Opportunistic Genetic Screening for Familial Hypercholesterolemia in Heart Transplant Patients

Abstract

Heart transplantation remains the gold standard for the treatment of advanced heart failure (HF). Identification of the etiology of HF is mandatory, as the specific pathology can determine subsequent treatment. Early identification of familial hypercholesterolemia (FH), the most common genetic disorder associated with premature cardiovascular disease, has a potential important impact on clinical management and public health. We evaluated the genetic information in the genes associated with FH in a cohort of 140 heart-transplanted patients. All patients underwent NGS genetic testing including LDLR, APOB, and PCSK9. We identified four carriers of rare pathogenic variants in LDLR and APOB. Although all four identified carriers had dyslipidemia, only the one carrying the pathogenic variant LDLR c.676T>C was transplanted due to CAD. Another patient with heart valvular disease was carrier of the controversial LDLR c.2096C>T. Two additional patients with non-ischemic dilated cardiomyopathy were carriers of variants in APOB (c.4672A>G and c.5600G>A). In our cohort, we identified the genetic cause of FH in patients that otherwise would not have been diagnosed. Opportunistic genetic testing for FH provides important information to perform personalized medicine and risk stratification not only for patients but also for relatives at concealed high cardiovascular risk. Including the LDLR gene in standard NGS cardiovascular diagnostics panels should be considered.

Genetic Evaluation and Screening in Cardiomyopathies: Opportunities and Challenges for Personalized Medicine

“…Orthotopic heart transplantation remains the gold standard for treating patients with advanced heart failure [ 55 ]. Genetic testing for heart transplant recipients with prior cardiomyopathy has not been consistently performed [ 55 ].…”

“…Orthotopic heart transplantation remains the gold standard for treating patients with advanced heart failure [ 55 ]. Genetic testing for heart transplant recipients with prior cardiomyopathy has not been consistently performed [ 55 ]. It is a window of opportunity for genetic testing, and recent studies have shown its crucial role in identifying relatives at risk [ 55 ].…”

“…Genetic testing for heart transplant recipients with prior cardiomyopathy has not been consistently performed [ 55 ]. It is a window of opportunity for genetic testing, and recent studies have shown its crucial role in identifying relatives at risk [ 55 ]. Approximately 60% of heart transplant recipients have an underlying etiology of non-ischemic cardiomyopathy [ 56 ].…”

“…Clinical genetic testing consideration is warranted beyond standard arrhythmogenic and cardiomyopathy gene variants when other causes leading to the need for advanced therapies may contribute [ 55 ]. For example, opportunistic genetic testing in patients with ischemic cardiomyopathy with early onset and/or strong family history can also be performed to identify familial hypercholesterolemia (FH) early on in heart transplant patients [ 55 ]. FH is the most common genetic disease linked to premature cardiovascular disease [ 55 ].…”

“…For example, opportunistic genetic testing in patients with ischemic cardiomyopathy with early onset and/or strong family history can also be performed to identify familial hypercholesterolemia (FH) early on in heart transplant patients [ 55 ]. FH is the most common genetic disease linked to premature cardiovascular disease [ 55 ]. Early identification of FH can prevent severe disease progression [ 55 ].…”