Cardioprotective medication in Duchenne muscular dystrophy: a single-centre cohort study

Abstract

Background: Duchenne muscular dystrophy (DMD) is a neuromuscular disorder characterised by progressive muscle wasting impacting mobility, ventilation and cardiac function. Associated neuromuscular cardiomyopathy remains a major cause of morbidity and mortality. We investigated the effects of cardioprotective medications [angiotensin-converting enzyme inhibitors (ACE-I), beta-blockers] on clinical outcomes in DMD patients.Methods: This was a retrospective cohort study (reference: 2021/12469) of DMD patients at a tertiary centre between 1993-2021 screening the electronic records for demographics, comorbidities, medication, disease specific features, echocardiography, hospitalisations, and ventilator use.Results: A total of 68 patients were identified aged 27.4 (6.6) years, of which 52 were still alive. There was a difference in body mass index (BMI) between survivors and deceased patients [23.8 (5.9) vs.19.9 (3.8) kg/m 2 , P=0.03]. Home mechanical ventilation (HMV) was required in 90% of patients, 85% had DMD associated cardiomyopathy. About 2/3 of all hospitalisations during the observation period were secondary to cardiopulmonary causes. The left ventricular ejection fraction (LVEF) at initial presentation was 44.8% (10.6%) and declined by 3.3% [95% confidence interval (CI): 0.4% to −7.0%] over the follow up period (P=0.002). A total of 61 patients were established on ACE-I for 75.9% (35.1%), and 62 were on betablockers for 73.6% (33.5%) of the follow up period. There was a significant LVEF decline in those taking ACE-I for limited periods compared to those permanently on ACE-I (P=0.002); a similar effect was recorded with beta-blockers (P=0.02).Conclusions: Long-term use of ACE-I and beta-blockers is associated with a reduced decline in LVEF in patients with DMD and may be protective of adverse cardiovascular ill health.

Cardiomyopathy as cause of death in Duchenne muscular dystrophy: a longitudinal observational study

“…Overall, we found that these patients tended to be undertreated compared with other patients with systolic heart failure (see percentages under medication and LVEF at transition to adult medicine and at last visit in table 1 ) and considering current heart failure guidelines [ 24 ]. These figures are comparable to a recently published cohort study from another tertiary centre [ 25 ]. Among the 32 out of 67 patients in our study with LVEF <35%, an ACE-I was used in 25 out of the 32 (78%) at some point during follow-up with LVEF <35%.…”

“…the longer the ACE-I use, the longer the survival, but perhaps the longer ACE-I use simply reflects the early onset of systolic heart failure. In another recent cohort study, longer usage of heart failure drugs during follow-up was associated with a smaller decline of LVEF during follow-up, but the authors did not study survival [ 25 ].…”

“…[24] These f igures are comparable to a recently published cohort study f rom another tertiary centre. [25] Among the 32/67 patients with LVEF < 35%, an ACE inhibitor was used in 25/32 (78%) at some point during f ollow-up with LVEF < 35%. Considering all echocardiography measurements in which LVEF < 35% was documented, an ACE inhibitor was used in 75.3% and a beta-blocker in 56.7%.…”

“…In another recent cohort study, longer usage of heart f ailure drugs during f ollow-up was associated with a smaller decline of LVEF during f ollow-up, but the authors did not study survival. [25] Overall, this study has yielded several important f indings: on the one hand, that the course of LVEF in DMD cardiomyopathy is variable over age and not necessarily genetically determined, that lower LVEF is strongly associated with shorter survival, that cardiac death is the most common cause of death nowadays, and on the other hand that DMD patients are at risk of undertreatment with respect to current heart f ailure management, although the most ef f ective heart f ailure therapies in this patient population remain to be explored . These f indings suggest that close collaboration between neuromuscular centres treating DMD patients and cardiologists is important, and international studies of heart f ailure therapy in DMD are needed to determine specif ic recommendations.…”

Cardiomyopathy as cause of death in Duchenne muscular dystrophy – a longitudinal observational study

“…Overall, we found that these patients tended to be undertreated compared with other patients with systolic heart failure (see percentages under medication and LVEF at transition to adult medicine and at last visit in table 1) and considering current heart failure guidelines [24]. These figures are comparable to a recently published cohort study from another tertiary centre [25]. Among the 32 out of 67 patients in our study with LVEF <35%, an ACE-I was used in 25 out of the 32 (78%) at some point during follow-up with LVEF <35%.…”