Controvérsias no tratamento das manifestações cardíacas na distrofia muscular de Duchenne
USA – Em 3 de dezembro de 2005 eu divulguei um artigo sobre o acompanhamento cardiológico dos portadores de distrofia muscular de Duchenne (Acompanhamento cardiológico de pessoas com distrofia muscular de Duchenne e Becker). No último número da mesma revista um outro artigo saiu criticando algumas colocações do primeiro artigo. O autor do primeiro artigo também publicou uma réplica as informações. Isto demonstra que não há um consenso médico sobre o melhor modo de acompanhar e tratar as manifestações cardíacas da distrofia muscular de Duchenne. No entanto eles são concordantes de que é preciso fazer exames periódicos e tratar precocemente. O texto desta polêmica pode ser lido abaixo:
1) Therapeutic Nihilism in Duchenne Cardiomyopathy
To the Editor.—
The recent American Academy of Pediatrics clinical report on cardiovascular supervision in Duchenne muscular dystrophy was overly nihilistic. Advances in diagnostic and therapeutic interventions were dismissed or ignored. The authors call for early recognition of cardiac dysfunction and acknowledge the limitations of echocardiography in scoliotic patients but do not mention B type natriuretic peptide. Assay of serum B-type natriuretic peptide is widely available and may identify patients with cardiac involvement even before symptoms develop. Several studies, including some cited in their report, suggest the possibility of significant benefit from both angiotensin-converting enzyme (ACE) inhibition and beta blockade in the treatment of Duchenne cardiomyopathy. There are no reports of significant unanticipated risk from these therapies. Unfortunately, optimal studies have not been conducted and may never be. The toll of cardiac disease on patients with muscular dystrophy is high, however, and safe, rational, and apparently effective modalities for evaluating and treating these patients are readily available. We should not dismiss their use out of hand.
Jeffrey Rein, MD, FAAP – El Rio Neighborhood Health Center – Tucson, AZ
2) In Reply.—
The Section on Cardiology and Cardiac Surgery appreciates the comments of Dr Rein in response to the American Academy of Pediatrics clinical report “Cardiovascular Health Supervision for Individuals Affected by Duchenne or Becker Muscular Dystrophy.” We believe the report is not “overly nihilistic” but provides cautious optimism to a group of patients who experience significant morbidity and mortality from the cardiomyopathy associated with their disease. As stated, the report provides “recommendations for optimal cardiovascular evaluation to health care specialists caring” for those with muscular dystrophy. The intent of the report was to alert the health care community to the need for earlier diagnosis and treatment and to provide minimum guidelines for cardiovascular care. Unfortunately, in many areas of this country, patients with Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) do not come to the attention of the cardiologist until they are approaching end-stage cardiomyopathy. At that point, traditional heart failure therapies are used although this approach has failed to alter the natural history of the disease. Until a cure is found, we are optimistic that early recognition can change DMD from a fatal to a chronic disease. The challenge lies in finding sensitive and specific markers to detect early cardiac dysfunction. Unfortunately, studies have not shown brain natriuretic peptide (BNP) elevation in DMD to meet the criteria as an early screening test. BNP levels become elevated in DMD relatively late in the disease process. In the article by Mori et al (cited by Rein), BNP elevation was minimal, with a shortening fraction as low as 15%. Individuals with shortening fractions < 15% did have dramatic increases in BNP. Demachi et al compared BNP levels between subjects with DMD/BMD and idiopathic dilated cardiomyopathy and ejection fraction < 50%. The study revealed dramatically lower BNP levels in subjects with DMD/BMD for a similar degree of dysfunction, leading the authors to conclude that “plasma BNP may underestimate the degree of systolic dysfunction in patients with muscular dystrophy.” This suggests that BNP is unlikely to be an ideal screening test for the presence of cardiac dysfunction in DMD/BMD. It is interesting to note that cardiovascular risk is inferred on the basis of genetic diagnosis, potentially allowing treatment to be initiated before the onset of clinical symptoms. In the absence of adequate clinical trials, cardiologists and families are left with only a handful of cited case series and reports to direct therapy. Although angiotensin-converting enzyme (ACE) inhibitor use is gaining attention in the presymptomatic patient with DMD/BMD, no multicenter prospective clinical trial exists regarding its efficacy at this time. Given the number of patients followed at each center in this country, a nationwide collaborative effort is required to obtain suitable evidence for inclusion of other therapies into official guidelines. A clinical report such as this leading to improved awareness is the first step to early cardiovascular evaluation and, ultimately, treatment.
