Managing the unsolicited: perspectives from health-care professionals on unsolicited findings predisposing to cardiac diseases
I Faassen, H G Yntema, D M E I Hellebrekers, M Heijligers, W Van Zelst-Stams, G H J M Ellenbroek, M R Hazebroek, V Van Der Schoot, J A J VerdonschotAbstract
Background
The widespread use of next generation sequencing methods creates the potential to uncover unsolicited findings (UFs): a relevant genetic finding that is not related to the clinical diagnosis of the patient (1)(2). Within the field of cardiogenetics, guidelines on reporting an UFs are lacking. Whether an UF is reported, depends on the possibilities of screening and intervention, also known as the concept of actionability. If a variant is deemed actionable, additional clinical care or follow-up should be provided to the patient without a phenotype. However, guidelines on the clinical care of patients with no phenotype and a cardiovascular-related UF are also lacking. Due to the lack of these guidelines, individuals with these UFs are often offered the same screening and interventions as family members of genotype and phenotype positive patients, although this is a different patient population with different risks for disease development...
Purpose
In preparation of developing clinical recommendations for patients with cardiogenetic UFs, the current perspective of geneticists and cardiologists is important besides ongoing research on disease penetrance.
Methods
In the current study, the perspectives of health care professionals (HCP) within the fields of cardiology and clinical genetics on reporting cardiogenetic UFs, clinical care and follow-up has been evaluated using a questionnaire with three fictional patient cases comprising variants in different genes (MYBPC3, SCN5A and TTN).
Results
The results illustrate that the majority of the participants (HCP in cardiology and clinical genetics) are in favor of reporting UFs. When stratified by profession, only on disclosure of the TTN variant there was no consensus amongst HCPs in cardiology. There is consensus on reporting the MYBPC3 and SCN5A variants (cardiology MYBPC3 78.3%, SCN5A 77.8%, 55.5% TTN; clinical genetics MYBPC3 96.4%, SCN5A 96.3%, TTN 81.5%). Variant disclosure did not differ between HCP in cardiology and clinical genetics, although cardiologists were a bit more reserved in reporting UFs (p=0.079; p=0.141; and p=0.094, respectively) (Fig. 1). No clear consensus was reached on the management of clinical care and follow-up of cardiogenetic UFs, possibly correlating with its ambiguous penetrance.
Conclusion
This study illustrates that guidelines are warranted to comply with the concept of actionability in cardiogenetic UF disclosure and to enable an optimized and eventually individualized treatment and follow-up plan. To contribute to this much needed consensus, we formulate a proposal for clinicians to manage UFs based on the findings of the questionnaire (Fig. 2).Reporting of unsolicited findingsFor image description, please refer to the figure legend and surrounding text.Flow chart follow-up adviceFor image description, please refer to the figure legend and surrounding text.