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Heart (British Cardiac Society) Nov 2018A prolonged QTc (LQT) is a surrogate for the risk of torsade de pointes (TdP). QTc interval duration is influenced by sex hormones: oestradiol prolongs and testosterone... (Comparative Study)
Comparative Study
OBJECTIVE
A prolonged QTc (LQT) is a surrogate for the risk of torsade de pointes (TdP). QTc interval duration is influenced by sex hormones: oestradiol prolongs and testosterone shortens QTc. Drugs used in the treatment of breast cancer have divergent effects on hormonal status.
METHODS
We performed a disproportionality analysis using the European database of suspected adverse drug reaction (ADR) reports to evaluate the reporting OR (ROR χ) of LQT, TdP and ventricular arrhythmias associated with selective oestrogen receptor modulators (SERMs: tamoxifen and toremifene) as opposed to aromatase inhibitors (AIs: anastrozole, exemestane and letrozole). When the proportion of an ADR is greater in patients exposed to a drug (SERMs) compared with patients exposed to control drug (AIs), this suggests an association between the specific drug and the reaction and is a potential signal for safety. Clinical and demographic characterisation of patients with SERMs-induced LQT and ventricular arrhythmias was performed.
RESULTS
SERMs were associated with higher proportion of LQT reports versus AIs (26/8318 vs 11/14851, ROR: 4.2 (2.11-8.55), p<0.001). SERMs were also associated with higher proportion of TdP and ventricular arrhythmia reports versus AIs (6/8318 vs 2/14851, ROR: 5.4 (1.29-26.15), p:0.02; 16/8318 vs 12/14851, ROR: 2.38 (1.15-4.94), p:0.02, respectively). Mortality was 38% in patients presenting ventricular arrhythmias associated with SERMs.
CONCLUSIONS
SERMs are associated with more reports of drug-induced LQT, TdP and ventricular arrhythmias compared with AIs. This finding is consistent with oestradiol-like properties of SERMs on the heart as opposed to effects of oestrogen deprivation and testosterone increase induced by AIs.
TRIAL REGISTRATION NUMBER
NCT03259711.
Topics: Action Potentials; Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Aromatase Inhibitors; Cardiotoxicity; Databases, Factual; Europe; Female; Heart Conduction System; Heart Rate; Humans; Long QT Syndrome; Middle Aged; Prognosis; Risk Assessment; Risk Factors; Selective Estrogen Receptor Modulators; Tamoxifen; Torsades de Pointes; Young Adult
PubMed: 29720397
DOI: 10.1136/heartjnl-2017-312934 -
Deutsches Arzteblatt International Oct 2011Many psychotropic drugs can delay cardiac repolarization and thereby prolong the rate-corrected QT interval (QTc). A prolonged QTc often arouses concern in clinical... (Review)
Review
INTRODUCTION
Many psychotropic drugs can delay cardiac repolarization and thereby prolong the rate-corrected QT interval (QTc). A prolonged QTc often arouses concern in clinical practice, as it can be followed, in rare cases, by the life-threatening polymorphic ventricular tachyarrhythmia called torsade de pointes (TdP).
METHOD
We searched PubMed for pertinent literature on the risk of QTc prolongation and/or TdP associated with commonly used psychotropic drugs.
RESULTS
Thioridazine and ziprasidone confer the highest risk of QTc prolongation and/or TdP. There is also a clinically significant risk associated with haloperidol given intravenously in high doses. TdP has been reported in a few cases in association with the use of newer antipsychotic drugs (mainly quetiapine and amisulpride), most of the tri- and tetracyclic antidepressants, and the selective monoamine reuptake inhibitors citalopram, fluoxetine, paroxetine, and venlafaxine. As a rule, however, QTc prolongation and/or TdP occur only in the presence of multiple additional risk factors, such as age over 65 years, pre-existing cardiovascular disease, bradycardia, female sex, hypokalemia, hypomagnesemia, a supratherapeutic or toxic serum concentration, or the simultaneous administration of other drugs that delay repolarization or interfere with drug metabolism.
CONCLUSION
Before prescribing a psychotropic drug, the physician should carefully assess its risks and benefits to avoid this type of adverse reaction, particularly when additional risk factors are present. The ECG and electrolytes should be regularly monitored in patients taking psychotropic drugs.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Long QT Syndrome; Prevalence; Psychotropic Drugs; Risk Assessment; Risk Factors; Torsades de Pointes
PubMed: 22114630
DOI: 10.3238/arztebl.2011.0687 -
The Journal of Physiology May 2016Drugs used to treat cardiovascular disease as well as those used in the treatment of multiple other conditions can occasionally produce exaggerated prolongation of the... (Review)
Review
Drugs used to treat cardiovascular disease as well as those used in the treatment of multiple other conditions can occasionally produce exaggerated prolongation of the QT interval on the electrocardiogram and the morphologically distinctive polymorphic ventricular tachycardia ('torsades de pointes'). This syndrome of drug-induced long QT syndrome has moved from an interesting academic exercise to become a key element in the development of any new drug entity. The prevailing view, which has driven both clinical care and drug regulation, holds that cardiac repolarization represents a balance between inward currents (primarily through calcium and sodium channels) and outward currents (primarily through rapid and slowed delayed rectifier potassium channels) and that block of the rapid delayed rectifier (IKr ) is the primary mechanism whereby drugs prolong individual action potentials, manifest on the surface electrocardiogram as QT interval prolongation. Such marked action potential prolongation in individual cardiac cells, in turn, is accompanied by arrhythmogenic afterdepolarizations thought to trigger torsades de pointes. This review describes the evidence in support of this construct, and describes the way in which clinical and whole heart experiments have informed molecular mechanisms and vice versa. New data that challenge these views and that may, as a result, lead to new clinical care and drug screening paradigms, are discussed.
Topics: Animals; Drug-Related Side Effects and Adverse Reactions; Humans; Long QT Syndrome; Myocytes, Cardiac; Torsades de Pointes
PubMed: 26660066
DOI: 10.1113/JP270526 -
Journal of the American Heart... Feb 2021
Topics: Arrhythmias, Cardiac; Gonadotropins; Humans; Testosterone; Torsades de Pointes
PubMed: 33599137
DOI: 10.1161/JAHA.120.020300 -
Indian Heart Journal 2013Torsades de pointes ("twisting of points") (TdP) is a broad complex tachyarrhythmia which was first described in 1966 by Francois Dessertenne and usually results from...
Torsades de pointes ("twisting of points") (TdP) is a broad complex tachyarrhythmia which was first described in 1966 by Francois Dessertenne and usually results from prolongation of the QT interval.(1) A wide variety of drugs have been shown to prolong the QT interval in susceptible individuals.(2) We present the case of a former intravenous heroin user presenting with several episodes of TdP which were caused by QT prolongation due to methadone treatment and exacerbated by hepatitis B/C infection. Despite aggressive medical treatment and withdrawal of methadone, he had recurrent episodes of TdP which required continuous temporary cardiac pacing for six days. He was found to have moderate LV dysfunction on his echocardiogram and unobstructed coronary arteries on coronary angiography. He underwent implantation of a defibrillator due to concerns about further episodes of ventricular arrhythmias which could recur even in the absence of further methadone use.
Topics: Adult; Analgesics, Opioid; Defibrillators, Implantable; Electric Countershock; Electrocardiography; Humans; Male; Methadone; Opiate Substitution Treatment; Torsades de Pointes; Water-Electrolyte Imbalance
PubMed: 23809388
DOI: 10.1016/j.ihj.2013.04.016 -
Annals of Noninvasive Electrocardiology... Jan 2022TdP is a form of polymorphic ventricular tachycardia which develops in the setting of a prolonged QT interval. There are limited data describing risk factors, treatment,...
BACKGROUND
TdP is a form of polymorphic ventricular tachycardia which develops in the setting of a prolonged QT interval. There are limited data describing risk factors, treatment, and outcomes of this potentially fatal arrhythmia.
OBJECTIVE
Our goals were as follows: (1) to validate cases presenting with Torsade de Pointes (TdP), (2) to identify modifiable risk factors, and (3) to describe the management strategies used for TdP and its prognosis in a real-world healthcare setting.
METHODS
Case-control study (with 2:1 matching on age, sex, and race/ethnicity) nested within the Genetic Epidemiology Research on Aging (GERA) cohort. Follow-up of the cohort for case ascertainment was between January 01, 2005 and December 31, 2018.
RESULTS
A total of 56 cases of TdP were confirmed (incidence rate = 3.6 per 100,000 persons/years). The average (SD) age of the TdP cases was 74 (13) years, 55 percent were female, and 16 percent were non-white. The independent predictors of TdP were potassium concentration <3.6 mEq/L (OR = 10.6), prior history of atrial fibrillation/flutter (OR = 6.2), QTc >480 ms (OR = 4.4) and prior history of coronary artery disease (OR = 2.6). Exposure to furosemide and amiodarone was significantly greater in cases than in controls. The most common treatment for TdP was IV magnesium (78.6%) and IV potassium repletion (73.2%). The in-hospital and 1-year mortality rates for TdP cases were 10.7% and 25.0% percent, respectively.
CONCLUSIONS
These findings may inform quantitative multivariate risk indices for the prediction of TdP and could guide practitioners on which patients may qualify for continuous ECG monitoring and/or electrolyte replacement therapy.
Topics: Aged; Case-Control Studies; Delivery of Health Care, Integrated; Electrocardiography; Female; Humans; Long QT Syndrome; Torsades de Pointes
PubMed: 34547155
DOI: 10.1111/anec.12888 -
Circulation Apr 2012
Review
Topics: Animals; Genetic Markers; Humans; Risk Factors; Torsades de Pointes
PubMed: 22474311
DOI: 10.1161/CIRCULATIONAHA.111.080887 -
JACC. Clinical Electrophysiology Dec 2017
Topics: Animals; Atrioventricular Block; Dogs; Electrocardiography; Long QT Syndrome; Torsades de Pointes
PubMed: 29759840
DOI: 10.1016/j.jacep.2017.09.174 -
Anesthesia and Analgesia Sep 2013Torsade de pointes is a rare but potentially fatal arrhythmia. More than 40 cases of perioperative torsade de pointes have been reported in the literature; however, the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Torsade de pointes is a rare but potentially fatal arrhythmia. More than 40 cases of perioperative torsade de pointes have been reported in the literature; however, the current evidence regarding this complication is very limited. To improve our understanding, we performed a systematic review and meta-analysis of all published case reports of perioperative torsade de pointes.
METHODS
MEDLINE was systematically searched for cases of perioperative torsade de pointes. We included patients of all age groups and cases that occurred from the immediate preoperative period to the third postoperative day. Patient and case characteristics as well as QT interval data were extracted.
RESULTS
Forty-six cases of perioperative torsade de pointes were identified; 29 occurred in women (67%), and 2 episodes were fatal (case fatality rate: 4%). Craniotomies and cardiac surgery accounted for 40% of all cases. Preceding events identified by the authors were hypokalemia (12/46, 26%; 99% confidence interval [CI], 9%-43%) and bradycardia (7/46, 15%; 99% CI, 2%-28%). Drugs were implicated in approximately one third of the events (14/46, 30%; 99% CI, 13%-48%). The mean corrected QT (QTc) at baseline was 457 ± 67 milliseconds (minimum 320 milliseconds; maximum 647 milliseconds; data available in 27/46 patients). At the time of the event, the mean QTc increased to 575 ± 77 milliseconds (minimum 413 milliseconds; maximum 766 milliseconds; data available in 33/46 patients). On average, QTc increased by +118 milliseconds (99% CI, 70-166 milliseconds; P < 0.001) between baseline and after the torsade de pointes event. All patients, except for 2, had a substantial prolongation of their QTc interval at the time of the event.
CONCLUSIONS
This systematic review identified several common risk factors for perioperative torsade de pointes. Given the nearly uniform presence of a substantial QTc interval prolongation at the time of a torsade de pointes episode, increased vigilance for perioperative QTc interval prolongation may be warranted.
Topics: Adolescent; Adult; Aged; Child; Data Interpretation, Statistical; Electrocardiography; Female; Humans; Intraoperative Complications; Long QT Syndrome; Male; Middle Aged; Perioperative Care; Postoperative Complications; Predictive Value of Tests; Torsades de Pointes; Young Adult
PubMed: 23744954
DOI: 10.1213/ANE.0b013e318290c380 -
Gut and Liver Nov 2022Approximately 30% to 70% of patients with cirrhosis have QT interval prolongation. In patients without cirrhosis, QT prolongation is associated with an increased risk of... (Review)
Review
Approximately 30% to 70% of patients with cirrhosis have QT interval prolongation. In patients without cirrhosis, QT prolongation is associated with an increased risk of ventricular arrhythmias, such as torsade de pointes (TdP). In cirrhotic patients, there is likely a significant association between the corrected QT (QTc) interval and the severity of liver disease, and possibly with increased mortality. We present a stepwise overview of the pathophysiology and management of acquired long QT syndrome in cirrhosis. The QT interval is mainly determined by ventricular repolarization. To compare the QT interval in time it should be corrected for heart rate (QTc), preferably by the Fridericia method. A QTc interval >450 ms in males and >470 ms in females is considered prolonged. The pathophysiological mechanism remains incompletely understood, but may include metabolic, autonomic or hormonal imbalances, cirrhotic heart failure and/or genetic predisposition. Additional external risk factors for QTc prolongation include medication (I blockade and altered cytochrome P450 activity), bradycardia, electrolyte abnormalities, underlying cardiomyopathy and acute illness. In patients with cirrhosis, multiple hits and cardiac-hepatic interactions are often required to sufficiently erode the repolarization reserve before long QT syndrome and TdP can occur. While some risk factors are unavoidable, overall risk can be mitigated by electrocardiogram monitoring and avoiding drug interactions and electrolyte and acidbase disturbances. In cirrhotic patients with prolonged QTc interval, a joint effort by cardiologists and hepatologists may be useful and significantly improve the clinical course and outcome.
Topics: Male; Female; Humans; Long QT Syndrome; Torsades de Pointes; Risk Factors; Liver Cirrhosis; DNA-Binding Proteins
PubMed: 35864808
DOI: 10.5009/gnl210537