Paediatric Cardiology Unit, Anna Meyer Children Hospital, Viale Pieraccini 24, 50139, Florence, Italy.
Inborn Metabolic and Muscular Disorders Unit, Anna Meyer Children Hospital, Florence, Italy.
Orphanet J Rare Dis. 2020 Jul 31;15(1):196. doi: 10.1186/s13023-020-01466-w.
Primary mitochondrial disorders (PMD) are rare conditions resulting in progressive multi-organ failure. Cardiovascular involvement (CVI) has been reported in paediatric patients. However, its age-related prevalence, clinical presentation and prognostic impact are unresolved. We detailed CVI in a cohort of children diagnosed with PMD over two decades at a tertiary referral centre.
We enrolled 86 PMD patients (M/F = 30/56; mean age 6.4 ± 8.58 years). CVI was detected in 31 patients (36%), with mean age at onset of 5.7 ± 7.8 years including the pre- and neonatal phase in 14, often representing the first sign of PMD (42% of those with CVI). Heart disease resulted more common in males and in children with specific aetiologies (Barth, TMEM70 and MELAS syndromes). Hypertrophic, non-compaction and dilated cardiomyopathies were the prevalent disorders, although pulmonary arterial hypertension was also found. Adverse cardiac events (heart failure, resuscitated cardiac arrest, ICD/PM implantation, sudden death) occurred in 19% of children with CVI over a follow-up period of 5.4 ± 4.3 years. All-cause mortality was higher in patients with CVI compared to those without CVI (45.1% vs 21.8%; p < 0.01); female sex, age at onset < 5 years, acute heart failure at presentation and diabetes also proved independent predictors of outcome.
Cardiovascular involvement occurred in over one-third of children diagnosed with PMD, often at a very early age, and was associated with adverse prognosis. Final outcome of PMD-related CVI was influenced by the specific underlying aetiology, suggesting the need for tailored management of heart failure and sudden death prevention.
原发性线粒体疾病（PMD）是一种罕见的疾病，可导致多器官进行性衰竭。儿科患者已有心血管受累（CVI）的报道。然而，其与年龄相关的患病率、临床表现和预后影响仍未得到解决。我们详细描述了在一家三级转诊中心 20 多年来诊断的 PMD 患儿队列中的 CVI。
我们纳入了 86 名 PMD 患者（男/女=30/56；平均年龄 6.4±8.58 岁）。31 名患者（36%）检测到 CVI，发病平均年龄为 5.7±7.8 岁，包括 14 名新生儿和围生期患者，CVI 常代表 PMD 的首发症状（42%的 CVI 患者）。心脏病在男性和具有特定病因（Barth、TMEM70 和 MELAS 综合征）的儿童中更为常见。肥厚性、非致密性和扩张性心肌病是常见的疾病，但也发现了肺动脉高压。在 5.4±4.3 年的随访中，19%的 CVI 患儿发生了不良心脏事件（心力衰竭、心肺复苏后心脏骤停、ICD/PM 植入、猝死）。与无 CVI 的患者相比，CVI 患者的全因死亡率更高（45.1% vs 21.8%；p<0.01）；女性、发病年龄<5 岁、首发时急性心力衰竭和糖尿病也是独立的预后预测因素。
超过三分之一的 PMD 患儿诊断为 CVI，且常发生在非常年幼的时候，与不良预后相关。PMD 相关 CVI 的最终结局受到特定潜在病因的影响，提示需要针对心力衰竭和预防猝死进行个体化管理。
