Peripartum Lipid Apheresis: Novel Management of Familial Hyperlipidemia in Pregnancy.

Familial hypercholesterolemia (FH) is a genetic lipid disorder associated with early-onset severe cardiovascular disease. Many FH therapeutics have not been studied in pregnancy, and management of patients with FH through pregnancy is limited. We present a patient with FH who was safely treated through pregnancy with combination therapy.

Outcomes of Endocarditis in Pregnancy: A Single-Center Experience.

Background: The incidence of infective endocarditis (IE) in pregnancy is rare (0.006%), with increasing prevalence during the opioid epidemic. IE in pregnancy is associated with high rates of mortality and morbidity, and existing data on outcomes in pregnancy are limited. Our study compares the outcomes of pregnant patients with IE with those of nonpregnant patients. Methods: Patients diagnosed with IE during pregnancy and 30 days postpartum between 2014 and 2021 were identified by International Classification of Diseases, Clinical Modification, Ninth and Tenth Edition codes. Pregnant cases were matched to nonpregnant reproductive-age endocarditis patients in a 1:4 ratio. Data were collected and validated through chart review. Results: One hundred eighty patients with IE were identified; 34 were pregnant or within 30 days postpartum at diagnosis. There were higher rates of hepatitis C and opioid maintenance therapy in the pregnant patients. The etiology of IE in pregnant patients was predominantly S. aureus (methicillin-resistant/sensitive S. aureus), whereas nonpregnant woman had greater microbiological variation. We observed comparable rates of valve replacement (32.4% vs 29%; P = .84) and 2-year mortality (20.6% vs 17.8%; P > .99) in pregnant patients. There were nonsignificantly higher rates of pulmonary emboli (17.6% vs 7.5%; P = .098) and arrhythmia (17.6% vs 9.6%; P = .222) among pregnant patients. There were high rates of intravenous drug use relapse in both groups (>40%). Conclusions: We observed similar rates of mortality in the pregnant IE patients. We observed a microbial predilection for S. aureus in pregnancy, suggesting that the pregnancy physiology may select for this microbiologic etiology. This study, which represents the largest single-center retrospective review of IE in pregnancy, suggests that surgical intervention may be performed safely in the postpartum period.

Experiences of athletes with arrhythmogenic cardiac conditions in returning to play.

Background: Recommendations for return to play (RTP) for athletes with genetic (or congenital) heart diseases (GHD) predisposing to sudden cardiac death (SCD) have evolved from an initially paternalistic and conservative approach, to supporting a more flexible approach to decision-making. The experiences of athletes and their families during the RTP process are unknown. Objective: To understand current RTP processes. Methods: We administered a mixed-methods telephone interview combining quantitative and qualitative components to 30 athletes with a GHD who had RTP, and 23 parents. Participants were identified from the Yale ICD Sports registry and Mayo Clinic's Windland Smith Rice Genetic Heart Rhythm Clinic. Qualitative data were analyzed using a grounded theory approach to identify common themes. Results: Most common diagnoses were long QT syndrome and hypertrophic cardiomyopathy and most common sports, soccer, basketball, and football. Twenty-three athletes encountered ≥1 perceived barrier(s) to RTP: 17 were restricted by their first cardiologist; 6 were required to meet with school administrators, 4 signed waivers, and 3 hired lawyers. Common themes expressed by athletes and their parents were frustration with poor communication, perceived lack of physician knowledge of their diagnosis, and unilateral, paternalistic decision-making, as well as cynicism that physicians and schools were primarily concerned with liability. After RTP, 26 athletes had some form of emergency action plan, although responsibility was often left to the family. Conclusion: Many perceived barriers exist for athletes with GHD who wish to RTP after their diagnoses. Shared decision-making from the onset is critical for RTP.

Management of infective endocarditis in pregnancy by a multidisciplinary team: a case series.

INTRODUCTION: The incidence of infective endocarditis (IE) in pregnancy is rare and has been increasing during the opioid epidemic. IE in pregnancy is associated with high rates of maternal and fetal morbidity and mortality. Multidisciplinary endocarditis teams for management of IE have been shown to reduce in-hospital and 1-year mortality. We present a single-center experience managing IE in pregnancy utilizing a multidisciplinary endocarditis team. METHODS: Patients diagnosed with IE while pregnant or within 30 days post-partum were identified. All patients discussed at the institution's weekly multidisciplinary endocarditis meeting were included. Demographic and clinical data and outcome-related variables were retrospectively reviewed and recorded. RESULTS: Between 1 October 2020 and 1 June 2021 6 pregnant or 30-day post-partum patients with IE were identified. All patients had co-morbid injection drug use; Staphylococcus aureus was the etiologic pathogen in all patients. All patients had embolic complications and 5 required ICU admission and mechanical ventilatory support. Four patients underwent valve replacement. There were no patient-directed discharges. All patients survived to hospital discharge and 90-days after diagnosis. Four pregnancies resulted in delivery at an average gestational age of 32.4 weeks with 3 requiring NICU admissions and prolonged lengths of stay. All patients were seen by addiction medicine and 5 were started on medication-assisted treatment for opioid use disorder. DISCUSSION: In a small retrospective cases series, coordination of care by a multidisciplinary endocarditis team led to a high-rate of surgical intervention with no patient-directed discharges and no in-hospital or 90-day mortality. CONCLUSION: Multidisciplinary endocarditis teams are a low-risk intervention that may improve outcomes in pregnant patients with IE.

Outcomes of mechanical circulatory support for acute myocardial infarction complicated by cardiogenic shock.

BACKGROUND: Mechanical circulatory support (MCS) with the Impella device (Abiomed, Danvers, MA) has been associated with higher in-hospital mortality than intra-aortic balloon pump (IABP) in the Premier Healthcare Database and National Cardiovascular Data Registry. METHODS: The objective of this retrospective cohort study was to describe trends and outcomes of Impella usage in acute myocardial infarction complicated by cardiogenic shock (AMICS) treated with MCS (Impella or IABP) using real-world observational data from the National Inpatient Sample (NIS) including hospitalizations for AMICS managed with MCS between January 2012 to December 2017. The primary outcomes included in-hospital mortality, transfusion, acute kidney injury, stroke, total costs, and length of stay. Propensity score matching was performed with hierarchical models using risk factor and Elixhauser comorbidity variables. RESULTS AND CONCLUSION: We identified 54,480 hospitalizations for AMICS managed with MCS including 5750 (10.5%) utilizing Impella. Throughout the study period, Impella usage increased yearly to 19.9% of AMICS cases in 2017. After propensity score matching, Impella was associated with higher in-hospital mortality (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.41-2.13) and transfusions (OR 1.97, 95% CI 1.40-2.78) than IABP, without association with acute kidney injury or stroke. Impella use was associated with higher hospital costs (mean difference $22,416.80 [95% CI $17,029-27,804]). Impella usage for AMICS increased significantly from 2012 to 2017 and was associated with increased in-hospital mortality and costs. Randomized controlled trials are urgently needed to assess the safety and efficacy of Impella.

Histologic evaluation of therapeutic responses in ischemic myocardium elicited by dual growth factor delivery from composite glycosaminoglycan hydrogels.

In this project, the ability of dual growth factor-preloaded, silk-reinforced, composite hyaluronic acid-based hydrogels to elicit advantageous histologic responses when secured to ischemic myocardium was evaluated in vivo. Reinforced hydrogels containing both Vascular Endothelial Growth Factor (VEGF) and Platelet-derived Growth Factor (PDGF) were prepared by crosslinking chemically modified hyaluronic acid and heparin with poly(ethylene glycol)-diacrylate around a reinforcing silk mesh. Composite patches were sutured to the ventricular surface of ischemic myocardium in Sprague-Dawley rats, and the resulting angiogenic response was followed for 28 days. The gross appearance of treated hearts showed significantly reduced ischemic area and fibrous deposition compared to untreated control hearts. Histologic evaluation showed growth factor delivery to restore myofiber orientation to pre-surgical levels and to significantly increase elicited microvessel density and maturity by day 28 in infarcted myocardial tissue (p < 0.05). In addition, growth factor delivery reduced cell apoptosis and decreased the density of elicited mast cells and both CD68+ and anti-inflammatory CD163+ macrophages. These findings suggest that HA-based, dual growth factor-loaded hydrogels can successfully induce a series of beneficial responses in ischemic myocardium, and offer the potential for therapeutic improvement of ischemic myocardial remodeling.

Increased Mortality in Patients With Preoperative and Persistent Postoperative Pulmonary Hypertension Undergoing Mitral Valve Surgery for Mitral Regurgitation: A Cohort Study.

Background Preoperative pulmonary hypertension (PH) is associated with excess mortality among patients with severe mitral regurgitation undergoing mitral valve surgery (MVS). However, the links between PH phenotype, pulmonary vascular remodeling, and persistent postoperative PH are not well understood. We aimed to describe the associations between components of pulmonary hemodynamics as well as postoperative residual PH with longitudinal mortality in patients with severe mitral regurgitation who received MVS. Methods and Results Patients undergoing MVS for severe mitral regurgitation from 2011 to 2016 were retrospectively identified within our health system (n=488). Mean pulmonary artery pressure and other hemodynamic variables were determined by presurgical right-heart catheterization. Postoperative pulmonary artery systolic pressure was assessed on echocardiogram 42 to 365 days post-MVS. Longitudinal survival over a mean 3.9 years of follow-up was evaluated using Cox proportional hazards modeling to compare survival after adjustment for demographics, surgical characteristics, and comorbidities. Pre-MVS prevalence of PH was high at 85%. After adjustment, each 10-mm Hg increase in preoperative mean pulmonary artery pressure was associated with a 1.38-fold increase in risk of death (95% CI, 1.13-1.68). Elevated preoperative pulmonary vascular resistance, transpulmonary gradient, and right atrial pressure were similarly associated with increased mortality. Among 231 patients with postoperative echocardiogram, evidence of PH on echocardiogram (pulmonary artery systolic pressure ≥35 mm Hg) was associated with increased risk of death (hazard ratio [HR], 2.02 [95% CI, 1.17-3.47]); however, this was no longer statistically significant after adjustment (HR, 1.55 [95% CI, 0.85-2.85]). Conclusions In patients undergoing MVS for mitral regurgitation, preoperative PH, and postoperative PH were associated with increased mortality.

Effect of institutional transcatheter aortic valve replacement volume on mortality: A systematic review and meta-analysis.

OBJECTIVE: We sought to conduct a systematic review and network meta-analysis to examine the association between institutional transcatheter aortic valve replacement (TAVR) volume and all-cause mortality. BACKGROUND: Since inception in 2011, there has been an exponential increase in the number of TAVR centers across the world. Multiple studies have questioned if a relationship exists between institutional TAVR volume and patient outcomes. METHODS: We performed a systematic literature search for relevant articles using a combination of free text terms in the title/abstract related to volume, TAVR, and patient outcomes. Two reviewers independently screened all titles/abstracts for eligibility based on pre-specified criteria. All-cause mortality data was pooled from eligible studies and centers were categorized as low-(30-50 cases), intermediate-, or high-volume (75-130 cases) based on their annual TAVR volumes. RESULTS: Our search yielded an initial list of 11,153 citations, 120 full text studies were reviewed and 7 studies met all inclusion and exclusion criteria, yielding a total of 1,93,498 TAVRs. Categorized according to center's annual volume; 25,062 TAVRs were performed in low-, 77,093 in intermediate- and 91,343 in high-volume centers. Network meta-analysis showed a relative reduction in mortality rates of 37%, 23% and 19%, for high volume versus low volume centers, high volume versus intermediate volume centers and intermediate versus low volume centers, respectively. CONCLUSIONS: Existing research clearly shows an inverse relationship between annual TAVR procedural volume and all-cause mortality. We need to focus on development of strong referral networks and consolidation rather than expansion of existing TAVR centers to improve patient outcomes, while ensuring adequate access-to-care.

Cardio-obstetrics: Recognizing and managing cardiovascular complications of pregnancy.

Pregnancy can exacerbate known cardiovascular disorders and unmask previously unrecognized problems. Patients with congenital heart disorders, valvular disease, primary pulmonary hypertension, hypertensive disorders of pregnancy, and acquired peripartum cardiomyopathy need a collaborative interdisciplinary team that includes a cardiologist with specialty training in obstetrics.

Subaortic Stenosis With Elevated Aortic Gradients in a Pregnant Patient.

Subaortic stenosis is an obstructive lesion that may be exacerbated by pregnancy. We describe the management of a 39-year-old woman presenting at 37 weeks of pregnancy with a murmur who is found to have a subaortic membrane with severely elevated left ventricular outflow gradients. (Level of Difficulty: Beginner.).

Endovascular Treatment of Inferior Vena Cava Thrombosis in Metastatic Malignancy: A Case Report and Review of Literature.

Inferior vena cava (IVC) thrombosis is a specific form of thromboembolism that occurs at a rate of 1.5% in all patients hospitalized with a deep vein thrombosis. Malignant IVC thrombosis may occur due to compression from a tumor mass or metastasis or may also occur through tumor invasion of the venous vasculature. Obstruction of the IVC can lead to IVC syndrome, marked by ascites, lower extremity edema, and even congestive hepatic failure. We present a case of extensive IVC thrombosis in a 69-year-old female with metastatic adrenal cell carcinoma, presenting with severe bilateral lower extremity edema and ascites. Computed tomography showed IVC compression by the caudate lobe due to a metastatic liver mass and extensive clot burden of the IVC extending from the renal veins to the right atrium (RA). She underwent percutaneous IVC stenting with 4 stents placed in tandem from the IVC to the RA. Her hospital course was complicated by gastrointestinal bleed requiring clipping, acute liver failure, and hypophysitis due to trial therapy. Although her IVC symptoms were partially relieved with percutaneous intervention, her acute liver failure worsened and she was ultimately transitioned to hospice care.

Cardiovascular Risk and Disease Among Masters Endurance Athletes: Insights from the Boston MASTER (Masters Athletes Survey To Evaluate Risk) Initiative.

BACKGROUND: Masters athletes (MAs), people over the age of 35 that participate in competitive sports, are a rapidly growing population that may be uniquely at risk for cardiovascular (CV) disease. The objective of this study was to develop a comprehensive clinical CV profile of MA. METHODS: An electronic Internet-based survey (survey response rate = 66 %) was used to characterize a community cohort of MAs residing in Eastern Massachusetts, USA. Clinical and lifestyle factors associated with prevalent CV disease were determined using logistic regression. RESULTS: Among 591 MAs (66 % men, age = 50 ± 9 years) with 21.3 ± 5.5 years of competitive endurance sport exposure, at least one CV risk factor was present in 64 % including the following: family history of premature atherosclerosis (32 %), prior/current tobacco exposure (23 %), hypertension (12.0 %), and dyslipidemia (7.4 %). There was a 9 % (54/591) prevalence of established CV disease which was accounted for largely by atrial fibrillation (AF) and coronary atherosclerosis (CAD). Prevalent AF was associated with years of exercise exposure [adjusted odds ratio, OR (95 % confidence intervals); OR = 1.10 (1.06, 1.21)] and hypertension [OR = 1.05 (1.01, 1.10)] while CAD was associated with dyslipidemia [OR = 9.09 (2.40, 34.39)] and tobacco use [OR = 1.78 (1.34, 3.10)] but was independent of exercise exposure. CONCLUSIONS: Among MAs, AF is associated with prior exercise exposure whereas CAD is associated with typical risk factors including dyslipidemia and prior tobacco use. These findings suggest that there are numerous opportunities to improve disease prevention and clinical care in this population.

Valvular interstitial cells suppress calcification of valvular endothelial cells.

BACKGROUND: Calcific aortic valve disease (CAVD) is the most common heart valve disease in the Western world. We previously proposed that valvular endothelial cells (VECs) replenish injured adult valve leaflets via endothelial-to-mesenchymal transformation (EndMT); however, whether EndMT contributes to valvular calcification is unknown. We hypothesized that aortic VECs undergo osteogenic differentiation via an EndMT process that can be inhibited by valvular interstitial cells (VICs). APPROACH AND RESULTS: VEC clones underwent TGF-ß1-mediated EndMT, shown by significantly increased mRNA expression of the EndMT markers α-SMA (5.3 ± 1.2), MMP-2 (13.5 ± 0.6) and Slug (12 ± 2.1) (p < 0.05), (compared to unstimulated controls). To study the effects of VIC on VEC EndMT, clonal populations of VICs were derived from the same valve leaflets, placed in co-culture with VECs, and grown in control/TGF-ß1 supplemented media. In the presence of VICs, EndMT was inhibited, shown by decreased mRNA expression of α-SMA (0.1 ± 0.5), MMP-2 (0.1 ± 0.1), and Slug (0.2 ± 0.2) (p < 0.05). When cultured in osteogenic media, VECs demonstrated osteogenic changes confirmed by increase in mRNA expression of osteocalcin (8.6 ± 1.3), osteopontin (3.7 ± 0.3), and Runx2 (5.5 ± 1.5). The VIC presence inhibited VEC osteogenesis, demonstrated by decreased expression of osteocalcin (0.4 ± 0.1) and osteopontin (0.2 ± 0.1) (p < 0.05). Time course analysis suggested that EndMT precedes osteogenesis, shown by an initial increase of α-SMA and MMP-2 (day 7), followed by an increase of osteopontin and osteocalcin (day 14). CONCLUSIONS: The data indicate that EndMT may precede VEC osteogenesis. This study shows that VICs inhibit VEC EndMT and osteogenesis, indicating the importance of VEC-VIC interactions in valve homeostasis.

Reciprocal interactions between mitral valve endothelial and interstitial cells reduce endothelial-to-mesenchymal transition and myofibroblastic activation.

Thickening of mitral leaflets, endothelial-to-mesenchymal transition (EndMT), and activated myofibroblast-like interstitial cells have been observed in ischemic mitral valve regurgitation. We set out to determine if interactions between mitral valve endothelial cells (VECs) and interstitial cells (VICs) might affect these alterations. We used in vitro co-culture in Transwell™ inserts to test the hypothesis that VICs secrete factors that inhibit EndMT and conversely, that VECs secrete factors that mitigate the activation of VICs to a myofibroblast-like, activated phenotype. Primary cultures and clonal populations of ovine mitral VICs and VECs were used. Western blot, quantitative reverse transcriptase PCR (qPCR) and functional assays were used to assess changes in cell phenotype and behavior. VICs or conditioned media from VICs inhibited transforming growth factor ß (TGFß)-induced EndMT in VECs, as indicated by reduced expression of EndMT markers α-smooth muscle actin (α-SMA), Slug, Snai1 and MMP-2 and maintained the ability of VECs to mediate leukocyte adhesion, an important endothelial function. VECs or conditioned media from VECs reversed the spontaneous cell culture-induced change in VICs to an activated phenotype, as indicated by reduced expression of α-SMA and type I collagen, increased expression chondromodulin-1 (Chm1), and reduced contractile activity. These results demonstrate that mitral VECs and VICs secrete soluble factors that can reduce VIC activation and inhibit TGFß-driven EndMT, respectively. These findings suggest that the endothelium of the mitral valve is critical for the maintenance of a quiescent VIC phenotype and that, in turn, VICs prevent EndMT. We speculate that the disturbance of the ongoing reciprocal interactions between VECs and VICs in vivo may contribute to the thickened and fibrotic leaflets observed in ischemic mitral regurgitation, and in other types of valve disease.

Electrospun PGS:PCL microfibers align human valvular interstitial cells and provide tunable scaffold anisotropy.

Tissue engineered heart valves (TEHV) can be useful in the repair of congenital or acquired valvular diseases due to their potential for growth and remodeling. The development of biomimetic scaffolds is a major challenge in heart valve tissue engineering. One of the most important structural characteristics of mature heart valve leaflets is their intrinsic anisotropy, which is derived from the microstructure of aligned collagen fibers in the extracellular matrix (ECM). In the present study, a directional electrospinning technique is used to fabricate fibrous poly(glycerol sebacate):poly(caprolactone) (PGS:PCL) scaffolds containing aligned fibers, which resemble native heart valve leaflet ECM networks. In addition, the anisotropic mechanical characteristics of fabricated scaffolds are tuned by changing the ratio of PGS:PCL to mimic the native heart valve's mechanical properties. Primary human valvular interstitial cells (VICs) attach and align along the anisotropic axes of all PGS:PCL scaffolds with various mechanical properties. The cells are also biochemically active in producing heart-valve-associated collagen, vimentin, and smooth muscle actin as determined by gene expression. The fibrous PGS:PCL scaffolds seeded with human VICs mimick the structure and mechanical properties of native valve leaflet tissues and would potentially be suitable for the replacement of heart valves in diverse patient populations.

Bacterial biosensors for evaluating potential impacts of estrogenic endocrine disrupting compounds in multiple species.

To study the effects and possible mechanisms of suspected endocrine disrupting compounds (EDCs), a wide variety of assays have been developed. In this work, we generated engineered Escherichia coli biosensor strains that incorporate the ligand-binding domains (LBDs) of the ß-subtype estrogen receptors (ERß) from Solea solea (sole), and Sus scrofa (pig). These strains indicate the presence of ligands for these receptors by changes in growth phenotype, and can differentiate agonist from antagonist and give a rough indication of binding affinity via dose-response curves. The resulting strains were compared with our previously reported Homo sapiens ERß biosensor strain. In initial tests, all three of the strains correctly identified estrogenic test compounds with a high degree of certainly (Z' typically greater than 0.5), including the weakly binding test compound bisphenol A (BPA) (Z' ≈ 0.1-0.3). The modular design of the sensing element in this strain allows quick development of new species-based biosensors by simple LBD swapping, suggesting its use in initial comparative analysis of EDC impacts across multiple species. Interestingly, the growth phenotypes of the biosensor strains indicate similar binding for highly estrogenic control compounds, but suggest differences in ligand binding for more weakly binding EDCs.

Time and space resolved uptake study of silica nanoparticles by human cells.

A spatio-temporal mapping of the uptake of silica (SiO(2)) nanoparticles of different sizes by lung epithelial cells has been obtained. Based on high control of nanoparticle dispersion in cell media and cell exposure, one obtains reproducible and quantitative time-resolved data using a combination of flow cytometry, fluorescence and electron microscopies. We are thereby able to give a rather detailed account of the journey of SiO(2) nanoparticles from the early events of uptake to their final sub-cellular localization.