TY - JOUR
T1 - Genetics of dilated cardiomyopathy
T2 - practical implications for heart failure management
AU - Rosenbaum, Andrew N.
AU - Agre, Katherine E.
AU - Pereira, Naveen L.
N1 - Funding Information:
Regarding screening for familial DCM, the 2013 ACC/AHA heart failure guidelines40, the 2009 Heart Failure Society of America (HFSA) guidelines29 (which were updated in 2018 in a joint publication with the American College of Medical Genetics (ACMG)25), the 2010 ESC guidelines for genetic testing and counselling41 and the 2016 AHA scientific statement on DCM42 recommend clinical screening of adult first-degree relatives of affected individuals, with electrocardiographic and echocardiographic examination of left ventricular function and size every 3–5 years. Additionally, according to a 2011 joint expert consensus statement from the Heart Rhythm Society (HRS) and European Heart Rhythm Association (EHRA)43, if a pathogenic or likely pathogenic variant is present in a proband, cascade screening should be conducted; this recommendation is supported by the guidelines from the ACMG, ESC and AHA25,41,42. If a family member undergoes genetic screening and a pathogenic variant is identified in the absence of phenotypic manifestations, both the 2018 HFSA guidelines and the 2010 ESC guidelines indicate that interval screening should occur for phenotypic manifestations, in addition to appropriate disease counselling25,41. In the absence of a family history or an identifiable pathogenic genetic variant, the ACC/AHA guidelines recommend that clinical screening of family members of patients with sporadic idiopathic DCM should be left to the discretion of the family members’ physicians and is not routinely recommended40. The AHA scientific statement on DCM similarly indicates that clinical screening of first-degree relatives might be reasonable42. However, because of uncertainties about the distinction between familial and sporadic cardiomyopathies, the ESC recommends routine clinical screening in all first-degree relatives of patients with DCM if genetic information is unavailable41.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Given the global burden of heart failure, strategies to understand the underlying cause or to provide prognostic information are critical to reducing the morbidity and mortality associated with this highly prevalent disease. Cardiomyopathies often have a genetic cause, and the field of heart failure genetics is progressing rapidly. Through a deliberate investigation, evaluation for a familial component of cardiomyopathy can lead to increased identification of pathogenic genetic variants. Much research has also been focused on identifying markers of risk in patients with cardiomyopathy with the use of genetic testing. Advances in our understanding of genetic variants have been slightly offset by an increased recognition of the heterogeneity of disease expression. Greater breadth of genetic testing can increase the likelihood of identifying a variant of uncertain significance, which is resolved only rarely by cellular functional validation and segregation analysis. To increase the use of genetics in heart failure clinics, increased availability of genetic counsellors and other providers with experience in genetics is necessary. Ultimately, through ongoing research and increased clinical experience in cardiomyopathy genetics, an improved understanding of the disease processes will facilitate better clinical decision-making about the therapies offered, exemplifying the implementation of precision medicine.
AB - Given the global burden of heart failure, strategies to understand the underlying cause or to provide prognostic information are critical to reducing the morbidity and mortality associated with this highly prevalent disease. Cardiomyopathies often have a genetic cause, and the field of heart failure genetics is progressing rapidly. Through a deliberate investigation, evaluation for a familial component of cardiomyopathy can lead to increased identification of pathogenic genetic variants. Much research has also been focused on identifying markers of risk in patients with cardiomyopathy with the use of genetic testing. Advances in our understanding of genetic variants have been slightly offset by an increased recognition of the heterogeneity of disease expression. Greater breadth of genetic testing can increase the likelihood of identifying a variant of uncertain significance, which is resolved only rarely by cellular functional validation and segregation analysis. To increase the use of genetics in heart failure clinics, increased availability of genetic counsellors and other providers with experience in genetics is necessary. Ultimately, through ongoing research and increased clinical experience in cardiomyopathy genetics, an improved understanding of the disease processes will facilitate better clinical decision-making about the therapies offered, exemplifying the implementation of precision medicine.
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U2 - 10.1038/s41569-019-0284-0
DO - 10.1038/s41569-019-0284-0
M3 - Review article
C2 - 31605094
AN - SCOPUS:85074479632
SN - 1759-5002
VL - 17
SP - 286
EP - 297
JO - Nature Reviews Cardiology
JF - Nature Reviews Cardiology
IS - 5
ER -