P335Genotype-driven phenotype differences in probands with long QT syndrome

EP Europace ◽  
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.

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

Circulation ◽  
2003 ◽  
Vol 107 (6) ◽  
pp. 838-844 ◽  
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

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

Circulation ◽  
2020 ◽  
Vol 142 (25) ◽  
pp. 2405-2415 ◽  
Author(s):  
Federica Dagradi ◽  
Carla Spazzolini ◽  
Silvia Castelletti ◽  
Matteo Pedrazzini ◽  
Maria-Christina Kotta ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Stress Test ◽  
Diagnostic Errors ◽  
Exercise Stress ◽  
Medical Visit ◽  
Long Qt ◽  
Qt Syndrome ◽  
Congenital Lqts ◽  
Ecg Abnormalities ◽  
Repolarization Abnormalities

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.

Long QT syndrome diagnosed in two sisters with propionic acidemia: a case report

2017 ◽  
Vol 30 (10) ◽  
Author(s):  
Ensar Duras ◽  
Ahmet İrdem ◽  
Ozan Özkaya
Keyword(s):  
Long Qt Syndrome ◽  
Stress Test ◽  
Holter Monitoring ◽  
Propionic Acidemia ◽  
Outpatient Setting ◽  
Cardiac Complications ◽  
Metabolic Decompensation ◽  
Long Qt ◽  
Asymptomatic Patients ◽  
Qt Syndrome

AbstractPropionic acidemia (PA) is a rare autosomal recessive metabolic disorder caused by deficiency of the mitochondrial enzyme propionyl-CoA carboxylase (PCC). This disorder mostly progresses with episodes of metabolic acidosis. Cardiomyopathy is among the cardiac complications known to occur during metabolic decompensation episodes. However, several recent papers emphasized the association of PA and long QT syndrome (LQTS) which may lead to extremely serious and fatal consequences. In this report, we describe two sisters with PA who have prolonged QT duration that were incidentally detected in an outpatient setting. LQTS was verified by electrocardiogram, stress test and 24 h rhythm holter monitoring. By this report, we want to emphasize the importance of early diagnosis of LQTS in asymptomatic patients with PA to prevent fatal complications.

scholarly journals Results of bicycle exercise stress test in patients with stable coronary heart disease depending on the angiographic signs of atherosclerotic lesions of coronary arteries

2021 ◽  
pp. 53-60
Author(s):  
Vira Tseluyko ◽  
Tetiana Pylova
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Exercise Test ◽  
Stress Test ◽  
Exercise Stress Test ◽  
Exercise Stress ◽  
Bicycle Exercise ◽  
Group I ◽  
Group Ii ◽  
Artery Disease

The aim. To identify features of exercise response in coronary heart disease (CHD) patients depending on coronary artery condition and to identify factors associated with a positive test in patients with no obstructive coronary artery disease (INOCA). Materials and methods. The study included 105 patients diagnosed with stable coronary artery disease (CAD) who were hospitalized at the City Clinical Hospital No. 8 of the Kharkiv City Council. The criteria for diagnosis of ischemia with no obstructive coronary artery disease (INOCA) were met by 53 patients who formed group I. Group II included 52 patients who were consistently hospitalized in the period from June to December 2020, and had obstructive CAD for more than 50 % according to their coronary angiography (CAG). Results. According to the results of bicycle exercise stress test, a positive test was significantly more often registered in group II – n=30 (57.7 %) patients compared to group I – n=19 (35.8 %) patients (p=0.0249). The duration of the test in patients of group I was significantly longer than 420 seconds [290–540], compared with group II – 300.0 [210.0–540.0] (р=0.0352). Also, in patients in group II, the maximum volume of the test performed was probably lower than in group I (p=0.0324). When calculating the double product, it was also found that in group I its value was significantly higher compared to group II (p=0.0292). In group I there was a significantly higher rate of chronotropic reserve (44.0 [26.0–60.0]), compared with group II (p=0.0168). Elevated total cholesterol (above 5 mmol/l) is a statistically significant and independent factor of a positive exercise test in patients with INOCA (OR, 1.98 [0.9992-3.926], p=0.05). A correlation was found between the level of exercise tolerance and smoking in INOCA-patients (r =-0.388975, p=0.010899). Patients who underwent MINOCA also showed reduced tolerance to exercise (r=-0.3104, p=0.042721) Conclusions. The sensitivity of bicycle exercise stress test in patients with CAD depends on the presence and severity of atherosclerotic lesions of the coronary arteries (63 % in stenotic atherosclerosis, 36 % in no obstructive coronary arteries. It was found that exercise test duration, double product, chronotropic and inotropic reserve of the heart in patients with a positive exercise test with INOCA were significantly higher compared with patients with obstructive CAD. Independent factors associated with a positive exercise test in patients with no obstructive CAD are an increase in total cholesterol (multivariate regression logistic analysis).

Effect of clinical phenotype on yield of long QT syndrome genetic testing

Heart Rhythm ◽  
2005 ◽  
Vol 2 (5) ◽  
pp. S46 ◽  
Author(s):  
David J. Tester ◽  
Melissa L. Will ◽  
Carla M. Haglund ◽  
Michael J. Ackerman
Keyword(s):  
Genetic Testing ◽  
Long Qt Syndrome ◽  
Clinical Phenotype ◽  
Long Qt ◽  
Qt Syndrome

Endocrinopathies mimicking gene negative long QT syndrome

2021 ◽  
pp. 1-3
Author(s):  
Praloy Chakraborty ◽  
Jason D. Roberts ◽  
Michael H. Gollob
Keyword(s):  
Genetic Testing ◽  
Long Qt Syndrome ◽  
Qt Prolongation ◽  
Long Qt ◽  
Ventricular Repolarisation ◽  
Qt Syndrome ◽  
Hormonal Milieu

Abstract Ventricular repolarisation can be influenced by hormonal milieu which may mimic long QT syndrome. We describe a series of patients referred for genetic testing for diagnosed long QT syndrome where a detailed clinical workup demonstrated endocrinopathies as the cause of presumed “gene negative” long QT syndrome and QT prolongation.

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

Circulation ◽  
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.

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