Methods
Study Population
To be enrolled, patients must have been at least 18 years of age, able
to provide informed consent, and indicated for de novo CRT-D device
implantation. Patients were excluded who did not exhibit left bundle
branch block (LBBB), had an epicardial ventricular lead system
implanted, exhibited an intrinsic atrial rate below 40 bpm, exhibited
atrial fibrillation (AF), had a life expectancy less than 1 year, were
pregnant, or dependent on IV inotropic agents. Patients were classified
as exhibiting AF if it was either (i) persistent, (ii) permanent and not
treated with AV node ablation within 2 weeks of CRT implant, or (iii)
documented as paroxysmal or persistent within 30 days of enrollment.
Study Design
This prospective, chronic, randomized, international study was conducted
at 13 centers in the Middle East: National Guard Hospital (Riyadh, KSA),
King Fahad Armed Forces Hospital (Jeddah, KSA), Prince Sultan Cardiac
Center (Riyadh, KSA), Royal Hospital (Muscat, Oman), Ibn Al-Bitar
Cardiac Center (Baghdad, Iraq), Nasiriya Heart Center (Nasiriya, Iraq),
King Khalid University Hospital (Riyadh, KSA), King Faisal Hospital and
Research Center (Riyadh, KSA), Bahrain Defense Force Hospital (Manama,
Bahrain), Aswan Heart Centre (Aswan, Egypt), King Abdulaziz University
Hospital (Jeddah, KSA), Cleveland Clinic Abu Dhabi (Abu Dhabi, UAE), and
Sabah Al-Ahmad Cardiac Center (Kuwait City, Kuwait). All patients
provided informed consent, and all study protocols were approved by the
ethics committee of each institution.
Enrolled patients were implanted with a de novo CRT-D device (Abbott
Unify Quadra MP™ or Quadra Assura MP™) and quadripolar LV lead (Abbott
Quartet™) according to standard practice. Prior to hospital discharge,
patients were randomized into one of two treatment groups, as follows.
- BiV Group : devices programmed to conventional BiV pacing, with
the single LV pacing vector selected according to the standard
practice of the implanting physician.
- MPP Group : devices programmed with MPP enabled, with the two LV
pacing vectors (LV1, LV2) selected using the automatic
VectSelectTM feature. Specifically, the VectSelect
feature was used to assign LV1 and LV2 cathodes to the LV electrodes
with the earliest and latest RV-LV conduction times
(RV-sensed to LV-sensed), respectively, with corresponding anodes
assigned to yield capture thresholds less than 3.5 V with no phrenic
nerve stimulation observed at an output of 1.5x capture threshold.
For both groups, programming of the atrioventricular delay was left to
the discretion of the implanting physician. For BiV, the
interventricular delay was set to the default value (LVRV, 10 ms). For
MPP, both the intraventricular and interventricular delays were set to
the default values (LV1LV2, 5 ms; LV2RV, 5 ms).
Echocardiography and 12-lead surface electrocardiography were performed
at implant and repeated 6 months post-implant. Echocardiographic metrics
were analyzed by blinded core labs. ECG QRS duration (QRSd) was defined
as the time from the earliest start-time (departure from isoelectric) to
the latest end-time (return to isoelectric) across all ECG leads,
following standard recommendations and ignoring any pre-QRS deflections
attributed to pacing artifacts.16
Study Endpoints
CRT response was characterized by changes in LV end-systolic volume
(ΔESV) and LV ejection fraction (ΔEF) at 6 months post-implant. Patients
were classified as ESV responders if they demonstrated a relative
reduction in ESV of at least 15% vs. baseline. The primary endpoint of
the study was a comparison of the proportion of ESV responders (i.e.,
ESV responder rate) between the BiV and MPP groups. In addition, a
combined ESV+EF response classification was also used, in which patients
were classified as ESV+EF responders if they demonstrated both a
relative reduction in ESV of at least 10% and an absolute elevation in
EF of at least 5% vs. baseline.17 Secondary endpoints
included the following comparisons between BiV and MPP groups: ESV
reduction, EF elevation, QRS duration (QRSd) reduction, ESV+EF responder
rate, and improvement in NYHA functional class.
Statistical Analysis
Statistical analyses were performed using Matlab (Statistics Toolbox,
The Mathworks). Categorical variables were reported by patient count and
patient percentage. Differences in categorical variables between groups
were tested using Fisher’s exact test.
Continuous variables were
reported as median and interquartile range (IQR), as none demonstrated
standard normal distributions according to one-sample Kolmogorov-Smirnov
tests. Differences in continuous variables between groups were tested
using the Mann–Whitney U test.
The impact of baseline characteristics on ESV responder rates was
quantified using binomial regression. For all statistical tests,
P<0.05 was considered statistically significant.