Risultati per: Linee Guida per le cure post-parto

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

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

Circulation, Volume 150, Issue Suppl_1, Page A4137665-A4137665, November 12, 2024. Background:Nearly one million individuals in the U.S. experience ischemic stroke annually and one-year recurrent stroke risk may exceed 10%. American Heart Association (AHA) Get-With-The-Guidelines-Stroke® Registry (GWTG-S) data suggests that up to 40% of stroke patients are discharged with an undocumented or cryptogenic etiology which may lead to suboptimal secondary prevention. Consequently, improved cardiology and neurology collaboration and evidence-based post-stroke evaluation may help identify stroke etiology, reduce recurrent stroke risk and improve outcomes.Methods:In 2022, the AHA, in collaboration with HCA Healthcare and HCA Healthcare Foundation, designed and launched Getting to the Heart Of StrokeTM(GTTHOS) in 10 HCA Healthcare comprehensive stroke centers to improve: 1) cardiology and neurology stroke care collaboration, 2) evidence-based post-stroke diagnostic evaluation and 3) assessment of social determinants of health and barriers to care. Components included a learning collaborative model, virtual performance improvement consultations, Plan-Do-Study-Acts, multidisciplinary teams, custom and existing GWTG-S metrics and performance improvement feedback.Results:Using existing and custom GWTG-S data, GTTHOS centers increased rates of documented stroke etiology (58.06% vs. 48.63%), while decreasing cryptogenic stroke rates (31.01% vs. 34.89%) and lack of a documented stroke etiology (10.93% vs. 16.48%) (all comparisons on discharge, follow-up vs. baseline, p

Circulation, Volume 150, Issue Suppl_1, Page A4139912-A4139912, November 12, 2024. Background:Tirzepatide (TZP) 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 examined biomarkers of inflammation in people living with obesity, or overweight, without and with T2D, from SURMOUNT-1 and SURMOUNT-2. Furthermore, we evaluated the contribution of weight reduction- associated and – unassociated effects on biomarkers of inflammation.Methods:A total of 700 participants were randomly selected from SURMOUNT-1 and SURMOUNT-2 (100 participants from each treatment arm: placebo, 5, 10, and 15 mg in SURMOUNT-1 and placebo, 10 and 15 mg in SURMOUNT-2). The association of treatment with change from baseline in the inflammation biomarkers interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP) at 24 and 72 weeks was assessed along with the estimated percentages of the association attributable to weight loss through a mediation analysis.Results:In SURMOUNT-1, following 72 weeks of treatment with TZP without T2D, TZP was associated with significantly decreased IL-6 (-26% to -31%) and hsCRP (-51% to -65%), compared to placebo in all dose groups. In SURMOUNT-2, following 72 weeks of treatment with TZP in participants with T2D, changes of -16% to -23% in IL-6 and -55% to -56% in hsCRP were observed (significance seen for all groups except for TZP 15mg on IL-6). At 24 weeks, only 18% and 31% of hsCRP changes were associated with weight reduction in SURMOUNT-1 and -2, respectively. In SURMOUNT-1, 77% of IL-6 changes and 87% of hsCRP changes at 72 weeks were associated with weight reduction. In SURMOUNT-2, 78% of IL-6 changes and 57% of hsCRP changes at 72 weeks were associated with body weight reduction.Conclusions:In this post hoc analysis of SURMOUNT-1 and -2, early changes in hsCRP (week 24) were weight reduction-unassociated, while at week 72, changes in the inflammation biomarkers IL-6 and hsCRP observed in TZP-treated participants were mainly weight reduction-associated. The relative contribution of weight reduction-dependent effects was more prominent in participants without T2D, compared to those with T2D. Collectively, these data suggest TZP was associated with reduced inflammation in people with overweight/obesity and/or T2D.

Circulation, Volume 150, Issue Suppl_1, Page A4144803-A4144803, November 12, 2024. Background:ST elevation myocardial infarction (STEMI) patients are at increased risk for secondary cardiovascular events. Modulation of purinergic signaling is the mainstay of post-MI antithrombotic therapy. CD39, encoded by theENTPD1gene, is a key modulator of vascular homeostasis that hydrolyzes prothrombotic and proinflammatory extracellular nucleotides. The goal of this study was to determine if theENTPD1promoter polymorphism rs3814159 genotype associates with inflammatory cell expression of CD39 and with secondary cardiovascular events in patients following STEMI.Approach and Results:FACS analysis of circulating inflammatory cells from volunteers and STEMI patients was conducted. We found that 1) the ENTPD1 promoter polymorphism rs3814159 genotype associates with the level of CD39 expression on T cells, 2) Integrated immunophenotype analysis depicts a temporal expression pattern of increased CD39 on Tregs following myocardial infarction, and 3) Treg phenotype differs by rs3814159 genotype early following STEMI. Next to determine if the rs3814159 genotype associates with STEMI outcomes we analyzed data from the POPular Genetics study. A total of 1964 patients from the original POPular Genetics study cohort had rs3814159 genotype assignment (Treg CD39highAA: 517 (24.3%);CD39intAG: 982 (46.2%);CD39lowGG: 625 (29.4%) consistent with expected frequencies. There were no differences in baseline characteristics by rs3814159 genotype. The primary endpoint of ischemic outcomes (all-cause death, myocardial infarction, target vessel revascularization, and/or stent thrombosis) was significantly higher in those patients homozygous for GG (Treg CD39low) versus AA (Treg CD39high) at rs3814159 by both univariate (HR:1.44; 95% CI:1.04-2.00, p=0.029) and multivariate (HR:1.43; 95% CI:1.03-1.98, p=0.034) analysis using an additive model. No significant differences in bleeding outcomes were observed by genotype using BARC criteria. Kaplan-Meier analysis revealed a significant increase in primary ischemic events in patient homozygous GG (Treg CD39low) versus homozygous AA (Treg CD39high) at rs3814159 (Figure).Conclusions:These data suggest for the first time thatENTPD1rs3814159 genotype associates with the level of CD39 expression on T-cells and with the incidence of the primary ischemic endpoint of all-cause death, myocardial infarction, target vessel revascularization, and/or stent thrombosis after ST elevation myocardial infarction.

Circulation, Volume 150, Issue Suppl_1, Page A4145932-A4145932, November 12, 2024. Background:A new ESC guidelines in 2023, the International Lipid Expert Panel (ILEP) 2021 recommendations, and a subsequent statement by EAS have been published based on recent advances in lipid lowering treatments. However, real world data are lacking regarding the implementation among the community of French cardiologists.Objective:To determine the current approach and therapeutic strategies concerning lipid lowering treatments post-acute coronary syndromes in France.Methods:This national survey was performed during October and November 2023 in France with an online questionnaire on the websites of 2 national French Societies of Cardiologists.Four mailings were sent to cardiologists to invite them to answer to the questionnaire. A total of 400 answers of cardiologists were collected during this 2-month period.Results:For ASCVD patients, cardiologists agreed with an LDL-C goal below 55 mg/dL (1.4 mmol/L) in 69%, below 70 mg/dL (1.8 mmol/L) in 16.5%, and 14.5% between 70 mg/dL and 100 mg/dL (1.8-2.5 mmol/L). An upfront lipid lowering combination strategy using fixed dose combination (FDC) of statins and ezetimibe was prescribed in less than 5% of patients, whereas high-intensity statins were prescribed in more than 90% of patients. No significant differences were observed in terms of sex of patients, geographical area, or strategies followed by male and female cardiologists (p > 0.05). A combination of statins and ezetimibe was prescribed only for a minority of patients, especially as an early upfront strategy. The use of PCSK9i remains marginal and the interval between the ACS and initiation of these medicines remains high.Conclusion:In this contemporary national survey, we report an excellent agreement of lipid goals in secondary prevention by cardiologists. Despite the declared consensus recommending a low LDL-C target in ACS patients, lipid lowering strategies are suboptimal, mainly consisting of high intensity statins. The lack of recommended use of ezetimibe and PCSK9i to lower LDL-C levels highlights the importance of better implementation of intensive and early upfront strategies to reduce recurrent ischemic events.

Circulation, Volume 150, Issue Suppl_1, Page A4138964-A4138964, November 12, 2024. Background:Post-ablation atrial fibrillation (AF) inducibility has been associated with AF recurrence and is often used as an endpoint for Pulmonary Vein Isolation (PVI). Little is known regarding factors affecting inducibility after PVI, as AF inducibility is common even after PV isolation. Prolonged episodes of untreated AF can result in remodeling of the atrium and the formation of new arrhythmogenic substrate, which may make treatment of AF more challenging. We hypothesized that longer diagnosis-to-ablation time (DAT) is associated with higher rates of post-PVI AF inducibility.Objective:To evaluate DATs in cases of inducible vs. non-inducible AF post ablation.Methods:A single-center, retrospective analysis of 168 consecutive patients who underwent 1sttime PVI between 1/1/2022 and 12/01/2023 was performed. Following PVI, inducibility of AF was tested by programmed stimulation using decremental pacing in 50ms windows for 10 seconds each (from 400 ms down to 200 ms or until loss of 1:1 atrial capture). Results were categorized by type of rhythm induced (non-inducible, AF) and duration (sustained, non-sustained). DAT was obtained from review of the medical records. Descriptive statistics were used to compare demographics and AF type, and parametric and non-parametric tests were used for analysis of the diagnosis-to-ablation window and its relationship to inducibility.Results:There was no difference in demographic data or AF type between the two groups. 85 patients (50.6%), had no inducible AF. 83 out of 168 cases (49.4%) had inducible sustained AF. Overall DATs ranged from 0 to 40 years. DAT was significantly higher in the inducible vs. non-inducible groups (3.810 vs. 2.906 years, p=0.023).Conclusion:Longer DAT is associated with AF inducibility post-PVI despite successful ablation. This association may reflect the increased persistence of AF as it progresses over time. Future studies are needed to evaluate the clinical implications of DAT times.

Circulation, Volume 150, Issue Suppl_1, Page A4139241-A4139241, November 12, 2024. Background:Percutaneous coronary intervention has significantly improved the prognosis of STEMI, though there is still the risk of fetal mechanical complications, particularly cardiac rupture(CR), which remains an international clinical problem unresolved.Hypothesis:We hypothesized that the combined triple medical therapy(ANT) withAtorvastatin,Nicorandil and Chinese patent medicineTongxinluo(TXL) could be effective in post-infarction CR precautions via significantly inhibiting macrophage activation and secondary ferroptosis of cardiac fibroblasts(CFs) through TRAF6/NF-κB/C/EBPβ pathway.Methods:The 14-day survival and CR rates of AMI mice treated with Atorvastatin, Nicorandil and Tongxinluo, singly or in dual and triple combination, were all compared via the Kaplan-Meier curves. Then the inflammation level and infarct region were measured via ELISA, immunoblot and histopathology. Sequentially immunoprecipitation, luciferase report gene and transcriptome sequencing were introduced to understand the role of the TRAF6/NF-κB/C/EBPβ pathway and its upstream micro-RNAs in CR prevention. Further,in-vitroexperiments were performed to demonstrate the crosstalk between macrophages activation and CFs ferroptosis in CR prevention.Results:Among all therapies involved, the triple combined ANT therapy supremely reduced the incidence of post-infarction CR (from 26.7% to 10.0%) and the mortality of AMI (from 30.0% to 13.3%), during which macrophages reduced most nuclear NF-κB p65 and C/EPBβ by nearly 70% simultaneously through miR215-5p-, miR122-5p-, miR-299b-3p-mediated TRAF6 inhibition, with 50%+ MMP9 cut and more extracellular matrix remaining, especially collagens, Syndecan-1, Laminin and Agrin. And, with the ANT administration, only 20% macrophages remained in peri-infarct areas, accompanied by the lowest serum inflammatory level. Furthermore, CF ferroptosis alleviated most, evidenced by the 4-fold GPX4 and 3-fold FSP-1 up-regulation. Two independent anti-ferroptotic system, GPX4 and FSP-1, worked equally in the nicorandil effect on CF survival, however, with GPX4 or FSP-1 overwhelmingly underlying atorvastatin or Tongxinluo protection against CF ferroptosis respectively.Conclusions:Our results indicated the ANT combination upmost alleviated the excessive excitation of M1 macrophages and its induced CF ferroptosis via prohibiting TRAF6-mediated NF-κB and C/EBPβ translocation, and facilitated myocardial repair to prevent post-infarction cardiac rupture onset.

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=

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

Circulation, Volume 150, Issue Suppl_1, Page A4145775-A4145775, November 12, 2024. Background:Cyclophosphamide is an alkylating agent of the nitrogen mustard class that has become standard of care for graft-versus-host disease prophylaxis after hematopoietic stem cell transplantation. Although its cardiac toxicity in conditioning regimens is well-documented, data on cardiac events after administration of post-transplant cyclophosphamide (PT-Cy) administration remains limited.Research Question:Is PT-Cy associated with a higher incidence of cardiac adverse events compared with no PT-Cy?Aims:We aimed to perform a systematic review and meta-analysis of cardiac events from studies comparing PT-Cy versus no PT-Cy in patients with hematological disorders who received hematopoietic stem cell transplantation.Methods:We searched PubMed, Embase, and Cochrane Library for studies comparing PT-Cy versus no PT-Cy in patients with hematological conditions who received hematopoietic stem cell transplantation. We pooled risk ratios (RR) with 95% confidence intervals (CI). Statistical analyses were performed using Review Manager 5.4.1, under a random-effects model. Heterogeneity was assessed using I2 statistics.Results:We included four studies, all of which were retrospective, with 1,546 patients, of whom 826 (53%) received PT-Cy. Age ranged from 18 to 77 years, and 840 (54%) were male. A total of 1549 allogeneic transplants were performed, primarily for malignant hematological conditions. The conditioning regimens used were myeloablative (52%), reduced intensity (33%), non-myeloablative (8%), and sequential (7%). The most common cardiac events in patients receiving PT-Cy were heart failure (28%) and cardiomyopathy (27%), followed by arrhythmias (25%), pericarditis/pericardial effusion (14%) and acute coronary syndrome (5%). The incidence of adverse cardiac events was significantly higher in patients who received PT-Cy compared with those who did not receive PT-Cy (RR 2.05; 95% CI 1.36, 3.10; p

Circulation, Volume 150, Issue Suppl_1, Page A4146727-A4146727, November 12, 2024. Introduction:High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with atherosclerotic cardiovascular disease (ASCVD) risk in type 2 diabetes (T2D). However, the association of longitudinal changes in these cardiac biomarkers with ASCVD risk in T2D is not well-established. Furthermore, the effects of an intensive lifestyle intervention (ILI) targeting weight loss on cardiac biomarkers is not well-characterized.Methods:Participants of the Look AHEAD (Action for Health in Diabetes) trial with T2D and overweight or obesity were included. Hs-cTnT and NT-proBNP were measured at baseline, 1- and 4-year follow-up (Roche Diagnostics). Adjusted Cox models were created to evaluate the associations of baseline, 1-, and 4-year change in cardiac biomarkers with ASCVD risk (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina). The effects of the ILI targeting weight loss versus diabetes support and education (DSE) on cardiac biomarker changes were summarized as the geometric mean ratio (GMR) and 95% confidence interval (CI).Results:Among 3,984 participants with available cardiac biomarker data, there were 771 ASCVD events (median follow-up: 12 years). Higher hs-cTnT and NT-proBNP at baseline were each significantly associated with higher ASCVD risk (Figure 1A). Changes in hs-cTnT and NT-proBNP over 1-year follow-up were not significantly associated with ASCVD risk. However, sustained increases in hs-cTnT and NT-proBNP over 4-year follow-up were each significantly associated with higher ASCVD risk. The ILI versus DSE was significantly associated with lower hs-cTnT at 1- and 4-year follow-up (GMR [95% CI]: 0.96 [0.93-0.99] and 0.94 [0.92-0.97]), respectively) (Figure 1B). In contrast, NT-proBNP increased with the ILI (vs. DSE) at 1-year (GMR [95% CI]: 1.11 [1.05-1.17]), but this difference was attenuated and no longer significant at 4-years.Conclusions:Among adults with T2D, sustained increases in hs-cTnT and NT-proBNP over 4-year follow-up were associated with higher ASCVD risk. An ILI targeting weight loss led to a significant reduction in hs-cTnT and transient rise in NT-proBNP that attenuated over time.

Circulation, Volume 150, Issue Suppl_1, Page A4126893-A4126893, November 12, 2024. Background:Suboptimal medication management is common in patients with heart failure (HF), particularly during transitions-of-care. To date, there are few studies assessing the feasibility of a nurse-pharmacist post-discharge telehealth service for medication optimisation in patients with HF. We performed a feasibility study to determine service uptake and acceptability, and ability to identify medication-related issues for HF patients as they transition from hospital to home.Methods:HF patients were referred to an existing post-discharge telehealth service and offered medication reconciliation and education in addition to their usual care; a service we termed ‘MedRec’ (MR). Primary outcomes were feasibility, measured through recruitment and successful MR completion, and acceptability, measured by an investigator-developed survey. Secondary outcomes were medication-related issues detected during MR.Results:A total of 100 HF patients were offered a post-discharge MR. Mean age of patients was 68.5 ±14.2 years, and mostly male sex (62%). Pharmacist MRs were requested by 80% of patients. In total 62 MRs (77.5%) were performed; 9 patients declined MR during follow-up and an additional 9 patients were uncontactable. Mean time to MR following nurse referral was 10.98 ±9.74 days. Drug-related toxicity or adverse effect presentation was identified in 25 (40.3%) MR recipients at the time of consultation and subsequently required general practitioner follow-up. Medication compliance issues were detected by the pharmacist in 13 (20.9%) patients; forgotten doses being the most common concern. Undertreated medical conditions, such as symptomatic HF and chronic pain, were identified in 12 (19.3%) MR recipients. Medications prescribed without any apparent indication were found in 8 (12.9%) patients. Drug or disease management information was requested by 35 (56.4%) MR recipients. A total of 35 (56.5%) post-MR surveys were successfully completed. All participants who completed a post-MR survey agreed that a post-discharge telehealth MR was an acceptable form of education provision. Engagement with a pharmacist MR was perceived to ease anxiety associated with understanding medication-related changes and empowered greater medication self-management.Conclusions:A post-discharge nurse-pharmacist telehealth service is a feasible and acceptable model of care. Inclusion of a routine MR post-discharge may be an effective means of maintaining continuity of care for HF patients.

Circulation, Volume 150, Issue Suppl_1, Page A4138062-A4138062, November 12, 2024. Introduction:Histone deacetylase (HDAC) 6 functions to remove acetyl groups from lysine residues on histone and non-histone proteins. We showed that the augmented activity of HDAC6 in diabetic mice undergoing myocardial ischemia/reperfusion injury (MIRI) was associated with mitochondrial damage. However, it remains unclear how the inhibition of HDAC6 activity affects post-MIRI cardiac remodeling and function in type 2 diabetes.Hypothesis:HDAC6 inhibition suppresses adverse cardiac remodeling and improves mitochondrial dynamics and cardiac function after MIRI in type 2 diabetic mice.Methods:Type 2 diabetic db/db, db/+, and C57BL/6 mice underwent coronary artery occlusion for 20 min followed by reperfusion. Tubastatin A, a selective inhibitor of HDAC6, was injected intraperitoneally 60 min before coronary artery occlusion and once daily after surgery. Mouse hearts were evaluated with echocardiography 28 days after surgery. Myocardium was imaged using electron microscopy, and the expression of mitochondrial dynamin-related protein 1 (DRP1) and fission 1 was measured by Western blotting analysis. H9c2 cardiomyocytes were subjected to hypoxia for 3 hours followed by normoxia for 24 hours in the presence of 5.5- or 25.0-mM D-dextrose and tubastatin A or vehicle.Results:There were no significant differences in the activity of HDAC6, left ventricular diameters and fractional shortening, mitochondrial density volume and surface area, and the ratios of DRP1/GAPDH and fission 1/GAPDH between the db/+ and C57BL/6 groups. Compared to both db/+ and C57BL/6 groups, HDAC6 activity was lower, left ventricular diameters at both end diastole and end systole were longer, fractional shortening and mitochondrial surface area were smaller, and the expression of DRP1 and fission 1 was increased in the db/db group 28 days after MIRI. Interestingly, 10 mg/kg Tubastatin A significantly mitigated these effects of MIRI in db/db mice. Hypoxia/reoxygenation in the presence of 25.0-mM D-dextrose augmented HDAC6 activity and increased the expression of DRP1 and FIS1, which were blocked by Tubastatin A.Conclusions:Tubastatin A prevents post-MIRI cardiac remodeling and improves cardiac function by limiting mitochondrial fission in type 2 diabetic mice.

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 ASa1208-ASa1208, November 12, 2024. Throughout the world, neurologically intact survival to discharge remains low. The Joint Commission (TJC) released post resuscitation requirements in January of 2022. Sanford Bemidji reviewed options that would meet the TJC requirements: Transfer the patient or develop a novel way to meet those needs in the current setting. With the latter, the positive impact on patients is significant in that they receive a high care level of care close to home without delay in care.Sanford Bemidji Medical Center is a rural regional 118-bed hospital in Minnesota with a 14-bed Intensive Care unit. We are unique in that despite our size we serve a large regional footprint of over 100,000 people including three Native American reservations. Our objective was to utilize evidence based guidelines to implement a post cardiac arrest care (PCAC) workflow for adult cardiac arrest patients who obtain return of spontaneous circulation (ROSC) by end of first quarter 2023. The project incorporated low cost equipment and staff training. We used the Plan, Do, Study, Act cycle for our methodology. The outcome metric was neurologically intact survival to hospital discharge. Process metrics included placement and use of the ROSC order set, fever avoidance, rapid EEG completed, MAP over 65, and oxygen saturations of 92-98%. Sixty-one adult patients (both in hospital and out of hospital) suffered cardiac arrest at Sanford Bemidji in the 9 months following project implementation in 2023. Demographics included 3 native americans and 2 caucasians, ages 57-73, 3 males and 2 females. Our overall survival rate remained above the national average. For the few patients who met criteria for ROSC interventions, 4 of 5 (80%) received the ROSC interventions, 2 of 4 (50%) survived hospital to discharge neurologically intact. Results showed an increase in maintaining optimal MAP from 81% in 2022 to 100% in 2023 and achieving oxygen saturation parameters 80% of the time in 2023 compared to 66% in 2022. Real time monitoring and coaching of the order set is needed to increase utilization of the order set in full (fever avoidance was at 20% and rapid EEG completed in 40% of cases with a goal of 100% for both).More data is needed to ascertain the outcomes of a ROSC workflow in like sized hospitals with similar resources. The novelty of this innovative project is in the implementation of an evidence based PCAC workflow in a 118-bed rural hospital giving all cardiac arrest patients a chance for a full recovery.