Implementation of a primary-tertiary shared care model to improve the detection of familial hypercholesterolaemia (FH): a mixed methods pre-post implementation study protocol.

INTRODUCTION: Familial hypercholesterolaemia (FH) is an autosomal dominant inherited disorder of lipid metabolism and a preventable cause of premature cardiovascular disease. Current detection rates for this highly treatable condition are low. Early detection and management of FH can significantly reduce cardiac morbidity and mortality. This study aims to implement a primary-tertiary shared care model to improve detection rates for FH. The primary objective is to evaluate the implementation of a shared care model and support package for genetic testing of FH. This protocol describes the design and methods used to evaluate the implementation of the shared care model and support package to improve the detection of FH. METHODS AND ANALYSIS: This mixed methods pre-post implementation study design will be used to evaluate increased detection rates for FH in the tertiary and primary care setting. The primary-tertiary shared care model will be implemented at NSW Health Pathology and Sydney Local Health District in NSW, Australia, over a 12-month period. Implementation of the shared care model will be evaluated using a modification of the implementation outcome taxonomy and will focus on the acceptability, evidence of delivery, appropriateness, feasibility, fidelity, implementation cost and timely initiation of the intervention. Quantitative pre-post and qualitative semistructured interview data will be collected. It is anticipated that data relating to at least 62 index patients will be collected over this period and a similar number obtained for the historical group for the quantitative data. We anticipate conducting approximately 20 interviews for the qualitative data. ETHICS AND DISSEMINATION: Ethical approval has been granted by the ethics review committee (Royal Prince Alfred Hospital Zone) of the Sydney Local Health District (Protocol ID: X23-0239). Findings will be disseminated through peer-reviewed publications, conference presentations and an end-of-study research report to stakeholders.

A prospective longitudinal study of health-related quality of life and psychological wellbeing after an implantable cardioverter-defibrillator in patients with genetic heart diseases.

Background: Genetic heart diseases (GHDs) can be clinically heterogeneous and pose an increased risk of sudden cardiac death (SCD). The implantable cardioverter-defibrillator (ICD) is a lifesaving therapy. Impacts on prospective and long-term psychological and health-related quality of life (HR-QoL) after ICD implant in patients with GHDs are unknown. Objectives: Investigate the psychological functioning and HR-QoL over time in patients with GHDs who receive an ICD, and identify risk factors for poor psychological functioning and HR-QoL. Methods: A longitudinal, prospective study design was used. Patients attending a specialized clinic, diagnosed with a GHD for which they received an ICD between May 2012 and January 2015, were eligible. Baseline surveys were completed prior to ICD implantation with 5-year follow-up after ICD implant. We measured psychological functioning (Hospital Anxiety Depression Scale, Florida Shock Anxiety Scale), HR-QoL (Short-Form 36v2), and device acceptance (Florida Patient Acceptance Scale). Results: Forty patients were included (mean age 46.3 ± 14.2 years; 65.0% male). Mean psychological and HR-QoL measures were within normative ranges during follow-up. After 12 months, 33.3% and 19.4% of participants showed clinically elevated levels of anxiety and depression, respectively. Longitudinal mixed-effect analysis showed significant improvements from baseline to first follow-up for the overall cohort, with variability increasing after 36 months. Nontertiary education and female sex predicted worse mental HR-QoL and anxiety over time, while comorbidities predicted depression and worse physical HR-QoL. Conclusion: While the majority of patients with a GHD adjust well to their ICD implant, a subset of patients experience poor psychological and HR-QoL outcomes.

Familial hypercholesterolaemia: Experience of a tertiary paediatric lipid clinic.

AIM: To review the experience of a dedicated paediatric multidisciplinary lipid clinic in the management of familial hypercholesterolaemia (FH) by studying the demographics, clinical presentations as well as statin therapy and outcomes. METHODS: Retrospective database review of all patients under 18 years old seen in the lipid clinic at an Australian tertiary paediatric hospital between April 1999 and August 2017. Outcome measures collected included patient demographics, family history, lipid profile, age at treatment commencement, treatment outcomes and complications. RESULTS: One hundred and eight patients (53 males) were seen in the lipid clinic. Eighty-five had low-density lipoprotein cholesterol (LDL-C) levels at or above the 75th percentile for sex prior to treatment. Of these, 75 had a first-degree relative with hypercholesterolaemia and/or early cardiac death. Four patients had clinical manifestations. Thirty-two patients (14 males) were started on statin therapy for likely FH. LDL-C levels reduced by 2.4 mmol/L (1.4 to 2.7) in boys and 1.9 mmol/L (0.8 to 2.8) in girls at 12 month follow-up. Five patients reported side effects requiring adjustment in therapy. Main reasons for not starting statin therapy in eligible patients were parental refusal and/or lost to follow up (77%). CONCLUSION: A dedicated multidisciplinary lipid clinic is helpful for streamlining and monitoring management of paediatric FH. Clinical manifestations of FH are rare in children and may represent more severe form of FH or other lipid disorder. Statin therapy is efficacious and well tolerated but current recommended targets of treatment are difficult to attain. Greater awareness and coordinated services are required to overcome poor family engagement.

Psychosocial Impact of a Positive Gene Result for Asymptomatic Relatives at Risk of Hypertrophic Cardiomyopathy.

Families with a history of hypertrophic cardiomyopathy (HCM) may be offered genetic testing in addition to clinical surveillance. Asymptomatic family members who are gene positive (silent gene carriers) represent a new group of "patients" who may not develop HCM, with little evidence available to assist clinical management. This study explored experiences of HCM genetic testing to identify potential benefits and harms. Thirty-two individuals previously offered genetic testing for HCM were recruited. Semi-structured interviews were conducted face-to-face or by phone, and transcribed audio-recordings were coded using framework analysis. Key themes were as follows: (1) helping the next generation, (2) misunderstanding risk, (3) discrepancy between actual/perceived impact. Participants described multiple psychological (shock, worry, uncertainty) and behavioural (career, sport, insurance, family planning) consequences, depending on perceived risk. Most considered only the benefits of genetic testing for children or grandchildren, but there were some cases of significant adverse impact. The interpretation of the HCM genetic test result is variable for silent gene carriers and can lead to psychological and behavioural changes. The impact of a positive gene result may be mitigated by increased clarity of the clinical consequences and efforts to ensure informed decision-making, highlighting even further the important role of cardiac genetic counselling.

Psychosocial Implications of Living with Catecholaminergic Polymorphic Ventricular Tachycardia in Adulthood.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited arrhythmogenic disease with a high risk of sudden cardiac death. The impact on health-related quality of life (HR-QoL) and psychosocial outcomes is not known. We sought to provide the first description of HR-QoL and psychosocial wellbeing of adults with CPVT, parents of affected children and at-risk relatives. Participants were recruited through the Australian Genetic Heart Disease Registry and invited to complete a cross-sectional survey comprising a number of validated scales and open-ended questions. Thirty-five participants completed surveys (response rate 65%), including 19 with CPVT, 10 unaffected parents of a child with CPVT, and 7 at-risk relatives (one participant considered patient and parent). Young patients <40 years were significantly more likely to report anxiety (p = 0.04), depression (p = 0.03) and posttraumatic stress symptoms (p = 0.02) compared to older CPVT patients. Further, young patients with an implantable cardioverter defibrillator (ICD) reported significantly worse device-related distress (p = 0.04) and shock anxiety (p = 0.003). Patients with a genetic diagnosis had worse psychological adaptation than those patients without a gene result. Parents perceived their affected children to have poor quality of life across all subdomains compared to healthy age-matched children, however quality of life of parents and at-risk relatives was comparable to population norms. Ongoing psychosocial care is required for young people with CPVT. Those with an ICD and/or undergoing genetic testing may require additional support. The challenges of CPVT management should extend beyond the clinical and genetic aspects of care to incorporate greater psychosocial support, and further reinforces the need for a multidisciplinary approach to care.

Development of a communication aid for explaining hypertrophic cardiomyopathy genetic test results.

BACKGROUND: Large gene panels are now commonplace for hypertrophic cardiomyopathy (HCM), increasing the yield of uncertain genetic findings. Few resources exist which aim to facilitate communication of HCM genetic test results. We sought to develop, pilot, and refine a communication aid for probands receiving HCM genetic test results. METHODS: Development was a multi-step process involving expertise of a multidisciplinary team, literature review, and empirical experience. The aid went through an iterative revision process throughout the piloting phase to incorporate feedback. HCM probands attending a specialized multidisciplinary HCM clinic, aged ≥ 18 years and genetic test results available for disclosure between May and August 2016, or recently received their gene results (January-April 2015) were eligible. A purposive sampling strategy was employed, recruiting those attending clinic during the study period or those who could attend without difficulty. RESULTS: We developed and pilot tested a genetic counsellor-led communication aid. Based on clinical expertise, the aid addresses (a) what genetic testing is, (b) implications for the patient, (c) reasoning for variant classification, and (d) implications for the family. Pilot data were sought to assess knowledge, feasibility, and acceptability using a self-report survey 2 weeks post-intervention. Twelve of 13 participants completed the follow-up questionnaire. Participants valued the individualised nature of the aid, recommended use of the aid, and indicated genetic knowledge, and family communication was better facilitated. Iterative modification of images helped to more simply depict important genetic concepts. CONCLUSIONS: We have developed a tool that is feasible, acceptable, and helpful to patients receiving genetic results. This is an important first step, and trial of the aid to assess effectiveness compared to usual care will follow.

Attitudes, knowledge and consequences of uncertain genetic findings in hypertrophic cardiomyopathy.

With the surge of next-generation sequencing (NGS) technologies making almost all genetic tests more affordable and available, cardiac genetic testing now routinely encompasses a large number of genes within a panel setting. The additional sensitivity of this practice is limited and has the potential to inflict a spectrum of uncertainty. We sought to explore attitudes, preferences, recall and psychological consequences of informative and uninformative genetic results amongst probands diagnosed with hypertrophic cardiomyopathy (HCM). We conducted semi-structured interviews and analysed the qualitative data using a framework analysis process. In general, we found probands were more concerned with their clinical diagnosis than gene result and in some, recall and understanding of genetic diagnosis was poor. Several participants expected genetic testing would alleviate uncertainty, often holding an altruistic view of participation in testing, removing their sense of self and failing to appreciate fully the familial implications. With the key utility of HCM genetic testing and counselling being for greater risk prediction for at-risk relatives, effective communication within the family is critical. While communication appeared adequate, further questioning found it was often vague, failing to translate into meaningful action by relatives. Based on these findings, a framework of key outcomes to assist multidisciplinary teams in genetic counselling of probands receiving an HCM gene result was developed.