“Hi, phoning from ED with a referral. We’ve got a 2-week-old down here with increased work of breathing and high respiratory rate, do you mind coming to see them?”
So far, so common on your typical paediatric on-call shift.
Except this baby is a bit different – they’re also really tachycardic and their peripheral perfusion is poor. The ED team helpfully did a gas while you headed down to review, and as you scan the numbers, you see that the baby has a severe mixed respiratory/lactic acidosis.
The baby’s parents tell you that the baby hasn’t been feeding well for a few days and today has been very sleepy.
What are your differentials?
- Bad bronchiolitis?
- Infection/sepsis?
- Congenital cardiac disease – maybe a duct-dependent lesion?
- A metabolic issue?
- Something intra-abdominal?
- Inflicted injury?
- Something else?
You begin to stabilize the baby – cannula, bloods, blood cultures…
You get the antibiotics in quickly, give a 10ml/kg fluid bolus, and send a nasopharyngeal aspirate for respiratory viruses. You chat with the team and everyone agrees to start alprostadil (Prostin) while you try and find someone to perform an echocardiogram.
Thankfully, the neonatal consultant is on hand; the left ventricle is dilated with poor function. The heart otherwise looks structurally normal.
Meanwhile, the baby is no better following a 10ml/kg fluid bolus and the repeat gas is unchanged. They start to tire with episodes of apnoea..
What are the next steps?
The local paediatric critical care retrieval service is contacted and you relay the story so far. They share your concerns and are worried this baby might have a cardiomyopathy.
They advise you to:
- Call the anaesthetic team and prepare for intubation.
- Get some more access and get a peripheral adrenaline infusion running.
- Aim for a “cardio-stable induction” – they suggest using low-dose ketamine and rocuronium.
- Be prepared for the baby to arrest during induction – get resus doses of adrenaline prepared, allocate roles, and make a plan
- Be really cautious about giving more fluid boluses – 5ml/kg aliquots only if really needed such as during induction.
- In the meantime, they’ll find a Paediatric Intensive Care Unit (PICU) bed and get on the road to come and retrieve the child.
The intubation goes smoothly. The retrieval team arrives and they whisk the patient to the nearest PICU bed with an ECMO (extracorporeal membrane oxygenation) service.
A few weeks later…
Formal echocardiography confirmed a dilated cardiomyopathy. No clear cause was found. The NT-proBNP level was significantly elevated and improved slowly over time.
The patient needed support with vasoactive infusions (milrinone and adrenaline) and positive-pressure ventilation. Following a period of stability, they were cautiously diuresed and slowly weaned. After extubation and a slow wean from CPAP, they were transferred to the cardiology ward to continue the milrinone infusion via a tunneled central venous catheter.
Background: Dilated cardiomyopathy in children
The term cardiomyopathy describes a disorder of cardiac myocyte structure or function. It may be primary or occur secondary to another disease process such as infection, rheumatological or metabolic condition,s or systemic hypertension.
Primary cardiomyopathies are generally classified according to phenotypic and functional characteristics:
- Dilated cardiomyopathy
- Hypertrophic cardiomyopathy
- Restrictive cardiomyopathy
- Arrhythmogenic cardiomyopathy
- Left ventricular non-compaction
41% of paediatric cases of dilated cardiomyopathy are diagnosed during the first year of life, highlighting the large influence of genetic causes in this age group. In a recent retrospective study, pathogenic or likely pathogenic genetic variants were identified in 37% of cases. A careful family history, screening of family members, and involvement of specialized cardiac and genetic services are vital.
Decreased ventricular function and progressive left ventricular (LV) dilatation are the hallmarks of dilated cardiomyopathy. The LV dysfunction is often asymptomatic in the early stages of the disease. A range of adaptive processes occurs to compensate for falling cardiac output. Stimulation of baroreceptors results in a catecholamine-mediated increase in heart rate, stroke volume, contractility, and systemic vascular resistance (SVR). Activation of the RAAS increases preload – promoting fluid retention. SVR is further increased by potent renin-induced peripheral vasoconstriction. Though adaptative in the short term, over time these processes become maladaptive, putting more strain on a failing heart, ultimately leading to congestive cardiac failure.
It’s worth considering congenital defects such as anomalous left coronary artery from pulmonary artery (ALCAPA), coarctation of the aorta, and aortic stenosis in neonates and young infants presenting with dilated cardiomyopathy. Chronic arrhythmias and inborn errors of metabolism are also more common in patients under one year old.
What are the long-term outcomes for children with dilated cardiomyopathy?
A UK retrospective observational cohort study looked at the potential for, and timing of, recovery in children with dilated cardiomyopathy over a 5-year period. One-year survival, in this cohort, was 70%, regardless of the severity at presentation. This included infants who received a heart transplant during this time. This is similar to two major registries in Australia and America. They reported transplant-free 1-year survival across all patients as 74% and 69% respectively. Meanwhile, a Dutch study demonstrated transplant-free 1-year survival of 82%, and a group in Turkey, with a smaller cohort of patients, reported 1-year survival as 57%, with no patients receiving a transplant.
Of those patients admitted to paediatric intensive care (n=82), 34% required mechanical support with ECMO, or a Berlin heart (ventricular assist device), and 35% required a transplant. 51% were alive without transplant at 1 year and 45% at 5 years.
During the same period, 69 new diagnoses of dilated cardiomyopathy were made through the outpatient setting. Management comprised anti-failure medications in the community. Transplant-free survival for these patients was 85% at 1 year and 50% at 5 years. Outcomes at 1 year seem to be influenced by the severity of illness at presentation. Outcomes at 5 years, though, are better amongst those patients admitted to intensive care. There is probably a degree of attrition in those patients with less severe heart failure initially managed in the community. Admission to intensive care was found to be an independent predictor of worsening LV function over time though 60% of patients had a normal echo at three years.
Over a 10-year period from 2008 to 2018, 334 heart transplants were performed on children in the UK. 31% were due to cardiomyopathy. Their 1-year survival was 91% and their 5-year survival (from the first 5 years of data) was 82%. A number of studies have been undertaken to identify factors that influence survival post-transplant.
NT-proBNP was significantly higher (p<0.001) in the PICU cohort (19,460) compared to the clinic cohort (5609). NT-proBNP has been identified as a key factor in determining recovery; levels return to normal in survivors before echocardiographic changes can be measured and may be the earliest marker of recovery. Additionally, mean fractional shortening was significantly lower (p<0.001) in the intensive care admission cohort (13.3%) compared to the clinic cohort (18%).
Several studies have focused on a link between LV function and long-term outcomes. A group in Toronto demonstrated a 7-year transplant-free survival of 41% in patients with reduced systolic function, compared to 92% for patients with normal function. Other groups have found similar significant differences. Increased LV posterior wall thickness was associated with a further reduction in survival.
Female sex and younger age favour better outcomes.
About PICSTAR
PICSTAR is a trainee-led research network open to all doctors, nurses and allied health trainees within Paediatric Intensive Care. We are the trainee arm of the Paediatric Critical Care Society – Study Group (PCCS-SG) and work with them on research, audit and service evaluation.
If you would like to join PICSTAR and get involved in projects, have ideas you would like to propose or get advice/mentorship via PCCS-SG, don’t hesitate to contact us at picstar.network@gmail.com. See their website for more: https://pccsociety.uk/research/picstar/
References
Annual Report on Cardiothoracic Organ Transplantation 2017/2018, NHS Blood and Transplant
Ashkanase A., et al. 2019. Outcomes in Pediatric Hypertrophic Cardiomyopathy Patients with Reduced Systolic Ventricular Function. The Journal of Heart and Lung Transplantation. 38; 4:467
Boer den SL, et al. 2015. Management of children with dilated cardiomyopathy in The Netherlands: Implications of a low early transplantation rate. Journal Heart Lung Transplant. 34; 963 – 969.
Bouziri A., et al. 2016. Paediatric dilated cardiomyopathy: Clinical profile and outcome. The experience of a paediatric intensive care unit. European Journal of Pediatrics; 2016: 175; 1461-1462
Cox, GF. 2007. Diagnostic approaches to pediatric cardiomyopathy of metabolic genetic etiologies and their relation to therapy. Progress in Pediatric Cardiology. 24; 15-25
Fenton M., et al. 2017. Potential for and timing of recovery in children with dilated cardiomyopathy. International Journal Cardiology. 266; 162-166.
Harmon, WG et al. Cardiomyopathy, myocarditis, and mechanical circulatory support. In: Nichols, DG and Shaffner, DH (eds.) Roger’s Textbook of Pediatric Intensive Care (5th edition). Philadelphia: Wolters Kluwer Health. 2016. p. 1148-1169
Khan, RS et al. 2021. Genotype and cardiac outcomes in pediatric dilated cardiomyopathy. Journal of the American Heart Association. 11; e022854
Selim Z et al. 2017. Twelve years experience with pediatric cardiomyopathy identifying outcome risk factors. Cardiology in the Young; 27, 4.
