Kawasaki Masato, Yamada Takahisa, Okuyama Yuji, Morita Takashi, Furukawa Yoshio, Tamaki Shunsuke, Iwasaki Yusuke, Kikuchi Atsushi, Sakata Yasushi, Fukunami Masatake
Division of Cardiology, Osaka General Medical Center, Osaka, Japan.
Cardiovascular Division, Osaka Minami Medical Center, Osaka, Japan.
Pacing Clin Electrophysiol. 2017 Oct;40(10):1096-1102. doi: 10.1111/pace.13169. Epub 2017 Sep 23.
Eplerenone is reported to reduce the development of atrial fibrillation (AF). The aim of this study was to clarify the mechanism of eplerenone for AF prevention from the viewpoint of P wave morphology, which is reported to correlate with atrial fibrosis.
Thirty-five patients with hypertension, who were randomized to receive eplerenone (n = 16) or amlodipine (n = 19) for 1 year, were evaluated. P wave signal-averaged electrocardiography was recorded at baseline and 1 year after entry, and P wave duration (Ad) and P wave dispersion (P-disp) were obtained. Serum levels of intact procollagen type I N-terminal propeptide (PINP) and N-terminal procollagen-III peptide (PIIIP) were also measured.
There were no significant differences in baseline clinical characteristics including Ad, P-disp, and the decrease in blood pressure at 1-year follow-up between the two groups. Ad and P-disp (mean ± standard deviation) significantly increased in patients on amlodipine after 1 year (140 ± 21 ms to 139 ± 19 ms vs 132 ± 10 ms to 136 ± 12 ms, P < 0.01 and 14 ± 7 ms to 9 ± 4 ms vs 12 ± 5 to 16 ± 8, P < 0.01, respectively). PINP was significantly more decreased in patients with eplerenone than amlodipine (56.6 ± 30.4 μg/mL to 46.6 ± 19.4 μg/mL vs 41.5 ± 16.2 μg/L to 48.7 ± 21.3 μg/L, P < 0.01). Percent changes of Ad, P-disp, PINP, and PIIIP were significantly smaller in patients with eplerenone than amlodipine (0.0 ± 4.7% vs 3.2 ± 4.4%, P < 0.05, - 28.6 ± 31.0% vs 46.3 ± 73.0%, P < 0.01, - 5.6 ± 38.1% vs 22.7 ± 42.7%, P < 0.05, and - 9.2 ± 25.1% vs 7.4 ± 19.0%, P < 0.05, respectively).
Eplerenone reduced the increase of Ad and P-disp with a decrease of PINP and PIIIP, which might translate into reduction of atrial fibrosis. This study showed that eplerenone may be useful as upstream therapy for AF in patients with hypertension.
依普利酮据报道可减少心房颤动（AF）的发生。本研究的目的是从P波形态的角度阐明依普利酮预防AF的机制，据报道P波形态与心房纤维化相关。
对35例高血压患者进行评估，这些患者被随机分为接受依普利酮（n = 16）或氨氯地平（n = 19）治疗1年。在基线和入组后1年记录P波信号平均心电图，并获得P波时限（Ad）和P波离散度（P-disp）。还测量了血清I型前胶原N端前肽（PINP）和III型前胶原N端肽（PIIIP）水平。
两组在基线临床特征方面无显著差异，包括Ad、P-disp以及1年随访时的血压下降情况。氨氯地平治疗的患者1年后Ad和P-disp（均值±标准差）显著增加（140±21毫秒至139±19毫秒，而132±10毫秒至136±12毫秒，P<0.01；14±7毫秒至9±4毫秒，而12±5至16±8，P<0.01）。依普利酮治疗的患者PINP较氨氯地平治疗的患者显著降低更多（56.6±30.4微克/毫升至46.6±19.4微克/毫升，而41.5±16.2微克/升至48.7±21.3微克/升，P<0.01）。依普利酮治疗的患者Ad、P-disp、PINP和PIIIP的百分比变化显著小于氨氯地平治疗的患者（0.0±4.7%对3.2±4.4%，P<0.05；-28.6±31.0%对46.3±73.0%，P<0.01；-5.6±38.1%对22.7±42.7%，P<0.05；以及-9.2±25.1%对7.4±19.0%，P<0.05）。
依普利酮减少了Ad和P-disp的增加，同时PINP和PIIIP降低，这可能转化为心房纤维化的减轻。本研究表明依普利酮可能作为高血压患者AF的上游治疗药物有用。
