COVID: cardiac injury common

A recent study from Wuhan found that markers of cardiac injury were common and associated with increased mortality (see covid cardiac injury inc mortality jamacard2020 in dropbox, or doi:10.1001/jamacardio.2020.0950)

Details:

-- over a three-week period in January 2020, a single hospital assessed 416 consecutive hospitalized patients with Covid

-- median age 64, 51% female

-- symptoms in whole sample: fever in 80%, cough in 35%, shortness of breath in 28%, fatigue in 13%

-- lab tests assessed: leukocyte count, C-reactive protein, pro-calcitonin, CK-MB, high-sensitivity troponin-1, BNP, AST, creatinine; also chest x-ray

-- cardiac injury was defined as increased high-sensitivity troponin-1, above the 99^th percentile of the upper reference limit, independent of EKG and echocardiography

Results:

-- 82 patients (20%) had evidence of cardiac injury

    -- overall, patients were older (74 vs 60 years old, p<0.001)

    -- and had more comorbidities: hypertension in 60% vs 23%, p<0.001

-- symptom differences: the only significant one was chest pain in 13% with cardiac injury and 1% without

--differences in laboratory parameters (will comment only on major clinically useful differences):

    -- leukocyte count: 9400 vs 5500

    -- CRP: 10 vs 4 mg/dL

    -- CK-MB: 3.2 vs 0.9 ng/mL

    -- high-sensitivity troponin-1: 0.19 vs <0.006 mcg/mL

    -- N-terminal pro-B-type natriuretic peptide: 1689 vs 139 pg/mL

    -- CXR: multiple mottling and ground-glass opacity: 65% vs 5%; though there was less unilateral pneumonia, 9% vs 29%

-- non-invasive mechanical ventilation: 46% with cardiac injury vs 4% without, p<0.001

-- invasive mechanical ventilation: 22% vs 4%, p<0.001

-- complications in those with cardiac injury vs not:

    -- ARDS 59% vs 15% , p<0.001

    -- acute kidney injury 9% vs 0.3%, p<0.001

    -- electrolyte disturbances 16% vs 5%, p=0.003

    -- hypokalemia: 13% vs 5%, p=0.01

    -- coagulation disorders: 7% vs 2%, p=0.02

-- those with cardiac vs without had a higher risk of death:

    -- mortality: 51% vs 5%, p<0.001: and controlling for age, pre-existing cardiovascular diseases including hypertension, cerebrovascular disease, diabetes, COPD, renal failure, cancer, ARDS, increased creatinine and increased NT-Pro-BNP:

        -- 4 times as high during time from symptom onset: HR 4.26 (1.92-9.49)

        -- 3 times as high from hospital admission: HR 3.41 (1.62-7.16)

    -- in those with cardiac injury, mortality was a mean of 16 days from symptom onset and 6 days from admission

    -- in those without cardiac injury, mortality was 17 days from symptom onset and 8 days from admission

Commentary:

-- at the time of the study, there were more than 130,000 laboratory-confirmed cases of Covid, and more than 80,000 in China

-- this study found that cardiac injury was common (20% patients), associated with a high death rate even after multivariate adjustment

-- though there was a low threshold to hospitalize patients in China, it was notable that only 35% had a cough and 80% had a fever. Also only 28% had shortness of breath. [ie, even hospitalized patients there mostly did NOT have a cough and 1/5 did NOT have a fever]

-- a small, 41 patient Chinese study also found a 12% of patients with Covid had evidence of acute cardiac injury (undefined abnormalities in EKG and echocardiogram, and increased troponin-1), see doi:10.1016/S0140-6736(20)30183-5.

-- there also may be more of cases of COVID-associated myocarditis (see http://gmodestmedblogs.blogspot.com/2020/03/covid-myocarditis.html)

-- it is unclear exactly what the relationship is between the virus and cardiac injury, with several possibilities or combinations of possibilities.

    -- those with cardiac injury are older, with likely more the existing cardiovascular disease, other comorbidities, and alterations in their immunologic function

    --ACE2 levels are higher in the heart (see http://gmodestmedblogs.blogspot.com/2020/03/covid-ace2-ibuprofen-and-grasping-for.html and http://gmodestmedblogs.blogspot.com/2020/03/covid-ace2-more-info.html), so there could be a direct viral myocardial invasion

    -- in this study, a higher number of patients with cardiac injury had known pre-existing cardiovascular disease (30%) and hypertension (60%), likely predisposing them to cardiac injury

    -- unclear role of the cytokine storm, associated with lots of systemic inflammation (and the study found high levels of inflammatory markers such as CRP, Pro calcitonin, and white cell counts). Perhaps this inflammation is related to the left ventricular dysfunction. Or perhaps acute inflammation leads to ischemia in those with pre-existing cardiovascular disease (in this study there was a higher incidence of pre-existing cardiovascular disease; and, with the increased age, there is likely more undiagnosed cardiovasc disease)

-- Limitations of the study:

    -- this was an observational study. It is difficult therefore to tease out which factors actually increased mortality. For example there was a difference in therapies in this study: similar numbers were given antiviral treatments, but in those with cardiac injury there were more glucocorticoids (89% vs 70%), intravenous immunoglobulin (83% vs 57%), and antibiotic therapy (3% vs 50%). ? What role do these play? positive or negative??

    -- there were no echocardiograms or cardiac MRIs done to evaluate cardiac function directly. In addition only 22 EKGs were performed after admission and only 14 of them, all abnormal, performed during the periods of elevated cardiac biomarkers.

so, 

--it does seem that cardiac injury is common with COVID. some anecdotal analyses i have seen suggest that a large percent of those dying in fact seemed to be related to acute cardiac events (arrhythmias etc) vs respiratory failure from ARDS or pneumonia.  

--it seems reasonable to check cardiac injury markers (esp high-sensitivity troponins and BNP assays) routinely on very sick patients, even without history of heart disease, and have a very low threshold to assess cardiac funtion with an echo, since the approach to treatment may be altered

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will add: i got the following message from Faisal Rahman, and interventional cardiology fellow at Hopkins (included with his permission):

Dear Geoff,

There is not a lot that seems to be clearly known about CoViD-19 and cardiac effects. In addition to fulminant myocarditis you present below, the presentation has triggered emergent cath for ST elevation which can sometimes appear to be in a anatomical distribution. For certain field cases we have used PPE empirically when history has been unclear.

Your readers might also want to watch: youtu.be/pmrrc2qkGvo

geoff​

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