Diagnosis Of Long QT Syndrome Research Articles

Low foetal heart rate, a potentially ominous finding: case report

Abstract Background Congenital long QT syndrome (LQTS) type 1 is characterized by abnormally prolonged ventricular repolarization caused by inherited defects in cardiac potassium channels. Patients are predisposed to ventricular arrhythmias and even sudden cardiac death. In some cases, foetal sinus bradycardia is the only sign, making prenatal diagnosis challenging. Physicians should be aware of this subtle presentation of LQTS. Early diagnosis and proactive treatment are crucial for preventing unexpected cardiac events. Case summary A healthy and asymptomatic 25-year-old pregnant woman was referred to our institute for cardiac evaluation after persistent foetal sinus bradycardia was detected during repeated ultrasounds, despite the absence of any foetal morphological or functional cardiac anomalies. After a thorough assessment, the mother was diagnosed with LQTS type 1, as confirmed by molecular genetic testing. Appropriate management, including maternal medication and increased surveillance, was initiated. The infant was delivered safely, and his electrocardiogram revealed a significantly prolonged QTc interval. Genetic testing confirmed the maternally inherited variant in KCNQ1 gene, and beta-blocker therapy was started. No arrhythmic events were noted. Discussion Detection and careful stratification of foetal heart rate (FHR) is crucial in every pregnancy. Foetal bradycardia can be caused by both maternal and foetal factors. Persistent low FHR should raise a high suspicion for LQTS. The condition may also present with atrioventricular blocks, torsades de pointes, or sudden intrauterine foetal demise. Accurate and early diagnosis of LQTS is essential for implementing appropriate management strategies, which include vigilant monitoring, effective medical treatment, careful planning of delivery, and post-natal care.

Integration of validated functional evidence to support the pathogenicity of KCNH2 variants

Functional investigation of genetic variants found in long QT syndrome can provide evidence that is needed to confirm the genetic diagnosis and establish the cause of the condition. We performed functional assessment to determine the z-score, using a clinically calibrated automated patch clamp assay, for 2 missense KCNH2 variants found in 2 families that have been diagnosed with long QT syndrome. These variants are currently classified as variant of uncertain significance in ClinVar. The z-scores for homozygous and heterozygous NM_000238.4:c.1819A>T p.(Ile607Phe) from family 1 were –5.16 and –3.97, respectively, and for heterozygous NM_000238.4:c.1832A>G p.(Tyr611Cys) from family 2 was –6.63. The z-scores for these variants are consistent with severe loss-of-function phenotypes. We have established the genetic cause of the long QT syndrome in these 2 families by providing validated functional evidence that supports the pathogenicity of p.(Ile607Phe) and p.(Tyr611Cys). Clinical diagnosis of long QT syndrome has been very successful in providing adequate clinical management for patients. However, functional assessment of variants found in these patients by using variant-specific z-scores can further enhance the current clinical management of patients with long QT syndrome through shared decision making based on validated experimental evidence.

Handgrip strength test for the diagnosis of long QT syndrome

Long QT syndrome (LQTS) assessment is based on the QT/ÖRR equation (the so-called Bazett's formula) and calculating the corrected QT (QTc). However, this formula reliably estimates the QT interval in the heart rate range (HR) of 60-90 bpm, which makes it difficult to diagnose LQTS in patients with sinus bradycardia, typical of this disease.Aim. To improve the LQTS diagnosis in patients with sinus bradycardia using the handgrip strength test.Material and methods. A total of 188 patients aged 5-53 years (16 [13;17]) were examined: group I — 40 healthy children aged 9-17 years (14 [12;16]); group II — 98 athletes with sinus bradycardia <60 bpm aged 16 [16;17] years; group III — 50 patients with LQTS aged 5-53 years (12 [10;16]). The handgrip strength test consisted of regular rhythmic compression of a hand expander with a resistance of 20 kg until the heart rate increased >60 bpm. The patients had an electrocardiogram recorded twice before and after the handgrip test. Heart rate, QT and QTc intervals were analyzed.Results. In all groups, after using the expander, there was a significant increase in heart rate, QT interval shortening and QTc interval prolongation. QTc interval prolongation after the handgrip test >460 ms was a highly sensitive marker of LQTS (Se 96%, Sp 60%).Conclusion. Proposed handgrip test for sinus bradycardia makes it possible to increase heart rate, which ensures a more correct use of the Bazett's formula for assessing the corrected QT interval (QTc). QTc interval prolongation over 460 ms after the handgrip test is a highly sensitive additional marker for identifying patients with LQTS.

Concealed Long-QT Syndrome with Rare KCNQ1 Gene Mutation in an Elderly Female: A Case Report

Long QT syndrome (LQTS) is a hereditary disorder that can lead to recurrent syncope, convulsive episodes, and sudden death due to ventricular arrhythmia. In most instances, LQTS remains concealed and primarily presents as unexplained syncope despite have a normal electrocardiogram (ECG) during periods of rest. This characteristic can be highly deceptive and may result in severe and potentially fatal consequences if treated incorrectly. In this report, we present a case of concealed LQTS in an elderly female patient who experienced an initial episode of syncope at the age of 76. Upon admission, the surface ECG showed no abnormalities. However, during the bedside ECG examination, typical manifestations of LQTS were detected, indicating an early stage of the ictal process. Subsequent treatment with βblockers provided symptomatic relief. Genetic testing identified a rare mutation, p. Arg366Trp (with a c.1096C>T variant), in the KCNQ1 gene, confirming the diagnosis of LQTS. Although congenital LQTS cases are more commonly found in young females, the potential for LQTS should not be overlooked in elderly patients who complain of unexplained syncope, even if their ECG normal. The use of an artificial intelligence (AI)-based diagnostic tool has the potential to offer a more precise means of identifying concealed LQTS in the future, but, until now, thorough examination and close observation during admission is necessary to avoid missed diagnoses of the concealed LQTS-syndrome.

Clinical and Genetic Characteristics of 18 Cases with Suspected Congenital Long QT Syndrome: A Retrospective Cross-Sectional Study

Background: Long QT syndrome (LQTS) is characterized by prolonged QT interval in electrocardiogram (ECG), which is highly associated with sudden cardiac death (malignant arrhythmia). The purpose of this study was to explore the clinical and genetic characteristics of LQTS in children. Materials and Methods: Whole-exome sequencing and Sanger sequencing were performed in 18 probands with prolonged QT interval on the surface ECG. The pathogenicity of the detected variants was evaluated. Results: 44.4% (8/18) of patients were diagnosed with LQTS in the QT prolongation cohort, among which five variants in KCNQ1 and three in SCN5A were detected. Syncope was the primary manifestation. The mean QTc for variant-positive patients was 522 ± 36 ms and that for patients with negative results was 481 ± 15 ms. High probability (7/11, 63.6%) of LQTS presented among the patients with high Schwartz score (Schwartz score ≥3.5). Partial variant carrier parents had no symptoms but prolonged QTc on ECG. Besides, a case masquerading as epilepsy was reported. Conclusions: For a rapid and accurate diagnosis of LQTS, genetic testing should be combined with assessment of clinical information and ECG. Moreover, routine ECG examination is proposed in seizure patients to avoid misdiagnosis. Two novel variants in SCN5A were detected and the variant spectrum of which was expanded. Besides, we discuss incomplete penetrance and phenotypic heterogeneity of LQTS and suggest focusing on the variant carriers with no obvious symptoms.

Proceed with caution: Standard protocol exercise stress tests fail to replicate the diagnostic utility of supine-stand tests for long QT syndrome.

Long QT syndrome (LQTS) is a sudden death predisposing condition characterized by ECG-derived prolongation of the QT interval. Previous studies have demonstrated that the supine-stand test may aid in the diagnosis of LQTS as patients fail to shorten their QT interval in response to standing up. The aim of this study was to evaluate the diagnostic accuracy of ECG data derived from standard protocol, clinically performed treadmill exercise stress tests (TESTs) in their ability to mimic the formal supine-stand test. We performed a retrospective review of 478 TESTs from patients evaluated for LQTS. Patients referred for evaluation of LQTS but who were dismissed as normal served as controls. Heart rate & QT values were obtained from standard protocol TESTs. Overall, 243 patients with LQTS (125 LQT1, 63 LQT2, 55 LQT3; 146 [60%] female, mean age at TEST 30±17 years) and 235 controls (142 [60%] female, mean age 24±15 years) were included. The paired ΔQTc (QTcStand -QTcSupine ) was similar between LQTS (-5±26) and controls (-2±25; p=.2). During position change, the QT interval shortened by ≥20ms in 33% of LQTS patients, remained unchanged in 62%, and increased in 5% of LQTS patients which was similar to controls (shortened in 40%, unchanged in 54%, and increased in 6% of controls; p=.2). Receiver-operator curve analysis to test the diagnostic ability of supine-stand ΔQT performed poorly in differentiating LQTS from controls with an of AUC 0.52 (p=.4). TESTs should be used with caution when trying to interpret supine-stand changes for diagnosis of LQTS.

SAT227 A 17-year old Teenager With Recurrent Syncopes In The Setting of Hypocalcemia

Abstract Disclosure: D.V. Chartoumpekis: None. P. Bountouris: None. K. Dimitropoulos: None. I.G. Habeos: None. Background: One of the main reasons of syncope is the long QT syndrome. The exercise-induced hypocalcemia in a background of primary hypoparathyroidism is sometimes overlooked in the differential diagnosis. Clinical Case: A 17-year old female was transferred to the emergency room of the University Hospital of Patras after having experienced a syncope while swimming. She described in the past 6 months similar episodes during exercise (running, cycling). A basic investigation with full blood count, sodium, potassium, cortisol and TSH levels along with a brain MRI and an ECG were performed at her primary care physician. Due to a discovered long QT she was addressed to a cardiology private office for further investigation. However, before the planned appointment she had this episode while swimming and she was admitted to the cardiology department. During her hospitalization a serum calcium of 4.7 mg/dl and a serum P of 9.4 mg/dl were discovered with a non-detectable PTH. The endocrinology division was called for further evaluation. Chvostek and Trousseau’s signs were positive. The patient was administered a calcium gluconate drip and in parallel a treatment with calcium carbonate and alphacalcidol was initiated. The possibility of an autoimmune polyendocrine syndrome was excluded as the patient did not present candidiasis, adrenal insufficiency, autoimmune thyroid disease or diabetes. After her exit from the hospital she was followed up at the outpatient endocrinology clinic and her daily doses of calcium carbonate and alphacalcidol was modified several times as the [CaxP] was always higher than 55 mg2/dl2 and when the dose of calcium carbonate was lowered she developed symptomatic hypocalcemia. During the first month of her follow-up a cataract in the right eye was discovered and a brain MRI unveiled basal ganglia calcifications. No signs of renal stones or nephrocalcinosis were seen in the ultrasound. As the calcium and phosphate levels, after almost 9 months of changes in the treatment schemes, were not optimal, a treatment with recombinant PTH was initiated. This treatment aided the patient to reach low normal levels of calcium and [CaxP] lower than 55 mg2/dl2. The patient is followed up every six months in the endocrinology outpatient clinic. Conclusion: This is an interesting case of primary hypoparathyroidism possibly of autoimmune origin. The presence of syncopes during exercise could be due to a further drop of calcium levels due to transient respiratory alkalosis. This case can be useful in the teaching of differential diagnosis of long QT syndrome, the management and evaluation of an hypocalcemia and the rule out of autoimmune polyendocrine syndromes in the context of a primary hypoparathyroidism. Presentation: Saturday, June 17, 2023

The differential diagnosis of long QT syndrome with arrhythmic syncope from epilepsy

The differential diagnosis of long QT syndrome with arrhythmic syncope from epilepsy

Diagnostic Accuracy of the Standing Test in Adults Suspected for Congenital Long-QT Syndrome.

Background An elegant bedside provocation test has been shown to aid the diagnosis of long-QT syndrome (LQTS) in a retrospective cohort by evaluation of QT intervals and T-wave morphology changes resulting from the brief tachycardia provoked by standing. We aimed to prospectively determine the potential diagnostic value of the standing test for LQTS. Methods and Results In adults suspected for LQTS who had a standing test, the QT interval was assessed manually and automated. In addition, T-wave morphology changes were determined. A total of 167 controls and 131 genetically confirmed patients with LQTS were included. A prolonged heart rate-corrected QT interval (QTc) (men ≥430 ms, women ≥450 ms) at baseline before standing yielded a sensitivity of 61% (95% CI, 47-74) in men and 54% (95% CI, 42-66) in women, with a specificity of 90% (95% CI, 80-96) and 89% (95% CI, 81-95), respectively. In both men and women, QTc≥460 ms after standing increased sensitivity (89% [95% CI, 83-94]) but decreased specificity (49% [95% CI, 41-57]). Sensitivity further increased (P<0.01) when a prolonged baseline QTc was accompanied by a QTc≥460 ms after standing in both men (93% [95% CI, 84-98]) and women (90% [95% CI, 81-96]). However, the area under the curve did not improve. T-wave abnormalities after standing did not further increase the sensitivity or the area under the curve significantly. Conclusions Despite earlier retrospective studies, a baseline ECG and the standing test in a prospective evaluation displayed a different diagnostic profile for congenital LQTS but no unequivocal synergism or advantage. This suggests that there is markedly reduced penetrance and incomplete expression in genetically confirmed LQTS with retention of repolarization reserve in response to the brief tachycardia provoked by standing.

The Clinical Diagnosis and Management of Long QT Syndrome: Insights from the 2022 ESC Guidelines.

Long QT syndrome (LQTS) is an uncommon disorder that is characterized by QT prolongation and torsade de pointes leading to sudden cardiac death. It is mainly triggered by adrenergic activation. Since LQTS is rare, it is often underdiagnosed. The updated 2022 European Society of Cardiology (ESC) guidelines aim to define the diagnosis of LQTS and spread its management. However, some unknowns and uncertainties still exist regarding the treatment of LQTS. This commentary is geared to the expansion of clinical applications of drug therapies for different subtypes of LQTS based on the 2022 ESC guidelines.

Long &lt;i&gt;QT&lt;/i&gt; Syndrome in Young Athletes

Long QT syndrome is a disease associated with a high risk of sudden cardiac (arrhythmic) death. The frequency of sudden cardiac death is approximately 1: 100,000 young athletes, while autopsies often do not detect changes, which indicates a primary arrhythmogenic death. The article describes two clinical cases of young athletes with prolongation of the QT interval. The possible causes of the long QT syndrome and the difficulties of diagnosing this syndrome in children and adolescents involved in sports are discussed. Regardless of the reasons leading to the prolongation of the QT interval, there is a risk of arrhythmic events. Timely diagnosis of long QT syndrome is the way to the primary prevention of sudden cardiac death in young athletes.

Individualized QT interval (QTi) is a powerful diagnostic tool in long QT syndrome: results from a large validation study.

Diagnosis of Long QT syndrome (LQTS) is based on prolongation of the QT interval corrected for heart rate (QTc) on surface ECG and genotyping. However, up to 25% of genotype positive patients have a normal QTc interval. We recently showed that individualized QT interval (QTi) derived from 24 h holter data and defined as the QT value at the intersection of an RR interval of 1,000 ms with the linear regression line fitted through QT-RR data points of each individual patient was superior over QTc to predict mutation status in LQTS families. This study aimed to confirm the diagnostic value of QTi, fine-tune its cut-off value and evaluate intra-individual variability in patients with LQTS. From the Telemetric and Holter ECG Warehouse, 201 recordings from control individuals and 393 recordings from 254 LQTS patients were analysed. Cut-off values were obtained from ROC curves and validated against an in house LQTS and control cohort. ROC curves indicated very good discrimination between controls and LQTS patients with QTi, both in females (AUC 0.96) and males (AUC 0.97). Using a gender dependent cut-off of 445 ms in females and 430 ms in males, a sensitivity of 88% and specificity of 96% were achieved, which was confirmed in the validation cohort. No significant intra-individual variability in QTi was observed in 76 LQTS patients for whom at least two holter recordings were available (483 ± 36 ms vs. 489 ± 42 ms, p = 0.11). This study confirms our initial findings and supports the use of QTi in the evaluation of LQTS families. Using the novel gender dependent cut-off values, a high diagnostic accuracy was achieved.

Dificultades en la estimación del intervalo QT y su corrección por la frecuencia cardiaca

The rational use of diagnostic methods in medicine is always a challenge, and cardiology is no exception. The conventional 12-lead electrocardiogram, taken at rest, remains essential in the diagnosis of cardiovascular diseases and is the most important tool for the diagnosis of long QT syndrome. The measured QT interval must be corrected for heart rate, and different mathematical formulas are used for this. This article shows some of the difficulties that both the measurement of the QT interval has as well as the use of the different formulas commonly used for the correction of the QT interval by heart rate. We must consider that, depending on the formula used, different corrected QT values are obtained, which could lead to the interpretation of said interval as normal, abnormal, or borderline, with the consequent diagnostic implications since this can make the difference between considering an individual as healthy or sick (a carrier of a long QT syndrome). To exemplify the importance that the results of the different formulas can have, we briefly present 2 pediatric cases.

PO-05-198 IN-HOSPITAL OUTCOMES OF PREGNANT WOMEN WITH LONG QT SYNDROME – INSIGHTS FROM THE NATIONAL INPATIENT SAMPLE.

Patients admitted with a history of long QT syndrome (LQTS) have a higher all-cause mortality when compared to the general population, a trend especially pronounced among males. Conversely, in pregnant women the risk of potentially life-threatening events is lower during pregnancy but increases significantly during the 9-month postpartum period, however, limited data exists. To describe the baseline demographics and in-hospital outcomes of adult (≥ 18 years old) pregnant women with a previous diagnosis of LQTS. The National Inpatient Sample Database was queried from 2016-2019 for relevant ICD-10 diagnostic and procedural codes to construct our cohort. Outcomes of interest included frequency of ventricular tachycardia and in-hospital all-cause mortality. A total of 513,890 patients with a diagnosis of LQTS were identified, of which 3,285 (0.6%) were pregnant women (average age 28.8 years; 56% white). Asthma (13%) and obesity (12%) were the most common comorbidities, followed by heart failure (5%), diabetes mellitus (4%), OSA (1.4%), and coronary artery disease (1.4%). Substance use disorder was reported in 14% subjects and 15.6% had an implanted cardiac device at the time of admission. For obstetric comorbidities, the most common was preeclampsia (8%) and stillbirth (0.8%). There was a prevalence of 2% for ventricular tachycardia and 0.3% inpatient all-cause mortality. Among patients admitted with LQTS, pregnant women represent a significantly high-risk cohort for adverse cardiac and non-cardiac events for both mother and child. A multidisciplinary approach to identify these patients early is critical to improving maternal-fetal outcomes.

Genetic Biomarkers of Antipsychotic-Induced Prolongation of the QT Interval in Patients with Schizophrenia.

Antipsychotics (AP) induced prolongation of the QT interval in patients with schizophrenia (Sch) is an actual interdisciplinary problem as it increases the risk of sudden death syndrome. Long QT syndrome (LQTS) as a cardiac adverse drug reaction is a multifactorial symptomatic disorder, the development of which is influenced by modifying factors (APs' dose, duration of APs therapy, APs polytherapy, and monotherapy, etc.) and non-modifying factors (genetic predisposition, gender, age, etc.). The genetic predisposition to AP-induced LQTS may be due to several causes, including causal mutations in the genes responsible for monoheme forms of LQTS, single nucleotide variants (SNVs) of the candidate genes encoding voltage-dependent ion channels expressed both in the brain and in the heart, and SNVs of candidate genes encoding key enzymes of APs metabolism. This narrative review summarizes the results of genetic studies on AP-induced LQTS and proposes a new personalized approach to assessing the risk of its development (low, moderate, high). We recommend implementation in protocols of primary diagnosis of AP-induced LQTS and medication dispensary additional observations of the risk category of patients receiving APs, deoxyribonucleic acid profiling, regular electrocardiogram monitoring, and regular therapeutic drug monitoring of the blood APs levels.

Clinical Case of a 36-year-old Patient with Paranoid Schizophrenia and Drug-Induced QT Prolongation

Heart rhythm and conduction disorders are a serious problem in chronic psychopharmacotherapy of schizophrenia. One potentially fatal antipsychotic-induced adverse reaction is drug[1]induced long QT syndrome, which is a phenomenon of prolongation of cardiac repolarization and leads to an increased risk of ventricular tachycardia, known as Torsades de pointes, in the presence of an administered drug [1]. The clinical diagnosis of this adverse drug reaction is difficult, however, electrocardiography and Holter ECG monitoring are the gold standard for the functional diagnosis of long QT syndrome, although they do not give the psychiatrist an answer about the possible correction of mono- or polytherapy for schizophrenia in a particular patient. Pharmacogenetic testing is an integral part of the personalized strategy of psychopharmacotherapy in modern psychiatry. Slowing the efflux of antipsychotics through the histohematic barriers and the membrane of neurons and cardiomyocytes, along with slowing down the metabolism of antipsychotics in the liver with the participation of cytochrome P450 enzymes, can significantly increase the risk of antipsychotics induced long QT syndrome and sudden death syndrome. The purpose of this clinical case is to update the existing problem of pharmacogenetic testing in real psychiatric practice and demonstrate possible ways to solve the problem of antipsychotic-induced long QT syndrome in a young man with paranoid schizophrenia.

EP News: Case Reports

Long QT syndrome (LQTS) is a typically inherited ion channelopathy associated with ventricular tachyarrhythmias, cardiac arrest, or sudden death at any age, including intrauterine demise. Early diagnosis of LQTS in a fetus can facilitate treatment and screening to lower the risk of complications. The fetus can present with ventricular tachyarrhythmias, torsades de pointes, and function 2:1 atrioventricular block due to prolonged repolarization. Zidere et al (https://doi.org/10.1016/j.hrcr.2022.07.007) shared 4 cases in which fetal LQTS was diagnosed after screening with fetal heart rate during the second trimester.

Sex Differences and Utility of Treadmill Testing in Long-QT Syndrome.

Background Diagnosis of congenital long-QT syndrome (LQTS) is complicated by phenotypic ambiguity, with a frequent normal-to-borderline resting QT interval. A 3-step algorithm based on exercise response of the corrected QT interval (QTc) was previously developed to diagnose patients with LQTS and predict subtype. This study evaluated the 3-step algorithm in a population that is more representative of the general population with LQTS with milder phenotypes and establishes sex-specific cutoffs beyond the resting QTc. Methods and Results We identified 208 LQTS likely pathogenic or pathogenic KCNQ1 or KCNH2 variant carriers in the Canadian NLQTS (National Long-QT Syndrome) Registry and 215 unaffected controls from the HiRO (Hearts in Rhythm Organization) Registry. Exercise treadmill tests were analyzed across the 5 stages of the Bruce protocol. The predictive value of exercise ECG characteristics was analyzed using receiver operating characteristic curve analysis to identify optimal cutoff values. A total of 78% of male carriers and 74% of female carriers had a resting QTc value in the normal-to-borderline range. The 4-minute recovery QTc demonstrated the best predictive value for carrier status in both sexes, with better LQTS ascertainment in female patients (area under the curve, 0.90 versus 0.82), with greater sensitivity and specificity. The optimal cutoff value for the 4-minute recovery period was 440 milliseconds for male patients and 450 milliseconds for female patients. The 1-minute recovery QTc had the best predictive value in female patients for differentiating LQTS1 versus LQTS2 (area under the curve, 0.82), and the peak exercise QTc had a marginally better predictive value in male patients for subtype with (area under the curve, 0.71). The optimal cutoff value for the 1-minute recovery period was 435 milliseconds for male patients and 455 milliseconds for femal patients. Conclusions The 3-step QT exercise algorithm is a valid tool for the diagnosis of LQTS in a general population with more frequent ambiguity in phenotype. The algorithm is a simple and reliable method for the identification and prediction of the 2 major genotypes of LQTS.

Does sports participation increase risk in patients with long QT syndrome? Results from a large French cohort.

Sports practice, especially in competition, is usually restrained in patients diagnosed with long QT syndrome (LQTS). Although data are scarce, a low incidence of cardiac arrhythmic events (CAEs) during sports practice is reported. We aim to evaluate the incidence of CAE during sports practice in LQTS patients. All consecutive patients above 18 years of age diagnosed with LQTS and prospectively followed at the referral centre for inherited arrhythmia syndrome received a survey to retrospectively assess their sports practice prior to and after the diagnosis of LQTS. Two hundred and forty-six patients were included (57% females). The median age was 43 years, and the median QTc was 457 ms (428; 482). Patients reported a total of 4092 years [1376 (34%) after diagnosis] of sports practice: 2905 (77%) [1138 (39%) after diagnosis] years of leisure practice and 1187 (23%) [238 (20%) after diagnosis] years of competitive practice. One hundred and eighty (73%) patients practiced sport prior to the diagnosis of LQTS and 170 (69%) after. Prior to the diagnosis, four (2%) patients presented a CAE during leisure sports practice and one during competition. After diagnosis, only one patient presented a CAE, appropriately treated by an implantable cardioverter defibrillator discharge, in the context of beta-blocker non-compliance. The CAE event rate was 0.0007 events/year in the 1376 years of total sports practice after the diagnosis of LQTS. After the diagnosis of LQTS, the occurrence of CAE is very low during sports practice, even in competitive practice. There was no CAE in patients properly treated with beta-blocker therapy with good compliance.

Utility of Provocative Testing in the Diagnosis and Genotyping of Congenital Long QT Syndrome: A Systematic Review and Meta-Analysis.

Background Diagnosis is particularly challenging in concealed or asymptomatic long QT syndrome (LQTS). Provocative testing, unmasking the characterization of LQTS, is a promising alternative method for the diagnosis of LQTS, but without uniform standards. Methods and Results A comprehensive search was conducted in PubMed, Embase, and the Cochrane Library through October 14, 2021. The fixed effects model was used to assess the effect of the provocative testing on QTc interval. A total of 22 studies with 1137 patients with LQTS were included. At baseline, QTc interval was 40ms longer in patients with LQTS than in controls (mean difference [MD], 40.54 [95% CI, 37.43-43.65]; P<0.001). Compared with the control group, patients with LQTS had 28ms longer ΔQTc upon standing (MD, 28.82 [95% CI, 23.05-34.58]; P<0.001), nearly 30ms longer both at peak exercise (MD, 27.31 [95% CI, 21.51-33.11]; P<0.001) and recovery 4 to 5minutes (MD, 29.85 [95% CI, 24.36-35.35]; P<0.001). With epinephrine infusion, QTc interval was prolonged both in controls and patients with QTS, most obviously in LQT1 (MD, 68.26 [95% CI, 58.91-77.60]; P<0.001) and LQT2 (MD, 60.17 [95% CI, 50.18-70.16]; P<0.001). Subgroup analysis showed QTc interval response to abrupt stand testing and exercise testing varied between LQT1, LQT2, and LQT3, named Type Ⅰ, Type Ⅱ, and Type Ⅲ. Conclusions QTc trend Type Ⅰ and Type Ⅲ during abrupt stand testing and exercise testing can be used to propose a prospective evaluation of LQT1 and LQT3, respectively. Type Ⅱ QTc trend combined epinephrine infusion testing could distinguish LQT2 from control. A preliminary diagnostic workflow was proposed but deserves further evaluation.