Treadmill Exercise Stress Echocardiography Exposes Impaired Left Ventricular Function in Patients Recovering from Hospitalization with COVID-19 Without Overt Myocarditis Versus Historical Controls
Authors: Goldstein Robert E , Hulten Edward A. , Arnold Thomas B. , Thomas Victoria M. , Heroy Andrew , Walker Erika N. , Fox Keiko , Lee Hyun , Libbus Joya , Markos Bethelhem , Hood Maureen N. , Harrell Travis E. , Haigney Mark C. 
Published: February 2024

Background

Usual clinical testing rarely reveals cardiac abnormalities persisting after hospitalization for COVID-19. Such testing may overlook residual changes responsible for increased adverse cardiac events post-discharge.

Methods

To further elucidate long-term status, we performed exercise stress echocardiography (ESE) in 15 patients age 30-63 without myocarditis 3 to 31 months after hospital discharge. We compared patient outcomes to published data in healthy comparisons (HC) exercising according to the same protocol.

Results

Patients’ treadmill exercise (Bruce protocol), averaging 8.2 min, was halted by dyspnea or fatigue. Pre-stress baselines in recovering patients (RP) matched HC except for higher heart rate: mean 81 bpm for RP and 63 for HC (p<0.0001). At peak stress, RP had significantly lower mean left ventricular (LV) ejection fraction (67% vs 73%, p<0.0017) and higher peak early mitral inflow velocity/early mitral annular velocity (E/e’, 9.1 vs 6.6, p<0.006) compared with HC performing equal exercise (8.5 min). Thus, when stressed, patients without known cardiac impairment showed modest but consistently diminished systolic contractile function and diastolic LV compliance during recovery vs HC. Peak HR during stress was significantly elevated in RP vs HC; peak SBP also trended higher. Average pulmonary artery systolic pressures among RP remained normal.

Conclusions

Our measurements during ESE uniquely identified residual abnormality in cardiac contractile function not evident in the unstressed condition. This finding exposes a previously-unrecognized residual influence of COVID-19, possibly related to underlying autonomic dysfunction, microvascular disease, or diffuse interstitial changes after subclinical myocarditis; it may have long-term implications for clinical management and later prognosis.

CLINICAL PERSPECTIVE

New Findings (relative to a historical comparison group)

Symptom-limited treadmill exercise 3-31 months after hospitalization with COVID-19 without overt myocarditis elicited a lesser rise in left ventricular ejection fraction than seen in similar subjects with no exposure to COVID-19.

The same symptom-limited exercise in these patients revealed evidence of diminished left ventricular diastolic function relative to subjects with no exposure to COVID-19.

These distinctive differences in left ventricular function were observed although overall exercise capacity was the same as in the uninfected comparison group.

Clinical Implications

Prior hospitalization with COVID-19 even in the absence of overt myocarditis was often associated with a modest but consistent decrement in left ventricular systolic contraction and diastolic relaxation; these functional abnormalities were evident after peak treadmill exercise stress despite lack of distinctive difference in contractile parameters at rest.

Patients recovering after hospitalization with COVID-19 may benefit from sustained observation of their cardiovascular status and adjustment of their exercise requirements appropriate to individual cardiovascular capabilities.

Treadmill stress testing with echocardiography uniquely identifies potentially important differences in the cardiovascular function of patients recovering after hospitalization with COVID-19.