Yamamoto Riona, Kataoka Naoya, Imamura Teruhiko, Izumida Toshihide, Kinugawa Koichiro
Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
J Clin Med. 2024 Jan 16;13(2):510. doi: 10.3390/jcm13020510.
Ivabradine reduces heart rate by inhibiting the "funny current" expressed on the sinoatrial node and improves mortality and morbidity in patients with systolic heart failure and sinus tachycardia. The funny current is known to be expressed also on the atrioventricular node according to experimental studies. However, the impact of ivabradine on PR interval remained unknown.
Patients with a left ventricular ejection fraction of less than 50% who received 1 month of ivabradine were screened. Electrocardiographic and echocardiographic data, particularly concerning heart rate, the PR interval, and trans-mitral flow pattern, were collected at baseline and 1-month follow-up. The primary endpoint was defined as the composite of cardiovascular death and hospital readmission for worsening heart failure following ivabradine administration.
In the cohort of 29 enrolled patients (median age: 66 years, 62% male), the median baseline heart rate was 86 beats per minute and the median PR interval was 168 milliseconds. Following ivabradine administration, a significant decrease of 20 beats per minute in the heart rate and a significant increase of 24 milliseconds in the PR interval were observed. The truncated interval of the A-wave, detected in the trans-mitral flow, consistently demonstrated a negative correlation with the PR interval both before and after the administration of ivabradine. During a median of 1.8 years of follow-up, six patients reached the primary endpoint. A combination of heart rate reduction and PR prolongation following ivabradine administration, both of which were independent factors associated with the primary endpoint ( < 0.05 for both), was associated with greater freedom from the primary endpoint compared with either/neither of them ( = 0.002).
Ivabradine seems to prolong PR interval, which is a novel surrogate marker of favorable clinical outcomes in patients with systolic heart failure. This effect may be associated with the dynamics of the trans-mitral flow pattern, in conjunction with heart rate and the PR interval. Clinical implications of PR interval-guided ivabradine therapy remains the future concern.
伊伐布雷定通过抑制窦房结上表达的“起搏电流”来降低心率，并改善收缩性心力衰竭和窦性心动过速患者的死亡率和发病率。根据实验研究，已知起搏电流也在房室结上表达。然而，伊伐布雷定对PR间期的影响仍不清楚。
筛选左心室射血分数低于50%且接受1个月伊伐布雷定治疗的患者。在基线和1个月随访时收集心电图和超声心动图数据，特别是关于心率、PR间期和二尖瓣血流模式的数据。主要终点定义为伊伐布雷定给药后心血管死亡和因心力衰竭恶化再次入院的复合终点。
在纳入的29例患者队列中（中位年龄：66岁，62%为男性），基线时的中位心率为每分钟86次，中位PR间期为168毫秒。给予伊伐布雷定后，观察到心率显著降低20次/分钟，PR间期显著增加24毫秒。在二尖瓣血流中检测到的A波截断间期在伊伐布雷定给药前后均与PR间期呈负相关。在中位1.8年的随访期间，6例患者达到主要终点。伊伐布雷定给药后心率降低和PR间期延长的联合作用，这两者均为与主要终点相关的独立因素（两者均P<0.05），与单独出现其中任何一个因素或两者都不出现相比，无主要终点事件的自由度更高（P = 0.002）。
伊伐布雷定似乎会延长PR间期，这是收缩性心力衰竭患者良好临床结局的一种新的替代标志物。这种效应可能与二尖瓣血流模式的动态变化、心率和PR间期有关。PR间期指导伊伐布雷定治疗的临床意义仍是未来关注的问题。
