Methods
This study was approved by the Institutional Review Board of Northwell Health and exempted from the investigational new drug (IND) based upon a Food and Drug Administration (FDA) review.
From February 2020 to October 2020, 40 non-consecutive patients scheduled for elective EPS, supraventricular tachycardia (SVT), atrial fibrillation (AF), and premature ventricular contraction (PVC) ablations at a single center were consented and prospectively enrolled for the use of dobutamine. The inclusion criteria were patients between the ages of 18 and 80 and those undergoing EPS. Patients were excluded from the study for the following conditions: (1) hypertrophic obstructive cardiomyopathy or other forms of left ventricular outflow tract obstruction, (2) severe aortic stenosis, (3) prior sustained ventricular tachycardia or ventricular fibrillation, (4) prior allergic reaction to dobutamine or sulfates, and (5) pregnancy.
All procedures were performed in the EP laboratory under general anesthesia or conscious sedation monitored by an anesthesiologist. Standard multi-electrode catheters were inserted via the femoral vein and positioned fluoroscopically at the His-bundle position, coronary sinus, and right ventricular apex. Stimulation was performed with a programmable stimulator EP-4TM (St. Jude Medical, Little Canada, MN, USA). The procedures were performed by three experienced electrophysiologists and the standard EPS protocol was performed as previously reported.5
At the conclusion of each ablation, the baseline blood pressure and the following parameters were recorded: (1) sinus cycle length (SCL), (2) AH interval, (3) HV interval, (4) QRS duration, (5) QT interval, (6) AV node block cycle length (AVNBCL), (7) AV node effective refractory period (AVNERP), and (8) VA block cycle length (VABCL), (9) atrial effective refractory period (AERP) and (10) ventricular effective refractory periods (VERP). Dobutamine was then infused at 5, 10, 15, and 20 mcg/kg/min with a waiting period of five minutes before the blood pressure and the same parameters noted from baseline were recorded. Blood pressures were recorded from an arterial line or manual cuff at five-minute interval. Electrogram intervals were measured using CardioLabTM (GE Healthcare, Chicago, IL, USA). The study endpoint was at protocol completion with measurements at baseline and at each incremental dose of dobutamine. If any sustained arrhythmia was induced, the arrhythmia was ablated and the study was stopped.
Stimulation was performed by pacing at the coronary sinus and the right ventricular apex at cycle lengths just shorter than the prevailing sinus cycle length, and then at progressively shorter cycle lengths to the point of AV or VA block. Programmed stimulation was then performed at each site beginning with an 8-beat drive train at 600 msec in the atrium and the ventricle with single extrastimuli beginning in late diastole, and then progressively earlier in 10-msec decrements (with increasing doses of dobutamine, the drive train cycle was decreased to avoid competition during sinus tachycardia), which understandably affected atrial, AV nodal and ventricular refractoriness. The SCL, and AH and HV intervals were measured from an average of at least ten consecutive intervals recorded from the His-bundle catheter. The AVNBCL and VABCL were determined as the longest pacing cycle length from the coronary sinus and right ventricular apex, respectively, which resulted in AV nodal block during gradually increasing pacing rates. The anterograde AVNERP was measured as the longest A1-A2 interval (measured in the His bundle recording), at a drive cycle length of 600 msec, in which the A2 failed to propagate through the AV node. Similarly, the retrograde AVNERP was the longest V1-V2 coupling interval, at a drive cycle length of 600 msec, at which the premature stimulus failed to propagate to the atrium. Pacing cycle lengths of 600, 500, 450 and 400 msec were used to measure the refractory periods, in view of the shortening of the sinus cycle length in response to dobutamine. Although we understand the limitation of pooling the refractory periods with varying drive cycle lengths, we preferred reporting a single mean refractory period for each dose of dobutamine.