**5. Treatment of conductive tissue disorders**

Cardiac CSDs are a major cause of morbidity and mortality. Approximately 1% of the general population has CSDs necessitating permanent pacemakers (PPM), with incident rates continuing to rise each year [41]. The first implantable pacemaker by Senning in Stockholm in 1957, was an extravascular pulse generator with leads implanted into the ventricular myocardium of a patient with complete heart block. Since then, several innovations have made pacemakers more robust. Most modern pacemakers comprise a pulse generator implanted subcutaneously, that is connected to lead(s) that traverse transvenously into the myocardium of the heart chamber(s). Pacing has gained complexity and now includes dual chamber pacing (right atrium and ventricle), continuous resynchronization therapy (CRT), leadless pacing and most recently, conductive tissue pacing as shown in **Figure 3**.

### **5.1 Single and dual chamber pacemakers**

Single chamber pacemakers are the simplest form of pacing: they have a single lead implanted into the myocardium of the right atrium or the right ventricle

*Conduction System Disorders Associated with Valvular Heart Disease and Interventions DOI: http://dx.doi.org/10.5772/intechopen.108558*

### **Figure 3.**

*Treatment of conduction system disease with different types of pacing techniques.*

(**Figure 4A**). Single lead pacing is a cure for symptomatic conductive tissue disorders in the short term. However, it was not physiologic as a ventricular contraction occurred irrespective of atrial activity; with loss of synchronized atrial contraction in ventricular single chamber pacing, the ventricular filling would theoretically be diminished. Thus, Ventricular single-chamber pacemakers are now primarily used in patients with poor atrial ejection fraction, namely persistent atrial fibrillation, where the atrial mechanical coupling is compromised. Atrial single-lead pacemakers are theoretically also useful in treating isolated sinus node dysfunction but are rarely used as there is usually concomitant AV and sub-AV node disease.

To preserve atrial and ventricular synchrony, dual-chamber pacemakers were developed, whereby both an atrial and ventricular lead are implanted into the myocardium (**Figure 4B**). Improved synchrony by dual-chamber pacemakers translates to improved outcomes in some but not all populations. A 2004 Cochrane review of 26 studies comparing dual to single-chamber pacemakers revealed a significant reduction in atrial fibrillation and a non-significant reduction in heart failure, stroke and mortality with dual-chamber pacing [42]. Interestingly, amongst elderly patients, there was no difference in clinical outcomes between single and dual chamber pacemakers, likely reflecting higher rates of baseline atrial fibrillation in this age group [43].

**Figure 4.**

*(A) CXR showing a single chamber pacemaker with pacing lead placed in the RV. (B). CXR showing a dual chamber pacemaker following mitral valve replacement and tricuspid valve annuloplasty.*

### **5.2 Leadless pacemaker**

Leadless pacing is a novel therapy whereby an electrical impulse generator is percutaneously implanted directly into the myocardium, obviating the need for leads (**Figure 5**). The lack of leads and subcutaneous pulse generator has the theoretical benefit of avoiding lead-related (ex. lead infections, lead failure, tricuspid regurgitation) and subcutaneous pocket (ex. Pocket infections, hematoma) complications.

At this time, the majority of literature is on two leadless pacemakers: Nanostim (St. Jude Medical, St. Paul, MN,USA) and Micra (Medtronic, Minneapolis, MN). Nanostim had promising results from initial trials but was recalled due to premature battery failure and spontaneous detachment from the myocardium. For these reasons, it did not gain FDA approval and is not currently being implanted. An updated Nansostim system called Aveir VR gained FDA approval in March 2022 but no trials have been completed thus far. As Micra is the only FDA-approved leadless pacemaker with short to medium-term data, it will be the focus of this review. Although there are no clinical trials directly comparing Micra to transvenous

**Figure 5.** *CXR of a leadless pacemaker. An anteroposterior (A) and a lateral (B) view show the position of the leadless pacemaker.*

### *Conduction System Disorders Associated with Valvular Heart Disease and Interventions DOI: http://dx.doi.org/10.5772/intechopen.108558*

pacing, observational studies up to 1-year post-implant have shown a significant reduction in the odds of developing infectious complications compared to transvenous pacing, while maintaining electrophysiologic pacing parameters [44–46]. Leadless pacing shows promise in reducing complications, but long-term trials are needed to verify electrophysiologic stability.

### **5.3 Cardiac resynchronization therapy**

CRT is a pacing strategy to improve dyssynchronous left and right ventricular contraction; it involves biventricular pacing (RV and LV lead as shown in **Figure 6**) and can also be achieved in left-sided persistent SVC, congenital heart disease and anomalous coronary sinus veins [47–49]. Cardiac mechanical desynchrony is of particular concern amongst select patients with heart failure with reduced ejection fraction (HFrEF) [50]. Patients with HFrEF undergo cardiac remodeling over time which results in electrical dysregulation and interventricular delays ultimately causing dyssynchronous contraction of the right and left ventricles and poor cardiac function; these interventricular delays can be in the form of left bundle branch block or non-specific electrical conduction delays that increased QRS duration. Indeed, QRS duration correlates with worsening heart failure and sudden cardiac death and death from any cause [50]. CRT is an effective strategy to mitigate interventricular delays as the electrical generator can be programmed to initiate optimal timing of contraction for each ventricle. CRT has been shown to reduce mortality by up to 36% compared to medical therapy alone in patients with interventricular delay [51]. Given the evidence, ACCF/AHA/HRS guidelines suggest CRT for patients with Left Ventricular Ejection Fraction <35%, sinus rhythm, LBBB with QRS > 150 ms and NYHA class 2–4 symptoms on goal-directed medical therapy (class 1) [52].

Amongst HFrEF patients who would otherwise benefit from CRT, the presence of atrial fibrillation (AF) can be problematic. The rapid ventricular response or irregularity of AF can interfere with biventricular pacing capture rendering CRT ineffective in up to 67% of patients with persistent AF [53]. One solution to this dilemma is ablation followed by biventricular pacing. A recent meta-analysis showed worse mortality in AF patients compared to normal sinus patients that underwent CRT [54]. However, when AF patients underwent ablation, all-cause mortality

### **Figure 6.**

*CXR of CRT. An anteroposterior and lateral view showing the leads in the right atrium, right ventricle and a quadripolar left ventricular pacing lead through the coronary sinus.*

was not different between the normal sinus and AF patients undergoing CRT [54]. Most recent ACCF/AHA/HRS guidelines recommend CRT for AF patients that a) otherwise meet CRT criteria as above and b) AV nodal ablation or pharmacologic rate control will achieve near 100% ventricular pacing with CRT (class IIa) [52].

### **5.4 Conductive system pacing**

International guidelines for pacing currently recommend the above conventional myocardial pacing whereby slow-conducting myocytes are activated and therefore only indirectly activate the fast-conductive cardiac tissue (i.e. His-Purkinje network). Direct conduction system pacing (CSP) is emerging as an alternative approach to myocardial pacing; by directly activating conductive tissue, CSP has the theoretical benefit of mitigating electrical and mechanical ventricular desynchrony.

Two methods of CSP that have garnered attention are His Bundle Pacing (HBP) whereby a lead is inserted proximally close to His bundle, and Left Bundle Branch area Pacing (LBBaP) whereby a lead is inserted more distally close to the LBB (**Figure 7**). Wang et al. recently showed that HBP was feasible and safe with improvements in LVEF in patients with persistent AF and HFrEF who indicated implantable cardioverter defibrillator [55]. Abdelrahman et al. showed that patients with HBP had better survival and heart failure hospitalization rates compared to conventional RV pacing [56]. While HBP can be effective, it can be technically challenging given the small target area for lead placement, with longer procedure times even amongst experienced electrophysiologists compared to conventional pacing [57]. Furthermore, HBP has higher rates of lead dislodgement, up to twice as compared to conventional RV pacing [58]. LBBaP may be a better alternative in some patient populations. For instance, in patients requiring AV node ablation LBBaP is technically less challenging and pacing output to correct the left bundle branch block is lower. However, given the relative recency of CSP, there is currently a paucity of data including complications, such that international cardiology societies have yet to make recommendations [59].

One possible advantage of CSP over conventional pacing is the concept of synchrony. While right ventricular pacing is effective for the treatment of bradycardia and syncope, this approach can lead to electrical and mechanical desynchrony (particularly between ventricles) with the remodeling of the heart long-term; the broad consequences are higher rates of atrial fibrillation, heart failure and mortality [60, 61]. As previously described, Cardiac Resynchronization therapy (CRT) can mitigate hemodynamic and structural complications associated with only right ventricular pacing. Clinical trials have demonstrated that CRT reverses remodeling, and improves left ventricular ejection fraction (LVEF) and overall mortality in patients with reduced ejection fraction heart failure (HFrEF) [62, 63]. However, up to 40% of patients eligible for CRT demonstrate "non-response" (i.e. poor improvement in NYHA class, QRS duration, or echocardiographic parameters) [64]. Furthermore, while conventional CRT does improve QRS duration, it does not return it to a range seen in patients with intact conduction tissue, suggesting better therapeutic benefits with shorter QRS [65]. Whether CSP can be used as an alternative to, or as rescue therapy for patients with an indication for CRT remains to be seen. Several centers, including our own, are undergoing trials to address this question.

### **5.5 Tricuspid regurgitation following pacing**

As mentioned in Section 4.3, TR is an independent cause of mortality [66]. Pacemaker-associated TR can be primary TR by direct damage of the tricuspid valve by leads, secondary TR by RV dilation and dysfunction due to pacemaker *Conduction System Disorders Associated with Valvular Heart Disease and Interventions DOI: http://dx.doi.org/10.5772/intechopen.108558*

### **Figure 7.**

*CXR of dual chamber pacemaker. An anteroposterior and lateral view showing the position of a dual chamber pacemaker. RV lead is placed in the apical position (A) in comparison to placement at the region of LBBAP (B). Contrast injection through the delivery sheath showing the lead penetrating the RV septum to successfully deliver LBBAP.*

cardiomyopathy, or a combination of both. As TR is a major complication of pacing, prevention of TR is an important consideration.

Leadless pacemakers (see 5.2) have the theoretical benefit of minimizing primary damage to the tricuspid valve. However, Beurskens et al. showed that 12-month follow-up for leadless pacing had comparable rates of TR to the dual-chamber paced group, suggesting that lead-related damage to the tricuspid valve may not be the primary mechanism of TR following pacing [67]. The TR observed in leadless pacing may be due to RV dysfunction from pacemaker cardiomyopathy or damage to the tricuspid apparatus while crossing the tricuspid valve during implantation [68]. One way to avoid tricuspid apparatus entirely is to implant lead into the left ventricle via the coronary sinus. Schliefer et al. tested this hypothesis in a prospective trial comparing rates of TR at 12 months between pacing at RV-apex vs. RV-septum vs. LV-coronary sinus; coronary sinus pacing failed to achieve a statistically significant reduction of TR [69]. More studies over longer follow-ups are required to verify these findings.

### **6. Conclusion**

Given the aging population of the Western world, the burden of Valvular Heart Diseases is predicted to increase. Advancement and development of new percutaneous valvular interventions have been a boon for patients, particularly those deemed to be poor surgical candidates. Alongside these percutaneous valvular interventions are increased rates of CSDs, often requiring artificial pacing. Pacing techniques have also seen rapid advancements, with the advent of CRT, leadless pacing and conductive tissue pacing. Each of these has merit and warrants further research, particularly in the need to tailor different pacing modalities to different valvular interventions.
