To the authors’ knowledge, this is the first time data has been collectively analyzed from a retrospective examination of pacemaker lead implantation performed in the preclinical laboratory setting. It should be emphasized that the preclinical research environment is well controlled, and studies are performed to show safety, not efficacy, for the regulatory agencies. Overall outcomes are based on evaluations in the short term, in overtly healthy patients. Complication rates in this review are therefore not directly comparable to real life clinical studies, due to the very different patient populations and co-morbidities found in clinical veterinary patients. However, the data may prove useful to veterinary cardiologists as baseline expectations for short term complications in near perfect conditions with young, healthy patients. Clinical management practices learned in the research laboratory may have applicability to practitioners who implant pacemakers in clinical canine patients. With the caveats noted above in mind, we did find some differences in complication rates between the data acquired in the study as compared to what has been documented in the literature gathered from the clinical canine setting. The reported rate of lead dislodgement in clinical patients varies from 6% [4] to 10% [7], with a value of 2.1% reported here. Reported infection rates for clinical veterinary patients vary from 1% [3, 14] to 6% [4], with 1.3% reported here. Reporting of the total number of major complications varies between studies, but includes reports of 9% of 104 dogs [14], 10% of 105 dogs [3], 23% of 136 dogs [7], and 27% of 33 dogs [4]; the total major in-life complication rate reported here was 5.4% for 74 dogs (1 infection, 2 RA appendage dislodgements, and 1 RV lead dislodgement).
Dogs are the model of choice for this type of preclinical research because of similar cardiac structure, function and size to that of humans. Much of the prior knowledge and experience related to bradycardia, tachycardia and pacemaker devices have been carried out using the in vivo canine model and this model is well characterized and well accepted by the FDA. Swine are a less useful model due to their growth dynamics and the historical observations that swine react differently to subcutaneous and sub muscular device implants, with a high incidence of abnormal reaction to foreign bodies, resulting in PGs eroding through the skin. There are several factors that may explain the lower rate of complications in this review. All study protocols for transvenous lead systems for this device company were implanted in larger (> 18 kg), USDA Class A origin, with little to no variability. This population inherently decreases the risk of inadequate vessel or chamber size for implantation and allows for appropriate lead slack, a more difficult procedure in smaller dogs in the real world setting. These research animals have no pre-existing disease and veterinarians or surgical research specialists working within a cardiovascular medical device company have the luxury of gaining considerable experience in lead implantation by sheer numbers alone, as that is the focus of much of the business development and innovation. Because of this, refinement of technique in lead site selection, tunneling, lead slack optimization, suture sleeve positioning and tightening, device pocket sizing and securement and being able to troubleshoot with electrical data challenges is easily achievable. Although nearly all the implants in this review were dual chamber device systems, which have comparable complication rates to single chambered systems in the veterinary field [4, 6], together, lack of patient morbidity, short to medium-term duration of implant, and operator experience likely play a large role in the incidence of complications, which is similar to what has been documented in human medicine [21]. Lastly, these animals are not discharged, but closely monitored on a daily basis, with highly technical human resources playing a big role in their aftercare. These animals are in a very well controlled environment, with close supervision on exercise restriction, daily observation of incision sites and daily bandage changes to insure constant pressure at the device pocket over a 2 week period, all which aid in limiting complication rates.
Descriptions of these procedures and processes, acquired from decades of research on preclinical canine pacemaker implantation, to share with the clinical veterinary cardiology community are provided in Additional file 1. Lead slack redundancy appears to be the most common difference between preclinical techniques and reports from the clinical veterinary field. In human medicine, and in images from clinical veterinary reports [3, 14], lead bodies positioned in either the atrium or ventricle are implanted with little slack, which is considered adequate. This is logical for humans due to the bipedal stance and passive disposition of a typical cardiac implant patient. For dogs however, adequate slack is defined differently, with a gentle “S” curve (Fig. 3) required for the ventricular lead, to mitigate the quadruped stance, the changing dynamics, physics and length of the neck, and their spirited disposition. Too little slack, visualized as a straight line out the tricuspid valve, increases the risk of dislodgement once the dog is awake because of the lack of accommodation for neck and body movement. For the atrial lead, there should be enough slack such that the lead body rests just above the tricuspid valve annulus (Fig. 3). Too little slack, or an “L” shape, can result in too much tension on the helix and increases the risk of dislodgement. Too much slack in the lead body impinges on the tricuspid valve and could also result in excessive force against the helix tissue interface and increase the risk of myocardial penetration. Of potential rare complications that can occur, asymptomatic perforation is a known phenomenon and in most cases does not result in electrophysiologic consequences [22]. Passive lead perforation was not noted in this review, but has been documented clinically 7 weeks after implantation into the RV apex [23]. Implementing a small change in slack can result in large reductions in lead dislodgements. Although this is likely much more challenging due to smaller chamber sizes in the smaller patients that are a significant proportion of the patient population seen clinically in veterinary cases, slack initiatives should be implemented to help limit dislodgement.
An understanding of lead type construction and fixation properties is also important. This review demonstrated that both active and passive lead types appear safe and reliable for implantation in either chamber. There was no statistical difference between the two groups (active vs. passive) in the incidence of dislodgement or perforation (Table 1); however, the study was not powered for this endpoint.
This review also suggests that an active fixation lead implanted into the RA appendage (44 implants in this review) by experienced operators using appropriate techniques is safe in the short term and effective (in terms of lead electrical performance). Such an approach has not been fully utilized clinically, due to the perception that an optimal lead design for veterinary patients does not yet exist, that the thin walled RA appendage will not necessarily allow for proper fixation into the tissue, the presumption that there is a greater risk of perforation, and recognition of the need to develop optimized techniques to make atrial pacing more reliable [5, 24].