From the phenotype to precision medicine: an update on the cardiomyopathies diagnostic workflow

Abstract

Cardiomyopathies are disease of the cardiac muscle largely due to genetic alterations of proteins with ‘structural’ or ‘functional’ roles within the cardiomyocyte, going from the regulation of contraction-relaxation, metabolic and energetic processes to ionic fluxes. Modifications occurring to these proteins are responsible, in the vast majority of cases, for the phenotypic manifestations of the disease, including hypertrophic, dilated, arrhythmogenic and restrictive cardiomyopathies. Secondary nonhereditary causes to be excluded include infections, toxicity from drugs or alcohol or medications, hormonal imbalance and so on. Obtaining a phenotypic definition and an etiological diagnosis is becoming increasingly relevant and feasible, thanks to the availability of new tailored treatments and the diagnostic advancements made particularly in the field of genetics. This is, for example, the case for transthyretin cardiac amyloidosis, Fabry disease or dilated cardiomyopathies due to laminopathies. For these diseases, specific medications have been developed, and a more tailored arrhythmic risk stratification guides the implantation of a defibrillator. In addition, new medications directly targeting the altered protein responsible for the phenotype are becoming available (including the myosin inhibitors mavacantem and aficamten, monoclonal antibodies against Ras-MAPK, genetic therapies for sarcoglycanopathies), thus making a precision medicine approach less unrealistic even in the field of cardiomyopathies. For these reasons, a contemporary approach to cardiomyopathies must consider diagnostic algorithms founded on the clinical suspicion of the disease and developed towards a more precise phenotypic definition and etiological diagnosis, based on a multidisciplinary methodology putting together specialists from different disciplines, facilities for advanced imaging testing and genetic and anatomopathological competencies.

Temporal implementation of a regional referral pathway in transthyretin cardiac amyloidosis: Emilia-Romagna experience

“…Diagnoses in these clinics are performed by the application of the recent algorithm proposed and supported by international experts and guidelines 3 . This was feasible thanks to the adoption over the last few years of all the diagnostic tools recommended: bone scintigraphy, CMR, and genetic testing for the presence of TTR mutations 3,18–21 . Our survey analysis also showed that the interviewed centers started to refer patients with confirmed ATTR-CA to the expert care center of Bologna in 2019 to continue their therapeutic path, with a decreasing trend of patients being referred to centers outside of the region.…”

Establishment of a Comprehensive Cardiac Amyloidosis Center in a Community Hospital Setting

“…Improving awareness among healthcare professionals is crucial in the early detection and intervention of CA [ 20 , 21 , 22 ]. Primary care physicians and various specialists, including cardiologists, hematologists, neurologists, gastroenterologists, nephrologists, and orthopedics, are among those who should be made aware of CA.…”