Outcomes of children with acute myocarditis and dilated cardiomyopathy admitted to a tertiary hospital in the Western Cape south africa: an 8 year study

[摘要] Introduction: Approximately 27% of new cases of paediatric cardiac failure in well-resourced settings are due to abnormalities of the myocardium. Acute myocarditis and dilated cardiomyopathy (DCMO) may be clinically indistinguishable at presentation but are distinct diseases. The clinical presentations of myocarditis and DCMO can range from asymptomatic, to fulminant cardiac failure or sudden death. The diagnoses are dependent upon early clinical suspicion as cardiac failure is present in 90%-100% of cases and this is commonly misdiagnosed as respiratory disease.Viral infections (in the case of myocarditis) and the sequelae of viral myocarditis (in the case of DCMO) are the most important causes of myocardial failure, but there are a number of other infections and conditions as well as toxins that are implicated in both these diseases. The cause of myocardial failure may remain obscure, particularly if cases are not rigorously investigated. Entero- and adenoviruses remain important viral pathogens associated with viral myocarditis although there seems to be a viral shift with parvovirus B19 and herpes virus now being commonly implicated. Increasing sophistication of genetic and metabolic evaluations is reducing the number of idiopathic cases.Diagnostic tests are directed at confirming the diagnosis of myocardial dysfunction and identifying the cause. Chest radiographs (CXR) and electrocardiograms (ECG) are widely used initial investigations and are abnormal in above 90% of cases. Echocardiographic (ECHO) examination is used to confirm the diagnosis, exclude structural and other causes of cardiac failure and establish a baseline for follow-up. Polymerase chain reaction (PCR) can detect viral genomes in many tissues and PCR identification of viruses on respiratory specimens correlates well with those obtained from the myocardium. Supportive therapy focusing on treatment of fluid overload and under perfusion is the mainstay of care. Access to ventilatory support, extracorporeal membrane oxygenation (ECMO), ventricular assist devices (VAD) and cardiac transplantation has dramatically changed the outcomes in well-resourced settings where children who survive an initial hospitalization have survival at 1 year of 94% and 89% at 5 years. The predictors and risk factors for death are age (neonatal period and older age at presentation), congestive cardiac failure, lower shortening fraction (SF<15%) and ejection fraction (EF <30%) and in the case of DCMO the aetiology. Nearly all data on the outcome of children presenting with and treated for acute myocarditis and DCMO are reported from developed countries with sophisticated medical services and interventions. There is little data on the clinical presentation, course, outcomes and causes of myocarditis and DCMO in children in middle and low resourced settings, where high burdens of complicating infectious diseases including tuberculosis and HIV exist. A single study from South Africa reports only on children who required paediatric intensive care (PICU) and shows an initial hospital survival of 47% of children. There are no data on the longer-term outcomes.Aims and Objectives: The aim of this study is to investigate the clinical presentation, course and outcome; including morbidity and mortality of children with myocarditis and DCMO, and to attempt to determine factors that predict for outcome. The results hope to guide local clinicians in developing guidelines for children, assist prognostication and potentially identify areas where management and the utilization of scarce resources can be improved.Methods: We conducted a retrospective descriptive review of children from birth to 13 years, diagnosed with acute myocarditis and DCMO from 1 January 2008 to 31 December 2015 at Tygerberg Hospital, a tertiary hospital in the Western Cape, South Africa. For the purposes of this study myocarditis and DCMO were studied as a single entity due to various complexities in separating these entities clearly and the continutuum/overlap that often pursues. Inclusion criteria for this study were all patients with the diagnosis of myocarditis or DCMO, based on ECHO findings of an EF <55% and/or a SF <25%, or antemortem or postmortem histology. Children were excluded if there were structural or vascular abnormalities of the heart, or where the myocardial dysfunction was thought to be due to septicemia with septic shock. We identified cases through the admission/discharge diagnoses using the International Statistical Classification of Diseases codes (ICD10 codes), reviewing ECHO request records and manually reviewing the 'Causes of deaths register. Data were collected from the paper and electronic notes made by doctors, cardiology outpatient records and autopsy reports. Demographic, clinical, laboratory, ECHO, ECG and CXR data were collected on case report forms. Viral myocarditis, for the purposes of this study was a case where a significant virus, known to be associated with myocarditis, was isolated on either PCR of tracheal aspirate (TA)/nasopharyngeal aspirate (NPA), urine or on blood test. In children where cytomegalovirus was found on any specimens we considered it a significant infection only if the blood viral load was shown to be more than 1000 copies/ml (Log 3). The metabolic, autoimmune screens and ECGs in these cases were normal. Statistical analysis was performed with StataCorp. 2015. Stata Statistical Software: Release 14. Standard descriptive analysis, including measures of central tendency and dispersion, was performed for measured variables while frequencies and proportions were described for categorical variables. For comparisons based on mortality, chi-squared test (or exact tests for sparse data) and t-and rank sums for parametric and non-parametric data were used. Analysis of survival/mortality used time to event methods including Kaplan-Meier graphs. For patients lost to follow up, survival was censored at the last known date to be alive. For all hypothesis tests a significance level of 0.05 was used while the 95% Results: We identified 227 potential cases within the broad diagnoses groups of myocarditis, dilated cardiomyopathy, myocardial dysfunction etc. Based on the inclusion and exclusion criteria stated in the methods 117 cases were included. Nineteen children were diagnosed at postmortem only. The median overall age at presentation was 18.9 months (Interquartile range (IQR) 8.9-52.2), with the children diagnosed at post mortem only slightly younger with a median of 10.6 months (IQR 2.2-28.8). Ninety-five percent (n=94/99) were in cardiac failure at presentation and 85.7% (n=90/105) were noted to have cardiovascular instability. Admission left ventricular ejection fraction was less than 30% in 68.2% (n=60/88). Eighty out of 117 (68.4%) children survived the first admission till hospital discharge and 65/117 (55.6%) children where noted to be alive at the end of the review period. On multivariate analysis the only factors that predicted death where renal dysfunction and cardiac failure at presentation. Thirty-three of 117 (28.2%) children had a short history of symptoms of less than 3 days. CXR at presentation was always abnormal and of the 97 CXR reviewed 90 (92.8%) had an increase in the cardiothoracic ratio. Seventy of 108 cases (64.8%) for which data was clear required pediatric intensive care admission; with the median length of ICU being 7 days (IQR 4-11 days). Forty-six of 107 (43%) children required ventilation for a median of 4 days (IQR 1-5) and 70/101 (69.3%) required inotropic support with 59/94 (62.8%) receiving dopamine and/ or dobutamine, 23/89 (25.8%) adrenaline infusions and 22/88 (25.0%) received milrinone. The overall duration of initial admission was 10 days (IQR 3-18), 5 days (IQR 1-15) for children who died and 12 days (8-20) for those who survived. Complications during hospitalization included acute kidney injury in 82/108 (75.9%) (3 needed dialysis), liver enzyme derangement in 69/81 (85.2%). Fourteen of the 91 children who had blood cultures taken (15.4%) at the time of admission had positive cultures, with 7/14 (50.0%) only diagnosed at postmortem. Aetiology was presumed to be viral myocarditis in 54/117 (36.7%) of the children. In 34/117 (29.1%) of cases, either their investigations/work-up was not complete hence classified as 'not determined or their full screen (excluding genetic testing) was negative hence 'idiopathic classification. Viral studies were positive in 73 (76.8%) of the 95 children where specimens were sent however not all cases with positive viruses where classified as having viral myocarditis, it depended on the virus isolated and other factors. Parvovirus PCR was positive in 17/41 (41.5%), significant CMV viral load in 16/40 (40%), Adenovirus in 5/69 (7.2%) and enteroviruses in 6/69 (8.7%). Two or more viruses where found in 37/95 (38.9%) patients. Twenty-four of the 117 (20.5%) children were known to be HIV exposed and of these 7 (29.2%) were HIV infected. 4 of the HIV infected children died, 5 (71.4%) dying within 7 days of diagnosis. The median duration of follow up time from first diagnosis was 474 days (IQR 147-820). 62 of the 80 first admission survivors attended cardiac OPD. Fourteen of the 62 children (22.6%) recovered fully and were discharged from the service, and in total 38 of the 62 clinic attenders (61.3%) were noted at a point with a normalized EF. Twenty-four of the 80 initial survivors (30%) were lost to follow-up. The median EF at the latest ECHO was 53% (IQR 35%-59%). The change in EF from diagnosis to latest ECHO was a median increase of 22.5% (IQR 9%-34%).ConclusionsThis study confirms that myocarditis and DCMO are an important cause of cardiac morbidity and mortality in South African. This study emphasises the need for a high index of suspicion of myocarditis and rapid PICU access to improve mortality. Bacterial infections are important contributors to death in this cohort and must be considered. Although we may be underestimating the total deaths in this cohort the survival after the first admission was good and supports the current recommendation to provide a full set of interventions to these patients.

[发布机构] Stellenbosch University