Heart failure in the young: Insights into myocardial recovery with ventricular assist device support.

BACKGROUND: Data on ventricular unloading-promoted myocardial recovery and post-weaning outcome in children is scarce. We analyzed the weaning outcome in children with heart failure (HF) supported with ventricular assist device (VAD). METHODS: A multi-institutional data on VAD implanted in 193 children and adolescents with HF between April 1990 and November 2015 was reviewed. Among them, 25 children (mean age 3.4±3.0, range, 0.058-16.3 years, 15 females) were weaned from VAD. Etiology of HF were myocarditis (n=11), dilated cardiomyopathy (DCMP) (n=7), ischemic HF (n=3), arrhythmogenic CMP (n=1), post-correction of congenital heart disease (CHD) (n=1) and acute graft failure (n=1). Mean duration of HF before VAD implantation was 59.4±3 days. RESULTS: Age, duration of HF, DCMP, cardiac arrest and duration of VAD are essential clinical characteristics to delineate who may have the potential to myocardial recovery. Echocardiographic parameters pre-implantation, during the final off-pump trial and during the post-explantation follow-ups revealed that LVEF, LVEDD and relative wall thickness (RWT) showed significant differences (P<0.001) among patients stratified by outcome to assess recovery. Presently, 21 (84.0%) of the weaned patients are alive with their native hearts 1.3-19.1 years after VAD explantation. An additional weaned patient had HF recurrence 3 months post-weaning and was transplanted. CONCLUSIONS: Post-weaning myocardial recovery and cardiac stability of children with HF from several etiologies supported with a VAD appears sustainable and durable. Young patients with short HF duration are more likely to recover. Absence of cardiac arrest, cardiac size, geometry and function may prospectively identify patients who may be likely to have myocardial recovery.

Resumé of the challenges and burden of living with transplanted hearts for >31 years.

Heart transplantation has extended the lives of many patients with end-stage heart failure. Although beset with the arduous aftermaths of immunosuppression, those who survived live meaningful lives similar to that of the general population. In this series, heart transplantation has led to a considerable extension of life span of >31-34 years. Development of cardiac allograft vasculopathy is a major concern in the long-term follow-up of transplant patients. Immunosuppressive drugs have a major impact on the development and progression of cardiac allograft vasculopathy and the main cause of cardiac allograft loss after the first post-transplantation year. Post-transplant neoplasia remains a challenging long-term problem for patients after orthotopic heart transplantation. Post-transplant lymphoproliferative disease appears to be largely the result of the effectiveness of current agents used for long-term immunosuppression, and the neoplasms typically harbor the Epstein Barr virus genome, which is presumed to play a major role in neoplastic transformation. Post-transplantation, new diseases may occur or there may be worsening of pre-existing diseases. By the end of the 5th year, all suffered from hypertension. Renal insufficiency developed within 5 years after transplantation, and 10% have a creatinine value of >2.5 mg/dL. Hyperlipidemia, mostly hypercholesterolemia occurs especially in patients on tacrolimus or everolimus. Quality of life is not impaired despite somatic problems. In this period >31 years post-post-orthotopic heart transplantation, they even reported a surprising increase in their emotional well-being. The 10 patients are active and satisfied with their daily lives. They regard their own life as meaningful, have good families and active social relations. Nonetheless, it is burdened by chronic allograft vasculopathy and immunosuppression sequelae, the main limiting factors for survival, which needed to be constantly addressed throughout their lifetime. This brief report provides an insight into the challenges and burden patients living >31 years with transplanted hearts are confronted with.

Evolution of heart transplantation since Barnard's first.

Barnard's first human heart transplantation in 1967 has paved the channel to numerous extensive researches and clinical experiences, mostly from the Stanford group, on orchestrating criteria for donor and recipient selection, immunosuppression, distant heart procurement, re-transplantation, and further global performance of the procedure until it became the gold standard therapy for end-stage heart failure, even in the face of an utterly limited organ availability. Much has happened since Barnard's first. There has been a rapid rise to 4,000-5,000 transplants per year. Previously, the number of transplants depended on the capacity of the units. Later on, it depended largely on the availability of donor organs. The widening of indications and reduction of contraindications to heart transplantations to include elderly patients >70 years, systemic diseases such as amyloidosis, has emerged. Indeed, heart transplantation has come a long way, and is considered a fruitful and stimulating episode in modern medicine. It is rather deplorable to watch that in the beginning of 1990s, the yearly number of heart transplantations began to decline-not because the operation had proved unsuccessful, but because donor hearts became scarce. It is rather poignant that although science and technology as well as increased experience accumulated over a long time have paved the way to make such an operation possible, its applicability is limited by lack of public awareness or its unwillingness to agree to organ donation. The average transplant survival is now over 10 years. Its prevalence and success, however, belies the fact that over 52 years ago, no one had ever attempted the procedure in man and that the procedure seemed destined for ignominy and failure just a year after the first transplant. Had it not been for the work of a few scientists and physicians, each who stepped on the broad shoulders of those who had come previously, the history of heart transplantation would be nothing more than a few legends and myths in dusty tomes.

The role of ventricular assist device in children.

The first and successful implantation of a ventricular assist device in 1990 has allowed an 8-year-old child with an end-stage heart failure to undergo a heart transplantation. This milestone paved the way to consider support with ventricular assist in the armamentarium of heart failure management in infants, children and adolescents. Several systems have evolved and faded owing to unacceptable complications. Indications and contraindications to implantation have been established. Anticoagulation management is still on its way to impeccability. Despite the challenges, issues and concerns revolving around ventricular assist devices, the system definitely supports pediatric patients with end-stage heart failure until heart transplantation and could allow recovery of the myocardium.

Organ-saving surgical alternatives to treatment of heart failure.

Over time, various surgical treatment strategies have evolved to manage advanced heart failure (HF). Scientific and technological breakthroughs through the last 50 years have put forward various surgical alternatives to patients with advanced HF encompassing surgical ventricular restoration to surgical gene therapy and stem cell replacement of the diseased ventricles. Organ-saving surgical options which used to be promising included dynamic cardiomyoplasty, partial resection of ventricle and cardiac wrapping with Acorn CorCap cardiac support device. These procedures were eventually abandoned due to negative outcomes and without proven disadvantages. Another organ-saving surgical option currently being considered but still make little sense is cardiac regeneration by stem cell therapy, i.e., cardiomyocyte restoration and replacement. Presently, the organ-saving surgical alternatives to treat end-stage HF are revascularization for ischemic cardiomyopathy, mitral valve surgery (repair or replacement) for ischemic mitral incompetence (IMI), left ventricular (LV) aneurysmectomy (surgical ventricular restoration) and mitral valve repair for IMI. These aforementioned procedures have become quite established approaches and with increasing experience are continuously being modified to improve outcome. Various mechanical circulatory support systems have emerged over time to improve functional status of patients with advanced HF, either as a bridge to heart transplantation or as a bridge to myocardial recovery. Likewise offered in those with contraindications to transplantation. Ventricular assist devices (VAD) can keep patients alive until an eventual transplantation. This article reviews the variety of the myriad of alternative organ-saving surgical alternatives that have been available or are currently available provided to patients with end-stage HF, their advantages and deficiencies, as well as prospects in HF therapy.

Heart transplantation: the Berlin experience and perspectives.

In patients with end-stage heart failure, heart transplants are now an ingrained practice, as they provide satisfying long-term results with good predictability and quality of life. The successful outcome has evolved from the development of effective immunosuppression, recognition of allograft rejection through diagnostic modalities and improvement in donor organ perfusion. Unfortunately, transplant availability is constrained by the shortage of donor organs and is therefore considered a casuistic therapy. The outcome is defined by unwanted effects of immunosuppressants, increased tumor occurrence and chronic transplant angiopathies. In the long term, patients fear primarily the occurrence of renal insufficiency and secondly osteoporosis with its skeletal complications and corresponding pain. Nevertheless, the overall quality of life is not very limited; on the contrary, patients demonstrate a surprisingly meaningful lives 10-20 years after the transplant. Their physical presentation is similar to those with varying co-morbidities. Most of the 20-year surviving patients are physically active and happy with their daily lives. Medical ambition has seen heart transplantation become reality and develop into an influential force regarding heart surgery, immunology, pharmacology, organ logistics and medical ethics. Its development has also molded our definitions of death and has driven public and health care approval of medical advances. It has provided a strong solidarity among politicians, sociologists, physicians and citizens. Problems regarding ethics continue to endure, and will forecast heart transplants as a defining, but temporary era in human medicine. The donor organ shortage has stimulated the use of resuscitated donor hearts and encouraged exploration and advancement of mechanical circulatory support systems and xenotransplantation as alternatives in the management of end-stage heart failure.

Weaning from ventricular assist device support after recovery from left ventricular failure with or without secondary right ventricular failure.

Although complete myocardial recovery after ventricular assist device (VAD) implantation is rather seldom, systematic search for recovery is worthwhile because for recovered patients weaning from VADs is feasible and can provide survival benefits with long-term freedom from heart failure (HF) recurrence, even if a chronic cardiomyopathy was the primary cause for the drug-refractory HF necessitating left ventricular (LVAD) or biventricular support (as bridge-to-transplantation or definitive therapy) and even if recovery remains incomplete. LVAD patients explanted for myoacardial recovery compared to those transplanted from LVAD support showed similar survival rates and a significant proportion of explanted patients can achieve cardiac and physical functional capacities that are within the normal range of healthy controls. In apparently sufficiently recovered patients, a major challenge remains still the pre-explant prediction of the weaning success which is meanwhile reliably possible for experienced clinicians. In weaning candidates, the combined use of certain echocardiography and right heart catheterization parameters recorded before VAD explantation can predict post-weaning cardiac stability with good accuracy. However, in the absence of standardization or binding recommendations, the protocols for assessment of native cardiac improvement and also the weaning criteria differ widely among centers. Currently there are still only few larger studies on myocardial recovery assessment after VAD implantation. Therefore, the weaning practice relies mostly on small case series, local practice patterns, and case reports, and the existing knowledge, as well as the partially differing recommendations which are based mainly on expert opinions, need to be periodically systematised. Addressing these shortcomings, our review aims to summarize the evidence and expert opinion on the evaluation of cardiac recovery during mechanical ventricular support by paying special attention to the reliability of the methods and parameters used for assessment of myocardial recovery and the challenges met in both evaluation of recovery and weaning decision making.

Mechanical circulatory support systems: evolution, the systems and outlook.

The joint efforts in the fields of surgery, medicine and biomedical engineering, sponsored by both the government and the industry, have led to the development of mechanical support devices that can provide reliable circulatory support, which can temporarily support a patient's circulation until either the heart recovers or until a new heart can be transplanted or permanently replace a failed heart. Their development has been driven by the shortage of donor organs. Various systems have eventually evolved for short or long-term support of patients suffering from cardiogenic and/or advanced heart failure (HF). Over time, several have been withdrawn from the market due to high rate of thromboembolism and pump-related complications, but many others remained with modern principles of circulatory support proved to be durable and reliable. Hopefully, the ever-evolving technology will yield several devices aimed at their miniaturization, with an energy supply without risk of infection, a system which is simple to implant and to exchange, minimalization of thrombus formation by optimal interior pump design, new antithrombotic medications and a system with demand-based pump activity. It is important to remember that such devices are only implanted to keep a patient alive or in an immediate life-threatening stage. In such circumstances, attribution of aforementioned difficulties to pump limitations or to advanced disease states remains difficult. In the coming years, ventricular assist devices (VADs) could be the most common surgical preference for treating severe HF.

Accurate assessment of right heart function before and after long-term left ventricular assist device implantation.

INTRODUCTION: Because end-stage heart failure (HF) often involves both ventricles even if its initial cause was left-sided heart disease, assessment of RV size, geometry and function before, during and after LVAD implantation is of crucial importance. AREAS COVERED: This review discusses the usefulness, benefits, particular challenges and limits of RV assessment in patients with end-stage HF due to primarily impaired LV function who necessitate LVAD support, with or without an additional RV mechanical support. EXPERT OPINION: Although LV unloading often induces reduction of the pulmonary vascular resistance facilitating RV reverse remodeling and functional improvement, drug-refractory RVF after LVAD implantation is not always avoidable. Therefore, patients who need a temporary or long-term biventri-cular mechanical support should already be identified preoperatively or at the latest intraoperatively. Proper assessment of RV function and its adaptability to hemodynamic overloading before LVAD implantation can predict post-implant RVF, thus helping to avoid complications generated by unforeseen RVF in LVAD recipients. Close monitoring of RV size, geometry and function in LVAD recipients with and without additional RV mechanical support is essential for early recognition of imminent RVF in those without RV support and for detection of RV recovery and weaning decision-making in those with a RV support.

Consecutive surgical sequelae in children and adolescents with Marfan syndrome after primary cardiovascular surgical interventions.

OBJECTIVES: This study focuses on the consecutive sequelae of children and adolescents with Marfan syndrome after primary cardiovascular surgical interventions and the long-term outcomes. METHODS: A retrospective review of children with Marfan syndrome who underwent primary surgical intervention in childhood (<18 years) and sequential cardiovascular operations between July 1986 and September 2014 was undertaken. RESULTS: Thirty-six children (mean age 12.38 ± 4.4, range 0.62-17.14 years, at the first operation; 12 females) underwent a total of 97 sequential cardiovascular operations. Primary pathologies were annuloaortic ectasia, aortic root and ascending aorta aneurysm, aortic valve insufficiency, floppy mitral valve and midaortic syndrome. Initial operations were emergency in 2 and urgent and elective in 10 and 24 patients, respectively. Associated skeletal abnormalities were seen in 8. All underwent a second operation; 17 underwent a third operation; 6 had a fourth; and 2 had a fifth. The survival rate of children <13 years of age at the first operation compared to those who were older and male, was not statistically significant (P = 0.244). The cumulative survival rate based on age at first operation was 63.24 ± 0.16% at a mean follow-up period of 13.9 ± 6.8 (median 11.8, range 2-32.6) years. CONCLUSIONS: Patients with Marfan syndrome undergoing surgery during childhood needed sequential reinterventions. However, even with multiple consecutive surgeries, long-term outcome is deemed satisfactory.

Pediatric ventricular assist devices: what are the key considerations and requirements?

Introduction: The development of ventricular assist devices (VADs) have enabled myocardial recovery and improved patient survival until heart transplantation. However, device options remain limited for children and lag in development.Areas covered: This review focuses on the evolution of pediatric VADs in becoming to be an accepted treatment option in advanced heart failure, discusses the classification of VADs available for children, i.e. types of pumps and duration of support, and defines implantation indications and explantation criteria, describes attendant complications and long-term outcome of VAD support. Furthermore, we emphasize the key considerations and requirements in the application of these devices in infants, children and adolescents.Expert opinion: Increasing use of VADs has facilitated a leading edge in management of advanced heart failure either as a bridge to transplantation or as a bridge to myocardial recovery. In newborns and small children, the EXCOR Pediatric VAD remains the only reliable option. In some patients ventricular unloading may lead to complete myocardial recovery. There is a strong need for pumps that are fully implantable, suitable for single ventricle physiology, such as the right ventricle.

Role of paediatric assist device in bridge to transplant.

BACKGROUND: While heart transplantation has gained recognition as the gold standard therapy for advanced heart failure, the scarcity of donor organs has become an important concern. The evolution of surgical alternatives such as ventricular assist devices (VADs), allow for recovery of the myocardium and ensure patient survival until heart transplantation becomes possible. This report elaborates the role of VADs as a bridge to heart transplantation in infants and children (≤18 years old) with end-stage heart failure. METHODS: A retrospective review of the medical records of 201 heart transplant recipients between May 1986 and September 2014 identified 78 children [38.8%; mean age 7.2 (7.8±6.0) years old; IQR: 2.6-11.8 years] with advanced heart failure who were supported with a VAD [left VAD (LVAD) =21; biventricular VAD (BVAD) =57] as a bridge to heart transplantation. Fourteen (17.9%) patients were less than 1 year old; 15 (19.2%) children had a cardiac arrest and underwent cardiopulmonary resuscitation, with 7 of these patients also requiring extracorporeal membrane oxygenation (ECMO) support prior to implantation of a VAD. The aetiology of heart failure was primarily cardiomyopathy (dilative, restrictive from endocardial fibrosis, idiopathic or toxic-induced), reported in 56 (71.8%) patients. The VADs employed were primarily Berlin Heart EXCOR® (n=63), HeartWare (n=13), Berlin Heart INCOR® (n=1), and Toyobo (n=1). RESULTS: Mean duration of VAD support was 59 (133.37±191.57) days (range, 1-945 days; IQR: 23-133 days) before a donor heart became available. The primary complication encountered while patients were being bridged to transplant was mediastinal bleeding (7.8%). The main indication for pump exchanges was thrombus formation in the valves. There was no incidence of technical failure of the blood pump or driving system components. Skin infections around the cannulae occurred in 2.5%. Adverse neurological symptoms (thromboembolism 11.1%, cerebral haemorrhage 3.6%) that occurred did not have any permanent neurological sequelae that could be detected on clinical examination in this study. Mean duration of follow-up was 9.4 (10.3±7.6) years (IQR: 3.74-15.14 years). Cumulative survival rates of patients bridged to transplantation with VAD were 93.6%±2.8%, 84.6%±4.1%, 79.1%±4.7%, 63.8%±6.2%, 61.6%±7.1%, and 52.1%±9.3% at 30 days, 1, 5, 10, 15 and 20 years, respectively. There was no statistically significant difference (P=0.79) in survival rates of patients bridged to heart transplantation with VAD compared to those who underwent primary heart transplantation. Post-transplant survival rates stratified according to the type of VAD implanted and number of ventricles supported were not statistically different (P=0.93 and 0.73, respectively). In addition, post-transplant survival rates were not significantly different when age, gender and diagnosis were adjusted for. Furthermore, no statistically significant difference was found when post-transplant survival rates of children who had episodes of rejection were compared to those who did not have episodes of rejection. CONCLUSIONS: The results in this series demonstrate that VADs satisfactorily support paediatric patients with advanced heart failure from a variety of aetiologies until heart transplantation. The data further suggests that patients bridged with VADs have comparable long-term post-transplant survival as those undergoing primary heart transplantation.

Extra-anatomical bypass in complex and recurrent aortic coarctation and hypoplastic arch.

OBJECTIVES: Our goal was to report the selection schemes, technical variations and long-term outcome of extra-anatomical bypass to correct complex, recurrent aortic coarctation and hypoplastic aortic arch. METHODS: Between 1989 and 2012, 53 patients (mean age 13.2 ± 4.3, median 11.6, range 9-23 years) with complex aortic coarctation (n = 33; long-segment hypoplastic aortic arch in 15), recurrent coarctation (n = 20; anastomosic pseudoaneurysm in 10), underwent correction using extra-anatomical bypass, either with (n = 18: femoral bypass = 13, left heart bypass = 5) or without (n = 35) extracorporeal circulation via a left lateral thoracotomy (n= 48) and combined median sternotomy and median laparotomy (n = 5). The decision to use extracorporeal circulation was based on the anatomical location of the coarctation, the length of the hypoplasia and a history of previous repair. Preoperatively, mean systolic blood pressure was 130 ± 30 mmHg at rest and 180 ± 40 mmHg during exercise, with a mean pressure gradient of 80 ± 11.6 (range 40-120) mmHg. RESULTS: Various extra-anatomical bypass strategies included left subclavian artery to descending aorta (n = 38), ascending aorta to left subclavian artery (n = 3), ascending aorta to descending aorta (n = 4), aortic arch to descending aorta (n = 3) and ascending aorta to abdominal aorta (n = 5). Graft size (median 18, range 10-26, mm) was chosen according to the diameter of the vessel proximal and distal to the planned graft. No operative deaths, paraplegia or abdominal malperfusion occurred. The mean reduction in systolic blood pressure was 60 ± 25 mmHg without pressure gradients. During a mean follow-up of 18.3 ± 3.7 years, there were no reoperations, graft complications or pseudoaneurysm formation on anastomotic sites. Seven (11.6%) patients are on antihypertensive medications. No patient presented with claudication nor did anyone experience orthostatic problems from the steal phenomenon. CONCLUSIONS: Extra-anatomical bypass is safe, an effective technique, and achieves satisfactory long-term results.

Extraanatomic bypass technique for the treatment of midaortic syndrome in children.

BACKGROUND: This report aims to introduce the extraanatomic bypass technique to treat the midaortic syndrome and to document its long-term effectiveness and durability. METHODS: Fourteen patients (mean age, 6.7 ± 3.76 years; range 8 months to 11 years) received diagnoses of midaortic syndrome, characterized by severe narrowing of the abdominal aorta with involvement of the renal and visceral branches. Angiography showed variable lengths of high-grade midaortic stenosis, with 7 children having visceral artery involvement and 9 having renal artery involvement. All children were hypertensive (mean blood pressure, 165 ± 15.7 mm Hg). Three had had previous nephrectomies. Six patients had had previous percutaneous transluminal renal artery angioplasties. The midaortic obstruction was relieved by descending abdominal aorta bypass (left thoracoabdominal approach) and by an ascending abdominal aorta bypass (median sternotomy and transabdominal approach) in 12 patients. No visceral artery revascularization was done. RESULTS: There was a considerable blood pressure reduction in all patients and relief of intermittent claudication in 6 affected patients. One patient had a bilateral renal artery bypass 2 weeks postoperatively because of recurrence of renal hypertension. At a mean follow-up time of 5.8 ± 1.36 years (range, 9 months to 15 years), there was no further reoperation nor mortality. Twelve patients had complete relief of hypertension, and 2 had mild hypertension. All patients have normal renal function and no signs or symptoms of visceral malperfusion. Growth and development have proceeded normally. Follow-up magnetic resonance tomography showed patent grafts without any strictures. CONCLUSIONS: Extraanatomic bypass provides very effective and long-term relief of hypertension and any malperfusion in midaortic syndrome.