Analysis of racial disparities in acute type A aortic dissection repair at a rural tertiary academic medical center.

BACKGROUND: To determine if racial disparities exist between African Americans (AA) and Non-Hispanic Whites (NHW) for patients undergoing repair of acute type A aortic dissection (ATAAD) at a rural tertiary academic medical center. METHODS: There were 215 consecutive AA and NHW patients who underwent ATAAD repair at our institution from 1999 to 2019 included in a retrospective analysis of our Society of Thoracic Surgeons Adult Cardiac Surgery Database. Statistical analysis was performed with a p value of less than .05 considered statistically significant. RESULTS: Patients undergoing ATAAD repair were 47% AA despite comprising only 27% of the total population in our region. AAs were significantly younger (54.0 vs. 61.2 years), were more likely to be hypertensive (94.1% vs. 79.7%), had higher creatinine levels (1.7 vs. 1.1 mg/dL), and higher body mass index (30.8 vs. 28.1 kg/m2 ) (all p values < .006). There were no significant differences in type of repair or intraoperative variables. A logistic regression analysis showed AAs had an increased rate of postoperative acute renal failure not requiring hemodialysis when compared to NHWs (20.8% vs. 10.6%, p value = .042). Thirty-day mortality was not significantly different (15.7% vs. 13.4%) nor was 1-year survival (78% vs. 79%) in AAs and NHWs, respectively. CONCLUSIONS: Despite AAs having more medical comorbidities at presentation, there were no differences in short- and intermediate-term survival. In our catchment of 1.8 million people, AAs appear to undergo ATAAD repair at a disproportionate rate versus NHWs. These findings may alter strategies for surveillance and prevention of aortic disease in this high-risk population.

Natural history of the proximal aorta in patients with descending thoracic aortic disease.

OBJECTIVE: This study investigated the growth and behavior of the ascending aorta in patients with descending thoracic aortic disease. METHODS: We examined 200 patients with descending thoracic aortic disease including acute type B dissection (n = 95), chronic type B dissection (n = 38), intramural hematoma (n = 23), and thoracoabdominal aortic aneurysms (n = 44). Images from computed tomography and magnetic resonance imaging were evaluated after three-dimensional reconstruction to examine the growth rate in those with >1 year of imaging follow-up (n = 108). Survival data were derived from all 200 patients in this study. RESULTS: Average proximal aortic dimensions at the index image were relatively small, measuring 3.65 ± 0.51 cm in the root, 3.67 ± 0.48 cm in the ascending aorta, and 3.50 ± 0.44 cm in the proximal arch. Average growth rate was low for the aortic root, ascending aorta, and proximal arch at 0.36 ± 0.64 mm/y, 0.26 ± 0.44 mm/y, and 0.25 ± 0.44 mm/y, respectively. There was no difference in baseline proximal aortic dimensions and growth rate between the four subgroups. An index aortic diameter ≥4.1 cm grew faster than those <4.1 cm at the ascending aorta (P = .028) and proximal arch (P = .019). There was no difference in aortic growth rates at the aortic root (P = .887). After the index scan, five patients underwent six ascending aortic replacement procedures, leading to a 3% ascending aortic intervention rate. Overall median life expectancy was 86.15 years. CONCLUSIONS: Native ascending aortic growth in patients with descending thoracic aortic disease is slow. We suggest regular follow-up for index ascending aorta ≥4.1 cm because of its larger initial size and more rapid growth.

Inhibition of Postinfarction Ventricular Remodeling by High Molecular Weight Polyethylene Glycol.

BACKGROUND: Myocardial infarction (MI) is a major etiology for the development of heart failure. We have previously shown that high molecular weight polyethylene glycol (PEG) can protect cardiac myocytes from hypoxia-reoxygenation injury in vitro. In this study, we investigated the potential protective effects of 15-20 kD PEG postinfarction without reperfusion. METHODS: One milliliter of PEG 15-20 was delivered intravenously following permanent left anterior descending ligation in adult male rats with phosphate buffer saline (PBS) as control (n = 9 in each group). Echocardiography was performed at baseline and at 8 wk post-MI. Left ventricles (LVs) were harvested to quantify fibrosis, apoptosis, cell survival signaling, regulation of ß-adrenergic signaling, and caveolin (Cav) expression. RESULTS: The PEG group had significant recovery of LV function at 8 wk compared with the PBS group. There was less LV fibrosis in both the infarct and remote territory. Cell survival signaling was upregulated in the PEG group with increased Akt and ERK phosphorylation. PEG inhibited apoptosis as measured by terminal deoxynucleotidyl transferase [TdT]-mediated dUTP nick-end labeling positive nuclei and caspase-3 activity. There was maintenance of Cav-1, Cav-2, and Cav-3 expression following PEG treatment versus a decline in the PBS group. Negative regulators of ß-adrenergic signaling, G protein-coupled receptor kinase-2, and ß-arrestin 1 and 2 were all upregulated in PBS-treated samples compared to normal control; however, PEG treatment led to decreased expression. CONCLUSIONS: These data suggest that PEG 15-20 may have significant protective effects post-MI even in the setting of no acute reperfusion. Upregulation of Cav expression appears to be a key mechanism for the beneficial effects of PEG on ventricular remodeling and function.

Acute retrograde type A aortic dissection: morphologic analysis and clinical implications.

BACKGROUND: This study compares the morphology and outcomes of acute retrograde type A dissections (RTADs) with acute antegrade type A dissections (ATADs), and acute type B dissections. MATERIALS AND METHODS: From 2000 to 2016, there were 12 acute RTADs, 96 ATADs, and 92 type B dissections with available imaging. Dissections were characterized using computerized tomography angiography images. We examined clinical features, tear characteristics, and various morphologic measurements. RESULTS: Compared with acute type B dissections, RTAD primary tears were more common in the distal arch (75% versus 43%, P = 0.04), and the false-to-true lumen contrast intensity ratio at the mid-descending thoracic aorta was lower (0.46 versus 0.71, P = 0.020). RTAD had less false lumen decompression because there were fewer aortic branch vessels distal to the subclavian that were perfused through the false lumen (0.40 versus 2.19, P < 0.001). Compared with ATAD, RTAD had less root involvement where root true-to-total lumen area ratio was higher (0.88 versus 0.76, P = 0.081). Furthermore, RTAD had a lower false-to-true lumen contrast intensity ratio at the root (0.25 versus 0.57, P < 0.05), ascending aorta (0.25 versus 0.72, P < 0.001), and proximal arch (0.39 versus 0.67, P < 0.05). RTAD were more likely to undergo aortic valve resuspension (100% versus 74%, P = 0.044). CONCLUSIONS: RTAD tends to occur when primary tears occur in close proximity to the aortic arch and when false lumen decompression through the distal aortic branches are less effective. Compared with ATAD, RTAD has less root involvement, and successful aortic valve resuspension is more likely.

Outpatient air leak management after lobectomy: a CMS cost analysis.

BACKGROUND: Air leaks after lobectomy are associated with increased length of stay (LOS) and protracted resource utilization. Portable drainage systems (PDS) allow for outpatient management of air leaks in patients otherwise meeting discharge criteria. We evaluated the safety and cost efficiency of a protocol for outpatient management of air leaks with a PDS. METHODS: We retrospectively assessed patients who underwent lobectomy for non-small-cell lung cancer at our institution between 2004 and 2014. All patients discharged with a PDS for air leak were included in the analysis. The study group was compared to an internally matched cohort of patients undergoing lobectomy for non-small-cell lung cancer managed without the need for outpatient PDS. Study end points included resource utilization, postoperative complications, and readmission. RESULTS: A total of 739 lobectomies were performed during the study period, 73 (10%) patients with air leaks were discharged with a PDS after fulfilling postoperative milestones. Shorter LOS was observed in the study group (3.88 ± 2.4 versus 5.68 ± 5.7 d, P = 0.014) without significant differences in 30-d readmission (11.7% versus 9.0%, P = 0.615). PDS-related complications occurred in 6.8% of study patients (5/73), and 2.7% (2/73) required overnight readmission. PDSs were used for 8.30 ± 4.5 outpatient days. A CMS-based cost analysis predicted an overall savings of $686.72/patient (4.9% of Medicare reimbursement for a major thoracic procedure), associated with significantly fewer hospital days and resources used. CONCLUSIONS: In patients otherwise meeting discharge criteria, outpatient management of air leaks is safe and effective. This strategy is associated with improved efficiency of postoperative care and a modest reduction in hospital costs. This model may be applicable to other thoracic procedures associated with protracted LOS.

ß-Arrestins regulate human cardiac fibroblast transformation and collagen synthesis in adverse ventricular remodeling.

Cardiac fibroblasts (CFs) produce and degrade the myocardial extracellular matrix and are critical in maladaptive ventricular remodeling that can result in heart failure (HF). ß-Arrestins are important signaling molecules involved in ß-adrenergic receptor (ß-AR) desensitization and can also mediate signaling in a G protein-independent fashion. We hypothesize that ß-arrestins play an important role in the regulation of adult human CF biology with regard to myofibroblast transformation, increased collagen synthesis, and myocardial fibrosis which are important in the development of HF. ß-Arrestin1 & 2 expression is significantly upregulated in adult human CF isolated from failing left ventricles and ß-AR signaling is uncoupled with loss of ß-agonist-mediated inhibition of collagen synthesis versus normal control CF. Knockdown of either ß-arrestin1 or 2 restored ß-AR signaling and ß-agonist mediated inhibition of collagen synthesis. Overexpression of ß-arrestins in normal CF led to a failing phenotype with increased baseline collagen synthesis, impaired ß-AR signaling, and loss of ß-agonist-mediated inhibition of collagen synthesis. ß-Arrestin knockdown in failing CF diminished TGF-ß stimulated collagen synthesis and also inhibited ERK phosphorylation. Overexpression of ß-arrestins in normal CF increased basal ERK1/2 and Smad2/3 phosphorylation and enhanced TGF-ß-stimulated collagen synthesis. This was prevented by pre-treatment with a MEK1/2 inhibitor. Enhanced ß-arrestin signaling appears to be deleterious in CF by promoting a pro-fibrotic phenotype via uncoupling of ß-AR signaling as well as potentiating ERK and Smad signaling. Targeted inhibition of ß-arrestins in CF may represent a therapeutic strategy to prevent maladaptive myocardial fibrosis.

Acute kidney injury and mortality following ventricular assist device implantation.

BACKGROUND: Ventricular assist devices (VADs) are increasingly common, and their surgical implantation predisposes patients to an increased risk of acute kidney injury (AKI). We sought to evaluate the incidence, risk factors and short- and long-term all-cause mortality of patients with AKI following VAD implantation. METHODS: We identified all patients who underwent VAD implantation at the University of Chicago between January 1, 2008, and January 31, 2012. We evaluated the incidence of AKI, defined as a ≥50% increase in serum creatinine over the first 7 postoperative days (RIFLE Risk-Creatinine). A logistic regression model was used to identify risk factors for the development of AKI, and a Cox proportional hazards model was used to examine factors associated with 30-day and 365-day all-cause mortality. RESULTS: A total of 157 eligible patients had VAD implantations with 44 (28%) developing postimplantation AKI. In a multivariate analysis, only diabetes mellitus [odds ratio = 2.25 (1.03-4.94), p = 0.04] was identified as a significant predictor of postoperative AKI. Using a multivariable model censored for heart transplantation, only AKI [hazard ratio, HR = 3.01 (1.15-7.92), p = 0.03] and cardiopulmonary bypass time [HR = 1.01 (1.001-1.02), p = 0.02] were independent predictors of 30-day mortality. Preoperative body mass index [HR = 0.95 (0.90-0.99), p = 0.03], preoperative diabetes mellitus [HR = 1.89 (1.07-3.35), p = 0.03] and postimplantation AKI [HR = 1.85 (1.06-3.21), p = 0.03] independently predicted 365-day mortality. CONCLUSION: AKI is common following VAD implantation and is an independent predictor of 30-day and 1-year all-cause mortality.

GRK2-mediated inhibition of adrenergic and dopaminergic signaling in right ventricular hypertrophy: therapeutic implications in pulmonary hypertension.

BACKGROUND: The cause and consequences of impaired adrenergic signaling in right ventricular failure/hypertrophy (RVH) are poorly understood. We hypothesized that G protein-coupled receptor kinase-2 (GRK2)-mediated uncoupling of ß-adrenergic receptor signaling impairs inotropic reserve. The implications of right ventricular (RV) adrenergic remodeling for inotrope selection and the therapeutic benefit of interrupting Gßγ-GRK2 interaction, using gallein, were tested. METHODS AND RESULTS: Chamber-specificity and cellular localization of adrenergic remodeling were compared in rodent RVH associated with pulmonary arterial hypertension (PAH-RVH; SU5416+chronic-hypoxia or Monocrotaline) versus pulmonary artery banding-induced RVH (PAB-RVH). Results were corroborated in RV arrays from 10 PAH patients versus controls. Inotropic reserve was assessed in RV- and left ventricular-Langendorff models and in vivo. Gallein therapy (1.8 mg/kg/day ×2-weeks) was assessed. Despite similar RVH, cardiac output (58.3±4.9 versus 82.9±4.8 mL/min; P<0.001) and treadmill distance (41.5±11.6 versus 244.1±12.4 m; P<0.001) were lower in PAH-RVH versus PAB-RVH. In PAH-RVH versus PAB-RVH there was greater downregulation of ß1-, α1- and dopamine-1 receptors, more left ventricular involvement, and greater impairment of RV contractile reserve. RV GRK2 activity increased in parallel with a reduction in both adrenergic receptor expression and inotrope-stimulated cAMP levels (P<0.01). ß1-receptor downregulation also occurred in human PAH-RVH. Dobutamine was superior to dopamine as an RV inotrope, both ex vivo and in vivo. CONCLUSIONS: GRK2-mediated desensitization-downregulation of adrenergic and dopaminergic receptors impairs inotropic reserve in PAH-RVH. Acute inotropic support in RVH is best accomplished by dobutamine, reflecting its better coupling to adenylyl cyclase and the reliance of dopamine on dopamine-1-receptor signaling, which is impaired in RVH. Inhibiting Gßγ-GRK2 interactions has therapeutic benefit in RVH.

Impact of timing of urgent coronary artery bypass grafting following coronary angiography on acute kidney injury.

OBJECTIVES: Prior studies have examined the association between timing of cardiac surgery after coronary angiography with risk of acute kidney injury, but this remains controversial. The purpose of this study was to investigate the association between interval from coronary angiography to urgent coronary artery bypass grafting with acute kidney injury, and to examine this possible effect in patients with preexisting kidney disease. METHODS: Patients from a single institution undergoing urgent, isolated coronary artery bypass grafting within 7 days of coronary angiography were included. Patients were subdivided by chronic kidney disease stage and angiography-to-surgery interval. Locally estimated scatterplot smoothing was used to evaluate the functional relationship of the probability of acute kidney injury and time interval. Adjusted odds ratios were calculated for each time interval group compared against the Day 0 to 1 interval group, controlling for multiple covariates. Analyses were repeated for each chronic kidney disease subgroup. RESULTS: A total of 2249 patients were included in this study. There were 271 (12.0%) patients with postoperative acute kidney injury. Plots demonstrated a decreasing risk of kidney injury from Day 0 to 1 to Day 3 following coronary angiography. Adjusted odds ratios also showed a significant decrease in risk of kidney injury on Day 3 compared with Day 0 to 1. Analyses repeated for each chronic kidney disease stage showed similar trends. CONCLUSIONS: For patients undergoing urgent coronary artery bypass grafting, there is a decreased risk of kidney injury in those having surgery on day 3 after coronary angiography compared with those having surgery on Day 0 to 1, regardless of preexisting kidney disease.