Use of Mayer wave activity to demonstrate aberrant cardiovascular autonomic control following sports concussion injury.

Dysregulation of cardiovascular autonomic control is gaining recognition as a prevailing consequence of concussion injury. Characterizing the presence of autonomic dysfunction in concussed persons is inconsistent and conventional metrics of autonomic function cannot differentiate the presence/absence of injury. Mayer wave (MW) activity originates through baroreflex adjustments to blood pressure (BP) oscillations that appear in the low-frequency (LF: 0.04-0.15 Hz) band of the BP and heart rate (HR) power spectrum after a fast Fourier transform. We prospectively explored MW activity (∼0.1 Hz) in 19 concussed and 19 noninjured athletes for 5 min while seated at rest within 48 h and 1 week of injury. MW activity was derived from the LF band of continuous digital electrocardiogram and beat-to-beat BP signals (LFHR, LF-SBP, MWHR, and MW-SBP, respectively); a proportion between MWBP and MWHR was computed (cMW). At 48 h, the concussion group had a significantly lower MWBP and cMW than controls; these differences were gone by 1 week. MWHR, LFHR, and LF-SBP were not different between groups at either visit. Attenuated sympathetic vasomotor tone was present and the central autonomic mechanisms regulating MW activity to the heart and peripheral vasculature became transiently discordant early after concussion with apparent resolution by 1 week.

Artificial Intelligence-Enhanced Electrocardiogram for the Early Detection of Cardiac Amyloidosis.

OBJECTIVE: To develop an artificial intelligence (AI)-based tool to detect cardiac amyloidosis (CA) from a standard 12-lead electrocardiogram (ECG). METHODS: We collected 12-lead ECG data from 2541 patients with light chain or transthyretin CA seen at Mayo Clinic between 2000 and 2019. Cases were nearest neighbor matched for age and sex, with 2454 controls. A subset of 2997 (60%) cases and controls were used to train a deep neural network to predict the presence of CA with an internal validation set (n=999; 20%) and a randomly selected holdout testing set (n=999; 20%). We performed experiments using single-lead and 6-lead ECG subsets. RESULTS: The area under the receiver operating characteristic curve (AUC) was 0.91 (CI, 0.90 to 0.93), with a positive predictive value for detecting either type of CA of 0.86. By use of a cutoff probability of 0.485 determined by the Youden index, 426 (84%) of the holdout patients with CA were detected by the model. Of the patients with CA and prediagnosis electrocardiographic studies, the AI model successfully predicted the presence of CA more than 6 months before the clinical diagnosis in 59%. The best single-lead model was V5 with an AUC of 0.86 and a precision of 0.78, with other single leads performing similarly. The 6-lead (bipolar leads) model had an AUC of 0.90 and a precision of 0.85. CONCLUSION: An AI-driven ECG model effectively detects CA and may promote early diagnosis of this life-threatening disease.

QTc Prolongation in COVID-19 Patients Using Chloroquine.

Chloroquine is used in the treatment of patients with COVID-19 infection, although there is no substantial evidence for a beneficial effect. Chloroquine is known to prolong the QRS and QTc interval on the ECG. To assess the effect of chloroquine on QRS and QTc intervals in COVID-19 patients, we included all inpatients treated with chloroquine for COVID-19 in the Spaarne Gasthuis (Haarlem/Hoofddorp, the Netherlands) and had an ECG performed both in the 72 h before and during or at least 48 h after treatment. We analyzed the (change in) QRS and QTc interval using the one-sample t-test. Of the 106 patients treated with chloroquine, 70 met the inclusion criteria. The average change in QRS interval was 6.0 ms (95% CI 3.3-8.7) and the average change in QTc interval was 32.6 ms (95% CI 24.9-40.2) corrected with the Bazett's formula and 38.1 ms (95% CI 30.4-45.9) corrected with the Fridericia's formula. In 19 of the 70 patients (27%), the QTc interval was above 500 ms after start of chloroquine treatment or the change in QTc interval was more than 60 ms. A heart rate above 90 bpm, renal dysfunction, and a QTc interval below 450 ms were risk factors for QTc interval prolongation. Chloroquine prolongs the QTc interval in a substantial number of patients, potentially causing rhythm disturbances. Since there is no substantial evidence for a beneficial effect of chloroquine, these results discourage its use in COVID-19 patients.

Spontaneous reported cardiotoxicity induced by lopinavir/ritonavir in COVID-19. An alleged past-resolved problem.

The antiretroviral drug lopinavir/ritonavir has been recently repurposed for the treatment of COVID-19. Its empirical use has been associated with multiple cardiac adverse reactions pertaining to its ancillary multi-channel blocking properties, vaguely characterized until now. We aimed to characterize qualitatively the cardiotoxicity associated with lopinavir/ritonavir in the setting of COVID-19. Spontaneous notifications of cardiac adverse drug reactions reported to the national Pharmacovigilance Network were collected for 8 weeks since March 1st 2020. The Nice Regional Center of Pharmacovigilance, whose scope of expertise is drug-induced long QT syndrome, analyzed the cases, including the reassessment of all available ECGs. QTc ≥ 500 ms and delta QTc > 60 ms from baseline were deemed serious. Twenty-two cases presented with 28 cardiac adverse reactions associated with the empirical use of lopinavir/ritonavir in a hospital setting. Most adverse reactions reflected lopinavir/ritonavir potency to block voltage-gated potassium channels with 5 ventricular arrhythmias and 17 QTc prolongations. An average QTc augmentation of 97 ± 69 ms was reported. Twelve QTc prolongations were deemed serious. Other cases were likely related to lopinavir/ritonavir potency to block sodium channels: 1 case of bundle branch block and 5 recurrent bradycardias. The incidence of cardiac adverse reactions of lopinavir/ritonavir was estimated between 0.3% and 0.4%. These cardiac adverse drug reactions offer a new insight in its ancillary multi-channel blocking functions. Lopinavir/ritonavir cardiotoxicity may be of concern for its empirical use during the COVID-19 pandemic. Caution should be exerted relative to this risk where lopinavir/ritonavir summary of product characteristics should be implemented accordingly.

Mexiletine in Myotonic Dystrophy Type 1: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To assess mexiletine's long-term safety and effect on 6-minute walk distance in a well-defined cohort of patients with myotonic dystrophy type 1 (DM1). METHODS: We performed a randomized, double-blind, placebo-controlled trial of mexiletine (150 mg 3 times daily) to evaluate its efficacy and safety in a homogenous cohort of adult ambulatory patients with DM1. The primary outcome was change in 6-minute walk distance at 6 months. Secondary outcomes included changes in hand grip myotonia, strength, swallowing, forced vital capacity, lean muscle mass, Myotonic Dystrophy Health Index scores, and 24-hour Holter and ECG results at 3 and 6 months. RESULTS: Forty-two participants were randomized and 40 completed the 6-month follow-up (n = 20 in both groups). No significant effects of mexiletine were observed on 6-minute walk distance, but hand grip myotonia was improved with mexiletine treatment. There were no differences between the mexiletine and placebo groups with respect to the frequency or type of adverse events. Changes in PR, QRS, and QTc intervals were similar in mexiletine- and placebo-treated participants. CONCLUSIONS: There was no benefit of mexiletine on 6-minute walk distance at 6 months. Although mexiletine had a sustained positive effect on objectively measured hand grip myotonia, this was not seen in measures reflecting participants' perceptions of their myotonia. No effects of mexiletine on cardiac conduction measures were seen over the 6-month follow-up period. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for ambulatory patients with DM1, mexiletine does not significantly change 6-minute walk distance at 6 months.

Assessing QT interval in COVID-19 patients:safety of hydroxychloroquine-azithromycin combination regimen.

BACKGROUND: Hydroxychloroquine (HCQ) and azithromycin (AZT) have been proposed for COVID-19 treatment. Data available in the literature reported a potential increased risk of fatal arrhythmias under these therapies. The aim of this study was to assess the effects of these drugs on QT interval and outcome in a COVID-19 population. METHOD: A total of 112 consecutive COVID-19 patients were included in this analysis and were divided in 3 groups according to the receiving therapeutic regimens: 19 (17%) patients in Group 1 (no treatment), 40 (36%) in Group 2 (HCQ only), 53 (47%) in Group 3 (HCQ/AZT). RESULTS: A prolonged QTc interval was found in 61% of patients treated with HCQ alone or in combination with AZT, but only 4 (4%) patients showed a QTc > 500 ms. HCQ/AZT combination determined a greater increase of QTc duration compared to the other two strategies (Group 3 452 ± 26.4 vs Group 2 436.3 ± 28.4 vs Group 1 424.4 ± 24.3 ms, respectively; p < 0.001). Multivariate analysis demonstrated that HCQ/AZT combination (OR 9.02, p = 0.001) and older age (OR 1.04, p = 0.031) were independent predictors of QTc prolongation. The risk increased with age (incremental utility analysis p = 0.02). Twenty patients (18%) died, and no cardiac arrest neither arrhythmic fatalities were documented. CONCLUSIONS: The HCQ/AZT combination therapy causes a significantly increase of QT interval compared to HCQ alone. Older patients under such regimen are at higher risk of experiencing QT prolongation. The use of such drugs may be considered as safe relating to arrhythmic risk in the treatment of COVID-19 patients as no arrhythmic fatalities occurred.

Global variations in the prevalence, treatment, and impact of atrial fibrillation in a multi-national cohort of 153 152 middle-aged individuals.

AIMS: To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine antithrombotic use and clinical outcomes. METHODS AND RESULTS: Baseline ECGs were collected in 153 152 middle-aged participants (ages 35-70 years) to document AF in two community-based studies, spanning 20 countries. Medication use and clinical outcome data (mean follow-up of 7.4 years) were available in one cohort. Cross-sectional analyses were performed to document the prevalence of AF and medication use, and associations between AF and clinical events were examined prospectively. Mean age of participants was 52.1 years, and 57.7% were female. Age and sex-standardized prevalence of AF varied 12-fold between regions; with the highest in North America, Europe, China, and Southeast Asia (270-360 cases per 100 000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100 000 persons) (P < 0.001). Compared with low-income countries (LICs), AF prevalence was 7-fold higher in middle-income countries (MICs) and 11-fold higher in high-income countries (HICs) (P < 0.001). Differences in AF prevalence remained significant after adjusting for traditional AF risk factors. In LICs/MICs, 24% of participants with AF and a CHADS2 score ≥1 received antithrombotic therapy, compared with 85% in HICs. AF was associated with an increased risk of stroke [hazard ratio (HR) 2.29; 95% confidence interval (CI) 1.49-3.52] and death (HR 2.97; 95% CI 2.25-3.93); with similar rates in different countries grouped by income level. CONCLUSIONS: Large variations in AF prevalence occur in different regions and countries grouped by income level, but this is only partially explained by traditional AF risk factors. Antithrombotic therapy is infrequently used in poorer countries despite the high risk of stroke associated with AF.

Atrial Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction and Atrial Fibrillation.

BACKGROUND: Paroxysmal and permanent atrial fibrillation (AF) are common in heart failure with preserved ejection fraction (HFpEF). OBJECTIVES: This study sought to determine the implications of left atrial (LA) myopathy and dysrhythmia across the spectrum of AF burden in HFpEF. METHODS: Consecutive patients with HFpEF (n = 285) and control subjects (n = 146) underwent invasive exercise testing and echocardiographic assessment of cardiac structure, function, and pericardial restraint. RESULTS: Patients with HFpEF were categorized into stages of AF progression: 181 (65%) had no history of AF, 49 (18%) had paroxysmal AF, and 48 (17%) had permanent AF. Patients with permanent AF were more congested with greater pulmonary vascular disease and lower cardiac output. LA volumes increased, while LA compliance, LA reservoir strain, and right ventricular function decreased with increasing AF burden. The presence of permanent AF was characterized by a distinct pathophysiology, with greater total heart volume caused by atrial dilatation, leading to elevated filling pressures through heightened pericardial restraint. Survival decreased with increasing AF burden. Ten-year progression to permanent AF was common, particularly in paroxysmal AF (52%), and the likelihood of AF progression increased with higher AF stage, poorer LA compliance, and lower LA strain. CONCLUSIONS: LA compliance and mechanics progressively decline with increasing AF burden in HFpEF, increasing risk for new onset AF and progressive AF. These changes promote development of a unique phenotype of HFpEF characterized by heightened ventricular interaction, right heart failure, and worsening pulmonary vascular disease. Further study is required to identify therapeutic interventions targeting LA myopathy to improve outcomes in HFpEF.

Cardiac biomarkers of prognostic importance in chronic obstructive pulmonary disease.

BACKGROUND: Ischemic heart disease is common in COPD and associated with worse prognosis. This study aimed to investigate the presence and prognostic impact of biomarkers of myocardial injury and ischemia among individuals with COPD and normal lung function, respectively. METHODS: In 2002-04, all individuals with airway obstruction (FEV1/VC < 0.70, n = 993) were identified from population-based cohorts, together with age and sex-matched non-obstructive referents. At re-examination in 2005, spirometry, Minnesota-coded ECG and analyses of high-sensitivity cardiac troponin I (hs-cTnI) were performed in individuals with COPD (n = 601) and those with normal lung function (n = 755). Deaths were recorded until December 31st, 2010. RESULTS: Hs-cTnI concentrations were above the risk stratification threshold of ≥5 ng/L in 31.1 and 24.9% of those with COPD and normal lung function, respectively. Ischemic ECG abnormalities were present in 14.8 and 13.4%, while 7.7 and 6.6% had both elevated hs-cTnI concentrations and ischemic ECG abnormalities. The 5-year cumulative mortality was higher in those with COPD than those with normal lung function (13.6% vs. 7.7%, p < 0.001). Among individuals with COPD, elevated hs-cTnI both independently and in combination with ischemic ECG abnormalities were associated with an increased risk for death (adjusted hazard ratio [HR]; 95% confidence interval [CI] 2.72; 1.46-5.07 and 4.54; 2.25-9.13, respectively). Similar associations were observed also among individuals with COPD without reported ischemic heart disease. CONCLUSIONS: In this study, elevated hs-cTnI concentrations in combination with myocardial ischemia on the electrocardiogram were associated with a more than four-fold increased risk for death in a population-based COPD-cohort, independent of disease severity.

Determinants of Use of Long-term Continuous Electrocardiographic Monitoring for Acute Ischemic Stroke Patients without Atrial Fibrillation at Baseline.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac rhythm disorder associated with stroke. Increased risk of stroke is the same regardless of whether the AF is permanent or paroxysmal. However, detecting paroxysmal AF is challenging and resource intensive. We aimed to develop a predictive model for AF in patients with acute ischemic stroke, which could improve the detection rate of paroxysmal AF. METHODS: We analyzed 10,034 adult patients with acute ischemic stroke. Differences in clinical characteristics between the patients with and without AF were analyzed in order to develop a predictive model of AF. The associated factors for AF were analyzed using multivariate logistic regression and classification and regression tree (CART) analyses. We used another dataset, which enrolled 860 acute ischemic stroke patients without AF at baseline, to test whether the developed model could improve the detection rate of paroxysmal AF. Among the study population, 1,658 patients (16.5%) had AF. RESULTS: Multivariate logistic regression revealed that sex, age, body weight, hypertension, diabetes mellitus, hyperlipidemia, pulse rate at admission, respiratory rate at admission, systolic blood pressure at admission, diastolic blood pressure at admission, National Institute of Health Stroke Scale (NIHSS) score at admission, total cholesterol level, triglyceride level, aspartate transaminase level, and sodium level were major factors associated with AF. CART analysis identified NIHSS score at admission, age, triglyceride level, and aspartate transaminase level as important factors for AF to classify the patients into subgroups. CONCLUSION: When selecting the high-risk group of patients (with an NIHSS score >12 and age >64.5 years, or with an NIHSS score ≤12, age >71.5 years, and triglyceride level ≤61.5 mg/dL) according to the CART model, the detection rate of paroxysmal AF was approximately double in the acute ischemic stroke patients without AF at baseline.

Electrocardiographic ST-T Abnormities Are Associated With Stroke Risk in the REGARDS Study.

Background and Purpose- In previous studies, isolated nonspecific ST-segment and T-wave abnormalities (NSSTTAs), a common finding on ECGs, were associated with greater risk for incident coronary artery disease. Their association with incident stroke remains unclear. Methods- The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a population-based, longitudinal study of 30 239 white and black adults enrolled from 2003 to 2007 in the United States. NSSTTAs were defined from baseline ECG using the standards of Minnesota ECG Classification (Minnesota codes 4-3, 4-4, 5-3, or 5-4). Participants with prior stroke, coronary heart disease, and major and minor ECG abnormalities other than NSSTTAs were excluded from analysis. Multivariable Cox proportional hazards regression was used to examine calculate hazard ratios of incident ischemic stroke by presence of baseline NSSTTAs. Results- Among 14 077 participants, 3111 (22.1%) had NSSTTAs at baseline. With a median of 9.6 years follow-up, 106 (3.4%) with NSSTTAs had ischemic stroke compared with 258 (2.4%) without NSSTTAs. The age-adjusted incidence rates (per 1000 person-years) of stroke were 2.93 in those with NSSTTAs and 2.19 in those without them. Adjusting for baseline age, sex, race, geographic location, and education level, isolated NSSTTAs were associated with a 32% higher risk of ischemic stroke (hazard ratio, 1.32 [95% CI, 1.05-1.67]). With additional adjustment for stroke risk factors, the risk of stroke was increased 27% (hazard ratio, 1.27 [95% CI, 1.00-1.62]) and did not differ by age, race, or sex. Conclusions- Presence of NSSTTAs in persons with an otherwise normal ECG was associated with a 27% increased risk of future ischemic stroke.

Adherence to guidelines in the management of patients with chronic heart failure follow-up: role of periodic echocardiographic examinations.

BACKGROUND AND AIM: The Adherence to Guidelines in the Treatment of patients with Chronic Heart Failure trial showed a poor adherence to the current therapeutic guidelines in 660 chronic heart failure (CHF) patients. The second phase, Adherence to Guidelines in the Treatment of patients with Chronic Heart Failure follow-up, was aimed to determine if periodic echocardiographic evaluations could improve the prognosis of CHF patients and/or increase the adherence to the guidelines. MATERIAL AND METHODS: Among 528 CHF patients with reduced ejection fraction from the ALERT registry, 436 patients accepted to participate in the second phase of the study between February and September 2013 and completed the 3-year follow-up phase between February and September 2016. They were randomized into two groups: Group A (n = 218) followed by clinical evaluation and ECG every 3 months, and echocardiography every 6 months and Group B (n = 218) monitored only with clinical evaluation and ECG every 3 months. RESULTS: The number of vascular events that occurred resulted as similar in both the groups: there were 78 hospitalizations (37 in Group A vs. 41 in Group B); 9 home-treated vascular events (4 in Group A and five in Group B); and 16 cardiovascular deaths (9 and 7, respectively). The adherence to the guidelines at the end of the trial resulted as significantly improved in both the groups in comparison with the basal evaluation, without differences between the two groups. CONCLUSION: A strict follow-up of CHF patients was associated with a lower number of events and an improvement in the adherence to the guidelines. Periodic echocardiography does not modify these results.

Combination of olanzapine and samidorphan has no clinically relevant effects on ECG parameters, including the QTc interval: Results from a phase 1 QT/QTc study.

BACKGROUND: OLZ/SAM is a combination of olanzapine, an atypical antipsychotic, and samidorphan, an opioid antagonist, and is in development for the treatment of schizophrenia and bipolar I disorder. OLZ/SAM is under development with the intent to provide the established antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain. This thorough QT study assessed the effects of therapeutic and supratherapeutic doses of OLZ/SAM on cardiac repolarization in patients with schizophrenia. METHODS: In this randomized, double-blind, placebo- and positive (moxifloxacin)-controlled, parallel-group study, 100 patients aged 18 to 60 years with stable schizophrenia were randomized 3:2 to the active arm and control arm. Subjects in the active arm received a therapeutic dose of 10/10 mg (10 mg olanzapine/10 mg samidorphan) on days 2-4, 20/20 mg on days 5-8, and a supratherapeutic dose of 30/30 mg (1.5 times and 3 times the maximum recommended daily dose of olanzapine and samidorphan, respectively) on days 9-13, and moxifloxacin-matched placebo on days 1 and 14. Subjects in the control arm received a single oral dose of moxifloxacin 400 mg and moxifloxacin-matched placebo on days 1 and 14 in a nested crossover fashion, along with OLZ/SAM-matched placebo on days 2-13. Serial electrocardiograms (ECGs) and simultaneous plasma drug concentrations were determined pre- and post-dose. The effects of OLZ/SAM on heart rate and ECG parameters (QT interval with Fridericia's correction [QTcF], PR and QRS interval, and T-wave morphology) were evaluated, and the primary endpoint was change from baseline in QTcF (ΔQTcF). The relationship between drug concentration and ΔQTcF (C-QTc) was evaluated using a linear mixed-effects model. Safety monitoring included adverse events reporting and clinical laboratory assessments. RESULTS: Based on primary analysis using C-QTc modeling, no clinically concerning QTc effect (ie, placebo-corrected ΔQTcF [ΔΔQTcF] ≥10 msec) was observed across the OLZ/SAM dose range tested (10/10 to 30/30 mg), up to olanzapine and samidorphan concentrations of approximately 110 and 160 ng/mL, respectively. The slope (90% confidence interval [CI]) of the C-QTc relationship was shallow and not significant for either olanzapine or samidorphan (0.03 [-0.01, 0.08] and 0.01 [-0.01, 0.04] msec per ng/mL, respectively). The predicted ΔΔQTcF (90% CI) was 2.33 (-2.72, 7.38) and 1.38 (-3.37, 6.12) msec at the observed geometric mean maximal concentration (Cmax) of olanzapine (62.6 ng/mL) and samidorphan (75.1 ng/mL) on day 13, respectively. The study's assay sensitivity was confirmed by the C-QTc relationship of moxifloxacin. OLZ/SAM was well tolerated at all doses; adverse events occurring in >5% of subjects treated with OLZ/SAM were somnolence, weight increased, nausea, and dizziness. CONCLUSIONS: This thorough QT study in patients with stable schizophrenia demonstrated that OLZ/SAM, in doses and plasma concentrations up to supratherapeutic levels, does not have a clinically relevant effect on ECG parameters, including QT/QTc prolongation.

Síndrome coronario agudo: un diagnóstico siempre difícil en urgencias -la regla del 9- / Acute coronary syndrome - always a difficult diagnosis in emergencies: the rule of 9

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Discovering hidden information in biosignals from patients using artificial intelligence.

Biosignals such as electrocardiogram or photoplethysmogram are widely used for determining and monitoring the medical condition of patients. It was recently discovered that more information could be gathered from biosignals by applying artificial intelligence (AI). At present, one of the most impactful advancements in AI is deep learning. Deep learning-based models can extract important features from raw data without feature engineering by humans, provided the amount of data is sufficient. This AI-enabled feature presents opportunities to obtain latent information that may be used as a digital biomarker for detecting or predicting a clinical outcome or event without further invasive evaluation. However, the black box model of deep learning is difficult to understand for clinicians familiar with a conventional method of analysis of biosignals. A basic knowledge of AI and machine learning is required for the clinicians to properly interpret the extracted information and to adopt it in clinical practice. This review covers the basics of AI and machine learning, and the feasibility of their application to real-life situations by clinicians in the near future.

Electrocardiographic predictors of adverse in-hospital outcomes in the Takotsubo syndrome.

BACKGROUND: Takotsubo syndrome (TS) is a life-threatening acute heart failure syndrome. However, little is known about risk factors for worse outcomes in TS and no high-risk ECG criteria have been defined. We sought to identify ECG predictors of life-threatening in-hospital complications in TS. METHOD AND RESULT: Using the nationwide Swedish Angiography and Angioplasty Registry (SCAAR) we obtained data on all consecutive patients undergoing coronary angiography at Sahlgrenska University Hospital between June 2008 and February 2019. For all patients with TS we conducted in-depth chart reviews to confirm the TS diagnosis. For those with confirmed TS we then evaluated all ECGs obtained during the index hospitalization. The primary endpoint was the occurrence of in-hospital major adverse cardiac event (MACE), defined as the composite of death, ventricular tachycardia or fibrillation (VT/VF), or atrioventricular block ≥2 or asystole ≫10 s. We identified 215 patients with TS (mean age 69 ±â€¯13 years; 93% women). MACE occurred in 34 patients (16%), of whom 20 had VT/VF (9,3%). Patients with MACE were less likely than those without MACE to have sinus rhythm (85% versus 96%, p = 0.025) or T-wave inversion (29% versus 51%, p = 0.025). After propensity score adjustment T-wave inversion was independently associated with lower MACE risk (adjusted odds ratio [AdjOR] 0.28, 95% confidence interval [CI] 0.10-0.76, p = 0.012) and VT/VF (AdjOR 0.24, 95% CI 0.06-0.94, p = 0.041). CONCLUSION: T-wave inversion is common in TS and is associated with lower risk of MACE, driven by a lower risk of VT/VF.