Survey of QRS Frequency at Various Left Ventricular Pacing Sites for Cardiac Resynchronization
Phase: NA
Conditions: Cardiomyopathies, Congestive Heart Failure
Sponsor: The Cleveland Clinic

Version 1 Date 16 MAY 2017 
 Survey of QRS frequency at various left ventricular pacing sites for cardiac resynchronization. 
 
Background 
Many heart failure patients with prolonged QRS complexes are candidates for cardiac resynchronization 
therapy (CRT). The accepted rationale for CRT is that the widened QRS slows left ventricular (LV) 
activation to such a degree that the contraction is dyssynchronous and the ejection of blood is 
significantly reduced. CRT is performed by the addition of a separate pacing lead within a branch of the 
coronary sinus (or surgically implanted on the LV surface) and pacing at that site simultaneously with 
right ventricular pacing.  Clinical studies have shown that patients with certain widened QRS patterns, 
such as left bundle branch block (LBBB), are more likely to exhibit contractile as well as clinical 
improvement. However, not all patients exhibit improvement. Improving the patient selection criteria 
for CRT based on intrinsic QRS properties as well as LV site of pacing has been an active area of clinical 
study.  
We have shown that frequency spectrum analysis of the intrinsic QRS complex using the Fourier 
transform algorithm can help identify patients who are likely to improve (AKA: responders)1. In addition, 
we have shown that the reduction of QRS low frequency power in certain ECG leads (in particular lead 
V3) shortly following implant also predicts CRT responders2.  We hope to begin a prospective trial to 
select the optimal LV pacing site based on paced QRS frequency characteristics. However, the effect of 
various locations of LV pacing sites on the resultant QRS frequency characteristics is not precisely known 
within any given patient. This study will provide us with more complete, spatially distributed QRS data in 
order to determine the variability in frequency signals between known locations. In this way, we will be 
able to design the eventual prospective study by utilizing the variance of frequency results we 
determine in this study to determine the study size required and specific frequency goals.  
Research procedures:  
Patients who are scheduled to undergo implantation of a left ventricular pacing lead via the coronary 
sinus branch veins will be approached for enrollment. This will include new CRT device implants 
(pacemaker or ICD) or upgrade of a currently implanted pacemaker or ICD.  Patients will be approached 
during clinical outpatient clinic visits as well as preprocedural visits just prior to entering the laboratory 
for the scheduled implant. We will plan to enroll an equal (or near equal) number of male and females 
for a total of 20-30 subjects (depending on the encountered variability of results). 
After cannulation of the coronary sinus, a clinically approved Biotronik Vision guidewire will be advanced 
into 3 coronary sinus branch veins receiving venous blood from the anterior, lateral and posterior 
regions of the left ventricle. This 0.014 in guidewire is electrically insulated except for a 15 mm section 
near the distal tip. When connected via the 30mm uninsulated section near the proximal end to a pacing 
circuit, it allows pacing impulses to be delivered to selected sites withing the venous branch. In each 
branch vein, 3 pacing sites will be tested: apical, mid ventricular and basal.We will test the anterior and 
posterior veins first, and then test the usually targeted lateral vein. Then, after all 3 sites within the 

Version 1 Date 16 MAY 2017 
lateral vein are tested, a standard LV pacing lead will be advanced over the guidewire, in the usual 
clinical manner, for final placement of that lead.  The additional time required to position and pace the 3 
sites (alone and in combination with a previously implanted RV pacing lead) should not excees 5-10 
minutes, with <2 minutes of fluoroscopy. In this manner, nine distributed sites around the LV will be 
assessed.  The procedural and fluoroscopic time required to locate and test each site will be measured 
starting after placing the coronary sinus delivery sheath until the delivery of the LV lead over the 
guidewire. 
The sensed and paced QRS complexes in the normal ECG limb leads and lead V3 will be saved digitally on 
our laboratory monitoring system (GE Prucka). These ECG signals will be then analyzed by our frequency 
algorithm, in which we will manually isolate the QRS complex for time frequency analysis in which the 
complex will be divided into 48 time segments. The algorithm will determine the average frequency of 
each segment and we will then average the first 16 segments together to represent the initial third of 
the QRS, the middle third will be derived from the next 16 segments and the final third from the 
remaining segments. We will then compare the frequency data from these QRS segments between the 
nine different ventricular locations to derive the positional variability. Once this is obtained, we should 
be able to determine the sample sizes required for a randomized comparison of frequency directed LV 
lead placement versus standard LV lead placement. Additionally, we will measure the time required to 
sense the signals paced at each LV site to the RV electrode and vice versa.  
 
References 
1. Niebauer MJ, Rickard J, Polakof L, Tchou PJ, Varma N.  QRS Frequency Characteristics Help 
Predict Response to Cardiac Resynchronization in Left Bundle Branch Block below 150 
Milliseconds. Heart Rhythm Journal 2014; 11:2183-2189. 
2. Niebauer MJ, Rickard J, Polakof L, Tchou PJ, Varma N.  Early Changes in QRS Frequency Following 
Cardiac Resynchronization Predict Hemodynamic Response in Left Bundle Branch Block Patients. 
J Cardiovasc Electrophysiol. 2016; 27: 594-599.