Title: Health-related quality of life in cardiac sarcoidosis
Funder: Health Education England

Abstract: BackgroundSarcoidosis is a rare inflammatory condition characterised by formation of granulomas that may affect any organ. Sarcoidosis occurs worldwide, affecting all ages, races, and both sexes. The annual incidence of sarcoidosis is 10-80 cases per 100,000, depending on geographic and demographic variation. Unfortunately, 30-35% of sarcoidosis patients will develop a clinically significant major organ involvement, and 6-8% will die from sarcoidosis. Most deaths (13-25%) in sarcoidosis are caused by cardiac involvement. Therefore, cardiac sarcoidosis (CS) is a potentially life-threatening condition, with a 60-90% 5-year survival. In UK, the mortality rate for CS is 19-25%.Sarcoidosis could affect physical, functional, psychosocial and economic aspects of people's life. Compared to other types of sarcoidosis, CS has been recognised to have greater impact in health-related quality of life (HRQoL). CS patients are likely to experience palpitations, syncope, arrhythmias, heart failure or even sudden death. However, there is a lack of information related to HRQoL in CS. Therefore, there is a need to develop and evaluate a disease-specific HRQoL questionnaire (Card-Sarc) to measure the impact of CS in HRQoL, which has the potential to influence clinical management and treatment, future research and health-economic stakeholders' decisions.Research questionWhat is the impact of cardiac sarcoidosis on HRQoL? Aims and objectivesThe overarching aim is to determine the impact of HRQoL in adults living with CS. The specific aims within this are: Aim 1: Identify and synthesise existing research exploring HRQoL in adults living with a diagnosis of CS Aim 2: Develop a uni-dimensional disease-specific HRQoL tool (Card-Sarc) to measure the impact of CS on HRQoL Aim 3: Evaluate the reliability, validity and responsiveness of the Card-Sarc MethodsA sequential exploratory mixed method design including two CS-specialist centres is proposed to address the three components: Component A: A systematic review (PROSPERO registration: 119752) exploring HRQoL in adults living with a diagnosis of cardiac sarcoidosis (April-August 2021). Synthesis will include descriptive statistics and narrative synthesis as appropriate. Component B: Development of a CS-specific HRQoL questionnaire (Card-Sarc) using clinimetric approach and the McMaster Framework (incorporating COSMIN recommendations) (September 2021-h;April 2022). Component C: Evaluation of the Card-Sarc questionnaire, as developed under aim 2, for reliability, validity and responsiveness (December 2021-h;September 2023). Patient and public involvementCS-patients have guided the research question and reviewed research methods, which have been revised according to their feedback. The UK Sarcoidosis charity (SarcoidosisUK) is actively engaged with this project. Five expert patients with CS confirmed their interest in co-production throughout the project. Anticipated impact and disseminationThe Card-Sarc questionnaire will determine the impact in HRQoL of living with CS. This provides the potential to improve clinical management, inform health-economic stakeholders and identify areas for future research, for example through evaluation of treatment and continuity of care. Results will be disseminated in collaboration with PPI partners via two peer-reviewed publications (systematic review and a development and internal validation paper), national and international conferences, professional networks and the charity SarcoidosisUK.

Lay abstract: What is the aim of this research?To explore the impact of cardiac sarcoidosis on the physical, mental, social and emotional health and the wellbeing of patients living with the disease. What is cardiac sarcoidosis?Sarcoidosis is a condition caused by the formation of lumps (granulomas) of abnormal tissue in any organ. These granulomas can destroy healthy tissue and affect the normal function of the organ. However, the exact cause of sarcoidosis is not known. Although sarcoidosis is primarily a lung disease, cardiac sarcoidosis occurs when the heart is affected by the accumulation of granulomas. This can prevent the heart from working properly which is associated with serious consequences. Cardiac sarcoidosis occurs in up to a third of all sarcoidosis patients, but only causes specific symptoms in around 5% of cases. Common symptoms in cardiac sarcoidosis may include chest pain, irregular heartbeats (pounding or fluttering sensation, or a 'skipping of beats'), heart malfunction, dizziness or fainting spells, and in rare cases sudden cardiac death (when the heart suddenly stops beating). There is no cure for cardiac sarcoidosis. However, there are treatment options to control symptoms including higher dose of anti-sarcoidosis medication, specific tablets or directed electrical impulses to reduce or stop irregular heartbeats, implantation of a pacemaker or defibrillator to reduce risk of sudden death, and heart transplant may be considered in very severe cases. Why is this research needed?Sarcoidosis can affect physical, functional, mental, social and economic aspects of people' life. Previous studies suggested that people living with cardiac sarcoidosis can experience a greater impact in their quality of life compared to other types of sarcoidosis, but this has not been studied yet.Measuring quality of life in people with cardiac sarcoidosis is difficult as questionnaires that do exist have been developed for other forms of sarcoidosis or for specific cardiac problems, but not specifically for people living with cardiac sarcoidosis. This means that we currently do not have a way of accurately measuring quality of life in patients with cardiac sarcoidosis which also means we cannot accurately then identify ways of being able to improve quality of life for these patients. What will this study involve?This study includes three parts based in two NHS specialist-centres: Part A: I will explore and review what is already known about cardiac sarcoidosis and its impact on quality of life. Part B: I will develop a questionnaire, specific to cardiac sarcoidosis patients, that will be able to measure the impact of cardiac sarcoidosis on quality of life (the Card-Sarc questionnaire). Part C: I will then evaluate how good the Card-Sarc questionnaire is at measuring quality of life changes in patients with cardiac sarcoidosis. How will patients or the public help guide the research?This work has been influenced and designed with people living with cardiac sarcoidosis. SarcoidosisUK, the UK sarcoidosis charity, has been supportive and engaged on this work. Likewise, five expert patients with cardiac sarcoidosis have also agreed to lead, contribute and advice on relevant aspects of the study, and to participate sharing the results to the public, patients and professional groups.How will the findings be shared?I am to publish the findings in scientific journals, national and international meetings and conferences. I will also discuss and share the results with study participants, professional sarcoidosis networks and patient support groups.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CARDIOVASCULAR