Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background Symptom cluster is an important concept in heart failure management, given the multiplicative rather than addictive effects of the symptoms on patients’ health outcomes. Previous reviews, which integrated findings at the cluster level, provided limited insights into how a wider range of symptoms relate to one another. Moreover, little attention has been given to the manifestation of symptom clusters throughout the disease course and the way patients’ profile relate to the symptom manifestation. Objectives The objectives of this study were 1) to determine how symptoms are clustered in HF patients, 2) to examine how symptom clusters change throughout the HF disease course, and 3) to determine the factors associated with the patterns of symptom presentation. Methods This systematic review and meta-analysis identified studies from 11 English and Chinese language databases (inception to March 2022). A systematic observation of how individual symptoms were clustered with one another, based on their correlation across studies, was performed to identify the overarching symptom clusters. These clusters were then mapped throughout the HF disease course, which was operationally defined in terms of the disease status of the study samples. To identify factors relating to pattern of symptom presentation, another narrative analysis was done to identify patient clusters based on the type and severity of symptom manifestation, and meta-analysis was performed to identify the factors relating to these clusters. Results Twenty-four studies (N = 11,027) were identified. Four overarching symptom clusters, including circulatory, ischaemic, vitality, and stress-related symptom clusters, were identified through symptom-level data synthesis. Circulatory and vitality symptom clusters were persistent throughout the heart failure disease course, whereas ischaemic and stress-related symptom clusters were predominant among who were hospitalized for heart failure exacerbation. Four patient clusters of different symptom presentations were identified, including low symptom cohort, moderate to high symptomatic cohort, and two incongruent symptom cohorts with one dominated by physical symptoms and another by psycho-cognitive symptoms. Meta-analysis indicated that younger age was related to moderate-to-high symptomatic cohort (SMD=-0.43 (95% CI: -0.72 to -0.15, p = 0.003), whereas female (pooled OR =1.69 (95% CI: 1.15–2.47, p = 0.007) and presence of diabetes (OR: 1.60, 95% CI: 1.04–2.46, p =0.03) were related to incongruent symptom cluster with physical dominance. Conclusions The overarching symptom clusters manifesting throughout the heart failure disease course signified four pivotal domains to guide proactive and comprehensive HF symptom assessment, and more attention need to direct to patients who are younger, female and with comorbid diabetes. Longitudinal investigation on symptom clusters based on comprehensive symptom surveillance is warranted.

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