265CHAPTER 28 Cardiac Failure and Ventricular Assist Devices obesity are considered contraindications 242 Other considerations include thickness of the ventricular wall, semilunar valve regurgi tation[.]
CHAPTER 28 Cardiac Failure and Ventricular Assist Devices obesity are considered contraindications.242 Other considerations include thickness of the ventricular wall, semilunar valve regurgitation, and intracardiac shunts Thick ventricles (such as those in hypertrophic cardiomyopathy) can prevent proper filling of the VAD; these patients should be considered on a case-by-case basis.243 Significant aortic insufficiency (or pulmonary insufficiency) will not permit adequate emptying of the ventricle and often necessitates closure of the aortic valve at the time of VAD implantation Closure of intracardiac defects will prevent embolization of thrombus or air.244 Determining the most ideal time for VAD implantation remains a challenge The majority of pediatric implants are performed for INTERMACS level However, patients who are critically ill at the time of implant (INTERMACS and 2) have significantly increased 30-day mortality when compared with those at INTERMACS levels and Determining risk/benefit ratio of VAD implantation at more stable INTERMACS levels is a difficult but important multidisciplinary decision Standardizing intraoperative and postoperative management, management of right HF and pulmonary hypertension, and anticoagulation protocols have the potential to optimize outcomes It is important and often challenging to avoid initiating mechanical support too late Moderate end-organ dysfunction often improves with MCS, especially renal and hepatic dysfunction, but can be irreversible when aggressive treatment is not implemented in a timely manner.242,245 Basic Management of Ventricular Assist Device Patients Anticoagulation and Antiplatelets Patients assisted with VADs are not anticoagulated for the first 24 to 48 hours to decrease risk of bleeding The traditional first line of anticoagulation has been heparin UH is usually started when chest tube output is #2 mL/kg per hour, initial infusion dose is 10 U/kg per hour (range, 10–20 U/kg per hour) titrated to goal aPTT 60 to 80 seconds and/or anti-Xa targets of 0.35 to 0.50 U/mL Underlying coagulopathy or thrombocytopenia should be corrected as clinically indicated Bivalirudin, a direct thrombin inhibitor, has been used successfully in pediatric patients with VADs, with argatroban being the other alternative.169 Bivalirudin use has significantly decreased the number of pump changes and thromboembolic complications Initial dose of bivalirudin is 0.15 mg/kg per hour with a target PTT of 60 to 90 seconds.229,246 As in the initial EXCOR protocol, these infusions can be transitioned at to weeks to warfarin in the older patients and to enoxaparin in the younger patients Once the initial agent has achieved therapeutic levels in the context of good hemostasis, antiplatelet therapy is started The Edmonton protocol163 involves a three-drug regimen that includes aspirin, dipyridamole, and either warfarin or enoxaparin and long-term agents depending on the patient’s age This protocol was used as a guideline in the Berlin EXCOR Investigational Device Exemption (IDE) prospective trial.200 Despite the guideline, the prevalence of major bleeding was significant: 42% in patients with a BSA less than 0.7 m2 and 50% in patients with a BSA of 0.7 to 1.5 m2 Unfortunately, there was also a significant prevalence of thrombosis with a high incidence of stroke (29% in both cohorts) With the high thrombotic complications noted with the Edmonton protocol, a more aggressive antiplatelet regimen was introduced by the Stanford group The usual agents 265 include aspirin and dipyridamole, with the addition of a second antiplatelet agent, clopidogrel.247 These agents are often initiated in sequence Initial doses of aspirin include mg/kg per day divided into two doses, with maximal therapy at 30 mg/kg per day Initial doses of dipyridamole include 2.5 mg/kg divided times per day with a maximal therapy of 15 mg/kg divided times per day TEG and platelet function assays had been used as a guide to antiplatelet therapy but more recently have fallen out of favor given a high coefficient of variation of the assay as well as confounding technical issues.248 Implementation of each of these protocols is institution specific Understanding optimal anticoagulation and antiplatelet therapy in children on VAD support remains a significant challenge With continuous-flow devices such as the HeartMate II or III or HeartWare VAD, aspirin is usually the only antiplatelet therapy needed Acquired von Willebrand syndrome is common in patients with VADs; the loss of large von Willebrand factor (vWF) multimers is caused by excessive cleavage of vWF under the constant high shear forces associated with VADs These alterations in vWF structure and adhesive activity recover rapidly after VAD explantation.249 Bleeding due to acquired vWF syndrome is usually managed with cryoprecipitate or purified vWF concentrate Antibiotic Prophylaxis Patients who are scheduled for VAD implantation require an antiseptic bath with an agent such as chlorhexidine day prior to surgery, preferably the day of VAD implant Infection prophylaxis using broad-spectrum antibiotics and antifungal drugs is continued for 48 hours after the implantation Antifungal therapy is especially considered if the patient is on ECMO support prior to VAD implant for more than to days Care of the Drive Line and Cannulas To prevent infection of the cannula sites, dressing changes must be done in a sterile and consistent fashion The frequency of dressing changes is increased if there are signs of infection Following the use of sterile precautions, an antiseptic swab or scrub, such as chlorhexidine, is used to clean the exit site Primary dressing material that is silver impregnated and nonadherent is used, such as Telfa In the case of the Berlin EXCOR VAD, abdominal wound pads are placed to secure the cannulas For implantable intracorporeal devices such as the HVAD or HeartMate II, place the adhesive dressing (e.g., Covaderm) over the site, ensuring that the dressing is completely occluded on all four sides Ventricular Assist Device—Congenital Heart Disease and Single-Ventricle Physiology Outcomes for pediatric patients with dilated cardiomyopathy/ myocarditis on a VAD have always been significantly better than those for patients with CHD.250 Over the years, the outcome for biventricular CHD has continued to evolve but one of the biggest challenges has been the support of patients with single-ventricle physiology Two general categories of patients with single-ventricle physiology may require MCS: those prior to palliative surgery but without complete separation of the systemic and pulmonary circulation and those who are post-Fontan in whom all systemic venous return flows passively into the pulmonary circulation In 266 S E C T I O N I V Pediatric Critical Care: Cardiovascular the first group, inflow is provided from the single ventricle with outflow to the ascending aorta, and pulmonary blood flow is maintained via a systemic-to-pulmonary artery shunt or a bidirectional Glenn shunt In patients with a failing Fontan, cardiac failure may result from primary ventricular dysfunction, producing high Fontan pressures or from failing Fontan physiology (preserved ventricular function but moderate to severe elevation of pulmonary vascular resistance), yielding chronic elevation of pressures in the Fontan pathway and sequelae of HF In patients with primary ventricular dysfunction and normal pulmonary vascular resistance, care for the failing physiology has been increasingly successful Some centers have used the pulsatile Berlin EXCOR for support, and others have used continuousflow devices such as the HeartWare VAD or HeartMate III.251,252 A subanalysis of the EXCOR IDE database identified that 26 out of 281 patients supported with VAD had single-ventricle physiology; fewer single-ventricle patients were bridged to transplant or recovery when compared with those with biventricular physiology, out of supported after stage I palliation survived, and out of patients with total cavopulmonary anastomosis were successfully bridged to transplant.247–253 In the setting of failing Fontan physiology, cannulation choices are more challenging If elevated pulmonary vascular resistance leads to systemic venous hypertension, then a second VAD may be required to support flow through the pulmonary circulation.114,254 As experience continues to grow, the outcome of failing Fontan circulation patients supported with VADs continues to improve.252 In contrast, the care of single-ventricle infants prior to and after stage I palliation continues to be challenging Postcardiotomy salvage VAD (postcardiotomy ECLS to durable VAD) in congenital heart surgery has dismal outcomes.235 Conway et al evaluated the Berlin EXCOR VAD in children weighing 10 kg or less Patients with HF in the context of CHD had worse outcomes, and none of the patients below kg with CHD who required ECLS support before VAD implantation survived.204 Some centers not offer VADs to patients with single-ventricle CHD and opt to support these children with ECLS or a combination of advanced inotropic support and mechanical ventilation Nevertheless, there are several case reports describing the use of VAD support for single-ventricle HF At our center, we have palliated patients with failing single-ventricle physiology in the context of hypoplastic left heart, with a combination of hybrid palliation for pulmonary blood flow and placing the single VAD with the outflow in the PA and inflow from the right atrium.202 We have used this strategy in close to 10 patients with approximately 60% survival to discharge Gazit et al reported a case series of seven patients with single-ventricle physiology after stage I palliation supported with MCS using a centrifugal extracorporeal pump The pump was attached to the cardiac chambers using the cannulas for a durable VAD The median support duration was 64 days Complications included a neurologic event in one patient and reoperation from bleeding in two; 43% of the supported patients were successfully discharged home.255 As more centers continue to support an increasing number of infants with singleventricle physiology, their combined experience continues to grow, with the final frontier being an implantable continuousflow VAD in these patients Outcomes PediMACS, the pediatric component of INTERMACS, presented all pediatric data (patients ,19 years) from September 2012 to December 2017.256 Thirty hospitals implanted 508 devices in 423 patients aged younger than 19 years (Figs 28.10and 28.11) Diagnoses included cardiomyopathy (62%), myocarditis (11%), and CHD (20%) Notably, 52 of these 86 patients with CHD had single-ventricle physiology LVAD support predominated in 81% and BiVADs in 15%; 80% of the patients were alive on device or bridged to transplant at months The patients with an implantable continuous-flow (IC) pump were older, age at implant, 13.4 3.8 years with only 12% having CHD They were significantly different from the paracorporeal continuousflow (PC) pump cohort (n 79; age, 3.9 5.2 years; 86% intubated at implant and 38% with CHD) and the paracorporeal PediMACS prospective implants: September 19, 2012 - December 31, 2017 cumulative hospital, patient, and device enrollment counts 500 Cumulative frequency Devices (n = 508) Patients (n = 423) 400 Hospitals (n = 30) 300 200 100 Jul 2012 Jan 2013 Jul Jan 2014 Jul Jan 2015 Jul Jan 2016 Jul Jan 2017 Jul Jan 2018 Implant date • Fig 28.10 PediMACS enrollment (From Morales D, Rossano J, VanderPluym C, et al Third Annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) Report: Preimplant characteristics and outcomes Ann Thorac Surg 2019;107:993–1004.) CHAPTER 28 Cardiac Failure and Ventricular Assist Devices Kaplan-Meier survival on a device by PediMACS overall (n = 423) Coverage: September 19, 2012 - December 31, 2017 100% 90% PediMACS (n = 423, Deaths = 86) 80% % Survival 70% 60% 50% 40% 30% 20% 10% 0% At Risk: 423 96 39 10 11 12 Months after device implant Shaded areas indicate 70% confidence limits P value (log-rank) = N/A Event: Death (censored at transplant or recovery) A Kaplan-Meier survival on a device by age group (n = 423) Coverage: September 19, 2012 - December 31, 2017 100% 11–19 years (n = 184, Deaths = 26) 90% 80% 6–11 years (n = 71, Deaths = 18 % Survival 70% 60% 1–6 years (n = 79, Deaths = 15) 50% < year (n = 89, Deaths = 27) 40% 30% At Risk: 184 71 79 89 20% 10% 0% 51 23 13 29 8 10 11 12 Months after device implant Shaded areas indicate 70% confidence limits P value (log-rank) = < 0001 Event: Death (censored at transplant or recovery) B Kaplan-Meier survival on a device by device class (n = 397) Coverage: September 19, 2012 - December 31, 2017 100% Implantable continuous (n = 197, Deaths = 23) 90% Paracorporeal pulsatile (n = 121, Deaths = 29) 80% % Survival 70% 60% Paracorporeal continuous (n = 79, Deaths = 23) 50% 40% 30% 20% 10% 0% At Risk: 198 79 120 68 23 36 1 10 11 12 Months after device implant Shaded areas indicate 70% confidence limits P value (log-rank) = < 0001 Event: Death (censored at transplant or recovery) C • Fig 28.11 (A) Kaplan-Meier survival curve for overall PediMACS group of 423 patients receiving implants September 2012 to December 2017 (B) Age at implant (C) Device type 267 268 S E C T I O N I V Pediatric Critical Care: Cardiovascular Kaplan-Meier survival on a device by patient profile (n = 421) Coverage: September 19, 2012 - December 31, 2017 100% 4–7 Resting symptoms or less sick (n = 7, Deaths = 0) Progressive decline (n = 232, Deaths = 33) 90% 80% Stable but inotrope dependent (n = 44, Deaths = 7) % Survival 70% 60% 50% 40% 30% 20% 10% 0% Critical cardiogenic shock (n = 138, Deaths = 45) At Risk: 44 323 138 15 55 21 24 10 11 12 Months after device implant Shaded areas indicate 70% confidence limits P value (log-rank) = < 0001 Event: Death (censored at transplant or recovery) D • Fig 28.11 cont’d (D) Interagency Registry for Mechanically Assisted Circulatory Support profiles (From Morales D, Rossano J, VandePluym C et al Third Annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) Report: Preimplant characteristics and Outcomes Ann Thorac Surg 2019;107:993-1004.) pulsatile (PP) pump cohort (n 121; age, 3.3 3.9 years; 77% intubated at implant and 21% with CHD) Diagnoses leading to pediatric heart transplantation are age specific and have also changed over time CHD remains the most common cause of HF leading to heart transplantation in infants but has significantly decreased, whereas cardiomyopathy is increasing Unfortunately, infants have the highest waiting period owing to lack of available organs and have the highest waitlist mortality.203,257 Analysis of the Pediatric Heart Transplant Study (PHTS) registry demonstrated an overall survival of 83% at years after transplantation.258 Renal failure, ECLS at time of listing, and ECLS at time of transplantation were correlated with worse outcomes A review of the UNOS database140 demonstrated improved survival when patients were supported with VADs Currently, the use of ECLS as a primary means of mechanical support and a bridge to cardiac transplantation is minimal, approximately 4% of all patients listed for transplant Unlike ECLS, duration of support is not a risk factor for worse outcomes in patients bridged to transplant with VADs Intraaortic Balloon Pump and Impella Device Since its invention and introduction into clinical practice in the 1960s, intraaortic balloon pumps (IABPs) have become a therapeutic tool for the management of refractory low CO states in adults In 1980, Pollock first described the use of an intraaortic balloon pump in pediatric patients with the advent of modified equipment and pediatric-sized balloon catheters The IABP is a polyethylene balloon mounted on a catheter, which is usually inserted into the aorta via the femoral artery The balloon is guided into the descending thoracic aorta 2 cm from the subclavian artery The balloon pump works by inflating during diastole (after aortic valve closure) for improved retrograde coronary flow augmentation, the balloon then deflates before systole to decrease LV afterload CO may be augmented by as much as 40%, decreasing LV stroke work and myocardial O2 requirements The pump is available in a wide range of sizes (2.5–50.0 mL) and is driven by an external console Advantages of the IABP include its relative ease of use and its placement without surgical dissection Disadvantages include infrequency of use, limitations of an isolated LV support modality, contraindication with certain anatomy/physiology (e.g., patent ductus arteriosus or aortic insufficiency), and serious complications that include mesenteric ischemia and arterial injury In children, failure to augment CO can occur owing to a highly elastic aorta Pediatric IABP catheters differ from adult catheters in a variety of ways The catheter shafts are smaller (4 or Fr) with balloon sizes of 0.75 to 10 mL Early failed reports of the use of IABP in children were primarily owing to the use of inappropriately sized balloons and failure to gate to the ECG at fast HRs Adequate timing of balloon inflation and deflation is essential Radial artery tracings were used in the past to aid timing of balloon inflation, but rapid HRs led to significant timing errors The use of M-mode echocardiography to aid in timing of balloon inflation and deflation with aortic valve opening and closing has significantly improved the efficiency of IABP therapy.263,264 A retrospective multicenter review of the use of the Impella device (Abiomed) from 2009 to 2015 in pediatrics was done across 16 centers The Impella device is a percutaneously transfemorally inserted microaxial LVAD that drains the LV distally and perfuses the aorta proximally A total of 39 implants were performed in 38 patients with a median duration of support of 45 hours Median age was 16 years (range, 4–21 years) Survival was 85% at days and 68% at 30 days The primary indication for implant was cardiogenic shock (n 28) Myocarditis, cardiomyopathy, and cardiac allograft rejection were the most common underlying diagnoses; 11 patients had CHD The majority of the patients recovered while almost half were transitioned to another device; one patient underwent heart transplantation and five patients died In the majority (n 16), function recovered, 12 patients were transitioned to another device, 11 patients died, and underwent heart transplantation An increase in aortic regurgitation was noted in three patients, without evidence of valve injury Major CHAPTER 28 Cardiac Failure and Ventricular Assist Devices complications occurred, including hemolysis (n 3), bleeding (n 2), stroke (n 1), sepsis (n 1) and critical leg ischemia (n 1).265 Emerging data indicate that the use of this form of temporary MCS in pediatric and adolescent patients can be successfully accomplished.266 Current Perspective and Future Directions VA ECLS or temporary VADs should be considered in the acute setting, after cardiac surgery, for impaired cardiac function, or when respiratory function is compromised If recovery is not promptly achieved, conversion to long-term VAD support is strongly recommended There is evidence of higher posttransplantation mortality in patients supported with VA ECLS compared with those with VAD support irrespective of the diagnosis.259 INTERMACS reported a changing pattern in MCS intent, with an increasing number of patients now receiving an implant under destination therapy indications There are multiple reasons for this trend, including a limited donor pool, improved patient selection for LVAD therapy, and increased number of VAD implant centers The growing population of patients supported by durable MCS devices has had an important effect on the infrastructure required to manage patients outside of the implanting hospital and on costs to the healthcare system According to the 2018 International Society for Heart and Lung report, 30% of pediatric heart transplant recipients from January 2009 to June 2017 were bridged using MCS The majority of the patients (18.8%) were bridged on LVAD alone.260 The superiority of VAD support compared with traditional ECLS among patients awaiting transplantation is evident from a study by the PHTS group demonstrating a survival of 56% a year after listing in the ECLS group versus 78% in those not on ECLS at the time of listing The data emphasize the poor outcome of patients who require ECLS and the need to reevaluate organ allocation for these high-risk patients.261 Furthermore, the survival of patients bridged with VADs compared equally to those bridged with medical therapy alone, while the survival of patients bridged on ECLS was lower.260 Despite the tremendous improvement in pediatric MCS, patients remain at risk for morbidity from thrombotic complications Thromboembolic strokes are twice as frequent as intracranial hemorrhagic events.258 Options for circulatory support of pediatric patients under the age of years are still limited to Berlin EXCOR The need for devices suitable for small patients has been addressed by the National Heart, Lung, and Blood Institute (NHLBI), with funding of research aiming for the development of mechanical support devices for children from to 25 kg with congenital or acquired cardiovascular disease In 2004, the Pediatric Circulatory Support Program,262 which is the predecessor to the PumpKIN program launched by the NHLBI, funded five novel pediatric circulatory support devices Only one investigational device remains currently funded in the PumpKIN trial: the Infant Jarvik 2015 VAD The development pathway of pediatric continuous-flow VADs has been challenging at many different levels As a result, it took more than a decade to reach the point that the Infant Jarvik was ready to be tested in a clinical trial Careful consideration was 269 given to the weight range for participants, with a final decision to include children in a weight range between to 20 kg The lower limit of kg was chosen based on the expected flow range (1200 mL/min 150 mL/kg kg).224 Although advances in medical management, surgical techniques, and MCS for pediatric patients with cardiomyopathy or congenital heart defects continue to improve outcomes, morbidity and mortality related to pediatric HF continue to exist Overall quality of life can be adversely affected in some patients owing to therapy-related complications In addition, caregivers of these patients may experience significant burden owing to posttraumatic stress disorder, anxiety, depression, or poor physical health Conclusions Implementation of MCS requires an individualized approach Indications include a variety of disease processes leading to LCOS, such as myocarditis, septic shock, and surgery to repair congenital heart defects Short-term experience with mechanical devices had been limited to ECLS, but pediatric experience with temporary and long-term VADs is growing Early institution of ECLS and transition to a VAD are necessary to avoid irreversible organ failure Pediatric MCS has demonstrated a number of significant advances in patients with refractory cardiogenic shock However, the limited options for mechanical support of the failing circulation in small children continue to be a challenge Despite positive outcomes, several significant complications remain, including bleeding, stroke, and infection Patient selection, timing of support, device selection, and perioperative care continue to be critical components in a successful outcome for these patients Key References Ouweneel DM, Schotborgh JV, Limpens J, et al Extracorporeal life support during cardiac arrest and cardiogenic shock: a systematic review and meta-analysis Intensive Care Med 2016;42:1922-1934 Lomivorotov VV, Efremov SM, Kirov MY, Fominskiy EV, Karaskov AM Low-cardiac-output syndrome after cardiac surgery J Cardiothorac Vasc Anesth 2017;31:291-308 Roeleveld PP What is new in pediatric ECMO? 2016, a year in review Eur J Heart Fail 2017;19(suppl 2):92-96 Buck ML Bivalirudin as an Alternative to heparin for anticoagulation in infants and children J Pediatr Pharmacol Ther 2015;20:408-417 Yarlagadda VV, Maeda K, Zhang Y, et al Temporary circulatory support in U.S children awaiting heart transplantation J Am Coll Cardiol 2017;70:2250-2260 Lorts A, Eghtesady P, Mehegan M, et al Outcomes of children supported with devices labeled as ‘temporary’ or short term: a report from the Pediatric Interagency Registry for Mechanical Circulatory Support J Heart Lung Transplant 2018;37:54-60 Horne D, Conway J, Rebeyka IM, Buchholz H Mechanical circulatory support in univentricular hearts: current management Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2015;18:17-24 The full reference list for this chapter is available at ExpertConsult.com ... placing the single VAD with the outflow in the PA and inflow from the right atrium.202 We have used this strategy in close to 10 patients with approximately 60% survival to discharge Gazit et al reported... INTERMACS, presented all pediatric data (patients ,19 years) from September 2012 to December 2017.256 Thirty hospitals implanted 508 devices in 423 patients aged younger than 19 years (Figs 28.10and... Implant date • Fig 28.10 PediMACS enrollment (From Morales D, Rossano J, VanderPluym C, et al Third Annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) Report: