Unger S A, Robinson M A, Horowitz J D
Cardiology Unit, Queen Elizabeth Hospital, North Western Adelaide Health Service, University of Adelaide, SA.
Aust N Z J Med. 1997 Feb;27(1):24-8. doi: 10.1111/j.1445-5994.1997.tb00909.x.
The prognosis of severe symptomatic aortic stenosis is poor without aortic valve replacement, with no previous reports of beneficial effects of any medical treatment on either symptoms or outcome. However, this condition is increasingly a disease of the elderly and cardiothoracic surgery is associated with significant mortality and morbidity in this group.
We postulated that perhexiline, a novel anti-ischaemic agent with an oxygen-sparing metabolic effect in the myocardium (via inhibition of carnitine palmitoyltransferase-1) and no adverse haemodynamic effects, may improve symptomatic status in elderly patients with severe aortic stenosis. We report here our initial experience with perhexiline treatment in such patients.
Elderly patients with symptomatic severe aortic stenosis, who were deemed unsuitable for aortic valve replacement, were treated with perhexiline, the drug dosage titrated according to steady state plasma perhexiline concentrations. NYHA functional class was determined prior to and three months following commencement of perhexiline, and changes were analysed using McNemar's test.
Fifteen patients, age range 73-87, were followed for up to 30 months (median 18 months). Symptomatic status improved in 13 of the 15 patients over the first three months of perhexiline therapy (p < 0.01), five patients becoming asymptomatic. Twelve month actuarial survival was 80% (95% CI = 57, 100). Perhexiline was well tolerated, with no withdrawals due to toxicity or deteriorating clinical status.
Therapy with perhexiline was associated with a marked improvement in clinical status in this group of elderly patients with severe aortic stenosis.
重度症状性主动脉瓣狭窄患者若不进行主动脉瓣置换,预后较差,此前尚无任何药物治疗对症状或预后有有益作用的报道。然而,这种疾病越来越多地见于老年人,而心胸外科手术在该群体中会带来显著的死亡率和发病率。
我们推测,哌克昔林是一种新型抗缺血药物,在心肌中具有氧节约代谢效应(通过抑制肉碱棕榈酰转移酶-1)且无不良血流动力学效应,可能改善重度主动脉瓣狭窄老年患者的症状状态。我们在此报告我们对这类患者使用哌克昔林治疗的初步经验。
对被认为不适合进行主动脉瓣置换的有症状重度主动脉瓣狭窄老年患者,给予哌克昔林治疗,药物剂量根据稳态血浆哌克昔林浓度进行滴定。在开始使用哌克昔林之前和之后三个月确定纽约心脏协会(NYHA)心功能分级,并使用麦克尼马尔检验分析变化情况。
15例患者,年龄在73 - 87岁之间,随访长达30个月(中位数18个月)。在哌克昔林治疗的前三个月,15例患者中有13例症状状态改善(p < 0.01),5例患者无症状。12个月精算生存率为80%(95%置信区间 = 57, 100)。哌克昔林耐受性良好,无因毒性或临床状态恶化而停药的情况。
在这组重度主动脉瓣狭窄老年患者中,哌克昔林治疗与临床状态的显著改善相关。