Since the advent of biventricular pacing in the late 1990s, the art and science of this technology — through both improved tools and demonstrated clinical benefits — continues to produce ever-improving patient benefits. Cardiac resynchronization therapy (CRT) is a proven and effective treatment for heart failure (CHF) patients with systolic dysfunction and ventricular electrical conduction delays. CRT has been shown to improve patient quality of life, cardiac function and patient functional capacity, as well as extend survival and reduce hospitalizations.1-6
Implementation of this vital technology can sometimes be very challenging. Various problems can occur from the start of the implantation process or develop at late post-implantation follow-up. Achieving efficient left ventricular (LV) lead pacing capture thresholds (PCT) is a primary goal to enhance pulse generator longevity. Placing the LV lead at sites not associated with phrenic nerve stimulation (PNS) is important, achieving precise lead positioning associated with “firm” lead stability to minimize that problem later. When post-implantation PNS does occur, subsequent LV lead vector programming is attempted through often tedious threshold testing, and is often disappointing with limited remaining electrode choices. Post implantation, optimal programming of the left ventricular stimulation parameters likely change over time as the heart continues to reverse remodel. Ideally, automatic device monitoring of sensed “electrical timing parameters” or associated physiologic changes could direct ongoing programming changes that will produce the best patient outcomes.
Gleaning usable and predictive clinical information from device-acquired data logging may ultimately be the most important feature of implanted biventricular systems. Rapidly obtainable longitudinal graphics reflecting surrogates of lung edema as well as other vital information such as atrial fibrillation (AF) burden, percent biventricular pacing, and treated and untreated ventricular arrhythmias are extremely useful. Indices of activity level, nocturnal heart rates, and heart rate variability (when available) can be integrated to better characterize the patient’s current or possibly changing hemodynamic status. Review of these data is also central to understanding increases in delivered ventricular arrhythmia-termination therapy or the development of AF. Review of these stored data may also highlight when timely changes in programmed device parameters could improve patient outcomes. Clinical trials have shown the value of many of these parameters to predict which patients may be at higher risk of CHF re-hospitalization — a key concern not only for the patient, but also the healthcare system that cares for them.
The patient was a 67-year-old man with ischemic cardiomyopathy who had a prior dual-chamber ICD placed for primary prevention. His device was to be upgraded in the setting of class III heart failure, a left bundle branch block and a first-degree AV block, with his current pulse generator at “recommended replacement time” status. Venous access was obtained from the original pocket, and the delivery system was quickly introduced into the coronary sinus and directed to the posterolateral (PL) branch. Complete LAO and RAO coronary sinus imaging from the PL branch was performed, allowing a full appreciation of all potential target veins. A dominant PL branch and a moderate-sized anterolateral branch were considered primary and secondary targets, respectively. (Figure 1) An Attain Performa Model 4298 quadripolar LV lead (Medtronic, Inc.) was passed over a guide wire to near the apex with good placement of the lead on the lateral wall and the most proximal electrode (#4) being well within the LV branch. Pacing thresholds showed PNS from vectors LV1 to LV2 and LV3 to LV4, but not from vector LV2 to LV3. The “middle pair” of this particular lead is designed with a short inter-electrode distance of only 1.3 mm, while the other LV lead electrode spacing is 21 mm. This shorter bipolar distance allows a smaller effective area of stimulation, which is potentially useful when trying to avoid adjacent tissue stimulation, including PNS.7 The device was a Viva Quad C CRT-D (Medtronic, Inc.). The Viva platform pulse generator has the newly released AdaptivCRT (aCRT) algorithm, which assesses intrinsic conduction and optimizes CRT programming every minute through adjustments of the AV/VV delays. Additionally, this device is capable of generating 16 different vectors of stimulation between the four lead electrodes and with the distal RV coil.
With this new lead comes the challenge of multiple potential pacing vectors for consideration, potentially requiring significant time to assess. VectorExpress, a new automated PCT measuring tool (available on the programmer), is now available. It can quickly (usually in less than three minutes) and accurately determine both individual vector PCTs and impedances. Based on these obtained data, VectorExpress can calculate the effect on device longevity for all the various vector options.8 In this patient, at a 12-month post-implantation thresholds check using VectorExpress, all but four vectors (LV2 to LV3 and LV3 to LV2 and LV2 to RV coil and LV3 to RV coil) continued to show PNS. Phrenic nerve PCT ranged from 4.75 V to as low as 0.75 V at 0.5 mms, with the average phrenic nerve PCT being 1.5V (Figure 2). Hence, in this difficult patient with few LV lead placement site options and an abundance of PNS noted from within that “best” vein choice, successful LV pacing was still possible because of the option of the closely-spaced electrode pair.
The patient continues to do well. Over one year, he has improved from functional Class III to Class II, and his EF has improved from 35% to 48%. He has had no heart failure hospitalizations, and device diagnostics showing excellent daily activity and low, stable lung impedance values with no fluid index excursions above 20 during the last 8 months. At 16 months, he was 99.2% biventricular paced, with no VT/VF or AF episodes, LV pacing output was at 1.25 V at 0.5 msec, and there was an estimated 7.2 years of remaining device longevity. Overall, this was an excellent clinical result, likely reflective of some of the enhanced features of the new lead design and the utility of the Viva ICD platform.
This patient’s case demonstrates some of the advances made in CRT technology. LV lead designs have progressively evolved from unipolar to bipolar, then to bipolar leads able to be used in varying combinations with the RV coil. The recent introduction of quadripolar leads now substantially increases the number of potential pacing vectors. These additional vectors provide greater flexibility in handling specific challenges beyond just PCT and avoidance of PNS.9 It is now possible and much simpler to test and reassign one of 16 different LV pacing vectors of a chronically implanted LV lead rather than having to resort to a possible LV lead revision procedure hoping to find a better location.
The market release of the new Attain Performa quadripolar lead family includes three different quadripolar lead models: 4298 (dual canted), 4398 (straight, two-tined), and 4598 (S-curved) — each with distinctive designs/shapes to best “fit” coronary venous anatomy and improve post-implantation stability. These quadripolar leads also possess steroid elution on each of the four electrodes, which has been shown to lower chronic PCTs as compared with quadripolar leads without steroid on each electrode.10 This translates not only into lesser battery drain, but potentially fewer problems with PNS.
Along with improved lead technology, recent strides in pulse generators have also been achieved. As mentioned, the aCRT algorithm’s ease of use and application consistency has shown improvements in patient response.11-12 Unique algorithms, like aCRT, were developed to achieve 1) more optimal LA to LV volume “transfer” prior to onset of ventricular pacing, and 2) LV-RV “staggered” pacing to pre-excite the otherwise later contracting portion of the LV due to native electrical delay or slowed conduction due to scar. In addition, the manner of ventricular pacing via “mode adaptation” (depending on intrinsic AV conduction) allows biventricular- or LV-“only” pacing with the goal of achieving continued left ventricular reverse modeling, best possible patient outcomes, and the potential for less battery consumption with single-site pacing.
There have been recent clinical trials that have resulted in the expansion of indications for the use of biventricular pacing in new patient populations. Biventricular pacing is to be combined with established and continued use of optimized medical therapy for CHF. Note that the strength of data supporting these differing patient populations varies considerably, with expert consensus statements reflecting Class I, IIa and IIb support for implantation. Qualifying features of NYHA functional class, EF, QRS duration and presence of LBBB have been itemized in these recommendations. Guideline compliance is best met for patients with NYHA Class III and IV patients with LVEF ≤35% and QRS duration of ≥150 msec with a LBBB.13 There is new additional support that the QRS duration alone may be the strongest predictor of benefit with this technology.14 More recently, expanded indications as reflected by FDA-approved labeling includes NYHA Class II ICD patients with LVEF ≤30% and QRS ≥130 msec. NYHA Class III/IV patients with EF ≤35% and a prolonged QRS (≥120 msec) are approved for either CRT-D or CRT-P usage. Additionally, the Medtronic-sponsored BLOCK HF trial demonstrated the value of biventricular pacing (CRT-P or CRT-D) in patients with AV block (either complete heart block or where a high percentage of ventricular pacing is expected) with EF ≤50%.15 The findings of BLOCK HF allow patients with Class I, II or III CHF to receive biventricular pacing, again on top of concomitant optimal medical therapy.
We have come a long way in our understanding and application of this technology, and while each of us has seen remarkable improvements in patients’ quality of life due to biventricular pacing, the elusive question is: How do we achieve consistent clinical improvement for every CRT patient? Advances will continue in lead delivery and design. At implant, we will receive more precise information leading to the optimal LV lead placement location. We can likely expect improvement in device monitoring of patients’ cardiac status and their response to biventricular pacing, refined patient selection criteria as well as many others. Ultimately, we should strive to place a pacing system (precise lead location and appropriate device support) that will collectively realize the best possible outcome for that individual’s (diseased) heart. We are getting there.
Disclosures: Outside the submitted work, the author reports he receives personal fees as a consultant to Medtronic.
Editor’s Note: This article underwent peer review by one or more members of EP Lab Digest®’s editorial board.
- Cleland JG, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005;352(15):1539-1549.
- Tang ASL, Wells GA, Talajic M, et al. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med. 2010;363:2385-2395.
- Linde C, Abraham WT, Gold MR, et al. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol. 2008;52(23):1834-1843.
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- Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004;350:2140-2150.
- Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. 2009;361:1329-1338.
- Biffi M, et al. Utilizing short spacing between quadripolar LV lead electrodes to avoid PNS. Cardiostim 2014, Poster Session 56P.
- Demmer W. VectorExpress performance results. Medtronic Data on File. January 2013.
- Crossley GH, Biffi M, Johnson WB, et al. A novel quadripolar lead with a narrow-spaced bipole allows for effective LV pacing while avoiding phrenic nerve stimulation – Attain Performa LV Lead study primary results. 2014 American Heart Association. AB14753.
- Lin A, et al. Do steroid eluting proximal electrodes in left ventricular cardiac vein quadripolar leads improve chronic pacing thresholds. EHRA Europace. 2013;P1216.
- Birnie D, Lemke B, Aonuma K, et al. Clinical outcomes with synchronized left ventricular pacing: analysis of the adaptive CRT trial. Heart Rhythm. 2013;10(9):1368-1374.
- Martin DO, Lemke B, Birnie D, et al. Investigation of a novel algorithm for synchronized left-ventricular pacing and ambulatory optimization of cardiac resynchronization therapy: results of the Adaptive CRT trial. Heart Rhythm. 2012;9(11):1807-1814.
- Zareba W, Klein H, Cygankiewicz I, et al. Effectiveness of cardiac resynchronization therapy by QRS morphology in the Multicenter Automatic Defibrillator Implantation Trial – Cardiac Resynchronization Therapy (MADIT-CRT) clinical perspective. Circulation. 2011;123:1061-1072.
- Cleland JG, Abraham WT, Linde C, et al. An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resynchronization therapy on morbidity and mortality in patients with symptomatic heart failure. Eur Heart J. 2013;34:3547-3556. doi:10.1093/eurheartj/eht290
- Curtis AB, Worley SJ, Adamson PB, et al. Biventricular pacing for atrioventricular block and systolic dysfunction. N Engl J Med. 2013;368:1585-1593.