Exercise Training-Induced Repolarization Abnormalities Masquerading as Congenital Long QT Syndrome

Background: The diagnosis of long QT syndrome (LQTS) is rather straightforward. We were surprised by realizing that, despite long-standing experience, we were making occasional diagnostic errors by considering as affected subjects who, over time, resulted as not affected. These individuals were all actively practicing sports—an observation that helped in the design of our study. Methods: We focused on subjects referred to our center by sports medicine doctors on suspicion of LQTS because of marked repolarization abnormalities on the ECG performed during the mandatory medical visit necessary in Italy to obtain the certificate of eligibility to practice sports. They all underwent our standard procedures involving both a resting and 12-lead ambulatory ECG, an exercise stress test, and genetic screening. Results: There were 310 such consecutive subjects, all actively practicing sports with many hours of intensive weekly training. Of them, 111 had a normal ECG, different cardiac diseases, or were lost to follow-up and exited the study. Of the remaining 199, all with either clear QTc prolongation and/or typical repolarization abnormalities, 121 were diagnosed as affected based on combination of ECG abnormalities with positive genotyping (QTc, 482±35 ms). Genetic testing was negative in 78 subjects, but 45 were nonetheless diagnosed as affected by LQTS based on unequivocal ECG abnormalities (QTc, 472±33 ms). The remaining 33, entirely asymptomatic and with a negative family history, showed an unexpected and practically complete normalization of the ECG abnormalities (their QTc shortened from 492±37 to 423±25 ms [ P <0.001]; their Schwartz score went from 3.0 to 0.06) after detraining. They were considered not affected by congenital LQTS and are henceforth referred to as “cases.” Furthermore, among them, those who resumed similarly heavy physical training showed reappearance of the repolarization abnormalities. Conclusion: It is not uncommon to suspect LQTS among individuals actively practicing sports based on marked repolarization abnormalities. Among those who are genotype-negative, >40% normalize their ECG after detraining, but the abnormalities tend to recur with resumption of training. These individuals are not affected by congenital LQTS but could have a form of acquired LQTS. Care should be exercised to avoid diagnostic errors.

Download Full-text

Sinus node function and ventricular repolarization during exercise stress test in long QT syndrome patients with KvLQT1 and HERG potassium channel defects

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(99)00255-7 ◽

1999 ◽

Vol 34 (3) ◽

pp. 823-829 ◽

Cited By ~ 133

Author(s):

Heikki Swan ◽

Matti Viitasalo ◽

Kirsi Piippo ◽

Päivi Laitinen ◽

Kimmo Kontula ◽

...

Keyword(s):

Potassium Channel ◽

Long Qt Syndrome ◽

Stress Test ◽

Sinus Node ◽

Exercise Stress Test ◽

Ventricular Repolarization ◽

Exercise Stress ◽

Long Qt ◽

Qt Syndrome

Download Full-text

Exercise Stress Test Amplifies Genotype-Phenotype Correlation in the LQT1 and LQT2 Forms of the Long-QT Syndrome

Circulation ◽

10.1161/01.cir.0000048142.85076.a2 ◽

2003 ◽

Vol 107 (6) ◽

pp. 838-844 ◽

Cited By ~ 166

Author(s):

Kotoe Takenaka ◽

Tomohiko Ai ◽

Wataru Shimizu ◽

Atsushi Kobori ◽

Tomonori Ninomiya ◽

...

Keyword(s):

Long Qt Syndrome ◽

Stress Test ◽

Exercise Stress Test ◽

Exercise Stress ◽

Phenotype Correlation ◽

Long Qt ◽

Genotype Phenotype Correlation ◽

Qt Syndrome

Download Full-text

Faculty Opinions recommendation of Vagal reflexes following an exercise stress test: a simple clinical tool for gene-specific risk stratification in the long QT syndrome.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717991561.793473369 ◽

2013 ◽

Author(s):

Macdonald Dick ◽

Ira Shetty

Keyword(s):

Risk Stratification ◽

Long Qt Syndrome ◽

Stress Test ◽

Exercise Stress Test ◽

Exercise Stress ◽

Clinical Tool ◽

Long Qt ◽

Specific Risk ◽

Qt Syndrome

Download Full-text

P335Genotype-driven phenotype differences in probands with long QT syndrome

EP Europace ◽

10.1093/europace/euaa162.229 ◽

2020 ◽

Vol 22 (Supplement_1) ◽

Author(s):

D Jancauskaite ◽

K Sulskute ◽

R Masiuliene ◽

T Adomavicius ◽

I Ramanauskaite ◽

...

Keyword(s):

Genetic Testing ◽

Long Qt Syndrome ◽

Stress Test ◽

Exercise Stress Test ◽

Holter Monitoring ◽

Exercise Stress ◽

Long Qt ◽

Group I ◽

Qt Syndrome ◽

Group Ii

Abstract Background/Introduction. Genetic abnormalities in heart ion channels can predispose life-threatening arrhythmias. Pathogenic genotype is found in the majority of individuals with phenotype of cardiac channelopathies of which long QT syndrome (LQTS) is the most common. However, incomplete penetrance and substantial heterogeneity in genotype-phenotype relationship results in broad clinical disease spectrum. Purpose. To review data gathered from Vilnius University Hospital Santaros klinikos (VUHSK) probands with LQTS and detect phenotypic differences between groups of individuals according to genetic testing results. Methods. We retrospectively reviewed data from clinical records of study participants with suspected LQTS who were clinically evaluated and treated at VUHSK in 2013-2019 year period. Probands with performed genetic testing were included for the final evaluation. Based on genetic testing results, the participants were divided into group I, involving patients with established genetic diagnosis, and group II, which included patients with no clinically relevant variants identified. Patients with variants of uncertain significance (VUS) were excluded from further analysis. Main characteristics of clinical manifestation (age during first symptoms, syncope, cardiac arrest, etc), results of instrumental examination (ECG, Holter monitoring, exercise stress test), Schwatz & Crotti score were compared between groups I and II. Results. LQTS was suspected for 137 patients; genetic testing was performed for 112 probands: 49 (43.8%) patients had pathogenic and likely pathogenic (P/LP) variant; 12 (10.7%) - VUS; 51 (45.5%) - no clinically relevant variant was determined. Phenotype differences of LQTS were compared between two groups: probands with P/PL variant (group I, n = 49); probands with no alteration found (group II, n = 51) (total of 100 patients). The median age of these two groups was 15 [6] years, 31 (31%) were adults, 56 (56%) were female. Most common P/LP variants among probands were identified in KCNQ1 (Type 1), KCNH2 (Type 2) and CACNA1C (Type 8) genes. Participants with P/PL variant had longer QTc interval on ECG (510 ms [37] vs. 500 ms [41], p = 0.011), 24-hour Holter monitoring (510 ms [34] vs. 500 ms [42], p = 0.013) and during 4th minute of recovery from exercise stress test (485 ms [35] vs. 458 ms [52], p = 0.021), compared to individuals without genetic alterations in LQTS genes. The Schwartz & Crotti score was higher in group I than in group II (3.5 [1.5] vs. 3 [1.25], p = 0.026). Other clinical findings did not differ statistically significantly. Conclusions. Probands with P/PL variants of LQTS had longer QTc intervals and higher Schwartz & Crotti score than patients with no alteration found. Genotype can affect clinical manifestation in patients with LQTS and consequently determine patient’s prognosis and further medical care. Larger scale study is required for more detailed analysis of genotype-driven phenotype differences.

Download Full-text

Exercise stress test amplifies genotype-phenotype correlation in the LQT1 and LQT2 forms of the long-QT syndrome

ACC Current Journal Review ◽

10.1016/s1062-1458(03)00202-2 ◽

2003 ◽

Vol 12 (3) ◽

pp. 81 ◽

Cited By ~ 1

Author(s):

K. Takenaka ◽

A. Tomohiko ◽

W. Shimizu

Keyword(s):

Long Qt Syndrome ◽

Stress Test ◽

Exercise Stress Test ◽

Exercise Stress ◽

Phenotype Correlation ◽

Long Qt ◽

Genotype Phenotype Correlation ◽

Qt Syndrome

Download Full-text

A rare indication of permanent pacemaker implantation in children: congenital long QT syndrome

Cardiology in the Young ◽

10.1017/s1047951120003108 ◽

2020 ◽

Vol 30 (12) ◽

pp. 1880-1881

Author(s):

Mehmet Taşar ◽

Nur Dikmen Yaman ◽

Huseyin Dursin ◽

Murat Şimşek ◽

Senem Özgür

Keyword(s):

Sudden Death ◽

Long Qt Syndrome ◽

Pacemaker Implantation ◽

Torsades De Pointes ◽

Permanent Pacemaker ◽

Long Qt ◽

Permanent Pacemaker Implantation ◽

Qt Syndrome ◽

Congenital Lqts ◽

Congenital Long Qt Syndrome

AbstractCongenital Long QT Syndrome (LQTS) is a dangerous arrhythmic disorder that can be diagnosed in children with bradycardia. It is characterised by a prolonged QT interval and torsades de pointes that may cause sudden death. Long QT syndrome is an ion channelopathy with complex molecular and physiological infrastructure. Unlike the acquired type, congenital LQTS has a genetic inheritance and it may be diagnosed by syncope, stress in activity, cardiac dysfunction, sudden death or sometimes incidentally. Permanent pacemaker implantation is required for LQTS with resistant bradycardia even in children to resolve symptoms and avoid sudden death.

Download Full-text

Abstract 14358: Treadmill Exercise Testing Improves Diagnostic Accuracy in Children With Concealed Congenital Long QT Syndrome

Circulation ◽

10.1161/circ.142.suppl_3.14358 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Trisha Patel ◽

Stanley Kamande ◽

Elizabeth Jarosz ◽

James Bost ◽

Sridhar hanumanthaiah ◽

...

Keyword(s):

Exercise Testing ◽

Long Qt Syndrome ◽

Stress Testing ◽

Normal Population ◽

Recovery Phase ◽

Exercise Stress ◽

Long Qt ◽

Qt Intervals ◽

Prolonged Qt ◽

Qt Syndrome

Introduction: Resting electrocardiogram (ECG) identification of long QT syndrome (LQTS) has limitations. Uncertainty exists on how to classify patients with borderline prolonged QT intervals. We tested if exercise testing could help serve as a guide for which children with borderline prolonged QT intervals may be gene positive for LQTS. Methods: Pediatric patients (n=139) were divided into three groups: Controls (n=76), gene positive LQTS with borderline QTc (n=21), and gene negative patients with borderline QTc (n=42). Borderline QTc was defined between 440 to 470 (male) and 440 to 480 (female) msec. ECGs were recorded while supine, sitting, and standing. Patients then underwent treadmill stress testing using the Bruce protocol followed by a 9-minute recovery phase. Statistical analysis was completed to compare the QTc intervals amongst all three of the groups using t-test, ANOVA, and the Youden method to calculate sensitivity and specificity cut points. Results: Supine resting QTc, age, and Schwartz score for the three groups were: 1) Gene positive: 446 ± 23 msec, 12.4 ± 3.4 yo, 3.2 ± 1.8; 2) Gene negative: 445 ± 20 msec, 12.1 ± 2.8 yo, 2.0 ± 1.2; and 3) Control: 400 ± 24 msec, 15.0 ± 3 yo. The three groups could be differentiated by their QTc response at two time points: standing and recovery phase at six minutes. Standing QTc ≥ 460 msec differentiated borderline prolonged QTc patients (Gene positive and Gene negative) from controls with a specificity of 90% for gene positive versus control and 83% for gene negative versus control. A late recovery QTc ≥ 480 msec at minute six distinguished Gene positive from Gene negative patients with a specificity of >97%. Conclusions: Exercise stress testing can be useful to identify Gene positive borderline LQTS from a normal population and Gene negative borderline QTc patients, allowing for increased cost effectiveness by selectively gene testing a higher risk group of patients with borderline QTc intervals and intermediate Schwartz scores.

Download Full-text

Role of mental stress test in diagnosis and treatment in patients with long QT syndrome

Resuscitation ◽

10.1016/0300-9572(93)90039-s ◽

1993 ◽

Vol 25 (1) ◽

pp. 85

Author(s):

E. Borowiecka ◽

W. Rydlewska-Sadowska ◽

W. Popławska ◽

B. Majewska ◽

R. Baranowski ◽

...

Keyword(s):

Long Qt Syndrome ◽

Mental Stress ◽

Stress Test ◽

Diagnosis And Treatment ◽

Long Qt ◽

Qt Syndrome

Download Full-text

Electrocardiographic Screening in the First Days of Life for Diagnosing Long QT Syndrome: Findings from a Birth Cohort Study in Germany

Neonatology ◽

10.1159/000511572 ◽

2020 ◽

pp. 1-8

Author(s):

Alexander Simma ◽

Antonia Potapow ◽

Susanne Brandstetter ◽

Holger Michel ◽

Michael Melter ◽

...

Keyword(s):

Cohort Study ◽

Birth Cohort ◽

Long Qt Syndrome ◽

Sudden Infant Death ◽

Birth Cohort Study ◽

Sudden Infant ◽

Cascade Screening ◽

Long Qt ◽

Qt Syndrome ◽

Congenital Lqts

Introduction: Newborn sudden infant death syndrome (SIDS) has failed to decrease in the last decades, and a third of the neonatal cases occurred within the first 6 days of life. The long QT syndrome (LQTS) is a genetic disease with a prevalence of 1 in 2,000 live births and contributes to almost 10% of SIDS cases. Early identification of LQTS through electrocardiogram (ECG) screening is likely to reduce mortality. Methods and Results: In this ongoing prospective study we evaluated 2,251 ECGs from newborns participating in the KUNO Kids birth cohort study between July 2015 and July 2018. ECGs were recorded at a mean age of 2.0 days (IQR 0 days). The QT interval was corrected for heart rate using Bazett’s formula (QTc). A QTc between 451 and 460, 461–470, and >470 ms was measured in 23 (1.0), 14 (0.6), and 62 (2.8%) participants, respectively. Fourteen neonates (0.62%) were admitted and monitored because their initial QTc was ≥500 ms. In 2 genetically analyzed participants, a mutation was found. One disease-causing for LQTS type 1 and the other of unclear significance. Cascade screening revealed affected members in both families. Conclusion: A standardized neonatal ECG screening in the first days of life is able to identify neonates with a relevant transient form of prolonged QT intervals and to aid diagnosing congenital LQTS.

Download Full-text