JACC: CARDIOVASCULAR IMAGING VOL. -, NO.

-, 2020
ª 2020 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

PUBLISHED BY ELSEVIER

ORIGINAL RESEARCH

Cardiac Involvement in
Patients Recovered From
COVID-2019 Identified Using
Magnetic Resonance Imaging
Lu Huang, MD, PHD,a,* Peijun Zhao, MD,a,* Dazhong Tang, MS,a Tong Zhu, MD,a Rui Han, MD,b
Chenao Zhan, MD, PHD,a Weiyong Liu, MD, PHD,c Hesong Zeng, MD, PHD,d Qian Tao, PHD,e Liming Xia, MD, PHDa

ABSTRACT

OBJECTIVES We evaluated cardiac involvement in patients recovered from coronavirus disease-2019 (COVID-19) using
cardiac magnetic resonance (CMR).

BACKGROUND Myocardial injury caused by COVID-19 was previously reported in hospitalized patients. It is unknown if
there is sustained cardiac involvement after patients’ recovery from COVID-19.

METHODS Twenty-six patients recovered from COVID-19 who reported cardiac symptoms and underwent CMR ex-
aminations were retrospectively included. CMR protocols consisted of conventional sequences (cine, T2-weighted im-
aging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume
[ECV] mapping). Edema ratio and LGE were assessed in post–COVID-19 patients. Cardiac function, native T1/T2, and ECV
were quantitatively evaluated and compared with controls.

RESULTS Fifteen patients (58%) had abnormal CMR findings on conventional CMR sequences: myocardial edema was
found in 14 (54%) patients and LGE was found in 8 (31%) patients. Decreased right ventricle functional parameters
including ejection fraction, cardiac index, and stroke volume/body surface area were found in patients with positive
conventional CMR findings. Using quantitative mapping, global native T1, T2, and ECV were all found to be significantly
elevated in patients with positive conventional CMR findings, compared with patients without positive findings and
controls (median [interquartile range], native T1 1,271 ms [1,243 to 1,298 ms] vs. 1,237 ms [1,216 to 1,262 ms] vs. 1,224 ms
[1,217 to 1,245 ms]; mean
SD, T2 42.7
3.1 ms vs. 38.1 ms
2.4 vs. 39.1 ms
3.1; median [interquartile range], 28.2%
[24.8% to 36.2%] vs. 24.8% [23.1% to 25.4%] vs. 23.7% [22.2% to 25.2%]; p ¼ 0.002; p < 0.001, and p ¼ 0.002,
respectively).

CONCLUSIONS Cardiac involvement was found in a proportion of patients recovered from COVID-19. CMR manifes-
tation included myocardial edema, fibrosis, and impaired right ventricle function. Attention should be paid to the possible
myocardial involvement in patients recovered from COVID-19 with cardiac symptoms.
(J Am Coll Cardiol Img 2020;-:-–-) © 2020 by the American College of Cardiology Foundation.

From the aDepartment of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology,
Wuhan, China; bDepartment of Radiology, Wuhan No.1 Hospital, Wuhan, China; cDepartment of Laboratory Medicine, Tongji
Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; dDepartment of Cardiology,
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and the eDivision of
Imaging Processing, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands. *Drs. Huang and
Zhao contributed equally to this work. This work was supported in part by the National Natural Science Foundation of China
(81471637 and 81873889), the National Mega Project on Major Infectious Disease Prevention (2017ZX10103005-007), and the
National Key Research and Development Program of China (2018YFE0204500). All authors have reported that they have no
relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’
institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information,
visit the JACC: Cardiovascular Imaging author instructions page.

Manuscript received April 17, 2020; revised manuscript received April 30, 2020, accepted May 4, 2020.

ISSN 1936-878X/$36.00 https://doi.org/10.1016/j.jcmg.2020.05.004

2 Huang et al. JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2020
CMR Findings in Recovered COVID-19 - 2020:-–-

C
ABBREVIATIONS oronavirus disease-2019 (COVID-19) SARS-CoV-2 infection using reverse transcription-
AND ACRONYMS has been a global outbreak since polymerase chain reaction (RT-PCR) swab test (12); 2)
March 2020 (1). To date, more than patients were considered recovered by the discharg-
ACE2 = angiotensin-converting
enzyme 2
2,725,000 patients have been confirmed ing criteria (normal temperature lasting longer than

AHA = American Heart

with severe acute respiratory syndrome- 3 days, resolved respiratory symptoms, and substan-
Association coronavirus-2 (SARS-CoV-2) infection in tially improved exudative lesions on chest CT images,
BSA = body surface area more than 200 countries. The lung is the ma- and 2 consecutive negative RT-PCR test results
CI = cardiac index jor organ involved in COVID-19, and separated by at least 24 h) and were isolated for

CO = cardiac output
angiotensin-converting enzyme 2 (ACE2) is 14 days (13); and 3) patients reported cardiac symp-
the path for SARS-CoV-2 to attack pulmonary toms after being discharged, including chest pain,
CMR = cardiac magnetic
resonance tissue (2). ACE2 is located not only in the palpitation, and chest distress. Exclusion criteria
COVID-19 = coronavirus lungs, but also in other organs, including were as follows: 1) a history of coronary artery disease
disease-2019 the cardiovascular system (3). Previous or myocarditis; 2) contradictions to gadolinium
ECV = extracellular volume studies (4,5) found that 12% to 15% of pa- contrast; and 3) CMR image quality that was not suf-
EDV = end-diastolic volume tients with COVID-19 had elevated high- ficient for analysis.
EF = ejection fraction sensitive cardiac troponin I (hs-cTnI) during Healthy controls of similar age and gender distri-

ER = edema ratio
hospital period, which indicated myocardial butions who previously underwent the same CMR
injury, and that cardiac involvement in examinations in our hospital were also included. The
ESV = end-systolic volume
severe-type patients was up to 31%. Howev- controls were selected from a database of healthy
FA = flip angle
er, it is unknown if there is sustained cardiac subjects without cardiovascular disease or systemic
FOV = field of view
involvement in patients after their recovery inflammation. This study was approved by the insti-
hs-cTnI = high-sensitive
from COVID-19, especially those with moder- tutional review board of Tongji Hospital, Tongji
cardiac troponin I
ate-type. Medical College (TJ-IRB20200417). The requirement
IQR = interquartile range
Cardiac involvement in myocarditis, for informed patient consent was waived by the
LGE = late gadolinium
enhancement
including myocardial fibrosis, edema, and ethics committee for this retrospective study.
pericarditis (6), is associated with adverse
LV = left ventricle CMR SCANNING PROTOCOL. All patients underwent
events and poor prognosis; it is important to
LVEF = left ventricular ejection CMR examination on a 3T MR scanner (Skyra,
fraction
identify such involvement at an early stage
Siemens, Healthineers, Erlangen, Germany). CMR
PSIR = phase-sensitive
for appropriate treatment. Cardiac magnetic
scanning protocol included the following: 1) conven-
inversion-recovery resonance (CMR) is the current gold standard
tional sequences: short-axis and long-axis cine, T2-
RT-PCR = reverse transcription to evaluate cardiac morphology and function
weighted imaging (T2WI), and late gadolinium
and polymerase chain reaction (7), and the recent CMR mapping techniques,
enhancement (LGE); and 2) quantitative mapping
RV = right ventricle including T1, T2, and extracellular volume
sequences: native T1/T2 mapping and post-contrast
RVEF = right ventricular (ECV), are unique tools to quantitatively
T1 mapping. The stack of short-axis slices covered
ejection fraction assess myocardial diffuse fibrosis and edema
the left ventricle (LV) from apex to mitral annulus.
SARS-CoV-2 = severe acute (8,9). Although hs-cTnI is highly specific for
respiratory syndrome-
Steady state free precession (SSFP) was used for car-
myocardial injury, CMR has reported higher
coronavirus-2 diac cine imaging with the following parameters:
sensitivity for detecting occult cardiac
SI = signal intensity echo time (TE) ¼ 1.4 ms, repetition time
involvement (10,11). The purpose of our
STIR = short tau inversion (TR) ¼ 37.7 ms, field of view (FOV) ¼ 360  360 mm,
study was to evaluate cardiac involvement in
recovery matrix ¼ 192  146, flip angle (FA) ¼ 55  , slice
patients recovered from COVID-19 who
SSFP = steady state free thickness ¼ 8 mm, and slice gap ¼ 2 mm. T2WI, native
precession reported cardiac symptoms, using cardiac
T1/T2 mapping, LGE, and post-contrast T1 mapping
SV = stroke volume CMR as a sensitive imaging tool.
had the same imaging plane as the short-axis cine.
T2WI = T2-weighted imaging METHODS T2WI, black blood T2-weight short tau inversion
TE = echo time recovery (STIR) sequence was performed using
TR = repetition time STUDY DESIGN AND PARTICIPANTS. This TR ¼ 2RR intervals, TE ¼ 41 ms, slice
single-center, retrospective, observational study was thickness ¼ 8 mm, and FOV ¼ 360 mm  360 mm.
performed at Tongji Hospital, Tongji Medical College, Native and post-contrast T1 mapping was acquired
Wuhan, China. Consecutive patients since March using an electrocardiograph-gated single-shot modi-
2020 who were initially referred for cardiac CMR ex- fied Look-Locker inversion recovery sequence with
amination due to cardiac symptoms and who met the protocol 5(3)3 and 4(1)3(1)2, respectively. The acqui-
following inclusion criteria were retrospectively sition parameters were TE ¼ 1.2 ms, TR ¼ 3.8 ms,
included: 1) patients were previously confirmed with FOV ¼ 320  360 mm, matrix ¼ 192  144, FA ¼ 35  ,
JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2020 Huang et al. 3
- 2020:-–- CMR Findings in Recovered COVID-19

T A B L E 1 Clinical Characteristics and Laboratory Measurements of Patients Recovered From COVID-19

Conventional CMR Findings

Total (N ¼ 26) Positive (n ¼ 15) Negative (n ¼ 11) p Value*

Age (yrs) 38 (32–45) 39 (29–49) 37 (34–39) 0.61

Male 10 (38) 4 (27) 6 (55) 0.23
BMI (kg/m2) 23.2
3.6 22.3
3.8 24.5
3.1 0.12
BSA (m2) 1.7
0.2 1.7
0.2 1.8
0.2 0.19
HR (beats/min) 77
10 74
8 81
10 0.06
Systolic pressure (mm Hg) 121
10 118
10 124
10 0.20
Diastolic pressure (mm Hg) 76
8 77
9 76
7 0.82
COVID-19 confirmed patient exposure 26 (100) 15 (100) 11 (100) NA
Duration between cardiac symptoms onset 47 (36–58) 48 (35–56) 50 (40–60) 0.62
to CMR examination (days)
Clinical types, moderate/severe/critical 22/4/0 12/3/0 10/1/0 0.61
Comorbidities
Hypertension 2 (8) 1 (7) 1 (9) >0.99
Diabetes mellites 0 0 0 NA
Coronary artery disease 0 0 0 NA
Chronic obstructive pulmonary diseases 0 0 0 NA
Cerebrovascular disease 0 0 0 NA
Chronic renal diseases 0 0 0 NA
Chronic liver diseases 0 0 0 NA
Cardiac symptoms
Precordial chest pain 3 (12) 2 (13) 1 (9) >0.99
Palpitation 23 (88) 12 (80) 11 (100) 0.24
Chest distress 6 (23) 4 (27) 2 (18) 0.67
Laboratory findings
White blood cell count (109/l) 5.4 (4.5–6.8) 4.7 (4.2–5.7) 6.6 (5.8–6.9) 0.06
Lymphocyte count (109/l) 1.6 (1.3–1.9) 1.5 (1.3–1.8) 1.9 (1.6–2.0) 0.38
Hs-CRP (mg/l) 1.4 (0.4–5.1) 1.0 (0.4–7.5) 2.3 (0.5–4.1) 0.80
DD (ug/ml FEU) 0.28 (0.22–0.41) 0.32 (0.24–0.44) 0.22 (0.20–0.29) 0.11
IL6 (pg/ml) 3.7 (2.2–14.4) 4.2 (2.3–12.9) 3.2 (2.2–11.6) 0.80
LDH (U/l) 180 (158–193) 185 (159–194) 168 (154–192) 0.43
Hs-cTnI (pg/ml) 2.0 (1.9–2.2) 2.0 (1.9–2.1) 2.0 (1.9–2.3) 0.77
NT-proBNP (pg/ml) 28 (11–36) 33 (20–57) 14 (11–18) 0.16
Treatment before discharge
Antiviral therapy 26 (100) 15 (100) 11 (100) NA
Antibiotic therapy 26 (100) 15 (100) 11 (100) NA
Use of corticosteroid 13 (50) 7 (47) 6 (55) >0.99
Nasal cannula oxygen 18 (69) 11(73) 7 (63) 0.68
Noninvasive ventilation or high-flow nasal cannula oxygen 3 (12) 2 (13) 1 (9) 0.62

Values are median (25th-75th percentiles), n (%), or mean
SD. *The p value is for patients with positive conventional CMR findings vs. patients without positive conventional CMR findings.
BMI ¼ body mass index; BSA ¼ body surface area; CMR ¼ cardiac magnetic resonance; COVID-19 ¼ coronavirus disease-2019; DD ¼ D-dimer; FEU ¼ fibrinogen equivalent units; HR ¼ heart rate; Hs-
CRP ¼ high-sensitivity C-reactive protein; IL6 ¼ inerfertin-6; LDH ¼ lactate dehydrogenase; Hs-cTnI ¼ high-sensitivity cardiac troponin I; IQR ¼ interquartile range; NA ¼ not applicable; NT-
proBNP ¼ amino-terminal pro-brain natriuretic peptide.

and slice thickness ¼ 8 mm. The T2 mapping tech- matrix ¼ 224  156, and FA ¼ 55  ). Hematocrit level
nique involved a T2 preparation module to produce was measured within 3 days of CMR scanning for ECV
single-shot T2 prepared SSFP images (T2p-SSFP), with calculation. All patients underwent laboratory hs-
different T2 preparation times (0 ms, 24 ms, and cTnI testing before cardiac CMR examination.
55 ms), TR ¼ 208 ms, FA ¼ 12  , and matrix ¼ 206 
256. LGE imaging was performed 10 to 15 min after CMR IMAGES ANALYSIS. Two radiologists (LH with
intravenous administration of gadobenate dimeglu- 10 years of CMR diagnosis experience and PZ with 4
mine (0.2 ml/kg of Multihance, Bracco Diagnostics, years of CMR diagnosis experience) evaluated all
Shanghai, China) using a phase-sensitive inversion- CMR images using commercial software cvi 42, v.5.3
recovery (PSIR) sequence (TR ¼ 5.2 ms, TE ¼ 1.2 ms, (Circle Cardiovascular Imaging, Calgary, Canada).
4 Huang et al. JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2020
CMR Findings in Recovered COVID-19 - 2020:-–-

C E N T R A L IL L U ST R A T I O N Dominant Location and Distribution of Myocardial Edema Segments

and Myocardial LGE Segments in Patients Recovered From COVID-19

A B
9 0

12 0
8 9 2 0
11
10 7 1 0 1

7 NA 5 0 NA 0

10 3 7 1 0 2
9 1
11 1
8 3

11 3

0 3-6 7-9 10-12 0 1 2 3

Huang, L. et al. J Am Coll Cardiol Img. 2020;-(-):-–-.

(A) Number of myocardial edemas distributed in the AHA 16 segments’ model in all 15 patients with positive conventional CMR findings. (B)
Number of myocardial LGEs distributed in the AHA 16 segments’ model in all 15 patients with positive conventional CMR findings.
AHA ¼ American Heart Association; COVID-19 ¼ Coronavirus Disease-2019; LGE ¼ late gadolinium enhancement; CMR ¼ cardiac magnetic
resonance; NA ¼ not applicable.

Myocardial edema was evaluated on T2WI images Global T1/T2 values were computed by manually
(14) and divided into 16 American Heart Association delineating the whole LV myocardium region
(AHA) segments. Myocardial edema ratio (ER) was (including regions of LGE lesion) on the T1/T2 map. To
defined as the ratio between myocardial signal in- assess the remote myocardium, T1/T2 values were also
tensity (SI) to skeletal muscle SI (7). An ER >2.0 was measured in the AHA myocardium segments free of
considered as abnormal (15). The location (16 seg- apparent LGE lesion. Native T1 and post-contrast T1 of
ments of AHA) and pattern (epicardial, mid-wall, or myocardium and blood pool were used to derive ECV
transmural) of LGE lesions on the LGE images were as the described equation in a previous study (15).
assessed by 2 observers who reviewed all PSIR im- LV and right ventricle (RV) function parameters
ages independently. A senior observer (LX, with 20 were automatically calculated from endocardial and
years of experience in CMR) adjudicated any dis- epicardial contours. Functional parameters included
crepancies between the 2 observers. For each patient, LV/RV end-diastolic volume (EDV), end-systolic vol-
the endo- and epicardial contours of LGE images ume (ESV), stroke volume (SV), cardiac output (CO),
were manually delineated, and LGE lesion was LV mass, and ejection fraction (EF). All volumes and
defined as SI >5 SDs above the mean SI of the remote mass were normalized by body surface area (BSA).
reference myocardium (16). Ratios between the LGE
volume and the total LV myocardium volume (LGE/ STATISTICAL ANALYSIS. All statistical analysis was
myocardium) in the LGE-positive patients were performed using SPSS version 23.0 (IBM statistics,
calculated. Patients were further divided into 2 sub- Armonk, New York) and GraphPad Prism version 8.1
groups based on the presence or absence of positive (GraphPad Software Inc., La Jolla, California). Cate-
conventional cardiac CMR findings, which were gorical variables were expressed as counts (percent-
defined as increased myocardial edema ratio (>2.0) age), and continuous variable as mean
SD or
and/or LGE presence. median (interquartile range [IQR]). Normality of
JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2020 Huang et al. 5
- 2020:-–- CMR Findings in Recovered COVID-19

F I G U R E 1 Focal Myocardial Fibrosis in Patients Recovered From COVID-19

PSIR sequence in short-axis view PSIR sequence in 2-chamber view

A B

PSIR sequence in short-axis view PSIR sequence in 4-chamber view

C D

A 29-year-old male patient (first row) underwent cardiac CMR 1 month after the onset of palpitations. A 60-year-old male patient (second
row) underwent cardiac CMR 2 months after the onset of palpitations. PSIR sequences in short-axis view (A, C) showed focal LGE (black
arrows) in inferior and septal segments of left ventricle, respectively. Results were confirmed on the PSIR sequences in 2-chamber view (C)
and 4-chamber view (D). Images A and D demonstrated a small pericardial effusion (white arrow) in both patients. COVID-19 ¼ Coronavirus
Disease-2019; LGE ¼ late gadolinium enhancement; CMR ¼ cardiac magnetic resonance; PSIR ¼ phase-sensitive inversion recovery.

distribution was tested using Shapiro-Wilk test. RESULTS

Comparison between 2 groups were performed using
unpaired Student’s t-test (for normal distribution) or PATIENT CHARACTERISTICS. Clinical characteristics
Mann-Whitney U test (for non-normal distribution) and laboratory results of patients with COVID-19 are
with continuous variables, or chi-square test with reported in Table 1. A total of 26 patients (age
categorical variable. Comparisons among 3 groups 38 years; IQR: 32 to 45 years; 10 male) were enrolled
were performed using ordinary 1-way analyses of in this study based on the inclusion and exclusion
variance with Bonferroni corrected post hoc compar- criteria. Twenty healthy controls of similar age and
isons (for normal distribution) or Kruskal-Wallis tests gender distributions (age 40 years; IQR: 29 to 50
with post hoc pairwise comparisons (for non-normal years; 7 male) who previously underwent the same
distribution), as appropriate. p < 0.05 was consid- CMR examinations in our hospital were also included.
ered statistically significant. All patients reported contact with patients who were
6 Huang et al. JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2020
CMR Findings in Recovered COVID-19 - 2020:-–-

T A B L E 2 Left and Right Ventricular Cardiac CMR Parameters of Patients Recovered From COVID-19 and Controls

Conventional CMR Findings

Positive (n ¼ 15) Negative (n ¼ 11) Controls (n ¼ 20) Adjusted p Value† Adjusted p Value‡ Adjusted p Value§ p Value*

Age (yrs) 39 (29–49) 37 (34–39) 40 (29–50) 0.83 0.99 0.69 0.78

Male 4 (27) 6 (55) 7 (35) 0.30 0.50 0.88 0.34
CMR parameters
Left ventricle
EF (%) 60.7
6.4 64.3
5.8 63.0
8.9 0.30 0.65 0.86 0.40
EF<50% 1 (7) 0 (0) 0 (0) NA NA NA NA
EDV (ml) 71.6 (61.4–86.4) 78.2 (64.0–92.1) 86.1 (70.8–92.8) 0.59 0.30 0.91 0.31
ESV (ml) 28.7
8.6 28.2
7.9 30.3
10.3 0.98 0.89 0.81 0.80
SV (ml) 43.5
8.0 49.9
8.7 50.2
12.1 0.16 0.13 >0.99 0.10
CO (l/min) 3.0 (2.6–3.7) 3.7 (3.5–4.5) 3.5 (2.8–4.3) 0.05 0.88 0.32 0.05
Myo mass (g) 57.1
12.4 69.1
17.2 63.9
14.7 0.15 0.31 0.68 0.14
EDV/BSA (ml/m2) 43.9
10.7 44.1
6.7 47.3
10.1 >0.99 >0.99 0.93 0.49
ESV/BSA (ml/m2) 17.5
5.6 15.9
4.1 18.0
6.8 0.68 0.96 0.52 0.58
SV/BSA (ml/m2) 26.4
6.2 28.2
4.0 29.3
5.5 0.64 0.34 0.81 0.29
CI (l/min/m2) 1.9
0.5 2.3
0.4 2.0
0.5 0.15 0.84 0.30 0.19
Myo mass/BSA (g/m2) 34.3
7.1 38.7
6.6 37.4
7.1 0.26 0.41 0.87 0.24
Global T1 (ms) 1,271 (1,243–1,298) 1,237 (1,216–1,262) 1,224 (1,217–1,245) 0.03 0.002 >0.99 0.002
Global T2 (ms) 42.7
3.1 38.1
2.4 39.1
3.1 <0.001 0.005 0.57 <0.001
Global ECV (%) 28.2 (24.8–36.2) 24.8 (23.1–25.4) 23.7 (22.2–25.2) 0.12 0.001 0.84 0.002
Right ventricle
EF (%) 36. 5
6.1 41.1
8.6 46.1
12.0 0.31 0.01 0.38 0.01
EDV (ml) 73.0
15.1 80.6
19.9 81.2
18.0 0.54 0.40 >0.99 0.42
ESV (ml) 46.6
11.5 47.8
15.0 43.9
14$8 0.97 0.82 0.76 0.72
SV (ml) 26.4
6.1 32.8
8.9 36.4
11.3 0.13 0.01 0.61 0.01
CO (l/min) 1.9
0.5 2.6
0.8 2.6
1.0 0.05 0.046 0.98 0.03
EDV/BSA (ml/m2) 44.1
10.2 45.3
8.8 47.2
10.3 0.93 0.63 0.85 0.62
ESV/BSA (ml/m2) 28.1
7.8 26.9
7.4 26.0
9.3 0.91 0.74 0.95 0.74
SV/BSA (ml/m2) 15.9
3.6 18.4
4.2 21.3
5.7 0.26 0.01 0.28 0.01
CI (l/min/m2) 1.2
0.3 1.5
0.4 1.5
0.4 0.09 0.03 0.98 0.03

Values are median (25th-75th percentiles), n (%), or mean
SD. Bold indicates adjusted p < 0.05. *p value is for patients with positive conventional CMR findings vs. patients with negative conventional
CMR findings vs. controls. †Statistical difference between patients with positive and with negative conventional CMR findings. ‡Statistical difference between patients with positive conventional CMR
findings and controls. §Statistical difference between patients with negative conventional CMR findings and controls.
CI ¼ cardiac index; CO ¼ cardiac output; EF ¼ ejection fraction; EDV ¼ end-diastolic volume; ESV ¼ end-systolic volume; Myo ¼ myocardium; NA ¼ not applicable; SV ¼ stroke volume; other abbreviations
as in Table 1.

diagnosed with COVID-19 pneumonia. Twenty-two (IQR: 36 to 58 days). Precordial chest pain, palpita-
patients of 26 (85%) were diagnosed as having tion, and chest distress were reported in 3 (12%), 23
moderate-type COVID-19 pneumonia and 4 (15%) as (88%), and 6 (23%) patients, respectively. At admis-
having severe-type, according to the Diagnosis and sion, 13 of 26 patients had hs-cTnI measurement
Treatment Protocol of Novel Coronavirus issued by during COVID-19 hospitalization, with median (IQR)
the National Health Commission of the People’s Re- peak value of 2.2 (IQR: 1.9 to 2.6) pg/ml. The hs-cTnI
public of China (13). The median age of the patients was in the normal range for all recovered patients at
was 38 years (IQR: 32 to 45 years; range 25 to 60 the time of CMR (2.0 [IQR: 1.9 to 2.2] pg/ml).
years), and 10 (38%) were men. Two (8%) patients had
a history of hypertension before COVID-19. During MYOCARDIAL HISTOLOGICAL ABNORMALITIES
hospitalization due to COVID-19, all patients were USING CONVENTIONAL T2WI AND LGE SEQUENCES.
administered antiviral and antibiotic therapy, and A total of 416 myocardial segments of 26 patients
oxygen support was given to 21 (81%) patients. Anti- were analyzed. Fifteen patients of 26 (58%) were
viral drugs included Kaletra and Arbidol, and antibi- observed with increased T2 signal and/or positive
otics included moxifloxacin and cefoperazone LGE. Myocardial edema was found in 14 (14 of 26
sulbactam. The median duration from onset of car- [54%]) patients, involving 33% (137 of 416) of LV
diac symptoms to CMR examination was 47 days segments (Central Illustration, A). Among them, 7 (7 of
JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2020 Huang et al. 7
- 2020:-–- CMR Findings in Recovered COVID-19

F I G U R E 2 Cardiac Involvement in Patients Recovered From COVID-19 Identified Using Quantitative Cardiac CMR

STIR sequence PSIR sequence T1 map T2 map ECV map

A B C D E

STIR sequence PSIR sequence T1 map T2 map ECV map

F G H I J

A 60-year-old male patient (first row) underwent cardiac CMR 2 months after the onset of palpitations. Short-axis STIR sequence (A) showed no evidence of myocardial
edema. However, PSIR image (B) of the same slice showed focal LGE in the LV septal and inferior segments (black arrows). Increased native T1 (1,434
43 ms), ECV
(30
2%), and normal T2 values (38
2 ms) were shown in the corresponding location of focal LGE on the T1 (C), T2 (D), and ECV maps (E) (black arrows). A 29-year-
old female patient (second row) underwent cardiac CMR 1 and a half months after the onset of palpitations. Short-axis STIR (F) and PSIR sequence (G) showed global
myocardial signal hyperintensity but no apparent LGE, global T1, and ECV values were significantly increased on the T1 (H) and ECV maps (J). T2-mapping sequence
(I) showed increased T2 values at inferior septal (41
8 ms), anterior (41
6 ms), and inferior lateral segments (43
5 ms), which matched the location with
significantly increased signal intensity on short-axis STIR sequence (F) (white arrows). ECV ¼ extracellular volume; LV ¼ left ventricle; STIR ¼ short tau inversion
recovery; other abbreviations as in Figure 1.

14 [50%]) and 7 (7 of 14 [50%]) patients were positive findings and healthy controls (native T1
observed with positive LGE and a small pericardial 1,271 ms [1,243 to 1,298 ms] vs. 1,237 ms [1,216 to 1,262
effusion, respectively. One patient (1 of 15 [4%]) was ms] vs. 1,224 ms [1,217 to 1,245 ms]; T2 42.7
3.1 ms
observed with positive LGE but without obvious vs. 38.1
2.4 ms vs. 39.1
3.1 ms; ECV 28.2% [IQR:
myocardial edema. A total of 8 cases (8 of 26 [31%]) 24.8% to 36.2%] vs. 24.8% [IQR: 23.1% to 25.4%] vs.
showed focal linear subepicardial and patchy mid- 23.7% [IQR: 22.2% to 25.2%]; p ¼ 0.002; p < 0.001, and
wall LGE, involving 15 (15 of 416 [4%]) myocardial p ¼ 0.002, respectively). The T1, T2, and ECV values
segments (Central Illustration, B). The median of in the remote myocardium of the 8 LGE-positive pa-
LGE/myocardium ratio was 7.2% (IQR: 6.2% to 8.4%; tients were elevated compared with healthy controls
range 5.3% to 14.5%). Most LGE (9 of 15 [60%]) le- (native T1 1,259 ms [IQR: 1,248 to 1,296 ms] vs.
sions were located at inferior and inferior-lateral 1,224 ms [IQR: 1,217 to 1,245 ms]; T2 42.9
3.1 ms vs.
segments at base and mid-chamber (Figure 1). 39.1
3.1 ms; ECV 28.7%
5.1%; vs. 23.8
1.9%;
Eleven patients (11 of 26 [42%]) had no positive p ¼ 0.01; p ¼ 0.03, and p ¼ 0.03, respectively).
cardiac CMR findings on the conventional T2WI and LV/RV FUNCTION. LV and RV morphological and
LGE sequences. Among 13 patients with admission functional parameters are summarized in Table 2.
cTnI data, 8 (62%) patients had no positive con- There was no significant difference of LV function
ventional CMR findings, 3 patients had myocardial among controls and patients with and without
edema without apparent LGE, 1 patient had LGE positive findings on conventional CMR sequences.
without myocardial edema, and 1 had both LGE and Among patients with positive conventional CMR
myocardial edema. findings, only 1 (1 of 15 [7%]) patient showed
ELEVATED T1/T2/ECV VALUES ON QUANTITATIVE impaired left ventricular ejection fraction (LVEF
CMR MAPPING SEQUENCES. Global native T1, T2, 45%), with obviously reduced contraction in the
and ECV values all showed significantly elevated in myocardial segments with edema. However,
recovered COVID-19 patients with positive conven- decreased RV function parameters including right
tional CMR findings, compared with patients without ventricular ejection fraction (RVEF), CO, cardiac
8 Huang et al. JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2020
CMR Findings in Recovered COVID-19 - 2020:-–-

index (CI), SV, and SV/BSA were found in patients Eleven of 26 patients recovered from COVID-19
with positive conventional CMR findings, compared reported cardiac symptoms, but had no positive
with healthy controls (p < 0.05). There was no CMR findings either on conventional cardiac CMR
significant difference of RV function parameters sequences (cine, T2WI, and LGE) or quantitative
between patients with no positive CMR findings and mapping sequences (T1/T2/ECV mapping). There may
healthy controls (p > 0.05). be 2 reasons accounting for this phenomenon. First, it
is possible that the chest symptoms were caused by
DISCUSSION the residual pulmonary disease, but further study is
needed to confirm this. Second, because the median
In this study, we present an CMR study of 26 patients duration between clinical symptoms onset and CMR
who had recovered from COVID-19 but reported car- scan was as long as 50 days, the patients may have
diac symptoms. None of the 26 patients selected for had acute myocarditis but were imaged at the sub-
this retrospective analysis had known previous acute stage when edema already resolved. In either
myocarditis or other heart diseases before COVID-19. case, there is no sustained cardiac involvement in this
However, 15 of 26 patients showed myocardial patient subgroup.
edema and/or foci LGE lesion. The presence of It was previously reported that myocarditis and
myocardial tissue abnormalities in otherwise healthy cardiac arrhythmias may be induced by COVID-19
subjects suggests cardiac involvement as a lasting associated with a high inflammatory burden (22). An
consequence of SARS-CoV-2 infection. autopsy study had reported infiltration of myocardial
Myocardial edema and foci LGE lesion are the tissue by mononuclear inflammatory cells in a patient
major image manifestations on conventional cardiac with COVID-19 postmortem (23). Our study also
CMR sequences in our patient cohort. The majority of showed myocardial edema as the major image mani-
T2 signal hyperintensity was located in the inter- festation. Two pathological mechanisms may be
ventricular septum, anterior, anterior-lateral, and involved in post-COVID-19 myocardial involvement
inferior wall at the base and mid-chamber. The loca- (24). First, SARS-CoV-2 can directly cause myocardial
tion of edema caused by SARS-CoV-2 appeared inflammation because ACE2 receptor binding domain
different from those caused by acute viral myocar- of spike protein coding S is similar in SARS-CoV-2 as
ditis, which commonly involves inferior and inferior- in SARS-CoV, which was found to cause viral
lateral wall (14,15). However, some recovered patients myocarditis after infection (25). Second, indirect
had subepicardial LGE lesions at inferior and inferior- injury may be caused by an inflammatory storm
lateral wall, similar to common types of viral induced by the immune response (4).
myocarditis (inferior-lateral wall) (17). Pericardial Impaired RV function was found in the subgroup of
involvement is a complication of myocardial damage, post–COVID-19 patients who demonstrated cardiac
which was also found in a proportion of our cohort. involvement. Because RV mainly acts as a passive
Global T1, T2, and ECV values were significantly conduit in cardiac functioning, it is easily affected by
elevated in patients with COVID-19 with positive a slight increase in pulmonary vascular resistance
conventional cardiac CMR findings, compared with (26). Previous studies have reported RV failure in
patients without positive findings and healthy con- acute lung injury and acute respiratory distress syn-
trols (Figure 2). Also, elevated T1, T2, and ECV values drome (26,27). Because the lungs are the main target
were observed in the remote myocardium of LGE- organ of SARS-CoV-2, RV may be more susceptible to
positive patients, indicating diffuse involvement. impairment compared with LV.
Previous studies showed that elevated T2 suggested In our cohort, LVEF was in the normal range for all
myocardial edema (17,18), whereas elevated native T1 patients except one. Previous studies suggested that
and ECV suggested myocardial interstitial fibrosis myocardial tissue remodeling may precede functional
(19). Therefore, the results suggest the existence of remodeling in LV (28,29), and our results agree with
diffuse myocardial edema and fibrosis in patients the finding because abnormalities were identified
with positive conventional CMR findings. We note mostly in myocardial tissue instead of LV function.
that the range of ECV value in the healthy controls is This also indicates that the patients were in a rela-
lower than previously reported by Gottbrecht et al. tively early stage of cardiac involvement, and they
(20), but close to that by Xu et al. (21) in a Chinese need to be followed up in a longer study. Quantitative
cohort. cardiac CMR is a sensitive tool for early detection of
JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2020 Huang et al. 9
- 2020:-–- CMR Findings in Recovered COVID-19

cardiac involvement, and it can also be used to professionalism, dedication, and courage in the face
monitor further progress. of the COVID-19 outbreak.

STUDY LIMITATIONS. First, the sample size was ADDRESS FOR CORRESPONDENCE: Professor Liming
small, limited by the current capacity of medical re- Xia, Department of Radiology, Tongji Hospital, Tongji
sources in the epidemic area. Second, most included Medical College, Huazhong University of Science and
patients had moderate COVID-19 previously, there- Technology, Jiefang Ave 1095, 430030 Wuhan, China.
fore, our report cannot reflect the full spectrum E-mail: [email protected] OR xialiming2017@
covering patients with severe and critical COVID-19. outlook.com. OR Dr. Qian Tao, Division of Imaging
With both limitations, the reported proportion of Processing, Department of Radiology, Leiden Uni-
cardiac involvement is limited to the present study versity Medical Center, Albinusdreef 2, 2333 ZA Lei-
and cannot be extrapolated to a larger population. den, the Netherlands. E-mail: [email protected]. OR
Nevertheless, this study demonstrates the phenom- Professor Hesong Zeng, Department of Cardiology,
enon of post–COVID-19 cardiac involvement, and the Tongji Hospital, Tongji Medical College, Huazhong
findings can be useful because cardiac involvement University of Science and Technology, Jiefang Ave
may be more easily overlooked in patients with mild 1095, 430030 Wuhan, China. E-mail: zenghs@tjh.
SARS-CoV-2 infection. Last, we only had a 1–time tjmu.edu.cn.
point CMR examination, whereas longitudinal follow-
ups will be valuable to confirm if the cardiac
PERSPECTIVES
involvement will progress or regress.

CONCLUSIONS COMPETENCY IN MEDICAL KNOWLEDGE: CMR is a sensi-

tive and quantitative imaging tool to study early cardiac
There may be sustained cardiac involvement in pa- involvement. Our results showed that CMR was able to identify
tients recovered from COVID-19, as demonstrated by fibrosis and edema on the myocardium in a proportion of the
our cardiac CMR study. Major CMR manifestation patients recovered from COVID-19. Impaired RV function was
included edema, fibrosis, and impaired RV contractile also observed this patient subgroup.
function. The cardiac status of patients with COVID-
19 and survivors needs to be closely monitored; car- TRANSLATIONAL OUTLOOK: Attention needs to be paid to
diac CMR can be a sensitive imaging tool in combi- the potential cardiac involvement and negative consequences in
nation with laboratory tests for identifying cardiac patients recovered from COVID-19. This is a relatively short-term
involvement in patients with COVID-19. small-cohort study; longitudinal follow-ups in a larger cohort are
needed to confirm the prognosis value of cardiac CMR for pa-
ACKNOWLEDGEMENTS We thank all colleagues who
tients recovered from COVID-19.
contributed to the present study. We are especially
grateful to our frontline medical staff for their

REFERENCES

1. World Health Organization. WHO Director- 5. Wang D, Hu B, Hu C, et al. Clinical characteris- 10. Amano Y, Aita K, Yamada F, Kitamura M,
General’s opening remarks at the media briefing tics of 138 hospitalized patients with 2019 Novel Kumita S. Distribution and clinical significance of
on COVID-19 - 30 March 2020. World Health Or- Coronavirus-infected pneumonia in Wuhan, China. high signal intensity of the myocardium on T2-
ganization. Available at: https://www.who.int/dg/ JAMA 2020;323:1601–9. weighted images in 2 phenotypes of hypertro-
speeches/detail/who-director-general-s-opening- phic cardiomyopathy. J Comput Assist Tomogr
6. Knockaert DC. Cardiac involvement in systemic
remarks-at-the-media-briefing-on-covid-19—30- 2015;39:951–5.
inflammatory diseases. Eur Heart J 2007;28:
march-2020. Accessed March 30, 2020.
1797–804. 11. Ho CY, Day SM, Colan SD, et al. The burden of
2. Shi H, Han X, Jiang N, et al. Radiological find- 7. Friedrich MG, Sechtem U, Schulz-Menger J, early phenotypes and the influence of wall thick-
ings from 81 patients with COVID-19 pneumonia in et al. Cardiovascular Magnetic Resonance in ness in hypertrophic cardiomyopathy mutation
Wuhan, China: a descriptive study. Lancet Infect Myocarditis: A JACC White Paper. J Am Coll Car- carriers. JAMA Cardiol 2017;2:419.
Dis 2020;3099:1–10. diol 2009;53:1475–87. 12. Tao A, Zhenlu Y, Hongyan H, et al. Correlation
3. Patel VB, Basu R, Oudit GY. ACE2/Ang 1-7 axis: a 8. Ferreira VM, Schulz-Menger J, Holmvang G, of chest CT and RT-PCR testing in Coronavirus
critical regulator of epicardial adipose tissue et al. Cardiovascular magnetic resonance in non- Disease 2019 (COVID-19) in China: a report of 1014
inflammation and cardiac dysfunction in obesity. ischemic myocardial inflammation: expert recom- Cases. Radiology 2020;296:E32–40.
Adipocyte 2016;5:306–11. mendations. J Am Coll Cardiol 2018;72:3158–76.
13. National Health Commission of the People’s
4. Huang C, Wang Y, Li X, et al. Clinical fea- 9. Kammerlander AA, Marzluf BA, Zotter-Tufaro C, Republic of China. Diagnosis and Treatment
tures of patients infected with 2019 novel et al. T1 mapping by CMR imaging: from histo- Protocol of Novel Coronavirus (trial version
coronavirus in Wuhan, China. Lancet 2020; logical validation to clinical implication. J Am Coll 7th). National Health Commission of the Peo-
6736:1–10. Cardiol Img 2016;9:14–23. ple’s Republic of China Website. Available at:
10 Huang et al. JACC: CARDIOVASCULAR IMAGING, VOL. -, NO. -, 2020
CMR Findings in Recovered COVID-19 - 2020:-–-

http://www.nhc.gov.cn/yzygj/s7653p/202003/ hypertensive heart disease and hypertrophic and inflammation in patients with SARS. Eur J Clin
46c9294a7dfe4cef80dc7f5912eb1989.shtml. cardiomyopathy: findings from the International Invest 2009;39:618–25.
Accessed March 4, 2020. T1 Multicenter Cardiovascular Magnetic Reso-
26. Repessé X, Charron C, Vieillard-Baron A. Right
nance Study. Circ Cardiovasc Imaging 2015;8:
14. Luetkens JA, Doerner J, Thomas DK, et al. ventricular failure in acute lung injury and acute
e003285.
Acute myocarditis: multiparametric cardiac MR respiratory distress syndrome. Minerva Anestesiol
imaging. Radiology 2014;273:383–92. 20. Gottbrecht M, Kramer CM, Salerno M. Native 2012;78:941–8.
T1 and extracellular volume measurements by
15. Chaikriangkrai K, Abbasi MA, Sarnari R, et al. 27. Osman D, Monnet X, Castelain V, et al. Inci-
cardiac MRI in healthy adults: a meta-analysis.
Prognostic value of myocardial extracellular vol- dence and prognostic value of right ventricular
Radiology 2019;290:317–26.
ume fraction and T2-mapping in heart transplant failure in acute respiratory distress syndrome.
patients. J Am Coll Cardiol Img 2020;13:1521–30. 21. Xu J, Zhuang B, Sirajuddin A, et al. MRI T1 Intensive Care Med 2009;35:69–76.
mapping in hypertrophic cardiomyopathy: evalu- 28. Huang L, Ran L, Zhao P, et al. MRI native T1
16. Bohnen S, Radunski UK, Lund GK, et al. Per-
ation in patients without late gadolinium and T2 mapping of myocardial segments in hy-
formance of T1 and T2 mapping cardiovascular
enhancement and hemodynamic obstruction. pertrophic cardiomyopathy: tissue remodeling
magnetic resonance to detect active myocarditis in
Radiology 2020;294:275–86. manifested prior to structure changes. Br J Radiol
patients with recent-onset heart failure. Circ Car-
diovasc Imaging 2015;8:e003073. 22. Madjid M, Safavi-Naeini P, Solomon SD, 2019;92:20190634.
Vardeny O. Potential effects of coronaviruses on 29. Florian A, Ludwig A, Rö Sch S, Yildiz H,
17. Li H, Zhu H, Yang Z, Tang D, Huang L, Xia L.
the cardiovascular system: a review. JAMA Cardiol Sechtem U, Yilmaz A. Myocardial fibrosis imaging
Tissue characterization by mapping and strain
2020 Mar 27 [E-pub ahead of print]. based on T1-mapping and extracellular volume
cardiac MRI to evaluate myocardial inflammation
in fulminant myocarditis. J Magn Reson Imaging 23. Xu Z, Shi L, Wang Y, et al. Case report patho- fraction (ECV) measurement in muscular dystro-
2020 Feb 20 [E-pub ahead of print]. logical findings of COVID-19 associated with acute phy patients: diagnostic value compared with
respiratory distress syndrome. Lancet Respir conventional late gadolinium enhancement (LGE)
18. Dolan RS, Rahsepar AA, Blaisdell J, et al.
2020;8:420–2. imaging. Eur Heart J Cardiovasc Img 2014;15:
Multiparametric cardiac magnetic resonance can
1004–12.
detect acute cardiac allograft rejection after heart 24. Zheng Y, Ma Y, Zhang J, Xie X. COVID-19 and
transplantation. J Am Coll Cardiol Img 2019;12: the cardiovascular system. Nat Rev Cardiol 2020;
1632–41. 17:259–60.
KEY WORDS cardiac involvement, cardiac
19. Hinojar R, Varma N, Child N, et al. T1 mapping 25. Oudit GY, Kassiri Z, Jiang C, et al. SARS-coro- magnetic resonance imaging, coronavirus
in discrimination of hypertrophic phenotypes: navirus modulation of myocardial ACE2 expression disease-2019