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Arthritis Care & Research Jul 2023Recent evidence suggests that hydroxychloroquine use is not associated with higher 1-year risk of long QT syndrome (LQTS) in patients with rheumatoid arthritis (RA)....
OBJECTIVE
Recent evidence suggests that hydroxychloroquine use is not associated with higher 1-year risk of long QT syndrome (LQTS) in patients with rheumatoid arthritis (RA). Less is known about its long-term risk, the examination of which was the objective of this study.
METHODS
We conducted a propensity score-matched active-comparator safety study of hydroxychloroquine in 8,852 veterans (mean age 64 ± 12 years, 14% women, 28% Black) with newly diagnosed RA. A total of 4,426 patients started on hydroxychloroquine and 4,426 started on another nonbiologic disease-modifying antirheumatic drug (DMARD) and were balanced on 87 baseline characteristics. The primary outcome was LQTS during 19-year follow-up through December 31, 2019.
RESULTS
Incident LQTS occurred in 4 (0.09%) and 5 (0.11%) patients in the hydroxychloroquine and other DMARD groups, respectively, during the first 2 years. Respective 5-year incidences were 17 (0.38%) and 6 (0.14%), representing 11 additional LQTS events in the hydroxychloroquine group (number needed to harm 403; [95% confidence interval (95% CI)], 217-1,740) and a 181% greater relative risk (95% CI 11%-613%; P = 0.030). Although overall 10-year risk remained significant (hazard ratio 2.17; 95% CI 1.13-4.18), only 5 extra LQTS occurred in hydroxychloroquine group over the next 5 years (years 6-10) and 1 over the next 9 years (years 11-19). There was no association with arrhythmia-related hospitalization or all-cause mortality.
CONCLUSIONS
Hydroxychloroquine use had no association with LQTS during the first 2 years after initiation of therapy. There was a higher risk thereafter that became significant after 5 years of therapy. However, the 5-year absolute risk was very low, and the absolute risk difference was even lower. Both risks attenuated during longer follow-up. These findings provide evidence for long-term safety of hydroxychloroquine in patients with RA.
Topics: Humans; Female; Middle Aged; Aged; Male; Hydroxychloroquine; Cohort Studies; Veterans; Follow-Up Studies; Retrospective Studies; Arthritis, Rheumatoid; Antirheumatic Agents; Long QT Syndrome; Methotrexate
PubMed: 36039941
DOI: 10.1002/acr.25005 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2022The aim: To present clinical cases of sudden cardiac death in patients with prolonged and shortened QT interval.
OBJECTIVE
The aim: To present clinical cases of sudden cardiac death in patients with prolonged and shortened QT interval.
PATIENTS AND METHODS
Materials and methods: The study includes description of two different clinical cases with prolonged and shortened QT interval after sudden cardiac death. Verification of the diagnosis was performed using the criteria recommended by the European Society of Cardiology (ESC) and European Heart Rhythm Association (EHRA).
RESULTS
Clinical case: Two clinical cases of syncopе with life-threatening arrhythmias, confirmed by electrocardiographic and clinical diagnostic criteria, indicating a change in the dispersion of the QT interval, are presented. The first case represents a patient with intermittent syncope. The patient had previously had attacks of sudden palpitations with fainting. The patient came after another episode of syncope. Further follow-up revealed clinical and electrocardiographic signs of ventricular tachycardia paroxysm. Than the prolongation of the QT interval is set. In this clinical case, verification of QT prolongation syndrome was established in the elderly. Another clinical case is associated with QT syndrome, which remains difficult to diagnose. Such cases have been described relatively recently. The clinical picture of the syndrome of short QT interval in the presented clinical case was characterized by the appearance of syncopal states. The patient showed changes in the adjusted QT interval <320 ms. The causes of syncope in a patient with a short QT interval were paroxysms of atrial fibrillation (AF) or ventricular arrhythmias. At the same time the anatomical structure of a myocardium remains normal and unchanged. The hereditary nature of the disease in the patient has been proven.
CONCLUSION
Conclusions: Timely diagnosis of prolongation (LQTS) or shortening (SQTS) of the QT interval after ECG and Holter monitoring allows you to identify a group of patients with an increased risk of developing ventricular arrhythmias, syncope and sudden cardiac death. Implantation of a cardioverter-defibrillator is an effective and safe method of preventing sudden cardiac death in patients with long and short QT syndromes.
Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Death, Sudden, Cardiac; Electrocardiography; Humans; Long QT Syndrome; Syncope
PubMed: 35962703
DOI: 10.36740/WLek202207113 -
Herzschrittmachertherapie &... Mar 2020Long QT syndrome (LQTS) is a rare inherited or acquired channelopathy associated with a relevant mortality if left untreated. Therapy can reduce the sudden cardiac... (Review)
Review
Long QT syndrome (LQTS) is a rare inherited or acquired channelopathy associated with a relevant mortality if left untreated. Therapy can reduce the sudden cardiac death (SCD) rate significantly. Of 17 subtypes, LQTS1-3 are the most common. Clinical presentation ranges from asymptomatic patients to torsade de pointes (TdP) and SCD. Emergency therapy includes defibrillation, administration of magnesium, betablockers and temporary pacing and sedation. Secondary prevention is based on betablocker therapy and implantation of an implantable cardioverter-defibrillator (ICD), if appropriate. Short QT syndrome (SQTS) is a rare channelopathy that manifests as SCD in 34%. So far 250 cases with mutations in 8 genes have been reported. ICDs are the only reliable protection against SCD. Drug therapy is based on hydroquinidine. Further therapeutic options exist for certain subtypes of both diseases. Patients should be referred to specialized centers.
Topics: Arrhythmias, Cardiac; Electrocardiography; Emergency Treatment; Humans; Long QT Syndrome; Secondary Prevention
PubMed: 32025785
DOI: 10.1007/s00399-020-00666-y -
Journal of Health Psychology Aug 2020Trait-like sensitivity to stress in long QT syndrome patients has been documented previously. In addition, mental stress has been associated with symptomatic status of...
Trait-like sensitivity to stress in long QT syndrome patients has been documented previously. In addition, mental stress has been associated with symptomatic status of long QT syndrome. We examined whether the symptomatic type 1 long QT syndrome patients would be more sensitive to mental stress compared to asymptomatic patients and whether there would be differences in task-related physiological stress reactions between type 1 long QT syndrome patients and healthy individuals. The study population consisted of 21 symptomatic and 23 asymptomatic molecularly defined KCNQ1 mutation carriers, their 32 non-carrier relatives and 46 non-related healthy controls, with mean ages of 37, 39, 35 and 23 years, respectively. Electrocardiography was utilised to calculate inter-beat interval and high frequency and low frequency heart rate variability. Blood pressure was measured and mean arterial pressure and pulse pressure were calculated. Stress was induced using three different tasks: mental arithmetic, reaction time and public speech. Stress responses of symptomatic and asymptomatic type 1 long QT syndrome patients were not statistically different in any of the stress tasks. Short-term physiological stress reactivity of symptomatic type 1 long QT syndrome patients appears to be normal and does not enhance the risk assessment of asymptomatic mutation carriers.
Topics: Adult; Case-Control Studies; Electrocardiography; Female; Heart Rate; Humans; KCNQ1 Potassium Channel; Laboratories; Long QT Syndrome; Male; Mutation; Risk Assessment; Stress, Psychological; Young Adult
PubMed: 29355047
DOI: 10.1177/1359105317751617 -
Biomolecules Aug 2020Significant advances in our understanding of the molecular mechanisms that cause congenital long QT syndrome (LQTS) have been made. A wide variety of experimental... (Review)
Review
Significant advances in our understanding of the molecular mechanisms that cause congenital long QT syndrome (LQTS) have been made. A wide variety of experimental approaches, including heterologous expression of mutant ion channel proteins and the use of inducible pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from LQTS patients offer insights into etiology and new therapeutic strategies. This review briefly discusses the major molecular mechanisms underlying LQTS type 2 (LQT2), which is caused by loss-of-function (LOF) mutations in the gene (also known as the human ether-à-go-go-related gene or ). Almost half of suspected LQT2-causing mutations are missense mutations, and functional studies suggest that about 90% of these mutations disrupt the intracellular transport, or trafficking, of the -encoded Kv11.1 channel protein to the cell surface membrane. In this review, we discuss emerging strategies that improve the trafficking and functional expression of trafficking-deficient LQT2 Kv11.1 channel proteins to the cell surface membrane and how new insights into the structure of the Kv11.1 channel protein will lead to computational approaches that identify which missense variants confer a high-risk for LQT2.
Topics: ERG1 Potassium Channel; Genetic Testing; Humans; Long QT Syndrome; Loss of Function Mutation
PubMed: 32759882
DOI: 10.3390/biom10081144 -
Europace : European Pacing,... Apr 2022
Topics: Death, Sudden, Cardiac; Humans; Long QT Syndrome
PubMed: 35303093
DOI: 10.1093/europace/euac012 -
Europace : European Pacing,... Nov 2023In long QT syndrome (LQTS), primary prevention improves outcome; thus, early identification is key. The most common LQTS phenotype is a foetal heart rate (FHR) < 3rd...
AIMS
In long QT syndrome (LQTS), primary prevention improves outcome; thus, early identification is key. The most common LQTS phenotype is a foetal heart rate (FHR) < 3rd percentile for gestational age (GA) but the effects of cohort, genotype, variant, and maternal β-blocker therapy on FHR are unknown. We assessed the influence of these factors on FHR in pregnancies with familial LQTS and developed a FHR/GA threshold for LQTS.
METHODS AND RESULTS
In an international cohort of pregnancies in which one parent had LQTS, LQTS genotype, familial variant, and maternal β-blocker effects on FHR were assessed. We developed a testing algorithm for LQTS using FHR and GA as continuous predictors. Data included 1966 FHRs at 7-42 weeks' GA from 267 pregnancies/164 LQTS families [220 LQTS type 1 (LQT1), 35 LQTS type 2 (LQT2), and 12 LQTS type 3 (LQT3)]. The FHRs were significantly lower in LQT1 and LQT2 but not LQT3 or LQTS negative. The LQT1 variants with non-nonsense and severe function loss (current density or β-adrenergic response) had lower FHR. Maternal β-blockers potentiated bradycardia in LQT1 and LQT2 but did not affect FHR in LQTS negative. A FHR/GA threshold predicted LQT1 and LQT2 with 74.9% accuracy, 71% sensitivity, and 81% specificity.
CONCLUSION
Genotype, LQT1 variant, and maternal β-blocker therapy affect FHR. A predictive threshold of FHR/GA significantly improves the accuracy, sensitivity, and specificity for LQT1 and LQT2, above the infant's a priori 50% probability. We speculate this model may be useful in screening for LQTS in perinatal subjects without a known LQTS family history.
Topics: Infant; Female; Pregnancy; Humans; Heart Rate, Fetal; Long QT Syndrome; Genotype; Adrenergic beta-Antagonists; Phenotype; Electrocardiography
PubMed: 37975542
DOI: 10.1093/europace/euad319 -
Circulation Research Aug 2019Long-QT syndrome, a frequently fatal inherited arrhythmia syndrome caused by genetic variants (congenital) or drugs (acquired), affects 1 in 2000 people worldwide. Its... (Review)
Review
Long-QT syndrome, a frequently fatal inherited arrhythmia syndrome caused by genetic variants (congenital) or drugs (acquired), affects 1 in 2000 people worldwide. Its sentinel event is often sudden cardiac death, which makes preclinical diagnosis by genetic testing potentially life-saving. Unfortunately, clinical experience with genetic testing has shown that it is difficult to correctly identify genetic variants as disease causing. These current deficiencies in accurately assigning pathogenicity led to the discovery of increasing numbers of rare variants classified as variant of uncertain significance. To overcome these challenges, new technologies such as clustered regularly interspaced short palindromic repeats (CRISPR) genome editing can be combined with human induced pluripotent stem cell-derived cardiomyocytes to provide a new approach to decipher pathogenicity of variants of uncertain significance and to better predict arrhythmia risk. To that end, the overarching goal of our network is to establish the utility of induced pluripotent stem cell-based platforms to solve major clinical problems associated with long-QT syndrome by determining how to (1) differentiate pathogenic mutations from background genetic noise, (2) assess existing and novel variants associated with congenital and acquired long-QT syndrome, and (3) provide genotype- and phenotype- guided risk stratification and pharmacological management of long-QT syndrome. To achieve these goals and to further advance the use of induced pluripotent stem cells in disease modeling and drug discovery, our team of investigators for this Leducq Foundation Transatlantic Networks of Excellence proposal will work together to (1) improve differentiation efficiency, cellular maturation, and lineage specificity, (2) develop new assays for high throughput cellular phenotyping, and (3) train young investigators to clinically implement patient-specific genetic modeling.
Topics: Channelopathies; Clustered Regularly Interspaced Short Palindromic Repeats; Humans; Induced Pluripotent Stem Cells; Long QT Syndrome; Precision Medicine
PubMed: 31465267
DOI: 10.1161/CIRCRESAHA.119.315209 -
JAMA Cardiology Aug 2023Syncope is the most powerful predictor for subsequent life-threatening events (LTEs) in patients with congenital long QT syndrome (LQTS). Whether distinct syncope...
IMPORTANCE
Syncope is the most powerful predictor for subsequent life-threatening events (LTEs) in patients with congenital long QT syndrome (LQTS). Whether distinct syncope triggers are associated with differential subsequent risk of LTEs is unknown.
OBJECTIVE
To evaluate the association between adrenergic (AD)- and nonadrenergic (non-AD)-triggered syncopal events and the risk of subsequent LTEs in patients with LQT types 1 to 3 (LQT1-3).
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study included data from 5 international LQTS registries (Rochester, New York; the Mayo Clinic, Rochester, Minnesota; Israel, the Netherlands, and Japan). The study population comprised 2938 patients with genetically confirmed LQT1, LQT2, or LQT3 stemming from a single LQTS-causative variant. Patients were enrolled from July 1979 to July 2021.
EXPOSURES
Syncope by AD and non-AD triggers.
MAIN OUTCOMES AND MEASURES
The primary end point was the first occurrence of an LTE. Multivariate Cox regression was used to determine the association of AD- or non-AD-triggered syncope on the risk of subsequent LTE by genotype. Separate analysis was performed in patients with β-blockers.
RESULTS
A total of 2938 patients were included (mean [SD] age at enrollment, 29 [7] years; 1645 [56%] female). In 1331 patients with LQT1, a first syncope occurred in 365 (27%) and was induced mostly with AD triggers (243 [67%]). Syncope preceded 43 subsequent LTEs (68%). Syncopal episodes associated with AD triggers were associated with the highest risk of subsequent LTE (hazard ratio [HR], 7.61; 95% CI, 4.18-14.20; P < .001), whereas the risk associated with syncopal events due to non-AD triggers was statistically nonsignificant (HR, 1.50; 95% CI, 0.21-4.77; P = .97). In 1106 patients with LQT2, a first syncope occurred in 283 (26%) and was associated with AD and non-AD triggers in 106 (37%) and 177 (63%), respectively. Syncope preceded 55 LTEs (56%). Both AD- and non-AD-triggered syncope were associated with a greater than 3-fold increased risk of subsequent LTE (HR, 3.07; 95% CI, 1.66-5.67; P ≤ .001 and HR, 3.45, 95% CI, 1.96-6.06; P ≤ .001, respectively). In contrast, in 501 patients with LQT3, LTE was preceded by a syncopal episode in 7 (12%). In patients with LQT1 and LQT2, treatment with β-blockers following a syncopal event was associated with a significant reduction in the risk of subsequent LTEs. The rate of breakthrough events during treatment with β-blockers was significantly higher among those treated with selective agents vs nonselective agents.
CONCLUSION AND RELEVANCE
In this study, trigger-specific syncope in LQTS patients was associated with differential risk of subsequent LTE and response to β-blocker therapy.
Topics: Humans; Female; Child; Male; Retrospective Studies; Risk Factors; Long QT Syndrome; Syncope; Adrenergic beta-Antagonists
PubMed: 37436769
DOI: 10.1001/jamacardio.2023.1951 -
Heart Rhythm May 2020Diagnosing long QT syndrome (LQTS) remains challenging because of a considerable overlap in QT interval between patients with LQTS and healthy subjects. Characterizing...
BACKGROUND
Diagnosing long QT syndrome (LQTS) remains challenging because of a considerable overlap in QT interval between patients with LQTS and healthy subjects. Characterizing T-wave morphology might improve LQTS diagnosis.
OBJECTIVE
The purpose of this study was to improve LQTS diagnosis by combining new polynomial-based T-wave morphology parameters with the corrected QT interval (QTc), age, and sex in a model.
METHODS
A retrospective cohort consisting of 333 patients with LQTS and 345 genotype-negative family members was used in this study. For each patient, a linear combination of the first 2 Hermite-Gauss (HG) polynomials was fitted to the STT segments of an average complex of all precordial leads and limb leads I and II. The weight coefficients as well as the error of the best fit were used to characterize T-wave morphology. Subjects were classified as patients with LQTS or controls by clinical QTc cutoffs and 3 support vector machine models fed with different features. An external cohort consisting of 72 patients and 45 controls was finally used to check the robustness of the models.
RESULTS
Baseline QTc cutoffs were specific but had low sensitivity in diagnosing LQTS. The model with T-wave morphology features, QTc, age, and sex had the best overall accuracy (84%), followed by a model with QTc, age, and sex (79%). The model with T-wave morphology features especially performed better in LQTS type 3 patients (69%).
CONCLUSION
T-wave morphologies can be characterized by fitting a linear combination of the first 2 Hermite-Gauss polynomials. Adding T-wave morphology characterization to age, sex, and QTc in a support vector machine model improves LQTS diagnosis.
Topics: Adult; Algorithms; Electrocardiography; Female; Follow-Up Studies; Genotype; Humans; Long QT Syndrome; Machine Learning; Male; Middle Aged; Reproducibility of Results; Retrospective Studies; Signal Processing, Computer-Assisted
PubMed: 31917370
DOI: 10.1016/j.hrthm.2019.12.020