Ambulatory 7-day mechanical circulatory support in sheep model of pulmonary hypertension and right heart failure.

BACKGROUND: Right heart failure is the major cause of death in pulmonary hypertension. Lung transplantation is the only long-term treatment option for patients who fail medical therapy. Due to the scarcity of donor lungs, there is a critical need to develop durable mechanical support for the failing right heart. A major design goal for durable support is to reduce the size and complexity of devices to facilitate ambulation. Toward this end, we sought to deploy wearable mechanical support technology in a sheep disease model of chronic right heart failure. METHODS: In 6 sheep with chronic right heart failure, a mechanical support system consisting of an extracorporeal blood pump coupled with a gas exchange unit was attached in a right atrium-to-left atrium configuration for up to 7 days. Circuit performance, hematologic parameters, and animal hemodynamics were analyzed. RESULTS: Six subjects underwent the chronic disease model for 56 to 71 days. Three of the subjects survived to the 7-day end-point for circulatory support. The circuit provided 2.8 (0.5) liter/min of flow compared to the native pulmonary blood flow of 3.5 (1.1) liter/min. The animals maintained physiologically balanced blood gas profile with a sweep flow of 1.2 (1.0) liter/min. Two animals freely ambulated while wearing the circuit. CONCLUSIONS: Our novel mechanical support system provided physiologic support for a large animal model of pulmonary hypertension with right heart failure. The small footprint of the circuit and the low sweep requirement demonstrate the feasibility of this technology to enable mobile ambulatory applications.

Xenogeneic cross-circulation for physiological support and recovery of ex vivo human livers.

BACKGROUND AND AIMS: The scarcity of suitable donor livers highlights a continuing need for innovation to recover organs with reversible injuries in liver transplantation. APPROACH AND RESULTS: Explanted human donor livers (n = 5) declined for transplantation were supported using xenogeneic cross-circulation of whole blood between livers and xeno-support swine. Livers and swine were assessed over 24 hours of xeno-support. Livers maintained normal global appearance, uniform perfusion, and preservation of histologic and subcellular architecture. Oxygen consumption increased by 75% ( p = 0.16). Lactate clearance increased from -0.4 ± 15.5% to 31.4 ± 19.0% ( p = 0.02). Blinded histopathologic assessment demonstrated improved injury scores at 24 hours compared with 12 hours. Vascular integrity and vasoconstrictive function were preserved. Bile volume and cholangiocellular viability markers improved for all livers. Biliary structural integrity was maintained. CONCLUSIONS: Xenogeneic cross-circulation provided multisystem physiological regulation of ex vivo human livers that enabled functional rehabilitation, histopathologic recovery, and improvement of viability markers. We envision xenogeneic cross-circulation as a complementary technique to other organ-preservation technologies in the recovery of marginal donor livers or as a research tool in the development of advanced bioengineering and pharmacologic strategies for organ recovery and rehabilitation.

Immune characterization of a xenogeneic human lung cross-circulation support system.

Improved approaches to expanding the pool of donor lungs suitable for transplantation are critically needed for the growing population with end-stage lung disease. Cross-circulation (XC) of whole blood between swine and explanted human lungs has previously been reported to enable the extracorporeal recovery of donor lungs that declined for transplantation due to acute, reversible injuries. However, immunologic interactions of this xenogeneic platform have not been characterized, thus limiting potential translational applications. Using flow cytometry and immunohistochemistry, we demonstrate that porcine immune cell and immunoglobulin infiltration occurs in this xenogeneic XC system, in the context of calcineurin-based immunosuppression and complement depletion. Despite this, xenogeneic XC supported the viability, tissue integrity, and physiologic improvement of human donor lungs over 24 hours of xeno-support. These findings provide targets for future immunomodulatory strategies to minimize immunologic interactions on this organ support biotechnology.

Large animal preclinical investigation into the optimal extracorporeal life support configuration for pulmonary hypertension and right ventricular failure.

INTRODUCTION: Right ventricular failure (RVF) is a major cause of mortality in pulmonary hypertension (PH). Mechanical circulatory support holds promise for patients with medically refractory PH, but there are no clinical devices for long-term right ventricular (RV) support. Investigations into optimal device parameters and circuit configurations for PH-induced RVF (PH-RVF) are needed. METHODS: Eleven sheep underwent previously published chronic PH model. We then evaluated a low-profile, ventricular assist device (VAD)-quality pump combined with a novel low-resistance membrane oxygenator (Pulmonary Assist Device, PAD) under one of four central cannulation strategies: right atrium-to-left atrium (RA-LA, N = 3), RA-to-pulmonary artery (RA-PA, N=3), pumpless pulmonary artery-to-left atrium (PA-LA, N = 2), and RA-to-ascending aorta (RA-Ao, N = 3). Acute-on-chronic RVF (AoC RVF) was induced, and mechanical support was provided for up to 6 hours at blood flow rates of 1 to 3 liter/min. Circuit parameters, physiologic, hemodynamic, and echocardiography data were collected. RESULTS: The RA-LA configuration achieved blood flow of 3 liter/min. Meanwhile, RA-PA and RA-Ao faced challenges maintaining 3 liter/min of flow due to higher circuit afterload. Pumpless PA-LA was flow-limited due to anatomical limitations inherent to this animal model. RA-LA and RA-Ao demonstrated serial RV unloading with increasing circuit flow, while RA-PA did not. RA-LA also improved left ventricular (LV) and septal geometry by echocardiographic assessment and had the lowest inotropic dependence. CONCLUSION: RA-LA and RA-Ao configurations unload the RV, while RA-LA also lowers pump speed and inotropic requirements, and improves LV mechanics. RA-PA provide inferior support for PH-RVF, while an alternate animal model is needed to evaluate PA-LA.

"Keep Your Move in the Tube" safely increases discharge home following cardiac surgery.

BACKGROUND: Restrictive sternal precautions intended to prevent cardiac surgery patients from damaging healing sternotomies lack supporting evidence and may decrease independence and increase postacute care utilization. Data regarding the impact of alternative approaches on safety and outcomes are needed to guide evidence-based best practices. OBJECTIVE: To examine whether an approach allowing greater freedom during activities of daily living than permitted under commonly used restrictive sternal precautions can safely decrease postacute care utilization. DESIGN: Before-and-after study, using propensity score adjustment to account for differences in patient clinical and demographic characteristics, surgery type, and surgeon. SETTING: 600-bed acute care hospital. INTERVENTION: Beginning March 2016, the acute care hospital replaced traditional weight- and time-based precautions given to patients who underwent median sternotomy with the "Keep Your Move in the Tube" (KMIT) approach for mindfully performing movements involved in the activities of daily living, guided by pain. MAIN OUTCOME MEASURES: The study compared sternal wound complications, discharge disposition, 30-day readmission, and functional status between consecutive cardiac surgery patients with "independent" or "modified independent" preoperative functional status who underwent median sternotomy in the 1.5 years before (n = 627, standard precautions group) and after (n = 477, KMIT group) KMIT implementation. RESULTS: The odds of discharge to home, versus to inpatient rehabilitation or skilled nursing facility, were ~3 times higher for KMIT than standard precautions patients (risk-adjusted odds ratio [rOR], 95% confidence interval [CI] = 2.90, 1.95-4.32, and 3.03, 1.57-5.86, respectively). KMIT patients also had significantly higher odds of demonstrating "independent" or "modified independent" functional status on final inpatient physical therapy treatment for bed mobility (rOR, 95% CI = 7.51, 5.48-10.30) and transfers (rOR, 95% CI = 3.40, 2.62-4.42). No significant difference was observed in sternal wound complications (in-hospital or causing readmission) (rOR, 95% CI = 1.27, 0.52-3.09) or all-cause 30-day readmissions (rOR, 95% CI = 0.55, 0.23-1.33). CONCLUSIONS: KMIT increases discharge-to-home for cardiac surgery patients without increasing risk for adverse events and reducing utilization of expensive institutional postacute care.

Using value-based analysis to influence outcomes in complex surgical systems.

BACKGROUND: Value-based analysis (VBA) is a management strategy used to determine changes in value (quality/cost) when a usual practice (UP) is replaced by a best practice (BP). Previously validated in clinical initiatives, its usefulness in complex systems is unknown. To answer this question, we used VBA to correct deficiencies in cardiac surgery at Memorial Healthcare System. STUDY DESIGN: Cardiac surgery is a complex surgical system that lends itself to VBA because outcomes metrics provided by the Society of Thoracic Surgeons provide an estimate of quality; cost is available from Centers for Medicare and Medicaid Services and other contemporary sources; the UP can be determined; and the best practice can be established. RESULTS: Analysis of the UP at Memorial Healthcare System revealed considerable deficiencies in selection of patients for surgery; the surgery itself, including choice of procedure and outcomes; after care; follow-up; and control of expenditures. To correct these deficiencies, each UP was replaced with a BP. Changes included replacement of most of the cardiac surgeons; conversion to an employed physician model; restructuring of a heart surgery unit; recruitment of cardiac anesthesiologists; introduction of an interactive educational program; eliminating unsafe practices; and reducing cost. CONCLUSIONS: There was a significant (p < 0.01) reduction in readmissions, complications, and mortality between 2009 and 2013. Memorial Healthcare System was only 1 of 17 (1.7%) database participants (n = 1,009) to achieve a Society of Thoracic Surgeons 3-star rating in all 3 measured categories. Despite substantial improvements in quality, the cost per case and the length of stay declined. These changes created a savings opportunity of $14 million, with actual savings of $10.4 million. These findings suggest that VBA can be a powerful tool to enhance value (quality/cost) in a complex surgical system.