Mortality Among Patients With Early-Onset Atrial Fibrillation and Rare Variants in Cardiomyopathy and Arrhythmia Genes

Yoneda, Zachary T.; Anderson, Katherine; Ye, Fei; Quintana, J.; O’Neill, Matthew J.; Sims, Richard A.; Sun, Lili; Glazer, Andrew M.; Davogustto, Giovanni; El‐Harasis, Majd A.; Laws, James L.; Saldivar, Brittany; Crawford, Diane M.; Stricker, Thomas; Wells, Quinn S.; Darbar, Dawood; Michaud, Gregory F.; Stevenson, Lynne Warner; Lubitz, Steven A.; Ellinor, Patrick T.; Roden, Dan M.; Shoemaker, M. Benjamin

doi:10.1001/jamacardio.2022.0810

Cited by 29 publications

(35 citation statements)

References 36 publications

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“…To date, a majority of the evidence for risk associated with P/LP variants is based on samples largely comprising individuals of European ancestry. Indeed, the UK Biobank and the Vanderbilt AF registry in the Yoneda study 8,9 are mainly inclusive of participants who self-reported White race in contrast with the Patel study that now extends similar conclusions to participants of African ancestry from the ARIC cohort. 10 A prior genotype-first, electronic health records study using the Geisinger and University of Pennsylvania biobanks demonstrated that TTNtv were associated with diagnostic codes for AF, HF, ventricular arrhythmias, and sudden death.…”

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confidence: 82%

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Genetic Testing for Early-Onset Atrial Fibrillation—Is It Time to Personalize Care?

McNally

Khan

2022

JAMA Cardiol

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appropriately reflect the progress of the evidence base, although they differ somewhat in substance and scope from the ACC/AHA guidelines. The lesson for all guideline-producing organizations is the importance of ensuring clear and broad-based communication strategies in the introduction of updated recommendations, and whom they affect and do not affect, based on new and improved evidence. Patients depend on us to do that.

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Section: Related Articles Pages 723 and 733mentioning

confidence: 82%

“…In this issue of JAMA Cardiology, Yoneda et al 9 now report the clinical outcomes in EOAF, comparing P/LP gene carriers with noncarriers and demonstrating that these P/LP variants are associated with poorer outcomes. Over 10 years of follow-up, 219 individuals or 17% of the overall EOAF cohort (n = 1293) died.…”

Section: Related Articles Pages 723 and 733mentioning

confidence: 99%

Genetic Testing for Early-Onset Atrial Fibrillation—Is It Time to Personalize Care?

McNally

Khan

2022

JAMA Cardiol

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“…Therefore, our data suggest that in these types of patients, a detailed examination of the heart’s morphology and function (using CMR imaging), as well as regular follow-ups are required, especially in TTNtv-related AF cases. Yoneda et al recently showed that the presence of disease-causing variants in cardiomyopathy- and arrhythmia-associated genes are related to a higher mortality risk in patients with early-onset AF, thus revealing this disease entity to be less benign than previously thought [ 41 ]. However, data on the impact of structural gene variants on AF burden, quality of life and risk of stroke is still missing.…”

Section: Discussionmentioning

confidence: 99%

Genetic Basis of Early Onset Atrial Fibrillation in Patients without Risk Factors

Rudaka

Vilne

Isakova

et al. 2023

JCDD

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Background: Atrial fibrillation (AF) is the most common arrhythmia and typically occurs in elderly patients with other cardiovascular and extracardiac diseases. However, up to 15% of AF develops without any related risk factors. Recently, the role of genetic factors has been highlighted in this particular form of AF. Aims: The aims of this study were to determine the prevalence of pathogenic variants in early-onset AF in patients without known disease-related risk factors and to identify any structural cardiac abnormalities in these patients. Materials and Methods: We conducted exome sequencing and interpretation in 54 risk factor-free early-onset AF patients and further validated our findings in a similar AF patient cohort from the UK Biobank. Results: Pathogenic/likely pathogenic variants were found in 13/54 (24%) patients. The variants were identified in cardiomyopathy-related and not arrhythmia-related genes. The majority of the identified variants were TTN gene truncating variants (TTNtvs) (9/13 (69%) patients). We also observed two TTNtvs founder variants in the analysed population—c.13696C>T p.(Gln4566Ter) and c.82240C>T p.(Arg27414Ter). Pathogenic/likely pathogenic variants were found in 9/107 (8%) individuals from an independent similar AF patient cohort from the UK Biobank. In correspondence with our Latvian patients, only variants in cardiomyopathy-associated genes were identified. In five (38%) of the thirteen Latvian patients with pathogenic/likely pathogenic variants, dilation of one or both ventricles was identified on a follow-up cardiac magnetic resonance scan. Conclusions: We observed a high prevalence of pathogenic/likely pathogenic variants in cardiomyopathy-associated genes in patients with risk factor-free early-onset AF. Moreover, our follow-up imaging data indicate that these types of patients are at risk of developing ventricular dilation. Furthermore, we identified two TTNtvs founder variants in our Latvian study population.

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“…The death risks were significantly higher in younger dementia patients with AF than older dementia patients with AF could be due to several reasons ( 3 , 5 , 39 ): First, a diagnosis of young onset dementia has a unique impact, differing from that experienced by older individuals. Besides, prior research indicated that uncommon genetic variations-related arrhythmia may increase the likelihood of mortality in patients suffering from early-onset AF, particularly in those diagnosed at a young age ( 40 ). For individuals who are diagnosed with both young-onset dementia and AF, the condition tends to be more severe and progress rapidly, contributing to a higher mortality rate ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Atrial fibrillation as a contributor to the mortality in patients with dementia: A nationwide cohort study

Chen

Lin

Hsieh

et al. 2023

Front. Cardiovasc. Med.

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BackgroundKnowledge of the risk of death in patients with dementia is essential for planning preventive strategies. This study aimed to evaluate the effect of atrial fibrillation (AF) on death risks and other factors associated with death in patients with dementia and AF.MethodsWe conducted a nationwide cohort study using Taiwan's National Health Insurance Research Database. We identified subjects with dementia diagnosed for the first time and AF diagnosed concomitantly between 2013 and 2014. Subjects under the age of 18 years were excluded. Age, sex, and CHA2DS2-VASc scores were 1: 4 matched for AF patients (N = 1,679) and non-AF controls (N = 6,176) using the propensity score technique. The conditional Cox regression model and competing risk analysis were applied. The risk of mortality was tracked till 2019.ResultsAF history was associated with higher risks of all-cause death (hazard ratio [HR]: 1.208; 95% confidence interval [CI]: 1.142–1.277) and cardiovascular death (subdistribution HR: 1.210; 95% CI: 1.077–1.359) in dementia patients than patients without a diagnosis of AF. For patients with both dementia and AF, they had a higher risk of death due to higher age, diabetes mellitus, congestive heart failure, chronic kidney disease, and prior stroke. Anti-arrhythmic drugs and novel oral anticoagulants significantly reduced the risk of death in patients with AF and dementia.ConclusionThis study found that AF is a risk factor for mortality in patients with dementia and explored several risk factors for AF-related mortality. This study highlights the importance of controlling AF especially in patients with dementia.

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Mortality Among Patients With Early-Onset Atrial Fibrillation and Rare Variants in Cardiomyopathy and Arrhythmia Genes

Cited by 29 publications

References 36 publications

Genetic Testing for Early-Onset Atrial Fibrillation—Is It Time to Personalize Care?

Genetic Testing for Early-Onset Atrial Fibrillation—Is It Time to Personalize Care?

Genetic Basis of Early Onset Atrial Fibrillation in Patients without Risk Factors

Atrial fibrillation as a contributor to the mortality in patients with dementia: A nationwide cohort study

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