that can be applied to the descriptive definition of NVRA&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Flat T waves are those whose amplitude is between 0&#46;1 and &#8722;0&#46;1&#8239;mV on the I&#44; II&#44; aVL &#40;with R wave &#62;0&#46;3&#8239;mV&#41;&#44; and V2-V6 leads whereas the term &#8220;low&#8221; should be used when the T-wave amplitude is less than 10&#37; of the R-wave amplitude on the same lead&#46; Inverted T waves are defined as those whose amplitude is between &#8722;0&#46;1 and &#8722;0&#46;5&#8239;mV and&#44; although they are not categorized as shallow&#44; they can be assumed as such based on the document&#8217;s definitions of deep inversion &#40;&#8722;0&#46;5 to &#8722;1&#46;0&#8239;mV&#41; and a giant negative T wave &#40;&#60;&#8722;1&#46;0&#8239;mV&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">ST&#47;T abnormalities can also be classified as primary and secondary&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> A primary abnormality is produced by direct myocardial injury&#44; which affects the characteristics of the action potential of ventricular myocytes&#46; Secondary abnormalities are the consequence of ventricular depolarization abnormalities which disrupt the normal way ventricular repolarization occurs&#44; as observed in ventricular hypertrophy &#40;strain pattern&#41;&#44; ventricular pre-excitation&#44; ventricular stimulation via a pacemaker&#44; bundle branch blocks&#44; and any rhythm of ventricular origin&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">NVRA should only be diagnosed when the ST&#47;T abnormalities are primary&#44; even if morphologically they meet the requirements of secondary abnormalities in some cases&#46; In the latter case&#44; the cause of ST&#47;T abnormality is evident and thus&#44; it cannot be considered a nonspecific change&#46; One exception would be left ventricular hypertrophy when the principal diagnostic criteria &#40;voltage indices&#41; are not met and the NVRA are the only secondary findings&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The Minnesota Code is used specifically to ensure uniformity in ECG descriptions in epidemiological studies &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; MVRA are represented by the codes 4&#46;3 &#40;J-point depression &#60;0&#46;5&#8239;mm&#41;&#59; 4&#46;4 &#40;J-point depression &#8805;1&#8239;mm with ascending or U-shaped ST segment&#41;&#59; 5&#46;3 &#40;flat&#44; biphasic&#44; or inverted T waves &#60;1&#8239;mm&#41;&#59; and 5&#46;4 &#40;positive T wave of a low amplitude&#44; T&#58;R index &#60;1&#58;20&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The Novacode classification version 5&#46;8 has also been used for this purpose&#46; Both the Minnesota Code and the Novacode classification are equally useful for predicting fatal cardiac events and overall mortality in epidemiological studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Epidemiology</span><p id="par0045" class="elsevierStylePara elsevierViewall">The majority of population studies concur that NVRA are frequent electrical findings&#44; with a prevalence that range from 5&#46;0&#37; to 22&#46;1&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;19</span></a> One out of every ten middle-aged &#40;45&#8211;64 years&#41; and older adults &#40;&#8805;65&#8239;years&#41; in the United States presents with minor ST-segment depression&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> The prevalence of NVRA is higher in patients who are older&#44; who are Black&#44; and who have cardiovascular risk factors&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;21&#8211;25</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In a minority of works&#44; the prevalence of NVRA is lower than what is indicated above&#46; Among individuals 40&#8722;64 years of age without a medical history of coronary disease&#44; Greenland et al&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> found nonspecific T-wave and ST-segment abnormalities in 1&#46;9&#37; and 1&#46;5&#37; of women&#44; respectively&#44; and in 1&#46;6&#37; and 1&#46;2&#37; of men&#44; respectively&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Among participants in the MINACOR study&#44; minor ST-segment abnormalities accounted for 1&#46;8&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> The electrocardiographic data from 24&#44;062 adolescents from secondary schools in Rome&#44; Italy&#44; revealed a low prevalence of NVRA&#44; despite having included persistent juvenile T-wave pattern and early repolarization in the definition of this term&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In 13&#44;179 Spanish workers &#40;16&#8211;74 years&#41; who underwent routine medical examinations&#44; very low prevalences of ST-segment deviation &#40;0&#46;2&#37;&#41; and T-wave abnormalities &#40;0&#46;7&#37;&#41; were found&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> In 16&#44;793 Koreans who consulted in a medical center for routine check-ups&#44; ST&#47;T disorders of any type were observed in 1037 individuals&#46; Of them&#44; at least one MVRA was documented in 95&#46;3&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The association of NVRA with female sex has been systematically confirmed&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13&#44;21&#8211;24&#44;30&#44;31</span></a> It is linked to modulating factors such as mitral valve prolapse&#44; hyperdynamic circulation&#44; hyperventilation&#44; and female hormones&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> For this reason&#44; it has even been proposed that different criteria for ST&#47;T abnormalities for men and women should be defined&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> Unlike what has been observed in most works&#44; in the HELIUS study&#44; a smaller proportion of women had any minor ECG abnormality compared to men&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Nonspecific ST-segment depression has been reported in focal myocarditis and indeed&#44; it may be one of the earliest clinical signs of it&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> In 20 children with acute fulminant myocarditis studied by Lv et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> NVRA were a frequent finding&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">High prevalences of NVRA were reported in patients with COVID-19&#44; with figures ranging from 29&#37; to 41&#37;&#44; similar values to what is reported in healthy centenarian subjects&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">36&#8211;39</span></a> In women with breast implants without any acute medical conditions&#44; ST-segment depression and a negative T wave are the most common type of electrocardiographic findings&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> NVRA have also been reported in patients with collagen diseases&#46; It is 3&#46;3 times more likely that they will be detected in patients with systemic lupus erythematosus than in those with rheumatoid arthritis&#44; regardless of age and sex&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> ST&#47;T abnormalities are also observed in cases of poisoning with tricyclic antidepressants&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> In patients with sickle cell disease &#40;homozygous S&#41;&#44; NVRA are present in up to 53&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Clinical significance</span><p id="par0080" class="elsevierStylePara elsevierViewall">Multiple causes of NVRA are recognized in addition to related factors in which it is difficult to establish a direct causal link &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Evidence gathered to date allows for interpreting these electrocardiographic patterns with greater precision&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Cardiovascular morbidity and mortality</span><p id="par0085" class="elsevierStylePara elsevierViewall">The association between NVRA and the presence of coronary disease&#44; atrial fibrillation&#44; and stimulation devices has been confirmed&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> NVRA were associated with a greater incidence of new-onset atrial fibrillation or flutter in a Korean study with a median follow-up time of 8&#46;5&#8239;years&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> However&#44; the data from that research study do not allow for knowing the specific prognostic value of MVRA&#44; as they were analyzed together with major ST&#47;T changes&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In adult populations&#44; NVRA predict reduced survival and an increased risk of sudden death&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> In an Israeli study on adults without known cardiovascular disease&#44; it was found that nonspecific T-wave changes appeared to be associated with an increase in long-term all-cause mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> Other results based on follow-up on a Belgian population showed that flat T-wave findings were among the electrical abnormalities most predictive of cardiac mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">In post-menopausal women&#44; the identification of minor ECG abnormalities &#40;analyzed jointly and classified according to the Novacode classification&#41; was associated with the onset of coronary &#40;hazard ratio &#40;HR&#41;&#8239;&#61;&#8239;1&#46;55&#59; 95&#37; confidence interval &#40;CI&#41;&#8239;&#61;&#8239;1&#46;14&#8211;2&#46;11&#41; and cardiovascular disease &#40;HR&#8239;&#61;&#8239;1&#46;39&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;14&#8211;1&#46;68&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">A recent investigation corroborated that cardiovascular risk factors are associated with future onset of NVRA&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> NVRA have been associated with an increased risk of mortality due to coronary disease&#44; the occurrence of coronary events&#44; and primary arrhythmias in older adult patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">49&#44;50</span></a> Minor ST&#47;T abnormalities on precordial leads have even been seen in patients with significant left main coronary artery lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> Minimal changes in non-ST-segment elevation acute coronary syndrome can also be observed&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a> Persistent NVRA not attributable to physiological disorders are associated with cardiovascular mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Greenland et al&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> determined the impact of NVRA on cardiovascular mortality and found that minor T-wave abnormalities &#40;in men&#41; and minor ST-segment depression &#40;in women&#41; were associated with an increased risk of death due to cardiovascular and coronary disease&#46; In two cohorts derived from the NHANES-III study&#44; a greater risk of cardiovascular mortality was found when NVRA was identified&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;53</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">In a cohort of middle-aged adult men without a medical history of cardiovascular disease who were followed-up on for 29 years&#44; the presence of NVRA was independently associated with mortality due to myocardial infarction&#44; cardiovascular disease&#44; and all causes&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> The risk was greater when NVRA were detected 2 or &#8805;3 times on annual examinations compared to just one observance in five consecutive years&#46; The presence of flat T waves was associated with a risk of major adverse cardiovascular events on a univariate and multivariate analysis in a low-risk general adult population&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">In a sample of 50-year-old Swedish men&#44; the identification of minor T-wave abnormalities increased the risk of overall and cardiovascular death by 56&#37; and 78&#37;&#44; respectively&#44; after follow-up over two decades&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> The significance of new-onset MVRA was examined by Sawai et al&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> in a prospective Japanese cohort&#46; Its identification was associated with increased risk of overall cardiovascular disease&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In the WOSCOPS study &#40;men between 55 and 64 years of age&#41;&#44; a univariate analysis showed that MVRA entailed a significant risk for the endpoint of death due to cardiovascular disease&#47;non-fatal myocardial infarction and for all-cause mortality at five years&#46; The risk was even greater than what was observed with other classical risk factors&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">The anatomical localization of T-wave inversion also influences the magnitude of cardiovascular risk&#46; In a representative sample of Finnish subjects&#44; a multivariate analysis showed that T-wave inversion on anterior and lateral leads&#44; but not on inferior leads&#44; was associated with a greater risk of coronary heart disease&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> Only lateral T-wave inversions were associated with a greater risk of mortality in the total study population&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Using data from 1393 subjects included in the CHAS study&#44; Vu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> reported new-onset MVRA in 9&#46;4&#37; after 39 years of follow-up&#46; A favorable cardiovascular risk profile at the start of the study or an improvement in the profile during follow-up were not significantly associated with the onset of these electrocardiographic abnormalities compared to other categories of greater cardiovascular risk&#46; However&#44; a low risk profile was associated with a lower rate of developing major ECG abnormalities&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The CARDIA study evaluated the possible link between NVRA and subclinical atherosclerosis through their association with coronary artery calcium measurements and common carotid intima-media thickness&#46; A multivariate analysis which included 2175 participants revealed no association with coronary artery calcium measurements &#40;odds ratio &#40;OR&#41;&#8239;&#61;&#8239;0&#46;91&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;77&#8211;1&#46;08&#41;&#44; although this was not the case for the common carotid intima-media thickness index &#40;OR&#8239;&#61;&#8239;1&#46;27&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;07&#8211;1&#46;50&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Hypertension&#47;left ventricular hypertrophy</span><p id="par0140" class="elsevierStylePara elsevierViewall">In a large Chinese study that included 15&#44;038 hypertensive individuals&#44; it was observed that NVRA behaved as independent predictors of poor blood pressure control&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a> During follow-up on 1970 hypertensive patients without ischemic heart disease&#44; the occurrence of coronary events was greater in patients with MVRA than in those with normal repolarization after adjusting for the effects of age&#44; sex&#44; diabetes mellitus&#44; serum cholesterol&#44; tobacco use&#44; left ventricular hypertrophy&#44; and pulse pressure&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> NVRA were associated with deterioration in left ventricular relaxation and left ventricular hypertrophy in a cross-sectional study comprising 74&#44;976 Koreans who underwent a comprehensive medical examination&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a> The association between NVRA and abnormal left ventricular relaxation was greater in the group at intermediate and high risk of cardiovascular disease&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Cerebrovascular disease</span><p id="par0145" class="elsevierStylePara elsevierViewall">A Japanese study established that men with MVRA had a 2&#46;3 times greater age-adjusted relative risk of both ischemic and hemorrhagic stroke&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> In another study on subjects of the same nationality&#44; MVRA were associated with an increased risk of cerebral infarction in the entire population studied&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">In the REGARDS study cohort&#44; it was demonstrated that the presence of NVRA significantly increased the risk of incident ischemic stroke independently of the existence of traditional or new risk factors or major ECG abnormalities&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> There was an independent nonlinear association between NVRA and mortality in patients with subarachnoid hemorrhage who underwent surgery for aneurysms &#40;OR&#8239;&#61;&#8239;3&#46;1&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;031&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Diabetes mellitus</span><p id="par0155" class="elsevierStylePara elsevierViewall">In individuals with diabetes&#44; a hypothesis has been proposed that the higher rate of NVRA development could be related to silent myocardial ischemia based on the notion that autonomic neuropathy eliminates the sensation of pain&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">64&#44;65</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Epilepsy</span><p id="par0160" class="elsevierStylePara elsevierViewall">A recent systematic review found that individuals who have epilepsy have a greater probability of having minor ST-segment abnormalities in interictal periods&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">66</span></a> Up to 40&#37; of epileptic seizures could cause ST-segment depression&#44; but troponin T levels remain normal in most patients&#46; This shows that if the change is induced by acute transitory ischemia&#44; the myocardial lesion is not severe&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">67</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">In 127 children diagnosed with epilepsy in whom pre-existing heart disease or ion channel diseases were ruled out&#44; the prevalence of nonspecific ST-segment abnormalities was 19&#37; and the prevalence of nonspecific T-wave abnormalities was 30&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">68</span></a> The duration of epilepsy was an independent risk factor for ECG changes in these children&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">COVID-19</span><p id="par0170" class="elsevierStylePara elsevierViewall">In 31 consecutive COVID-19 cases&#44; the presence of myocardial damage gave rise to T-wave inversions of up to 5&#8239;mm&#44; but never greater than 2&#8239;mm&#44; in patients without heart involvement&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">69</span></a> NVRA significantly predicted death due to COVID-19 in a retrospective cohort that comprised 756 patients&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> ST&#47;T abnormalities are more probable in severe COVID-19 than in mild forms&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">70</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">The presence of NVRA in patients with COVID-19 is associated with myocardial lesion and poor outcomes&#44; including among others&#58; greater need for intensive care unit admission&#44; more frequent mechanical ventilatory support&#44; and greater mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">38&#44;71</span></a> Recently&#44; Angeli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">72</span></a> concluded in a study that ECG abnormalities during hospitalization due to COVID-19 pneumonia reflect a wide spectrum of cardiovascular complications&#44; have a late onset&#44; do not progress in parallel with lung abnormalities&#44; and can occur after negative swabs&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">In 82 children with asymptomatic&#44; mild&#44; or moderate COVID-19 who did not require hospitalization&#44; Heching et al&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">73</span></a> demonstrated electrocardiographic changes in 21&#37;&#44; but borderline abnormalities&#8212;which included NVRA&#8212;were only detected in ten patients &#40;12&#37;&#41;&#46; In patients with moderate&#44; severe&#44; and critical COVID-19 who were discharged &#40;n&#8239;&#61;&#8239;594&#41;&#44; ST&#47;T changes were identified &#40;without indicating specific or nonspecific abnormalities&#41; at three months in 19&#46;9&#37; of cases&#59; their prevalence was greater among those with moderate disease&#46; In 23&#46;5&#37; of cases&#44; these abnormalities persisted at six months from discharge&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">74</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">The prevalence of ST&#47;T changes remained elevated at one year of follow-up &#40;20&#37;&#44; n&#8239;&#61;&#8239;486&#41; and was higher among patients who had moderate and critical COVID-19&#46; The electrocardiographic changes in COVID-19 can be explained by the following factors acting jointly or individually&#58; 1&#41; cytokine storm&#44; 2&#41; hypoxic lesion&#44; 3&#41; electrolyte abnormalities&#44; 4&#41; plaque rupture&#44; 5&#41; coronary artery spasm&#44; and 6&#41; microthrombi or direct endothelial or myocardial lesion&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">75</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Other clinical contexts</span><p id="par0190" class="elsevierStylePara elsevierViewall">In an independent analysis of the CARDIA study&#44; no relationship was found between occasional marijuana use among young adults and the existence of minor ECG changes&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">76</span></a> Recently&#44; Xiao et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">77</span></a> reported that non-alcoholic fatty liver disease constituted an independent predictor of NVRA after analyzing data from 32&#44;922 patients &#40;adjusted OR&#8239;&#61;&#8239;1&#46;29&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;12&#8211;1&#46;48&#41;&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">The clinical value of NVRA increases if we take into account that most studies find a much lower prevalence of major ST&#47;T abnormalities&#44; which varies according to age&#44; sex&#44; type of population analyzed&#44; and pre-existing comorbidities&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">78&#44;79</span></a> At present&#44; it is accepted that NVRA have potential from a preventative point of view&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">The mechanism by which NVRA act as cardiovascular predictors is not known&#46; There has been speculation about the following mechanisms&#58; &#40;1&#41; markers of patent heart disease expressed incompletely on the ECG&#59; &#40;2&#41; subclinical myocardial damage&#44; and &#40;3&#41; systemic disease with cardiac involvement&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">In a nontrivial number of cases&#44; patients with NVRA present with symptoms that point to ischemic heart disease&#46; The presence of such symptoms is more important as a predictor of risk than the electrocardiographic changes themselves&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Negative results</span><p id="par0210" class="elsevierStylePara elsevierViewall">Contrary to the aforementioned findings&#44; in the MINACOR study&#44; which analyzed an initial cohort of 352 hypertensive&#44; non-diabetic patients without associated cardiovascular disease who were followed-up on for 16 years&#44; no significant association between NVRA and cardiovascular morbidity and mortality was found &#40;HR&#8239;&#61;&#8239;0&#46;97&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;49&#8211;1&#46;90&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Some authors have argued that the cause of this lack of an association could be related to the binary form of the analysis &#40;presence of NVRA or not&#41; and suggest that a dose-response analysis based on the exponential increase in cardiovascular mortality as the number of minor ECG abnormalities increases would be better&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">In patients with peripheral arterial disease&#44; minor ECG abnormalities were not significant predictors of major cardiovascular events&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> After 19 years of follow-up on 1306 patients with type 1 diabetes mellitus &#40;mean age 35&#46;5&#8239;&#177;&#8239;6&#46;9 years&#41; who formed part of the EDIC study&#44; it was not found that minor ECG abnormalities were significant predictors of cardiovascular events&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">In the last two studies mentioned&#44; a general classification was used for ECG abnormalities &#40;major and minor abnormalities&#41;&#46; Although this simplifies the analysis from a practical point of view&#44; the lack of a separate approach to the different types of changes may have affected their conclusions&#46; The investigators of the EDIC study themselves recognized in the study limitations that if ECG abnormalities had been analyzed separately&#44; different associations with cardiovascular disease may have been drawn&#46; However&#44; they argued that the overall classification had been satisfactorily used before and that statistical power increases with it&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">A summary of the main prognostic studies can be seen in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Recommendations</span><p id="par0230" class="elsevierStylePara elsevierViewall">Most available studies demonstrate that the presence of NVRA entails significant cardiovascular risk&#46; As such&#44; we recommend that they should be added to the classical cardiovascular risk factors examined during the clinical evaluation&#46; The variety of contexts in which they may appear means that different approaches should be considered for their analysis&#46; When NVRA occur in acute scenarios&#44; such as precordial pain indicative of acute myocardial ischemia&#44; symptoms that imply electrolyte disorders &#40;diarrhea&#44; chronic kidney disease&#41;&#44; the post-seizure period&#44; or active COVID-19&#44; the interpretation should be more causal&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">The biggest challenge is the case of asymptomatic patients in whom whether there are identifiable cardiovascular risk factors must be taken into account &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; In the event they are present&#44; a possible causal nexus aimed at the heart as the target organ should be searched for&#46; Working with identified risk factors will be the primordial task&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Improving blood pressure control&#44; improving glycemic control&#44; reducing body weight in individuals with obesity&#44; stopping smoking and excessive alcohol intake&#44; doing physical activity&#44; and eating a healthy diet should be recommended in these cases&#46; Due to these patients&#8217; increased risk of cardiovascular events&#44; quarterly monitoring in a medical consultation should be planned in all cases&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusions</span><p id="par0245" class="elsevierStylePara elsevierViewall">Many clinical studies demonstrate that NVRA should be considered in a cardiovascular risk evaluation&#46; They may represent initial forms of left ventricular hypertrophy or a subtle expression of significant coronary disease or various cardiomyopathies&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">In other non-cardiovascular contexts&#44; the presence of NVRA indicates a cardiac repercussion&#46; Their appearance in asymptomatic adults should not be taken lightly and this scenario represent the greatest clinical challenge&#46; The cumulative evidence reveals their capacity for predicting cardiovascular morbidity and mortality&#46; Therefore&#44; when present&#44; a diligent analysis must be conducted before concluding that they are a benign finding&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">NVRA must be included as another risk factor in preventative medicine&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Funding</span><p id="par0260" class="elsevierStylePara elsevierViewall">This review has not received specific grants from agencies in the public&#44; commercial&#44; or non-profit sectors&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicts of interest</span><p id="par0265" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Introduction"
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          "titulo" => "Clinical significance"
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            0 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Cardiovascular morbidity and mortality"
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            1 => array:2 [
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              "titulo" => "Hypertension&#47;left ventricular hypertrophy"
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              "titulo" => "Cerebrovascular disease"
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              "titulo" => "Diabetes mellitus"
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              "titulo" => "COVID-19"
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              "titulo" => "Other clinical contexts"
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    "fechaRecibido" => "2022-02-21"
    "fechaAceptado" => "2022-03-16"
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            0 => "Minor nonspecific ST-T abnormalities"
            1 => "Electrocardiogram"
            2 => "Cardiovascular mortality"
            3 => "Nonspecific ventricular repolarization abnormalities"
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          "palabras" => array:4 [
            0 => "Alteraciones menores inespec&#237;ficas del ST-T"
            1 => "Electrocardiograma"
            2 => "Mortalidad cardiovascular"
            3 => "Trastornos inespec&#237;ficos de la repolarizaci&#243;n ventricular"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The term nonspecific ventricular repolarization abnormalities refers to a set of minor alterations of the ST segment and&#47;or the T wave&#46; For a long time&#44; they have been of little clinical interest as they do not translate into specific diagnoses&#46; It has even been asserted that they constitute benign electrocardiographic findings&#46; Their presence has been reported in various cardiovascular and non-cardiovascular diseases&#46; However&#44; it is frequently identified in apparently healthy asymptomatic people&#46; A growing number of studies demonstrate their importance as predictors of cardiovascular morbidity and mortality&#44; expanding their spectrum towards cardiovascular prevention&#46; In light of the body of scientific evidence&#44; it is imperative that the traditional view of nonspecific ventricular repolarization abnormalities changes&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">El t&#233;rmino trastornos inespec&#237;ficos de la repolarizaci&#243;n ventricular se refiere a un conjunto de alteraciones menores del segmento ST y&#47;o la onda T&#46; Durante mucho tiempo han sido de escaso inter&#233;s cl&#237;nico al no traducir diagn&#243;sticos espec&#237;ficos&#46; De forma extrema&#44; se ha aseverado que constituyen hallazgos electrocardiogr&#225;ficos benignos&#46; Su presencia se ha reportado en diversos estados patol&#243;gicos cardiovasculares y no cardiovasculares&#46; Sin embargo&#44; con frecuencia se identifica en personas asintom&#225;ticas aparentemente sanas&#46; Un creciente n&#250;mero de estudios demuestran su importancia como predictores de morbimortalidad cardiovascular&#44; expandiendo su espectro hacia la prevenci&#243;n cardiovascular&#46; A la luz de las evidencias cient&#237;ficas acumuladas se impone un cambio en la visi&#243;n tradicional que se ha tenido con los trastornos inespec&#237;ficos de la repolarizaci&#243;n ventricular&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Carmona-Puerta R&#44; Lorenzo-Mart&#237;nez E&#46; Trastornos inespec&#237;ficos de la repolarizaci&#243;n ventricular&#58; un lobo con piel de oveja&#46; Rev Clin Esp&#46; 2022&#59;222&#58;549&#8211;562&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Twelve-lead electrocardiogram that shows nonspecific ventricular repolarization abnormalities in a 43-year-old asymptomatic man&#46; Flat T waves are observed on the I&#44; aVL&#44; V5&#44; and V6 leads&#46; The patient had a diagnosis of controlled hypertension and had a normal echocardiogram&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Proposed clinical management algorithm for asymptomatic patients with nonspecific ventricular repolarization disorders&#46;</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">&#42;The algorithm may vary depending on clinical progress&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">ECG&#58; electrocardiogram&#59; NVRA&#58; nonspecific ventricular repolarization abnormalities&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleBold">Physiological</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Minor T-wave inversion in young adults and women on V2 and inferior leads</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Hyperventilation</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">After food intake</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Changes in position</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Changes in sympathetic tone</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Pathophysiological &#40;directly or indirectly associated&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cardiac stimulation &#40;cardiac memory in its shallow forms&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ventricular arrhythmias &#40;cardiac memory in its shallow forms&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Intermittent left bundle branch block &#40;cardiac memory in its shallow forms&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Intermittent ventricular pre-excitation &#40;cardiac memory in its shallow forms&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Myocardial ischemia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pericarditis &#40;stage 3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mitral valve prolapse &#40;frequently on inferior leads&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pericardial effusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pericardial abscess&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Infiltrative cardiac diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pulmonary embolism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Electrolyte abnormalities</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mild hypokalemia&#47;hypomagnesemia&#47;hypocalcemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Endocrine abnormalities</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diabetes mellitus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hypothyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hypopituitarism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Adrenal gland failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Connective tissue diseases</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Systemic lupus erythematosus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rheumatoid arthritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Neurological diseases</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Epilepsy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ischemic and hemorrhagic stroke&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Becker muscular dystrophy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Other</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Post-resuscitation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Left pleural effusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>COVID-19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Malignant hyperthermia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Use of certain drugs &#40;antiarrhythmics&#44; psychotropics&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Acute exposure to ambient particles &#60;2&#46;5 &#181;m in diameter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Electroconvulsive therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Gastroenteritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cholecystitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sickle cell anemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Truncal vagotomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Breast implants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">MTWA&#58; minor T-wave abnormalities&#59; MSTD&#58; minor ST-segment depression&#59; ECG&#58; electrocardiogram&#59; HR&#58; hazard ratio&#59; HT&#58; hypertension&#59; CI&#58; confidence interval&#59; OR&#58; odds ratio&#59; RR&#58; relative risk&#59; NVRA&#58; nonspecific ventricular repolarization abnormalities&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">References&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Electrocardiographic definitions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study population&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Main outcomes related to NVRA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Istolahti et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> 2021<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inverted T wave if amplitude &#60;0 &#181;VIn isodiphasic T waves&#44; the lowest part of the wave indicated the levelLead groups&#58; lateral &#40;I&#44; aVL&#44; V5&#44; and V6&#41;&#44; inferior &#40;II&#44; aVF&#41;&#44; and anterior &#40;V2&#44; V3&#44; and V4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational&#44; prospective study with 15&#8239;years of follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;6354Age&#58; &#62;30 yearsFinnish&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Risk of coronary heart disease for inverted T waves in anterior &#40;HR&#8239;&#61;&#8239;2&#46;37&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;20&#8722;4&#46;68&#41; and inferior localizations &#40;HR&#8239;&#61;&#8239;1&#46;65&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;27&#8722;2&#46;15&#41;Risk of death with inverted T waves on lateral leads &#40;HR&#8239;&#61;&#8239;1&#46;59&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;29&#8722;1&#46;96&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Shin et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minnesota Code&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational&#44; prospective study with 12 years of follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;8444Age&#58; 40&#8722;69 yearsLow-risk Korean population&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Flat T waves&#44; increased risk of major cardiovascular eventsUnivariate&#58; HR&#8239;&#61;&#8239;1&#46;70&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;27&#8722;2&#46;28Multivariate&#58; HR&#8239;&#61;&#8239;1&#46;42&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;05&#8722;1&#46;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sj&#246;land et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minnesota Code&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational&#44; prospective study with &#62; 20 years of follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;839Randomly selected 50-year-old Swedish males followed-up on until death&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased risk in cases of minor T-wave abnormalitiesRisk of overall mortality&#58; HR&#8239;&#61;&#8239;1&#46;56&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;10&#8722;2&#46;21Risk of cardiovascular mortality&#58; HR&#8239;&#61;&#8239;1&#46;78&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;13&#8722;2&#46;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sawano et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minnesota Code&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational&#44; prospective study with a mean follow-up of 9&#46;6 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;14&#44;077Average age&#58; 63&#46;4&#8239;&#177;&#8239;9&#46;1 yearsWomen&#58; 59&#46;1&#37;Black&#58; 41&#46;4&#37;North Americans living in areas with high prevalences of stroke &#40;50&#37;&#41; and other continental areas &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased risk of ischemic stroke in patients with isolated NVRAMultivariate analysis&#58;HR&#8239;&#61;&#8239;1&#46;32&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;05&#8722;1&#46;67Adjusted for age&#44; sex&#44; race&#44; geographic location&#44; educational level&#44; and age-race interaction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">McCullough et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">According to the judgment of 2 electrocardiographers with more than 100&#44;000 reports&#47;year between them&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational&#44; retrospective cohort study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;756Average age&#58; 63&#46;3&#8239;&#177;&#8239;16&#46;0 years37&#37; women&#44; 61&#37; non-white&#44; 57&#37; hypertensivePatients hospitalized in a large university hospital in New York&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The presence of NVRA on the ECG taken upon hospital admission was associated with a greater risk of death due to COVID-19Univariate OR&#8239;&#61;&#8239;1&#46;86&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;18&#8722;2&#46;92 and multivariate OR&#8239;&#61;&#8239;2&#46;31&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;27&#8722;4&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hari et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> 2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minnesota Code&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational&#44; prospective study with a mean follow-up of 13&#46;9 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;6467Average age&#58; 58&#46;9 years old&#46;Representative sample of noninstitutionalized North American civilians49&#37; non-Hispanic whites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The presence of minor isolated ST&#47;T abnormalities increases the risk of cardiovascular mortalityModel adjusted for age&#44; sex&#44; race&#44; various cardiovascular risk factors&#44; and other minor ECG abnormalities&#58;HR&#8239;&#61;&#8239;1&#46;22&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;00&#8722;1&#46;47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Goldman et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> 2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minnesota Code&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational&#44; prospective study with a mean follow-up of 31 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;2&#44;601&#44; randomized selectionAge&#58; 54&#46;5&#8239;&#177;&#8239;8&#46;0 years52&#37; womenNo known cardiovascular diseaseIsraeli population&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nonspecific T-wave changes were associated with overall mortality risk on the multivariate analysisHR&#8239;&#61;&#8239;1&#46;18&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;05&#8722;1&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ishikawa et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minnesota Code&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational&#44; prospective study with annual follow-up for 10 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;10&#44;642Average age&#58; 55&#46;4&#8239;&#177;&#8239;11&#46;2 years37&#46;6&#37; menGeneral Japanese population&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Association between NVRA and occurrence of cerebral infarctionHR&#8239;&#61;&#8239;2&#46;10&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;57&#8722;2&#46;81NVRA in cases with hyperlipidemia&#58; HR&#8239;&#61;&#8239;1&#46;75&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;15&#8722;2&#46;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sawai et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> 2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minnesota Code&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational&#44; prospective study with a median follow-up of 23 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;9374 &#40;3545 men&#47;5829 women&#41;Japanese individuals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minor ST-segment abnormalities&#58; 19&#37; increase in total cardiovascular disease riskMinor T-wave abnormalities&#58; 42&#37; increase in total cardiovascular disease risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Badheka et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a> 2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minnesota Code&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational retrospective study with data collected prospectively&#46; Mean follow-up&#58; 13&#46;5&#8239;&#177;&#8239;3&#46;8 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;4426 North AmericansAge&#58; 40&#8722;90 yearsNo coronary disease or equivalents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Risk of overall mortality according to presence of NVRA&#58; HR&#8239;&#61;&#8239;1&#46;37&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;03&#8722;1&#46;81&#46; Risk of cardiovascular mortality according to presence of NVRA&#58; HR&#8239;&#61;&#8239;1&#46;71&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;04&#8722;2&#46;83The model was adjusted for age&#44; sex&#44; race&#44; body mass index&#44; smoking habit&#44; hypercholesterolemia&#44; glomerular filtration rate&#44; heart rate&#44; corrected QT interval&#44; and left ventricular mass index&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Macfarlane and Norris&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a> 2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minnesota Code&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational&#44; prospective study&#46;Estimation of risk at 5&#8239;years of follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;6&#44;595&#44; Scottish menAge&#58; 55&#8722;65&#8239;years at the start of the study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Risk of cardiovascular disease&#47;non-fatal myocardial infarction at five years&#58; HR&#8239;&#61;&#8239;1&#46;70&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;28&#8722;2&#46;26Risk of all-cause death at five years&#58; HR&#8239;&#61;&#8239;2&#46;16&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;53&#8722;3&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Schillaci et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> 2004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minnesota Code&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational&#44; prospective study with a mean follow-up of 4&#46;7 years&#44; maximum 9&#46;1 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;1970 hypertensive patients without ischemic heart disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased risk of coronary events in hypertensive patients with NVRAHR&#8239;&#61;&#8239;2&#46;07&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;23&#8722;3&#46;47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ohira et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> 2003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minnesota Code&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational&#44; prospective study with follow-up for 15&#46;4 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;10&#44;741Age&#58; 40&#8722;69 yearsPopulation of four Japanese communities&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased risk of ischemic or hemorrhagic stroke in men with NVRA &#40;RR adjusted for age&#8239;&#61;&#8239;2&#46;3&#41;After adjusting for HT&#44; the risk remained significant&#58;RR total stroke&#8239;&#61;&#8239;1&#46;8&#59; 95&#37; IC&#8239;&#61;&#8239;1&#46;3&#8722;2&#46;4RR ischemic stroke&#8239;&#61;&#8239;1&#46;9&#59; 95&#37; IC&#8239;&#61;&#8239;1&#46;3&#8722;2&#46;8RR hemorrhagic stroke&#8239;&#61;&#8239;1&#46;7&#59; 95&#37; IC&#8239;&#61;&#8239;1&#46;0&#8722;3&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Greenland et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> 2003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minnesota Code&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational&#44; prospective study with follow-up for 22 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;17&#44;6157556 Caucasian and 429 African American women9144 Caucasian and 486 African American menAge&#58; 40&#8722;64 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MTWA in men&#58; increased risk of mortality due to cardiovascular disease&#58; Age-adjusted HR&#8239;&#61;&#8239;2&#46;24&#44; <span class="elsevierStyleItalic">p</span>&#60;0&#46;001 and coronary disease&#58; Age-adjusted HR&#8239;&#61;&#8239;2&#46;21&#44; <span class="elsevierStyleItalic">p</span>&#60;0&#46;001MSTD in women&#58; increased risk of mortality due to cardiovascular disease&#58; HR&#8239;&#61;&#8239;1&#46;93 and coronary disease&#58; HR&#8239;&#61;&#8239;1&#46;91All HR are adjusted for age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Daviglus et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> 1999&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minnesota Code&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational&#44; prospective study with follow-up for 29 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;1673Age upon entering the study&#58; 40&#8722;55&#8239;yearsWithout evidence of coronary disease or major ECG abnormalities in the first five years of follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RR of death adjusted for age since an ECG with minor ST&#47;T abnormalities up to &#8805;3Due to myocardial infarction&#58; one ECG-RR&#8239;&#61;&#8239;1&#46;66 &#40;95&#37; CI&#8239;&#61;&#8239;1&#46;05&#8722;2&#46;62&#41;&#44; &#8805;3 ECG-RR&#8239;&#61;&#8239;2&#46;63 &#40;95&#37; CI&#8239;&#61;&#8239;1&#46;35&#8722;5&#46;12&#41;Due to cardiovascular diseases&#58; one ECG-RR&#8239;&#61;&#8239;1&#46;42 &#40;95&#37; CI&#8239;&#61;&#8239;1&#46;01&#8722;2&#46;02&#41;&#44; &#8805;3 ECG-RR&#8239;&#61;&#8239;2&#46;88 &#40;95&#37; CI&#8239;&#61;&#8239;1&#46;81&#8722;4&#46;56&#41;Due to all causes&#58; one ECG-RR&#8239;&#61;&#8239;1&#46;34 &#40;95&#37; CI&#8239;&#61;&#8239;1&#46;04&#8722;1&#46;73&#41;&#44; &#8805;3 ECG-RR&#8239;&#61;&#8239;1&#46;88 &#40;95&#37; CI&#8239;&#61;&#8239;1&#46;25&#8722;2&#46;82&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">De Bacquer et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> 1998&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minnesota Code&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational&#44; prospective study with follow-up for at least 10 years regarding cause of death&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;5208 men and 4746 women selected by random sampling stratified based on age and sexAge&#58; 25&#8722;74 yearsBelgian populationNo evidence of coronary disease at the start of the study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Flat T waves predicted cardiovascular mortality&#58;RR&#8239;&#61;&#8239;2&#46;47&#59; 95&#37; CI&#8239;&#61;&#8239;1&#46;83&#8722;3&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Main studies which show the prognostic value of nonspecific ventricular repolarization abnormalities&#46;</p>"
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