Long-term cardiac pathology in individuals with mild initial COVID-19 illness, 2022, Puntmann et al

[SNT Gatchaman]

Long-term cardiac pathology in individuals with mild initial COVID-19 illness
Valentina O. Puntmann, Simon Martin, Anastasia Shchendrygina, Jedrzej Hoffmann, Mame Madjiguène Ka, Eleni Giokoglu, Byambasuren Vanchin, Niels Holm, Argyro Karyou, Gerald S. Laux, Christophe Arendt, Philipp De Leuw, Kai Zacharowski , Yascha Khodamoradi, Maria J. G. T. Vehreschild, Gernot Rohde, Andreas M. Zeiher, Thomas J. Vogl, Carsten Schwenke, Eike Nagel

Cardiac symptoms are increasingly recognized as late complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in previously well individuals with mild initial illness, but the underlying pathophysiology leading to long-term cardiac symptoms remains unclear.

In this study, we conducted serial cardiac assessments in a selected population of individuals with Coronavirus Disease 2019 (COVID-19) with no previous cardiac disease or notable comorbidities by measuring blood biomarkers of heart injury or dysfunction and by performing magnetic resonance imaging. Baseline measurements from 346 individuals with COVID-19 (52% females) were obtained at a median of 109 days (interquartile range (IQR), 77–177 days) after infection, when 73% of participants reported cardiac symptoms, such as exertional dyspnea (62%), palpitations (28%), atypical chest pain (27%) and syncope (3%).

Symptomatic individuals had higher heart rates and higher imaging values or contrast agent accumulation, denoting inflammatory cardiac involvement, compared to asymptomatic individuals. Structural heart disease or high levels of biomarkers of cardiac injury or dysfunction were rare in symptomatic individuals.

At follow-up (329 days (IQR, 274–383 days) after infection), 57% of participants had persistent cardiac symptoms. Diffuse myocardial edema was more pronounced in participants who remained symptomatic at follow-up as compared to those who improved. Female gender and diffuse myocardial involvement on baseline imaging independently predicted the presence of cardiac symptoms at follow-up.

Ongoing inflammatory cardiac involvement may, at least in part, explain the lingering cardiac symptoms in previously well individuals with mild initial COVID-19 illness.

Link | PDF (Nature Medicine)

 

[SNT Gatchaman]

In univariate analyses, female gender, small LV volumes and mass and native T1 at baseline were associated with symptomatic status at follow-up. In the final multivariate model, female gender and increased native T1 at baseline independently predicted the presence of cardiac symptoms at follow-up.

Our findings suggest that persistent cardiac symptoms in previously well, home-isolated individuals may, at least in part, relate to mild chronic inflammatory cardiac involvement in the absence of significant structural heart disease or increased levels of cardiac biomarkers.

The more affected participants refrained from leaving their homes due to sudden onset of general physical weakness, dizziness or even blackouts.

At baseline, participants showed higher myocardial mapping measurements, more pericardial involvement and more non-ischemic scar, but not higher troponin and NT-proBNP levels, compared to controls. Second, these findings were found to be significantly more pronounced in participants with cardiac symptoms.

The reduction of myocardial mapping values was detectable across the whole cohort; however, native T2 remained higher in the subgroup with persistent cardiac symptoms. Thus, the imaging findings suggest that inflammatory cardiac involvement after COVID may be a pathophysiological commonality shared among all individuals, regardless of the expression of cardiac symptoms.

The observation of higher systolic BP and resting heart rate in a previously prevalently non-hypertensive cohort are interesting and suggest an underlying mechanism of an increase of vascular stiffness, adding to the afterload, while coupled with myocardial edema, further hindering the efficiency of diastolic filling

The non-ischemic [Late Gadolinium Enhancement] pattern resembles the changes frequently observed in chronic systemic inflammatory conditions, where increased vascular stiffness is well-established. The latter conditions tend to be more frequent in females, potentially explaining the higher proportion of symptomatic females after COVID. Small-vessel endothelial dysfunction and microthrombosis could explain the few cases with ischemic subendocardial LGE pattern, which is otherwise more likely associated with coronary artery disease.

 

[obeat]

Is this a description of viral myocarditis, which can cause a range of symptoms from asymptomatic to heart failure.? Numerous viruses cause viral myocarditis but it is never been investigated in mild patients.

One study of RSV showed that 50% of the children at asymptomatic MRI changes.

 

[SNT Gatchaman]

Is this a description of viral myocarditis, which can cause a range of symptoms from asymptomatic to heart failure.?

No.

The underlying pathological mechanism for the detected increase in myocardial water content remains unclear at this stage and may relate to changes in vascular, cellular or interstitial permeability, but it is unlikely explained by direct myocyte injury/necrosis, as thought to be the core mechanism in classical viral myocarditis. The absence of myocardial necrosis may also explain the absence of profoundly reduced ejection fraction or dilated heart cavities in this previously healthy population that had not sustained a considerable cardiac or pulmonary injury during the initial illness.

 

[rvallee]

Significant, but unlikely to be a major cause of the main PEM population given how widely fluctuating it is. Spontaneous remissions, even if temporary and partial, don't work well with any structural damage.

It could be a significant driver of fatigue, but is very unlikely to explain most of the symptoms, especially systemic neurological and GI symptoms.

 

[SNT Gatchaman]

Yes, I think it's another window into what's happening in the cardiovascular system more generally (emphasis on vascular rather than cardiac), esp endothelial dysfunction. Similar to the observations via xenon-MRI lung studies showing what might be happening with the lung vasculature. Agree this doesn't encompass the immunometabolic side of things, but neuro/GI could be mostly secondary to vascular disruption: blood-brain barrier -> neuroinflammation/microglial activation and loss of mucosal barrier integrity, respectively.