Circulation, Volume 150, Issue Suppl_1, Page A4139209-A4139209, November 12, 2024. Background:There has been growing awareness and recognition of discrepant health outcomes based on ethnic and racial background in patients undergoing cardiovascular procedures. Transcatheter aortic valve procedures has become the primary treatment for aortic stenosis and is currently the standard of care. Despite widespread adoption of TAVR, African Americans (AA) have continued to remain underrepresented and typically suffer poorer outcomes. Thus, we conducted a systematic review and meta-analysis to compare TAVR outcomes between AA and non-AA populations.Methodology:We systematically searched all electronic databases (PubMed, EMBASE, Scopus, Web of science) from inception until May 25th, 2024. A pooled analysis of data from observational studies and randomized controlled trials reporting post-TAVR outcomes based on racial background were included. The key endpoints evaluated were in-hospital mortality, post-procedure myocardial infarction (MI), pacemaker placement, in-hospital stroke, vascular complications, major bleeding, acute kidney injury (AKI). We used the I2 statistic to assess heterogeneity among studies using the Random-Effects model, with significance set at I2 > 50%. All analysis was carried out using R version 4.3.2.Results:The meta-analysis of eleven observational studies, involving 953,892 TAVR patients [912,301 (95.64%) Caucasians and 41,591 (4.36%) AAs], showed a statistically significant higher risk of post-procedure pacemaker placement (OR 1.08, 95% CI: 0.77-1.51, p=
Risultati per: La fase post-acuta del COVID-19: una nuova sfida per il medico di medicina generale
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Abstract 4119613: Evaluation of Gender, Racial and Ethnic Differences in Time to PCI in the Pre and Post Covid-19 Era
Circulation, Volume 150, Issue Suppl_1, Page A4119613-A4119613, November 12, 2024. Introduction:Percutaneous Coronary Intervention (PCI) is recommended for reperfusion of patients presenting with ST-segment myocardial infarction (STEMI) within 90 minutes. In this study, we sought to identify differences in PCI timing based on gender, race and ethnicity in the pre- and post-COVID era.Methods:We collected retrospective data on 760 patients admitted with STEMI at our quaternary academic medical center from 2018-2022. We defined our binary outcome as time to PCI less than 90 minutes, and adjusted for transfers from outside hospitals. We utilized univariate logistic regression analysis to analyze the association of demographic, clinical, and cardiac catheterization details on our outcome. We then utilized multivariate logistic regression analysis to determine the association of our covariates of interests with time to PCI. The logistic regression model was adjusted for collinearity which were deemed not significant.Results:Among our study population, COVID did not significantly impact whether or not a patient had a diagnostic cardiac catheterization on univariate analysis (OR 2.68, 95% CI 0.61-18.40, p=0.23). However, the post-COVID era was significantly associated with a delayed time to PCI on multivariate analysis [OR 1.62, 95% CI 1.04-2.55, p=0.035) [Figure 1]. In addition, females were 1.8x more likely to have a delayed PCI than males on multivariate regression [OR 1.80, 95% CI 1.10-2.95, p= 0.019) [Figure 1]. Interestingly, on multivariate analysis, females were more likely to have delayed reperfusion in the pre-COVID era (OR 2.92, 1.29-6.77,p= 0.01) but not the post-COVID era (OR 1.54, 0.78-3.06,p=0.2134). Patients in the post-COVID era had increased risk of having their culprit coronary not revascularized on multivariate analysis (OR 2.85, 1.2-8.03, p= 0.03).Conclusions:At our center, COVID did not significantly impact cardiac catheterization rates. However, COVID was significantly associated with delayed reperfusion timing and not revascularizing culprit vessels. Females were much more likely to have a delayed PCI than males in the pre-COVID era which was not seen following COVID-19.
Abstract 4145154: A Pilot Study of Post-Discharge Atrial Fibrillation Using a Novel Mobile Electrocardiography Monitoring Device
Circulation, Volume 150, Issue Suppl_1, Page A4145154-A4145154, November 12, 2024. Introduction:Post-operative atrial fibrillation (AF) is the most common arrhythmic complication after CABG. Following inpatient treatment, data on the frequency and duration of recurrent AF after hospital discharge remain sparse.Research Question:Do patients who experience in-hospital post-operative AF have recurrent arrhythmias in the 30 days post discharge?Goals:To characterize the burden of AF after hospital discharge using a wearable telemetry device.Methods:Patients enrolled in the CTSN PACeS trial were eligible for this sub-study. PACeS is a randomized trial of anticoagulation versus no-anticoagulation in patients with new-onset post-operative AF. Eligibility criteria include patients with new onset AF defined as AF > lasting 60 minutes or recurrent AF episodes within 7 days after CABG and before hospital discharge. All patients in this sub-study wore a 3-lead mobile telemetry device upon hospital discharge that provided continuous beat-to-beat data for 30 days. For this analysis, an AF event was counted if it was at least 30 seconds in duration.Results:Forty-six patients participated in this sub-study. The mean age was 68.8 years, 21.7% were women, 78.3% White and 11% Hispanic. The mean and median device wear times were 23 and 29 days, respectively. The average total available analytic time (i.e., total time of interpretable electrocardiographic signal) was 20.3±3.3 hours/day. At least one episode of AF post-discharge was detected in 38 (82.6%) of patients. Among these, the median number of days in which patients had an episode of AF was 6. The mean duration of time in AF was 1.6±1.7 hours/day and the overall percent time in AF was 7.5%. Most patients (78.3%, n=36) had AF for
Abstract 4145096: Postural Orthostatic Tachycardia Syndrome and Inappropriate Sinus Tachycardia – Two Distinct Phenotypes in Post-COVID-19 Cardiovascular Dysautonomia: Prevalence, Overlap and Clinical Characteristics
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
Abstract 4140452: Impact of Beta-Blocker Dosage on All-Cause Mortality Post-Myocardial Infarction in Patients with Ejection Fraction ≥50%
Circulation, Volume 150, Issue Suppl_1, Page A4140452-A4140452, November 12, 2024. Background:The recent REDUCE-AMI trial showed no benefit to beta-blockers (BB) for patients post-myocardial infarction (MI) with preserved ejection fraction (EF≥50%). Target doses were metoprolol 100 mg and bisoprolol 5 mg daily (50% of the target doses used in the initial randomized clinical trials [RCTs] of BB post-MI).Research question:Do lower BB doses improve survival in post-MI patients with EF≥50%?Aims:To compare the effect of BB dose on all-cause mortality post-MI in patients with EF≥50%.Methods:This is a sub-study from the OBTAIN prospective multi-center registry. Of 7057 patients enrolled with acute MI, 3402 with EF≥50% were discharged alive (age:62.5±13.4 years, 67% male, 28% diabetics, length of stay 6.1±6.0 days). Discharge BB dose was indexed to the target daily BB dose used in RCTs, reported as %. Dosage groups were >0-12.5%, >12.5-25%, >25-50%, and >50% of the target dose. Follow-up vital status was obtained by chart review, Social Security Death Index, or direct contact up to 3 years post-MI. Kaplan-Meier (KM) method was used to calculate three-year survival. Cox proportional hazard regression model was used to identify significant predictors and conduct univariate and multivariate analysis.Results:The KM 3 year survival estimates were 89.0% and 84.3% for patients on and off BB, respectively (unadjusted hazard ratio (HR)=0.66, p=0.012; adjusted HR=0.52, p=0.18). The KM 3 year survival estimates(figure) were 89.8%, 91.0%, 87.9%, and 83.1% for patients on >0-12.5%, >12.5-25%, >25- 50%, and >50% of the BB target dose (unadjusted HR of 0.58, p=0.007; 0.58, p=0.003; 0.70; p=0.066; and 0.98, p=0.93), respectively, compared to no BB. After multivariate analysis, BB target dose showed similar trend, but not statistically significant (adjusted HR=0.65, p=0.46; 0.42, p=0.13; 0.53, p=0.31; 1.01, p=0.92).Conclusion:In OBTAIN, patients treated with low dose BB (≤25% of the target dose) had improved survival post-MI. As this dose was not studied in REDUCE-AMI, these findings are complementary and confirm only that high dose BB therapy provides no benefit post-MI in patients with preserved EF. RCTs to assess the benefit of low dose BB therapy post-MI with preserved EF are needed.
Abstract 4143186: Prior Statin Therapy Reduces Inflammation and Improves Outcomes in Patients Hospitalized for Covid-19: A Prospective Multicenter Cohort Study
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.
Abstract 4146512: Modifiability of Post-Exercise Oxygen Uptake Recovery Patterns: A Substudy of the SEQUOIA-HCM Randomized Trial
Circulation, Volume 150, Issue Suppl_1, Page A4146512-A4146512, November 12, 2024. Background:Recent heart failure studies show that post-exercise VO2recovery (VO2Rec) patterns track closely with exercise cardiac output and outcomes, but not with peripheral oxygen (O2) extraction. In patients with obstructive hypertrophic cardiomyopathy (oHCM), studies of VO2Rec changes with effective cardio-specific interventions are lacking. We hypothesized that treatment with aficamten, a next-in-class cardiac myosin inhibitor, would shorten VO2Rec in patients with oHCM.Methods:SEQUOIA-HCM is the pivotal phase 3 trial of aficamten in symptomatic patients with oHCM (New York Heart Association functional class [NYHA FC] II-III, peak VO2[pVO2] ≤90% predicted, respiratory exchange ratio ≥1.05). Patients were randomized 1:1 to aficamten or placebo for 24 weeks with the primary endpoint of change from baseline (BL) in pVO2. For this analysis, VO2Rec was measured as the time taken after exercise cessation for VO2to decline by 12.5% (t12.5%), 25%, or 50% of pVO2. Response rates for achieving clinically meaningful threshold reductions ( >15 seconds) in t12.5%, and correlations with changes in cardiac function (echocardiographic parameters/cardiac biomarkers) were assessed.Results:Among 282 randomized patients (mean age 59.1±12.9 years, 115 female [41%]), 263 (93%) had CPETs at BL and W24 with VO2Rec values as shown (Table). At W24, t12.5%improved by 8sec (95% CI, -12, -5sec, p
Abstract 4140906: Cardiovascular Prognosis in Patients with Diabetes Mellitus Mediated by the Functional Post-revascularization Level
Circulation, Volume 150, Issue Suppl_1, Page A4140906-A4140906, November 12, 2024. Background and Aims:Functional complete revascularization (FCR) subsequent to percutaneous coronary intervention (PCI), as assessed by the residual functional SYNTAX score (rFSS), has been correlated with enhanced prognostic outcomes. This study sought to comprehensively apprehend the adverse cardiovascular prognosis within diabetic cohorts, determining what extent the association of diabetes with clinical outcomes is explained by functional revascularization.Methods:A total of 1,555 patients with available post-PCI quantitative flow ratio (QFR) were included, whose data were collected from PANDA III trial (Figure 1). FCR was defined as rFSS = 0, while anatomic complete revascularization (ACR) was defined as residual SYNTAX score (rSS) = 0. Firstly, we determined the ACR and FCR among DM and non-DM cohorts. Second, multiple cox regression was used to screen for potential mediating variables. Finally, we used structural equation modeling to analysis whether FCR explained the relationship between DM and the risk of 2-year rates of major adverse cardiac events (MACE).Results:Patients with DM had a significant lower percentage of FCR (71.9% vs 80.2%, P
Abstract 4136204: Clearing Senescent Cells Improves Mouse Survival Rate Post Myocardial Infarction through Alteration of Cardiomyocyte and Immune Cell Subpopulations
Circulation, Volume 150, Issue Suppl_1, Page A4136204-A4136204, November 12, 2024. Introduction:Cellular senescence often involves a p16-pathway, and p16 overexpression is a hallmark of senescent cells. The role of cellular senescence in myocardial infarction (MI) and any mediating mechanisms remain unclear.Aims:To investigate the effect of p16+cell clearance on survival post MI and elucidate underlying mechanisms.Methods:We utilized INK-ATTAC transgenic mice, in which p16+cells undergo targeted apoptosis upon exposure to AP20187 (AP). Sham and MI mice were treated with AP or vehicle (V) twice-weekly for one month, starting 3-4 hours post-MI. Survival rate improvement post MI in the AP group (Fig A, P
Abstract 4139977: Aggressive LDL cholesterol lowering post ACS with triple combination therapy: Insights from the multicentric LAI-REACT study
Circulation, Volume 150, Issue Suppl_1, Page A4139977-A4139977, November 12, 2024. Background:Patients with acute coronary syndrome (ACS) face a high risk of recurrent events in the early post ACS period. Rapid reduction of low-density lipoprotein cholesterol (LDL-C) is crucial, but high-intensity statins (HIS) alone often fall short of goals.Research Hypothesis:Early use of triple combination therapy of HIS with non-statin drugs: ezetimibe and bempedoic acid (BA) is likely to help achieving the target goals rapidly.Aim:The LAI-REACT (Lipid Association of India Recommended Early and aggressive lipid lowering in ACS with triple Combination Therapy) study evaluated the LDL-C lowering efficacy of a novel triple combination REB (40 mg rosuvastatin, 10 mg ezetimibe, and 180 mg bempedoic acid daily), in patients with ACS.Methods:The multicentric LAI-REACT study enrolled 369 statin-naïve ACS patients across five Indian centers. All received the triple REB combination upon admission. Lipid profiles were assessed at baseline and weeks 1, 2, 4, and 6.Results:The mean age of the study population was 56.3 ± 11.3 years. The mean LDL-C at admission was 119.2 ± 37.1 mg/dL, which significantly decreased to 49.4 ± 19.3 mg/dL at week 1, 44.7 ± 17.4 mg/dL at week 2, 44.6 ± 16.6 mg/dL at week 4, and 46.7 ± 18.3 mg/dL at week 6. The percentage reductions in LDL-C at weeks 1, 2, 4, and 6 were 58.6%, 62.5%, 62.6%, and 60.8% respectively (repeated measures ANOVA, p
Abstract 4141078: Hearing the Voices of Families: Barriers and Facilitators of Pediatric Cardiac Ambulatory Care During the COVID-19 Pandemic
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.
Abstract 4141358: Body weight reduction-associated and -unassociated changes in lipid profile in people with obesity, with or without T2D, treated with tirzepatide: post-hoc analysis of SURMOUNT-1 and SURMOUNT-2
Circulation, Volume 150, Issue Suppl_1, Page A4141358-A4141358, November 12, 2024. Background:Tirzepatide is a once weekly GIP and GLP-1 receptor agonist approved for the treatment of type 2 diabetes (T2D) and obesity. This post hoc analysis evaluated the contribution of body weight reduction-associated and -unassociated effects on the lipid profile of tirzepatide-treated participants living with obesity, without and with T2D, from the SURMOUNT-1 and SURMOUNT-2 clinical trials, respectively.Methods:Participants treated with tirzepatide (pooled doses of 5, 10, 15 mg in SURMOUNT-1 [N=1765] and 10 and 15 mg in SURMOUNT-2 [N=587]) were included in this analysis. The estimated treatment effects and the body weight reduction-associated and -unassociated attribution on changes from baseline in lipid profile (total cholesterol, HDL-C, LDL-C, non-HDL-C, VLDL-C, and triglycerides) at 24 and 72 weeks were assessed via the SAS CAUSALMED procedure.Results:In SURMOUNT-1, after 24 weeks of tirzepatide treatment in participants without T2D, 69-85% of the changes in total cholesterol, HDL-C, LDL-C, and non-HDL-C, and 41-43% of the changes in VLDL-C and triglycerides occurred unassociated with body weight reduction (Table). At 72 weeks, most of the effect on the lipid profile was associated with body weight reduction. In SURMOUNT-2, after 24 weeks of tirzepatide treatment in participants with T2D, most of the changes in the lipid profile occurred unassociated with body weight reduction. At 72 weeks, changes observed in the lipid profile were predominantly associated with body weight reduction, although 43-50% of those changes also occurred unassociated with body weight reduction, except for LDL-C which was almost completely (92%) associated with body weight reduction.Conclusions:In this post hoc analysis from SURMOUNT-1 and SURMOUNT-2, changes in lipid profile were mostly unassociated with body weight reduction after 24 weeks of tirzepatide treatment and associated with of body weight reduction at 72 weeks. Body weight reduction-unassociated mechanisms responsible for the initial changes in lipid profile in participants with obesity treated with tirzepatide warrants further research studies.
Abstract 4144690: Impact of Apolipoprotein A-1 Infusion on Coronary Atherosclerosis Post-Acute Coronary Syndrome: A Network Meta-Analysis of randomized controlled trials.
Circulation, Volume 150, Issue Suppl_1, Page A4144690-A4144690, November 12, 2024. Background:High-density lipoproteins (HDLs) have various potentially beneficial circulatory effects. Apolipoprotein A-1, one of the HDL mimetics, has been shown in several studies to slow the progression of atherosclerosis after an acute coronary syndrome (ACS) event.Aim:To evaluate the comparative efficacy of Apo A1 on Total Atheroma Volume (TAV), Percent Atheroma Volume (PAV), and changes in these parameters.Methods:We systematically searched articles in PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase published up to June 2024. Eligible randomized controlled trials (RCTs) enrolled adults who received Apo A1 infusion, compared to placebo, within 2 weeks of an ACS event (defined as unstable angina, non-ST or ST-segment elevation myocardial infarction) or with at least one narrowing of ≥20% on coronary angiography at baseline. Apo A1 infusion preparations evaluated include ETC-216, CER-001, CSL-111, and MDCO-216. Network meta-analysis was performed.Results:A total of 5 RCTs were included in our analysis. Outcomes evaluated include PAV, TAV (measured by intravascular ultrasonography catheter), and changes in these values from baseline to follow-up. For changes in PAV, only ETC-216 45 mg was statistically significant (MD: -12.74, [-20.70; -4.78]). All other regimens were statistically insignificant: ETC-216 15 mg, ETC-216 15 and 45 mg combined, CER-001 3 mg, CER-001 6 mg, CER-001 12 mg, MDCO-216 20 mg, and CSL-111 40 or 80 mg. In addition, changes in TAV showed no significant treatment effects. PAV was lowest at follow-up in the CER-001 3 mg (MD: -1.68, [-4.73; 1.38]) and MDCO-216 20 mg (MD: 1.00, [-3.64; 5.64]) groups; all other ETC-216 and CER-001 regimens were insignificant. For TAV, only MDCO-216 20 mg (MD: -10.00, [-39.58; 19.58]) and CER-001 3 mg (MD: -2.47, [-19.84; 14.90]) showed insignificant treatment effects, while all ETC-216 regimens had no beneficial effect.Conclusion:Our analysis concludes that ETC-216, 45 mg showed a significant reduction in PAV. Other regimens were insignificant in their effect on atheroma reduction. This analysis highlights the need for further clinical trials to explore this regimen for enhancing responses in ACS patients.
Abstract 4143118: Association of Left Atrial Fibrosis with AF Burden Post-Ablation: Insights from the DECAAF II Study
Circulation, Volume 150, Issue Suppl_1, Page A4143118-A4143118, November 12, 2024. Introduction:Left atrial (LA) fibrosis identified by delayed enhancement MRI has been linked to poor outcomes post-AF ablation. We aim to assess the relationship between LA fibrosis and post-ablation AF burden in a persistent AF population.Methods:This is a subanalysis from the DECAAF II trial which included persistent AF undergoing catheter ablation. Delayed enhancement MRI was performed up to 30 days pre-ablation. Fibrosis was quantified at a core lab and categorized into 4 stages: 1 (
Abstract 4140585: Shifting in the settings of stroke fatalities during the COVID-19 pandemic
Circulation, Volume 150, Issue Suppl_1, Page A4140585-A4140585, November 12, 2024. Introduction:Stroke-related mortality poses significant challenges in the US. Increased at-home deaths since COVID-19 pandemic prompted changes in the provision of end-of-life care.Question:What were the settings of stroke deaths in the US during COVID-19 pandemic?Methods:Decedent-level mortality data from death certificates in CDC repository were obtained for the year 2020 (pandemic) and 2019 (comparison). Demographic data include age, sex, race/ethnicity, education, marital status, and place of stroke death, including inpatient, outpatient/emergency room (ER), hospice/nursing facilities (H/NF), and at-home. Multivariable logistic regression models assessed demographic impact on stroke mortality by place-of-death, yielding odds ratios (OR) with significance threshold of p65 years were more likely to die in H/NF (OR 10.05, p
Abstract 4143985: Post-acute Sequelae of COVID-19 (PASC) is Related to Endothelial Dysfunction and Elevated Asymmetric-dimethylarginine
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.