Clinical and ECG variables to predict the outcome of genetic testing in hypertrophic cardiomyopathy

Robyns, Tomas; Breckpot, Jeroen; Nuyens, Dieter; Vandenberk, Bert; Corveleyn, Anniek; Kuipéri, Cuno; Aelst, Lucas Van; Cleemput, Johan Van; Willems, Rik

doi:10.1016/j.ejmg.2019.103754

Cited by 12 publications

(13 citation statements)

References 23 publications

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“…Robyns et al 40 investigated their Belgian HCM cohort and found unexplained syncope to be a significant positive predictor of a genetic mutation. They also found patients with a positive genetic mutation suffered more frequent syncope then those patients with a negative genotype 40 . The 3 most common genes associated with syncope were MYBPC3, MYH7 and TNNT2, and this study was limited due to the fact some patients were tested with the extended gene panel and some were just tested with these 3 mutations mentioned 40 .…”

Section: Resultsmentioning

confidence: 99%

“…27,28,31,34 It is well known that a common presentation of HCM is unexplained syncope, which later is found to be due to ventricular arrhythmia or LVOT obstruction. Robyns et al 40 investigated their Belgian HCM cohort and found unexplained syncope to be a significant positive predictor of a genetic mutation. They also found patients with a positive genetic mutation suffered more frequent syncope then those patients with a negative genotype.…”

Section: Clinical Characteristicsmentioning

confidence: 99%

“…They also found patients with a positive genetic mutation suffered more frequent syncope then those patients with a negative genotype. 40 The 3 most common genes associated with syncope were MYBPC3, MYH7 and TNNT2, and this study was limited due to the fact some patients were tested with the extended gene panel and some were just tested with these 3 mutations mentioned. 40 Life-threatening ventricular arrhythmias and aborted sudden cardiac death has been associated with certain genetic mutations.…”

Section: Clinical Characteristicsmentioning

confidence: 99%

“…40 The 3 most common genes associated with syncope were MYBPC3, MYH7 and TNNT2, and this study was limited due to the fact some patients were tested with the extended gene panel and some were just tested with these 3 mutations mentioned. 40 Life-threatening ventricular arrhythmias and aborted sudden cardiac death has been associated with certain genetic mutations. These include a specific mutation in the MYBPC3 gene 41 and a mutation in the TNNC1 gene.…”

Section: Clinical Characteristicsmentioning

confidence: 99%

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Clinical prediction of genotypes in hypertrophic cardiomyopathy: A systematic review

Aziz

Musiol

Moody

et al. 2021

Eur J Clin Investigation

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Introduction: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac condition and the most common cause of sudden cardiac death (SCD) in patients below the age of 35. Genetic testing is a vital part of HCM diagnostics, yet correlation with clinical phenotypes remains complex. Identifying clinical predictors of informative genetic testing may prevent unnecessary investigations and improve cost-effectiveness of services. This article reviews the current literature pertinent to identifying such predictors. Methods: Five literature databases were screened using a suitably designed search strategy. Studies investigating the correlation between having a positive genetic test for HCM and a range of clinical and radiological parameters were included in the systematic review. Results: Twenty-nine observational studies of a total of 9,486 patients were included. The main predictors of informative genetic testing were younger age, higher septal thickness, reverse septal curvature, family history of HCM and SCD and the absence of hypertension. Two externally validated scoring systems have also been developed: the Mayo and Toronto scores. Novel imaging markers and complex algorithmic models are emerging predictors. Conclusion: Using clinical predictors to decide whom to test is a feasible alternative to investigating all comers. Nonetheless, currently there is not enough evidence to unequivocally recommend for or against this strategy. Further validation of current predictors and identification of new ones remain open research avenues. K E Y W O R D S genotype, hypertrophic cardiomyopathy 2 of 16 | AZIZ et Al.

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Section: Resultsmentioning

confidence: 99%

Section: Clinical Characteristicsmentioning

confidence: 99%

Section: Clinical Characteristicsmentioning

confidence: 99%

Section: Clinical Characteristicsmentioning

confidence: 99%

See 2 more Smart Citations

Clinical prediction of genotypes in hypertrophic cardiomyopathy: A systematic review

Aziz

Musiol

Moody

et al. 2021

Eur J Clin Investigation

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“…59 Lastly, genetic testing in certain cases may contribute to a better risk stratification for SCD by identifying mutations (ie, MYBPC3) associated with lethal arrhythmias. 60…”

Section: Future Perspectivesmentioning

confidence: 99%

Sudden Arrhythmic Death at the Higher End of the Heart Failure Spectrum

et al. 2019

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The risk of sudden cardiac death (SCD) is high in heart failure (HF) patients. Sudden arrhythmic death (SAD) is a frequent cause of exit in HF patients at the lower end of the HF spectrum, and implantable cardioverter–defibrillators have been recommended to prevent these life-threatening rhythm disturbances in select patients. However, less is known regarding the cause of SCD in patients at the upper end of the HF spectrum, despite the fact that the majority of out-of-hospital SCD victims have unknown or near-normal/normal left ventricular ejection fraction (LVEF). In this review, we report the epidemiology, summarize the mechanisms, discuss the diagnostic challenges, and propose a stepwise approach for the prevention of SAD in HF with near-normal/normal LVEF.

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Identification of a novel likely pathogenic TPM1 variant linked to hypertrophic cardiomyopathy in a family with sudden cardiac death

Azimi,

Soveizi,

Salmanipour

et al. 2024

ESC Heart Failure

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AimsHypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic cardiac disorder characterized by unexplained left ventricular hypertrophy. It can cause a wide spectrum of clinical manifestations, ranging from asymptomatic to heart failure and sudden cardiac death (SCD). Approximately half of HCM cases are caused by variants in sarcomeric proteins, including α‐tropomyosin (TPM1). In this study, we aimed to characterize the clinical and molecular phenotype of HCM in an Iranian pedigree with SCD.Methods and ResultsThe proband and available family members underwent comprehensive clinical evaluations, including echocardiography, cardiac magnetic resonance (CMR) imaging and electrocardiography (ECG). Whole‐exome sequencing (WES) was performed in all available family members to identify the causal variant, which was validated, and segregation analysis was conducted via Sanger sequencing. WES identified a novel missense variant, c.761A>G:p.D254G (NM_001018005.2), in the TPM1 gene, in the proband, his father and one of his sisters. Bioinformatic analysis predicted it to be likely pathogenic. Clinical features in affected individuals were consistent with HCM.ConclusionsThe identification of a novel TPM1 variant in a family with HCM and SCD underscores the critical role of genetic screening in at‐risk families. Early detection of pathogenic variants can facilitate timely intervention and management, potentially reducing the risk of SCD in individuals with HCM.

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Clinical and ECG variables to predict the outcome of genetic testing in hypertrophic cardiomyopathy

Cited by 12 publications

References 23 publications

Clinical prediction of genotypes in hypertrophic cardiomyopathy: A systematic review

Clinical prediction of genotypes in hypertrophic cardiomyopathy: A systematic review

Sudden Arrhythmic Death at the Higher End of the Heart Failure Spectrum

Identification of a novel likely pathogenic TPM1 variant linked to hypertrophic cardiomyopathy in a family with sudden cardiac death

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