key: cord-0929329-n60ql8a9
authors: Moody, William E.; Liu, Boyang; Mahmoud-Elsayed, Hani M.; Senior, Jonathan; Lalla, Sasha S.; Khan-Kheil, Ayisha M.; Brown, Stewart; Saif, Abdullah; Moss, Alastair; Bradlow, William M.; Khoo, Jeffrey; Ahamed, Mubarak; McAloon, Christopher; Hothi, Sandeep S.; Steeds, Richard P.
title: Persisting Adverse Ventricular Remodeling in COVID-19 Survivors: A Longitudinal Echocardiographic Study
date: 2021-02-01
journal: J Am Soc Echocardiogr
DOI: 10.1016/j.echo.2021.01.020
sha: 9b55c7a735ea86bcb05b6f746e4299be1e6ee3a6
doc_id: 929329
cord_uid: n60ql8a9

nan

Persisting Adverse Ventricular Remodeling in Survivors: A Longitudinal Echocardiographic Study Abnormalities in cardiac structure and function are common in patients hospitalized with severe COVID-19 pneumonia who have evidence of myocardial injury based on elevated high-sensitivity cardiac troponin (HScTn). 1 Studies performing transthoracic echocardiography (TTE) in an acute setting have consistently demonstrated a high prevalence of right ventricular (RV) dilation and dysfunction, a finding that is associated with early mortality independent of standard clinical and biomarker risk stratification. 1, 2 These studies have, however, been limited by their cross-sectional design; to date, there have been no lon-gitudinal studies aimed at determining whether adverse ventricular remodeling is transient or permanent. To address this, we elected to perform repeat echocardiographic assessment at 3 months in survivors following hospitalization for severe COVID-19 pneumonia.

This was a multicenter, prospective, observational, cohort study of adults ages $ 18 years hospitalized with COVID-19 pneumonia (study CONSORT, Figure 1A ). The methodology for baseline assessment was published in a retrospective observational analysis 2 ; survivors are included in the current study. In brief, baseline TTE followed a modified level 1 focused protocol limited to assessment of chamber size and function, valvular disease, and likelihood of pulmonary hypertension. At 3 months after the first TTE, a comprehensive departmental study was performed according to standard guidelines. 3 All measurements were performed retrospectively and off-line using archived images by British Society of Echocardiography The results of echocardiography performed at baseline and 3 months are detailed in Table 1 . At entry, 36 (46%) patients had a normal TTE. In those with any abnormality, 32 (41%) had RV remodeling, 5 (6%) had LV remodeling, and 6 (8%) had biventricular involvement. Right ventricular dilation was present in over a third of patients (39%), a 1.5-fold higher prevalence than that of RV dysfunction (27%). Conversely, left ventricular (LV) dilation and LV dysfunction were only found in 4% and 13% of patients, respectively.

Follow-up TTE was undertaken at a median of 91 days (IQR, 92-99) after the baseline study. At 3 months, 56 (71%) patients had a normal TTE. In those with any abnormality, 16 (20%) had only RV adverse remodeling, 5 (6%) had only adverse LV remodeling, and 2 (3%) had biventricular involvement. There was reverse RV remodeling in the majority (Figure 1B) , reflected by a significantly lower RV basal dimension and an augmented RV fractional area change compared with baseline. There was no significant change in peak tricuspid regurgitant velocity at follow-up compared with baseline, although most had a low echocardiographic probability of pulmonary hypertension, acknowledging that the number of patients with a measurable Doppler signal was small. There were no significant changes in LV parameters at 3 months compared with baseline. Of the 16 patients (20%) with persisting RV changes at 3 months, 7 (44%) had pulmonary embolism diagnosed on computed tomography pulmonary angiography during hospital admission. There was no effect of gender (male 25% vs female 26%; P = .95) or ethnicity (nonwhite 35% vs white 33%, P = .89) on the frequency of patients with abnormal RV size

Hypoxic pulmonary vasoconstric on Ven lator induced lung injury Pulmonary thromboembolic disease Direct myocardial injury

Normaliza on of RV size and func on HScTn, median (IQR), ng/L 27 (9-129) 2 (0-5) <.001

HScTn above the 99% percentile, n (%) 27 (60) 0 (0) <.001

HScTn (Table 1) . Despite persistent LV and/or RV abnormalities in 11 (24%) patients, no patient at 3 months had a HScTn above the 99th percentile for age and sex. We found a higher rate of abnormal ventricular dilation or dysfunction than cross-sectional cardiac magnetic resonance studies performed at approximately 10 weeks, although these included a majority of patients cared for at home and few who were ventilated. 5, 6 Our results also differed from a smaller TTE study that enrolled predominantly HScTn-negative patients in whom both TTE abnormalities and cardiac biomarkers resolved within a median 41 days. 7 This difference is likely explained by the severity of COVID-19 pneumonia in our population. The high frequency of adverse RV remodeling at baseline may in part relate to acute effects from mechanical ventilation. Nonetheless, the prevalence of isolated RV dysfunction did not change at follow-up, which implicates other factors such as direct myocardial injury and thromboembolic disease.

While our cohort is modest in size and is highly selected, this is the largest echocardiographic follow-up study to date in COVID-19 and included a cohort at the highest risk of adverse outcomes. Our patients were referred for echocardiography on clinical grounds, most had elevated HScTn on admission and required ventilation, and those with previous abnormalities on echocardiography were excluded. These results are not, therefore, generalizable to all patients hospitalized with COVID-19 or to those not requiring admission.

In summary, although acute abnormalities in ventricular size or function among hospitalized patients with COVID-19 pneumonia resolved in most patients after 3 months, there was persistent evidence of adverse ventricular remodeling in nearly one-third (29%). Furthermore, repeat TTE appears necessary for surveillance because a significant proportion in whom biomarkers normalized continued to demonstrate ventricular abnormalities. 

Prognostic utility of right ventricular remodeling over conventional risk stratification in patients with COVID-19

Impact of right ventricular dysfunction on mortality in patients hospitalized with COVID-19 according to race

A minimum dataset for a standard adult transthoracic echocardiogram: a guideline protocol from the British Society of Echocardiography

Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging

COVID-19: myocardial injury in survivors

Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19)

Echocardiographic comparison of COVID-19 patients with or without prior biochemical evidence of cardiac injury after recovery

We thank the accredited sonographers for performing the echocardiography studies within their respective departments. This work was supported by a British Heart Foundation Accelerator Award (AA/ 18/2/34218).