CCAS 2020 Annual Meeting Review
Session 1: Innovations in Pediatric Ventricular Assist Device Management: What’s New in 2020?
By Sana Ullah, MB, ChB, FRCA
The first morning session, “Innovations in Pediatric Ventricular Assist Device Management: What’s New in 2020?”, was moderated by James Spaeth, MD of Cincinnati Children’s Hospital. This was a series of five excellent talks discussing the medical, surgical, and anesthetic considerations for this complex and high-risk group of patients. It is clear that ventricular assist devices (VADs) will play an increasing role in the management of children with end-stage or acute heart failure, and pediatric cardiac anesthesiologists will see increasing numbers of these patients in their practices.
The first talk “Management of Heart Failure with a VAD: Indications and Preoperative Considerations” was given by Dr. Joseph Rossano, who is Chief of Cardiology at the Children’s Hospital of Philadelphia. This presentation set the scene for subsequent talks by discussing the epidemiology of heart failure in children, indications for mechanical support and, most importantly, the timing of initiating VAD support as this strongly impacts the outcome of post-transplant survival.
Dr. Rossano presented adult data that shows a steady increase in projected heart failure prevalence such that by 2030 there will be 8 million adults with heart failure with a parallel increase in the cost of healthcare of around $70 billion. In adults, the major causes of heart failure are coronary artery disease, hypertension, and valvular disease. There is also a slower but steady increase in heart failure admissions in children. The relative proportions of the causes of heart failure in children have essentially remained unchanged – approximately 70% from congenital heart disease (CHD), 15% from cardiomyopathy, and about 3% from myocarditis.
Comparing advanced therapies for heart failure between children and adults; transplants, VADs, and extracorporeal membrane oxygenation (ECMO) are used much more frequently in children. In the current era, 2010-2018, mechanical circulatory support (MCS) is used in the vast majority of children as a bridge to transplant, although fewer patients with CHD were supported with VADs than those with dilated cardiomyopathy (DCM). In infants where there are limited options for durable VADs, about equal numbers were bridged with VADs or ECMO. In older children with dilated cardiomyopathy (DCM), ECMO was only used in about 3% of patients compared to MCS devices, which were used in over 50% of patients as a bridge to transplant. In-hospital mortality for children with advanced heart failure from CHD is approximately 30% with infants and single-ventricle patients forming the highest risk groups.
Dr. Rossano then discussed factors that affect outcomes from acute heart failure. Acute heart failure can be categorized into four clinical profiles based on the presence or absence of increased filling pressures (“wet” and “dry”) and whether there is adequate or compromised tissue perfusion (“warm” and “cold”).
A 2017 study of children on the transplant waiting list showed that the highest mortality was in the category of those with both congestion and low cardiac output. Medical therapy is always first line but comes at a significant cost of increasing myocardial oxygen consumption and increased vascular resistance with milrinone having the least detrimental effects. Once medical therapy - which may include escalating respiratory support - is maximized, the key question then becomes when to institute MCS to prevent cardiovascular collapse.
The important guiding principle of MCS should be to have the best possible outcome AFTER the transplant, not merely survival TO transplant. He presented compelling evidence that pre-transplant morbidity strongly influences post-transplant outcomes. Placing a Ferrari engine into a 20-year-old Camry is unlikely to have a good result. Key points were: (1) Survival after VAD placement is much better in patients who are stable but inotrope dependent versus those in cardiogenic shock; (2) Mortality is worst in patients on ECMO or ECMO+VAD versus VAD alone or no VAD; (3) Patients on mechanical ventilation had significantly worse outcomes compared with no mechanical ventilation.
In concluding his talk, Dr. Rossano emphasized that MCS is invaluable in improving the functional status and survival of patients before and after transplant. However, early implantation is important before the onset of multisystem organ failure.
The next presentation “Picking the Right MCS Device for Children” was given by Dr. David L. S. Morales, who is the Director of Congenital Heart Surgery at Cincinnati Children’s Hospital Medical Center. The central message was that “timing is everything” when considering MCS for acute heart failure. Each center needs to have realistic expectations of outcomes based on their experience and the devices available to them.
Dr. Morales suggested that the tendency is to wait too long based on the perception that instituting MCS too early may lead to more device-related complications. Too often; however, this leads to sequential multiple organ dysfunction, poor nutrition, and general debilitation, such that at the time of transplant the patient is in a very sub-optimal state which leads to poor post-transplant outcomes.
In a 2019 study based on a United Network for Organ Sharing (UNOS) database, the Cincinnati group compared one-year post-transplant survival in pediatric patients with non-modifiable (age, diagnosis) and modifiable (or potentially modifiable) risk factors (renal dysfunction, hepatic dysfunction, and mechanical ventilation). Patients with no modifiable risk factors had a one-year survival of 93%. The addition of each modifiable risk factor resulted in a cumulative decrease in survival. For example, mechanical ventilation alone reduced the survival to 76% (odds ratio of 4); while mechanical ventilation and hepatic dysfunction and renal dysfunction reduced survival to 60% at one year (odds ratio 8.3).
In another UNOS database study, the same group showed that the use of VADs resulted in a 50% decrease in wait-list mortality. In addition, children bridged with VADs, even though they were sicker, had similar outcomes as those children without a VAD. Dr. Morales emphasized that programs should consider VAD placement early before the onset of multi-system organ dysfunction and that “limping to transplant” is not a good strategy.
If a patient is in heart failure on inotropic therapy, then evidence of one other organ dysfunction should prompt the consideration for VAD placement. The choice of device depends on the patient’s diagnosis, age, and size as well as the institution’s experience and device availability. VADs can be broadly categorized into “short-term” support and “long-term” or “durable” support. Dr. Morales presented a comprehensive algorithm outlining the decision-making process in choosing the appropriate device. If there is reasonable expectation that myocardial recovery will take place in less than two weeks, then a temporary VAD such as a PediMag/CentriMag, Rotaflow, or Impella is appropriate. For long-term support the two most common devices currently being used are the Heartware LVAD and the Heartmate 3, both of which are centrifugal flow devices.
The Syncardia Total Artificial Heart replaces both atria and ventricles but is a large device suitable only for patients with a body surface area (BSA) over 1.5 and an antero-posterior thoracic distance of 10 cm at the 10th thoracic vertebra. The most difficult population of patients is those between 15 – 25 kgs. The Berlin EXCOR is generally accepted as primary therapy for children under 15 kg, although many centers are moving towards continuous flow devices such as PediMag or Rotaflow.
The relatively new Heartmate 3 is being increasingly used but the lower size limit is not clear at this time. Up until recently, BSA has been used for determining device-patient match. However, BSA is a relatively crude measure, particularly in the “gray zone “of 15-25 kg. Dr. Morales described the use of 3D CT imaging and virtual reality technology in visualizing and determining the optimal fit of device to patient.
As device technology improves and experience increases, VADs will find expanding uses. Dr. Morales concluded the presentation by showing several case studies of VAD use in single-ventricle patients, which are very challenging due to their unique anatomy. Many institutions are now also offering VADs as destination therapy to patients with Duchenne muscular dystrophy with fairly impressive results of improvement in quality of life despite the very high-risk nature of this undertaking.
The take-home message of this talk was to consider VAD placement early before the onset of organ dysfunction so that the patient is in the most optimized condition at the time of transplant for the best post-transplant outcomes.
The next talk titled, “Anesthesia for Implantation of a Ventricular Assist Device”, was given by Dr. Claire Barker, who is a Consultant Anesthetist at the Freeman Hospital in Newcastle, UK. They have one of the largest experiences in the UK with pediatric VADs and transplants.
Dr. Barker gave an excellent overview of the role of the anesthesia team in the perioperative management of these critically ill patients. She emphasized the importance of the anesthesia team being actively involved in the decision-making process from the outset. The key points of this talk were; (1) Maintaining hemodynamic stability during anesthesia induction and the pre-bypass phase; (2) Optimizing hemodynamics and VAD function during separation from bypass and (3) Assessing and optimizing right ventricular (RV) function and determining the need for a right ventricular device (RVAD) if there is intractable RV failure.
Preparations should be made for cardiovascular collapse during anesthesia induction and intubation with the immediate availability of the cardiac surgeon and an ECMO circuit with the appropriate peripheral cannulas if immediate sternotomy is not feasible, such as in re-do sternotomy operations. Ketamine was the most commonly used induction agent in their experience. Once the LVAD is placed, the transition from bypass can be fraught with hemodynamic instability and should be carried out in a controlled and systematic fashion by assessing inflow, pump parameters, outflow, and RV function.
The anesthesiologist must process information from the perfusionist, the VAD specialist, the surgeon, and the echocardiographer to optimize the hemodynamics and device function. For continuous flow VADs, the only programmable parameter is the revolutions per minute (RPM). For intracorporeal pumps, such as the Heartware and Heartmate 2 and 3, the flow rate on the display is a calculated number based on the RPM’s and power. In contrast, with the extracorporeal continuous flow devices such as the PediMag, the flow is actually measured with a flow probe and gives a much more accurate assessment of cardiac index.
Echocardiography is critically important in optimizing baseline VAD parameters. As VAD flow is gradually increased, the position of the ventricular septum is carefully assessed. It should stay in the neutral position. If the septum is bowing into the LV, this suggests inadequate preload to the VAD or too high RPM’s leading to excessive unloading of the LV. This will also impact RV function by reducing the contribution of the ventricular septum to RV contraction as well as worsening tricuspid regurgitation.
Echocardiography is also important in checking that the inflow cannula at the LV apex is as parallel to the ventricular septum as possible to avoid “sucking” in the ventricular septum, which can cause arrhythmias and reduce pump preload. Afterload must be balanced to provide adequate perfusion pressures but not too high that it reduces VAD flow. A high systemic vascular resistance will also increase the risk of stroke and surgical bleeding. The mean arterial pressures should be appropriate to the patient’s age and size. Unexpected hypoxemia may indicate an unrecognized right to left shunt such as an atrial septal defect which will need repair.
Although RV dysfunction is quite common after left ventricular assist device (LVAD) (approximately 55% in a recent study), the actual need for an RVAD is relatively small – about 4% in the same study. RV failure leads to significant morbidity and every effort should be made to optimize RV function by optimizing preload, RV contractility, and reducing afterload (ventilatory maneuvers, milrinone, inhaled nitric oxide). Many of these patients will need cardiac and non-cardiac surgical procedures and Dr. Barker emphasized that it is important to have a systematic approach to device management during the perioperative period – consider inflow, pump function, outflow, and RV function. Other important perioperative considerations include anticoagulation management, induction, type of airway and ventilation strategy, and intraoperative monitoring (invasive vs non-invasive).
Dr. Joseph Rossano discussed the important and complex problem of anticoagulation in VAD patients in the next talk “New Approaches to Anticoagulation in Pediatric VAD Patients”. All VAD patients need anticoagulation but balancing the risk of thromboembolism against the risk of bleeding is very challenging.
The most devastating complication of VADs is stroke, which occurred in a third of patients in the original Berlin EXCOR trial in the US. That trial required anticoagulation using the “Edmonton Protocol” and using thromboelastography with platelet mapping to titrate the dose of anti-platelet medications. However, it has been shown that there is a weak correlation between aspirin and dipyridamole doses and percentage inhibition of arachidonic acid and adenine diphosphate respectively (LJ May, JHLT, 2019).
An alternative protocol (Stanford Guidelines) uses weight-based dosing and includes the addition of steroids if there is evidence of inflammation. This approach has resulted in significant reduction in stroke rates. Dr. Rossano also discussed several alternatives to heparin; the direct thrombin inhibitors bivalirudin and argatroban. These work independently of antithrombin, have a short half-life, and are easily titratable. He also mentioned one of the new direct oral anticoagulants, rivaroxaban, and its reversal agent, andexanet, which are currently undergoing clinical trials.
Finally, Dr. Rossano discussed improvements in anticoagulation by the use of dedicated “anticoagulation teams” consisting of specialists in hematology, intensive care, cardiology and VAD specialists.
The final talk of the VADs session was given by Dr. Morales, titled “ACTION: Learning Network for Pediatric VADS”. This was an excellent presentation describing a different approach to improving outcomes in pediatric patients with VADs. ACTION is the acronym for Advanced Cardiac Therapies Improving Outcomes Network. It was established in April 2017 with the mission to “improve critical outcomes and the patient/family experience for children with heart failure by developing an international collaborative learning health network that unites all key stakeholders (patients, families, providers, researchers, industry, and regulatory bodies)”.
It is not a registry, which is essentially a repository of data for specific patient groups or conditions. Currently there are almost 40 institutions in the network. ACTION came about through evidence showing vast differences in outcomes across many institutions with VAD programs stemming from small numbers of patients and wide variations in practice.
No single institution will be able to accrue enough clinical experience in a timely fashion to affect clinical practice and improve outcomes. Therefore, one of the key activities of the ACTION network is to conduct collaborative quality improvement (QI) projects across the whole learning system.
As an example, Dr. Morales described the first QI initiative to reduce the rate of strokes in patients with VADs. A quality improvement bundle was developed to standardize anticoagulation using bivalirudin, standardize blood pressure measurement and control within narrow parameters, and collect data using a standardized tool. As a result, there was an impressive reduction in the rate of strokes in continuous flow VADs. All this was achieved in less than two years. This is in contrast to the standard clinical trial protocol which can take more than a decade to affect clinical practice.
More information and resources can be found on the ACTION webpage: actionlearningnetwork.org
Overall, the morning session on VADs was an excellent update on a rapidly expanding field with new devices being trialed, such as the Jarvik 2015, and VADs being used in more challenging patient populations such as the single ventricle and muscular dystrophy patients.