Archives

  • 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04
  • 2024-05
  • 2024-06
  • 2024-07
  • 2024-08
  • 2024-09
  • 2024-10

    • br Introduction Sudden cardiac death

    2019-05-21


    Introduction Sudden cardiac death (SCD) in patients with low ventricular function remains a substantial problem despite improved medical therapies [1–3]. Many patients require antiarrhythmic drugs to prevent recurrent arrhythmias and reduce the number of shocks from implanted cardioverter-defibrillators (ICDs) [4]. Amiodarone, a class III antiarrhythmic drug, which prolongs myocardial repolarization homogeneously via potassium channel blockade, has been used extensively to treat life-threatening arrhythmias. The major forms of amiodarone toxicity during chronic therapy are extracardiac [5]. Several adverse effects in many organs have been reported [5]. Among these, amiodarone toxicity, sodium salt pneumonia, and pulmonary fibrosis are the most life-threatening [5,6]. According to previous studies, amiodarone-induced pulmonary toxicity has been observed in 1%–20% of patients receiving this drug [5,7–9], and there may be ethnic or racial differences in the susceptibility [7,10]. Early detection is needed to prevent amiodarone-induced interstitial pneumonia (AMD-IP). However, it has been difficult to predict which patients are at the greatest risk of the development of AMD-IP [11]. The aims of this study were to evaluate the incidence and prognosis of AMD-IP and to identify the predictors of AMD-IP in Japanese patients treated with low-dose oral amiodarone.
    Methods
    Results
    Discussion Amiodarone is an antiarrhythmic drug, which is widely used around the world. However, its pulmonary side effects are sometimes lethal. In this study, we found that 10.2% of patients developed AMD-IP during prolonged low-dose amiodarone therapy (mean follow-up period, 66.0±38.2 months). We show 2 major findings. First, although the maintenance doses of this observation was relatively low compared to that of previous studies (mean dosage, 152mg/day) [1–5], higher maintenance doses were related to the occurrence of AMD-IP. Second, the patients with a smoking history and preexisting COPD were more likely to develop AMD-IP. In particular, we showed for the first time that smoking history was an independent predictor of AMD-IP. In addition, the AMD-IP patients with COPD had a poor prognosis resulting from relapsing AMD-IP. Neurologic and gastrointestinal tract toxicity of amiodarone are dose related [6,13], but pulmonary toxicity has been reported to be related in part to drug dosage [6,13–15]. It has been reported that pulmonary toxicity is uncommon at maintenance doses less than 300mg/day [14,15]. Some studies indicate that there is no statistically significant difference in the rate of pulmonary adverse effects between placebo and low-dose amiodarone [13,16]. However, AMD-IP can occur during prolonged therapy with doses at below 200mg/day [17,18]. The average dose of amiodarone in the present study was relatively low (152mg/day) compared with previous studies; however, the doses used in the AMD-IP group were significantly higher than those in the non-AMD-IP group. Yamada et al. reported the incidence of AMD-IP to be 7.8% and 10.6% at 3 and 5 years, respectively, even though the mean maintenance dose was only 141mg/day in their study [10]. AMD-IP was significantly associated with a poor prognosis. Mortality in AMD-IP is reported to range between 21% and 33% in patients who were admitted to the hospital [9,19–21]. In the present study, AMD-IP was not only a major cause of acute respiratory failure leading to death but also increased the risk of SCD. We use amiodarone commonly for ventricular arrhythmia patients with organic heart disease and poor left ventricular function, rather than atrial arrhythmias. For patients with poor left ventricular function, AMD-IP might worsen heart failure caused by hypoxemia and secondary pulmonary hypertension, and withdrawal of amiodarone may result in sudden death or poor prognosis. Higher age [7,9], cumulative dosage [5], reduced predrug diffusion capacity [12], underlying lung disease [5,7–9,22,23], and recent pulmonary insults [5] are reported to be risk factors of AMD-IP. Although it is arguable whether pulmonary toxicity occurs to a greater degree in patients who have underlying pulmonary disease, such as COPD [6,11], we clearly showed that the likelihood of developing AMD-IP was higher in patients with COPD and a smoking history than in patients without COPD or a smoking history. Many studies support our results that COPD is a risk factor for AMD-IP [23–25]. However, we showed for the first time that smoking history per se could predict AMD-IP. The mechanisms of pulmonary toxicity are unclear, but amiodarone may interfere with lysosomal phospholipases, leading to phospholipidosis [26]. It has been suggested that an immunologic reaction may also produce a hypersensitivity response [22]. Some studies have suggested that preexisting lung disease might predispose the patient to lung toxicity [12,27], even though this has not been verified by other studies [25,28]. We also showed that patients with COPD had a higher relapse rate and poor prognosis.