Disparities in Health and Healthcare: Impact of Race on Resource Utilization and Costs Following Transcatheter Edge-to-Edge Repair.

BACKGROUND: This study sought to investigate health and healthcare disparities in the management of severe mitral regurgitation with transcatheter edge-to-edge repair using MitraClip and how racial differences impact resource utilization and costs. METHODS: We retrospectively analyzed the National Inpatient Sample (NIS) for patients who underwent Transcatheter Edge-to-Edge Repair (TEER) using MitraClip between 2016 and 2018. The patients were stratified into four racial cohorts and study outcomes included high resource utilization (HRU), periprocedural complications, and total procedural costs. High resource utilization (HRU) was defined as length of stay (LOS) ≥7 days or a nonhome disposition at discharge. Multivariate logistic regression models were utilized to determine independent predictors of HRU. RESULTS: 17,100 weighted TEER patients were segregated by race: Caucasian (n = 13,270), others (n = 1510), African Americans, AA (n = 1245) and Hispanics (n = 1075). More African Americans and Hispanics had TEER at Urban facilities (P < 0.001), which were teaching hospitals as well (P < 0.001) but were less likely to be covered by public insurance options -Medicare or Medicaid (P < 0.001). More AA (52.2 %) and Hispanics (27.6 %) were likely to be in the lowest median annual income quartile versus Caucasians (19.2 %) (P = 0.003). AA and Hispanics had higher resource utilization (HRU), prolonged length of stay, nonhome disposition at discharge, higher procedural costs and periprocedural complications versus Caucasians. The logistic regression model revealed acute kidney injury (AKI) and actual procedural costs as independent predictors of HRU in both African American and Hispanic groups. CONCLUSION: Significant Health and healthcare disparities do exist among underrepresented, racial minority patients undergoing transcatheter edge-to-edge repair in the US. These disparities were associated with higher resource utilization and actual costs in patients with mitral regurgitation treated with TEER.

Adverse Events Following Transcatheter Edge-to-Edge Repair (TEER) Using MitraClip: Lessons Learned From the Manufacturer and User Facility Device Experience (MAUDE) Registry.

OBJECTIVE: The MitraClip from Abbott is FDA approved intracardiac implantable device for transcatheter edge-to-edge repair (TEER). Despite a few previously published studies, there is limited safety data for its use in clinical practice, hence, we designed this study using data obtained from a safety nationwide database to demonstrate the safety profile of MitraClip. METHODS: The first two of the five authors independently queried all reported adverse events from the United State Food and Drug Administration [FDA] Manufacturer and User Facility Device Experience [MAUDE] registry from January 2014 to December 2020. The primary end point was trend in reported fatal events obtained from this database. The secondary end points included the causes of reported nonfatal reports from the MAUDE registry. The trend of reported fatal events was assessed using the Cochran Armitage trend test over the period of the study. RESULTS: During the study period, subjects included 3370 patients whose MitraClip-associated adverse events were reported and captured by MAUDE registry. Of these, 211 were fatal and 3159 nonfatal events. Fatal event reports resulted deaths and reported nonfatal events were from injuries and device system malfunction. This study demonstrated an initial upward trend from 2014 to 2015 then a subsequent statistically significant downward trend in reported fatal events from 2015 to 2020 (Cochran-Armitage test P = 0.039). The peak proportion of reported fatal events occurred in 2015, (n = 44; representing 1.25% of reported adverse events) and lowest proportion of reported fatal events took place in 2020 (n = 19; representing 0.56% of reported adverse events). The most reported nonfatal events were from malfunctioning of MitraClip system (n = 1170; representing 37% of reported nonfatal events), new unremarkable repolarization abnormalities on periprocedural EKG (n = 864; representing 27% of reported nonfatal events), leaflet rupture (n = 651; representing 21% of reported nonfatal events), and cardiogenic shock (n = 170; representing 5% of reported nonfatal events). CONCLUSIONS: This analysis of the MAUDE Registry indicated, especially within the confines of this study's limitations and poor data quality of information, an apparent downward trend of reported fatal events over the study period. Even though conclusive attributions cannot be made regarding this important finding, perhaps, this points to early evidence of a potential institutional or operator learning curve with this device. However, in view of the inferior quality of the data accrued from the MAUDE Registry, more high-precision studies are needed to better understand these changes, as the utility of MitraClip, becomes more established in clinical practice.

Type 1 diabetes mellitus abrogates compensatory augmentation of myocardial neuregulin-1ß/ErbB in response to myocardial infarction resulting in worsening heart failure.

BACKGROUND: Diabetes mellitus (DM) patients surviving myocardial infarction (MI) exhibit a substantially higher incidence of subsequent heart failure (HF). Neuregulin (NRG)-1 and erythroblastic leukemia viral oncogene homolog (ErbB) receptors have been shown to play a critical role in maintenance of cardiac function. However, whether myocardial NRG-1/ErbB is altered during post-MI HF associated with DM remains unknown. The aim of this study was to determine the impact of type 1 DM on the myocardial NRG-1/ErbB system following MI in relation to residual left ventricular (LV) function. METHODS: Type 1 DM was induced in rats via administration of streptozotocin (65 mg/kg, i.p.). Control rats were injected with citrate buffer (vehicle) only. Two weeks after induction of type 1 DM, MI was produced in DM and non-DM rats by ligation of the left coronary artery. Sham MI rats underwent the same surgical procedure with the exception that the left coronary artery was not ligated. At 4 weeks after surgery, residual in vivo LV function was assessed via echocardiography. Myocardial protein expression of NRG-1ß, ErbB2 and ErbB4 receptors, and MDM2 (a downstream signaling pathway induced by NRG-1 that has been implicated in cell survival) was assessed in the remaining, viable LV myocardium by Western blotting. Changes in ErbB receptor localization in the surviving LV myocardium of diabetic and non-diabetic post-MI rats was determined using immunohistochemistry techniques. RESULTS: At 4 weeks post-MI, echocardiography revealed that LV fractional shortening (FS) and LV ejection fraction (EF) were significantly lower in the DM + MI group compared to the MI group (LVFS: 17.9 ± 0.7 vs. 25.2 ± 2.2; LVEF: 35.5 ± 1.4 vs. 47.5 ± 3.5, respectively; P < 0.05), indicating an increased functional severity of HF among the DM + MI rats. Up-regulation of NRG-1ß and ErbB2 protein expression in the MI group was abrogated in the DM + MI group concurrent with degradation of MDM2, a downstream negative regulator of p53. ErbB2 and ErbB4 receptors re-localized to cardiac myocyte nuclei in failing type 1 diabetic post-MI hearts. CONCLUSIONS: Type 1 DM prevents compensatory up-regulation of myocardial NRG-1/ErbB after MI coincident with an increased severity of HF.

Intravenous glial growth factor 2 (GGF2) isoform of neuregulin-1ß improves left ventricular function, gene and protein expression in rats after myocardial infarction.

AIMS: Recombinant Neuregulin (NRG)-1ß has multiple beneficial effects on cardiac myocytes in culture, and has potential as a clinical therapy for heart failure (HF). A number of factors may influence the effect of NRG-1ß on cardiac function via ErbB receptor coupling and expression. We examined the effect of the NRG-1ß isoform, glial growth factor 2 (GGF2), in rats with myocardial infarction (MI) and determined the impact of high-fat diet as well as chronicity of disease on GGF2 induced improvement in left ventricular systolic function. Potential mechanisms for GGF2 effects on the remote myocardium were explored using microarray and proteomic analysis. METHODS AND RESULTS: Rats with MI were randomized to receive vehicle, 0.625 mg/kg, or 3.25 mg/kg GGF2 in the presence and absence of high-fat feeding beginning at day 7 post-MI and continuing for 4 weeks. Residual left ventricular (LV) function was improved in both of the GGF2 treatment groups compared with the vehicle treated MI group at 4 weeks of treatment as assessed by echocardiography. High-fat diet did not prevent the effects of high dose GGF2. In experiments where treatment was delayed until 8 weeks after MI, high but not low dose GGF2 treatment was associated with improved systolic function. mRNA and protein expression analysis of remote left ventricular tissue revealed a number of changes in myocardial gene and protein expression altered by MI that were normalized by GGF2 treatment, many of which are involved in energy production. CONCLUSIONS: This study demonstrates that in rats with MI induced systolic dysfunction, GGF2 treatment improves cardiac function. There are differences in sensitivity of the myocardium to GGF2 effects when administered early vs. late post-MI that may be important to consider in the development of GGF2 in humans.

Neuregulin in cardiovascular development and disease.

Studies in genetically modified mice have demonstrated that neuregulin-1 (NRG-1), along with the erythroblastic leukemia viral oncogene homolog (ErbB) 2, 3, and 4 receptor tyrosine kinases, is necessary for multiple aspects of cardiovascular development. These observations stimulated in vitro and in vivo animal studies, implicating NRG-1/ErbB signaling in the regulation of cardiac cell biology throughout life. Cardiovascular effects of ErbB2-targeted cancer therapies provide evidence in humans that ErbB signaling plays a role in the maintenance of cardiac function. These and other studies suggest a conceptual model in which a key function of NRG-1/ErbB signaling is to mediate adaptations of the heart to physiological and pathological stimuli through activation of intracellular kinase cascades that regulate tissue plasticity. Recent work implicates NRG-1/ErbB signaling in the regulation of multiple aspects of cardiovascular biology, including angiogenesis, blood pressure, and skeletal muscle responses to exercise. The therapeutic potential of recombinant NRG-1 as a potential treatment for heart failure has been demonstrated in animal models and is now being explored in clinical studies. NRG-1 is found in human serum and plasma, and it correlates with some clinical parameters, suggesting that it may have value as an indicator of prognosis. In this review, we bring together this growing literature on NRG-1 and its significance in cardiovascular development and disease.

Biventricular noncompaction cardiomyopathy in a patient presenting with new onset seizure: case report.

Ventricular noncompaction (VNC) of the myocardium is a rare genetic cardiomyopathy caused by a disorder during endocardial morphogenesis and could be accompanied by life-threatening complications. The major clinical manifestations of VNC are heart failure, arrhythmias, and embolic events. The left ventricle is the most commonly reported affected site, but a few cases of right ventricular involvement have also been reported. We report a case of biventricular noncompaction cardiomyopathy in a 31-year-old woman presenting with a new onset seizure. On the second day of her telemetry-monitored hospitalization, she suffered a witnessed ventricular fibrillation arrest requiring emergency direct-current cardioversion and induced hypothermia. Transthoracic echocardiography (TTE) showed isolated left ventricular (LV) noncompaction and depressed LV systolic function. Subsequent cardiac magnetic resonance imaging (MRI) revealed both left and right ventricular noncompaction. This unusual presentation highlights the importance of a complete and thorough evaluation of patients even when presenting with apparently noncardiac symptom(s).

Pneumococcal tricuspid valve endocarditis in a young african american: a case for inclusion of african americans in pneumococcal vaccine criteria.

Following the development of penicillin, complications from streptococcus pneumonia such as endocarditis have become rare. However, certain independent risk factors such as cigarette smoking and being of African-American (AA) decent have been associated with a higher incidence of invasive pneumococcal disease, but only cigarette smoking has been targeted by current recommendations from the Advisory Committee on Immunological Practices (ACIPs). We report a case of a young AA smoker, who developed an isolated tricuspid valve pneumococcal endocarditis. This case will illustrate the high susceptibility for invasive pneumococcus sequelae in AA, thereby raising the argument for the consideration of AA in the Pneumococcal Conjugate Vaccine (PCV) criteria, regardless of smoking history.