GUIDELINE-DIRECTED MEDICAL THERAPY IN A SICKKIDS PAEDIATRIC DILATED CARDIOMYOPATHY COHORT: REAL-WORLD UTILIZATION DATA

Abstract

BACKGROUND Dilated cardiomyopathy (DCM) is the most common cause of pediatric end-stage heart failure (HF). Guideline-directed medical treatment (GDMT) for HF improves outcomes in adults. The effect of being on GDMT is not as well established in children. We aim to determine the utilization and associated outcomes of HF medications in a SickKids DCM cohort. METHODS AND RESULTS The SickKids HF Database identified patients diagnosed between Jan 1, 2001 – July 1, 2018 and included those with idiopathic or genetic/familial DCM. Descriptive statistics and Kaplan-Meier survival curves were used for transplant-free (Tx-free) survival. Angiotensin-converting enzyme inhibitors, beta-blockers, and mineralocorticoid receptor antagonist were at target if achieved 70% of therapeutic dosing (Table 1). Of the 126 patients, 56% were males, the median age at diagnosis was 1.1y (IQR=0.3-10.9) and median follow-up duration was 1.4y (IQR=0.3-5.5). Patients on ≥2 target HF medications (≥2meds) were compared to patients on < 2 HF medications, of which 25% (n=31) were on ≥2meds at 3 months. Patients on ≥2meds had higher left-ventricular end-diastolic dimension at baseline [median 7.9(IQR=3.6-10.2) vs. 4.4(IQR=2.4-7.3) p=0.005] and likely to be on diuretics [(26(84%) vs. 44(46%) p < 0.0003)] or anticoagulation [(21(68%) vs. 41(43%) p=0.02)]. Patients on ≥2meds were more likely to have at least moderately reduced left-ventricular (LV) function [31 (100%) vs. 78 (82%) p=0.01] and at least moderate mitral regurgitation (MR) [22 (71%) vs. 44 (46%) p=0.02] at 3 months. Independent risk factors for death/transplant were lower baseline ejection fraction and the need for cardiopulmonary resuscitation (CPR). Tx-free survival was improved for patients with ≥2meds ever during follow-up versus no medications (Figure 1). CONCLUSION Majority of paediatric DCM patients fail to reach GDMT target dosing. Those able to achieve ≥2meds have improved Tx-free survival, compared to those on less or no medications, despite being more likely to have reduced LV function and MR on echocardiogram. These patients are also more likely to require additional medications to manage their HF. Patients with lower baseline ejection fraction or needing CPR during follow-up have worse Tx-free survival. This study indicates further quality improvement work is needed to improve GDMT for pediatric HF patients. Dilated cardiomyopathy (DCM) is the most common cause of pediatric end-stage heart failure (HF). Guideline-directed medical treatment (GDMT) for HF improves outcomes in adults. The effect of being on GDMT is not as well established in children. We aim to determine the utilization and associated outcomes of HF medications in a SickKids DCM cohort. The SickKids HF Database identified patients diagnosed between Jan 1, 2001 – July 1, 2018 and included those with idiopathic or genetic/familial DCM. Descriptive statistics and Kaplan-Meier survival curves were used for transplant-free (Tx-free) survival. Angiotensin-converting enzyme inhibitors, beta-blockers, and mineralocorticoid receptor antagonist were at target if achieved 70% of therapeutic dosing (Table 1). Of the 126 patients, 56% were males, the median age at diagnosis was 1.1y (IQR=0.3-10.9) and median follow-up duration was 1.4y (IQR=0.3-5.5). Patients on ≥2 target HF medications (≥2meds) were compared to patients on < 2 HF medications, of which 25% (n=31) were on ≥2meds at 3 months. Patients on ≥2meds had higher left-ventricular end-diastolic dimension at baseline [median 7.9(IQR=3.6-10.2) vs. 4.4(IQR=2.4-7.3) p=0.005] and likely to be on diuretics [(26(84%) vs. 44(46%) p < 0.0003)] or anticoagulation [(21(68%) vs. 41(43%) p=0.02)]. Patients on ≥2meds were more likely to have at least moderately reduced left-ventricular (LV) function [31 (100%) vs. 78 (82%) p=0.01] and at least moderate mitral regurgitation (MR) [22 (71%) vs. 44 (46%) p=0.02] at 3 months. Independent risk factors for death/transplant were lower baseline ejection fraction and the need for cardiopulmonary resuscitation (CPR). Tx-free survival was improved for patients with ≥2meds ever during follow-up versus no medications (Figure 1). Majority of paediatric DCM patients fail to reach GDMT target dosing. Those able to achieve ≥2meds have improved Tx-free survival, compared to those on less or no medications, despite being more likely to have reduced LV function and MR on echocardiogram. These patients are also more likely to require additional medications to manage their HF. Patients with lower baseline ejection fraction or needing CPR during follow-up have worse Tx-free survival. This study indicates further quality improvement work is needed to improve GDMT for pediatric HF patients.