Right Ventricular Sizing and Pulmonary Vascular Resistance: How Much Mass Do You Need?

OBJECTIVE: Right ventricular (RV) donor-recipient sizing has been demonstrated to be a sensitive predictor for mortality after heart transplantation. We sought to understand the relationship between donor-recipient RV mass (RVM) ratio and pulmonary vascular resistance (PVR) on outcomes after heart transplantation. METHODS: Adult heart transplant recipients from the UNOS database were included (N=42,594). The impact of RVM ratio and PVR on 1-year mortality was assessed by logistic regression after multivariable adjustment. RESULTS: Among transplant recipients, median PVR was 2.4 (1.7-3.3) WU and median RVM ratio was 1.2 (1.0-1.3). Without considering PVR, RVM ratio was highly associated with postoperative dialysis (OR=0.49, P<0.001) and 1-year mortality (OR=0.64, P<0.001). Without considering RVM ratio, PVR was highly associated with 1-year mortality (OR=1.05, P<0.001), but not postoperative dialysis (OR=0.98, P=0.156). When considering both RVM ratio and PVR, the risk associated with each remained significant, but PVR did not modify the effect of RVM ratio on 1-year mortality (RVM ratio*PVR: OR=0.99, P=0.858). In order to maintain a consistent predicted 1-year mortality, RVM ratio would need to increase by 0.12 for each WU increase in PVR. Secondary analyses found that a 1 WU change in PVR was associated with an 11% increase in mortality risk in RVM ratio mismatched patients (RVM ratio <1; P=0.001), but only a 5% increase in RVM ratio matched patients (RVM ratio ≥1; P=0.003). CONCLUSION: RVM ratio and recipient PVR are independent predictors of 1-year mortality. Still, a larger RV mass may be utilized to mediate the effects of an elevated PVR.

Thoraco-abdominal normothermic regional perfusion for thoracic transplantation in the United States: current state and future directions.

PURPOSE OF REVIEW: To provide an update regarding the state of thoracoabdominal normothermic regional perfusion (taNRP) when used for thoracic organ recovery. RECENT FINDINGS: taNRP is growing in its utilization for thoracic organ recovery from donation after circulatory death donors, partly because of its cost effectiveness. taNRP has been shown to yield cardiac allograft recipient outcomes similar to those of brain-dead donors. Regarding the use of taNRP to recover donor lungs, United Network for Organ Sharing (UNOS) analysis shows that taNRP recovered lungs are noninferior, and taNRP has been used to consistently recover excellent lungs at high volume centers. Despite its growth, ethical debate regarding taNRP continues, though clinical data now supports the notion that there is no meaningful brain perfusion after clamping the aortic arch vessels. SUMMARY: taNRP is an excellent method for recovering both heart and lungs from donation after circulatory death donors and yields satisfactory recipient outcomes in a cost-effective manner. taNRP is now endorsed by the American Society of Transplant Surgeons, though ethical debate continues.

Outcomes of Heart Transplant Donation After Circulatory Death.

BACKGROUND: Heart transplantation using donation after circulatory death (DCD) allografts is increasingly common, expanding the donor pool and reducing transplant wait times. However, data remain limited on clinical outcomes. OBJECTIVES: We sought to compare 6-month and 1-year clinical outcomes between recipients of DCD hearts, most of them recovered with the use of normothermic regional perfusion (NRP), and recipients of donation after brain death (DBD) hearts. METHODS: We conducted a single-center retrospective observational study of all adult heart-only transplants from January 2020 to January 2023. Recipient and donor data were abstracted from medical records and the United Network for Organ Sharing registry, respectively. Survival analysis and Cox regression were used to compare the groups. RESULTS: During the study period, 385 adults (median age 57.4 years [IQR: 48.0-63.7 years]) underwent heart-only transplantation, including 122 (32%) from DCD donors, 83% of which were recovered with the use of NRP. DCD donors were younger and had fewer comorbidities than DBD donors. DCD recipients were less often hospitalized before transplantation and less likely to require pretransplantation temporary mechanical circulatory support compared with DBD recipients. There were no significant differences between groups in 1-year survival, incidence of severe primary graft dysfunction, treated rejection during the first year, or likelihood of cardiac allograft vasculopathy at 1 year after transplantation. CONCLUSIONS: In the largest single-center comparison of DCD and DBD heart transplantations to date, outcomes among DCD recipients are noninferior to those of DBD recipients. This study adds to the published data supporting DCD donors as a safe means to expand the heart donor pool.

Early Assessment of Cardiac Allograft Vasculopathy Risk Among Recipients of Hepatitis C Virus-infected Donors in the Current Era.

BACKGROUND: Transplantation of hearts from hepatitis C virus (HCV)-positive donors has increased substantially in recent years following development of highly effective direct-acting antiviral therapies for treatment and cure of HCV. Although historical data from the pre-direct-acting antiviral era demonstrated an association between HCV-positive donors and accelerated cardiac allograft vasculopathy (CAV) in recipients, the relationship between the use of HCV nucleic acid test-positive (NAT+) donors and the development of CAV in the direct-acting antiviral era remains unclear. METHODS AND RESULTS: We performed a retrospective, single-center observational study comparing coronary angiographic CAV outcomes during the first year after transplant in 84 heart transplant recipients of HCV NAT+ donors and 231 recipients of HCV NAT- donors. Additionally, in a subsample of 149 patients (including 55 in the NAT+ cohort and 94 in the NAT- cohort) who had serial adjunctive intravascular ultrasound examination performed, we compared development of rapidly progressive CAV, defined as an increase in maximal intimal thickening of ≥0.5 mm in matched vessel segments during the first year post-transplant. In an unadjusted analysis, recipients of HCV NAT+ hearts had reduced survival free of CAV ≥1 over the first year after heart transplant compared with recipients of HCV NAT- hearts. After adjustment for known CAV risk factors, however, there was no significant difference between cohorts in the likelihood of the primary outcome, nor was there a difference in development of rapidly progressive CAV. CONCLUSIONS: These findings support larger, longer-term follow-up studies to better elucidate CAV outcomes in recipients of HCV NAT+ hearts and to inform post-transplant management strategies.

Extracorporeal Life Support for Cardiogenic Shock in Adult Congenital Heart Disease-An ELSO Registry Analysis.

There are minimal data on the use of venoarterial extracorporeal membrane life support (VA-ECLS) in adult congenital heart disease (ACHD) patients presenting with cardiogenic shock (CS). This study sought to describe the population of ACHD patients with CS who received VA-ECLS in the Extracorporeal Life Support Organization (ELSO) Registry. This was a retrospective analysis of adult patients with diagnoses of ACHD and CS in ELSO from 2009-2021. Anatomic complexity was categorized using the American College of Cardiology/American Heart Association 2018 guidelines. We described patient characteristics, complications, and outcomes, as well as trends in mortality and VA-ECLS utilization. Of 528 patients who met inclusion criteria, there were 32 patients with high-complexity anatomy, 196 with moderate-complexity anatomy, and 300 with low-complexity anatomy. The median age was 59.6 years (interquartile range, 45.8-68.2). The number of VA-ECLS implants increased from five implants in 2010 to 81 implants in 2021. Overall mortality was 58.3% and decreased year-by-year (ß= -2.03 [95% confidence interval, -3.36 to -0.70], p = 0.007). Six patients (1.1%) were bridged to heart transplantation and 21 (4.0%) to durable ventricular assist device. Complications included cardiac arrhythmia/tamponade (21.6%), surgical site bleeding (17.6%), cannula site bleeding (11.4%), limb ischemia (7.4%), and stroke (8.7%). Utilization of VA-ECLS for CS in ACHD patients has increased over time with a trend toward improvement in survival to discharge.

Normothermic regional perfusion for donation after circulatory death donors.

PURPOSE OF REVIEW: This review is intended to provide an update on the logistics, technique, and outcomes associated with normothermic regional perfusion (NRP), as well as provide a discussion of the associated ethical issues. RECENT FINDINGS: There has been renewed interest in utilizing NRP to increase quality and availability of organs from donation after circulatory death (DCD) donors. Our institution has increasing experience with thoraco-abdominal NRP (TA-NRP) in controlled DCD donors (cDCD), whereas abdominal NRP (A-NRP) has been used with success in both cDCD and uncontrolled DCD (uDCD). There is increasing evidence that NRP can be conducted in a practical and cost-efficient manner, and that the organ yield may be of better quality than standard direct procurement and perfusion (DPP). SUMMARY: NRP is increasingly successful and will likely prove to be a superior method for cDCD recovery. However, before TA-NRP can be widely accepted the ethical debate surrounding this technique must be settled. VIDEO ABSTRACT: http://links.lww.com/COOT/A11.

How to Turn It Down: The Evidence and Opinions Behind Adult Venoarterial Extracorporeal Membrane Oxygenation Weaning.

Adequate and durable recovery in patients supported with venoarterial (VA) extracorporeal membrane oxygenation (ECMO) can be challenging to predict. Extracorporeal membrane oxygenation weaning is the process by which the ECMO flows are decreased to assess if a patient is ready for decannulation. The optimal strategies for deciding who to wean and how to wean VA ECMO remain undefined. A retrospective literature review was performed to understand the evidence supporting current practices in ECMO weaning and in particular patient selection and methods. Most published work and expert opinions agree that once the underlying process has resolved, the minimum required physiologic parameters for weaning from ECMO include: hemodynamic stability and cardiac pulsatility, adequate lung function to support oxygenation and ventilation, and evidence of recovered end organ function. Echocardiography is universally used to assess cardiac function during the weaning process. Currently, there is no consensus regarding who is eligible to wean or how to wean ECMO in adults. We have reviewed the literature to summarize the evidence and expert opinions behind VA ECMO weaning, and give an example of the protocol used at our center. We believe this protocol optimizes patient selection for weaning and helps to predict successful decannulation.

Veno-venous Extracorporeal Membrane Oxygenation for Respiratory Failure in COVID-19 Patients: Early Experience From a Major Academic Medical Center in North America.

AND BACKGROUND DATA: VV ECMO can be utilized as an advanced therapy in select patients with COVID-19 respiratory failure refractory to traditional critical care management and optimal mechanical ventilation. Anticipating a need for such therapies during the pandemic, our center created a targeted protocol for ECMO therapy in COVID-19 patients that allows us to provide this life-saving therapy to our sickest patients without overburdening already stretched resources or excessively exposing healthcare staff to infection risk. METHODS: As a major regional referral program, we used the framework of our well-established ECMO service-line to outline specific team structures, modified patient eligibility criteria, cannulation strategies, and management protocols for the COVID-19 ECMO program. RESULTS: During the first month of the COVID-19 outbreak in Massachusetts, 6 patients were placed on VV ECMO for refractory hypoxemic respiratory failure. The median (interquartile range) age was 47 years (43-53) with most patients being male (83%) and obese (67%). All cannulations were performed at the bedside in the intensive care unit in patients who had undergone a trial of rescue therapies for acute respiratory distress syndrome including lung protective ventilation, paralysis, prone positioning, and inhaled nitric oxide. At the time of this report, 83% (5/6) of the patients are still alive with 1 death on ECMO, attributed to hemorrhagic stroke. 67% of patients (4/6) have been successfully decannulated, including 2 that have been successfully extubated and one who was discharged from the hospital. The median duration of VV ECMO therapy for patients who have been decannulated is 12 days (4-18 days). CONCLUSIONS: This is 1 the first case series describing VV ECMO outcomes in COVID-19 patients. Our initial data suggest that VV ECMO can be successfully utilized in appropriately selected COVID-19 patients with advanced respiratory failure.

Open Tacking of a Migrated Thoracic Endovascular Aortic Graft.

Complications of thoracic endovascular aortic repair (TEVAR) are beginning to emerge as novel vascular issues. While endovascular solutions exist for most, some graft complications require a more traditional open solution. These operations are most commonly performed for endoleak or disease progression. Much less frequently observed is the migration of the endograft requiring open reintervention. Herein we present a case of a proximally migrated TEVAR graft, which required open fixation under deep hypothermic circulatory arrest (DHCA).

Emergent Transcatheter Aortic Valve Replacement for Aortic Insufficiency.

There are few case reports in the literature of transcatheter aortic valve replacement used as emergent therapy for aortic insufficiency. We present a case in which transcatheter aortic valve replacement was implemented successfully as a salvage therapy in a hemodynamically unstable patient having aortic insufficiency as a result of a torn bioprosthetic leaflet during an unrelated abdominal operation. The successful use of this technique in a noncardiac operating room allowed the patient to be placed on extracorporeal support and ultimately to be discharged home.

Normothermic Ex Vivo Heart Perfusion: Effects of Live Animal Blood and Plasma Cross Circulation.

Prolonged normothermic ex vivo heart perfusion could transform cardiac transplantation. To help identify perfusate components that might enable long-term perfusion, we evaluated the effects of cross-circulated whole blood and cross-circulated plasma from a live paracorporeal animal on donor porcine hearts preserved via normothermic ex vivo heart perfusion. Standard perfusion (SP; n = 40) utilized red blood cell/plasma perfusate and Langendorff technique for a goal of 12 hours. Cross-circulation groups used a similar circuit with the addition of cross-circulated venous whole blood (XC-blood; n = 6) or cross-circulated filtered plasma (XC-plasma; n = 7) between a live paracorporeal pig under anesthesia and the perfusate reservoir. Data included oxygen metabolism, vascular resistance, lactate production, left ventricular function, myocardial electrical impedance, and histopathologic injury score. All cross-circulation hearts were successfully perfused for 12 hours, compared with 22 of 40 SP hearts (55%; p = 0.002). Both cross-circulation groups demonstrated higher oxygen consumption and vascular resistance than standard hearts from hours 3-12. No significant differences were seen between XC-blood and XC-plasma hearts in any variable, including left ventricular dP/dT after 12 hours (1478 ± 700 mm Hg/s vs. 872 ± 500; p = 0.17). We conclude that cross circulation of whole blood or plasma from a live animal improves preservation of function of perfused hearts, and cross-circulated plasma performs similarly to cross-circulated whole blood.

Development of a Model of Pediatric Lung Failure Pathophysiology.

A pediatric artificial lung (PAL) is under development as a bridge to transplantation or lung remodeling for children with end-stage lung failure (ESLF). To evaluate the efficiency of a PAL, a disease model mimicking the physiologic derangements of pediatric ESLF is needed. Our previous right pulmonary artery (rPA) ligation model (rPA-LM) achieved that goal, but caused immediate mortality in nearly half of the animals. In this study, we evaluated a new technique of gradual postoperative right pulmonary artery occlusion using a Rummel tourniquet (rPA-RT) in seven (25-40 kg) sheep. This technique created a stable model of ESLF pathophysiology, characterized by high alveolar dead space (58.0% ± 3.8%), pulmonary hypertension (38.4 ± 2.2 mm Hg), tachypnea (79 ± 20 breaths per minute), and intermittent supplemental oxygen requirement. This improvement to our technique provides the necessary physiologic derangements for testing a PAL, whereas avoiding the problem of high immediate perioperative mortality.

Extracorporeal Support for Chronic Obstructive Pulmonary Disease: A Bright Future.

In the past the only option for the treatment of respiratory failure due to acute exacerbation of chronic obstructive pulmonary disease (aeCOPD) was invasive mechanical ventilation. In recent decades, the potential for extracorporeal carbon dioxide (CO2) removal has been realized. We review the various types of extracorporeal CO2 removal, outline the optimal use of these therapies for aeCOPD, and make suggestions for future controlled trials. We also describe the advantages and requirements for an ideal long-term ambulatory CO2 removal system for palliation of COPD.

Pediatric Artificial Lung: A Low-Resistance Pumpless Artificial Lung Alleviates an Acute Lamb Model of Increased Right Ventricle Afterload.

Lung disease in children often results in pulmonary hypertension and right heart failure. The availability of a pediatric artificial lung (PAL) would open new approaches to the management of these conditions by bridging to recovery in acute disease or transplantation in chronic disease. This study investigates the efficacy of a novel PAL in alleviating an animal model of pulmonary hypertension and increased right ventricle afterload. Five juvenile lambs (20-30 kg) underwent PAL implantation in a pulmonary artery to left atrium configuration. Induction of disease involved temporary, reversible occlusion of the right main pulmonary artery. Hemodynamics, pulmonary vascular input impedance, and right ventricle efficiency were measured under 1) baseline, 2) disease, and 3) disease + PAL conditions. The disease model altered hemodynamics variables in a manner consistent with pulmonary hypertension. Subsequent PAL attachment improved pulmonary artery pressure (p = 0.018), cardiac output (p = 0.050), pulmonary vascular input impedance (Z.0 p = 0.028; Z.1 p = 0.058), and right ventricle efficiency (p = 0.001). The PAL averaged resistance of 2.3 ± 0.8 mm Hg/L/min and blood flow of 1.3 ± 0.6 L/min. This novel low-resistance PAL can alleviate pulmonary hypertension in an acute animal model and demonstrates potential for use as a bridge to lung recovery or transplantation in pediatric patients with significant pulmonary hypertension refractory to medical therapies.

Achieving 12 Hour Normothermic Ex Situ Heart Perfusion: An Experience of 40 Porcine Hearts.

Although total body perfusion with extracorporeal life support (ECLS) can be maintained for weeks, individual organ perfusion beyond 12 hours has yet to be achieved clinically. Normothermic ex situ heart perfusion (ESHP) offers the potential for prolonged cardiac preservation. We developed an ESHP system to study the effect of perfusate variables on organ preservation, with the ultimate goal of extending organ perfusion for ≥24 hours. Forty porcine hearts were perfused for a target of 12 hours. Hearts that maintained electromechanical activity and had a <3× increase in vascular resistance were considered successful preservations. Perfusion variables, metabolic byproducts, and histopathology were monitored and sampled to identify factors associated with preservation failure. Twenty-two of 40 hearts were successfully preserved at 12 hours. Successful 12 hour experiments demonstrated lower potassium (4.3 ± 0.8 vs. 5.0 ± 1.2 mmol/L; p = 0.018) and lactate (3.5 ± 2.8 vs. 4.5 ± 2.9 mmol/L; p = 0.139) levels, and histopathology revealed less tissue damage (p = 0.003) and less weight gain (p = 0.072). Results of these early experiments suggest prolonged ESHP is feasible, and that elevated lactate and potassium levels are associated with organ failure. Further studies are necessary to identify the ideal perfusate for normothermic ESHP.

"Treating Lungs": The Scientific Contributions of Dr. Theodor Kolobow.

We are fortunate to live in an age in which biomedical technology has provided us with unprecedented ability to supplant the functions of organs and support the physiologic processes of the human body. Ingenious doctors, physiologists, and engineers helped create these advances with new and innovative ideas. One of these pioneers was Dr. Theodor Kolobow. He is best known for one of his earliest inventions, the spiral coil membrane lung. His contributions to medical innovation, however, are diverse, as he also contributed to advances in hemodialysis, improvements in extracorporeal life support technology/circuit components, and through his laboratory experiments helped shape our current understanding of cardiopulmonary pathophysiology. In retrospect, much of Kolobow's work was unified by the theme of preventing iatrogenic lung injury caused by mechanical ventilation. This tenet became more obvious as his later studies progressed to developing techniques and devices intended to limit ventilator pressures, and prevent bacterial colonization of the lungs. Although he formally retired from his research endeavors in 2009, the impact of his contributions remains prominent in our everyday use of techniques and equipment that he either originated or helped to develop.

Large Animal Model of Pumpless Arteriovenous Extracorporeal CO2 Removal Using Room Air via Subclavian Vessels.

End-stage lung disease (ESLD) causes progressive hypercapnia and dyspnea and impacts quality of life. Many extracorporeal support (ECS) configurations for CO2 removal resolve symptoms but limit ambulation. An ovine model of pumpless ECS using subclavian vessels was developed to allow for ambulatory support. Vascular grafts were anastomosed to the left subclavian vessels in four healthy sheep. A low-resistance membrane oxygenator was attached in an arteriovenous (AV) configuration. Device function was evaluated in each animal while awake and spontaneously breathing and while mechanically ventilated with hypercapnia induced. Sweep gas (FiO2 = 0.21) to the device was increased from 0 to 15 L/min, and arterial and postdevice blood gases, as well as postdevice air, were sampled. Hemodynamics remained stable with average AV shunt flows of 1.34 ± 0.14 L/min. In awake animals, CO2 removal was 3.4 ± 1.0 ml/kg/min at maximum sweep gas flow. Respiratory rate decreased from 60 ± 25 at baseline to 30 ± 11 breaths per minute. In animals with induced hypercapnia, PaCO2 increased to 73.9 ± 15.1. At maximum sweep gas flow, CO2 removal was 3.4 ± 0.4 ml/kg/min and PaCO2 decreased to 49.1 ± 6.7 mm Hg. Subclavian AV access is effective in lowering PaCO2 and respiratory rate and is potentially an effective ambulatory destination therapy for ESLD patients.