Impact of Advanced Therapy Centers on Characteristics and Outcomes of Heart Failure Admissions.

BACKGROUND: Although much attention has been paid to admission and transfer patterns for cardiogenic shock, contemporary data are lacking on decompensated heart failure (HF) admissions and transfers and the impact of advanced therapy centers (ATCs) on outcomes. METHODS: HF hospitalizations were obtained from the Nationwide Readmissions Database 2016 to 2019. Centers performing at least 1 heart transplant or left ventricular assist device were classified as ATCs. Patient characteristics, outcomes, and procedural volume were compared among 3 cohorts: admissions to non-ATCs, admissions to ATCs, and transfers to ATCs. A secondary analysis evaluated outcomes for severe HF hospitalizations (cardiogenic shock, cardiac arrest, and mechanical ventilation). Multivariable logistic regression was performed to adjust for the presence of HF decompensations and significant clinical variables during univariate analysis. RESULTS: A total of 2 331 690 hospitalizations (81.2%) were admissions to non-ATCs (94.5% of centers), 525 037 (18.3%) were admissions to ATCs (5.5% of centers), and 15 541 (0.5%) were transferred to ATCs. Patients treated at ATCs (especially those transferred) had higher rates of HF decompensations, procedural frequency, lengths of stay, and costs. Unadjusted mortality was 2.6% at non-ATCs and was higher at ATCs, both for directly admitted (2.9%, P<0.001) and transferred (11.2%, P<0.001) patients. However, multivariable-adjusted mortality was significantly lower at ATCs, both for directly admitted (odds ratio, 0.82 [95% CI, 0.78-0.87]; P<0.001) and transferred (odds ratio, 0.66 [95% CI, 0.57-0.78]; P<0.001) patients. For severe HF admissions, unadjusted mortality was 37.2% at non-ATCs and was lower at ATCs, both for directly admitted (25.3%, P<0.001) and transferred (25.2%, P<0.001) patients, with similarly lower multivariable-adjusted mortality. CONCLUSIONS: Patients with HF treated at ATCs were sicker but associated with higher procedural volume and lower adjusted mortality.

Impella Versus Intra-Aortic Balloon Pump in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: An Observational Study.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used for patients with cardiogenic shock. Although Impella or intra-aortic balloon pump (IABP) is frequently used for left ventricular unloading (LVU) during VA-ECMO treatment, there are limited data on comparative outcomes. We compared outcomes of Impella and IABP for LVU during VA-ECMO. METHODS AND RESULTS: Using the Nationwide Readmissions Database between 2016 and 2020, we analyzed outcomes in 3 groups of patients with cardiogenic shock requiring VA-ECMO based on LVU strategies: extracorporeal membrane oxygenation (ECMO) only, ECMO with IABP, and ECMO with Impella. Of 15 980 patients on VA-ECMO, IABP and Impella were used in 19.4% and 16.4%, respectively. The proportion of patients receiving Impella significantly increased from 2016 to 2020 (6.5% versus 25.8%; P-trend<0.001). In-hospital mortality was higher with ECMO with Impella (54.8%) compared with ECMO only (50.4%) and ECMO with IABP (48.4%). After adjustment, ECMO with IABP versus ECMO only was associated with lower in-hospital mortality (adjusted odds ratio [aOR], 0.83; P=0.02). ECMO with Impella versus ECMO only had similar in-hospital mortality (aOR, 1.09; P=0.695) but was associated with more bleeding (aOR, 1.21; P=0.007) and more acute kidney injury requiring hemodialysis (aOR, 1.42; P<0.001). ECMO with Impella versus ECMO with IABP was associated with greater risk of acute kidney injury requiring hemodialysis (aOR, 1.49; P=0.002), higher in-hospital mortality (aOR, 1.32; P=0.001), and higher 40-day mortality (hazard ratio, 1.25; P<0.001). CONCLUSIONS: In patients with cardiogenic shock on VA-ECMO, LVU with Impella, particularly with 2.5/CP, was not associated with improved survival at 40 days but was associated with increased adverse events compared with IABP. More data are needed to assess Impella platform-specific comparative outcomes of LVU.

Trends in the Incidence of Cardiogenic Shock, and Utilization of Mechanical Circulatory Support in Myocarditis: Insights from the National Inpatient Sample 2016 to 2019.

A subset of patients with myocarditis present with cardiogenic shock. There is a lack of contemporary data assessing the use of mechanical circulatory support (MCS) in these patients. Myocarditis hospitalizations were analyzed using the National Inpatient Sample between 2016 and 2019. Characteristics of patients with and without cardiogenic shock were assessed. Trends in mortality, MCS, right-sided cardiac catheterization (RHC) and endomyocardial biopsy were evaluated. The impact of RHC on consequent MCS and mortality was studied. A total of 38,300 hospitalizations for myocarditis were included in the study, of which 3,490 hospitalizations (9.1%) had cardiogenic shock. Patients with cardiogenic shock were older (p <0.001) and had more chronic kidney disease and atrial fibrillation. Between 2016 and 2019, there was an increase in myocarditis admissions but no difference in rates of cardiogenic shock and mortality and the use of extracorporeal membrane oxygenation, percutaneous ventricular assist devices, intra-aortic balloon pumps, left ventricular assist devices, and cardiac transplant. The most common form of MCS used in myocarditis was extracorporeal membrane oxygenation. The rates of RHC (p = 0.02) and endomyocardial biopsy (p = 0.03) increased over time. Patients who underwent RHC were more likely to receive mechanical support, and in patients with shock, RHC was associated with lower mortality (adjusted odds ratio 0.34, p <0.01). Myocarditis admissions increased over time but with no increase in the rates of cardiogenic shock and MCS. In patients with cardiogenic shock, RHC resulted in lower mortality.

Sex-Based Disparities in Outcomes With Abdominal Aortic Aneurysms.

Although abdominal aortic aneurysms (AAA) are more common in men, women with AAA have increased morbidity and mortality. Additionally, there are discrepancies among professional society guidelines for AAA screening in women. In this retrospective study from the Nationwide Inpatient Sample (NIS) database from 2003 to 2014, we compared rates of AAA repair (rupture and elective) and AAA-related mortality in men vs. women to identify predictors of death among men and women with AAA. We divided the population into 1) AAA rupture 2) elective AAA repair. The main outcomes included temporal trends in AAA rupture, rupture-related death, AAA repair, in-hospital death, and predictors of AAA-related death. There were 570,253 discharge records for AAA admissions between 2003 and 2014, including 22.8% women and 77.2% men. Women had a higher proportion of rupture (18.4% vs 12.6%, p <0.01). A smaller proportion of women underwent endovascular aortic repair (EVAR) compared with men in the ruptured AAA (13.9% vs. 20.3%, p <0.01) and elective repair (55.7% vs. 67.4%, p <0.01) cohorts. Within the ruptured cohort, a higher proportion of women did not receive repair (46.4% vs. 26.1%, p <0.01). On multivariable analysis, female gender was a significant predictor of death with rupture (OR 1.39, 95% CI 1.16 to 1.66) and elective repair (OR 1.74, 95% CI 1.36 to 2.22), with both elective EVAR (OR 2.52, 95% CI 2.06 to 3.09) and elective open aortic repair (OAR; OR 1.50, 95% CI 1.33 to 1.68). Propensity score matching confirmed a higher risk of death in women in both the rupture (OR 1.19, 95% CI 1.09 to 1.30) and elective repair (OR 1.50, 95% CI 1.35 to 1.67) cohorts. In conclusion, AAA poses significant morbidity and mortality, especially in women. Women were more likely to die before repair with AAA rupture and female gender was an independent predictor of mortality in both the rupture and elective repair groups.

Impact of hospital transfer to hubs on outcomes of cardiogenic shock in the real world.

AIMS: Cardiogenic shock (CS) is associated with significant mortality, and there is a movement towards regional 'hub-and-spoke' triage systems to coordinate care and resources. Limited data exist on outcomes of patients treated at CS transfer hubs. METHODS AND RESULTS: Cardiogenic shock hospitalizations were obtained from the Nationwide Readmissions Database 2010-2014. Centres receiving any interhospital transfers with CS in a given year were classified as CS transfer 'hubs'; those without transfers were classified as 'spokes.' In-hospital mortality was compared among three cohorts: (A) direct admissions to spokes, (B) direct admissions to hubs, and (C) interhospital transfer to hubs. Among hospitals treating CS, 70.6% were classified as spokes and 29.4% as hubs. A total of 130 656 (31.7%) hospitalizations with CS were direct admission to spokes, 253 234 (61.4%) were direct admissions to hubs, and 28 777 (7.0%) were transfer to hubs. CS mortality was 47.8% at spoke hospitals and was lower at hub hospitals, both for directly admitted (39.3%, P < 0.01) and transferred (33.4%, P < 0.01) patients. Hospitalizations at hubs had higher procedural frequency (including coronary artery bypass graft, right heart catheterization, mechanical circulatory support), greater length of stay, and greater costs. On multivariable analysis, direct admission to CS hubs [odds ratio (OR) 0.86, 95% confidence interval (CI) 0.84-0.89, P < 0.01] and transfer to hubs (OR 0.72, 95% CI 0.69-0.76, P < 0.01) were both associated with lower mortality. CONCLUSION: While acknowledging the limited ability of the Nationwide Readmissions Database to classify CS severity on presentation, treatment of CS at transfer hubs was associated with significantly lower mortality within this large real-world sample.

Sex-Based Differences in Revascularization and 30-Day Readmission After ST-Segment-Elevation Myocardial Infarction in the United States.

BACKGROUND: Cardiovascular disease is the leading cause of death for women in the United States. Revascularization is considered the standard of care for treatment of ST-segment elevation myocardial infarction (STEMI) and is known to reduce readmission. However there is a paucity of data that examines the sex-dependent impact of revascularization on readmission. We aimed to investigate sex differences in revascularization rates, 30-day readmission rates, and primary cause of readmissions following STEMIs. METHODS: STEMI hospitalizations were selected in the Nationwide Readmissions Database from 2010 to 2014. Revascularization rates, 30-day readmission rates, and primary cause of readmission were examined. Interaction between sex and revascularization was assessed. Multivariable regression analysis was performed to identify predictors of 30-day readmission and revascularization for both sexes. RESULTS: 219,944 women and 489,605 men were admitted with STEMIs. Women were more likely to be older, and have more comorbidities. Women were less likely to undergo revascularization by percutaneous coronary intervention (adjusted odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.66-0.70) or coronary artery bypass graft surgery (adjusted OR 0.40; CI 0.39-0.44). Women had higher 30-day readmission rates (15.7% vs. 10.8%, p < 0.001; OR 1.20, CI 1.17-1.23), and revascularization in women was not associated with a decreased likelihood of 30-day readmission. The primary cardiac cause of readmission in women was heart failure. CONCLUSION: Compared to men, women with STEMIs had lower rates of revascularization and higher rates of 30-day readmission. When revascularized, women were still more likely to be readmitted as compared to non-revascularized women.

Outcomes of Hospitalizations for Cardiogenic Shock at Left Ventricular Assist Device Versus Non-Left Ventricular Assist Device Centers.

Background Cardiogenic shock (CS) is a complex syndrome associated with high morbidity and mortality. In recent years, many US hospitals have formed multidisciplinary shock teams capable of rapid diagnosis and triage. Because of preexisting collaborative systems of care, hospitals with left ventricular assist device (LVAD) programs may also represent "centers of excellence" for CS care. However, the outcomes of patients with CS at LVAD centers have not been previously evaluated. Methods and Results Patients with CS were identified in the 2012 to 2014 National Inpatient Sample. Clinical characteristics, revascularization rates, and use of mechanical circulatory support were analyzed in LVAD versus non-LVAD centers. The association between hospital type and in-hospital mortality was examined using multivariable logistic regression models. Of 272 075 hospitalizations, 26.0% were in LVAD centers. CS attributable to causes other than acute myocardial infarction represented most cases. In-hospital mortality was lower in LVAD centers (38.9% versus 43.3%; P<0.001). In multivariable analysis, the odds of mortality remained significantly lower for hospitalizations in LVAD centers (odds ratio, 0.89; P<0.001). In patients with CS secondary to acute myocardial infarction, revascularization rates were similar between LVAD and non-LVAD centers. The use of intra-aortic balloon pump (18.7% versus 18.8%) and Impella/TandemHeart (2.6% versus 1.9%) was similar between hospital types, whereas extracorporeal membrane oxygenation was used more frequently in LVAD centers (4.3% versus 0.2%; P<0.001). Conclusions Risk-adjusted mortality was lower in patients with CS who were hospitalized at LVAD centers. These centers likely represent specialized, shock team capable institutions across the country that may be best suited to manage patients with CS.

Impact Of Cirrhosis On 90-Day Outcomes After Percutaneous Coronary Intervention (from A Nationwide Database).

Patients with cirrhosis often have concomitant coronary artery disease and require percutaneous coronary intervention (PCI). PCI in cirrhotics can be associated with significant risks due to thrombocytopenia, possible coagulopathies, bleeding, and renal failure. Longer term risks of PCI in cirrhotics have not been well studied. Our study seeks to evaluate the 90-day outcomes of PCI in patients with cirrhosis. Patients receiving PCI were identified from the Nationwide Readmissions Database from 2010 to 2014 and stratified by the presence of co-morbid cirrhosis. The total mortality during index admission and 90-day readmissions as well as the readmissions rate were examined. Adverse events including bleeding, stroke, kidney injury, and vascular complications were also compared. Patients with cirrhosis had a significantly higher number of co-morbidities. The cirrhosis group had a higher overall 90-day mortality (10.3% vs 2.5%, p < 0.01), including during the index hospitalization (7.0% vs 1.8%, p < 0.01), as well as a higher 90-day readmission rate (38.2% vs 20.2%, p < 0.01). Patients with cirrhosis also had higher frequencies of overall 90-day adverse events (44.7% vs 17.7%, p < 0.01), including gastrointestinal bleeding (15.3% vs 2.7%, p < 0.01) and acute kidney injury (28.4% vs 10.1%, p < 0.01). In conclusion, patients with cirrhosis face a significantly higher risk of adverse outcomes including mortality, readmissions, and adverse events in the 90 days after hospitalization for PCI compared with the general population.

One-Year Outcomes of Percutaneous Coronary Intervention in Patients with End-Stage Liver Disease.

BACKGROUND: Patients with cirrhosis and coronary artery disease (CAD) are at high risk for morbidity during surgical revascularization so they are often referred for complex percutaneous coronary intervention (PCI). Percutaneous coronary intervention in the cirrhotic population also has inherent risks; however, quantifiable data on long-term outcomes are lacking. METHODS: Patients with angiographically significant CAD and cirrhosis were identified from the catheterization lab databases of the University of Pennsylvania Health System between 2007 and 2015. Outcomes were obtained from the medical record and telephonic contact with patients/families. RESULTS: Percutaneous coronary intervention was successfully performed in 42 patients (51 PCIs). Twenty-nine patients with significant CAD were managed medically (36 angiograms). The primary outcome (a composite of mortality, subsequent revascularization, and myocardial infarction) was not significantly different between the 2 groups during a follow-up period at 1 year (PCI: 50%, Control: 40%, P = .383). In the PCI group, a composite adverse outcome rate that included acute kidney injury (AKI), severe bleed, and peri-procedural stroke was elevated (40%), with severe bleeding occurring after 23% of PCI events and post-procedural AKI occurring after 26% of events. The medical management group had significantly fewer total matched adverse outcomes (17% vs 40% in the PCI group, P = .03), with severe bleeding occurring after 11% of events and AKI occurring after 6% of events. Increased risk of adverse events following PCI was associated with severity of liver disease by Child-Pugh class. CONCLUSIONS: Percutaneous coronary intervention in patients with cirrhosis is associated with an elevated risk of adverse events, including severe bleeding and AKI.

Complete Versus Culprit-Only Revascularization in STEMI: a Contemporary Review.

PURPOSE OF REVIEW: In ST-segment elevation myocardial infarction, urgent revascularization of the culprit coronary vessel and restoration of coronary flow is the goal of the initial management. However, obstructive non-culprit disease is frequently concomitantly found during initial angiography and portends a poor prognosis. Management of non-culprit lesions in ST-segment elevation myocardial infarction (STEMI) has been the subject of extensive debate. This review will examine the currently available evidence, with a specific focus on randomized clinical trials performed to date. RECENT FINDINGS: Although early observational data suggested better outcomes with culprit-only revascularization, more recent data from several randomized trials have suggested improved outcomes with complete multivessel revascularization, either during the index PCI procedure or as a staged procedure. Data from recent randomized controlled trials have suggested the superiority of complete or multivessel revascularization and have subsequently led to changes to the most recent iterations of STEMI guidelines. However, the optimal management and timing of revascularization of non-culprit lesions in STEMI remain controversial.

Ventricular Septal Defect from Takotsubo Syndrome.

Takotsubo Syndrome is a transient condition characterized by left ventricular systolic dysfunction with apical akinesis/dyskinesis and ballooning. Although the prognosis with medical management is excellent in most cases, rare cases of serious complications can occur. We present here a case of a 71-year-old woman presenting with acute decompensated heart failure with initial findings consistent with a myocardial infarction, who was found instead to have an acute ventricular septal defect as a complication of Takotsubo Syndrome.

Publication and reporting of clinical trial results: cross sectional analysis across academic medical centers.

OBJECTIVE: To determine rates of publication and reporting of results within two years for all completed clinical trials registered in ClinicalTrials.gov across leading academic medical centers in the United States. DESIGN: Cross sectional analysis. SETTING: Academic medical centers in the United States. PARTICIPANTS: Academic medical centers with 40 or more completed interventional trials registered on ClinicalTrials.gov. METHODS: Using the Aggregate Analysis of ClinicalTrials.gov database and manual review, we identified all interventional clinical trials registered on ClinicalTrials.gov with a primary completion date between October 2007 and September 2010 and with a lead investigator affiliated with an academic medical center. MAIN OUTCOME MEASURES: The proportion of trials that disseminated results, defined as publication or reporting of results on ClinicalTrials.gov, overall and within 24 months of study completion. RESULTS: We identified 4347 interventional clinical trials across 51 academic medical centers. Among the trials, 1005 (23%) enrolled more than 100 patients, 1216 (28%) were double blind, and 2169 (50%) were phase II through IV. Overall, academic medical centers disseminated results for 2892 (66%) trials, with 1560 (35.9%) achieving this within 24 months of study completion. The proportion of clinical trials with results disseminated within 24 months of study completion ranged from 16.2% (6/37) to 55.3% (57/103) across academic medical centers. The proportion of clinical trials published within 24 months of study completion ranged from 10.8% (4/37) to 40.3% (31/77) across academic medical centers, whereas results reporting on ClinicalTrials.gov ranged from 1.6% (2/122) to 40.7% (72/177). CONCLUSIONS: Despite the ethical mandate and expressed values and mission of academic institutions, there is poor performance and noticeable variation in the dissemination of clinical trial results across leading academic medical centers.

Ephrin type-B receptor 4 activation reduces neointimal hyperplasia in human saphenous vein in vitro.

BACKGROUND: Vein bypass is an essential therapy for patients with advanced peripheral and coronary artery disease despite development of neointimal hyperplasia. We have shown that stimulation of the receptor tyrosine kinase ephrin type-B receptor 4 (Eph-B4) with its ligand ephrin-B2 prevents neointimal hyperplasia in murine vein grafts. This study determines whether Eph-B4 in adult human veins is capable of phosphorylation and activation of downstream signaling pathways, as well as functional to release nitric oxide (NO) and prevent neointimal hyperplasia in vitro. METHODS: Discarded human saphenous veins were taken from the operating room and placed in organ culture without or with ephrin-B2/Fc (2 µg/mL) for 14 days, and the neointima/media ratio was measured in matched veins. Primary human umbilical vein endothelial cells were treated with ephrin-B2/Fc (2 µg/mL) and examined with quantitative polymerase chain reaction, Western blot, immunoassays, and for release of NO. Ephrin-B2/Fc (2 µg/mL) was placed on the adventitia of saphenous veins treated with arterial shear stress for 24 hours in a bioreactor and activated Eph-B4 examined with immunofluorescence. RESULTS: The baseline intima/media ratio in saphenous vein rings was 0.456 ± 0.097, which increased to 0.726 ± 0.142 in untreated veins after 14 days in organ culture but only to 0.630 ± 0.132 in veins treated with ephrin-B2/Fc (n = 19, P = .017). Ephrin-B2/Fc stimulated Akt, endothelial NO synthase and caveolin-1 phosphorylation, and NO release (P = .007) from human umbilical vein endothelial cells (n = 6). Ephrin-B2/Fc delivered to the adventitia stimulated endothelial Eph-B4 phosphorylation after 24 hours of arterial stress in a bioreactor (n = 3). CONCLUSIONS: Eph-B4 is present and functional in adult human saphenous veins, with intact downstream signaling pathways capable of NO release and prevention of neointimal hyperplasia in vitro. Adventitial delivery of ephrin-B2/Fc activates endothelial Eph-B4 in saphenous veins treated with arterial shear stress in vitro. These results suggest that stimulation of Eph-B4 function may be a candidate strategy for translation to human clinical trials designed to inhibit venous neointimal hyperplasia.

Chronic kidney disease predicts long-term mortality after major lower extremity amputation.

BACKGROUND: Despite low peri-operative mortality after major lower extremity amputation, long-term mortality remains substantial. Metabolic syndrome is increasing in incidence and prevalence at an alarming rate in the USA. AIM: This study was to determine whether metabolic syndrome predicts outcome after major lower extremity amputation. PATIENTS AND METHODS: A retrospective review of charts between July 2005 and June 2010. RESULTS: Fifty-four patients underwent a total of 60 major lower extremity amputations. Sixty percent underwent below-knee amputation and 40% underwent above-knee amputation. The 30-day mortality was 7% with no difference in level (below-knee amputation, 8%; above-knee amputation, 4%; P = 0.53). The mean follow-up time was 39.7 months. The 5-year survival was 54% in the whole group, and was independent of level of amputation (P = 0.24) or urgency of the procedure (P = 0.51). Survival was significantly decreased by the presence of underlying chronic kidney disease (P = 0.04) but not by other comorbidities (history of myocardial infarction, P = 0.79; metabolic syndrome, P = 0.64; diabetes mellitus, P = 0.56). CONCLUSION: Metabolic syndrome is not associated with increased risk of adverse outcomes after lower extremity amputation. However, patients with chronic kidney disease constitute a sub-group of patients at higher risk of postoperative long-term mortality and may be a group to target for intervention.

Metabolic syndrome predicts restenosis after carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is an effective surgical option for stroke prophylaxis for most patients. Restenosis after CEA can lead to additional interventions and adverse outcomes, but the factors that predict restenosis are poorly understood. This study examined which risk factors, such as metabolic syndrome (MetS), are associated with restenosis after CEA. STUDY DESIGN: This retrospective study examined the records of all patients who underwent CEA at the Veterans Affairs Connecticut Healthcare System during a 4-year period. Metabolic syndrome was defined as the presence of 3 or more of the following: hypertension (blood pressure ≥130 mmHg/≥85 mmHg); serum triglycerides ≥150 mg/dL; high-density lipoprotein ≤40 mg/dL; BMI ≥25 kg/m(2); and fasting blood glucose ≥110 mg/dL. Major adverse events were defined as death, stroke, or MI. Restenosis was defined as >50% stenosis on follow-up imaging. RESULTS: Seventy-eight patients underwent 79 CEAs during the study period. All patients were male and 76% were white. Mean patient age was 72.6 years. The mean duration of follow-up was 5.2 years. Sixty-seven percent of patients had MetS. Patients with MetS were comparable with those without MetS in demographics and preoperative comorbidities, except for increased hypertension and diabetes, as expected, and chronic renal insufficiency (p = 0.05). There was no significant difference in long-term survival or freedom from MAE between patients with and without MetS. Restenosis was significantly higher in patients with MetS (p = 0.02) and occurred 2 years after CEA in patients with MetS only, with a large increase in restenosis after 5 years (p = 0.018). MetS was an independent predictor of restenosis in multivariable analysis (p = 0.01). CONCLUSIONS: Metabolic syndrome is an independent predictor for restenosis after CEA in a high-risk population. More frequent and/or long-term surveillance might be warranted in patients with MetS after CEA.

Vein graft adaptation and fistula maturation in the arterial environment.

Veins are exposed to the arterial environment during two common surgical procedures, creation of vein grafts and arteriovenous fistulae (AVF). In both cases, veins adapt to the arterial environment that is characterized by different hemodynamic conditions and increased oxygen tension compared with the venous environment. Successful venous adaptation to the arterial environment is critical for long-term success of the vein graft or AVF and, in both cases, is generally characterized by venous dilation and wall thickening. However, AVF are exposed to a high flow, high shear stress, low-pressure arterial environment and adapt mainly via outward dilation with less intimal thickening. Vein grafts are exposed to a moderate flow, moderate shear stress, high-pressure arterial environment and adapt mainly via increased wall thickening with less outward dilation. We review the data that describe these differences, as well as the underlying molecular mechanisms that mediate these processes. Despite extensive research, there are few differences in the molecular pathways that regulate cell proliferation and migration or matrix synthesis, secretion, or degradation currently identified between vein graft adaptation and AVF maturation that account for the different types of venous adaptation to arterial environments.

The mouse aortocaval fistula recapitulates human arteriovenous fistula maturation.

Several models of arteriovenous fistula (AVF) have excellent patency and help in understanding the mechanisms of venous adaptation to the arterial environment. However, these models fail to exhibit either maturation failure or fail to develop stenoses, both of which are critical modes of AVF failure in human patients. We used high-resolution Doppler ultrasound to serially follow mice with AVFs created by direct 25-gauge needle puncture. By day 21, 75% of AVFs dilate, thicken, and increase flow, i.e., mature, and 25% fail due to immediate thrombosis or maturation failure. Mature AVF thicken due to increased amounts of smooth muscle cells. By day 42, 67% of mature AVFs remain patent, but 33% of AVFs fail due to perianastomotic thickening. These results show that the mouse aortocaval model has an easily detectable maturation phase in the first 21 days followed by a potential failure phase in the subsequent 21 days. This model is the first animal model of AVF to show a course that recapitulates aspects of human AVF maturation.