Evolving practice pattern changes and outcomes in the era of hybrid aortic arch repair.

OBJECTIVE: The role of hybrid repair in the management of aortic arch pathology, and long-term outcomes with these techniques, remains uncertain. We report a decade of experience with hybrid arch repair (HAR) and assess institutional practice patterns with regard to the use of hybrid and open techniques. METHODS: Hybrid and open total and distal arch procedures performed between July 2005 and January 2015 were identified from a prospectively maintained, institutional aortic surgery database. Perioperative morbidity and mortality, freedom from reintervention, and long-term survival were calculated. Hybrid and open procedural volumes over the study period were assessed to evaluate for potential practice pattern changes. RESULTS: During the study period 148 consecutive procedures were performed for repair of transverse and distal aortic arch pathology, including 101 hybrid repairs and 47 open total or distal arch repairs. Patients in the hybrid repair group were significantly older with a greater incidence of chronic kidney disease, peripheral vascular disease, and chronic lung disease. Perioperative mortality and outcomes were not significantly different between the hybrid and open groups, aside from decreased median length of stay after hybrid repair. Need for subsequent reintervention was significantly greater after hybrid repair. Unadjusted long-term survival was superior after open repair (70% 5-year survival open vs 47% hybrid; P = .03), although aorta-specific survival was similar (98% 5-year aorta-specific survival open vs 93% hybrid; P = .59). Institutional use of HAR decreased over the final 3 years of the study, with an associated increased use of open total or distal arch repairs. This was primarily the result of decreased use of native zone 0 hybrid procedures. Concurrent with this apparent increased stringency around patient selection for HAR, perioperative morbidity and mortality was reduced, including avoidance of retrograde type A dissection. CONCLUSIONS: HAR remains a viable option for higher-risk patients with transverse arch pathology with perioperative outcomes and long-term aorta-specific survival similar to open repair, albeit at a cost of increased reintervention. This observational single-institution study would suggest decreased use in more recent years in favor of open repair due to avoidance of native zone 0 hybrid procedures. This decline in the institutional use of native zone 0 hybrid repairs was associated with improved perioperative outcomes.

Complementary roles of open and hybrid approaches to thoracoabdominal aortic aneurysm repair.

OBJECTIVE: Thoracoabdominal aortic aneurysm (TAAA) repair remains a significant challenge with considerable perioperative morbidity and mortality. A hybrid approach utilizing visceral debranching with endovascular aneurysm exclusion has been used to treat high-risk patients and therefore allow repair in more patients. Limited data exist regarding long-term outcomes with this procedure as well as comparison to conventional open repair. This study describes our institutional algorithmic approach to TAAA repair using both open and hybrid techniques. METHODS: Hybrid and open TAAA repairs performed between July 2005 and August 2015 were identified from a prospectively maintained institutional aortic surgery database. Perioperative morbidity and mortality, freedom from reintervention, and long-term and aorta-specific survival were calculated and compared between the two groups. RESULTS: During the study period, 165 consecutive TAAA repairs were performed, including 84 open repairs and 81 hybrid repairs. Patients in the hybrid repair group were significantly older, were more frequently female, and had a generally greater comorbid disease burden, including significantly more chronic kidney disease. Despite the older and sicker cohort, there was no difference in in-hospital mortality between the two groups (9.9% hybrid vs 7.1% open; P = .59). Major morbidity rates differed by procedure, with patients undergoing open repair having a significantly higher rate of postoperative stroke (9.5% open vs 0% hybrid; P = .017), whereas patients undergoing hybrid repair had a higher rate of new permanent dialysis (14.8% hybrid vs 3.6% open; P = .043). There was no difference between groups in the rate of postoperative permanent paraplegia/paresis (8.3% open vs 7.4% hybrid; P = .294). There was a significantly increased rate of reintervention in the hybrid repair group (12.3% hybrid vs 1.2% open, P = .004), with all hybrid reinterventions performed because of endoleak. One-year survival was similar between groups at 69% in hybrid repairs vs 77% in open repairs. Long-term survival was worse in the hybrid group (5-year survival, 32% hybrid vs 56% open), although late survival appeared to be influenced mainly by comorbid disease burden, given the similar long-term aorta-specific survival between groups. CONCLUSIONS: Use of an algorithmic approach whereby higher risk patients with TAAA are treated by a hybrid approach and lower risk patients with conventional open repair yields satisfactory short- and long-term outcomes. The availability of multiple options for TAAA repair within a single center likely allows repair in more patients with consequent decrease in the risk of aorta-related death, at the expense of increased reinterventions for endoleak.

Surgical Resection of the Primary Tumor in Stage IV Colorectal Cancer Without Metastasectomy is Associated With Improved Overall Survival Compared With Chemotherapy/Radiation Therapy Alone.

BACKGROUND: Controversy exists over whether resection of the primary tumor in stage IV colorectal cancer with inoperable metastases improves patient outcomes. OBJECTIVE: The purpose of this study was to evaluate whether resection of the primary tumor without metastasectomy in patients with stage IV colorectal cancer is associated with improved overall survival compared with patients undergoing chemotherapy and/or radiation therapy alone. DESIGN: This was a retrospective review of a multi-institutional dataset. SETTINGS: This study was conducted in all participating commission on cancer (CoC)-accredited facilities. PATIENTS: The 2003-2006 National Cancer Data Base was reviewed to identify patients with stage IV adenocarcinoma of the colon or rectum who underwent palliative treatment without curative intent, either in the form of surgical resection of the primary tumor without metastasectomy consisting of a colectomy or rectal resection with or without chemotherapy and/or radiation or chemotherapy and/or radiation alone. MAIN OUTCOME MEASURES: Groups were compared for baseline characteristics. Overall survival was compared using Kaplan-Meier analysis before and after propensity matching with a 1:1 nearest-neighbor algorithm. RESULTS: Of the 1446 patients included in the analysis, 231 (16%) underwent surgical resection of the primary tumor without metastasectomy. Surgical resection was associated with a significant survival benefit on unadjusted analysis (median survival, 9.2 vs. 7.6 months; p < 0.01). After propensity matching to adjust for nonrandom treatment selection, surgical resection continued to be associated with a significant survival benefit (median survival, 9.2 vs. 7.3 months; p < 0.01). LIMITATIONS: This study was limited by the potential for selection bias regarding which patients received surgical resection. There was also a lack of data regarding the indication for operation, specifically whether a patient was symptomatic or asymptomatic before resection. The inability to account for tumor size or grade among patients who did not receive surgical resection was another limitation. CONCLUSIONS: Surgical resection of the primary tumor without metastasectomy in patients with metastatic colorectal cancer is associated with improved survival as compared with chemotherapy/radiation therapy alone. Additional research is necessary to determine which patients may benefit from this intervention.

Feeding jejunostomy tube placement during resection of gastric cancers.

BACKGROUND: Feeding tube placement is common among patients undergoing gastrectomy, and national guidelines currently recommend consideration of a feeding jejunostomy tube (FJT) for all patients undergoing resection for gastric cancer. However, data are limited regarding the safety of FJT placement at the time of gastrectomy for gastric cancer. METHODS: The 2005-2011 American College of Surgeons National Surgical Quality Improvement Program Participant User Files were queried to identify patients who underwent gastrectomy for gastric cancer. Subjects were classified by the concomitant placement of an FJT. Groups were then propensity matched using a 1:1 nearest neighbor algorithm, and outcomes were compared between groups. The primary outcomes of interest were overall 30-d overall complications and mortality. Secondary end points included major complications, surgical site infection, and early reoperation. RESULTS: In total, 2980 subjects underwent gastrectomy for gastric cancer, among whom 715 (24%) also had an FJT placed. Patients who had an FJT placed were more likely to be male (61.6% versus 56.6%, P = 0.02), have recent weight loss (21.0% versus 14.8%, P < 0.01), and have undergone recent chemotherapy (7.9% versus 4.2%, P < 0.01) and radiation therapy (4.2% versus 1.3%, P < 0.01). They were also more likely to have undergone total (compared with partial) gastrectomy (66.6% versus 28.6%, P < 0.01) and have concomitant resection of an adjacent organ (40.4 versus 24.1%, P < 0.01). After adjustment with propensity matching, however, all baseline characteristics and treatment variables were highly similar. Between groups, there were no statistically significant differences in 30-d overall complications (38.8% versus 36.1%, P = 0.32) or mortality (5.8 versus 3.7%, P = 0.08). There were also no differences in major complications, surgical site infection, or early reoperation. Operative time was slightly longer among patients with feeding tubes placed (median, 248 versus 233 min, P = 0.01), but otherwise there were no significant differences in any outcomes between groups. CONCLUSIONS: Concomitant placement of FJT at the time of gastrectomy may result in slightly increased operative times but does not appear to lead to increased perioperative morbidity or mortality. Further investigation is needed to identify the patients most likely to benefit from FJT placement.

Optimal timing of tracheostomy after trauma without associated head injury.

BACKGROUND: Controversy exists over optimal timing of tracheostomy in patients with respiratory failure after blunt trauma. The study aimed to determine whether the timing of tracheostomy affects mortality in this population. METHODS: The 2008-2011 National Trauma Data Bank was queried to identify blunt trauma patients without concomitant head injury who required tracheostomy for respiratory failure between hospital days 4 and 21. Restricted cubic spline analysis was performed to evaluate the relationship between tracheostomy timing and the odds of inhospital mortality. The cohort was stratified based on this analysis. Unadjusted characteristics and outcomes were compared. Multivariable logistic regression was used to evaluate the effect of tracheostomy timing on mortality after adjustment for age, gender, race, payor status, level of trauma center, injury severity score, presentation Glasgow coma scale, and thoracic and abdominal abbreviated injury score. RESULTS: There were 9662 patients included in the study. Restricted cubic spline analysis demonstrated a nonlinear relationship between timing of tracheostomy and mortality, with higher odds of mortality occurring with tracheostomy placement within 10 d of admission compared with later time points. The cohort was therefore stratified into early and delayed tracheostomy groups relative to this time point. The resulting groups contained 5402 (55.9%) and 4260 (44.1%) patients, respectively. After multivariable adjustment, the delayed tracheostomy group continued to have significantly reduced odds of mortality (Adjusted odds ratio, 0.82, 95% confidence interval, 0.71-0.95, C-statistic, 0.700). CONCLUSIONS: Among non-head injured blunt trauma patients with prolonged respiratory failure, tracheostomy placement within 10 d of admission may result in increased mortality compared with later time points.

Donor Heart Recovery and Preservation Modalities in 2024.

Historically, heart transplantation (HT) has relied on the use of traditional cold storage for donor heart preservation. This organ preservation modality has several limitations, including the risk for ischemic and cold-induced graft injuries that may contribute to primary graft dysfunction and poor post-HT outcomes. In recent years, several novel donor heart preservation modalities have entered clinical practice, including the SherpaPak Cardiac Transport System of controlled hypothermic preservation, and the Transmedics Organ Care System of ex vivo perfusion. Such technologies are altering the landscape of HT by expanding the geographic reach of procurement teams and enabling both donation after cardiac death and the use of expanded criteria donor hearts. This paper will review the emerging evidence on the association of these modalities with improved post-HT outcomes, and will also suggest best practices for selecting between donor heart preservation techniques.

The History of Durable Left Ventricular Assist Devices and Comparison of Outcomes: HeartWare, HeartMate II, HeartMate 3, and the Future of Mechanical Circulatory Support.

The utilization of left ventricular assist devices (LVADs) in end-stage heart failure has doubled in the past ten years and is bound to continue to increase. Since the first of these devices was approved in 1994, the technology has changed tremendously, and so has the medical and surgical management of these patients. In this review, we discuss the history of LVADs, evaluating survival and complications over time. We also aim to discuss practical aspects of the medical and surgical management of LVAD patients and future directions for outcome improvement in this population.

Right heart failure after left ventricular assist device: From mechanisms to treatments.

Left ventricular assist device (LVAD) therapy is a lifesaving option for patients with medical therapy-refractory advanced heart failure. Depending on the definition, 5-44% of people supported with an LVAD develop right heart failure (RHF), which is associated with worse outcomes. The mechanisms related to RHF include patient, surgical, and hemodynamic factors. Despite significant progress in understanding the roles of these factors and improvements in surgical techniques and LVAD technology, this complication is still a substantial cause of morbidity and mortality among LVAD patients. Additionally, specific medical therapies for this complication still are lacking, leaving cardiac transplantation or supportive management as the only options for LVAD patients who develop RHF. While significant effort has been made to create algorithms aimed at stratifying risk for RHF in patients undergoing LVAD implantation, the predictive value of these algorithms has been limited, especially when attempts at external validation have been undertaken. Perhaps one of the reasons for poor performance in external validation is related to differing definitions of RHF in external cohorts. Additionally, most research in this field has focused on RHF occurring in the early phase (i.e., ≤1 month) post LVAD implantation. However, there is emerging recognition of late-onset RHF (i.e., > 1 month post-surgery) as a significant cause of morbidity and mortality. Late-onset RHF, which likely has a unique physiology and pathogenic mechanisms, remains poorly characterized. In this review of the literature, we will describe the unique right ventricular physiology and changes elicited by LVADs that might cause both early- and late-onset RHF. Finally, we will analyze the currently available treatments for RHF, including mechanical circulatory support options and medical therapies.

Pathophysiology and management of valvular disease in patients with destination left ventricular assist devices.

Over the last two decades, implantable continuous flow left ventricular assist devices (LVAD) have proven to be invaluable tools for the management of selected advanced heart failure patients, improving patient longevity and quality of life. The presence of concomitant valvular pathology, including that involving the tricuspid, mitral, and aortic valve, has important implications relating to the decision to move forward with LVAD implantation. Furthermore, the presence of concomitant valvular pathology often influences the surgical strategy for LVAD implantation. Concomitant valve repair or replacement is not uncommonly required in such circumstances, which increases surgical complexity and has demonstrated prognostic implications both short and longer term following LVAD implantation. Beyond the index operation, it is also well established that certain valvular pathologies may develop or worsen over time following LVAD support. The presence of pre-existing valvular pathology or that which develops following LVAD implant is of particular importance to the destination therapy LVAD patient population. As these patients are not expected to have the opportunity for heart transplantation in the future, optimization of LVAD support including ameliorating valvular disease is critical for the maximization of patient longevity and quality of life. As collective experience has grown over time, the ability of clinicians to effectively address concomitant valvular pathology in LVAD patients has improved in the pre-implant, implant, and post-implant phase, through both medical management and procedural optimization. Nevertheless, there remains uncertainty over many facets of concomitant valvular pathology in advanced heart failure patients, and the understanding of how to best approach these conditions in the LVAD patient population continues to evolve. Herein, we present a comprehensive review of the current state of the field relating to the pathophysiology and management of valvular disease in destination LVAD patients.

Does deeper hypothermia reduce the risk of acute kidney injury after circulatory arrest for aortic arch surgery?

OBJECTIVES: The impact of hypothermic circulatory arrest (HCA) temperature on postoperative acute kidney injury (AKI) has not been evaluated. This study examined the association between circulatory arrest temperatures and AKI in patients undergoing proximal aortic surgery with HCA. METHODS: A total of 759 consecutive patients who underwent proximal aortic surgery (ascending ± valve ± root) including arch replacement requiring HCA between July 2005 and December 2016 were identified from a prospectively maintained institutional aortic surgery database. The primary outcome was AKI as defined by Risk, Injury, Failure, Loss, End Stage Renal Disease (ESRD) criteria. The association between minimum nasopharyngeal (NP) and bladder temperatures during HCA and postoperative AKI was assessed, adjusting for patient-level factors using multivariable logistic regression. RESULTS: A total of 85% (n = 645) of patients underwent deep hypothermia (14.1-20.0°C), 11% (n = 83) low-moderate hypothermia (20.1-24.0°C) and 4% (n = 31) high-moderate hypothermia (24.1-28.0°C) as classified by NP temperature. When analysed by bladder temperature, 59% (n = 447) underwent deep hypothermia, 22% (n = 170) low-moderate, 16% (n = 118) high-moderate and 3% mild (n = 24) (28.1-34.0°C) hypothermia. The median systemic circulatory arrest time was 17 min. The incidence of AKI did not differ between hypothermia groups, whether analysed using minimum NP or bladder temperature. In the multivariable analysis, the association between degree of hypothermia and AKI remained non-significant whether analysed as a categorical variable (hypothermia group) or as a continuous variable (minimum NP or bladder temperature) (all P > 0.05). CONCLUSIONS: In patients undergoing proximal aortic surgery including arch replacement requiring HCA, degree of systemic hypothermia was not associated with the risk of AKI. These data suggest that moderate hypothermia does not confer increased risk of AKI for patients requiring circulatory arrest, although additional prospective data are needed.

Successful aneurysm resection and coronary artery revascularization following saphenous vein graft aneurysm rupture.

Saphenous vein graft aneurysms after coronary artery bypass grafting (CABG) have been rarely reported. Their incidence and natural history are poorly defined. Herein, we present a patient who presented acutely with contained rupture of a large saphenous vein graft aneurysm 12 years after CABG, which was successfully managed with open aneurysm resection and regrafting.

Risk Prediction Model for Major Adverse Outcome in Proximal Thoracic Aortic Surgery.

BACKGROUND: Proximal thoracic aortic surgery utilizing hypothermic circulatory arrest carries risks of mortality and major morbidity; however, these risks are not the same for every patient. The goal of the current study was to establish a risk prediction model for risk-stratifying patients undergoing proximal thoracic aortic surgery with hypothermic circulatory arrest for degenerative pathology, to facilitate preoperative physician-patient counseling. METHODS: A retrospective analysis was conducted on 489 patients who underwent proximal thoracic aortic surgery with hypothermic circulatory arrest for degenerative pathology between July 2005 and August 2014 at a single referral institution; patients with acute dissection (n = 139) were excluded. Multivariable logistic regression was used to build a risk prediction model and identify preoperative predictors of major adverse outcome-the composite endpoint of 30-day/inhospital mortality, stroke, acute renal failure, prolonged ventilation, or discharge to a location other than home. The results were validated using an independent cohort of 120 patients operated on from September 2014 to September 2016. RESULTS: Multivariable analysis identified age (p = 0.0002, odds ratio [OR] 2.01), total arch replacement (p ≤ 0.0001, OR 6.75), and procedure status (p = 0.0028; OR 2.73 for urgent, OR 43.58 for emergent) as independent predictors associated with major adverse outcome. The calibration curve for probability of major adverse outcome showed excellent agreement between the model and observations. The concordance index was 0.93 in external validation. CONCLUSIONS: The current study identified risk factors for major adverse outcome after proximal thoracic aortic surgery with hypothermic circulatory arrest for degenerative pathology. The proposed simple, accurate model can quantify risk and facilitate physician-patient counseling before possible surgical intervention.

Adjuvant Chemotherapy Improves Survival Following Resection of Locally Advanced Rectal Cancer with Pathologic Complete Response.

BACKGROUND: Controversy exists over the use of adjuvant chemotherapy for locally advanced (stages II-III) rectal cancer (LARC) patients who demonstrate pathologic complete response (pCR) following neoadjuvant chemoradiation. We conducted a retrospective analysis to determine whether adjuvant chemotherapy imparts survival benefit among this population. METHODS: The National Cancer Database (NCDB) was queried to identify LARC patients with pCR following neoadjuvant chemoradiation. The cohort was stratified by receipt of adjuvant chemotherapy. Multiple imputation and a Cox proportional hazards model were employed to estimate the effect of adjuvant chemotherapy on overall survival. RESULTS: There were 24,418 patients identified in the NCDB with clinically staged II or III rectal cancer who received neoadjuvant chemoradiation. Of these, 5606 (23.0%) had pCR. Among patients with pCR, 1401 (25%) received adjuvant chemotherapy and 4205 (75%) did not. Patients who received adjuvant chemotherapy were slightly younger, more likely to have private insurance, and more likely to have clinically staged III disease, but did not differ significantly in comparison to patients who did not receive adjuvant chemotherapy with respect to race, sex, facility type, Charlson comorbidity score, histologic tumor grade, procedure type, length of stay, or rate of 30-day readmission following surgery. On adjusted analysis, receipt of adjuvant chemotherapy was associated with a lower risk of death at a given time compared to patients who did not receive adjuvant chemotherapy (HR 0.808; 95% CI 0.679-0.961; p = 0.016). CONCLUSION: Supporting existing NCCN guidelines, the findings from this study suggest that adjuvant chemotherapy improves survival for LARC with pCR following neoadjuvant chemoradiation.

A novel mutation in NFKBIA/IKBA results in a degradation-resistant N-truncated protein and is associated with ectodermal dysplasia with immunodeficiency.

Alterations in nuclear factor kappa B (NF-kappaB) essential modulator (NEMO; HUGO-approved symbol IKBKG) underlie most cases of ectodermal dysplasia with immune deficiency (EDI), a human disorder characterized by anhidrosis with diminished immunity. EDI has also been associated with a single heterozygous mutation at position Ser32 of the NF-kappaB inhibitor IkappaBalpha, one of two phosphorylation sites that are essential for targeting IkappaBalpha for proteasomal degradation and hence for activation of NF-kappaB. We report a novel heterozygous nonsense mutation in the IKBA (HUGO-approved symbol, NFKBIA) gene of a 1-year-old male child with EDI that introduces a premature termination codon at position Glu14. An in-frame methionine downstream of the nonsense mutation allows for reinitiation of translation. The resulting N-terminally truncated protein lacks both serine phosphorylation sites and inhibits NF-kappaB signaling by functioning as a dominant negative on NF-kappaB activity in lymphocytes and monocytes. These findings support the scanning model for translation initiation in eukaryotes and confirm the critical role of the NF-kappaB in the human immune response.

Crystal structure of the cofactor-binding domain of the human phase II drug-metabolism enzyme UDP-glucuronosyltransferase 2B7.

Human UDP-glucuronosyltransferases (UGT) are the dominant phase II conjugative drug metabolism enzymes that also play a central role in processing a range of endobiotic compounds. UGTs catalyze the covalent addition of glucuronic acid sugar moieties to a host of therapeutics and environmental toxins, as well as to a variety of endogenous steroids and other signaling molecules. We report the 1.8-A resolution apo crystal structure of the UDP-glucuronic acid binding domain of human UGT isoform 2B7 (UGT2B7), which catalyzes the conjugative elimination of opioid, antiviral, and anticancer drugs. This is the first crystal structure of any region of a mammalian UGT drug metabolism enzyme. Designated UGT2B7 mutants at residues predicted to interact with the UDP-glucuronic acid cofactor exhibited significantly impaired catalytic activity, with maximum effects observed for amino acids closest to the glucuronic acid sugar transferred to the acceptor molecule. Homology modeling of UGT2B7 with related plant flavonoid glucosyltransferases indicates human UGTs share a common catalytic mechanism. Point mutations at predicted catalytic residues in UGT2B7 abrogated activity, strongly suggesting human UGTs also utilize a serine hydrolase-like catalytic mechanism to facilitate glucuronic acid transfer.

Vascular Complications and Use of a Distal Perfusion Cannula in Femorally Cannulated Patients on Extracorporeal Membrane Oxygenation.

Femoral arterial cannulation in adult venoarterial (VA) extracorporeal membrane oxygenation (ECMO) predisposes patients to ipsilateral limb ischemia. Placement of a distal perfusion catheter (DPC) is one of few techniques available to prevent or manage this complication. Although frequently used, the indications for and timing of DPC placement are poorly characterized, and no guidelines are available to guide its use. The purpose of this study was to compare the incidences of vascular complications and limb ischemia between patients who did and did not receive a DPC at the time of primary ECMO cannulation. Between June 2009 and April 2015, 132 adults underwent VA ECMO cannulation at our institution. Of the 80 femoral cannulations comprising this retrospective single-center study cohort, 14 (17.5%) received a DPC at the time of primary cannulation. Demographics, indications for ECMO, and cardiovascular history and risk factors were not significantly different between comparison groups. Median arterial cannula size was 17 French in both groups. Vascular complications occurred in 2 of the 14 patients with initial DPC (14.3%) compared with 21 of 66 without initial DPC (31.8%; p = 0.188). Limb ischemia occurred in 2 of 14 patients in the DPC group (14.3%) and 15 of 66 in the non-DPC group (22.7%; p = 0.483). In-hospital mortality was comparable between groups. DPC placement at the time of primary cannulation may lower the incidence of limb ischemia. The benefit of DPC placement once evidence of limb ischemia is apparent remains unclear.

Mitochondrial quality-control dysregulation in conditional HO-1-/- mice.

The heme oxygenase-1 (Hmox1; HO-1) pathway was tested for defense of mitochondrial quality control in cardiomyocyte-specific Hmox1 KO mice (HO-1[CM]-/-) exposed to oxidative stress (100% O2). After 48 hours of exposure, these mice showed persistent cardiac inflammation and oxidative tissue damage that caused sarcomeric disruption, cardiomyocyte death, left ventricular dysfunction, and cardiomyopathy, while control hearts showed minimal damage. After hyperoxia, HO-1(CM)-/- hearts showed suppression of the Pgc-1α/nuclear respiratory factor-1 (NRF-1) axis, swelling, low electron density mitochondria by electron microscopy (EM), increased cell death, and extensive collagen deposition. The damage mechanism involves structurally deficient autophagy/mitophagy, impaired LC3II processing, and failure to upregulate Pink1- and Park2-mediated mitophagy. The mitophagy pathway was suppressed through loss of NRF-1 binding to proximal promoter sites on both genes. These results indicate that cardiac Hmox1 induction not only prevents heme toxicity, but also regulates the timing and registration of genetic programs for mitochondrial quality control that limit cell death, pathological remodeling, and cardiac fibrosis.

Central Cannulation as a Viable Alternative to Peripheral Cannulation in Extracorporeal Membrane Oxygenation.

Arterial cannulation for veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) is most commonly established via the aorta, axillary, or femoral vessels, yet their inherent complications are not well characterized. The purpose of this study was to compare the outcomes and complication rates of central vs peripheral cannulation. Adult patients undergoing VA ECMO between June 2009 and April 2015 were reviewed in this retrospective single-center study. Patient characteristics, clinical outcomes, and details related to deployment were extracted from the medical record. Complications and survival rates were compared between patients by cannulation strategy. Of 131 VA ECMO patients, there were 36 aortic (27.5%), 16 axillary (12.2%), and 79 femoral (60.3%) cannulations. Other than a lower mean age with femoral cannulations (53.9 ± 13.9 years) vs aortic (60.3 ± 12.2 years) and axillary (59.8 ± 12.4 years) (P = 0.032), the baseline patient characteristics were not statistically different. Central cannulation was more common in patients transferred from outside facilities (74.3% central vs 51.6% peripheral) (P = 0.053). Seven of 36 aortic cannulations were via anterior thoracotomy (19.4%). Forty of 131 patients underwent extracorporeal cardiopulmonary resuscitation (30.5%), 33 of whom were femorally cannulated. Peripheral cannulation carried a 29.5% rate of vascular complications compared with an 11.1% rate of mediastinal bleeding with central cannulation. Incidence of stroke and overall survival between groups were not statistically different. Central cannulation is a viable alternative to peripheral cannulation. Central cannulation avoids high rates of extremity morbidity without causing significant risks of alternative morbidity or death.