Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 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

    • order Thiorphan Upon examining his previous hospital records

    2019-06-18

    Upon examining his previous hospital records from 4 years prior, we found that he was diagnosed with acute heart failure at the second hospitalization 1 week after catheter ablation for atrial fibrillation. His symptoms and chest radiographic findings had improved by standard therapy for heart failure, and the cause of the heart failure had been thought to be a complication of negative inotropic drugs or the cardiac catheter ablation, but this had not been clarified at the time. We noticed that bepridil was administered for 3 weeks before the first hospitalization for catheter ablation and bepridil (100mg/day) was administered after the catheter ablation for 7 days prior to the second hospitalization for acute heart failure. From these details, we speculated that the diagnosis of heart failure of unknown etiology at the second hospitalization could have been due to bepridil-induced interstitial pneumonia and, therefore, was possibly relieved by the fortuitous cessation of bepridil (clinical course, medication, and laboratory data are summarized in Fig. 3). The results of right ventricular catheterization were normal (mean pulmonary artery wedge pressure, 8mmHg; cardiac index, 3.98mL/min/m2) and heart failure was ruled out. Results of blood tests after the appearance of dyspnea with exertion revealed high concentrations of surfactant protein A (SP-A, 206ng/mL) and surfactant protein D (SP-D, 268ng/mL), but KL-6 (311U/mL) was still within the normal range. However, KL-6 level increased to 1132U/mL, and SP-A and SP-D levels gradually decreased in the late phase of pneumonia (Fig. 3). Bronchial alveolar lavage fluid (BALF) revealed inflammatory order Thiorphan (3.5×105/mL); increased percentages of neutrophils (13%), lymphocytes (37%), and eosinocytes (9%); decreased percentage of macrophages (41%); 59.9% CD4+ lymphocytes; and 17.9% CD8+ lymphocytes. The CD4+/CD8+ ratio was 3.35. Although the increases in inflammatory cells and mixed cellularity in the BALF findings indicated interstitial lung disease, this information was insufficient for making a definitive diagnosis. The drug lymphocyte stimulation test (DLST) for bepridil was negative (90%), and a previous study indicated that DLST is not always positive in bepridil-induced interstitial pneumonia [5]. Our eventual diagnosis of drug-induced interstitial pneumonia caused by bepridil was based on chest radiographic findings, chest CT, BALF, and clinical processes. We stopped bepridil administration on the 14th day and began administration of 30mg of oral prednisolone after intravenous steroid pulse therapy (methylprednisolone, 1000mg/day) for 3 days. The patient\'s symptoms and chest radiography findings improved gradually. We gradually reduced the dose of prednisolone, and 39 days after starting prednisolone therapy, his respiratory failure had improved from Hugh-Jones class V to class I and he was discharged. At the time of discharge, he was able to walk by himself.
    Discussion Among anti-arrhythmic drugs, amiodarone is well known to induce interstitial pneumonia [6]. In view of bepridil\'s blocking action on sodium, potassium, and calcium channels in cardiomyocytes, it is expected to have similar effects to amiodarone. However, the induction of interstitial pneumonia may be a rare secondary effect of bepridil, although some cases have been reported recently [3,4]. Our patient experienced respiratory symptoms and fever on the fourth day when bepridil was administered for the third time. The onset of bepridil-induced interstitial pneumonia was earlier in our case than in previously reported cases, in which patients developed bepridil-induced interstitial pneumonia at any time from 14 days to >200 days after administration of bepridil [3]. In the present case, we noted that the underlying mechanism of bepridil-induced interstitial pneumonia may have involved an immunoallergic reaction rather than pulmonary toxicity resulting from drug accumulation, as is sometimes the case with amiodarone. In the current case, the longest period of administration of bepridil was only 3 weeks before the first hospitalization. If the interstitial pneumonia had been induced by the direct pulmonary toxicity of bepridil, it would have occurred more than 3 weeks after beginning administration. At the time of the third hospitalization, the respiratory symptoms occurred after only 4 days of bepridil administration, which is too rapid to be caused by pulmonary toxicity.