Massimo Griselli

Cardiac transplantation in adults with congenital heart disease

Background Due to increasing success with repair or palliation in childhood, there is a rapidly growing population of adult patients with complex congenital heart disease who may require transplantation. There remains little data on outcomes of cardiac transplantation in this group. Methods 38 orthotopic cardiac transplants were performed in 37 patients (18 men) ≥18 years of age with congenital heart disease (CHD) from 1988 to 2009 in our institution. Outcomes were reviewed using medical records and transplant databases. Results 15 patients (41%) had univentricular and 22 (59%) biventricular physiology. The biggest group was transposition of the great arteries following atrial switch in eight patients (22%). Six (16%) had no previous surgical intervention. Mean age at transplant was 33.5 years (range 19.1–59.9 years). 11 patients (30%) required additional surgical procedures at transplant. 16 (43%) died, 12 early and 4 late deaths (1.8, 2.4, 2.7 and 7 years). Survival was 70% at 30 days, 68% at 1 year, 58% at 5 years and 53% at 10 and 15 years. Outcome improved in later eras with reduction in 30-day mortality from 50% to 18% and increase in 5-year survival from 50% to 69%. Two patients developed post-transplant lymphoproliferative disease. None required long-term renal replacement therapy. One patient was re-transplanted for cardiac allograft vasculopathy. Conclusions While operative mortality following cardiac transplantation for adult congenital heart disease is higher than for other diagnostic groups, long-term survival is good and comparable to patients without CHD. Disappointing early results are improved with increasing experience.

Changing Patterns of Bridging to Heart Transplantation in Children

BACKGROUND Mechanical support as a bridge to cardiac transplantation in children is an accepted treatment. With improved devices and increasing experience, the length of time that children can be supported has increased. Donor organs remain scarce and there is significant associated morbidity. METHODS Retrospective review of all children offered mechanical support as a bridge to heart transplant over 10 years in one of the two UK pediatric heart transplant centers. Outcomes during the years 1998 to 2002 were compared with outcomes during the years 2003 to 2007. RESULTS Forty children in 41 separate patient episodes received mechanical support as a bridge to transplantation or, in 1 case, to recovery. Survival to transplant or recovery was achieved in 29 of 41 (71%); 26 of 40 children (63%) survived to hospital discharge. Devices used were extracorporeal membrane oxygenation (ECMO), the Medos HIAA, the Berlin Heart (from November 2005) and the Levitronix ventricular assist device (VAD) from 2007. All 3 children supported with the Levitronix survived to transplant (median duration of support 10 days). Ten of 13 children (77%) supported by the Berlin Heart survived to transplant or recovery (median duration of support 44 days). Four of 7 (57%) children supported using the Medos device survived to transplant (median duration of support 7 days). Neurologic events were the most common cause of death in both eras (1998 to 2002 and 2003 to 2008). CONCLUSIONS Waiting times to pediatric cardiac transplant in the UK have increased. The Berlin Heart allows children to be bridged to transplant over long periods. Neurologic morbidity remains as a major concern.

Successful Bridge to Transplant With the Berlin Heart After Cavopulmonary Shunt

Mechanical cardiac assistance for infants and children may be accomplished using extracorporeal membrane oxygenation or ventricular assist device support, and are now well established as a bridge to cardiac transplantation or recovery in biventricular hearts, usually in the setting of low cardiac output states due to cardiomyopathy or acute myocarditis. Ventricular assist device support remains less well described in the setting of single ventricle physiology. We report the case of a 3-year-old girl who developed severe right ventricular failure 2 years after cavopulmonary shunt after an initial Stage I Norwood operation for hypoplastic left heart syndrome. She was successfully supported to cardiac transplantation using a single chamber Berlin Heart EXCOR ventricular assist device using right ventricular apex and aortic cannulation and is now well at home 10 months after transplant.

A multicenter study of the HeartWare ventricular assist device in small children

A multicenter study of the HeartWare ventricular assist device in small children Oliver Miera, MD, Richard Kirk, MD, Holger Buchholz, MD, Katharina R.L. Schmitt, MD, Christina VanderPluym, MD, Ivan M. Rebeyka, MD, Neil Wrightson, MD, Felix Berger, MD, Massimo Griselli, MD, and Jennifer Conway, MD From the Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany; Department of Pediatric Cardiology, Freeman Hospital, Newcastle Upon Tyne, UK; Stollery Children’s Hospital, University of Alberta, Edmonton, Alberta, Canada; and the Department of Cardiology, Boston Children’s Hospital, Boston, Massachusetts, USA

Mechanical cardiac support in children with congenital heart disease with intention to bridge to heart transplantation

OBJECTIVES A significant number of children affected by congenital heart disease (CHD) develop heart failure early or late after surgery, and heart transplantation (OHTx) remains the last treatment option. Due to shortage of donor organs in paediatric group, mechanical circulatory support (MCS) is now routinely applied as bridging strategy to increase survival on the waiting list for OTHx. We sought to assess the impact of MCS as intention to bridge to OHTx in patients with CHD less than 16 years of age. METHODS From 1998 to 2013, 106 patients received 113 episodes of MCS with paracorporeal devices as intention to bridge to OHTx. Twenty-nine had CHD, 15 (52%) with two-ventricle (Group A) and 14 (48%) with single-ventricle physiology (Group B). In Group A, 5 children had venoarterial extracorporeal membrane oxygenation (VA ECMO), 6 left ventricular assist device (LVAD), 2 biventricular assist device (BIVAD), 1 VA ECMO followed by BIVAD and 1 BIVAD followed by VA ECMO. In Group B, VA ECMO was used in 7 children, univentricular assist device (UVAD) changed to VA ECMO in 4, UVAD in 2 and surgical conversion to two-ventricles physiology with BIVAD support changed to VA ECMO in 1. RESULTS Twenty-one of 29 (72%) children survived to recovery/OHTx. Seven of 29 (59%) survived to discharge. In Group A, 11/15 (73%) survived to recovery/OHTx and 9/15 (60%) survived to discharge. Four of 15 (27%) died awaiting OHTx. One child had graft failure requiring VA ECMO and was bridged successfully to retransplantation. One child dying after OHTx had acute rejection, was supported with VA ECMO and then BIVAD but did not recover. One patient had an unsuccessful second run on BIVAD 1 year after recovery from VA ECMO. In Group B, 10/14 (71%) survived to recovery/OHTx and 8/14 (57%) survived to discharge. Four of 14 (29%) died awaiting OHTx. Of deaths after OHTx, 1 occurred intraoperatively and 1 was consequent to graft failure and had an unsuccessful second run with VA ECMO. CONCLUSIONS Children with CHD can be successfully bridged with MCS to heart transplantation. Single-ventricle circulation compared with biventricular physiology does not increase the risk of death before transplant or before hospital discharge.

Effect of persistent versus transient donor-specific HLA antibodies on graft outcomes in pediatric cardiac transplantation

BACKGROUND De novo donor-specific HLA antibodies (DSA) are a risk for poor graft outcomes, but there is little evidence of their long-term effect in pediatric cardiac transplantation or of the effect of transient versus persistent DSA found using newer antibody testing methods. METHODS Archived serum samples were obtained from patients <18 years of age who underwent primary cardiac transplantation during the period from 1996 to 2009. Luminex antibody testing was performed at 3 months, 6 months and 1 year post-transplant, and then annually. Outcomes including cardiac allograft vasculopathy (CAV), rejection and graft loss were correlated with the presence or absence of DSA or non-donor-specific HLA (non-DSA) antibodies. RESULTS Six hundred ninety-one samples from 108 patients, with mean age at transplant of 7.4 (0.1 to 15.9) years and mean follow-up 8.2 (1.9 to 15.7) years, were studied. Forty-three (40%) patients had DSA (which were persistent in 58%), 41 (38%) had non-DSA (persistent in 46%) and 24 (22%) had no antibodies. In those with DSA, 30% had Class I antibodies, 47% Class II and 23% both Class I and II, whereas, in the subgroup with persistent DSA, 88% had Class II antibodies. There were 14 cases of graft loss, 9 of these in patients with persistent DSA. All had Class II antibodies. There was an increased incidence of CAV, rejection and graft loss in those with persistent DSA. Outcomes were similar between the group with non-DSA antibodies and the group with no antibodies. CONCLUSIONS De novo HLA antibodies are detectable post-transplant in the majority of patients, but non-DSA and transient DSA do not appear to be associated with poor outcomes. Patients with persistent DSA, especially those with Class II DQ antibodies, have worse survival.

Successful Bridge to Recovery With 120 Days of Mechanical Support in an Infant With Myocarditis

An 8-month-old boy with acute myocarditis was mechanically supported with the Berlin Heart EXCOR biventricular assist device. Signs of myocardial recovery were not apparent until 40 days from presentation and ventricular function continued to improve with device removal possible after 120 days of support. He had normal cardiac function 3 months after device removal. Recovery from myocarditis in infants can take much longer than previously recognized and an extended wait for recovery is possible with the Berlin Heart.

The impact of mechanical circulatory support on outcomes in paediatric heart transplantation

OBJECTIVES Internationally, the number of donors for cardiac transplantation has remained static, while the number of patients requiring transplantation for congenital heart disease (CHD) has increased. Although the availability of mechanical circulatory support (MCS) may increase the number of transplants performed by reducing deaths while waiting, it may also lead to increased morbidity post-transplantation. We sought to assess the impact of mechanical support on post-transplant outcomes in a single centre. METHODS We assessed the outcomes of paediatric (age ≤16 years) heart transplantation in a single unit in the era of mechanical support (1998-2012) by retrospective cohort study. Outcomes before (1998-2005) and after (2005-2012) the routine use of the Berlin Heart EXCOR device were contrasted. RESULTS A total of 167 patients underwent heart transplantation during this period. The diagnosis was dilated cardiomyopathy in 61.7%, two-ventricle CHD in 11.4%, single ventricle CHD in 16.8% and miscellaneous in 10.1%. Sixty-nine (41%) were bridged to transplant by mechanical support; with extracorporeal membrane oxygenation in 19 (28%), ventricular assist device in 40 (58%) and a combination in 10 (14.0%). Post-transplant mortality at 30 days was significantly greater in those supported by MCS than without (7 vs 1%, P < 0.05), and a greater proportion of patients had neurological (23 vs 8%, P < 0.01) and major respiratory sequelae (20 vs 4%, P < 0.001). There was no significant increase in the need for post-transplant mechanical support (10 vs 6%, P = 0.3) in those supported prior to transplant. The number of transplants performed increased from 67 in 1998-2005 to 100 in the most recent era (2005-2012), and an increased proportion of these patients have been supported mechanically prior to transplantation (51 vs 27%, P < 0.01). CONCLUSION Along with strategies to increase donor utilization, MCS has allowed an increase in cardiac transplant activity at the expense of a higher early mortality and morbidity.

Outcome of mechanical cardiac support in children using more than one modality as a bridge to heart transplantation

OBJECTIVES Mechanical cardiac support (MCS) can successfully be applied as a bridging strategy for heart transplantation (OHTx) in children with life-threatening heart failure. Emergent use of MCS is often required before establishing the likelihood of OHTx. This can require bridge-to-bridge strategies to increase survival on the waiting list. We compared the outcome of children with heart failure who underwent single MCS with those who required multiple MCS as a bridge to OHTx. METHODS A retrospective study of patients aged less than 16 years was conducted. From March 1998 to October 2005, we used either a veno-arterial extracorporeal membrane oxygenator (VA-ECMO), or the Medos® para-corporeal ventricular assist device (VAD). From November 2005 onwards, the Berlin Heart EXCOR® (BHE) device was implanted in the majority of cases. Several combinations of bridge-to-bridge strategies have been used: VA-ECMO and then conversion to BHE; BHE and then conversion to VA-ECMO; left VAD and then upgraded to biventricular support (BIVAD); conversion from pulsatile to continuous-flow pumps. RESULTS A total of 92 patients received MCS with the intent to bridge to OHTx, including 21 (23%) supported with more than one modality. The mean age and weight at support was similar in both groups, but multimodality MCS was used more often in infancy (P = 0.008) and in children less than 10 kg in weight (P = 0.02). The mean duration of support was longer in the multiple MCS group: 40 ± 48 vs 84 ± 43 days (P = 0.0003). Usage of multimodality MCS in dilated cardiomyopathy (19%) and in other diagnoses (29%) was comparable. Incidence of major morbidity (haematological sequelae, cerebrovascular events and sepsis) was similar in both groups. Survival to OHTx/explantation of the device (recovery) and survival to discharge did not differ between single MCS and multiple MCS groups (78 vs 81% and 72 vs 76%, respectively). CONCLUSION Bridge to OHTx with multiple MCS does not seem to influence the outcome in our population. Infancy and body weight less than 10 kg do not tend to produce higher mortality in the multiple MCS group. However, children receiving more than one modality are supported for longer durations.

Is alternative cardiac surgery an option in adults with congenital heart disease referred for thoracic organ transplantation

OBJECTIVES We analysed the outcomes of adults with congenital heart disease (ACHD) referred for thoracic organ transplantation who underwent non-transplant cardiac surgery as an alternative management option. METHODS Adult patients with congenital heart disease assessed for heart or heart-lung transplant were identified from the departmental database. A retrospective analysis of the medical records, transplant assessment data and surgical notes was carried out. RESULTS One hundred and twenty-six patients were assessed between January 2000 and July 2011. Non-transplant cardiac surgery was performed in 14 (11%) patients. There were nine males with a median age of 37 years (range 21-42). The patients can be divided into four subgroups [left-sided lesions (n = 4), right-sided lesions (n = 3), systemic right ventricle (n = 5) and Fontan circulation (n = 2)]. Surgical procedures performed were: relief of systemic obstructive/regurgitant lesions ± endocardial fibroelastosis resection (n = 4, three pulmonary vascular resistance >6 Wood units), correction of right-sided regurgitant/stenotic lesions (n = 3), ventricular assist device for patients with a systemic right ventricle (n = 5) and re-fashioning of the Fontan pathway (n = 2). There were two early (5 and 30 days) and three late deaths (64, 232 and 374 days) with a 1-year mortality of 28%. None of the deaths occurred in patients with a two-ventricle circulation and atrio-ventricular concordance. Nine patients are alive at a median of 433 days (range 204-2456). The New York Heart Association class has improved in all survivors by at least one class at 3 and 6 months (P = 0.004 and 0.003). CONCLUSIONS Alternative cardiac surgery can be undertaken in selected patients with ACHD referred for cardiopulmonary transplantation with a low mortality in patients with two ventricles and a systemic left ventricle. Ventricular assist devices carry a significant mortality in patients with a systemic right ventricle, although this offers a valuable palliation when there are no other options. The medium and long-term results are awaited.