In the epicenter of the current Italian epidemic, sudden cardiac death (SCD) likely occurred in many non-hospitalized patients with mild symptoms who were found dead home while in quarantine.

ompared with patients without cardiac injury, patients with cardiac injury presented with more severe acute illness, manifested by abnormal laboratory and radiographic findings, such as higher levels of C-reactive protein, NT-proBNP, and creatinine levels; more multiple mottling and ground-glass opacity; and a greater proportion requiring noninvasive or invasive ventilation.

Consistently, our study also found 19.7% of patients with cardiac injury and first demonstrated that cardiac injury was independently associated with an increased risk of mortality in patients with COVID-19.

After adjusting for age, preexisting cardiovascular diseases (hypertension, coronary heart disease, and chronic heart failure), cerebrovascular diseases, diabetes mellitus, chronic obstructive pulmonary disease, renal failure, cancer, ARDS, creatinine levels greater than 133 μmol/L, and NT-proBNP levels greater than 900 pg/mL, the multivariable adjusted Cox proportional hazard regression model showed a significantly higher risk of death in patients with cardiac injury than in those without cardiac injury, either during time from symptom onset (hazard ratio [HR], 4.26 [95% CI, 1.92-9.49]) or time from admission to study end point (HR, 3.41 [95% CI, 1.62-7.16]) (Table 3).

The mortality rate was higher among patients with vs without cardiac injury (42 [51.2%] vs 15 [4.5%]; P < .001) as shown in Table 2 and the Kaplan-Meier survival curves in Figure 2. The mortality rate increased in association with the magnitude of the reference value of hs-TNI

Patients with cardiac injury vs those without cardiac injury had shorter durations from symptom onset to follow-up (mean, 15.6 [range, 1-37] days vs 16.9 [range, 3-37] days; P = .001) and admission to follow-up (6.3 [range, 1-16] days vs 7.8 [range, 1-23] days; P = .039).

In terms of radiologic findings, bilateral pneumonia (75 of 82 patients [91.5%] vs 236 of 334 patients [70.7%]) and multiple mottling and ground-glass opacity (53 [64.6%] vs 15 [4.5%]) were more prevalent in patients with than those without cardiac injury (both P < .001, Table 1).

The duration of hospitalization before testing was longer in patients with cardiac injury than those without cardiac injury (median [range] time, 3 [1-15] days vs 2 [1-8] days; P < .001).

Thus, because of the current limited evidence, the question of whether the SARS-CoV-2 virus can directly injure the heart requires further demonstration.

Greater proportions of patients with cardiac injury required noninvasive mechanical ventilation (38 of 82 [46.3%] vs 13 of 334 [3.9%]; P < .001) or invasive mechanical ventilation (18 of 82 [22.0%] vs 14 of 334 [4.2%]; P < .001) than those without cardiac injury.

The most common cause of death in 81 of the 85 patients was respiratory failure (38, 46.91%), followed by septic shock (16, 19.75%), multiple organ failure (13, 16.05%) and cardiac arrest (7, 8.64%).

The clinical effects of pneumonia have been linked to increased risk of cardiovascular disease up to 10-year follow-up16 and it is likely that cases infected via respiratory virus outbreaks will experience similar adverse outcomes. Therapeutic use of corticosteroids further augments the possibility of adverse cardiovascular events. However, long-term follow-up data concerning the survivors of respiratory virus epidemics are scarce. Lipid metabolism remained disrupted 12 years after clinical recovery in a metabolomic study amongst 25 SARS survivors,17 whereas cardiac abnormalities observed during hospitalisation in eight patients with H7N9 influenza returned to normal at 1-year follow-up.

CMR (day 7) showed a recovery of systolic function (from 52% by CTA to 64% by CMR), although with persistence of a mild hypokinesia at basal and mid left ventricular segments; at the same sites, diffuse myocardial oedema, determining wall pseudo-hypertrophy, was observed on short T1 inversion recovery (STIR) sequences (Panel D) and confirmed by T1 and T2 mapping (average native T1 = 1188 ms, normal value <1045; average T2 = 61 ms, normal value <50). Late gadolinium enhancement sequences demonstrated absence of detectable myocardial scar/necrotic foci.

While the spectrum of clinical manifestation is highly related to the inflammation process of the respiratory tract, this case provides evidence of cardiac involvement as a possible late phenomenon of the viral respiratory infection. This process can be subclinical with few interstitial inflammatory cells, as reported by an autopsy study,10 or can present with overt manifestations even without respiratory symptoms, as in the present case.

Chest radiography was repeated on day 4 and showed no thoracic abnormalities. Transthoracic echocardiography, performed on day 6, revealed a significant reduction of LV wall thickness (interventricular septum, 11 mm; posterior wall, 10 mm), an improvement of LVEF to 44%, and a slight decrease of pericardial effusion (maximum, 8-9 mm). At the time of submission, the patient was hospitalized with progressive clinical and hemodynamic improvement.

Transthoracic echocardiography revealed normal left ventricular (LV) dimensions with an increased wall thickness (interventricular septum, 14 mm, posterior wall, 14 mm) and a diffuse echo-bright appearance of the myocardium. There was diffuse hypokinesis, with an estimated LV ejection fraction (LVEF) of 40%. There was no evidence of heart valve disease. Left ventricular diastolic function was mildly impaired with mitral inflow patterns, with an E/A ratio of 0.7 and an average E/e′ ratio of 12. There was a circumferential pericardial effusion that was most notable around the right cardiac chambers (maximum, 11 mm) without signs of tamponade. Cardiac magnetic resonance imaging (MRI) confirmed the increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, and severe LV dysfunction (LVEF of 35%) (Video 1 and Video 2). Short tau inversion recovery and T2-mapping sequences showed marked biventricular myocardial interstitial edema. Phase-sensitive inversion recovery sequences showed diffuse late gadolinium enhancement extended to the entire biventricular wall (Figure 2). The myocardial edema and pattern of late gadolinium enhancement fulfilled all the Lake Louise criteria for the diagnosis of acute myocarditis.6 The circumferential pericardial effusion was confirmed, especially around the right cardiac chambers (maximum, 12 mm).

Cardiac magnetic resonance imaging showed increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, and severe left ventricular dysfunction (left ventricular ejection fraction of 35%). Short tau inversion recovery and T2-mapping sequences showed marked biventricular myocardial interstitial edema, and there was also diffuse late gadolinium enhancement involving the entire biventricular wall. There was a circumferential pericardial effusion that was most notable around the right cardiac chambers. These findings were all consistent with acute myopericarditis.

The data again showed a significant higher incidence of acute cardiac injury in ICU/severe patients compared to the non-ICU/severe patients [RR = 13.48, 95% CI (3.60, 50.47), Z = 3.86, P = 0.0001]

Two studies that gave clear data were statistically analyzed, and the data showed that 8.0% (95% CI 4.1–12.0%) patients might be suffered from an acute cardiac injury.

Among survivors, secondary infection, acute kidney injury, and acute cardiac injury were observed in one patient each, occurring 9 days (acute kidney injury), 14 days (secondary infection), and 21 days (acute cardiac injury) after illness onset.

Heart failure44 (23%)28 (52%)16 (12%)<0·0001Septic shock38 (20%)38 (70%)0<0·0001Coagulopathy37 (19%)27 (50%)10 (7%)<0·0001Acute cardiac injury33 (17%)32 (59%)1 (1%)<0·0001Acute kidney injury28 (15%)27 (50%)1 (1%)<0·0001

Cardiac injury3 (15%)9 (28%)12 (23%)

By Jan 26, 2020, 710 patients had been admitted to Wuhan Jin Yin-tan hospital with confirmed SARS-CoV-2 pneumonia, of whom 658 (93%) were considered ineligible, including three patients who had cardiac arrest immediately after admission.

When Ace2 is transgenically overexpressed in mouse heart, cardiac defects are again observed, most notably a lethal ventricular arrhythmia, which is associated with disruption of gap junction formation [9Donoghue M et al.Heart block, ventricular tachycardia, and sudden death in ACE2 transgenic mice with downregulated connexins.J. Mol. Cell. Cardiol. 2003; 35: 1043-1053Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar]. The high incidence of sudden death in these mice correlated with the levels of Ace2 transgene expression. Surviving older mice showed a spontaneous downregulation of the transgene and restoration of normal cardiac function.

Common complications among the 138 patients included shock (12 [8.7%]), ARDS (27 [19.6%]), arrhythmia (23 [16.7%]), and acute cardiac injury (10 [7.2%]). Patients who received care in the ICU were more likely to have one of these complications than non-ICU patients.