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Journal of the American Heart... Dec 2017The cardiovascular complications of cancer therapeutics are the focus of the burgeoning field of cardio-oncology. A common challenge in this field is the impact of... (Review)
Review
BACKGROUND
The cardiovascular complications of cancer therapeutics are the focus of the burgeoning field of cardio-oncology. A common challenge in this field is the impact of cancer drugs on cardiac repolarization (ie, QT prolongation) and the potential risk for the life-threatening arrhythmia torsades de pointes. Although QT prolongation is not a perfect marker of arrhythmia risk, this has become a primary safety metric among oncologists. Cardiologists caring for patients receiving cancer treatment should become familiar with the drugs associated with QT prolongation, its incidence, and appropriate management strategies to provide meaningful consultation in this complex clinical scenario.
METHODS AND RESULTS
In this article, we performed a systematic review (using Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines) of commonly used cancer drugs to determine the incidence of QT prolongation and clinically relevant arrhythmias. We calculated summary estimates of the incidence of all and clinically relevant QT prolongation as well as arrhythmias and sudden cardiac death. We then describe strategies to prevent, identify, and manage QT prolongation in patients receiving cancer therapy. We identified a total of 173 relevant publications. The weighted incidence of any corrected QT (QTc) prolongation in our systematic review in patients treated with conventional therapies (eg, anthracyclines) ranged from 0% to 22%, although QTc >500 ms, arrhythmias, or sudden cardiac death was extremely rare. The risk of QTc prolongation with targeted therapies (eg, small molecular tyrosine kinase inhibitors) ranged between 0% and 22.7% with severe prolongation (QTc >500 ms) reported in 0% to 5.2% of the patients. Arrhythmias and sudden cardiac death were rare.
CONCLUSIONS
Our systematic review demonstrates that there is variability in the incidence of QTc prolongation of various cancer drugs; however, the clinical consequence, as defined by arrhythmias or sudden cardiac death, remains rare.
Topics: Antineoplastic Agents; Death, Sudden, Cardiac; Electrocardiography; Global Health; Humans; Incidence; Long QT Syndrome; Neoplasms
PubMed: 29217664
DOI: 10.1161/JAHA.117.007724 -
Annals of Noninvasive Electrocardiology... Jan 2023QTc prolongation is key in diagnosing long QT syndrome (LQTS), however 25%-50% with congenital LQTS (cLQTS) demonstrate a normal resting QTc. T wave morphology (TWM) can... (Review)
Review
INTRODUCTION
QTc prolongation is key in diagnosing long QT syndrome (LQTS), however 25%-50% with congenital LQTS (cLQTS) demonstrate a normal resting QTc. T wave morphology (TWM) can distinguish cLQTS subtypes but its role in acquired LQTS (aLQTS) is unclear.
METHODS
Electronic databases were searched using the terms "LQTS," "long QT syndrome," "QTc prolongation," "prolonged QT," and "T wave," "T wave morphology," "T wave pattern," "T wave biomarkers." Whole text articles assessing TWM, independent of QTc, were included.
RESULTS
Seventeen studies met criteria. TWM measurements included T-wave amplitude, duration, magnitude, Tpeak-Tend, QTpeak, left and right slope, center of gravity (COG), sigmoidal and polynomial classifiers, repolarizing integral, morphology combination score (MCS) and principal component analysis (PCA); and vectorcardiographic biomarkers. cLQTS were distinguished from controls by sigmoidal and polynomial classifiers, MCS, QTpeak, Tpeak-Tend, left slope; and COG x axis. MCS detected aLQTS more significantly than QTc. Flatness, asymmetry and notching, J-Tpeak; and Tpeak-Tend correlated with QTc in aLQTS. Multichannel block in aLQTS was identified by early repolarization (ERD ) and late repolarization (LRD ), with ERD reflecting hERG-specific blockade. Cardiac events were predicted in cLQTS by T wave flatness, notching, and inversion in leads II and V , left slope in lead V ; and COG last 25% in lead I. T wave right slope in lead I and T-roundness achieved this in aLQTS.
CONCLUSION
Numerous TWM biomarkers which supplement QTc assessment were identified. Their diagnostic capabilities include differentiation of genotypes, identification of concealed LQTS, differentiating aLQTS from cLQTS; and determining multichannel versus hERG channel blockade.
Topics: Humans; Electrocardiography; Long QT Syndrome; Genotype; Biomarkers
PubMed: 36345173
DOI: 10.1111/anec.13015 -
Cureus Sep 2021Long QT syndrome (LQTS) is one of the most common inherited cardiac channelopathies with a prevalence of 1:2000. The condition can be congenital or acquired with 15... (Review)
Review
Long QT syndrome (LQTS) is one of the most common inherited cardiac channelopathies with a prevalence of 1:2000. The condition can be congenital or acquired with 15 recognized genotypes; the most common subtypes are LQTS 1, 2, and 3 making up to 85%-90% of the cases. LQTS is characterized by delayed ventricular cardiomyocyte repolarization manifesting on the surface electrocardiogram (EKG) by a prolonged corrected QT (QTc) interval. The mainstay of treatment for this condition involves in part or combination medical therapy via β-blockers as first-line (or other anti-arrhythmic), left cardiac sympathectomy, or implantable cardiac defibrillator placement. Given the high rate of adverse cardiac events (ACE) or sudden cardiac death (SCD) in this population of patients with this disease, this review seeks to highlight the genotype-specific treatment consensus in β-blocker therapy of the most common subtypes. A database search of PubMed, PMC, and Medline was conducted to ascertain the most recent data in the last five years on the management of LQTS types 1-3 and the role of β-blockers in reducing ACE in these types. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adhered to in the study selection, and selected studies focused on humans, written in the English Language, and within the last five years of LQTS subtypes 1, 2, and 3. Eleven relevant studies were selected after considering inclusion criteria, exclusion criteria, and quality appraisal within the last five years, focusing on β-blocker selection directed based on the subtypes of LQTS. Two meta-analyses, one cohort study, and eight reviews provided significant data that non-selective β-blockers unequivocally are of benefit in these LQTS types. Summary of findings suggested nadolol followed by propranolol yields the best results in LQTS 1, while nadolol would yield the best effect in LQTS 2 and 3.
PubMed: 34646680
DOI: 10.7759/cureus.17632 -
Journal of the American Heart... Jul 2022Background Diagnosis is particularly challenging in concealed or asymptomatic long QT syndrome (LQTS). Provocative testing, unmasking the characterization of LQTS, is a... (Meta-Analysis)
Meta-Analysis Review
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 40 ms longer in patients with LQTS than in controls (mean difference [MD], 40.54 [95% CI, 37.43-43.65]; <0.001). Compared with the control group, patients with LQTS had 28 ms longer ΔQTc upon standing (MD, 28.82 [95% CI, 23.05-34.58]; <0.001), nearly 30 ms longer both at peak exercise (MD, 27.31 [95% CI, 21.51-33.11]; <0.001) and recovery 4 to 5 minutes (MD, 29.85 [95% CI, 24.36-35.35]; <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]; <0.001) and LQT2 (MD, 60.17 [95% CI, 50.18-70.16]; <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.
Topics: Electrocardiography; Epinephrine; Exercise Test; Genotype; Humans; Long QT Syndrome
PubMed: 35861842
DOI: 10.1161/JAHA.122.025246 -
Value in Health : the Journal of the... Jul 2015Recent improvements in the identification of the genetic basis of long QT syndrome (LQTS) have led to significant changes in the diagnosis and management of this... (Review)
Review
BACKGROUND
Recent improvements in the identification of the genetic basis of long QT syndrome (LQTS) have led to significant changes in the diagnosis and management of this life-threatening condition. Genetic and electrocardiogram (ECG) tests are the most relevant examples among testing strategies for LQTS, yet their cost-effectiveness remains controversial.
OBJECTIVE
The aim of this work was to review the available evidence on the cost-effectiveness of genetic and ECG testing strategies for the diagnosis of LQTS.
METHODS
We performed a systematic review of the literature on the cost-effectiveness of genetic and ECG screening strategies for the early detection of LQTS using MEDLINE, EMBASE, and CRD databases between 2000 and 2013. A weighted version of Drummond checklist was instrumental in further assessing the quality of the included studies.
RESULTS
We identified four eligible articles. Among them, genetic testing in the early detection of LQTS was cost-effective compared with no testing in symptomatic cases and not cost-effective when compared with watchful waiting in asymptomatic first-degree relatives of patients with established LQTS although it reached cost-effectiveness in higher risk subgroups, whereas ECG testing in neonates was highly cost-effective when compared with any screening strategy.
CONCLUSIONS
LQTS profiling and patients' stratification have the potential to improve the disease management. Because of the limited current knowledge in this field, the present review recommends to perform further cost-effectiveness evaluations of the genetic and ECG screening alternatives, especially within European health care systems, which are still not available in the literature on genetic testing.
Topics: Age Factors; Comparative Effectiveness Research; Cost-Benefit Analysis; Electrocardiography; Genetic Predisposition to Disease; Genetic Testing; Health Care Costs; Heart Rate; Humans; Infant, Newborn; Long QT Syndrome; Models, Economic; Phenotype; Predictive Value of Tests; Young Adult
PubMed: 26297099
DOI: 10.1016/j.jval.2015.03.1788 -
The European Respiratory Journal Nov 2017
Topics: Antitubercular Agents; Diarylquinolines; Electrocardiography; Humans; Long QT Syndrome; Tuberculosis, Multidrug-Resistant
PubMed: 29146605
DOI: 10.1183/13993003.01462-2017 -
European Journal of Clinical... May 2022Many drugs are associated with the risk of QT prolongation and torsades de pointes (TdP), and different risk assessment tools (RATs) are developed to help clinicians to... (Review)
Review
PURPOSE
Many drugs are associated with the risk of QT prolongation and torsades de pointes (TdP), and different risk assessment tools (RATs) are developed to help clinicians to manage related risk. The aim of this systematic review was to summarize the evidence of different RATs for QT prolonging pharmacotherapy.
METHODS
A systematic review was conducted using PubMed and Scopus databases. Studies concerning risk assessment tools for QT prolonging pharmacotherapy, including older adults, were included. Screening and selection of the studies, data extraction, and risk of bias assessment were undertaken.
RESULTS
A total of 21 studies were included, involving different risk assessment tools. Most commonly used tools were risk scores (n = 9), computerized physician order entry systems (n = 3), and clinical decision support systems (n = 6). The tools were developed mainly for physicians and pharmacists. Risk scores included a high number of risk factors, both pharmacological and non-pharmacological, for QT prolongation and TdP. The inclusion of patients' risk factors in computerized physician order entry and clinical decision support systems varied.
CONCLUSION
Most of the risk assessment tools for QT prolonging pharmacotherapy give a comprehensive overview of patient-specific risks of QT prolongation and TdP and reduce modifiable risk factors and actual events. The risk assessment tools could be better adapted to different health information systems to help in clinical decision-making. Further studies on clinical validation of risk assessment tools with randomized controlled trials are needed.
Topics: Aged; DNA-Binding Proteins; Electrocardiography; Humans; Long QT Syndrome; Risk Assessment; Risk Factors; Torsades de Pointes
PubMed: 35156131
DOI: 10.1007/s00228-022-03285-3 -
Frontiers in Cardiovascular Medicine 2023To perform a meta-analysis to discover the performance of ML algorithms in identifying Congenital long QT syndrome (LQTS). (Review)
Review
INTRODUCTION
To perform a meta-analysis to discover the performance of ML algorithms in identifying Congenital long QT syndrome (LQTS).
METHODS
The searched databases included Cochrane, EMBASE, Web of Science, and PubMed. Our study considered all English-language studies that reported the detection of LQTS using ML algorithms. Quality was assessed using QUADAS-2 and QUADAS-AI tools. The bivariate mixed effects models were used in our study. Based on genotype data for LQTS, we performed a subgroup analysis.
RESULTS
Out of 536 studies, 8 met all inclusion criteria. The pooled area under the receiving operating curve (SAUROC) for detecting LQTS was 0.95 (95% CI: 0.31-1.00); sensitivity was 0.87 (95% CI: 0.83-0.90), and specificity was 0.91 (95% CI: 0.88-0.93). Additionally, diagnostic odd ratio (DOR) was 65 (95% CI: 39-109). The positive likelihood ratio (PLR) was 9.3 (95% CI: 7.0-12.3) and the negative likelihood ratio (NLR) was 0.14 (95% CI: 0.11-0.20), with very low heterogeneity (= 16%).
DISCUSSION
We found that machine learning can be used to detect features of rare cardiovascular disease like LQTS, thus increasing our understanding of intelligent interpretation of ECG. To improve ML performance in the classification of LQTS subtypes, further research is required.
SYSTEMATIC REVIEW REGISTRATION
identifier PROSPERO CRD42022360122.
PubMed: 37351282
DOI: 10.3389/fcvm.2023.1172451 -
Heart & Lung : the Journal of Critical... 2023The potential benefit of implantable cardioverter-defibrillator (ICD) therapy in individuals with inherited arrhythmia syndromes is well known. However, it is not... (Review)
Review
BACKGROUND
The potential benefit of implantable cardioverter-defibrillator (ICD) therapy in individuals with inherited arrhythmia syndromes is well known. However, it is not deprived of morbidity, in the form of inappropriate therapies and other ICD-related complications.
OBJECTIVE
The aim of this systematic review is to estimate the rate of appropriate and inappropriate therapy, as well as other ICD-related complications, in individuals with inherited arrhythmia syndromes.
METHODS
A systematic review was performed, regarding appropriate and inappropriate therapy, and other ICD-related complications, in individuals with inherited arrhythmia syndromes (Brugada Syndrome, Catecholaminergic Polymorphic Ventricular Tachycardia, Early Repolarization Syndrome, Long QT Syndrome and Short QT syndrome). Studies were identified by searching published papers in PubMed and Embase up to August 23rd, 2022.
RESULTS
From data gathered of 36 studies, with a total of 2750 individuals, during a mean follow-up time of 69 months, appropriate therapies occurred in 21% of the individuals and inappropriate therapies in 20% of the individuals. Concerning the other ICD-related complications, 456 complications were observed, amongst 2084 individuals (22%), with the most frequent being lead malfunction (46%), followed by infectious complications (13%).
CONCLUSIONS
ICD-related complications are not uncommon, especially when one considers the exposure time of young individuals. The incidence of inappropriate therapies was 20%, although lower rates were reported in recent publications. S-ICD is an effective alternative to transvenous ICD for sudden death prevention. The decision to implant an ICD should be individualized, taking into account the risk profile of each patient, as well as the possibility of complications.
Topics: Humans; Defibrillators, Implantable; Electrocardiography; Arrhythmias, Cardiac; Tachycardia, Ventricular; Long QT Syndrome; Death, Sudden, Cardiac; Treatment Outcome
PubMed: 36863123
DOI: 10.1016/j.hrtlng.2023.02.012 -
Biochemical and Biophysical Research... Nov 2023QT prolongation is one of the main unwanted cardiac effects caused by drugs, such as anti-psychotics and anti-depressants, inducing mainly via hERG channel dysfunction....
PURPOSE
QT prolongation is one of the main unwanted cardiac effects caused by drugs, such as anti-psychotics and anti-depressants, inducing mainly via hERG channel dysfunction. The precise and underlying mechanism of adverse effects on hERG channel are still indecisive, but these effects limit their use in patients with cardiac risk factors. The aim of this review was studying mechanism of Long-term QT syndrome induction via hERG channel dysfunction by these Drugs.
METHOD
Search was performed in PubMed, and Scopus. All human, animals, and cell lines studies, English and full text publications were included. Among 1280 papers, 23 studies were eligible for more assessments. Quality of studies cheeked by two researchers independently.
KEY FINDING
most of studies were done on anti-psychotic drugs, especially typical class. Most used investigated method to long-term QT induction was patch clamp.
SIGNIFICANCE
results suggests in susceptible cases with heart risk factors, these drugs should be taken with caution and monitored.
PubMed: 37774574
DOI: 10.1016/j.bbrc.2023.09.043