Two researchers trained in qualitative research methods (KH and HF) conducted the interviews between December 2019 and November 2020. The interviews lasted approximately 30-minutes and were audio recorded, professionally transcribed, de-identified, and checked for accuracy. In appreciation for their time, participants could choose between a $25 gift card or a $25 donation to the Sudden Arrhythmia Death Syndromes Foundation.

The first phase in the genetic testing workflow involves identifying patients who may benefit from genetic testing. Some participants managed patients who had undergone genetic testing elsewhere and were referred to them for more specialized care. In most other cases, participants reported determining the appropriateness of genetic testing for their patients. The extent to which genetic testing was integrated into clinical practice varied based on cardiac condition and patient characteristics. For some conditions, such as cardiomyopathies or aortopathies, ordering genetic testing was considered standard practice: “When I see patients with cardiomyopathy or heart muscle disease problems, we almost always send a genetic panel to try to uncover the cause of the disease” (MD, Fellow). A genetic counselor was often involved in cases that required more complex evaluations.

Participants described two primary reasons for recommending genetic testing. It was commonly recommended for patients with a clinical diagnosis of a heritable cardiovascular disease, such as cardiomyopathies or arrhythmic disorders, to determine the cause and guide management. In other instances, genetic testing was ordered to evaluate patients for a new cardiac disease or to confirm a suspected diagnosis, as described by one participant:

Sometimes it's because they have a concern for a new diagnosis of a cardiomyopathy. They’ve been out in the world living their life not knowing anything’s wrong, then they come into us because they’ve become symptomatic from a new heart problem. Then lo and behold, they have some degree of heart failure, so they’re getting worked up for a handful of different possibilities, and an underlying genetic problem is in the mix. (MD, Fellow).

This type of diagnostic testing was commonly done on children who were admitted to the CICU for sudden collapse or cardiac arrhythmia, or for children with aortopathies. Some participants reported ordering chromosome microarrays (CMA) to screen newborns with congenital heart defects for copy number variants (i.e., missing or extra chromosome material).

Once patients were identified as potentially benefiting from genetic testing, participants discussed the option with them. The conversation was described as a multi-step process involving different types of clinicians at various time points, depending on the case’s complexity. For microarrays for newborns, many clinicians talked directly with the patients without involving other clinicians:

So if we’re going to send just basic genetic testing, like a microarray, then I would talk to the family about that. If we’re actually looking for very specific gene markers, I want to do anything more extensive than that, then I would refer to [genetic counselors]. (APN).

For patients who needed more complex genetic testing such as gene panels, exome, or genome, the clinician offered basic information and counseling, followed by a more in-depth discussion, generally led by a genetic counselor, and sometimes combined with or followed by another discussion with a specialized clinician. “The nitty-gritty is usually done by either the subspecialty service who is evaluating the patients, so whether it be the electrophysiology team, or the cardiomyopathy team, or by the geneticist if they’re in the mix already” (MD, Fellow). Within those conversations, participants acknowledged that genetic testing results may have implications for family members. Some also addressed financial concerns: “Some families are a little hesitant because if something comes up, it could affect that person’s insurance in the future even if they don't have the disease” (MD, Fellow).

One participant highlighted the importance of preparing patients for the implications of their test results and medical management decisions in the initial discussion to avoid confusion and anxiety post-testing: “I mean usually I’ve at least given them a reason as to why I am doing the test before we actually get it done. To sort of lay the groundwork for the potential outcomes that it could be” (MD, Attending).

After consent, most participants involved a genetic counselor or geneticist if they were not already involved: “[The genetic experts] say for us to get it ordered just right, there is a particular way it needs to be done, and sometimes I’ll include them and either have them help me order it or have them order it.” (MD, Fellow). One challenge was the identification of appropriate tests. Typically, participants consulted a genetics expert who told them what test to order. Regardless of who identified the appropriate test, most participants believed that a genetics expert approved the order. However, there was some uncertainty about whether this was true for all tests.

Once the appropriate test was identified, the order for testing was placed and insurance approval was obtained, although this may differ between inpatient and outpatient testing. The person ordering was commonly chosen on a case-by-case basis, which made one participant wish for a more standardized protocol: “We would love to have one, but there’s no standardized protocol. We don't have the staff for that” (APN). After the order was submitted, test results were typically returned within several days (for rapid inpatient testing) or several weeks (for outpatient testing).

Most test results were returned to the clinician through the electronic medical record (EMR) system, although one participant noted that in rare cases, they were returned via email or fax. Participants described various pathways in which they received a copy of the test results and how they were shared with the healthcare team. In many cases, a genetic counselor first received the results and then informed the healthcare team: “The genetic counselor usually knows about the results first and will inform me about the result and its significance. But also I can see this through their Epic chart” (MD, Fellow). In other cases, the ordering clinician received a notification through the EMR and then discussed the results with the genetics team. Sharing and discussing results commonly occurred through spontaneous face-to-face encounters on the floor: “We are always bumping into one another so … it's really easy to find them. If you send it to them in your EMR they may or may not see it right away, but if you need some information from them faster than that you just have to knock on their door.” (MD, Fellow).

Several participants expressed uncertainty about who received a copy of the results: “The ones I’ve ordered, if it's an outpatient, I typically have gotten back into my in-basket. Now whether or not the genetics folks get a separate copy or not when it comes back, I’m not certain” (MD, 2). The same participant described difficulties finding results.

The results are updated in our media tab, so we would just have to search through it. Sometimes it is a little bit difficult to find. Once we find it out, we would put it in our most recent notes, so that it gets forwarded. (MD, Attending).

Two participants reported challenges with test results that took several weeks to obtain, although this occurred rarely.

Results interpretation was described as a team effort. The report provided detailed information commonly used for initial interpretation. When reports were not complete enough, participants would contact the testing company to request more information. Most participants then consulted the genetics team, and some a genetic expert to help interpret the report or confirm their interpretation. The extent to which participants consulted other specialized clinicians depended on the complexity of the results and participants’ familiarity with the test. One participant explained.

If they fall into one of the handful of genetic mutations that we see all the time and we treat all the time, take care of all the time, we’re pretty comfortable with it, but I would probably get out of my comfort zone pretty quickly if it was just all newcomers for genetic mutations. (MD, Fellow).

Others needed help understanding the results when they involved a variant of uncertain significance (VUS) which cannot be used for diagnosis or medical management decisions due to lack of information about the potential pathogenicity of the variant.

In those cases, I really do rely on the genetic counselor because there are some VUSs that are felt to be a little bit more suspicious than others, in which case they might recommend testing family members to try to get more data. (MD, Fellow).

Participants often managed negative test results without the help of a genetic expert. However, the ease of access to a genetics expert was described as invaluable to the process of interpreting genetic testing results.

Commonly, positive test results had less of an impact on the patient’s medical management than on their family members. “Our patients are mostly pediatrics, so it doesn't directly help the patients immediately, but it helps us risk stratify or evaluate the other family members to see if they also have the potential to develop a heart disease” (MD, Resident).

Sometimes, positive test results directly impacted the patient and were used to inform prognoses, adjust medication, or even alter newborn nutrition. For example, one participant explained: Occasionally the genetic testing can give us some idea as to what to expect with the disease because certain mutations in certain genes have better or worse prognosis (MD, Fellow). Even if there is a negative genetic test result, participants noted the value of clinical cardiac screening for family members. For example, one participant explained:

So if a patient has the disease but has a negative genetic test, then unfortunately, that tells me we just don't know what caused their disease. […] And so in those cases we have the family members continue to get periodic screening with Echo [and] EKG, since we can't rule in or rule out their risk for disease using genetics. (MD, Fellow)

All participants reported consulting a genetic expert to help interpret and make sense of VUS results. Additional research and considerations of clinical factors were necessary for optimal decision-making. One participant explained:

If there’s some inkling that it [VUS] may be an actually pathogenic variant we can’t confirm it, but that’s a suspicion, then we’re probably more likely to consider it to be pathogenic given the clinical context. Then when it's truly a VUS, like we have no idea, there’s nothing that we know about it, it is noise but it doesn't actually, probably contribute much to what we’re doing. (MD, Fellow).

The last step of the workflow involved disclosing test results to the patients and their families. Only one participant reported communicating test results to the family independently; all others relied on a genetic counselor to support or conduct the conversation. One participant described approaching the genetic counselor before talking with the family.

If it's positive, I usually talk to genetic counselor first and figure out if there’s anything specific about the counseling that I would need to know in terms of how she would counsel them, and if in talking with her I find out that this discussion is going to be more complex or is not going to be a straight forward, then I will usually have her do it or have her do it with me. (MD, Fellow).

Participants appreciated the presence of genetic counselors and their knowledge and counseling skills.

I say our genetic counselors, they do a lot of research before they come to talk to us and the family so that they have a lot of background on whatever it is that comes up. They always come with a lot of information because we forget these things in between patients, to be perfectly honest. (APN).

The discussion was informed by the type of result. The return of positive results typically included an explanation of the variant, the effect of test results on medical management and prognosis, and a discussion of implications like future pregnancies and cascade testing for at-risk family members. For negative test results, participants explained that there was no identifiable genetic cause of the disease or condition at this time and that they would continue their periodic medical checkups. Several participants described the field of genetics as rapidly evolving, which may change the implications of a negative test result:

I usually just say that obviously the field in and of itself is exploding and our knowledge is growing. There would be new diagnoses and things and if new information becomes available, I’ll obviously bring that to their attention. (MD, Attending).

The disclosure of test results was more complex when VUS were involved. All but one participant reported deferring to a genetic counselor when VUS results were involved because of the inherent uncertainty in these results and the belief that VUS require more explanation. Discussions typically included an explanation of VUS and its potential for re-classification:

I'll tell them that we found variants that aren't necessarily at this time associated with what were their underlying heart disease in terms of what we were looking for … but if it's variants that seem potentially significant, then I mean we definitely involve genetic counseling to explain more about what that could mean for this patient. (MD, Fellow)

Most of our participants were in training, had worked less than 5 years at their current practice (n = 9; 75%), and had access to a dedicated cardiovascular genetics team. While this map may not be valid for more experienced clinicians or those working outside a tertiary care center, it represents a cohort of young clinicians who are the future of clinical medicine with easy access to genetic experts. Importantly, all data were collected from one children’s hospital in the Midwest that has access to a cardiovascular genetic clinic and a board-certified genetic counselor. The study findings may differ in clinics with varying levels of access to genetic counselors and related resources. Furthermore, this work provides novel data specific to pediatric cardiology, but future studies will be required to compare and extrapolate these data to other healthcare systems and disciplines. Finally, this was a secondary analysis of data; the interview guide was not optimized for an in-depth exploration of thoughts and emotions, which is typical of the journey mapping methodology.

Developing standardized protocols, streamlining the genetic testing and genetic counseling workflow, and enhancing EMR capabilities may improve clinical efficiency, increase genetic testing uptake, and ultimately enhance patient care.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving humans were approved by Northwestern Institutional Review Board. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

KH: Conceptualization, Data curation, Formal Analysis, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing–original draft, Writing–review and editing. CS: Conceptualization, Formal Analysis, Funding acquisition, Investigation, Supervision, Writing–original draft, Writing–review and editing. HF: Conceptualization, Data curation, Formal Analysis, Investigation, Writing–original draft, Writing–review and editing. SR: Investigation, Writing–review and editing. LD-C: Funding acquisition, Resources, Validation, Writing–review and editing. DD: Funding acquisition, Resources, Validation, Writing–review and editing. SC: Validation, Writing–review and editing. EM: Funding acquisition, Resources, Validation, Writing–review and editing. GW: Funding acquisition, Validation, Writing–review and editing. LR-T: Funding acquisition, Resources, Supervision, Validation, Writing–review and editing.

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This project was funded, in part, by the American Heart Association Cardiac Death Strategically Focused Research Network (grants 19SFRN32830054 and 19SFRN34850101), a Strategically Focused Research Network grant from the American Heart Association. REDCap is supported at FSM by the Northwestern University Clinical and Translational Science (NUCATS) Institute. Research reported in this publication was supported, in part, by the National Institutes of Health’s National Center for Advancing Translational Sciences, Grant Number UL1TR001422. The content is solely the authors’ responsibility and does not necessarily represent the official views of the National Institutes of Health.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.