The impact of post-acute sequelae of COVID-19 on cardiac function and structure: A systematic review and a hybrid individual participant data meta-analysis

• This study examines the impact of persistent symptoms following COVID-19 infection (known as Post-Acute Sequelae of SARS-CoV-2 infection or PASC) on heart function. • Individuals with PASC show measurable impairments in cardiac function, particularly in global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF). • Cardiac abnormalities are more pronounced in older adults and in those with diabetes or hypertension, indicating increased cardiovascular vulnerability and supporting a risk-stratified surveillance approach. Post-acute sequelae of SARS-CoV-2 infection (PASC), also referred to as Long COVID, affect a significant proportion of COVID-19 survivors, with evidence suggesting cardiovascular involvement. However, the nature, extent, and clinical significance of these alterations remain uncertain. To synthesize evidence on structural and functional cardiac alterations in individuals with PASC compared with those without PASC. We systematically searched seven databases. Random-effects meta-analyses were performed and supplemented by individual participant data (IPD) analyses from three studies. Univariable and multivariable meta-regressions examined associations with study-level characteristics. Publication bias and evidence certainty were assessed using standard methods (funnel plots, Egger’s test, trim-and-fill, and GRADE). From 3,580 records, 17 studies with 4,852 participants (3,173 PASC, 1,679 controls) met the inclusion criteria. IPD analysis revealed an impairment in global longitudinal strain (GLS) (mean difference (MD) = 3.63%) in individuals with PASC. When using categorical thresholds, 58% of individuals with PASC had GLS < 16%, indicating a significant prevalence of subclinical left ventricular dysfunction. Meta-analysis supported these findings, showing impaired GLS (MD = 1.07%), along with reductions in left ventricular ejection fraction (MD = -1.30%) and left ventricular end-diastolic volume (MD=-3.98 mL). Meta-regression showed that cardiac dysfunction was more frequently observed in individuals with older age, diabetes, and hypertension. This review indicates that PASC is associated with modest, subclinical alterations in cardiac function. These alterations appear more pronounced in older adults and those with cardiometabolic comorbidities, highlighting the potential value of risk-stratified cardiovascular surveillance in individuals with PASC. The long-term clinical relevance of these changes remains unclear and warrants further study.