Intraprocedural Assessment of Stimulation, Sensing, Detection, and Defibrillation

Physiology of Cardiac Pacing

Cardiac myocytes are nucleated specialized muscle cells that activate as a unit following cellular depolarization generating systemic perfusion with every contraction. They are composed of a phospholipid membranous outer layer, and their electrical state is characterized by a resting transmembrane electrochemical potential stemming from an actively maintained milieu of ions and charged particle gradients. In the normal steady state, the outer membrane is permeable to K ⁺ ions generating a predominantly negative inner and positive outer charge distribution steering the membrane potential towards −90 mV. Membrane depolarization mediated by the activation of voltage-gated ion channels or transporters can result from adjacent cellular action potential propagation or direct local electrical stimulation. During this process, the positively charged Na ⁺ and Ca ²⁺ ions are transported or enabled to flow intracellularly, whereas negatively charged ions, such as Cl ⁻ , flow out into the extracellular space yielding a change in the membranes electrochemical distribution with the intracellular compartment becoming more positive (+40 mV or greater) and the extracellular more negative. Following the rapid depolarization of the outer membrane, a repolarization efflux of K ⁺ to the extracellular compartment is initiated and mediated by various types of potassium channels. The more rapid inactivation of the Na ⁺ and gradual inactivation of Ca ²⁺ channels leads to the partial repolarization and plateau features of the action potential ( Fig. 29-1 ). The resting transmembrane potential is subsequently reestablished and maintained by energy-consuming processes such as the sodium-potassium exchange pump. The above features of depolarization and repolarization are characteristic for the majority of cardiac myocytes. However, specialized cardiac pacemaker cells, such as sinoatrial nodal cells, display unique action potentials characterized by more gradual and spontaneous depolarization patterns governed by Ca ²⁺ currents cycling dynamics.

Electrical excitation by myocardial pacing and the resultant mechanical contraction of the heart are dependent on free intracellular calcium. During an action potential a small amount of calcium ions is transported into the cytoplasm by the activated voltage-gated L-type calcium current and sodium-calcium exchanger. The free cytoplasmic calcium binds to the ryanodine receptors of the sarcoplasmic reticulum and leads to a rapid and extensive surge in intracellular calcium by means of the calcium-induced calcium-release positive feedback mechanism ( Fig. 29-2 ). The increased level of free calcium in the cytoplasm leads to myofilament contraction via binding of the troponin-tropomysin complex. This leads to a conformational change of that complex and allows binding of the myosin head to the exposed actin-binding sites. This excitation-contraction coupling occurs in near unison throughout the heart given the rapid action potential spread along myocytes under normal circumstances.

Determining Optimal Lead Position

In order to ensure adequate electromechanical coupling, pacing leads need to be positioned in a location within the desired chamber where adequate and stable contact with viable healthy tissue is achieved. Determining the most appropriate location for a pacing lead depends on the indication for lead implantation, the anatomic features of the targeted chamber, and the type of lead utilized (i.e., passive or active fixation lead).

Imaging for Lead Placement

Accurate positioning of a lead requires the implanter to be familiar with the fluoroscopic views and/or other imaging modalities, such as transesophageal echocardiography (TEE) or intracardiac echo (ICE), that may be used to guide lead positioning. Most leads are positioned using standard posterior-anterior (PA) fluoroscopy. Although this is convenient, it is not necessarily the optimal view. A standard PA view is not sufficient when targeting a standard pacing lead to the atrial septum, right ventricular outflow tract, or a specific region of the left ventricle. Further, the use of a single view may lead to inappropriate positioning if the cardiac and mediastinal anatomy is unconventional. Hence angulated views such as right anterior oblique (RAO) or left anterior oblique (LAO) should be utilized to ensure accurate lead positioning ( Fig. 29-3 ). Finally, fluoroscopic guidance alone has been shown to have suboptimal accuracy. In a prospective series of patients who had their pacing lead positioned in the midseptal position according to standard criteria in the LAO 40-degree view, actual lead positioning along the septum as confirmed by postoperative computed tomography was correct in fewer than 50% of cases, whereas in more patients (59%) the lead was anchored in the adjacent anterior wall. Given the limitation of utilizing only standard fluoroscopic views, selective views or adjuvant intraprocedural imaging modalities, such as TEE or ICE, should be considered when targeting lead location is desired. Paced QRS morphology and standard QRS axis evaluation of lead position can also be utilized and may be particularly useful in determining an apical versus nonapical site of pacing, as well as a septal versus lateral position ( Fig. 29-4 ).

Lead Placement

Right Atrial Leads

For right atrial leads the location providing the lowest pacing threshold and greatest sensed P waves is typically desired. Positioning the lead in the right atrial appendage (RAA) is often preferred for stability (i.e., lower risk of dislodgement) and a lower risk of perforation. It is also thought by some that right atrial lead location may alter the development of atrial fibrillation (AF). However, there does not appear to be an advantage of pacing a specific region (right atrial free wall, RAA, or coronary sinus [CS] ostium) or simultaneously pacing the CS ostium and RAA in terms of the frequency of AF. However, CS ostial pacing results in a higher rate of lead dislodgement. Further, rates of perforation and right-sided pneumothoraxes are higher when active fixation atrial leads are positioned along the lateral wall of the right atrium, although these complications may also occur with RAA lead placement ( Fig. 29-5 ). Pneumomediastinum may also occur with active fixation atrial lead delivery. Accurate lead positioning and careful implant technique are both useful in minimizing complications. Passive fixation leads have comparable durability to active fixation leads and tend to require shorter fluoroscopy time for implantation, demonstrate a better pacing threshold acutely, and are less likely to cause myocardial perforation. However, passive fixation leads have higher rates of dislodgement, may be more challenging to position due to a lack of trabeculae, and may be more difficult to extract chronically. By testing fixation (e.g., applying slight pulling tension on the lead to ensure it is well attached) and providing adequate lead slack, passive fixation lead dislodgement can be minimized.

Left Ventricular Leads

Optimal left ventricular (LV) pacing requires placement of the lead in a stable location that is free of significant phrenic nerve stimulation (PNS) and is likely to result in clinical benefit. Typically, the posterolateral aspect of the LV is the site of latest activation and is most often used as a target site. The heterogeneous nature of cardiomyopathy, along with variations in conduction patterns, CS venous anatomy, and operator experience, may mandate placement in a different region. In general, the LV pacing sites yielding most optimal clinical response are located in the nonapical, basal to midventricular regions of the LV with the anterior, lateral, and posterior sites yielding comparable outcomes.

LV lead positioning may be guided to sites with later ventricular activation, as measured by the intraprocedural Q-LV. The Q-LV is the interval from the onset of the surface QRS complex to the peak of the sensed LV intracardiac electrogram (EGM) ( Fig. 29-6 ). A Q-LV greater than 95 msec has been independently associated with reverse remodeling and improved clinical response with cardiac resynchronization therapy (CRT). Hence implanters may wish to consider repositioning an LV lead if electrical delay of this magnitude or greater is not identified. At our center we typically reposition an LV lead when a delay is less than 85% of the QRS duration. Although Q-LV is often helpful, it can be markedly prolonged if the area is surrounded by scar. Hence it is important to look at the Q-LV value in combination with anatomic location, paced QRS morphology/axis, and other variables. RV lead positioning may also important for CRT response, but the evidence for this is inconclusive.

Evaluation for Extracardiac Stimulation

Intraprocedural evaluation of pacing-induced extracardiac stimulation should be undertaken for all leads. It may reflect a position with a higher risk of perforation with right atrial (RA) and RV leads or a position that is too anterior for RV leads. Assessment for PNS is essential for all LV lead positions. PNS has been documented to occur in one third of patients receiving unipolar or bipolar LV leads. Assessment for all types of extracardiac stimulation is done in a similar manner. It usually involves pacing at high output (10 V @ 0.4 or 0.5 msec pulse width [PW]) and using visual, manual, and fluoroscopic evaluations to determine whether PNS is present or absent. Despite using this approach, a significant number of patients will have PNS related to LV lead pacing in follow-up. The reasons for this vary, but anatomic factors (changes in physical position, alteration in LV volumes) and small movement of the LV lead that may be difficult to detect are likely the main factors influencing this. As a general guide, if PNS is present at a pacing capture threshold (PCT) ≤3.5 V @ 0.5 msec PW, an alternate pacing vector polarity, a new anatomic position, or pacing from a pair of narrow dipoles should be considered. The initial experience with quadripolar LV leads indicates that PNS is more readily manageable with these leads due to the larger number of pacing vectors and other lead spacing options that are available.

Despite technologic advancements and refinement of surgical delivery techniques, optimal lead placement remains a challenge at times. Suboptimal lead slack, a nonclinically significant dislodgement, or suboptimal lead placement does not necessarily warrant reintervention given the risks of surgical reintervention. It is generally preferred to reevaluate pacing and sensing thresholds, as well as clinical response due to these risks.

Assessing for Current of Injury

When a pacing or defibrillation lead tip is fixated to the endocardium (e.g., when the helix screws into the tissue), local injury occurs. This is referred to as a current of injury (COI) pattern. COI is reflected acutely as an increase in amplitude of the local intracardiac EGM, along with ST segment elevation in this signal ( Fig. 29-7 ). This process can be observed with both active and passive fixation leads but is more pronounced for active fixation leads due the direct trauma from the helix entering the myocardium. Assessing the acute magnitude of COI has been associated with adequate active lead fixation. The average COI amplitude 80 msec into the onset of the EGM for adequately fixated leads is usually approximately 10 mV versus values <5 mV for unstable leads ( Fig. 29-8 ). Despite the potential utility of COI assessment, it is not possible to provide specific values for COI that do or do not indicate adequate local fixation given a lack of prospective data.

Wavelet Size, Slew Rate, and Lead Impedance

In general, an ideal site for lead placement is one with a large sensed signal and low PCT. Yet achievement of these outcomes is not always possible.

Slew Rates

The slew rates of electrocardiogram recordings describe the change in voltage with respect to time ( Fig. 29-9 ). With larger or steeper slew rates, the signals become sharper and easier to identify and record. Signals with very high slew rates likely represent good tissue contact. However, slurred signals with low slew rates can also be recorded despite good tissue contact between the lead tip and myocardium (e.g., when the lead is in contact with scar tissue). The evaluation of slew rates can be an adjunctive tool with other previously mentioned measures of adequate lead positioning, but it should not be relied on in isolation. When evaluated in patients undergoing active fixation pacing leads, slew rate values alone during the fixation process do not distinguish better from poorer fixation attempts.

Stimulation Threshold Testing and the Strength-Duration Curve

Measuring a PCT can begin decrementing voltage output starting from a modest level, such as 5 V, meanwhile maintaining a fixed PW, nominally at 0.5 msec. As capture begins to fail with lower outputs, the voltage level at which constant capture is observed is the PCT ( Fig. 29-10 ). Subsequently, similar steps are taken with a fixed voltage amplitude and decrementing the PW to determine its minimal PCT. A strength-duration curve is automatically constructed in most modern CIEDs to aid in the optimization of pacing output programming with the aim of prolonging battery longevity. The identification of rheobase and chronaxie from the strength-duration curve is essential for such programming ( Fig. 29-11 ). Rheobase represents the minimum amplitude (V) with the longest duration (PW) to reach pacing threshold. Chronaxie is the PW at double rheobase. Programming pulse duration to chronaxie with a doubling of voltage threshold at this point to achieve a safety margin has been shown to reduce battery drain and prolonged device longevity. Programming the PCTs at both extremes of too long a PW or amplitude will significantly increase battery drain and decrease battery longevity.

The strength-duration curve has direct relevance to clinical practice. As noted earlier, low PCTs can sometimes be difficult to obtain due to the presence of myocardial disease, scar, and other factors. Hence higher PCTs may be all that can be achieved in some situations. This may have a profound impact on device longevity. This situation is more commonly observed with LV leads due to anatomic limitations, the desire to pace from nonapical sites, and the occurrence of PNS. Clinically deciding between multiple vectors, particularly with a quadrapolar LV lead, can be enhanced by employing the strength-duration relationship information ( Case Study 29-1 ). Extending the PW is one method of reducing the energy output and extending device longevity.

Case Study 29-1

Clinical Application of the Strength-Duration Curve

A 69-year-old female with anthracycline-induced cardiomyopathy (ejection fraction 28%), left bundle branch block (QRS duration 155 msec), and a remote single chamber implantable cardioverter-defibrillator (ICD) implantation (primary prevention) presents with progressive heart failure symptoms (now class III limitation). The patient's functional status has worsened over the past 6 months despite heart failure medical optimization. She is considered to be a good candidate for cardiac resynchronization therapy (CRT-D) and undergoes a successful implant. She also had a new right ventricular high-voltage ICD lead added, and the old one was abandoned due to lead fracture. Her left ventricular pacing lead is a quadrupolar Medtronic 4298 pacing lead and ICD generator was a Medtronic Viva Quad XT CRT-D device (Medtronic, Minneapolis, MN).

The patient had a good recovery and her device was being tested on the first day postoperatively. Figure E29-1 illustrates all the possible programmable options for her left ventricular (LV) pacing lead and Figure E29-2 depicts the anatomic location of her LV lead. Which configuration should be selected?

Discussion

Optimal response to CRT hinges on ideal positioning of the left ventricular pacing lead. It should be in the most basal and lateral position if possible. With the advent of quadrapolar pacing lead technology, the pacing lead can now be positioned in more stable locations, even if more mid or distal in the left ventricular epicardial venous system, and still pace more basal with the proximal pacing poles. In this particular case, the lead was positioned in a stable basal location; thus pacing from any electrode configuration is acceptable in terms of location of activation. As such, the most important guiding principle in selecting the most ideal pacing configuration is choosing one that requires the least energy and battery expenditure for pacing to prolong battery longevity. Figure E29-3 illustrates how increasing pacing amplitudes and pulse widths are associated with greater energy expenditure with the most ideal pacing output being at chronaxie. In this particular CRT system, the device provides all of this integrated pacing information based on the strength-duration principle for each pacing configuration and provides the anticipated battery longevity. Thus selecting the configuration providing the longest battery longevity in this case makes any of the true bipolar LV1-LV2, LV1-LV3, and LV1-LV4 configurations acceptable options.

Wedensky Effect and Wedensky Facilitation

During pacing threshold testing, after decreasing the amplitude of stimulation and reaching the PCT, increasing the pacing amplitude of stimulation slightly above that capture threshold often does not resume capture. Repeat pacing at much higher amplitudes may be necessary to resume capture at the minimal threshold or even at a new subthreshold amplitude. For instance, if loss of tissue capture occurred with 1 V @ 0.5 msec PW, increasing the amplitude back to 1.2 V @ 0.5 msec PW may not resume pacing but rather a 2 V @ 0.5 msec PW output may be necessary to reinitiate capture. This phenomenon can be explained by the Wedensky effect, consisting of a prolonged lowering of excitability threshold induced by a strong stimulus ; changes in passive membrane properties are presumed to be the mediating processes. Wedensky first described this effect in 1886 and subsequently described another interesting observation now termed Wedensky facilitation. Wedensky facilitation may be observed during PCT and refers to increased excitability distal to the site at which impulse propagation is arrested. An example of Wedensky facilitation can be observed in patients with complete heart block whereby a ventricular escape complex or paced beat result in enhanced AV nodal conduction ( Fig. 29-12 ).

Bipolar and Unipolar Stimulation

Most contemporary pacing leads are bipolar; being comprised of two electrodes; a cathode and an anode. Conventional electric current flows through individual conductors from cathode to anode. A true bipolar circuit, either pacing or sensing, refers to one between two relatively narrow spaced electrodes on the same lead ( Fig. 29-13 ). This is typically from a cathode on the electrode tip to an anode, which is typically the ring electrode. A wider circuit on the same lead or between leads is referred to as integrated bipolar ( Fig. 29-14 ). An integrated bipolar circuit typically involves a lead tip cathode and a defibrillation coil or ring anode. Unipolar circuits include the lead tip (cathode) and pulse generator (anode) and are large (i.e., the upper body). Intraprocedurally, a unipolar circuit can be readily accomplished by connecting the cathode (black) programmer pacing cable connector to the lead tip and the anode (red) connector to a surgical instrument (e.g., self-retaining retractor or forceps) that is in direct contact with the wound. Unipolar pacing is more readily identified on surface electrocardiography by a much larger pacing stimulus artifact, is more susceptible to detecting noncardiac signals, and stimulating extramyocardial tissues as compared with bipolar circuits. There are subtle differences between impedance and PCT with bipolar and unipolar leads, but these are not large enough to be clinically significant.

Finally, if a unipolar circuit is utilized (e.g., older leads, bipolar leads have been reprogrammed to unipolar due to partial lead failure, the CIED has automatically changed the pacing to unipolar due to end of battery or power-on rest issues) it is vital to ensure the CIED is fully inserted into the device pocket to complete the unipolar circuit. Careful review of the pacing circuit preprocedure can prevent adverse events from occurring during the procedure, particularly in situations where a patients does not have an underlying escape rhythm (i.e., in pacemaker-dependent patients).