Wellens' Syndrome from COVID-19 Infection Assessed by Enhanced Transthoracic Coronary Echo Doppler: A Case Report.

Wellens' syndrome (WS) is a preinfarction state caused by a sub-occlusion of the proximal left anterior descending coronary artery (LAD). In this case report, for the first time, we describe how this syndrome can be caused by COVID-19 infection and, most importantly, that it can be assessed bedside by enhanced transthoracic coronary echo Doppler (E-Doppler TTE). This seasoned technique allows blood flow Doppler to be recorded in the coronaries and at the stenosis site but has never been tested in an acute setting. Two weeks after clinical recovery from bronchitis allegedly caused by COVID-19 infection on the basis of epidemiologic criteria (no swab performed during the acute phase but only during recovery, at which time it was negative), our patient developed typical angina for the first time, mainly during effort but also at rest. He was admitted to our tertiary center, where pharyngeal swabs tested positive for COVID-19. A typical EKG finding supporting WS prompted an assessment of the left main coronary artery (LMCA) and the whole LAD blood flow velocity by E-Doppler TTE. Localized high velocity (transtenotic velocity) (100 cm/s) was recorded in the proximal LAD, with the reference velocity being 20 cm/s. This indicated severe stenosis with 90% area narrowing according to the continuity equation, as confirmed by coronary angiography. During follow-up after successful stenting, E-Doppler TTE showed a decrease in the transtenotic acceleration, confirming stent patency and a normal coronary flow reserve (3.2) and illustrating a normal microcirculatory function. Conclusion: COVID infection can trigger a coronary syndrome like WS. E-Doppler TTE, an ionizing radiation-free method, allows safe and rapid bedside management of the syndrome. This new strategy can be pivotal in distinguishing true WS from pseudo-WS. In cases of pseudo-WS, coronary angiography can be avoided. If E-Doppler TTE confirms the stenosis and PCI (percutaneous coronary intervention) is performed, the same method can allow assessment over time of the precise residual stenosis after stenting and verify the microvasculature status by evaluating coronary flow reserve.

Association of COVID-19 with impaired endothelial glycocalyx, vascular function and myocardial efficiency four months after infection

Aims: SARS-CoV-2 infection may lead to endothelial and vascular dysfunction. We investigated alterations of arterial stiffness, endothelial coronary and myocardial function markers four months after COVID-19 infection. Methods: In a case-control prospective study, we included 100 patients four months after COVID-19 infection, 50 age- and sex-matched healthy individuals. We measured a) pulse wave velocity (PWV), b) flow-mediated dilation (FMD) of brachial artery, c) coronary Flow Reserve (CFR) by Doppler echocardiography d) left ventricular (LV) global longitudinal strain (GLS), e) left ventricular myocardial work index, constructive work, wasted work and work efficiency and e) von-Willenbrand factor and thrombomodulin as endothelial biomarkers. Results: COVID-19 patients had lower CFR and FMD values than controls (2.39 ± 0.39 vs 3.31 ± 0.59, p = 0.0122, 5.12 ± 2.95% vs 8.12 ± 2.23%, p = 0.006 respectively). Compared to controls, COVID-19 patients had higher PWV (PWVc-f 12.32 ± 2.44 vs 10.11 ± 1.85 m/sec, p = 0.033) and impaired LV GLS (-19.11 ± 2.14% vs -20.41 ± 1.61%, p = 0.001). Compared to controls, COVID-19 patients had higher myocardial work index, and wasted work (2067.7 ± 325.9 mmHg% vs 1929.4 ± 312.7 mmHg%, p = 0.026, 104.6 ± 58.9 mmHg% vs 75.1 ± 52.6 mmHg%, p = 0.008, respectively), while myocardial efficiency was lower (94.8 ± 2.5% vs 96.06 ± 2.3%, p = 0.008). and thrombomodulin were higher in COVID-19 patients than controls (3716.63 ± 188.36 vs 2590.02 ± 156.51pg/ml, p < 0.001). MDA was higher in COVID-19 patients than controls (10.55 ± 2.45 vs 1.01 ± 0.50 nmole/L, p = 0.001). Residual cardiovascular symptoms at 4 months were associated with oxidative stress markers. Myocardial work efficiency was related with PWV (F=-0.309, p = 0.016) and vWillenbrand (F=-0.541, p = 0.037). Myocardial wasted work was related with PWV (F = 0.255, p = 0.047) and vWillenbrand (F = 0.610, p = 0.016). Conclusions: SARS-CoV-2 may cause vascular dysfunction, followed by a waste of cardiac work, in order to compensate for increased arterial stiffness 4 months after infection.

Association of COVID-19 with impaired endothelial glycocalyx, coronary flow and longitudinal strain four months after infection

Aims: SARS-CoV-2 infection may lead to endothelial and vascular dysfunction. We investigated alterations of arterial stiffness, endothelial coronary and myocardial function markers four months after COVID-19 infection. Methods: In a case-control prospective study, we included 100 patients four months after COVID-19 infection, 50 age- and sex-matched healthy individuals. We measured a) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), b) flow-mediated dilation (FMD), c) coronary Flow Reserve (CFR) by Doppler echocardiography d) pulse wave velocity (PWV) e) global left (LV) and right (RV) ventricular longitudinal strain (GLS), f) malondialdehyde (MDA), an oxidative stress marker, von-Willenbrand factor and thrombomodulin as endothelial biomarkers. Results: COVID-19 patients had lower CFR and FMD values than controls (2.39 ± 0.39 vs 3.31 ± 0.59, p = 0.0122, 5.12 ± 2.95% vs 8.12 ± 2.23%, p = 0.006 respectively). Compared to controls, COVID-19 had greater PBR5-25 (2.11 ± 0.14μm vs 1.87 ± 0.16μm, p = 0.002), higher PWV (PWVc-f 12.32 ± 2.44 vs 10.11 ± 1.85 m/sec, p = 0.033) and impaired LV and RV GLS (-19.11 ± 2.14% vs -20.41 ± 1.61%, p = 0.001 and -16.45 ± 3.33% vs -20.11 ± 2.48%, p < 0.001). MDA and thrombomodulin were higher in COVID-19 patients than controls (10.55 ± 2.45 vs 1.01 ± 0.50 nmole/L, p = 0.001 and 3716.63 ± 188.36 vs 2590.02 ± 156.51pg/ml, p < 0.001). Residual cardiovascular symptoms at 4 months were associated with oxidative stress and endothelial dysfunction markers. Conclusions: SARS-CoV-2 may cause endothelial and vascular dysfunction linked to.

Impaired coronary flow reserve in athletes with long-term cardiovascular symptoms after COVID-19

Introduction: Cardiovascular symptoms post-acute sequelae of SARS-CoV-2 infection (CV-PASC) have been increasingly recognized, but the underlying pathobiology is unclear. Endothelial and cardiac pericyte ACE2 receptors are important targets of SARS-CoV-2, resulting in virally-induced endothelial activation, which may adversely affect the coronary microvasculature and impair myocardial performance. We hypothesized that athletes with CV-PASC have microvascular and subclinical myocardial dysfunction. Methods: We compared 15 athletes with CV-PASC with 7 control athletes without prior COVID-19 using regadenoson stress cardiac magnetic resonance (CMR). All athletes participated in >6 hours of endurance activities per week. We analyzed CMR volumes, function, global circumferential strain (GCS), late gadolinium enhancement (LGE), and coronary flow reserve (CFR) by coronary sinus method. Values presented as median [IQR]. Results: CMR in CV-PASC athletes occurred 102 [66,123] days post-SARS-CoV-2 infection. There were no differences in chamber volumes, function, or LGE between groups. One CV-PASC athlete had acute myocarditis (7%). CVPASC athletes had decreased CFR compared with control athletes (Figure 1). Multiple CV-PASC participants had CFR below the 95% CI of the controls and reported normal values from the literature (2.9 and 2.5, respectively). GCS was worse in CV-PASC athletes at the base (-23.7% [-21.6,-26.4] vs -31.1% [-27.3,-33.0], p=0.01), mid-LV (-21.5% [-18.5,-22.8] vs -28.5 [-25.4,-29.9], p=0.008), and apex (-27.1% [-24.1,-29.9] vs -30.6% [-27.8,-38], p=0.07), though the apex did not reach statistical significance. Conclusions: This pilot case-control study found CV-PASC athletes had reduced CFR and associated subclinical myocardial dysfunction as assessed by GCS compared to control athletes. These findings suggest coronary microvascular dysfunction related to endothelial injury may mediate CV-PASC symptoms.

COVID-19 patients present impaired endothelial glycocalyx, vascular dysfunction and myocardial deformation resembling those observed in hypertensives four months after infection

Background/Introduction: COVID-19 infection has been associated with increase arterial stiffness, endothelial dysfunction, and impairment in coronary and cardiac performance. Inflammation and oxidative stress have been suggested as possible pathophysiological mechanisms leading to vascular and endothelial deregulation after COVID-19 infection. Purpose: The objective of our study is to evaluate premature alterations in arterial stiffness, endothelial, coronary, and myocardial function markers four months after SARS-CoV-2 infection. Methods: We conducted a case-control prospective study, including 70 patients four months after COVID-19 infection, 70 age- and sex-matched untreated hypertensive patients (positive control) and 70 healthy individuals. We measured a) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness b) flow-mediated dilation (FMD), c) coronary Flow Reserve (CFR) by Doppler echocardiography d) pulse wave velocity (PWV) and central systolic (SBP) e) global LV longitudinal strain (GLS) by speckle tracking imaging and f) malondialdehyde (MDA) as oxidative stress marker. Results: COVID-19 patients had similar CFR and FMD with hypertensives (2.48±0.41 vs 2.58±0.88, p=0.562, 5.86±2.82% vs 5.80±2.07%, p=0.872 respectively), but lower CFR and FMD than controls (3.42±0.65, p=0.0135 9.06±2.11%, p=0.002 respectively) Both COVID-19 and hypertensive group had greater PBR than controls (PBR5-25: 2.07±0.15 μm and 2.07±0.26 μm p=0.8 vs 1.89±0.17 μm, p=0.001). COVID-19 patients and hypertensives had higher PWV and central SBP than controls (PWVcf 12.09±2.50 and 11.92±2.94, p=0.7 vs 10.04±1.80 m/sec, p=0.036). COVID-19 patients and hypertensives had impaired values of GLS compared to controls (-19.50±2.56% and -19.23±2.67%, p=0.864 vs -21.98±1.51%, p=0.020). Increased PBR5-25 was associated with increased SBP central which in turn was related with impaired GLS (p<0.05). MDA was found increased in COVID-19 patients compared to both hypertensives and controls (10.67±2.75 vs 1.76±0.30, p=0.003 vs 1.01±0.50 nmole/L, p=0.001). Conclusions: SARS-CoV-2 may cause impaired coronary microcirculatory, endothelial and vascular deregulation which remain four months after initial infection and are associated with reduced cardiac performance. The 10-fold increase of MDA compared to healthy individuals four months after COVID-19 infection indicate oxidative stress as possible pathophysiological mechanism.

Myocardial ischaemia of non-obstructive origin as a cause of new onset anginal chest pain in the long COVID syndrome

Background: New-onset chest pain occurs in around 20% of patients with long COVID syndrome (LCS). Being the vascular endothelium one of the targets of the SARS-CoV-2 virus, we hypothesized that new onset anginal symptoms in LCS could be due to endothelium dysfunction and other non-obstructive causes of myocardial ischaemia. Methods: We investigated 11 consecutive patients who developed new onset anginal chest pain, suggestive of myocardial ischaemia, after documented SARS-CoV-2 infection. Intracoronary assessment included endothelium-dependent evaluation with acetylcholine testing (Ach), and endothelium-independent assessment with coronary flow reserve (CFR) and microcirculatory resistance (MR). Criteria for positiveness of these tests and medical treatment recommendation were obtained from 2019 ESC guidelines and 2020 EAPCI consensus document on ischaemia with non-obstructive coronary arteries (INOCA). Results: Mean patient age was 56 years (SD ± 15);10 (91%) were female. In the acute COVID-19 phase, 4 patients (36%) had had pulmonary infiltrates and 2 (18%) required hospitalization. Conclusive non-invasive tests were obtained in 7 (64%), showing exercise-related myocardial ischaemia in 6 (86%). Coronary angiography ruled out obstructive epicardial stenoses in all the patients. Ach testing revealed abnormal endothelium-dependent responses in 9 (82%) patients: 5 (56%) had epicardial vessel and 4 (44%) microvascular spasm. Endothelium-independent assessment was abnormal in 6 (54%) cases, with abnormal CFR in 2 (33%), abnormal MR in 2 (33) and both abnormal CFR and MR in 2 (33%) patients. The most frequent endotype was combined endothelium dependent- and independent abnormalities (6/9, 67%). Stratified medical treatment according to endotype led to significant improvement in Seattle Angina Scores for angina frequency (+22 points, p=0.013) and a notable trend towards angina stability (+25 points, p=0.093) at a mean follow-up time of 222 days. Conclusions: Myocardial ischaemia of non-obstructive origin is common in patients with chest pain and LCS. Vasomotor abnormalities related to endothelial dysfunction occurred in 82% of patients, frequently associated to impaired microvascular vasodilation or high microvascular resistance. Stratified medical treatment led to significant improvement in angina stability and frequency.