High-density mapping of the slow pathway in a patient with atrioventricular nodal reentry given intranasal Etripamil during the NODE-1 study

Pharmacokinetics and Pharmacodynamics of Etripamil, an Intranasally Administered, Fast‐Acting, Nondihydropyridine Calcium Channel Blocker

“…Notably in this regard, limited invasively obtained, intracardiac electrophysiological assessments of AV node conduction and refractory period parameters performed during the Phase 2 NODE‐1 electrophysiology laboratory study found that etripamil prolonged AV nodal effective refractory periods and Wenckebach cycle length lengths (ie, AV nodal conduction time) with greater dose‐dependent effects at higher doses without significantly changing the HV interval (ie, His‐Purkinje conduction time) measured at 100 bpm 17 . A case report describing a patient with AVNRT who received 105‐mg etripamil in the NODE‐1 study while undergoing electrophysiological mapping for ablation, however, did document transient slowing and gradual recovery of AV nodal conduction at 3 minutes following nasal administration of etripamil 18 . Another important limitation in comparing results between the 2 Phase 1 studies is the larger body size of the all‐male participants in Study MSP‐2017‐1096, as height and weight may affect pharmacokinetics.…”

“…17 A case report describing a patient with AVNRT who received 105mg etripamil in the NODE-1 study while undergoing electrophysiological mapping for ablation, however, did document transient slowing and gradual recovery of AV nodal conduction at 3 minutes following nasal administration of etripamil. 18 Another important limitation in comparing results between the 2 Phase 1 studies is the larger body size of the all-male participants in Study MSP-2017-1096, as height and weight may affect pharmacokinetics. The fact that there were no female participants in MSP-2017-1096 and 50% female participants in the NODE-102 study is relevant, as PSVT occurs twice as commonly in women as in men.…”

Intranasal etripamil for rapid treatment of paroxysmal supraventricular tachycardia

“…A case study undertaken during the NODE-1 trial used 3D electroanatomic mapping of the slow pathway to further our understanding of this mechanism. The investigators demonstrated that after etripamil administration, slow pathway voltages decreased to a level comparable with postablation status [ 19 ]. Concurrently, there was an increase in the AV cycle length from 330 to 550 ms after 3 min, recovering back to 350 ms after 30 min.…”

Update on Etripamil Nasal Spray for the At-home Treatment of Acute Paroxysmal Supraventricular Tachycardia

“…High-density electroanatomic mapping has further suggested that etripamil causes loss of voltage in the slow pathway bridge with gradual recovery, mirroring observed changes in atrioventricular block cycle length. 16 The potent combination of a convenient intra-nasal mode of delivery and rapid onset of action, as well as a short half-life, make etripamil an attractive proposition for patient self-administration outside of the formal healthcare environment. The use of etripamil is directed towards the two most common subtypes of PSVT that involve the atrioventricular node: atrioventricular nodal re-entrant tachycardia (AVNRT) and atrioventricular re-entrant tachycardia (AVRT), which together account for up to 90% of PSVT cases.…”