Kathleen E. Simpson

Diagnosis and Treatment of Myocarditis in Children in the Current Era

Myocarditis has been defined by the World Health Organization/International Society and Federation of Cardiology as an inflammatory disease of the heart muscle diagnosed by established histological, immunologic, and immunohistological criteria.1 Insights into its clinical manifestation and treatment in both adults2–7 and children8–12 have been the subject of a number of recent reviews. It is caused primarily by numerous infectious agents, but it may also accompany autoimmune disease, hypersensitivity reactions, and toxins (Table 1). In North America and developed countries, it primarily has a viral origin. In Central and South America, Trypanosoma cruzi (Chagas disease) is a common cause. Diphtheria often causes myocarditis in countries without widespread immunization.13 Although enteroviruses have classically been identified as the prime viral agent, new techniques to extract viral genome from myocardium with polymerase chain reaction techniques have in both children and adults revealed previously unrecognized viruses such as adenovirus, parvovirus B19, human herpesvirus 6, hepatitis C, Epstein-Barr virus, and cytomegalovirus.2,3,14–19 Interestingly, the pattern of identified viral pathogens in myocarditis has evolved over the last 20 years from enteroviruses and adenoviruses to primarily parvovirus and herpesvirus 6. Endomyocardial fibroelastosis, a once frequent cause of infantile dilated cardiomyopathy that is now rarely seen, was linked to the mumps virus via viral polymerase chain reaction analysis of archived pathological sample, suggesting that its reduced prevalence might be attributed to immunization.20 View this table: Table 1. Various Causes of Myocarditis3,5 In a somewhat confusing fashion, the American Heart Association’s contemporary definitions of cardiomyopathies classify myocarditis as an inflammatory cardiomyopathy but also lists the same infectious causes of dilated cardiomyopathy as those found with myocarditis.21 This conundrum typifies myocarditis. Its myriad presentations range from minimal symptoms to severe heart failure and sudden death. It is commonly associated …

Liver cirrhosis in Fontan patients does not affect 1-year post-heart transplant mortality or markers of liver function

BACKGROUND Liver cirrhosis is recognized with long-term follow-up of patients after the Fontan procedure. The effect of liver cirrhosis on the use of heart transplant (HT) and on post-HT outcomes is unknown. METHODS We reviewed Fontan patients evaluated for HT from 2004 to 2012 with hepatic computed tomography (CT) imaging, classified as normal, non-cirrhotic changes, or cirrhosis. The primary outcome was 1-year all-cause mortality, and the secondary outcome was differences in serial post-HT liver evaluation. RESULTS CT imaging in 32 Fontan patients evaluated for HT revealed 20 (63%) with evidence of liver disease, including 13 (41%) with cirrhosis. Twenty underwent HT, including 5 non-cirrhotic and 7 cirrhosis patients. Characteristics at listing between normal or non-cirrhotic (n = 13) and cirrhosis (n = 7) groups were similar, except cirrhosis patients were older (median 17.6 vs 9.6 years, p = 0.002) and further from Fontan (median 180 vs 50 months, p < 0.05). Serial liver evaluation was similar, including aspartate aminotransferase, alanine aminotransferase, bilirubin, albumin, and tacrolimus dose at 1, 3, 6, 9, and 12 months. Overall patient survival was 80% at 1 year, with no difference between cirrhosis and non-cirrhosis patients (86% vs 77%, p = 0.681). Liver biopsies were performed in 7 patients before HT, and all specimens showed architectural changes with bridging fibrosis. CONCLUSIONS Most patients evaluated for HT had abnormal liver findings by CT, with cirrhosis in 41%. One-year mortality and serial liver evaluation were similar between groups after HT. Liver cirrhosis identified by CT imaging may not be an absolute contraindication to HT alone in this population.

Successful subxyphoid hybrid approach for placement of a Melody percutaneous pulmonary valve.

A variety of complex congenital heart defects in the pediatric population involve placement of a right ventricle to pulmonary artery conduit as part of surgical repair. With the advent of percutaneous pulmonary valve implantation (PPVI), patients may avoid the risks of serial surgical reinterventions as the PPVI acts to prolong the life of a previously placed conduit. As the experience with PPVI is growing, new challenges arise from complicated anatomy and severe conduit stenosis. We present a case of a 16‐year‐old male who underwent successful pulmonary valve placement with a Melody valve via a subxyphoid hybrid approach after an unsuccessful attempt at percutaneous placement.

Continuous Flow Device Support in Children Using the HeartWare HVAD: 1,000 Days of Lessons Learned From a Single Center Experience.

The purpose of this study is to provide a single center experience with a continuous flow device in adolescents with end-stage heart failure. A retrospective single center analysis of patients aged 18 years or younger implanted with HVAD (HeartWare Inc, Framingham, MA) between October 2012 and March 2014 was performed. Demographics, preimplant and postimplant clinical data, survival, and adverse events (AEs) were recorded. A matched group of adults based on diagnosis, body surface area (BSA), and time period were used for outcome comparisons. Six adolescents with dilated cardiomyopathy were implanted with the HVAD. Median age and BSA were 13.4 years and 1.45 m2, respectively. All were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile-1 or profile-2. Median days on device were 108 with total patient-days on device of 1,017. Four adolescents were discharged home on device all in New York Heart Association 1. Five underwent transplantation with 100% survival. There were 18 AEs with one AE per 170 days on device. Compared with the adult cohort (n = 5), there was no difference in 1 year survival (p = 0.32). HVAD support in adolescents is highly successful as a bridge to transplantation. It provides early rehabilitation and improvement in quality of life. Morbidity is not negligible but appears comparable with that seen in adults.

Improved survival after heart transplant for failed Fontan patients with preserved ventricular function.

BACKGROUND Patients with a failing Fontan continue to have decreased survival after heart transplant (HT), particularly those with preserved ventricular function (PVF) compared with impaired ventricular function (IVF). In this study we evaluated the effect of institutional changes on post-HT outcomes. METHODS Data were retrospectively collected for all Fontan patients who underwent HT. Mode of failure was defined by the last echocardiogram before HT, with mild or no dysfunction considered PVF and moderate or severe considered IVF. Outcomes were compared between early era (EE, 1995 to 2008) and current era (CE, 2009 to 2014). Management changes in the CE included volume load reduction with aortopulmonary collateral (APC) embolization, advanced cardiothoracic imaging, higher goal donor/recipient weight ratio and aggressive monitoring for post-HT vasoplegia. RESULTS A total of 47 patients were included: 27 in the EE (13 PVF, 14 IVF) and 20 in the CE (12 PVF, 8 IVF). Groups were similar pre-HT, except for more PLE in PVF patients. More patients underwent APC embolization in the CE (80% vs 28%, p < 0.01). There was no difference in donor/recipient weight ratio between eras. There was a trend toward higher primary graft failure for PVF in the EE (77% vs 36%, p = 0.05) but not the CE (42% vs 75%, p = 0.20). Overall, 1-year survival improved in the CE (90%) from the EE (63%) (p = 0.05), mainly due to increased survival for PVF (82 vs 38%, p = 0.04). CONCLUSIONS Post-HT survival for failing Fontan patients has improved, particularly for PVF. In the CE, our Fontan patients had a 1-year post-HT survival similar to other indications.

Intravenous Home Inotropic Use Is Safe in Pediatric Patients Awaiting Transplantation

Background—Intravenous inotropic therapy can be used to support children awaiting heart transplantation. Although use of this therapy is discouraged in adults because of poor outcomes, its use in children, particularly outpatient, has had limited evaluation. We aimed to evaluate the safety and efficacy of this practice. Methods and Results—A retrospective analysis of an intent to treat protocol was completed on United Network for Organ Sharing status 1A patients discharged on inotropic therapy from 1999 until 2012. Intravenous inotropic therapy was initiated for cardiac symptoms not amenable to oral therapy. Patients who were not status 1A or required >1 inotrope were excluded. Efficacy was analyzed by time to first event: transplantation; readmission until transplantation; improvement leading to inotrope withdrawal; or death. Safety included analysis of infection rates, line malfunctions, temporary hospitalization, neurological events, and arrhythmias. One hundred six patients met inclusion criteria. The mean age was 10.1±6.4 years, 47% of patients had congenital heart disease, and 80% of these patients had single ventricle physiology. In patients without congenital heart disease, 53% had dilated cardiomyopathy, 91% of patients received milrinone, 85% of patients underwent transplantation, 8% of patients successfully weaned from support as outpatients, whereas 6% died. Fifty percent of patients were readmitted before transplantation or weaning from support, of which 64% required only 1 readmission. The majority of readmissions were for heart failure. Conclusions—Outpatient intravenous inotropic therapy can be safely used as a bridge to transplantation in pediatric patients. A minority of patients can discontinue inotropic therapy because of clinical improvement.

Acute myocarditis in children.

Myocarditis is an uncommon but significant disease in children. Diagnosis requires a high index of suspicion and understanding of the clinical presentation of this disease. The understanding of the mechanisms of disease–host immune response and host response has improved, but is not completely known. Therapy remains mainly supportive, while the use of immunotherapy in children is still controversial. The majority of children will improve; however, a substantial portion of children will die or develop persistent dilated cardiomyopathy leading to necessary heart transplantion.

Early Biventricular Assist Device Use in Children: A Single-Center Review of 31 Patients.

Biventricular assist device (BiVAD) support is considered a risk factor for worse outcomes compared with left ventricular assist device (LVAD) alone for children with end-stage heart failure. It remains unclear whether this is because of the morbidity associated with a second device or the underlying disease severity. We aimed to show that early BiVAD support can result in good survival by analyzing our prospectively collected database for all pediatric patients who underwent BiVAD implantation. From 2005 to 2009, BiVADs were used exclusively. From 2010 to 2014, LVAD alone was considered, maintaining a low threshold for BiVAD support. All BiVADs were pulsatile devices. Thirty-one patients with median age of 3.5 years received BiVAD support. Diagnoses included dilated cardiomyopathy in 17 (55%), myocarditis in 6 (19%), and congenital heart disease in 3 (10%). Survival to transplant was achieved in 27 (87%) with a median duration of 41 days (interquartile range, 15–69). Adverse event rates (per 100 days of support) were bleeding at 0.52, infection at 1.17, and central nervous system dysfunction at 0.78. Of those who survived to transplant, 26 (96%) remain alive with a median follow-up of 55 months. These results show that BiVAD support can bridge patients to transplant with excellent long-term survival.

Pediatric Quality of Life while Supported with a Ventricular Assist Device

OBJECTIVE Ventricular assist devices (VADs) have emerged as an important treatment option for bridging pediatric patients with heart failure to transplant. VADs have shown improved survival; however, the pediatric quality of life (QoL) while on VAD support is unknown. We aimed to evaluate the QoL of our pediatric patients while supported with a VAD. DESIGN In this prospective study, pediatric patients who underwent VAD placement, and their parents, were administered a generic Pediatric Quality of Life Inventory (PedsQL) 4.0 pre-VAD implant, when feasible, after the acute postoperative period, and then periodically until heart transplant or death. Their final scores while on support were compared with three previously reported groups: healthy controls, outpatients with severe heart disease, and children after heart transplant. RESULTS From January 2008 to July 2014, 13 pediatric patients required VAD support greater than 2 weeks and completed a PedsQL. The mean age at implant was 10.0 ± 4.2 years and median duration of support was 1.6 (0.5-19.7) months. Eleven (85%) patients survived to transplant with one (8%) patient remaining alive on support. The median duration of support prior to their final PedsQL was 1.4 (0.5-11.4) months. Patients self-reported significantly (P < .05) lower total and physical QoL scores when compared with all three comparison groups. Self-reported psychosocial QoL scores were significantly lower than healthy controls only. Parent proxy-reported scores were significantly lower than all three comparison groups for all three categories (P < .05). CONCLUSIONS A large deficit exists in the total QoL of pediatric patients supported by a VAD compared with outpatient management of severe heart disease or postheart transplant patients; however, VAD patients do represent a group with more severe heart failure. Improvements in QoL must be made, as time spent with a VAD will likely continue to increase.

Atrial Tachyarrhythmias in Neonatal Enterovirus Myocarditis

Enterovirus myocarditis can be a serious infection in neonates, complicated by cardiac dysfunction and arrhythmias. Although decreased systolic function and ventricular arrhythmias have been reported, there is limited description of significant atrial involvement. We present an unusual series of three infants at our institution with enterovirus myocarditis in the neonatal period associated with atrial arrhythmias and dilation.