The Time Has Come to Explore Plasma Biomarkers in Genetic Cardiomyopathies

Abstract

For patients with hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM), screening for pathogenic variants has become standard clinical practice. Genetic cascade screening also allows the identification of relatives that carry the same mutation as the proband, but disease onset and severity in mutation carriers often remains uncertain. Early detection of disease onset may allow timely treatment before irreversible changes are present. Although plasma biomarkers may aid in the prediction of disease onset, monitoring relies predominantly on identifying early clinical symptoms, on imaging techniques like echocardiography (Echo) and cardiac magnetic resonance imaging (CMR), and on (ambulatory) electrocardiography (electrocardiograms (ECGs)). In contrast to most other cardiac diseases, which are explained by a combination of risk factors and comorbidities, genetic cardiomyopathies have a clear primary genetically defined cardiac background. Cardiomyopathy cohorts could therefore have excellent value in biomarker studies and in distinguishing biomarkers related to the primary cardiac disease from those related to extracardiac, secondary organ dysfunction. Despite this advantage, biomarker investigations in cardiomyopathies are still limited, most likely due to the limited number of carriers in the past. Here, we discuss not only the potential use of established plasma biomarkers, including natriuretic peptides and troponins, but also the use of novel biomarkers, such as cardiac autoantibodies in genetic cardiomyopathy, and discuss how we can gauge biomarker studies in cardiomyopathy cohorts for heart failure at large.

Titin-Related Dilated Cardiomyopathy: The Clinical Trajectory and the Role of Circulating Biomarkers in the Clinical Assessment

“…The role of circulating cardiac biomarkers in the detection of HF is widely recognized [ 29 ]. In community-based studies, multiple cardiac biomarkers are detectable in ambulatory individuals and add prognostic value to standard risk factors for predicting mortality, overall cardiovascular events and HF [ 30 , 31 ]. However, little is known about the significance of circulating biomarkers in the early stage of DCM in humans [ 30 , 32 ].…”

Attenuation of Cardiomyopathy Induced in Sub-Chronic Exposure of Acrolein by Sulforaphane via Indirect PPARy Expression Promoter

“…38 Elevated levels of cardiac troponin have been described as an early marker for cardiomyopathy. 39 Whereas Li et al 40 after reporting the association of elevated cardiac troponin with cardiomyopathy, advocated for drugs that can modulate troponin for the treatment of cardiomyopathy, signifying the role of troponin in the disease progression. In like manner, cardiac troponin was also found to be elevated by ACL and attenuated by pretreatment with SPN and LTN, as were also documented by various workers.…”

The Emerging Role of Epigenetics in Therapeutic Targeting of Cardiomyopathies

“…In contrast to other cardiac disorders, including heart failure or myocardial infarction, the use of cardiac biomarkers has not received great attention for the diagnosis or prognosis of genetic cardiomyopathies [99]. So far, the diagnosis and the management of genetic cardiomyopathies mainly rely on genetic testing, clinical symptoms, ECG measurements, and cardiac imaging, to detect functional, structural, and morphological alterations [99].…”

“…In contrast to other cardiac disorders, including heart failure or myocardial infarction, the use of cardiac biomarkers has not received great attention for the diagnosis or prognosis of genetic cardiomyopathies [99]. So far, the diagnosis and the management of genetic cardiomyopathies mainly rely on genetic testing, clinical symptoms, ECG measurements, and cardiac imaging, to detect functional, structural, and morphological alterations [99]. Cardiac-specific plasma protein biomarkers such as BNP, NT-proBNP, and cTns have been questioned regarding their effective value in the diagnosis of CMPs, since they may not be sufficient for early detection or for a better risk stratification of these genetic disorders.…”

“…Cardiac-specific plasma protein biomarkers such as BNP, NT-proBNP, and cTns have been questioned regarding their effective value in the diagnosis of CMPs, since they may not be sufficient for early detection or for a better risk stratification of these genetic disorders. Thus, additional biomarkers are currently needed to better guide the intensity of imaging surveillance, refine current risk stratification criteria, and track disease progression [99]. The use of circulating miRNAs as diagnostic tools has been increasing steadily over the last few years [100]; combining genome-wide RNA sequencing in order to standardize miRNAs specific to each CMP will be an important step in overcoming some of the limitations of current diagnostic tools (Table 3).…”