The study demonstrates that children with DCM and severe HF at diagnosis were older, more likely to be male, have lower systolic blood pressure measurements, be admitted to the ICU and be treated with β-blockers, loop diuretics, spironolactone and digoxin. They are also more likely to have larger diastolic LV end-diastolic dimensional z-scores and poorer LV function. Compared with children with DCM and mild HF, those with DCM and severe HF at diagnosis were at a higher risk of death. Severe HF was related to an accumulated risk of death. These associations were not affected by sex, age at diagnosis, heart rate, ventricular function and use of medication.
These results are similar to those found in a study by Rusconi [11]. They showed similar results with respect to survival between family-associated DCM and idiopathic DCM after modulation for other variates. However, HF, older age, and larger left ventricular end-diastolic dimension (LVEDD) at diagnosis were independently related to increased risks of the major adverse events of heart transplantation or death. In a retrospective analysis, HF with NYHA III/IV were significantly associated with overall death risk[12]. A meta-analysis of 57 researches of medication adherence interventions for HF treatment from adults found an obvious association between improvement of HF and a decrease of mortality[13]. These findings lend support to the idea that an improvement in HF may be a key goal for DCM therapy.
Angiotensin-converting enzyme inhibitors (ACEI) is the cornerstone of HF treatment and can significantly improve cardiac remodeling. The beneficial effects of ACEI for HF in children with DCM have been proven in previous studies[14, 15]. One prospective and large-sample study which included 5,955 adult patients with DCM and LVEF < 40% also confirmed that use of ACEI was related to the recovery of the LVEF coupled with an improvement of HF at 3 years of follow-up[16]. In a European survey between pediatric HF and ACEI use patterns conducted between January and May 2015, ACEI appeared to be essential in pediatric HF treatment strategies[17]. Nowadays, the angiotensin II receptor blocker, neprilysin inhibitor (ARNI), is more effective when compared with ACEI, and this drug has now been recommended to be the preferred treatment in patients with HF[8, 9, 18].
In children with DCM and HF, elevated heart rate is often accompanied by worsening HF. Thus, the heart rate may be a target for HF treatment. Beta blockers can reduce heart rate. Three meta-analysis on the use of beta-blockers for congestive HF in children showed that children with congestive HF might benefit from treatment with these drugs[19–21]. Additionally, ivabradine is a novel drug which can reduce the heart rate. A study randomized 116 patients diagnosed with DCM and class II to IV HF. In this study, the heart rate was reduced by ≥ 20% from baseline without leading to symptoms or bradycardia were more likely to occur in the patients taking ivabradine rather than taking the placebo. This reduction was accompanied with a significant increase in the LVEF, an improvement of the cardiac function as well as in the quality of life[22]. Another adult study also showed that the reduction of heart rate in the ivabradine group could improve the prognosis of HF[23].
In our study, loop diuretics was related to a decreased risk of death. Diuretics are also another important treatment for HF. A meta-analysis of 14 studies with 525 participants of the use of diuretic in HF suggested that these were able to reduce mortality and retard progression of HF [24]. In a study of 25,345 elder patients with HF, patients with loop diuretics as a discharge prescription had a better clinical improvement comparing with those not taking loop diuretics[25]. One study included 108 children and showed that an increase of loop diuretic responsiveness during the first 72 hours of treatment was accompanied by shorter length of hospital stays and a decrease of inpatient deaths or use of mechanical circulatory support[26]. In addition to loop diuretics, a mineralocorticoid receptor antagonist (MRA), such as spironolactone, which can also have a diuretic effect, is fundamental during the long-term management of HF[27].
There are several emerging treatments for HF in children with DCM. In a meta-analysis study, sodium-glucose co-transporter-2 (SGLT2) inhibitors were shown to reduce all-cause and cardiovascular death in patients with HF [28], and these drugs are recommended to be the preferred choice of treatment in patients with HF[8, 9]. Pulmonary artery banding (PAB) treatment, as a new indication for end-stage DCM in pediatric patients, has also been shown to be safe and effective[29, 30]. Left ventricular mechanical assist can be indicated as destination therapy for end-stage DCM[31]. Cardiac pacemaker can be an effective tool for treating HF, especially in patients who have a complete left bundle branch block[32]. Cardiac stem cell therapy is yet another feasible and safe treatment in children with DCM and HF, and can improve left ventricular function[33]. If none of the above methods work, heart transplantation could be considered as a last resort[34].
As we have already confirmed that severe HF is related to a higher risk of death in children with DCM, so therapies that improve HF can increase survival. Through a more comprehensive understanding of DCM, especially with respect to the genetics of DCM and the potential of finding new early markers and treatment for HF, it is envisaged that the treatment of HF caused by DCM will become more personalized and lead to earlier interventions [35–37]. Thus, a larger and prospective study combining all these factors should be performed to evaluate the efficacy between the treatment of HF and outcomes in children with DCM.