Phenotypes of Overdiagnosed Long QT Syndrome
- In a single quaternary medical center experience, >1 out of 6 patients presenting with the diagnosis of long QT syndrome (LQTS) are found not to have the diagnosis after a thorough evaluation.
- The main causes of LQTS overdiagnoses were prolonged QTc interval secondary to vasovagal syncope, a seemingly positive genetic test result for a variant in one of the main LQTS genes, a positive family history of sudden cardiac death that was deemed unrelated to LQTS, isolated/transient QT prolongation, and misinterpretation of the QTc interval as a result of inclusion of the U wave.
What are the diagnostic miscues underlying the overdiagnosis of long QT syndrome (LQTS)?
The authors reviewed the electronic medical records of patients who presented with an outside diagnosis of LQTS, but were found to have normal findings.
About 16% (290/1,841) of patients with original diagnosis of LQTS were found to have normal findings. The main causes of LQTS overdiagnoses were: prolonged QTc interval secondary to vasovagal syncope (30%), a seemingly positive genetic test result for a variant in one of the main LQTS genes (23%), a positive family history of sudden cardiac death (SCD) that was deemed unrelated to LQTS (16%), isolated/transient QT prolongation (15%), and misinterpretation of the QTc interval as a result of inclusion of the U wave (14%).
The authors conclude that vasovagal syncope, “pseudo”-positive genetic test result in LQTS-causative genes, family history of SCD, transient QT prolongation, and misinterpretation of the QTc interval due to the inclusion of the U wave are factors most commonly associated with LQTS overdiagnosis.
The authors address an important issue of accurate diagnosis of LQTS, as such diagnosis may have profound consequences on the lives of patients suspected of having the life-threatening condition. Overdiagnosis of LQTS brings a host of undesirable effects, such as inappropriate lifelong medication, sports disqualification, unnecessary implantable cardioverter-defibrillator (ICD) implantation, inappropriate ICD shocks, etc. It is notable that >1 of every 6 patients who arrive with a diagnosis of LQTS at the authors’ institution are eventually found not to have the diagnosis! The authors group factors associated with an incorrect diagnosis of LQTS into four domains: clinical, diagnostic, genetic, and family history. There are many reasons for temporary QT prolongation. One prominent instance of QT prolongation occurs early after vasovagal syncope due to dynamic changes in the autonomic tone. It is critical that the clinical history is consistent with an arrhythmogenic type of syncope, and that QT prolongation is documented on >1 electrocardiogram. Judicious use of genetic testing may mitigate the erroneous diagnosis of LQTS, as many variants of unknown significance skew toward misdiagnosis. Finally, it is key to perform a thorough multigenerational family history and accurate QT measurement excluding the U wave. Once a patient is given the ominous misdiagnosis, it may be difficult to rescind.
Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Implantable Devices, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, Acute Heart Failure
Keywords: Arrhythmias, Cardiac, Death, Sudden, Cardiac, Defibrillators, Implantable, Diagnostic Errors, Diagnostic Tests, Routine, Electrocardiography, Genetic Testing, Heart Failure, Long QT Syndrome, Missed Diagnosis, Phenotype, Syncope, Syncope, Vasovagal
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