Early U.S. Heart Transplant Experience With Normothermic Regional Perfusion Following Donation After Circulatory Death.

BACKGROUND: Heart transplantation following donation after circulatory death (DCD HT) has short-term survival outcomes comparable to donation after brain death and has led to a significant increase in transplantation volume. The U.S. experience with the normothermic regional perfusion (NRP) DCD HT procurement method has not been evaluated. OBJECTIVES: The aim of this study was to examine short-term outcomes associated with NRP vs direct procurement and perfusion (DPP) methods used during DCD HT in the United States. METHODS: The UNOS (United Network for Organ Sharing) registry was queried for all adult (age ≥18 years) heart recipients and corresponding donors of controlled DCD HT from January 2019-December 2023. Transplantations were stratified by NRP or DPP reperfusion methods. The primary outcome was overall survival. RESULTS: A total of 918 heart donors and recipients met inclusion criteria, including 622 (68%) DPP and 296 (32%) NRP transplantations. Unadjusted Kaplan-Meier survival analysis demonstrated improved short-term survival associated with NRP (log-rank P = 0.005). After adjustment, DCD HT with NRP was independently associated with improved survival (HR: 0.39 [95% CI: 0.22-0.70]; P = 0.002). A propensity-matched analysis similarly demonstrated a cumulative survival benefit to NRP (log-rank P = 0.006). CONCLUSIONS: In this largest national series of DCD HT procurement perfusion strategies, NRP is associated with improved short-term survival as compared with DPP. This study evaluates the U.S. early experience with DCD HT, and longer-term follow-up data are needed to further assess the impact of DPP and NRP methods on post-heart transplantation outcomes.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Neurophysiological Intraoperative Monitoring During Aortic Arch Surgery.

Circulatory management during replacement of the aortic arch is complex and involves a period of circulatory arrest to provide a bloodless field during arch vessel anastomosis. To guard against ischemic brain injury, tissue metabolic demand is reduced by systemically cooling the patient prior to circulatory arrest. Neurophysiological intraoperative monitoring (NIOM) is often used during the course of these procedures to provide contemporaneous assessment of brain status to help direct circulatory management decisions and detect brain ischemia. In this review, we discuss the characteristics of electrocerebral activity through the process of cooling, circulatory arrest, and rewarming as depicted through commonly used NIOM modalities, including electroencephalography and peripheral nerve somatosensory-evoked potentials. Attention is directed toward the role NIOM has traditionally played during deep hypothermic circulatory arrest, where it is used to define the point of electrocerebral inactivity or maximal cerebral metabolic suppression prior to initiating circulatory arrest while also discussing the evolving utility of NIOM when systemic circulatory arrest is initiated at more moderate degrees of hypothermia in conjunction with regional brain perfusion. The use of cerebral tissue oximetry by near-infrared spectroscopy as an alternative NIOM modality during surgery of the aortic arch is addressed as well. Finally, special considerations for NIOM and the detection of spinal cord ischemia during hybrid aortic arch repair and emerging operative techniques are also discussed.

Does moderate hypothermia really carry less bleeding risk than deep hypothermia for circulatory arrest? A propensity-matched comparison in hemiarch replacement.

BACKGROUND: Moderate (MHCA) versus deep (DHCA) hypothermia for circulatory arrest in aortic arch surgery has been purported to reduce coagulopathy and bleeding complications, although there are limited data supporting this claim. This study aimed to compare bleeding-related events after aortic hemiarch replacement with MHCA versus DHCA. METHODS: Patients who underwent hemiarch replacement at a single institution from July 2005 to August 2014 were stratified into DHCA and MHCA groups (minimum systemic temperature ≤20°C and >20°C, respectively) and compared. Then, 1:1 propensity matching was performed to adjust for baseline differences. RESULTS: During the study period, 571 patients underwent hemiarch replacement: 401 (70.2%) with DHCA and 170 (29.8%) with MHCA. After propensity matching, 155 patients remained in each group. There were no significant differences between matched groups with regard to the proportion transfused with red blood cells, plasma, platelet concentrates, or cryoprecipitate on the operative day, the rate of reoperation for bleeding, or postoperative hematologic laboratory values. Among patients who received plasma, the median transfusion volume was statistically greater in the DHCA group (6 vs 5 units, P = .01). MHCA also resulted in a slight reduction in median volume of blood returned via cell saver (500 vs 472 mL, P < .01) and 12-hour postoperative chest tube output (440 vs 350, P < .01). Thirty-day mortality and morbidity did not differ significantly between groups. CONCLUSIONS: MHCA compared with DHCA during hermiarch replacement may slightly reduce perioperative blood-loss and plasma transfusion requirement, although these differences do not translate into reduced reoperation for bleeding or postoperative mortality and morbidity.

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.