COVID: ?longterm cardiac and neuro effects

 A recent article examined some potential long-term cardiac problems from Covid-19 infection (see covid myocardial injury jacc2020 in dropbox, or doi.org/10.1016/j.jacc.2020.08.069) 

 

Details: 

-- 305 patients from 7 hospitals in New York City and Milan who had PCR-positive Covid-19 infection as well as transthoracic echocardiographic (TTE) and electrocardiographic evaluation, from March to May 2020 

--190 had myocardial injury (defined as any elevation of cardiac troponin above the normal reference limits either at the time of clinical presentation or during hospitalization), 115 did not

-- mean age 63 (those with myocardial injury were older: 66 vs 58), 67% male, 57% white/14% black/9% Asian/27% Hispanic, BMI 28 

-- underlying medical problems without significant difference between those with and without myocardial injury: prior MI 7%, prior PCI 11%, prior stroke 10%, COPD 6%, history of atrial fibrillation 10%, asthma 9%, history of heart failure 8%

-- significantly more common in those with myocardial injury: hypertension 59% (68% vs 44% in those with vs without myocardial injury), diabetes 37% (42% vs 30%), CKD 19% (26% vs 9%) 

-- Covid symptoms: shortness of breath 60%, cough 59%, fever 53%, myalgia 22%, chest pain 17%, dizziness 7%, nausea or vomiting 13%, diarrhea 15%. 

-- assessment was 5 days from symptom onset

-- median hospital stay was 14 days (including time to discharge or death) 

-- laboratory tests in patients with myocardial injury vs those without (all statistically highly significant differences): 

    -- peak troponin I: 0.46 vs 0.01 ng/mL 

    -- high-sensitivity peak troponin T: 63 vs 9 mg/mL 

        -- time to peak troponin level was 5 days 

    -- BNP: 437 vs 59 pg/mL 

    -- CRP: 240 vs 170 mg/L 

    -- peak IL-6: 116 vs 58 pg/mL 

    -- peak LDH: 763 vs 445 units/L 

    -- d-dimer: 3.7 vs 1.5 µg/mL 

-- myocardial injury: 118 had myocardial injury at the time of admission, 72 developed injury during the hospitalization  

-- primary clinical endpoints: in-hospital all-cause mortality 

-- additional endpoints: admission to the ICU, need for mechanical ventilation, ARDS, stroke, AKI, shock, ventricular fibrillation or tachycardia 

-- covariates included in adjusted model: age, sex, race, Hispanic ethnicity, history of heart disease, ARDS, AKI stage 2 or 3, cardiocirculatory shock, myocardial injury, and hospital identifier 

-- differences in in-hospital treatments: those with myocardial injury were more likely to have gotten glucocorticoids (50% vs 36%), anticoagulation (64% vs 41%), unfractionated heparin (26% vs 11%) and less likely to have been given hydroxychloroquine (69% vs 82%) 

 

Results: 

-- compared to patients without myocardial injury, those with injury had (all statistically significant): 

    -- higher inflammatory biomarkers, as noted above 

    -- increased prevalence of major TTE abnormalities (overall 63% vs 22%) 

        --LVEF: <40 (21% vs 1%), 40-49 (14% vs 9%) 

        -- left ventricular wall motion abnormalities: 24% vs 4%  

        -- global left ventricular dysfunction: 18% vs 8% 

        -- left ventricular diastolic dysfunction grade 2: 14% vs 2%, grade 3: 8% vs 0 

        -- right ventricular dysfunction: normal 73% vs 89%, mildly abnormal 15% vs 9%, moderately abnormal 10% vs 2% 

        -- pericardial effusion: small 8% vs 0 

    -- increased EKG abnormalities: 

        -- patients with chest pain had more ST-segment changes, and those with regional ST-segment changes had higher troponin levels

-- catheterization: performed only in 11 patients, 8 had confirmed acute coronary syndromes (7 with total thrombotic occlusion of a major epicardial artery requiring PCI), 3 with normal coronaries 

-- association between TEE and EKG: 

    -- those with wall motion abnormalities were more likely to have regional ST-segment changes vs diffuse changes (64% vs 25%), less likely to have global LV dysfunction (0% vs 63%), and more likely to have normal RV size (86 % vs 43%) and normal RV function (86% vs 29%) 

 

-- rates of in-hospital mortality: 

    -- patients without myocardial injury: 5.2% 

    -- patients with myocardial injury without TTE abnormalities: 18.6% 

    -- patients with myocardial injury and TTE abnormalities: 31.7% 

    -- only the latter significant after multivariable adjustment, with OR 3.87 (1.27-11.80) 

 

-- In-hospital outcomes (all highly statistically significant): higher ICU admission (52% vs 30%), mechanical ventilation (43% vs 20%,), ARDS (49% vs 27%), AKI (50% vs 14%), shock (38% vs 12%) 

 

Commentary: 

-- this study reinforces that patients who have high troponin levels are at high risk for abnormal echocardiograms and EKGs. 

    --though 22% of those without abnormal troponin levels had abnormal TTEs

-- The study also found that patients with high troponins and abnormal TTEs are at very high risk for much more severe disease and bad outcomes, such as in-hospital mortality

-- the data from other studies are quite mixed on the incidence of myocardial injury in patients hospitalized with Covid-19 infections, with numbers in the 7% to 40% range 

 

limitations: 

--this was not a systematic study of all patients admitted to the hospital with Covid-19 infection, so results cannot be generalized to the general population of those infected 

-- each hospital had independent criteria. Including differences in cutpoints for elevated troponin levels 

-- it is not clear whether these echocardiographic changes will persist.  perhaps get better?, or perhaps lead to long-term problems with cardiomyopathy, for example 

-- we do not have a clear idea as to why patients were selected to have these studies in the different hospitals. Was it everyone with high troponin levels in some hospitals? Or other inflammatory markers? Perhaps at the interest/whim of their individual providers? And who were the 115 patients who had these cardiac studies but did not have prior evidence of myocardial damage? why did they get these cardiac studies?

-- Also, we do not have a good baseline in general. Were these TTE changes new? Or do they reflect old cardiac damage? They did find that 22% without covid-related myocardial injury had abnormal TTEs...

So, a few things: 

-- this study adds to the cumulative data of potential long-term problems from Covid-19 infection: eg,  increasing concern that there may be significant Covid-related cardiac dysfunction in the future, including progressive cardiomyopathy. 

-- Given the very high mortality in those with significant myocardial injury associated with TTE abnormalities, about 1/3 of patients, TTE may be a useful prognostic test that could lead to earlier and more aggressive Covid therapies (as they become more available), esp in those with evidence of cardiac injury (increased troponins)

-- and, given the large Covid surge we are entering with more than 100,000 new cases per day in the US, if even 10% of those hospitalized had high troponin levels, and, as in the study, 60+% of those with myocardial injury had abnormal TEEs, we may be seeing many, many people who have short-term and/or long-term cardiac problems. 

prior relevant blogs:

http://gmodestmedblogs.blogspot.com/2020/03/covid-cardiac-injury-common.html : 20% of 416 consecutive patients in China had evidence of cardiac injury, found more in those with hypertension (as in the current study); and those with cardiac injury had hugely increased mortality (51% vs 5%)

http://gmodestmedblogs.blogspot.com/2020/03/covid-myocarditis.html : case of fulminant myocarditis with covid

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As a related issue, another study found that 3 months after a Covid-19 infection, there were important MRI-documented cerebral changes (see covid neuro changes recovered pts eclinmed2020 in dropbox, or doi.org/10.1016/j.eclinm.2020.100484)

Briefly, 

--60 people who had recovered from Covid-19 (all PCR-positive) had detailed assessment of their CNS for microstructural changes by MR imaging, compared with age- and sex-matched controls in a prospective study (these patients were recruited without regard to their clinical presentations) 

    --57% male, mean age 46

--during the Covid-19 infections, 41 of the 60 (68%) had neurologic symptoms: mood change in 42%, fatigue in 27%, headache 25%, vision changes 22%, myalgia 15%, impaired mobility 12%, memory loss 13%, taste loss/limb numbness/tremor/smell loss/hearing loss all in <10% 

--neurologic symptoms were present in 55% on follow-up 3 months later 

--no significant difference was found between patients with severe vs non-severe Covid-19 symptoms overall, with some exceptions 

--imaging studies found: significantly higher bilateral gray matter volumes in the olfactory cortices, hippocampi, insulars, left Rolandic operculum, left Heschl's gyrus and right cingulate gyrus, and a decline in mean diffusivity, axial diffusivity, and radial diffusivity but increase in fractional anisotropy in the white matter. 

--these changes correlated with memory loss, smell loss, and LDH levels (a marker of tissue breakdown, and found in those with encephalitis) 

so, again, not sure how this will play out in the future (though pretty scary that these MRI changes were so pervasive and present 3 months later). 

geoff

 

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