Cost-Effectiveness of Genetic Testing in Family Members of Patients With Long-QT Syndrome

Pérez, Marco; Kumarasamy, Narmadan A; Owens, Douglas K; Wang, Paul J.; Hlatky, Mark A.

doi:10.1161/circoutcomes.110.957365

Cited by 33 publications

(35 citation statements)

References 61 publications

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“…[22][23][24][25] Many of the studies that involve modeling or data analysis have examined genes that, when mutant, predispose to disease at considerably less than 100% penetrance. For example, people at higher than age-adjusted risk for colorectal cancer, based on family history or genetic testing of tumor tissue in relatives, benefit clinically from earlier institution of colonoscopic monitoring.…”

Section: Discussionmentioning

confidence: 99%

Cost savings through molecular diagnosis for hereditary hemorrhagic telangiectasia

Zayac

Trerotola

Asch

et al. 2012

Genetics in Medicine

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Purpose: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder of vascular development resulting in direct connections between the arterial and venous systems, bypassing capillaries. Symptoms and signs can appear throughout life and marked intrafamilial variability confounds diagnosis based purely on clinical criteria. We set out to determine the impact of genetic testing on the cost of screening for HHT in at-risk relatives. methods:We performed economic modeling of idealized pedigrees following two scenarios: repeated clinical screening until an HHT diagnosis could be either affirmed or excluded, and mutation testing in the proband, followed by genetic testing of at-risk relatives and clinical monitoring of only those relatives who test positive for the familial mutation.Results: Based on actual reimbursement data from our region's largest health insurer, the molecular diagnostic model saved over $22,000 for a family with four relatives at risk for the initial diagnostic work-up. For a cohort of 100 probands, the total savings for the molecular diagnostic model over a reasonable period of follow-up was greater than $9 million. conclusion: In this idealized setting in which all probands and at-risk relatives accepted molecular testing, the economic advantages of genetic screening over repeated clinical screening are substantial. 2012:14(6):604-610 Genet Med

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Section: Discussionmentioning

confidence: 99%

Cost savings through molecular diagnosis for hereditary hemorrhagic telangiectasia

Zayac

Trerotola

Asch

et al. 2012

Genetics in Medicine

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“…This approach could facilitate targeted genetic screening and help improve the yield and cost-effectiveness of genetic testing. 35,36 Early and accurate diagnosis of LQTS is important because early drug treatment can reduce the risk of sudden cardiac death compared with a watchful waiting strategy. 36 Future work describing the potential role of the ECG features in patients with Holter monitor or on exercise ECGs should be explored to determine diagnostic yield.…”

Section: Clinical Significance and Applicationmentioning

confidence: 99%

Identification of Concealed and Manifest Long QT Syndrome Using a Novel T Wave Analysis Program

Sugrue

Noseworthy

Kremen

et al. 2016

Circ: Arrhythmia and Electrophysiology

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C ongenital long QT syndrome (LQTS) affects ≈1 in 2000 people and is an important cause of sudden cardiac death in the young. 1 There are 17 known LQTS-susceptibility genes (LQT1-17), but the most common types LQT1, LQT2, and LQT3 account for ≈75% to 80% of all congenital LQTS and over 95% of genetically proven cases.2 The current diagnostic approach is based on measurement of the heart rate-corrected QT interval (QTc) and clinical factors, such as the medical and family history and clinical presentation. However, unless the QTc is repeatedly ≥500 ms without alternative acquired factors present, the QTc from the resting 12-lead ECG is insufficient for diagnosis.3 Genetic testing plays an important role in the diagnosis, risk stratification, tailoring of genotypedirected therapies and for mutation-specific confirmatory testing of appropriate relatives once the index case's diseasecausing mutation has been identified. 4,5 However, despite its excellent diagnostic yield, some genetic test results are difficult to interpret, 6 and access to genetic testing in general can be hampered by insurance reimbursement considerations. Accordingly, there is ongoing need for more refined diagnosis and risk stratification based on readily available, noninvasive means.The 12-lead surface ECG is an inexpensive test that is performed widely and could be used as an efficient diagnostic © 2016 American Heart Association, Inc. Original ArticleBackground-Congenital long QT syndrome (LQTS) is characterized by QT prolongation. However, the QT interval itself is insufficient for diagnosis, unless the corrected QT interval is repeatedly ≥500 ms without an acquired explanation. Further, the majority of LQTS patients have a corrected QT interval below this threshold, and a significant minority has normal resting corrected QT interval values. Here, we aimed to develop and validate a novel, quantitative T wave morphological analysis program to differentiate LQTS patients from healthy controls. Methods and Results-We analyzed a genotyped cohort of 420 patients (22±16 years, 43% male) with either LQT1 (61%) or LQT2 (39%). ECG analysis was conducted using a novel, proprietary T wave analysis program that quantitates subtle changes in T wave morphology. The top 3 discriminating features in each ECG lead were determined and the lead with the best discrimination selected. Classification was performed using a linear discriminant classifier and validated on an untouched cohort. The top 3 features were Tpeak-Tend interval, T wave left slope, and T wave center of gravity x axis (last 25% of the T wave). Lead V6 had the best discrimination. It could distinguish 86.8% of LQTS patients from healthy controls. Moreover, it distinguished 83.33% of patients with concealed LQTS from controls, despite having essentially identical resting corrected QT interval values. Conclusions-T wave quantitative analysis on the 12-lead surface ECG provides an effective, novel tool to distinguish patients with either LQT1/LQT2 from healthy matched controls. It can provide guid...

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“…17 Mutation-specific cascade testing of family members is a highly sensitive and specific mechanism (with rigorously defined pathogenic mutations) to identify genetically affected individuals, especially in those with ambiguous clinical findings or nonpenetrant disease.…”

Section: Genetic Evaluationmentioning

confidence: 99%

Long QT Syndrome

Abrams

MacRae

2014

Circulation

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Cost-Effectiveness of Genetic Testing in Family Members of Patients With Long-QT Syndrome

Cited by 33 publications

References 61 publications

Cost savings through molecular diagnosis for hereditary hemorrhagic telangiectasia

Cost savings through molecular diagnosis for hereditary hemorrhagic telangiectasia

Identification of Concealed and Manifest Long QT Syndrome Using a Novel T Wave Analysis Program

Long QT Syndrome

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