Risultati per: Long COVID: principali risultati, meccanismi e raccomandazioni

Circulation, Volume 150, Issue Suppl_1, Page A4146890-A4146890, November 12, 2024. Background:COVID-19 has introduced new complexities in the management of patients undergoing the transcatheter edge-to-edge repair (TEER) procedure of the mitral valve. This study compares outcomes of mitral valve TEER in patients with and without COVID-19, utilizing data from the National Inpatient Sample (2020-2021).Methods:We conducted a retrospective cohort study on 23,465 patients without COVID-19 and 85 patients with COVID-19 undergoing mitral valve TEER. Multivariate logistic regression was employed to compare outcomes, adjusting for potential confounders. Primary outcomes included mortality and major complications, while secondary outcomes encompassed specific procedural complications.Results:Patients with COVID-19 were younger (mean age: 73.176 vs. 76.178 years, p-value

Circulation, Volume 150, Issue Suppl_1, Page A4142266-A4142266, November 12, 2024. Introduction:Supraventricular tachycardia (SVT) is common and poorly tolerated in patients who have undergone Fontan procedure. Recurrence rates after catheter ablation in these patients are high. Recent data on the outcomes of SVT ablation and the predictors of recurrence in this population is lacking.Objective:Our study aimed to characterize clinical variables in patients with a Fontan undergoing EP ablation, investigate long-term outcomes, and determine factors that are associated with recurrence.Methods: Charts of patients who had undergone Fontan procedure and underwent SVT ablation between January 1, 1995, and October 1, 2023, at a tertiary care center were reviewed. Demographic, clinical, and outcome variables over 5 years were compared between patients with and without SVT recurrence.Results:Mean age of 25 patients (56% male) at time of SVT ablation was 31.5 ± 7.2 years. Ablation success rate was 92%. Recurrence occurred in 12 (48%) patients, with 7 (28%) requiring repeat ablations repeat within 5 years. Rate of recurrence did not differ between those who had the procedure before or after 2018. During the 5-year follow up period, 13 (59%) patients with follow up had cardiovascular (CV) hospitalization and 1 patient died. Atrial Tachycardia (70%) and Typical Atrial Flutter (65%) were the most common SVTs ablated. A trans-baffle puncture during the ablation was performed in 6 (23%) patients. Tricuspid atresia and elevated BNP levels were associated with increased risk of SVT recurrence (Table).Conclusion:Recurrence and cardiac hospitalization rates after SVT ablation in this population remain high. This study underscores the need for risk stratification in patients with Fontan physiology undergoing SVT ablation and informs future research directions for enhancing ablation outcomes.

Circulation, Volume 150, Issue Suppl_1, Page A4114220-A4114220, November 12, 2024. Background:It is still not well understood whether cardiac injury observed during acute COVID-19 infection extends after recovery from the initial viral infection. The purpose of this study was to determine the incidence of left and right ventricular dysfunction in patients hospitalized with acute COVID-19 and evaluate for cardiac recovery.Methods:A multicenter, retrospective cohort study was conducted. Adult patients were identified by hospitalizations using ICD-10 code U07.1 from March 2020 to October 2021. Patients were included if they had: 1) acute COVID-19 infection confirmed by RT-PCR and 2) a transthoracic echocardiogram (TTE) performed during their hospitalization. Clinical and echocardiographic data were collected and analyzed. Longitudinal TTE parameters were obtained from follow-up studies performed after discharge.Results:A total of 750 patients (mean age 64.3 ± 15.3 years, 60.0% male) were included. The average time to follow-up TTE was 8.7± 7.4 months. 133 patients (17.7%) had new LV dysfunction seen on TTE (Figure 1). LV recovery (defined as normalization of LVEF or improvement of LVEF by >10% from baseline) was observed in 28 of 74 (37.8%) survivors. 9 of 26 patients (34.6%) who had a follow-up TTE

Circulation, Volume 150, Issue Suppl_1, Page A4146081-A4146081, November 12, 2024. Background:Long QT Syndrome (LQTS) is an inherited arrhythmia syndrome that predisposes patients to sudden death. Prior studies on racial disparities in LQTS have shown similar number of cardiac events, but longer QTc in Black patients compared to non-Hispanic Whites (NHW). There is limited data on cardiac events in Hispanic children with LQTS. We hypothesized that Hispanic children with LQTS have worse outcomes compared to NHW children.Methods:This retrospective cohort study of the Pediatric Health Information System (PHIS) database included children ages 0 – 17 years hospitalized from 2013-2024 with an International Classification of Disease 9thor 10thedition code for LQTS listed in the first five admission diagnoses. Patients with congenital heart disease and chromosomal abnormalities were excluded. The primary predictor variable was race/ethnicity, with covariables including age, sex, and insurance type. Our primary outcome variable was a documented lethal arrhythmia, and secondary outcomes included pacemaker and/or implantable cardioverter defibrillator (ICD) placement. Chi-square was used to assess patient characteristics. Univariable mixed-effect log-binomial regression was used to assess risk of outcomes by characteristics using hospital as a random effect with multivariable models generated via backward elimination.Results:We identified 6,476 children (24% Hispanic, 76% NHW). Compared to NHW children, Hispanic children were more often male and presented earlier (median age 11y vs 13y, 25-75 IQR 6-15; p

Circulation, Volume 150, Issue Suppl_1, Page A4144377-A4144377, November 12, 2024. Mammalian cells have several adaptive mechanisms to counteract the adverse effects of metabolic and redox stress induced by ischemia. Hypoxia, a hallmark of ischemia, results in the selective reduction of the tricarboxylic acid cycle metabolite, α-ketoglutarate, to theL-(S)-enantiomer of 2-hydroxyglutarate (L2HG) in several cell types. L2HG protects hypoxic cells by buffering increases in the NADH/NAD+redox couple and inhibiting mitochondrial electron transport. In addition, the accumulation of L2HG induced by genetic knockout of L2HG dehydrogenase (L2HGDH), the only known enzyme capable of oxidizing L2HG back to α-ketoglutarate, protects mice against myocardial injury during ischemia. This protection by L2HG manifests as decreased myocardial infarct size and improved cardiac function, owing partly to a metabolic shift in carbon flux from glycolysis towards the pentose phosphate pathway. However, myocardial ischemia also leads to perturbations in fatty acid metabolism as manifest by accumulation of acylcarnitines and acyl-CoA’s. It remains unclear as to whether or not L2HG accumulation affects fatty acid metabolic homeostasis during myocardial ischemia. Here, we induced L2HG accumulation by homozygous deletion of thel2hgdhgene in male mice (l2hgdh-/-; n=12). Hearts isolated from these mice and their wild-type littermates (l2hgdh+/+; n=13) were subjected toex vivoLangendorff perfusion at coronary perfusion pressure of 80 mmHg for 30 min with (ischemic group) or without (control group) subsequent perfusion at ~10% pressure for 90 min. Using liquid chromatography tandem mass spectrometry (LC-MS/MS)-based nontargeted lipidomics, we identified several species of long chain acylcarnitines that accumulated by ischemia in hearts obtained fromL2HGDH+/+mice [linoleoyl carnitine, palmitoyl carnitine, and hydroxy-linoleoyl carnitine increased by 13.2-fold (p=4.2 x 10-6), 10.7-fold (p=1.7 x 10-6), and 10.0-fold (p=5.8 x 10-6), respectively]. Interestingly, however, this accumulation was attenuated substantially in ischemic hearts obtained fromL2HGDH-/-mice [hydroxy-linoleoyl carnitine, palmitoyl carnitine, and linoleoyl carnitine were downregulated by 62.6% (p=0.034), 54.2% (p=0.018), and 35.4% (p=0.054) in ischemic hearts fromL2HGDH-/-mice when compared toL2HGD+/+littermates]. Overall, these findings highlight a novel and potentially important role for L2HG in restoring the perturbations in fatty acid metabolism induced by myocardial ischemia.

Circulation, Volume 150, Issue Suppl_1, Page A4141811-A4141811, November 12, 2024. Background:Ambulatory ECG (AECG) enables heart rhythm monitoring during daily activities, with a focus on arrythmia detection. Detection and quantification of sleep and activity patterns during monitoring may provide insights into lifestyle and aid in contextualizing arrhythmia events.Aims:We developed an AI algorithm to classify sleep, activity, and inactivity periods using a novel AECG patch with embedded accelerometry. We assessed algorithm performance and compared it to FDA-cleared actigraphy and consumer devices, which have shown 93-99% sensitivity (SE) and 39-54% specificity (SP) in classifying sleep vs. polysomnography (PSG).Methods:We conducted a prospective study of 81 participants at 3 sites who wore the Zio®monitor AECG patch (iRhythm Technologies, San Francisco, CA) and Actigraph wGT3X (Pensacola, FL) simultaneously for 14 days. Sleep disordered breathing was excluded. Participants underwent a 6-minute walk test at the beginning of wear and in-clinic overnight PSG sleep testing at 7±3 days.Data were split into training (n=40) and validation (n=41) sets. Feature and model selection utilized five-fold cross-validation on the training set, focusing on total activity and body angle. The final machine model was trained on selected features using the entire training set. In validation, SE and SP for sleep were assessed based on 1-minute epochs vs. PSG and also vs. a 24-hour reference (combined PSG and actigraphy-wake labeling). SE and SP for activity were assessed vs. actigraphy over 8 minutes sampled per subject (4min walk test, 4min PSG wake periods).Results:The study population was diverse (age 43±14 years, 57% female, 64% White, 25% Black, 20% Hispanic). In the validation set, average sleep and wake times were 5.9 and 1.2 hours, respectively, during PSG. SE and SP were 88.8% and 54.0%, respectively, in sleep detection vs. PSG, or 88.8% SE and 95.6% SP vs. the 24-hour reference (Table 1). SE and SP for activity detection were 97.0% and 100%, respectively.Conclusion:Assessment of sleep and activity during AECG is feasible, with performance comparable to FDA-cleared actigraphy. This feature offers insights into patient wellness patterns, highlighting its potential for personalized healthcare monitoring.

Circulation, Volume 150, Issue Suppl_1, Page A4136554-A4136554, November 12, 2024. Background:In 2023, the AHA published the PREVENT equations for estimating atherosclerotic cardiovascular disease (ASCVD) risk in adults aged 30-79 years.Research Questions:In young adults aged 20-39 years, does PREVENT improve risk prediction for 10- and 30-year ASCVD compared with existing risk assessment tools recommended in the current US guidelines (i.e., Pooled Cohort Equations [PCEs] and Pencina et al. equations)?Aims:To compare the performance of PREVENT vs. PCEs in predicting 10-year ASCVD, and PREVENT vs. Pencina equations in predicting 30-year ASCVD in young adults.Methods:We analyzed data from two complementary sources: (1) pooled data from two large cohorts: Coronary Artery Risk Development in Young Adults (CARDIA) and Framingham Heart Study (FHS; including the Offspring, Third Generation, Omni 1, and Omni 2 cohorts), and (2) electronic health records from Kaiser Permanente Southern California (KPSC). We included adults aged 20-39 years without a history of ASCVD at baseline. The outcome was incident ASCVD (defined as myocardial infarction, fatal coronary heart disease, fatal and nonfatal stroke) at 10 or 30 years. Model discrimination (Harrell’s C) and mean calibration (estimated as the ratio of predicted to observed event rates) were calculated for the overall population and stratified by sex and race/ethnicity.Results:We included 7,606 young adults (mean age 29 years, 53% female, 30% Black) from the pooled cohorts, and 284,667 (mean age 32 years, 61% female, 8% Black, 46% Hispanic) from KPSC. When predicting 10-year risk, PREVENT improved discrimination in both the pooled cohort (ΔHarrell’s C=0.052; 95% CI: 0.014, 0.095) and KPSC (ΔHarrell’s C=0.039; 95% CI: 0.028, 0.049) compared with the PCEs. PREVENT had good calibration (mean calibration ranged from 0.77 to 1.54), whereas the PCEs overestimated 10-year risk (mean calibration ranged from 1.99 to 4.82). When predicting 30-year risk, discrimination was similar for PREVENT and Pencina equations, but both algorithms underestimated 30-year risk with PREVENT showing worse calibration (mean calibration 0.61).Conclusion:PREVENT improved 10-year ASCVD risk prediction in young adults compared to the PCEs but underestimated 30-year risk.

Circulation, Volume 150, Issue Suppl_1, Page A4134935-A4134935, November 12, 2024. Introduction:Recent data demonstrated that the COVID-19 pandemic adversely affected cardiovascular fellows in training (cFIT) and faculty in terms of educational disruption and search for job prospects, respectively. However, less is known about the pandemic’s effect on cFIT and faculty in terms of general well-being, shifts in personal and professional priorities, quantitative measures of stress levels, and research productivity.Methods:A national survey targeting cFIT and faculty was developed to assess the effect of the pandemic two years later on these parameters. Fifty-four participants, including 21 cFIT and 33 faculty, responded to the survey. The survey was distributed between October 2021 and May 2022 to program directors of ACGME-accredited general cardiology fellowship programs in the United States.Results:30% of cFITs perceived impaired clinical training during the pandemic; 36% of fellows experienced a decline in their clinical skills in the cardiac catheterization lab, while 27% experienced a decrease in their echocardiographic skills. Additionally, a significant percentage of cFIT reported negative interference in their competencies in nuclear cardiology (27%) and electrophysiology (12%). Most participants (76%), including faculty and fellows, reported several health issues such as sleep problems, low energy, changes in appetite, difficulty concentrating, and restlessness due to the pandemic. 43% of the faculty and 61% of cFIT reported high rates of impaired short-term productivity (Figure).Conclusion:In this national survey, we found that two years after the onset of the COVID-19 pandemic, cardiology fellows and faculty continued to experience significant concerns for decreased hands-on training and diminished research productivity. While faculty were not distressed regarding decreased clinical competencies, concerns about short-term and long-term research productivity persisted. Faculty and fellows all experienced increased stress levels and impaired productivity. Although limited by a small sample size, which can introduce bias, these results signal the importance of performing a follow-up study on the impact of COVID-19 on wellness as well as the impact on career.

Circulation, Volume 150, Issue Suppl_1, Page A4143784-A4143784, November 12, 2024. Background:Hypertension is the leading preventable risk factor for cardiovascular disease (CVD) and all-cause mortality worldwide. Community health worker (CHW)-led intervention has been effective in lowering blood pressure (BP) and CVD risk. However, the long-term effectiveness of CHW-led intervention is unknown.Aim:We assessed the long-term effectiveness of a CHW-led intensive BP intervention on CVD incidence and all-cause mortality.Methods:The China Rural Hypertension Control Project (CRHCP) involved 33,995 hypertensive individuals aged ≥40 years from 326 villages in rural China. A total of 163 villages were randomly assigned to a CHW-led intervention, while the other 163 villages were assigned to usual care. CHWs were trained village doctors who initiated and titrated antihypertensive medications using a simple stepped-care protocol according to ACC/AHA clinical guidelines. They also conducted health coaching and delivered free or discounted antihypertensive medications to participants. The primary effectiveness outcome was a composite of myocardial infarction, stroke, heart failure, or CVD death during the 48-month follow-up period. Secondary outcomes included CVD death and all-cause death. Safety outcomes were also assessed at 48 months.Results:During a median follow-up of 48 months, 1,744 CVD events (2.6% per year) were documented in the intervention group, compared to 2,191 CVD events (3.5% per year) in the usual care group. The CHW-led intervention resulted in a 27% reduction in CVD (hazard ratio [HR] 0.73; 95% CI 0.69 to 0.78). Furthermore, CVD deaths were reduced by 24% (HR 0.76; 95% CI 0.68 to 0.84), and all-cause deaths were reduced by 14% (HR 0.86; 95% CI 0.80 to 0.94) in the intervention group compared to the usual care group. Participants in the intervention group had a significantly lower rate of serious adverse events compared to usual care participants (risk ratio 0.94; 95% CI: 0.91 to 0.98). However, there was no statistically significant difference in injurious falls, symptomatic hypotension, or syncope between the two groups.Conclusion:This randomized cluster trial showed that a CHW-led intervention significantly reduced CVD risk and all-cause mortality over 48 months among rural residents in China. This feasible and effective BP intervention strategy should be scaled up in China and other low- and middle-income countries to reduce the burden of CVD worldwide.

Circulation, Volume 150, Issue Suppl_1, Page A4140703-A4140703, November 12, 2024. Background:The mRNA vaccines against COVID-19 are highly effective but have been associated with a rare non-infective form of myocarditis, particularly in young males after receiving the second dose. Understanding the mediators of this adverse effect is crucial to enhance the safety of future mRNA vaccines.Hypothesis:Myocardial injury following COVID-19 mRNA vaccination is mediated by overproduced cytokines, and estrogens have a protective effect on this adverse effect.Approach:Candidate cytokine mediators were identified through analysis of proteomics data from plasma samples of vaccinated individuals. Human iPSC-derived macrophages and cardiomyocytes were used to model cytokine-induced effects. An in vivo mouse model of cytokine-induced myocardial injury was employed to assess the impact of the cytokine cocktail and estrogens.Results:CXCL10 and IFN-γ were consistently upregulated in vaccinated individuals on day 1 and further elevated in patients with myocarditis following mRNA vaccination. Consistently, iPSC-derived macrophages exposed to COVID-19 mRNA vaccines produced these cytokines. Next, iPSC-derived cardiomyocytes exposed to these cytokines showed impaired contractility, arrhythmogenicity, and pro-inflammatory gene expression. The phytoestrogen genistein mitigated these effects in vitro, reducing cytokine-induced proteasomal degradation of cardiac proteins and preserving contractile function. In vivo, genistein significantly decreased cardiac injury markers and immune cell infiltration in a mouse model of cytokine-induced myocardial injury.Conclusion:CXCL10 and IFN-γ are key mediators of myocardial injury post-mRNA vaccination. Genistein shows potential as a therapeutic agent to mitigate associated cardiovascular risks.

Circulation, Volume 150, Issue Suppl_1, Page A4146171-A4146171, November 12, 2024. Introduction:Arterial aneurysms, particularly abdominal aortic aneurysms (AAA), are life-threatening conditions. Human genetic studies and preclinical mouse models have supported LDL-C reduction through PCSK9i as a strategy to slow the progression of arterial aneurysms.Aims:To investigate the rates of arterial aneurysm events among patients randomized to the PCSK9i evolocumab vs. placebo.Methods:In FOURIER, 27,564 patients with stable ASCVD and LDL-C ≥70 or non-HDL-C ≥100 mg/dL on statins were randomized to evolocumab vs. placebo and followed for a median of 2.2 years. 6,635 patients entered the open-label extension period and received evolocumab for 5 years, irrespective of initial assignment. The primary endpoint of this analysis was any aneurysm event, defined as diagnosis, progression, or intervention related to an arterial aneurysm. Adverse events were reported by the local site and potential aneurysm events were centrally identified by blinded investigators. Procedure-related pseudoaneurysms were excluded. A Cox model, adjusted for randomization stratification factors and an indicator for inclusion in the open-label cohort, was used to compare randomized groups throughout the two trial periods.Results:A total of 236 patients had aneurysm events (58% AAA) during follow-up. Patients who had aneurysm events were older (median age 67 vs. 63 yrs), more likely to be male (86% vs. 75%) and have a history of PAD (21% vs. 13%). Patients randomized to evolocumab had significantly lower rates of aneurysm events during follow-up (HR 0.77 [0.59–0.99]; p=0.041) (Figure). The association between randomization to evolocumab and fewer aneurysm events was consistent for both AAA (HR 0.78 [0.56–1.09]) and non-AAA (HR 0.81 [0.55–1.18]).Conclusion:In patients with stable ASCVD on optimized statin therapy, early initiation of long-term evolocumab was associated with fewer arterial aneurysm events compared with delayed initiation. These data support earlier intensive LDL-C reduction with PCSK9i as a promising strategy to prevent the formation and progression of arterial aneurysms, including AAA.

Circulation, Volume 150, Issue Suppl_1, Page A4142555-A4142555, November 12, 2024. Background:Myocardial fibrosis could be detected by cardiac MRI (CMR) with late gadolinium enhancement (LGE) which provides important prognostic information of risk stratification for adult hypertrophic cardiomyopathy (HCM). However, in childhood HCM, it remains uncertain the prevalence, pattern of LGE, and whether it is associated with adverse outcomes.Aims:This study aims to explore the characteristics of LGE in childhood HCM and to evaluate the prognostic value of LGE for adverse outcomes.Methods:In this retrospective study, a total of 231 consecutive childhood patients with primary HCM who were ≤18 years of age at diagnosis and underwent contrast-enhanced CMR from January 2011 to December 2019 were enrolled. The extent of LGE was quantified by measuring areas with the increased signal intensity of ≥6 standard deviations above the mean of normal myocardium. The primary outcome included a composite of sudden cardiac death (SCD) or equivalent events (resuscitated sudden cardiac arrest or aborted SCD), heart failure-related events (heart transplantation, death from heart failure, rehospitalization for heart failure).Results:Patients were 15±3 years of age at baseline and 65% were male. During a median follow-up of 61.7 months (IQR:39.2-84.5), 26(11.3%) patients with HCM reached the primary end points, 13 of whom experienced SCD events. LGE was present in 195(84.4%) childhood HCM patients with a median LGE extent 4.77%(IQR:2.01-9.18) and higher in the mid regions. After univariable analysis, multivariable Cox analysis adjusting clinical and cardiac functional factors, LGE extent was an independent predictor for the primary endpoints (HR, 1.11; P

Circulation, Volume 150, Issue Suppl_1, Page A4139757-A4139757, November 12, 2024. Background:The COVID-19 pandemic has significantly exacerbated sleep problems. Pandemic-related lockdowns and drastic changes in daily life have disrupted sleep patterns, resulting in a marked increase in sleep disturbances.Research questions:This study aims to investigate the primary factors contributing to the increase in sleep disturbances during the COVID-19 pandemic in Korea. By utilizing nationally representative data encompassing various variables, this study seeks to identify COVID-19-related factors associated with sleep disturbances during the pandemic.Method:We analyzed data from the nationally representative Korea Community Health Survey conducted in 2020, including 216,809 adults. Changes in daily life due to COVID-19 were assessed by asking participants to score their current situation compared to their pre-pandemic situation, ranging from 100 (no change) to 0 (complete cessation of daily activities). COVID-19 concerns were assessed with five questions: 1) fear of contracting the virus; 2) fear of mortality if infected; 3) fear of blame from others; 4) concerns about the health of vulnerable family members; and 5) concerns about economic impacts. Sleep disturbances were defined as sleeping 5 hours or less per night on average. Logistic regression analyses with a complex sample design were performed to examine the relationship between COVID-19-related factors and sleep disturbances, adjusting for socioeconomic and health-related variables.Results:A high level of lifestyle changes due to COVID-19 (OR = 1.15, 95% CI = 1.11–1.19) and high COVID-19 concerns (OR = 1.04, 95% CI = 1.01–1.08) were associated with an increased likelihood of sleep disturbances. Conversely, resting during COVID-19 symptoms (OR = 0.81, 95% CI = 0.76–0.87), having support during quarantine (OR = 0.93, 95% CI = 0.89–0.97), and trust in the government and neighbors (OR = 0.92, 95% CI = 0.89–0.96) were associated with a decreased likelihood of sleep disturbances.Conclusion:These findings suggest that sleep disturbances during the COVID-19 pandemic were mediated by lifestyle disruptions and high levels of concern. Social support and trust mitigated the impact of COVID-19-related risk factors. As part of preparedness, improving the environment to facilitate adequate rest during illness, ensuring strong social support, and fostering high levels of trust in the government and neighbors may be important to protect sleep health during future public health emergencies.

Circulation, Volume 150, Issue Suppl_1, Page A4143745-A4143745, November 12, 2024. Background:Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is a complex procedure to restore blood flow in completely occluded coronary arteries with the aim of improving symptoms and quality of life. While CTO-PCI success rates have increased owing to advancements in antegrade and retrograde techniques, the choice of approach remains crucial. The antegrade approach is often the initial method chosen because of its relative simplicity, whereas the retrograde approach is considered in more complex cases or when the antegrade approach fails.Aims:The data suggest that the retrograde approach is associated with higher periprocedural complications, although the reports are conflicting. Our meta-analysis aimed to compare the efficacy and safety of the antegrade and retrograde approaches for CTO-PCI.Methods:A comprehensive literature search was conducted on PubMed, Embase, Google Scholar, and Scopus from inception until June 5, 2024. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using Review Manager, with a p-value of

Circulation, Volume 150, Issue Suppl_1, Page A4139876-A4139876, November 12, 2024. Introduction:It has been described that both skin and coronary microvascular dysfunction occur in coronary heart disease patients, being a critical pathogenesis of cardiovascular diseases, mainly driven by a reduced endothelium-derived relaxing factor nitric oxide availability, the main homeostatic antioxidant in microcirculation. Various dietary factors could modulate endothelial function. Our goal was to evaluate the relationship between nutrition and long-term microvascular endothelial function in patients in secondary cardiovascular prevention. To do this, we evaluated the consumption of two healthy diets (Mediterranean Diet and Low-fat diet) and the total antioxidant content of the diet.Methods:With an analytical, longitudinal, experimental, and retrospective design, this work included all patients from the Cordioprev study who had completed endothelial function measures and dietary evaluations at the start of the study and after six years of intervention (n=520). Endothelial function (basal flow and area of reactive hyperemia) was measured using laser-Doppler flowmetry in the second phalanx of the third finger of the dominant hand. Food intake was evaluated using a food frequency questionnaire and the antioxidant quality of the diet using the dietary antioxidant index.Results:In the entire population, we observed a significant direct correlation between the evolution of the dietary antioxidant index and basal flow after 6 years of dietary intervention (p=0.024). When we studied the effect of the two diets investigated, in the Mediterranean diet group, an increase in the average dietary antioxidant index score was observed at the end of the study, and a direct relationship was also found between the dietary antioxidant index and endothelial function markers (basal flow (p=0.037); area of reactive hyperemia (p=0.015)). These findings were not observed after the low-fat diet.Conclusions:Our study indicates that, after six years of dietary intervention, changes in the total antioxidant content of the diet are directly correlated with changes in microvascular endothelial function in patients with coronary disease. These findings are especially evident with the Mediterranean Diet.

Circulation, Volume 150, Issue Suppl_1, Page A4142506-A4142506, November 12, 2024. Introduction:Myocarditis has been reported after mRNA-based COVID-19 vaccination, but the immune mechanisms remain unclear. This study aimed to identify the proteome-based immunopathogenesis of post-vaccination myocarditis compared to viral myocarditis in the pre-COVID-19 era.Methods:Proteomic analysis of right ventricle (RV) biopsy specimens was performed in myocarditis patients (pre-pandemic viral myocarditis: n=3, post-vaccination myocarditis: n=3) and controls (normal endomyocardial biopsy specimens of heart transplant recipients, n=4) using mass spectrometry. Differentially expressed proteins were analyzed with CIBERSORTx, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA). To examine the relationship between the SARS-CoV-2 spike protein and post-vaccination myocarditis, immunohistochemistry (IHC), mass spectrometry analysis of spike protein, and activation-induced marker (AIM) assay in T cells from RV samples were conducted.Results:In the proteomic analysis, 6,861 proteins were identified. Post-vaccination myocarditis showed increased extracellular matrix formation and cardiac fibrosis. Both pre-pandemic and post-vaccination myocarditis had elevated pro-inflammatory cytokine activities. However, post-vaccination myocarditis exhibited higher expression of interferon-alpha (IFNα) and pattern recognition receptor activation, including TLR3 and TLR7. Pre-pandemic myocarditis showed higher activation of the complement system, neutrophils, and NK cells, whereas post-vaccination myocarditis showed increased Th2 cell activation and classical macrophage activation. Spike protein and related T-cell activation were not detected.Conclusion:The immune activation in myocarditis after COVID-19 mRNA vaccination may be triggered by the mRNA in the vaccine via an IFNα-driven immune response, leading to autoimmune-like features. Further studies are necessary to validate whether these proteins correlate with clinical characteristics.