Risultati per: Linee Guida per le cure post-parto

Circulation, Volume 146, Issue Suppl_1, Page A12760-A12760, November 8, 2022. Introduction:Post-acute sequelae of COVID-19 (PASC) is a novel clinical syndrome. We have previously reported that PASC patients can develop postural orthostatic tachycardia syndrome (POTS) and that COVID-19 induce microvascular endothelial dysfunction in acutely ill, hospitalized patients, that persist up to four months post discharge. Whether microvascular endothelial dysfunction contributes to POTS pathophysiology in PASC remains unclear.Hypothesis:Patients with PACS combined with POTS have impaired microvascular endothelial function.Methods:PASC patients (n=44) with mild SARS-CoV-2 infection (not hospitalized) were recruited from the post-COVID multidisciplinary clinic at Karolinska University Hospital. PASC diagnosis was based on the WHO PASC criteria. POTS was diagnosed in 21 patients (PASC + POTS) while 23 had a negative head-up tilt test (PASC – POTS). Age- and gender-matched healthy subjects (n=15) served as controls. Microvascular endothelial function was quantified as reactive hyperemia index (RHI) determined from the changes in pulse amplitude tonometry before and after a 5 min episode of arterial occlusion. Stress-perfusion cardiac magnetic resonance imaging (cMRI) with adenosine was performed in a subset of patients.Results:Mean age was 42±11 years and 95 % were women among PACS patients. Time from COVID-19 symptom onset to study inclusion was 18±3 months. RHI was significantly lower in PASC + POTS than in healthy controls and PASC – POTS (Figure 1). The prevalence of cardiac microvascular dysfunction on cMRI did not differ between the PASC groups (8% in PASC + POTS vs. 13% in PASC – POTS, p=1.00). All subjects with microvascular dysfunction on cMRI except one had a RHI below the cutoff (1.67) indicating microvascular dysfunction.Conclusions:Microvascular endothelial dysfunction is common in patients with PACS-associated POTS and may cause stress-induced myocardial ischemia up to 18 months after a mild primary infection.

Circulation, Volume 146, Issue Suppl_1, Page A11732-A11732, November 8, 2022. Introduction:Recent data shows that when adults are discharged after hospitalization for acute heart failure (HF), a clinic follow up with either cardiology or general medicine within 7 days results in significantly lower chances of 30 day readmissions. We sought to analyze the trends of clinic follow up after acute HF hospitalization and the associated barriers and facilitators at our safety net hospital.Methods:Data was extracted from the electronic medical records using ICD 9,10 codes for acute HF admissions between Jan 2019 and Dec 2021. Quarterly trends of rates of clinic follow up were analyzed over the past 3 years; t-test was used to assess for statistical significance. Multivariable logistic regression models were constructed to test the association between patient level factors and clinic follow up after adjusting for sociodemographic factors. A p value < 0.05 was used to establish significance.Results:Of 1,037 patients admitted for acute HF between 2019-2021, 29.5% were 65 years or older, 64.7% were males, 48.7% were Black and 16.6% were uninsured. Only 8% and 23.1% had a 7 and 14 day clinic follow up respectively. Of those with scheduled follow up 65% and 56% showed up to their appointments at 7 and 14 days respectively. Overtime we noted an increase in the proportion of encounters with a 7 day follow up although the effective follow up (after accounting for no-shows) remained unchanged. Patients that had an inpatient cardiology consult had higher odds of getting a 7 day follow up (OR=1.42, p value = 0.001) after adjusting for age, gender, insurance status and race (black > white, OR = 1.34, p

Circulation, Volume 146, Issue Suppl_1, Page A9492-A9492, November 8, 2022. Introduction:Left Ventricular Pseudoaneurysm (LVP) is defined as cardiac wall rupture leading to a formation of wall with thrombus, pericardial, or scar tissue functioning as a pouch for blood. A loculated pericardial effusion (LPE), and right ventricular pericardial fistula (RVPF) have never been reported in literature. Here, we report the first case of a 70 year old male who developed a LVP, LPE, and RVPF.Case Description:A 70 year old male with a past medical history of hypertension presented with inferior wall STEMI. Cardiac catheterization demonstrated left anterior descending (LAD) with 80% occlusion and right coronary artery (RCA) with 100% occlusion. Percutaneous intervention of RCA with aspiration thrombectomy and two drug eluting stents was performed. Echocardiogram the following day demonstrated a LVP. A transesophageal echocardiogram (TEE) demonstrated LVP near the mid-inferior interventricular septum draining into the pericardial space, and LPE from the apical inferior left ventricle (LV) extending to the apical cap of the right ventricle (RV). Computed tomography angiography (CTA) demonstrated a multiloculated collection at the inferior septal aspect of LV contained by the pericardial space. Patient was a high risk for surgery. LVP was closed via a 24 mm atrial septal defect (ASD) occluder device. Intraoperative TEE demonstrated an ASD occluder device at the mid inferior septum at the location of the LVP neck with minimal residual flow into the LPE and a fistula connecting the LPE space with RV. RVFP was managed conservatively. LAD was managed medically. Patient was discharged home safely on guideline directed medical therapy.Discussion:LVP rate is 0.0026% following myocardial injury. It is reported that untreated LVP have a rupture risk of about 30% and a mortality rate of 50%. Prompt treatment is required to prevent mortality. Surgical management is the standard of care. A multidisciplinary heart team deemed the patient a high risk. Therefore, transcatheter treatment was sought in the patient above.Conclusions:Surgical treatment is standard of care for LVP, but transcatheter wall closure with an ASD device is a promising technique not only for high-risk surgical candidates such as above, but as a gold standard of treatment for LVP.

Circulation, Volume 146, Issue Suppl_1, Page A12949-A12949, November 8, 2022. Introduction:Pulmonary hypertension due to left heart disease (Group 2) is the most common type of pulmonary hypertension and has two subtypes: isolated post-capillary pulmonary hypertension (Ipc-PH) and combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH). Little is known about the molecular characteristics that distinguish these two subphenotypes or if Cpc-PH shares molecular similarities to pulmonary arterial hypertension (PAH), as has previously been suggested. Many lipid metabolites, including a diverse group of bioactive lipid mediators known as oxylipins, have been associated with cardiovascular disease and other inflammatory conditions. Therefore, we sought to characterize oxylipin and other bioactive lipid profiles among patients with Ipc-PH and Cpc-PH, as well as those with PAH.Methods:We studied 129 patients with Ipc-PH (n=38), Cpc-PH (n=52), or PAH (n=39) between June 2006 and March 2012. Liquid chromatography-mass spectrometry was used to assess 350 lipid metabolite analytes in each patient.Results:In multivariable analyses adjusting for age, sex, BMI, and pulmonary hypertension medications, we observed 34 metabolites were significantly increased and 10 were decreased in Ipc-PH compared to Cpc-PH (Figure). Among these same metabolites, only 9 were significantly different between Cpc-PH and PAH. Compared to patients with Ipc-PH, those with Cpc-PH had elevated levels of fatty acyl esters of hydroxy fatty acids and polyunsaturated fatty acids as well as lower levels of anti-inflammatory and pulmonary vascular relaxant oxylipins.Conclusions:Overall, these findings suggest that Cpc-PH may diverge from Ipc-PH and share some molecular similarities with PAH. Identifying key molecular targets involved in Cpc-PH pathophysiology may be critical for diagnostic purposes and in the development of novel therapeutic avenues for patients with Cpc-PH.

Circulation, Volume 146, Issue Suppl_1, Page A14461-A14461, November 8, 2022. Background:Transcatheter aortic valve replacement (TAVR) is indicated in patients with severely reduced left ventricular ejection fraction (LVEF) and can restore left ventricular (LV) function. However, mortality outcomes in this unique subset of patients has been studied only in limited cohorts.Methods:Extensive search on PubMed and Google Scholar yielded 1069 reports meeting inclusion criteria. These studies were independently evaluated by 2 physicians. Nine studies comparing all-cause mortality in patients undergoing TAVR with and without severely reduced LVEF (30% was considered an indicator of statistical heterogeneity among the studies. A Mantel-Haenszel Random effects model was used to calculate the Odds Ratio for homogeneous endpoints. A p value

Circulation, Volume 146, Issue Suppl_1, Page A11765-A11765, November 8, 2022. Introduction:Catheter ablation therapy (CAT) is recommended for the management of symptomatic atrial fibrillation (AF). Previous real-world studies using the National Inpatient Sample (NIS) have described a disproportionately higher burden of post-CAT complications in womenHypothesis:We sought to determine whether the prior gender disparities in complications post-CAT for AF still exist. We hypothesize that with increasing CAT proficiency women would be no more likely to suffer complications compared to menMethods:We identified all percutaneous AF CAT hospitalizations in the NIS 2016-2019. We used Inverse-Probability Weighting (IPW) to create a pseudo-population where gender was independent of the following confounders: age, race/ethnicity, primary payor, median income, CHA2DS2VASc and Elixhauser scores, comorbidities including obesity, alcohol use disorder, obstructive sleep apnea, chronic pulmonary disease, and hospital characteristics-region, teaching-status, and bed-size. We compared in-hospital mortality rate, total procedural complications including pericardial (tamponade/effusion/pericarditis); cardiac (heart failure/perioperative MI/shock); respiratory (pneumothorax/respiratory failure); esophageal (perforation/injury); vascular (access-site fistulas/bleeding); and renal (acute kidney injury) between men and womenResults:Of the 5,835 AF CATs identified (representing 29,175 nationally), 43.2% were performed in women. Before IPW, women were older, and had higher proportions of comorbidities. After applying weights, baseline characters were well-balanced. In the weighted-cohort, there was no difference in mortality (0.48% vs 0.29%, p=0.52) or total complications (8.3% vs 9.6%, p=0.20). Likewise, pericardial (4.5% vs 4.1%, p=0.26); cardiac (0.3% vs 0.4%, p=0.40); vascular (3.6% vs 3.4%, p=0.37); respiratory (0.7% vs 0.8%, p=0.70); esophageal (0.5% vs 0.4%, p=0.31); and renal (1.2% vs 2.3%, p=0.38) complications, were similar across genderConclusion:In this real-world cohort, the burden of complications after CAT for AF was similar across gender. Sustained national efforts at maintaining awareness of gender disparities in complications post-AF CAT are needed to keep this new status quo

Circulation, Volume 146, Issue Suppl_1, Page A12876-A12876, November 8, 2022. Introduction:Heart failure (HF) is characterized by a switch from predominantly fatty acid (FA) to glucose metabolism, but the molecular pathways involved in this switch are not totally understood. Identification of novel pathways regulating cellular metabolism could facilitate the development of new therapies. Tristetraprolin (TTP) is a tandem zinc finger protein that binds to AU-rich elements (AREs) in the 3’ untranslated region (UTR) of mRNA molecules and causes their degradation. Its expression is regulated by mTOR, a key protein involved in cellular metabolism. Our preliminary data suggested a link between TTP and FA metabolism in the heart. Thus, we hypothesized that TTP regulates cardiac FA metabolism and that its deletion prevents the development of HF by increasing FA uptake and metabolism in the heart.Results:TTP downregulation in cultured cardiomyocytes resulted in higher palmitate uptake and oxidation, while its overexpression had the opposite effect. Since TTP regulates its targets at the mRNA level, we studied the mRNA levels of ARE-containing genes involved in lipid metabolism, and found that only PPARα mRNA to be significantly increased with TTP downregulation. Furthermore, we demonstrated that TTP physically interacts with PPARα mRNA, and the activity of a luciferase reporter harboring full-length PPARα 3’UTR is increased with TTP downregulation. Additionally, PPARα mRNA is stabilized with TTP knockdown. We then studied the role of TTP in cardiac FA metabolism using mice with cardiac-specific (cs) TTP knockout (KO). Consistent with our in vitro data, cs-TTP KO mice displayed higher fatty acid utilization compared to littermate controls but maintained normal cardiac function at baseline. We also demonstrated a significantly higher TTP levels in failing human and mouse cardiac samples, suggesting that TTP levels are altered in HF.Conclusion:Our results demonstrate that TTP is a novel regulator of cardiac FA metabolism through its effect on PPARα, and that its levels are increased in HF. Thus, modulation of TTP may be a viable therapeutic approach for HF.

Circulation, Volume 146, Issue Suppl_1, Page A15128-A15128, November 8, 2022. Background:The development of mRNA vaccines was essential in combatting the COVID-19 pandemic. Emergency use authorization for COVID-19 vaccine was granted to adolescents aged 12 and older in May 2021. Subsequently, an increase in myocarditis was observed related to the mRNA vaccine. Previous reports estimate a 5% incidence of ventricular arrhythmias in patients with vaccine-associated myocarditis.Hypothesis:The incidence of ventricular ectopy in patients with post-COVID vaccine myocarditis is higher than previously described.Methods:We analyzed data retrospectively for patients admitted to our cardiac center with clinically suspected myocarditis who received COVID-19 vaccine within 30-days prior to onset of symptoms and had no other clinical cause for myocarditis. We separated this cohort into 3 groups based on the presence of rhythm monitoring post discharge: normal monitor post discharge (Lown grade 0 or 1), abnormal monitor post discharge (Lown grade ≥ 2), and no monitor post discharge. Data are shown as mean ± standard deviation.Results:We included 16 patients with a mean age of 14.9 ± 3.1 years. 12 patients were discharged with ambulatory monitoring and 3 were categorized as abnormal (25%). Abnormal findings included non-sustained ventricular tachycardia, ventricular ectopy with bigeminy and trigeminy patterns, and sustained monomorphic ventricular tachycardia. 1 patient was readmitted for sustained ventricular tachycardia. Mean troponin levels were higher in the arrhythmia group (17.3 ±4) compared to the non-arrhythmia group (4.3 ±4.3). 2 of the 3 patients in the arrhythmia group had myocardial edema on cMRI. Only one patient had LGE.Conclusion:At our center, 25% of patients with post-COVID vaccine myocarditis experienced ventricular arrhythmias, and these patients had higher troponin levels during acute illness. Awareness of this increased rate of arrhythmia is necessary to safely monitor patients with post-COVID vaccine myocarditis.

Circulation, Volume 146, Issue Suppl_1, Page A9525-A9525, November 8, 2022. Introduction:Supporting self-management is essential to improving health outcomes after stroke. More evidence on the stroke survivors’ experiences and perceived usefulness of the self-management interventions are needed to provide better support.Purpose:This study was aimed to explore stroke survivors’ experiences of attending an 8-week programme which consisted of four home visits and five follow-up phone calls and delivered by a collaborative team of nurses and trained lay volunteers.Methods:A qualitative study was conducted with a convenience sample of the survivors who had received the programme. After completing the programme, the survivors were interviewed individually by phone using a semi-structured interview guide about their changes in perceiving and responding to post-stroke physical and psychosocial challenges. Suggestions to improve their experience of participation were collected. Interview data were transcribed verbatim and analysed thematically.Results:Thirty stroke survivors (mean age=60 years, SD=11.74) were interviewed. Most of them were male (60%), married (63.3%) and had a first-ever ischaemic stroke (50%). The mean duration of onset after stroke was 5.63 years (SD=3.12). About 63% of them walked unaided or with a stick. Four (13.3%) had mild dysphasia. Four themes were derived: developed short-term goals with lifestyle-integrated action plans; resumed social activities or work; increased satisfaction with life and sense of being cared for; more effective communication and relief of negative emotions; increased adoption of new and creative strategies to improve limb functions. Suggestions for improving the programme included longer duration, more home visits, earlier support upon discharge from the hospital, meetings with other survivors for mutual support while working towards the goals, and more structured follow-up phone calls.Conclusions:The self-management programme was found helpful in improving the survivors’ confidence and performance of self-management behaviours. Making the programme available upon discharge, and extending its duration with more home visits, group sessions and structured phone calls would build stronger self-management capabilities in survivors.

Circulation, Volume 146, Issue Suppl_1, Page A10282-A10282, November 8, 2022. Introduction:Despite anticoagulation (AC), up to 50% of proximal deep vein thrombosis (DVT) patients will develop the post-thrombotic syndrome (PTS). In a substudy of the ATTRACT DVT trial, catheter-directedthrombectomy/thrombolysis (CDT) in addition to AC improved PTS outcomes for patients presenting at an intermediate day (D) 4-8 symptom-onset-to-randomization (SOR) timeframe, but not at an early D0-3 or late D9+ SOR timeframe. Mechanisms underlying the role of early AC and CDT are unknown, particularly iliofemoral DVT (IFDVT) patients that preferentially benefit from CDT.Methods:First, we assessed the temporal impact of AC on Villalta and VEINES-QoL PTS scores in a post-hoc analysis of the IFDVT ATTRACT patients (N=391). Mean scores were estimated by a piecewise linear-regression growth-curve model. Next, to mechanistically explore the effects of AC on PTS measures, C57/BL6 mice (N=76) underwent inferior vena cava (IVC) ligation to produce stasis DVT. Mice then underwent true or sham de-ligation at D2 to spur restoration of blood flow (RBF). Last, enoxaparin AC was initiated at D2 and given daily until D8, at either 0, 10, or 30 mg/kg/d SQ. D4 RBF rates in the IVC, and D8 thrombus burden were assessed.Results:In IFDVT ATTRACT patients, CDT+AC improved PTS scores in the intermediate D4-8 SOR timeframe (p0.05 vs. AC alone). In the AC alone groups, early AC D0-3 significantly improved PTS scores over delayed AC (p

Circulation, Volume 146, Issue Suppl_1, Page A10900-A10900, November 8, 2022. Pulmonary Arterial Hypertension (PAH) is characterized by progressive pulmonary arteries (PAs) obstruction leading to heart failure and death. PA smooth muscle cells (PASMCs) of PAH patients display a “cancer-like” phenotype that contributes to PA remodeling. Eukaryotic translation initiation factor 5A (eIF5A) was shown to provide cancer cells with a competitive advantage by increasing translation of mRNAs with oncogenic proprieties, many of them containing proline/glycine-rich patterns. Strikingly, eIF5A is the only protein containing the unique, polyamine-derived amino acid hypusine, which is required for its function. Hypusine formation is catalyzed by the sequential actions of deoxyhypusine synthase (DHPS) and deoxyhypusine hydrolase (DOHH). We hypothesized that increased eiF5AHypin PAH-PASMCs is required to promote translational efficiency of a set of factors conferring a higher survival and fibroproliferative capacity, leading to pulmonary vascular remodeling.Data derived from a comparative proteomic analysis (LC-MSMS) between normal and PAH-PASMCs and confirmed by Western blot indicate that DHPS and DOHH are overexpressed in PAH-PASMCs compared to controls (p

Circulation, Volume 146, Issue Suppl_1, Page A10985-A10985, November 8, 2022. Introduction:Studies have demonstrated a reduction in peak oxygen consumption (VO2) post-acute COVID-19. We sought to determine the association between acute COVID-19 severity, post-acute symptoms and peak VO2after recovery.Methods:This study analyzed data from patients who recovered from COVID-19 and underwent cardiopulmonary exercise testing (CPET) as part of prospective studies in 5 centers across UK and Europe. Patients were asked to report current symptoms. Peak VO2, lung volumes, gas exchange, ventilatory efficiency, heart rate and O2pulse were measured in a standard symptom-limited incremental cycle ergometer CPET.Results:Among 417 patients examined 136±63 days after recovery from COVID-19, 164 (39%) were female. Mean age was 56.9±13.3 years. The spectrum of acute COVID-19 severity included critical (N=47; 11.3%), severe (180; 43.2%), moderate (75; 18.0%) and mild (115; 27.5%) illness. The most common post-acute symptom was dyspnea (200; 48%), followed by muscle pain (173; 41%). Mean peak respiratory exchange ratio was 1.13±0.1, and did not vary across acute disease severity or post-acute symptom status. There was no significant difference in peak VO2as % from predicted in mild to critical acute disease: 84.0±2.1%, 91.4±2.6%, 82.9±1.7% and 83.7±3.2%, respectively (p=0.06). Patients with dyspnea or muscle pain had each lower peak VO2as % from predicted, compared to patients free of the specific symptom (81.3±21.2% vs. 88.1±22.9%, p=0.002 and 78.6±19.1% vs. 88.2±22.0%, p

Circulation, Volume 146, Issue Suppl_1, Page A13321-A13321, November 8, 2022. Background:The conduct of clinical trials during COVID-19 created challenges to ensuring access to clinical trials, healthy clinical teams, and patients. Innovative methods such as remote patient follow-up and monitoring visits can lead to successful completion of device trials.Objective:The INGEVITY+ Active Fixation Pace/Sense Lead Study examined the safety/ efficacy of the INGEVITY+ Lead in a prospective, non-randomized, multicenter, post-approval study.Methods:Subjects met indications for a pacing device with INGEVITY+ leads implanted in the RA and RV. The primary safety endpoint was the 3-month lead-related complication-free (LRC-free) rate. The primary efficacy endpoint evaluated the 3-month pacing capture threshold with the secondary efficacy endpoint evaluating the other lead-related electrical parameters. Implanter experience was assessed. Telephone visits with LATITUDE remote transmission of lead measurement data and remote monitoring visits were allowed.Results:A total of 201 leads were evaluated in 101 subjects, 46.8% female with a mean age of 73.2 years, at 13 centers in the United States. The study took 6.8 months, with a median follow-up of 3.4 months. The 3-month follow-up was completed by 98% of subjects, of which 36% were remote. A total of 98% of monitoring visits were done remotely. The study met all primary and secondary endpoints. The LRC-free rate through 3-months was 98.5% (lower CL 95.4%). Three leads were repositioned and reimplanted; two were RA dislodgements, and one was a RA perforation and hemothorax requiring thoracentesis. The pacing capture threshold was ≤ 2V in 98.9% of subjects with a mean of 0.77 V at 0.4-ms pulse width, mean pacing impedance of 712 ohms, and a median P-wave amplitude of 4.3 mV, and median R-wave amplitude of 15.9 mV at 3-months. No helix performance issues were reported. The mean turn count for helix extension was 6.7 and retraction was 7.6. More than 85% of physicians rated the lead as ‘very good’ or higher on all aspects of lead handling.Conclusions:The INGEVITY+ Lead was found to be safe and effective with a very favorable implant experience. This study was entirely conducted successfully during COVID-19 with remote follow-up and monitoring visits, and nearly half of the subjects were females.

Circulation, Volume 146, Issue Suppl_1, Page A11491-A11491, November 8, 2022. Introduction:Post-acute sequelae of SARS-CoV-2 cardiovascular syndrome (PASC-CVS) is a heterogeneous disorder of post-COVID syndrome that involves a wide range of cardiovascular symptoms including palpitations, chest pain, dyspnea and dizziness. The clinical time-course of PASC-CVS is not well characterized. We sought to understand predictors of time to symptom improvement for patients with PASC-CVS.Methods:Patients with PASC-CVS undergoing evaluation in a dedicated post-COVID cardiology clinic were recruited after informed consent. Information was obtained from chart review and included demographics, comorbidities, symptoms, time of infection to time of presentation to the clinic and time to improvement in symptoms. A multivariate linear regression model was used to determine predictors of time to improvement.Results:A total of 144 consecutive patients were included that had complete records available for review. Average age was 46 years, 74% were female and 94% were Caucasian. Comorbities included obesity (49%), mental health disorder (25%), hypertension (24%), hyperlipidemia (24%), pulmonary disease (18%), type II diabetes (9%), atrial arrhythmia (5%) and coronary artery disease (3%). Time from infection to presentation (p

Circulation, Volume 146, Issue Suppl_1, Page A15140-A15140, November 8, 2022. Mixed connective tissue disorder (MCTD) is associated with a broad range of cardiovascular abnormalities, including coronary artery disease (CAD). It has been proposed that chronic systemic inflammation plays a key role in the development of atherosclerotic disease.A 66-year-old female with a history of MCTD and hypertension presented with mild dyspnea and pleuritic chest pain after one week of persistent flu-like symptoms. Her blood pressure was 108/77 mmHg, pulse 92 bpm, saturating 98% on room air. She was comfortable and denied other risk factors such as diabetes, hyperlipidemia, or prior smoking history. On exam she was found to have a soft holosystolic murmur across her precordium. EKG showed sinus rhythm with small Q waves and ST elevation in V1-V6. She was taken for cardiac catheterization which revealed a thrombotic occlusion in the proximal left anterior descending artery (LAD) and a severe lesion in the left circumflex artery. She underwent angioplasty with one drug eluted stent placed to LAD. Left ventriculography revealed a VSD near the apex, and transthoracic echocardiogram showed a 7.6 mm muscular VSD with left to right shunt, ejection fraction of 35% and hypokinesis of the anterior wall. She became hypotensive and required vasopressors prior to coronary artery bypass grafting and primary closure of her apical VSD. Intraoperatively, a 2 cm VSD with 5 cm of necrotic surrounding tissue was noted. Post-operative complications included asystolic cardiac arrest, marked cardiogenic shock and multiorgan failure to which she ultimately succumbed.Post-myocardial infarction VSD is a rare complication of MI occurring in approximately 0.2% of cases. However, patients with MCTD can develop atypical symptoms, resulting in delayed presentation and therefore higher risk of mechanical complications. We highlight the importance of a thorough physical exam and high suspicion for mechanical complications in these patients even when hemodynamically stable.

Circulation, Volume 146, Issue Suppl_1, Page A15008-A15008, November 8, 2022. Introduction:Myocardial infarction (MI) is a leading cause of death worldwide. Although available treatments improve prognosis post-MI, they do not remediate cardiomyocyte death and loss of cardiac vasculature, resulting in chronic maladaptive remodeling and subsequently, heart failure. Extracellular vesicles (EVs) derived from endothelial colony-forming cells (ECFCs) show therapeutic potential, facilitating adaptive cardiac remodeling post-MI. However, ECFCs function is compromised in patients with type-2 diabetes, a common risk factor for MI, limiting the applicability of autologous cell-based therapies. Therapeutic administration is a further challenge, as current strategies present difficulties regarding invasiveness, retention, and efficacy.Hypothesis:We hypothesized that the minimally invasive intra-pericardial (IP) injection of ECFCs-EVs within a hydrogel would improve cardiac retention and promote sustained therapeutic release, facilitating cardiac repair in a murine model of MI. We anticipated that this repair would be greater with the use of EVs derived from wildtype mice than from diabetic mice.Methods:The impact of wildtype and diabetic ECFCs-EVs was evaluated on both in vitro EVs retention and angiogenesis. In a murine model of MI, the left anterior descending coronary artery was ligated while the pericardium was preserved. We evaluated whether IP injection is an effective and safe method of delivering hydrogels containing ECFCs-EVs, in addition to its long-term effects on cardiac morphology and function.Results:Our findings indicate that hydrogel use facilitates sustained EVs release. Besides that, the administration of ECFCs-EVs increased coronary endothelial cell proliferation, migration, and vascularization in vitro, and reduced maladaptive cardiac remodeling, improving cardiac contractility and function in vivo. These effects appear to be more pronounced with the administration of wildtype ECFCs-EVs.Conclusions:Collectively, our results underscore the therapeutic promise of ECFCs-EVs to improve cardiac repair after MI.