Risultati per: COVID-19 grave collegato all’invecchiamento cerebrale

New England Journal of Medicine, Volume 391, Issue 19, Page 1860-1862, November 14, 2024.

This Viewpoint summarizes the factors contributing to increased risk of severe outcomes and hospitalization associated with COVID-19 among older adults, stresses the importance of assessing COVID-19 risk before infection occurs, calls for all immunocompromised older adults to be considered for COVID-19 treatment, and details 3 recommended COVID-19 therapies.

Annals of Internal Medicine, Ahead of Print.

Circulation, Volume 150, Issue Suppl_1, Page A4143186-A4143186, November 12, 2024. Introduction:Statins are lipid-lowering agents with anti-inflammatory effects. Data surrounding the benefits of statins in patients with coronavirus disease 2019 (Covid-19) are conflicting. We sought to better understand the impact of statins in the context of Covid-19-related inflammation.Methods:We leveraged the International Study of Inflammation in Covid-19, a prospective multicenter cohort study of patients hospitalized specifically for Covid-19 between February 1, 2020 and October 30, 2022. Participants underwent systematic assessment of biomarkers of inflammation. We used logistic regression modeling and inverse probability-of-treatment weighting (IPTW) to examine the association between prior statin use and the composite outcome of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy.Results:A total of 4,464 patients were included in the study, of whom 1,364 (27.5%) were taking a statin prior to admission. There were 1,061 primary outcome events, including 540 deaths, 854 mechanical ventilation and 313 renal replacement therapy. Amongst biomarkers of inflammation, statin use was associated solely with lower levels of soluble urokinase plasminogen activator receptor (suPAR) after adjusting for known confounders. In multivariable logistic regression analysis, statin use was associated with lower odds of the composite outcome (adjusted odds ratio (aOR) 0.63, 95%CI[0.53-0.76]) compared to patients not on statins. Findings were consistent with IPTW (aOR 0.92, 95%CI [0.89- 0.95]). The proportion of the effect of statin on the primary outcome mediated by suPAR was estimated at 31.5%.Conclusion:Prior statin use is associated with improved outcomes and lower inflammation as measured by suPAR levels in patients hospitalized for Covid-19.

Circulation, Volume 150, Issue Suppl_1, Page A4145299-A4145299, November 12, 2024. Background:COVID-19 can present with a wide spectrum of clinical manifestations ranging from asymptomatic to life-threatening. It is often thought of as a primarily pulmonary infection and different systemic presentations are sometimes overlooked. We present a case of COVID-19 induced myocarditis leading to hemodynamic instability and end-organ dysfunction.Case presentation:A 77-year-old male with a history of CKD, paroxysmal atrial fibrillation, and COPD was transferred to our hospital for a higher level of care due to worsening cardiogenic shock. He was cold and wet (Forrester class IV) with a High Sensitivity troponin of 331 and a BNP level of 21,503. EKG showed atrial fibrillation with RVR but no evidence of acute ischemic changes. A TTE was done which revealed an EF of 30-35% and diffuse hypokinesis with regional variation, a significant reduction from an EF of 50-55% just 4 weeks prior. The patient exhibited end-organ dysfunction, as evidenced by deranged liver function tests and a rise in creatinine from a baseline of 2 to 4.6, indicating congestive hepatopathy and cardiorenal syndrome respectively. The patient’s hemodynamics necessitated milrinone and norepinephrine infusions and efforts to wean them off were unsuccessful due to repeated failed fluid bolus challenges. Considering the patient’s clinical picture, there was a strong suspicion of viral-induced cardiomyopathy, and a COVID-19 infection was confirmed by PCR testing; his last COVID-19 booster dose was in 2021. The patient was promptly started on remdesivir and IV steroids. Unfortunately, the patient’s condition continued to deteriorate, and he succumbed to his illness.Discussion:A myriad of cardiovascular manifestations have been implicated with COVID-19, including ACS, myocarditis, and heart failure. Although the exact underlying mechanisms for each of these conditions are unclear, a complex interplay between direct viral injury, systemic inflammation, and cytokine storm has been hypothesized. Our case illustrates the quick progression of heart failure into cardiogenic shock requiring pressor support, with subsequent rapid decompensation rendering CMR, cardiac catheterization, and biopsy timely impractical. It serves as a reminder to explore COVID-19 as a potential cause of biventricular failure in individuals with no evident reason and rapid clinical deterioration, particularly as early initiation of antiviral therapy could improve prognoses.

Circulation, Volume 150, Issue Suppl_1, Page A4145096-A4145096, November 12, 2024. Introduction:Postural orthostatic tachycardia syndrome (POTS) and Inappropriate sinus tachycardia (IST) are common manifestations of cardiovascular dysautonomia (CVAD) in patients with post-COVID-19 syndrome. Studies regarding differences between post-COVID-19 POTS and post-COVID-19 IST have been sparse and based on small patient series.Aims:To examine clinical differences between POTS and IST in patients with post-COVID-19 syndrome.Methods:A cross-sectional observational study based on a dataset of patients diagnosed with post-COVID-19 syndrome and POTS/IST, at Karolinska University Hospital, Stockholm in 2020-2023, was performed. Data was retrieved using patients’ medical records. ANOVA, chi-square tests and Fisher’s exact tests were used for analysis.Results:A total of 200 patients diagnosed with post-COVID POTS/IST (ICD-10 codes, I.498 + U.099) were included (female, 85%) and divided into a POTS-group (n=110) and IST-group (n=90). Sixty-one patients (31%) met the diagnostic criteria of both and were included in the IST-group. The mean ages were 38 years for the POTS-group and 42 years for the IST-group (p=0.027). Hypertension was more common within the IST-group (p

Circulation, Volume 150, Issue Suppl_1, Page A4142935-A4142935, November 12, 2024. Background.Post-COVID syndrome is related to a multisystem disorder that affects in part the cardiovascular system. This disease involves symptoms, and conditions that continue or develop after acute COVID-19. SARS-CoV-2 infection of immune and endothelial cells are associated with NETosis, microthrombosis and endothelial dysfunction that could persist several weeks after acute phase of infection. Damaged endothelial cells can expose the vessel pro-coagulant area leading to platelet and neutrophil clumps. Increased levels of circulating endothelial cells (CECs) have been described as biomarkers for cardiovascular diseases. Therefore, we hypothesize that CECs and microthrombosis are potential biomarkers of vascular dysfunction in Long COVID.Methods.A cross-sectional study was conducted at the Miami VA long COVID clinic. Long COVID cases and controls were recruited according to WHO definition for long COVID. A total of 23 patients and 7 controls were included in this study. Blood samples were collected in Heparin and Sodium Citrate tubes. Cell immunophenotyping and NETosis markers (MPO) were quantified on a Cytek Aurora spectral flow cytometer system. Microclots (CD62P+PAC-1+) and platelet response were assessed by flow cytometry and response to Adenosine di-phosphate (ADP), respectively. A ttest was used for statistical analysis. Differences were considered significant when p < 0.05.Results.The age and gender were similar between cases and controls while their symptom score was significantly different. There was a significant increase in the number of CECs (CD31+CD309+CD45-CD133-) in Long COVID cases. MPO expression in neutrophils (CD11b+CD66b+CD15+) and classical monocytes (CD14+CD16-) was significantly higher in Long COVID. Microclots were significantly elevated, and the platelet aggregation response was dysregulated in Long COVID.Conclusions.CECs and microthrombosis including NETosis are present in Long COVID and may serve as potential biomarkers or causative mechanisms for vascular dysfunction.

Circulation, Volume 150, Issue Suppl_1, Page A4142129-A4142129, November 12, 2024. Background:The clinical impact of neutrophil to lymphocyte ratio (NLR) and right ventricular (RV) dysfunction on clinical outcomes in COVID-19 have not been studied in the often-underrepresented Indonesian population.Aim:To investigate the role of NLR and RV dysfunction in Indonesian patients hospitalized for COVID-19.Methods:A retrospective cohort study was conducted at a COVID-19 referral hospital in Indonesia. We included all adult patients hospitalized with COVID-19 between April 2020 – April 2021 who had transthoracic echocardiography (TTE) during admission. Clinical data were extracted from electronic medical records. TTE variables were defined according to the American Society of Echocardiography criteria. All statistical analyses were conducted using the SPSS software. This study was approved by the IRB at Universitas Indonesia (#2022-01-135).Results:A total of 488 patients were included – 29 with and 459 without RV dysfunction. The mean age of the population was 54.8 (SD ± 13.5), and 42% were females. Receiver operating curve analysis and Youden’s J statistics were used to determine the optimal NLR cut-off (Figure 1). An NLR > 4.79 was considered elevated, and had a sensitivity of 70.6% and a specificity of 80.6% in predicting severe – critical COVID-19. A high NLR (OR: 3.38, P = 0.02) and LV systolic dysfunction (OR: 9.76, P < 0.01) were independently associated with RV dysfunction. In multivariate cox regression analysis, older age (HR: 1.02, P = 0.01), obesity (HR: 1.85, P < 0.01), chronic kidney disease (HR: 1.69, P = 0.01), high NLR (HR: 2.75, P < 0.01), and RV dysfunction (HR: 2.07, P = 0.02) increased the risk of 30-day mortality.Conclusions:In Indonesian patients hospitalized with COVID-19, A high NLR is predictive of severe – critical COVID-19 and is associated with RV dysfunction. A high NLR at admission and RV dysfunction independently increase the risk of 30-day mortality in hospitalized Indonesian adults with COVID-19.

Circulation, Volume 150, Issue Suppl_1, Page A4143985-A4143985, November 12, 2024. Introduction:Endothelial dysfunction can trigger the development and progression of cardiovascular disease. We hypothesize that cardiovascular PASC is induced by persistent endothelial dysfunction mediated via asymmetric-dimethylarginine (ADMA, the endogenous inhibitor of endothelial nitric oxide synthase). ADMA levels rise in response to viral infections, but it is usually degraded by the enzyme DDAH1, which is inhibited by chronic inflammation and oxidative stress. This study aims to determine whether cardiovascular PASC is associated with endothelial dysfunction and to clarify the role of ADMA in this relationship.Methods:We recruited subjects who had been previously infected and developed cardiovascular symptoms (PASC+), those who had been infected but did not have PASC (PASC-), and those who had never been infected (controls) (n=20 each). Groups were matched for age, sex, and BMI and underwent blood draws and fat biopsies. Vascular function was assessedin-vivovia ultrasound imaging andex-vivoin fat-isolated arterioles.Results:Compared to PASC- and controls, PASC+ subjects exhibited 80% higher serum levels of ADMA and 40% reduced nitric oxide levels. DDAH1 activity was elevated in the PASC+, suggesting a compensatory mechanism for the elevated ADMA levels. However, PASC+ obese subjects exhibited substantially lower DDAH1 activity than non-obese subjects, which was associated with lower insulin sensitivity and higher ADMA levels. Compared to the other two groups, the PASC+ group exhibited lower brachial artery vasoreactivity, while nitroglycerin-induced dilation did not differ statistically, suggesting impaired endothelial function. In the PASC+ group, microvascular recruitment in response to reactive hyperemia was diminished, as was the ex vivo measured flow-induced arteriolar dilation and NO generation. Left ventricle (LV) dysfunction was observed in 80% of the PASC+ group, as opposed to 5% of the PASC- and controls. The LV ejection fraction and global longitudinal strain (GLS) were substantially reduced in the PASC+ group, which was correlated with higher ADMA, C-reactive protein, and troponin-1, as well as lower NO and vascular function. Obese PASC+ subjects had the highest ADMA and the lowest endothelial-dependent vasodilation and insulin sensitivity.Conclusion:Cardiovascular PASC symptoms are related to persistent endothelial dysfunction and elevated ADMA levels, which may be further exacerbated by obesity and reduced DDAH1 activity.

Circulation, Volume 150, Issue Suppl_1, Page A4141333-A4141333, November 12, 2024. Background:COVID-19 is a multiorgan disease characterized by a prothrombotic state and increased risk of venous thromboembolism (VTE), especially in hospitalized patients. Although prior studies have attempted to identify predictors of VTE, restricted sample size and use of administrative claims data have limited such analyses. We conducted a multivariable analysis to identify predictors of VTE in hospitalized patients with COVID-19 in a multicenter patient-level registry.Methods:We utilized data from the CORONA-VTE Network, a US multicenter registry of 10,420 adult (≥18 years) patients with PCR-confirmed COVID-19 of whom 3,844 were hospitalized. The primary outcome was time-to-first-event for a composite of adjudicated pulmonary embolism and deep vein thrombosis (e.g. lower extremity, mesenteric, gonadal vein, etc.) during 90-day follow-up. The candidate variables were selected by a priori clinical consensus. The variables with ≥20% missing data were excluded, whereas those with missing data

Circulation, Volume 150, Issue Suppl_1, Page A4126987-A4126987, November 12, 2024. Background:COVID-19 infection has been associated with a broad range of clinical manifestations. There are very few reported cases of COVID-19 patients presenting with syncope as an initial symptom. We present an extraordinary case of recurrent neurocardiogenic syncope in a COVID-19 patient.Case:A 66-year-old male presented after experiencing two episodes of syncope. He denied any prodromal or anginal symptoms. His medications included propranolol 10 mg twice daily for essential tremors. He had no family history of unexplained syncope or sudden cardiac death. He was hemodynamically stable and had one episode of fever at 102°F. Telemetry recording showed vagal-mediated sinus arrest and pauses without escape. Blood work showed normal cell counts, electrolytes, thyroid-stimulating hormone, and erythrocyte sedimentation rate, with a slightly elevated C-reactive protein of 22.2 mg/L. He tested positive for COVID-19 and had negative Lyme and Ehrlichia serologies.Decision Making:Due to symptomatic long sinus pauses, propranolol was discontinued, and he received a temporary pacemaker set at 50 beats per minute (bpm). He had another syncopal episode while being paced at 50 bpm, suggesting a neurocardiogenic mechanism, so the pacing rate was increased to 70 bpm. An echocardiogram showed a normal ejection fraction without any significant valvular disease. The syncope was determined to be vasovagal due to autonomic dysfunction in the setting of COVID-19. After 72 hours without further syncope, the temporary pacemaker was removed, and he was discharged home with an implantable loop recorder (ILR). A one-month follow-up showed no syncope, and ILR interrogation showed no bradycardia or pauses.Conclusion:Neurocardiogenic syncope with prolonged asystole and sinus pauses is an uncommon presentation of COVID-19 infection. The clinical course of autonomic dysfunction following COVID-19 is not very clear, and monitoring with an ILR is reasonable before considering permanent pacemaker implantation.

Circulation, Volume 150, Issue Suppl_1, Page A4148010-A4148010, November 12, 2024. Background:Severe COVID-19 infection has been associated with acute respiratory distress syndrome (ARDS) and right ventricular (RV) dysfunction. In this study, we report associations between echocardiographic findings and laboratory markers that portend RV failure in patients with ARDS secondary to COVID-19 infection on ECMO.Methods:A single-center study was conducted in the cardiovascular ICU of our institute. A retrospective chart review was performed on 41 patients with COVID-19 on ECMO between March and October 2020. Twenty-two patients had transthoracic echocardiograms (TTE) completed while on ECMO (VV-ECMO = 19, VA-ECMO = 3). Echocardiograms (echo) were obtained pre-cannulation, during ECMO, and post-ECMO decannulation. RV parameters analyzed included tricuspid annular plane systolic excursion (TAPSE), basal diastolic RV diameter, right ventricular fractional area of change (RV FAC), and S’. Laboratory values including BNP, CRP, D-dimer, ferritin, fibrinogen, lactate and troponin were analyzed for correlation with echo findings.Results:TAPSE was significantly lower in deceased patients (1.9± 0.4cm vs 1.3±0.6 cm, P< 0.05). RV FAC and S’ were also lower in the deceased group. TAPSE while on ECMO showed a positive association with peak D-dimer levels in survivors and a negative association in deceased patients. Peri-ECMO fibrinogen and CRP levels were negatively associated with TAPSE in survivors while fibrinogen showed positive association in deceased patients. LDH peak, fibrinogen initial and lactate peak were higher in the deceased[ZQ1] group. There is a trend of increased RV basal diameter in the deceased group (3.9±0.9 vs 4.2±0.9 cm). Last troponin levels were negatively associated with basal diastolic RV diameter while on ECMO in deceased patients.Conclusion:Preservation of RV longitudinal contractility, as reflected by TAPSE, may play an important role in the survival of COVID-19 patients on ECMO. Laboratory markers such as LDH, D-dimer, fibrinogen and lactate may have prognostic value in predicting RV failure. Further studies are required to determine if early initiation of therapies to improve RV systolic function in COVID-19 ECMO patients with ARDS improves outcomes.

Circulation, Volume 150, Issue Suppl_1, Page A4146592-A4146592, November 12, 2024. Introduction:Low physical activity (PA) has been identified as a risk factor for development of atrial fibrillation (AF). However, the effect of changes in PA on directly recorded AF burden has not been well studied. The COVID-19 pandemic offered an opportunity to observe whether changes in activity were correlated with changes in AF burden. To determine if reduced PA is associated with higher AF burden, we assessed daily PA and AF burden data from patients with cardiac implantable electronic devices (CIEDs) enrolled in a prospective clinical trial, Targeting Risk Interventions and Metformin for Atrial Fibrillation (TRIM-AF, NCT03603912).Methods:Daily AF burden and activity were determined from implantable cardiac devices with atrial leads. The pandemic lockdown period was analyzed for up to 1 year. Pre-pandemic periods were matched by month to pandemic periods. To test the potential confounding of aging, pre-pre-pandemic periods were matched by month to pre-pandemic periods. To reduce the confounding of study interventions, matched periods were taken on one side of the study enrollment date. For PA and AF burden, Gaussian linear mixed models and a Bayesian mixed effect model were fitted and adjusted for age, sex, and device manufacturers. A Gaussian model was used to correlate daily activity minutes and AF%. Time splines were added to adjust for non-linear time effects. Outcomes are reported as mean activity minutes and daily AF%.Results:Comparing Pandemic vs. Pre-periods (N=82 periods; 55 male, 27 female), daily activity minutes decreased by a mean of 13.16±1.06 minutes/day, and daily AF burden increased by 16% [5%-26%]. Comparing Pre vs. Pre-Pre-Pandemic periods (N=60 periods; 41 male, 19 female), mean activity decreased by 2.28±1.13 mins/day, and AF burden increased by 57% [50%-64%]. A significant negative correlation between activity and AF burden was demonstrated (coefficient -2.0, 95% CI -2.4, -1.6). A decrease in 2.0 activity minutes was associated with a 10% increase in AF burden.Conclusions:This natural history analysis of PA and AF burden demonstrated decreases in activity and increases in AF burden with time and the pandemic. Activity and AF burden were significantly negatively correlated.

Circulation, Volume 150, Issue Suppl_1, Page A4140201-A4140201, November 12, 2024. Introduction:While implantable cardiac defibrillators (ICD) decrease sudden cardiac death, disparities in ICD use remain. The COVID-19 pandemic created strains on the US healthcare system that may have exacerbated these disparities.Methods:Using the US NCDR registry of primary and secondary prevention ICD implants, we compared sex, racial and ethnic disparities for 239,014 patients, aged 19-90 years, grouped into three time intervals from 2016 to 2022: Pre-COVID, COVID and Post-COVID. Centers without consistent reporting were excluded, as were patients with incomplete sex, race or ethnicity data. ICD implantation rates were compared using a Poisson regression model with interaction tests for sex, race and ethnicity by time window to see if disparities changed within this period. Implant rates by indication were also assessed.Results:Overall ICD implants decreased over the study period (Figure 1) with an average monthly rate of 3271 in the first three months of 2016 declining to 2334 in the last three months of 2022 (p=0.017). Disparities in ICD implantation for women, racial and ethnic minorities were observed pre-COVID and persisted (Table 1). Average ICD implant rates during these time periods varied by race with predominance in White patients. While gaps in ICD implant persisted, the disparities did not worsen during COVID-19 by sex, race or ethnicity (p-value for interactions were 0.79; 0.47; and 0.095, respectively). There was a more significant decrease in primary prevention ICD compared to secondary prevention ICD (p

Circulation, Volume 150, Issue Suppl_1, Page A4141078-A4141078, November 12, 2024. Background:Social determinants of health (SDOH),exacerbated by the COVID-19 pandemic, impact access to medical care.Research Question:Through descriptive qualitative inquiry, we explored barriers and facilitators to pediatric cardiology ambulatory care for patients with complex congenital heart disease (CCHD) during COVID-19.Methods:English- and Spanish-speaking caregivers of children with CCHD who missed at least one clinic visit during the first year of COVID-19 were recruited, with purposeful sampling of Black and Hispanic patients. Semi-structured interviews inquired about the impact of the pandemic, experience with telehealth and communication with providers, effects of SDOH, and perceived impact of their race/ethnicity on care. Content analysis summarized information and identified themes.Results:Interviews (19) were conducted: 14 in English (6 Black, 2 Hispanic, 2 White, 3 mixed race, 1 American Indian), and 5 in Spanish (5 Hispanic). Overarching themes were: Barriers to Care, Facilitators of Returning/Staying in Care, Impact of Diagnosis, and Recommendations for Improvement (Image 1). Despite challenges with finances and transportation, as well as concern for infection risk, the majority of caregivers preferred in-person care over telehealth due to physical exam, diagnostic testing, and interpersonal connection with providers. SDOH challenges including housing, transportation, and employment contributed to missing care. For some families, social vulnerability was exacerbated by their child’s CCHD diagnosis and then again by COVID-19. Universally, caregivers felt their child’s race/ethnicity did not affect the care they received. Spanish-speaking caregivers expressed their primary language as a barrier to care and their desire for more thorough explanations and teach-back from the medical team.Conclusion:While SDOH can hinder access to ambulatory cardiac care, trusting relationships with care teams facilitated engagement. Social vulnerability contributed to dynamic situations for families, especially during COVID-19, highlighting the need for routine SDOH assessment and support. English- and Spanish-speaking caregivers echoed the same challenges. Race/ethnicity was not felt to impact care received.

Circulation, Volume 150, Issue Suppl_1, Page A4113573-A4113573, November 12, 2024. Introduction/Background:Cardiovascular and neurological diseases develop in a significant proportion of COVID-19 patients. Minimally invasive tools to predict outcome after SARS-CoV-2 infection would enable personalized healthcare, potentially easing the disease burden. We showed that blood levels of the long noncoding RNA lymphoid enhancer-binding factor-1 antisense 1 (LEF1-AS1) predict COVID-19 in-hospital mortality.Hypothesis:LEF1-AS1 is associated with long-term clinical outcomes of COVID-19.Aim:Test the capacity of LEF1-AS1 to predict neuro-cardio-vascular outcomes post-SARS-CoV-2 infection.Methods/Approach:We enrolled 104 primo-infected COVID-19 patients aged 18+ recruited from April to December 2020 in the PrediCOVID national cohort for which 12-month follow-up data were available (Ethics Committee approvals 202003/07 and 202310/02-SU-202003/07). Whole blood samples were collected at baseline and expression levels of LEF1-AS1 were assessed by quantitative PCR.Results/Data:Of the 104 patients, 35 had at least one neurological symptom and one cardiovascular symptom at month 12. Levels of LEF1-AS1 at baseline were lower (p=0.019) in patients who developed neurological and cardiovascular symptoms as compared to patients who did not. Lower LEF1-AS1 was associated with symptoms development with an odds ratio of 0.48 (95% CI 0.28-0.83) from logistic regression model adjusted for age, sex, comorbidities and disease severity at baseline. Addition of LEF1-AS1 to a clinical model including age, sex, comorbidities and baseline severity yielded an incremental predictive value as attested by an increased AUC from 0.79 to 0.83 (likelihood ratio test p=0.005), a net reclassification index of 0.54 (p=0.007) and an integrated discrimination improvement of 0.08 (p=0.009).Conclusion:Blood levels of LEF1-AS1 predict 12-month neurological and cardiovascular outcomes of COVID-19 patients. This needs to be validated in larger populations.