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.