Long-term LVEF decline occurs following COVID-19

Individuals with SARS‐CoV‐2 infection, especially those who are hospitalized, face long‐term declines in left ventricular ejection fraction (LVEF), according to a retrospective study.

Over a median follow-up of 2.32 years, participants who were COVID-19–positive had lower LVEF values than those who were negative for the infection (control) (60.65 percent vs 61.53 percent, p<0.005), with an average reduction of −2.40 percent vs −1.44 percent, respectively (p<0.005). [J Am Heart Assoc 2025;doi:10.1161/JAHA.125.043976]

Significantly more patients in the COVID group than in the control group experienced LVEF declines of <50 percent (10.62 percent vs 7.24 percent; p<0.005), 40 percent to 49 percent (6.27 percent vs 4.29 percent; p<0.005), and 30 percent (1.75 percent vs 0.91 percent; p<0.005). For all LVEF decline thresholds, participants who were hospitalized with COVID-19 had the highest cumulative incidence, followed by nonhospitalized participants with COVID-19 and controls who were COVID-19–negative.

In multivariable regression analysis, the association between COVID-19 and the risk of LVEF dropping below 50 percent was pronounced among both hospitalized (adjusted hazard ratio [aHR], 1.57, 95 percent confidence interval [CI], 1.30–1.91) and nonhospitalized participants (aHR, 1.48, 95 percent CI, 1.18–1.85) relative to controls. Meanwhile, the association between COVID-19 and the risk of LVEF dropping below 40 percent and 30 percent was observed only among hospitalized participants vs controls (<40 percent: aHR, 1.81, 95 percent CI, 1.35–2.43; <30 percent: aHR, 2.79, 95 percent CI, 1.72–4.54).

Older participants, men, and those with a lower baseline LVEF or a history of established cardiovascular risk factors (eg, congestive heart failure, MI, and chronic kidney disease) had a higher risk of COVID-19–associated LVEF decline. Elevations in blood-based biomarkers such as troponin and B‐type natriuretic peptide, as well as D‐dimer and platelets, during acute COVID‐19 were predictive of LVEF decline.

“Our findings carry significant clinical implications and underscore the need for vigilant monitoring of cardiac function in survivors of COVID‐19, especially for those with risk factors,” the investigators said.

“Early detection of LVEF decline would allow for timely optimization of guideline‐directed medical therapy, such as angiotensin receptor‐neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists, or sodium‐glucose cotransporter 2 inhibitors,” they added. [Circulation 2016;134:e579-e646; J Am Coll Cardiol 2024;83:1444-1488]

From a drug development perspective, the study points to the potential of investigating interventions targeting inflammation and myocardial remodelling for mitigating the long‐term cardiac sequelae of COVID‐19, according to the investigators. Inflammatory cytokines such as IL‐6 may contribute to adverse myocardial remodelling weeks to months after severe illness. Therefore, drugs that block IL-6 warrant investigation in this context, especially because they have been shown to reduce circulating levels of N‐terminal proBNP. [Cardiovasc Res 2024;120:174-187; Int J Mol Sci 2023;2:510; Int J Mol Sci 2021;22:22; Scand J Rheumatol 2018;47:364-370]

The present analysis included 2,853 participants in the COVID group (mean age at index date 64.94 years, 61.51 percent female) and 3,963 in the control group (mean age at index date 65.15 years, 64.5 percent female). All participants had baseline LVEF of ≥50 percent and at least one follow‐up echocardiogram. Compared with the control group, the COVID group had a higher prevalence of all pre-existing comorbidities (p<0.05). Of the participants, 34.21 percent in the COVID group and 24.8 percent in the control group had received at least one dose of COVID‐19 vaccine before index date.