COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may induce serious cardiovascular disorders including heart failure, myocarditis, arrhythmias, and severe thromboembolic complications. Indeed, myocardial injury and cardiovascular complications might occur in more than half of patients after COVID-19 and portend a worse prognosis. Accumulating data suggest that SARS-CoV-2 affects endothelial function via inflammation of endothelium, causing microvascular disturbances and microthrombosis. Nowadays, COVID-19 is considered to be a systemic microvascular endothelial disorder with various clinical manifestations [1].
A 34-year-old-woman, with an unremarkable medical history, was referred to our cardiology outpatient clinic due to reduced exercise tolerance, dyspnea, tiredness, and palpitations for about 3 weeks after the diagnosis of SARS-CoV-2 infection. On admission, the levels of D-dimer, B-type natriuretic peptide, and cardiac troponin were within reference ranges. Two-dimensional echocardiography revealed mildly reduced left ventricular ejection fraction (LVEF, 49%) and enlargement of left ventricular (LV) volume. Global longitudinal strain (GLS) was also slightly reduced (–16.9%) (Figure 1A). Electrocardiography revealed ST-segment depression in leads V3-V6 and negative T wave in leads II, III, and aVF, whereas 24-hour electrocardiogram recording showed numerous premature ventricular complexes.
We subsequently performed microcirculation measurements on the forearm during and following a brachial artery occlusion using both laser speckle contrast imaging (LSCI, PeriCam PSI System, Perimed, Järfälla, Sweden) and flow-mediated skin fluorescence (FMSF, Angionica Ltd, Łódź, Poland) based on monitoring the intensity of a nicotinamide adenine dinucleotide (NADH) fluorescence [2]. LSCI revealed low microvascular perfusion and relatively weak post-occlusive reactive hyperemic response suggesting impairment of the endothelium-dependent vasodilatation potential (Figure 1B). Similarly, using FMSF, we observed very modest oscillations, negative ischemic response, and a significantly reduced hyperemic response also suggesting endothelial dysfunction (Figure 1C).
Based on the multifactorial beneficial role of sacubitril/valsartan (S/V) in the management of heart failure and improvement of endothelial function [3], therapy with this molecule (24 mg/26 mg, twice a day) and additionally bisoprolol (2.5 mg once a day) was started.
After three months of pharmacological therapy and absence of physical activity, a significant symptom reduction was noted. Echocardiography showed improved regional contractility with LVEF — 55%, normalized LV volumes, and GLS (–20%) (Figure 1D). Likewise, microvascular parameters improved significantly. We observed better microvascular perfusion in LSCI (Figure 1E) and amelioration in all FMSF parameters (Figure 1F). Especially, the microvascular oscillations and endothelium-dependent hyperemic response showed marked recovery, suggesting a role of endothelial inflammation in the pathogenesis of COVID-19. Indeed, hyperinflammation and hypercoagulation are essential elements that drive the immunothrombotic vicious circle in COVID-19 [4].
Our diagnostic process has led us to the hypothesis of SARS-CoV-2-induced endotheliitis, which provides the rationale for therapies to stabilize and protect the endothelium. Indeed, the S/V molecule has been demonstrated to reduce proliferation and fibrosis, preserve endothelial function and integrity, and mitigate inflammation [5].
The presented case provides new insight into SARS-CoV2- induced cardiac and endothelial dysfunction and points out the possible role of sacubitril/valsartan. Its multifaceted protective influence on the cardiovascular system calls for considering this molecule an additional therapeutic option in COVID-19-related cardiovascular complications.
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