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Introduction: Women with a history of preeclampsia (PreE) or preterm (PreT) birth are at elevated risk of future hypertension, ischemic heart disease, and stroke. Mechanisms for this increased risk are unknown. Flow-mediated dilation of the brachial artery (FMD) is an established surrogate for cardiovascular risk.Hypothesis: In this pilot study, we hypothesize that maternal vascular dysfunction associated with PreE is reversible, and the extent of recovery is predicated on specific maternal characteristics. Method(s): In this prospective study, subjects were recruited to three groups: PreE with delivery at 27-34 weeks;PreT delivery at 27-34 weeks without preeclampsia;and healthy controls at 39-40 weeks. Vascular function (FMD), nutrition (validated questionnaire), and physical activity (accelerometers) data were collected at 1-2 days post-partum and 3 months. Result(s): Fourteen subjects were enrolled (mean age 32+/-6 years). Systolic blood pressure was higher for PreE subjects (average 131+/-6) compared to controls (109 +/- 9, p=0.004) and PreT (110+/-8, p=0.008) at visit 1. This difference resolved at visit 2. Though non-significant, FMD (mean+/-SE) was higher in controls compared to PreE and PreT groups at visit 1 (7.7%+/-0.8 v. 7.4%+/-0.7 and 6.9%+/-1.0, Figure 1). FMD remains depressed at 3 months, but subject follow-up was impacted by the Covid 19 pandemic. Alternate Healthy Eating Index scores were non-significantly higher in the PreT group than PreE and controls. PreT subjects were less sedentary and more physically active (higher moderate-vigorous physical activity, higher total steps). Conclusion(s): Maternal FMD is reduced immediately post-partum in PreE and PreT births. The PreT group had lower FMD despite better nutrition and physical activity scores. This is a pilot study, and we are not powered for significance. Data from our small cohort support the ability to collect meaningful data in these understudied populations which could inform future studies of long-term cardiovascular risk.
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Background: Coronavirus disease (COVID)-19 is an entity characterized by a cytokine storm and profound endotheliitis. Although several reports have pointed to the presence of endothelial dysfunction in the acute phase, data is accumulating regarding a possible prolonged adverse effect of COVID-19 on endothelial function. Purpose(s): This systematic review and meta-analysis aims to evaluate the degree of endothelial impairment, assessed by flow-mediated dilation (FMD) of the brachial artery, in individuals recovering from COVID-19. Method(s): We conducted a systematic literature search for studies assessing FMD between in patients post-COVID-19 and controls. Exclusion criteria consisted of the absence of a control group, measurement of FMD only during the acute phase of the disease, and not reporting FMD in % change. Effect sizes were pooled via random-effect model and the results are expressed as uncorrected standardized mean difference (SMD), using the Cohen's d as the effect size metric, with 95% confidence intervals (CI). Between-study heterogeneity was assessed through the calculation of I2. Subgroup analysis according to follow-up duration and the presence of cardiovascular risk factor-matched controls was also carried out. Result(s): Database search identified 51 studies. Following the application of the exclusion criteria, 7 studies were included in the meta-analysis (post-COVID-19: 342 subjects, Control: 273 subjects). Compared to controls, patients post-COVID-19 had significantly lower FMD% values (SMD: -1.06, 95% CI: -1.74 to -0.38, p<0.01, I2: 86%) (Figure 1). Results remained unaffected after exclusion of any single study using the leave-oneout method. Subgroup analysis revealed no significant differences in FMD between post-COVID-19 patients and controls according to follow-up duration or the presence of cardiovascular risk factor-matched control group. Conclusion(s): Flow-mediated dilation of the brachial artery, indicative of endothelial dysfunction, was significantly reduced in post-COVID-19 subjects compared to non-infected controls. This finding may be an alarming sign towards a higher risk of incident cardiovascular events. (Figure Presented) .
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Background: Growing evidence focuses on the role of hypoalbuminemia in the COVID-19 course and the role of vascular inflammation in the progression to Capillary Leak Syndrome (CLS). CLS may be mediated by a derangement of endothelial barrier following vascular endothelial dysfunction. We investigated the role of cardiometabolic risk factors in the association of hypoalbuminemia with endothelial dysfunction of hospitalized COVID-19 patients. Method(s): In this cross-sectional study, patients hospitalized for COVID- 19 at the medical ward or Intensive Care Unit (ICU) were enrolled. Medical history and laboratory examinations were collected while the endothelial function was assessed by brachial artery flow-mediated dilation (FMD) between the first 24-72 hours of their admission to the hospital. According to the body mass index, history of hypertension, dyslipidemia, and diabetes mellitus, COVID-19 patients were categorized in those with Cardiometabolic Risk Factors (CRFact) or without CRFact (no-CRFact). From the study population, we excluded subjects with established cardiovascular disease. Result(s): Sixty-six patients with COVID-19 (37% admitted in ICU) were recruited. From the study population, 41 were in the group of CRFact and 25 in the no-CRFact. Patients with CFRact were older (65+/-9 years vs. 53+/-14 years, p<0.001), had more impaired FMD (1.16+/-2.13% vs. 2.60+/-2.44%, p=0.01), and lower serum albumin levels (3.10+/-0.68 g/dL vs. 3.52+/-0.26 g/dL, p=0.006) compared to the no-CRFact group. Between CRFact and no-CRFact, there was no difference in CRP and IL-6 levels. Interestingly, serum albumin in patients with CRFact was significantly lower than the lower reference limit (LRL) (=3.5 g/dl) of albumin (p=0.001), while no such finding was noted in subjects with no CRFact (p=0.64). Furthermore, regression analysis revealed that, even after adjustment for age, the presence of CRFact was associated with decreased serum albumin levels by 0.31mg/dl (95% CI 0.08 to 0.63, p=0.04). In the CRFact population, there was a correlation of albumin with FMD (R=0.29, p=0.05) and an inverse correlation with CRP (rho=-0.48, p=0.02) and IL-6 (rho=-0.66, p<0.001), while in the no-CRFact group no such correlation were observed (p=NS for all). Conclusion(s): COVID-19 patients with cardiometabolic risk factors present with low serum albumin levels early at the course of the disease, which may be driven by endothelial dysfunction and vascular inflammation. This data gives insights into the potential association of a dysfunctional endothelial layer and the progression to capillary leak syndrome. (Figure Presented).
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Background: Endotheliilitis COVID-19 related endothelial dysfunction plays a key role in the cardiovascular complications of the disease. Vaccine against SARS-CoV-2 protects against severe COVID-19 and from adverse effects. We evaluated the impact of vaccination on COVID-19 induced endothelial dysfunction. Method(s): We enrolled 45 patients hospitalized for COVID-19 (either vaccinated or not against SARS-CoV-2). Clinical information and laboratory findings were collected, and brachial artery flow-mediated dilation (FMD) was evaluated as a measure of endothelial function. Subjects without COVID- 19 were used as the control group. All patients were hospitalized in a medical ward classified according to the World Health Organization (WHO) scale. Result(s): There was no difference in age (62+/-10 years vs. 65+/-8 years, p=0.12) and male sex prevalence (56% vs. 49%, p=0.53) between patients with COVID-19 and control subjects. Of the patients with COVID-19, 44% (20) were vaccinated against SARS-CoV-2. FMD was impaired in patients with COVID-19 compared to controls (4.35+/-3.56% vs. 7.36+/-2.91%, p<0.001). In patients with COVID-19, FMD was impaired in non-vaccinated subjects compared to vaccinated (2.05+/-2.41% vs. 7.24+/-2.52%, p<0.001). There was no difference in FMD between controls and vaccinated against COVID-19 patients (7.36+/-2.91% vs. 7.24+/-2.52%, p=0.86). There was no difference in the WHO scale clinical status for vaccinated and not vaccinated COVID-19 subjects (For Vaccinated WHO scale 3: 35%;scale 4: 35%;scale 5: 30% vs. For Non-vaccinated WHO scale 3: 20;scale 4: 60%;scale 5: 20%, p=0.24). Conclusion(s): Hospitalized patients with COVID-19 present endothelial dysfunction in the acute phase of the disease. Endothelial function in unvaccinated patients with COVID-19 is impaired compared to control subjects as well as compared to vaccinated patients with COVID-19. This data provides insights on the protective role of vaccination against COVID-19 related endotheliitis. (Figure Presented) .
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The following case report is an overview of an unusual presentation of bilateral axillo-brachial artery occlusion following messenger ribonucleic acid (mRNA) vaccination against severe acute respiratory coronavirus 2 (COVID-19). A 64-year-old female presented with symptoms initially consistent with polymyalgia rheumatica five weeks following the first booster of the Pfizer-BioNTech COVID-19 vaccine. She was successfully treated with prednisone therapy; however, despite the normalization of inflammatory markers, she later presented with bilaterally occluded axillo-brachial arteries. She successfully underwent endovascular management for the treatment of her symptoms. To our knowledge, this is the first case report of chronically occluded bilateral axillo-brachial artery disease following mRNA vaccination for COVID-19 successfully treated with endovascular therapy. The unusual pathogenesis of upper extremity arterial disease is reviewed and a review of endovascular treatment options is presented. A literature review of the types of vasculitis seen following mRNA COVID-19 vaccination is also presented.
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Background: A significant proportion of patients recovering from SARS-CoV-2 infection (Covid-19) complain a wide variety of bothersome symptoms, including symptoms potentially related to cardiac involvement, that may significantly impair their quality of life (post-Covid or long-Covid syndrome). However, full diagnostic investigation usually does not reveal significant structural or functional cardiac abnormalities. Whether cardiac autonomic dysfunction and/or endothelial dysfunction may play a role in post-COVID-19 symptoms, however, has poorly been investigated. Method(s): We prospectively enrolled 63 young adult patients (age 18-55 years) without any previous cardiovascular disease, referred to our "Post-COVID-19" Day Hospital ward for a clinical follow-up after 3 months from SARS-CoV-2 infection. In all patients endothelium-dependent vasodilator function was assessed noninvasively by measuring the change of brachial artery diameter in response to hyperaemia after 5 minutes of forearm ischemia (flow-mediated dilatation, FMD);furthermore, endothelium-independent vasodilator function was assessed by measuring the change of brachial artery diameter in response to sublingual nitroglycerine (25 mug) (nitrate-mediated dilatation, NMD). A 24-hour ECG Holter monitoring (HM) was performed to assess cardiac autonomic function by obtaining timedomain and frequency-domain parameters of heart rate variability (HRV). Result(s): Symptoms of potential cardiac origin (dyspnoea on exertion, chest pain, arrhythmic symptoms) were referred by 47 patients (74.6%, Group 1), whereas 16 (25.4%, Group 2) were free from any possible cardiac symptom. The two groups did not differ in age, sex and cardiovascular risk factors. FMD was 7.29+/-3.4% and 7.01+/-2.3% in Group 1 and 2, respectively (p=0.77), whereas NMD was 11.1+/-3.8% and 14.2+/-4.9 in the two groups, respectively (p=0.013). No significant differences were observed for HRV parameters between the two groups (see Table). Conclusion(s): Our data do not support a role for both endothelial dysfunction and cardiac autonomic dysfunction in the persistence of symptoms of potential cardiac origin in patients with a recent SARS-CoV-2 infection. The lower endothelium-independent arterial vasodilator found in these patients, however, deserves further investigation.
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Background: Cardiac Rehabilitation (CR) is a supervised exercise and risk factor modification program for patients with cardiac conditions. Endothelial dysfunction is often present and is associated with worsening cardiac prognosis, and several studies have indicated that standard onsite CR has improved endothelial function in heart disease patients. However, during the COVID-19 pandemic, many CR programs transitioned to a virtual or hybrid model of care to increase safety of CR programs. Objective(s): The objective of this study was to determine vascular function of patients with coronary artery disease (CAD) measured before and after 4 months of outpatient CR using a virtual model of care. Method(s): Virtual CR included 1 virtual group session/week by videoconferencing and hybrid CR included 1 session/week (4 on-site and 12 virtual group sessions) for a total of 16 weeks. CAD patients (6 females, 4 males) mean age 68.1+/-7.5 years rested in a supine position to measure 1) brachial artery flow-mediated dilation (FMD), 2) microvascular function, and 3) augmentation index (AI) using ultrasound sonography (n=8) and an EndoPAT 2000 (n=9). Two patients completed virtual CR and the rest underwent hybrid CR. These measurements were obtained concurrently using an ultrasound transducer at the brachial artery proximal to a blood pressure cuff on the forearm with EndoPAT cuffs on the index fingers during 5-minute intervals of baseline, occlusion, and recovery. FMD results were analyzed using automated Cardiovascular Suite software. AI and Reactive Hyperemia Index (LnRHI) were determined using automatic analysis via the EndoPAT 2000. Anthropometrics, blood pressure, and food intake were recorded at each visit. Patients were advised to refrain from strenuous exercise, alcohol, caffeine, and highly saturated foods at least 12 hours prior to the study appointment. One tailed paired t-tests were conducted between baseline and completion. Result(s): Adherence to CR averaged 10.3+/-3.2 out of 16 sessions. FMD improved from (2.75+/-1.71% to 5.63+/-4.37%, p=0.048) while there was no improvement in AI (14.2+/-18.8 to 13.2+/-19.6, p=0.45) or LnRHI (0.56+/-0.12 to 0.52+/-0.20, p=0.24). Conclusion(s): While there was no improvement in LnRHI or AI after CR, FMD improved in CAD patients after 4 months of adapted CR. Our results indicate that while virtual and hybrid models of CR may not be sufficient for improving microvascular function and aortic stiffness in CAD, there is an improvement of endothelial function. Future studies should examine the effects of adherence, duration and exercise intensity within these alternative models of CR on aortic and microvascular improvements.
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Objective: To fight the COVID-19 pandemic, messenger RNA (mRNA) vaccines were the first to be adopted by vaccination programs worldwide. We sought to investigate the short-term effect of mRNA vaccine administration on endothelial function and arterial stiffness. Design and method: Thirty-two participants (mean age 37 ± 8 years, 20 men) that received the BNT162b2 mRNA COVID-19 vaccine were studied in 3 sessions in a sequence-randomized, sham-controlled, assessor-blinded, cross-over design. The primary outcome was endothelial function assessed by brachial artery flow-mediated dilatation (FMD), and secondary outcomes were aortic stiffness, evaluated with carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx@75), and inflammation measured by high-sensitivity C-reactive protein (hsCRP) in blood samples. The outcomes were assessed prior to, and at 8 h, 24 h post the 1st dose of vaccination, and 8 h, 24 h, and 48 h post the 2nd. Results: There was an increase in hsCRP that was apparent at 24 h after both the 1st dose (-0.60 [95% Confidence intervals [CI]: -1.60 to -0.20], p = 0.013) and the 2nd dose (max median difference at 48 h -6.60 [95% CI: -9.80 to -3.40], p < 0.001) compared to sham. The vaccine did not change PWV or AIx@75. FMD remained unchanged during the 1st dose but decreased significantly by 1.5% (95% CI: 0.1% to 2.9%, p = 0.037) at 24 h post the 2nd dose. FMD values returned towards baseline at 48 h. Conclusions: Our study shows that the mRNA vaccine causes a prominent increase in inflammatory markers, especially after the 2nd dose, and a transient deterioration of endothelial function at 24 h that returns towards baseline at 48 h. These results confirm the short-term cardiovascular safety of the vaccine.
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Pegylated Interferon (PegIFN) is the recommended first-line cytoreductive therapy in patients aged <40 years with essential thrombocythaemia (ET) or polycythaemia vera (PV). However, its use in patients >60 years is often limited due to concerns about tolerability. In this study, we evaluate the efficacy and tolerability of PegIFN in patients >60 years at University College London Hospitals (UCLH). Using electronic medical records, we identified patients with ET, PV or myelofibrosis at UCLH who commenced treatment with PegIFN between 2010 and 2020 and were aged >60 years on starting therapy. Data were collected until April 2021 to allow a minimum of 1-year follow-up. Complete Haematological responses were defined as per standard European Leukaemia Net criteria. Adverse events (AE) were graded 1-5 according to Common Terminology Criteria for Adverse Events (CTCAE). Thrombosis risk was graded according to IPSET criteria for ET patients. Patients with PV were classed as high risk if they were aged >65 or had a previous history of thrombosis. Eighteen patients were included in the study. The median age was 75.1 years (range 63-91), 61% were female. Ten out of 18 (56%) had a diagnosis of ET, seven out of 18 (39%) of PV and 1/18 (6%) of post-ET myelofibrosis. Fifteen out of 18 (83%) were positive for JAK2 V617F, and two out of 18 (17%) were positive for CALR mutation. Ten out of 18 (56%) had significant cardiovascular co-morbidities at diagnosis. Five out of 18 (28%) had arterial or venous thromboembolic disease at diagnosis. Sixteen out of 18 (89%) were high-risk for thromboembolic events at diagnosis. Seventeen (94%) patients had PegIFN as a second-or thirdline agent. Of these, 15 out of 17 had received hydroxycarbamide (HU) as first-line therapy;two out of 17 had interferon alpha. PegIFN was started at a median age of 70 years (range 50-86) and continued for 5.7 years (range 2-13). Twelve out of 18 (67%) patients achieved complete remission (CR) on PegIFN monotherapy;1 out of 18 (6%) achieved CR on PegIFN and HU combination therapy, and the remaining 5 out of 18 (28%) achieved a partial remission (PR). The median time to CR was 5 months (range 1-40 months). Ten out of 18 (56%) had grade 1-2 AEs including skin rashes, cytopenia and fatigue. Three out of 18 (17%) developed a major thromboembolic event while on treatment (brachial artery embolism, transient ischaemic attack and a non-ST elevation myocardial infarction). Of these, two out of three failed to achieve a CR on PegIFN and required ongoing venesection. The third had suboptimal response due to dose escalation limited by grade 3 neutropenia. Thirteen patients (72%) remained on pegIFN at the end of the study period. Of those who discontinued, three out of five stopped due to cytopenias, one out of five died during the study period of Covid-19 infection and one out of five transformed to myelodysplastic syndrome. In this study, we present a group of patients who were at high risk for thrombosis due to their age and cardiovascular risk factors. The majority of AEs documented were grade 1-2, with only three out of 18 (17%) patients discontinuing due to AEs. The rate of CR 72% similar to that quoted in imminent studies including MPN-RC (Knudsen et al, 2018) and DALIAH trials (Mascarenhas et al, 2018), which recruited larger numbers of youngers ET and PV patients on PegIFN. Over 20% of MPN patients develop resistance or intolerance to HU (Sever et al, 2014);therefore, there is a need for alternative cytoreductive agents. Our study demonstrates PegIFN to be effective and well-tolerated for use in patients >60 years and is an excellent cytoreductive option in this cohort.
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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.
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Introduction: Coronavirus disease 2019 (COVID-19) has become one of the more dramatic health problems in the century. This disease has enormous consequence for the health care worldwide. In addition to high mortality rate, patients recovered from COVID-19 present short and long-term cardiovascular sequelae including chest pain, myocardial dysfunction, arrhythmia, dyspnea, breathlessness, postural tachycardia syndrome, and thrombotic complications. The explanations for these clinical manifestations are still uncertain but can involve a constellation of physiological alterations. Hypothesis: To test if COVID-19 survivors have augmented sympathetic outflow, diminished endothelial function, elevated aortic stiffness, and reduced physical capacity compared to healthy individuals. Methods: Nineteen COVID-19 survivors [age: 47.0±2.3 years, BMI: 30.1±1.2 Kg/m2] and eighteen well-matched healthy controls (age: 44.0±2.0 years, BMI: 28.4 ±1.2 Kg.m2] were included in study. COVID-19 survivors were evaluated within 6 months of original diagnosis by RT-PCR. Muscle sympathetic nerve activity (MSNA) from fibular nerve (Microneurography), brachial artery flowmediated dilation (BAFMD;Doppler-Ultrasound), carotid-femoral pulse wave velocity (cf-PWV;Complior), beat-to-beat blood pressure (Peripheral BP;Finometer), heart rate (HR;Electrocardiography) and peak oxygen uptake (VO2peak, Cardiopulmonary exercise testing) were measured in both groups. Results: MSNA was higher in COVID-19 survivors compared to controls (33.0±1.0 vs. 22.0±1.0 bursts/min, p=0.001). Both BAFMD and VO2peakwere lower in COVID-19 survivors compared to controls (4.6±0.7 vs. 8.2 ±0.8%, p=0.005 and 22.2±1.5 vs. 29.7±1.6 mL/Kg/min p=0.001, respectively). Although COVID-19 survivors had greater cf-PWV than controls (8.6±0.5 m/s vs. 7.4±0.4 m/s, p=0.03), BP and HR were not different between groups. Conclusions: Our study revealed that patients recently recovered from COVID-19 have abnormal neurovascular control, vascular alterations and reduced physical capacity. These findings strongly indicate the need of further long-term investigations to uncover cardiovascular sequelae provoked by COVID-19.
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Introduction: Obstructive sleep apnea (OSA) is considered a low-grade chronic inflammatory disease. OSA impairs endothelial function and increases cardiovascular mortality. Hydroxychloroquine (HCQ), an antiinflammatory drug, seems to reduce cardiovascular mortality. In animal and in vitro models, HCQ improved endothelial function. Its effects on endothelial function of patients with OSA is unknown. Hypothesis: Hydroxychloroquine can improve endothelial function in patients with OSA. Methods: Adults older than 65 years with an apnea-hypopnea index (AHI) greater than 15 events/hour were allocated to receive either 400mg of HCQ or placebo daily for eight-weeks. The randomization was computer-generated and pharmacycontrolled. Participants and outcome evaluators were blinded to the group allocation. Home sleep apnea test and measurements of flow-mediated dilation of brachial artery (FMD) and peripheral artery tonometry (PAT) were performed at baseline and follow-up in a research facility. The primary outcomes were the change in FMD (Δ%FMD) and change in PAT reactive-hyperemia index (ΔRHI). Change in AHI (ΔAHI) was a secondary outcome. Generalized estimating equations were used to verify time∗group interaction. Results: Fourteen patients were assigned to the HCQ group and fifteen patients to the placebo group between April 2019 and May 2020 with no losses to follow-up. The recruitment was interrupted due to COVID-19 pandemic. Mean Δ%FMD was 0.35 (95% CI -4.26 to 4.97) in placebo group and 0.48 (95% CI -4.08 to 5.04) in HCQ group. Mean ΔRHI was 0.02 (95% CI -0.11 to 0.07) in placebo group and 0.05 (95% CI -0.24 to 0.13) in HCQ group. Mean ΔAHI was 7 (95% CI -1 to 15) in placebo group and -4 (95% CI -11 to 2) in HCQ group. P values for time∗group interaction were 0.97, 0.74 and 0.04, respectively. No important adverse events have occurred. Conclusions: In this trial, HCQ did not improve endothelial function measured by FMD and PAT in older adults with OSA. A slight but significant reduction in AHI was observed in HCQ group, suggesting that some specific inflammatory mechanisms participate in OSA causation that could become a future therapeutic approach.
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Vascular dysfunction and inflammation are precursors to cardiovascular disease (CVD). Notably, young adults who were symptomatic from COVID-19 during the acute phase of illness (within 4 weeks from diagnosis) have shown to exhibit peripheral vascular dysfunction. Importantly, many young adults report persistent symptoms from COVID-19 for several months, including cognitive difficulties. However, it remains unknown whether vascular dysfunction persists beyond the acute phase of COVID-19 in symptomatic young adults. We tested the hypothesis that peripheral and cerebral vascular function would be blunted in symptomatic (SYM) young adults who are beyond 4 weeks from a COVID-19 diagnosis, compared to asymptomatic adults (ASYM). Since COVID-19 causes inflammation that may negatively impact vascular function, we also hypothesized that serum hsCRP would be elevated in SYM compared to ASYM. We studied 15 otherwise healthy adults (age = 23 ± 1 years;mean ± SE) with a positive lab diagnosis of COVID-19. Eight were SYM (14 ± 1 weeks from diagnosis) while seven were ASYM (13 ± 2 weeks from diagnosis) at time of testing. Brachial artery flow-mediated dilation (FMD;duplex Doppler ultrasound) was performed, and macroand microvascular function were quantified as FMD% and peak blood velocity after cuff release, respectively. Cerebral vasomotor reactivity (CVMR) was quantified as percent increase in middle cerebral artery blood velocity (transcranial Doppler ultrasound) to rebreathing induced hypercapnia. Serum hsCRP level was measured. FMD was lower in SYM (3.81 ± 0.60%) compared to ASYM (7.10 ± 0.94%, P = 0.010). Likewise, peak blood velocity after cuff release was lower in SYM (47 ± 3 cm/s vs. ASYM: 65 ± 8 cm/s, P = 0.037). However, CVMR was not different between the two groups (P = 0.91). Serum hsCRP was higher in SYM (3.4 ± 1.0 mg/L vs. ASYM: 0.7 ± 0.1 mg/L, P = 0.036). These preliminary results indicate that peripheral macro-and microvascular function remain blunted beyond the acute phase in young adults with persistent symptoms from COVID-19, whereas cerebral vascular function appears unaffected. The extent to which this sustained vascular impairment and elevated hsCRP contributes to increased CVD risk in these otherwise healthy young adults remains to be determined.
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Severe coronavirus disease 2019 (COVID-19) has been complicated by coagulopathy and thrombotic events including venous thromboembolism, pulmonary embolism, and arterial thrombus at a rate higher than has traditionally been seen with sepsis-induced coagulopathy or disseminated intravascular coagulation leading most centers to treat hospitalized patients with prophylactic anticoagulation. We present a case of a patient with thoracic outlet syndrome who presents with brachial artery thrombosis in the setting of infection with COVID-19. Both thoracic outlet syndrome and COVID-19 infection are independently associated with increased risk of thrombotic events. The induced hypercoagulable state from COVID-19 infection may result in acute arterial thrombosis in patients with predisposing anatomic differences consistent with thoracic outlet syndrome. Level of Evidence: V.
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Background: The SARS-CoV-2 pandemia has often oriented the diagnosis of complex pathologies towards CoViD with complications while the main diagnosis could be different. Description of the clinical case: A 76 yo man was hospitalized for confusion and heart failure;in the emergency department, CoViD Ab testing and PCR swab were positive with focal interstitial pneumonia;then splenomegaly, bilateral splenic and renal infarcts and thrombosis of the superior mesenteric artery were confirmed by chest-abdomen CT scan, Doppler US found thrombosis of brachial artery. Antithrombotic therapy was intensified but a new episode of confusion with fever occurred. Brain CT revealed multiple target lesions with hemorrhagic areas, suspected to be neoplastic. LMW heparin was suspended, blood cultures came back positive for Enterococcus faecalis;echocardiography showed a vegetation on the aortic valve;thus the patient's history was reconsidered based on the findings of bacterial endocarditis. When he tested negative, he underwent valve replacement with bioprosthesis. A new positive CoViD swab interrupted the cardiological rehabilitation but finally he was discharged. Conclusions: SARS-CoV-2 pneumonia in this patient was complicated by aortic endocarditis with systemic septic embolization. The antibiotic and steroid therapy administered upon admission may have covered or favored sepsis, that could have been perhaps already onsetting at the time of patient presentation in the ER. The patient's overall hospital stay was 80 days due to recurrent swab positivity even though in the absence of specific symptoms.
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Introduction: Cardiovascular complications of Coronavirus disease (COVID-19), resulting from the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), have been documented. Endothelium-induced cytokine storm in critically ill COVID-19 patients is one of the leading causes of morbidity and mortality. Vascular endothelial damage caused by COVID-19 emphasizes the crucial role of endothelium in COVID-19 clinical impact. Purpose: To examine the mid-term (1-month) impact of COVID-19 in endothelial function. Methods: In this case control study, 20 consecutive patients who were hospitalized for COVID-19 either on Intensive Care Unit (ICU) or non-ICU were examined one month following hospital discharge. In the control group we recruited 12 consecutive subjects from the outpatient cardiology clinic. Demographic and clinical data were collected, and endothelial function was evaluated by brachial artery flow-mediated dilation (FMD). Results: There was no difference in age between COVID-19 patients and control subjects (66±12 years vs. 71±5 years, p<0.17), in male sex (63% vs. 54%, p=0.66) in history of diabetes mellitus (27% vs. 36%, p=0.64), hypertension (36% vs. 54%, p=0.39), cardiovascular disease (27% vs.18%, p=0.61). From the COVID-19 subjects 65% were overweight or obese. During their hospitalization [3 ICU (15%)/17 non-ICU (85%), mean days: 17±6.7], 4 (20%) of COVID-19 patients developed ARDS, while single cases of stress-induced cardiomyopathy, pulmonary embolism, and acute coronary syndrome were detected. One month post discharge D-dimers (0.71±0.55 μg/ml) levels were above upper reference limit. Importantly, FMD one month after hospital discharge date, was significantly impaired in the COVID-19 group (3.59±1.63% vs. 9.31±2.98%, p<0.001) compared to control group. Conclusion: Post COVID-19 subjects one month post discharge have significant impaired endothelial function compared to control subjects. These findings highlight the significant interaction of COVID-19 with arterial endothelium and merit further research to conclude on the exact impact of vascular endothelium in physical history of SARS-CoV-2 infection.