**Abstract**

The aging population of the Western world will lead to an increase in cardiac pathologies. Valvular disorders include a spectrum of progressive diseases that confers mechanical and functional impairment, including issues with the cardiac conduction system. Pacemakers are a therapeutic standard to reinstate the synchrony of cardiac contraction. Permanent pacemakers are often required for severe, chronic presentations and have been effective in nullifying symptoms and improving cardiac function. Yet, these devices impart new risks and complications that require additional interventions. However, recent advancements in leadless pacemakers and cardiac resynchronization therapy provide a novel approach to applying pacemaker technology and have been shown to reduce associated risks and improve patient outcomes.

**Keywords:** aortic stenosis (AS), mitral regurgitation (MR), infectious endocarditis (IE), mitral valve, aortic valve, left ventricular hypertrophy

### **1. Introduction**

Amongst all cardiac procedures carried out in the United States, it is estimated that 10–20% were related to Valvular Heart Disease (VHD) [1]. Moreover, given the increasing age of the Western and developed population, the burden of VHD is expected to increase. As VHDs become severe and/or symptomatic, surgery is eventually required. There are invasive and minimally invasive percutaneous interventions for valve repair and surgery, with varying conductive tissue complications. Conversely, treatment for the underlying conductive disease (i.e. pacemakers) has valvular complications. This review will outline these complications.

### **2. Conduction tissue anatomy**

The heart's pumping action is mediated by specialized muscle fibers known as cardiomyocytes. Unlike typical myocytes, they possess the capacity to self-initiate an electrical impulse for muscular contraction. They are regulated by a highly specialized group of cells compacted to form the conduction system (**Figure 1**).

The sinoatrial (SA) node (the pacemaker) is the site of impulse generation and is located between the superior vena cava (SVC) and the right atrium (RA).

The generated electrical pulse propagates from the SA node and travels along the myocardium of the left and right atria, stimulating contraction and propelling blood from the atria into the ventricles. The electrical signal then travels along specialized cardiac muscle fibers to the atrioventricular (AV) node. The specialized cells that guide the signal are collectively known as the internodal pathways; 3 of which originate from the RA and 1 from the left atrium (LA). Upon reaching the AV node (AVN), the electrical impulse slows down, allowing the adequate filling of the ventricles before contraction. The electrical impulse then travels to a group of specialized cardiac cells called the His Bundle, which divides along the septum into left and right branches terminating into the Purkinje fibers. Signal transduction along these fibers results in ventricular contraction to expel the blood from the heart and into pulmonary (from the right ventricle) and systemic (from the left ventricle) circulation.

## **3. Conduction tissue disease**

Cardiac conduction tissue disorders are a group of disorders that impair the above system. They are classified according to the area affected by disease processes as shown in **Figure 2**.

### **3.1 Sinus node dysfunction**

Sinus Node Dysfunction (SND) refers to the ailment in the SA node's ability to generate electrical impulses. SND primarily affects older individuals (over 65 years of age), however, individuals of any age can present with it. As such, the most common pathological mechanism is degenerative fibrosis of the SA node and its subsequent remodeling. Any factors that affect the ionic currents of the pacemaker cells can lead to the presentation of SND. These include beta-blockers, calcium channel blockers and antiarrhythmic medication. SND is often associated with electrolyte imbalances such as hyperkalemia, hypokalemia or hypercalcemia.

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

**Figure 2.** *Conditions associated with conduction system abnormalities.*

A characteristic form of SND is a tachycardia-bradycardia syndrome, whereby tachycardia persists but devolves into severe bradycardia either spontaneously or as an attempt to medically manage tachycardia [2]. SND can also present with varying degrees of severity with differing ECG findings. First-degree SA block is asymptomatic and cannot be detected on the ECG. The second-degree SA block is characterized by a dropped P wave but is not associated with any change in the P–P interval. Third-degree SA block is complete dysfunction of the SA pacemaker cells with no discernable P wave on the ECG (23).

### **3.2 Atrioventricular block**

Atrioventricular block (AVB) refers to disorders whereby the propagation of impulse generated in the SA node is impaired from propagating to the ventricles in varying degrees. AVB can be secondary to defined cardiomyopathy but often is idiopathic. AVB can also be a consequence of intervention for valvular disease. Diagnosis and progression of AVB are determined by the abnormalities in the AV electrical activity and which cardiac structure is affected.

First-degree AVB (AVB I) is associated with a prolonged PR interval, indicating a delay in the AVN, which is typically considered benign due to normal ventricular filling. However, the patient may become symptomatic with increased activity due to deterioration of AVN conduction associated with a faster heart rate. Moreover, cases with marked first-degree AVB (delay greater than 300 ms) can result in shorter diastolic time and produce "pacemaker-like syndrome" symptoms. This is a major mechanism of increased risk of future atrial fibrillation and indicates the need for pacemaker implantation [3].

Second-degree AVB (AVB II) is further sub-classed into Mobitz Type I (Wenckebach) and Mobitz Type II. Mobitz Type I AVB classically presents with progressive prolongation of the PR intervals until there is a non-conducted P wave. Mobitz Type I AVB typically affects the AV node itself and is deemed to be benign and reversible. Mobitz Type II presents with constant PR intervals that are preceded and followed by a non-conducted P wave. Mobitz Type II AVB is a challenging diagnosis as the PR interval may appear normal and the mere presence of non-conducted P waves is not an automatic indication of Type II AVB. Type II AVB affects the conduction system distal to the AV node in the His Bundle system.

Third-degree AVB (AVB III) is also known as complete AVB in which there is complete dissociation between atrial and ventricular conductive tissue. Thus, any presence of QRS complexes is independent of the generation of P waves. Ventricular contraction is due to intrinsic junctional or ventricular rhythm and poses the greatest risk of hemodynamic instability and fatal cardiac arrhythmias resulting in death.

### **3.3 Left bundle branch block**

Left bundle branch block (LBBB) refers to impaired conduction of branches of the His Bundle system, specifically the narrow anterior fascicle and the broader posterior fascicle. Typically, LBBB presents with prolonged QRS (>120 ms), absent Q wave in V6 and rS complexes in V1-V2 [4]. In isolation, LBBBs are asymptomatic and confer no risk to the patient. However, LBBBs underlying etiology is dilated cardiomyopathy, which itself can be caused by ischemic, infective, infiltrative or valvular cardiac disease [5]. Moreover, it has been shown that individuals with LBBB and incomplete AVB carry a greater risk of progressing to complete AVB [5].

Whilst there is no complete treatment for LBBB, cardiac resynchronization therapy (Section 5.3) has been shown to benefit patients who present with heart failure alongside LBBB (27).

## **4. Conductive tissue disorders associated with Valvular interventions**

Historically, heart surgery has been the only option amongst patients with symptomatic severe valvular heart disease. However, for patients that are not surgical candidates, minimally invasive transcatheter approaches are increasingly employed for valve repair and/or replacement. Each of these interventions can be associated with differing rates of Conductive System Disorders (CSDs). Complete or high-degree AVB is a particular concern, for which guidelines from the American College of Cardiology/American Heart Association recommend permanent pacemakers if there is no resolution after 1-week post-surgical intervention [6]. The conductive tissue complications following invasive and minimally-invasive VHD interventions will be outlined here.

### **4.1 Aortic valve interventions**

Transcatheter aortic valve replacement (TAVR) is a minimally invasive technique for symptomatic severe AS that has gained wide adoption, having been performed in over 400,000 patients worldwide as of 2017 [7]. While initially reserved for patients at high surgical risk, TAVR has shown non-inferior or superiority to SAVR for all-cause mortality, cardiovascular mortality and stroke amongst medium and low surgical risk populations up to 5-year follow-up [8, 9]. However, TAVR has lower valve durability and higher rates of paravalvular leaks and CSD, namely left bundle branch blocks and AVBs requiring pacemaker insertion [8–10]. The rates of pacemaker insertion post-TAVR vary based on type (self-expanding vs. balloon expanding) and generation of valve used. Meta-analyses have reported pacemaker insertion rates of approximately 3.8–6.5% for balloon-expanding vs. 12–25.8% for self-expanding valves [11, 12]. The self-expanding valves do have increased effective orifice area at the cost of worse rates of CSD, though the clinical significance

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

of better orifice area is not born out in short to medium-term studies done thus far [11]. The mechanism of conductive tissue disruption is thought to be from injury to the AV node while the deployment of the valve into the left ventricular outflow tract; self-expanding valves by their nature exert a greater radial and compressive force on peri-valvular conductive tissue over time which is likely results in the observed outcome of increased pacemaker requirement. There is ongoing research about the predictors of pacemaker requirement following TAVR in either type of valve, but strong associations include male sex, baseline Mobitz type 1, baseline wide QRS, depth of valve implant, and intraprocedural AV block [13–15]. Given the increased risk of LBBB post-TAVR, pre-existing right bundle disease (RBBB or bifascicular block) predisposes to complete AVB requiring pacemaker [13].

Surgical Aortic Valve Replacement (SAVR) is a well-established procedure for the treatment of severe aortic stenosis or regurgitation. An important benefit of SAVR over TAVR is valve durability, particularly with mechanical valves as these are not possible currently with TAVR. SAVR has traditionally been performed using sutured valves, with post-surgical pacemaker requirement in 2–4% of cases [16–18]. However, with the advent of TAVR, sutureless valves (similar in concept to balloonexpanded TAVR valves) are increasingly being used in SAVR as they minimize procedure and hospital time [19]. Given the stent-expanding nature of sutureless SAVR, they result in higher rates of pacemaker requirement compared to conventional SAVR [20, 21]. There are limited trials comparing SAVR to TAVR; many have shown worse rates of pacemaker requirement in TAVR but the TAVR cohorts include both self-expanding and balloon-expanded valves [22–24]. When comparing balloon-expanded TAVR to sutureless SAVR however, the rates of pacemaker requirement were similar over a two-year follow-up [25]. More studies are quired for recommendations between sutureless SAVR and TAVR.

### **4.2 Mitral valve interventions**

The Mitral valve (MV) is significantly more complex than the aortic valve due to the papillary muscles and chordae tendinea that tether leaflets to the left ventricle, as well as its ovoid annulus. The definitive treatment for severe MV stenosis or regurgitation is surgical replacement or repair, but this is limited by surgical risk. The incidence of AVBs following Mitral valve surgical replacement is up to 18% AVB I, 5% AVB II, and 5% AVB III [26–29]. Following mitral valve surgical replacement, a permanent pacemaker is required in approximately 2–11% of cases [30]. Notably, Mitral valve surgical replacement is associated with an approximately 20% higher risk of CSD requiring a permanent pacemaker compared to aortic valve surgical replacement [28]. This is likely related to the proximity of the mitral valve (MV) annulus to the AV node, Specifically, the posterolateral artery which supplies the AV node is adjacent to the mitral annulus and may be damaged intra or post-surgically.

While AVBs are well-document in the surgical intervention of MV, Conductive tissue abnormalities are uncommon following mitral transcatheter edge-to-edge repair (TEER). A case report of a patient with a baseline trifascicular block did show complete AVB following the MitraClip procedure with a proposed mechanism of injury being the instrumentation of MV apparatus during the procedure [31]. Similarly, a case reported the development of Mobitz type II following the Cardioband procedure subsequently degrading into complete AVB. The mechanism of conductive tissue injury was thought to be the deployment of screws into the MV annulus to anchor the Cardioband system. These case reports highlight the significance of MV annulus instrumentation. Nevertheless, transcatheter mitral valve repair is generally not complicated by CSDs.

Transcatheter Mitral Valve Replacement (TMVR) is technically challenging given the complexity of the mitral valve apparatus. Given its infancy, several TMVR systems are undergoing development and research and as of 2020, ACC/AHA guidelines for VHD do not offer any recommendations for TMVR [10]. The TMVR techniques currently in development vary in the approach to valve deployment (transapical vs. transfemoral/transeptal) and mechanism of expansion into valve apparatus (self-expanding vs. balloon-expanding), which theoretically could have implications for CSDs. Yet, AV blocks or bundle branch blocks have not been reported as complications post-valve deployment shortterm in feasibility studies thus far [32–35].

### **4.3 Tricuspid valve interventions**

Moderate to severe tricuspid regurgitation is often overlooked as a contributor to mortality, despite its association with increased mortality even after adjusting for LV dysfunction and pulmonary hypertension [36]. It can be categorized as primary (congenital or acquired abnormality of tricuspid apparatus itself) or secondary (abnormality of tricuspid apparatus occurring as a consequence of pulmonary hypertension, right or left ventricular dysfunction). RV damage because of TR can become irreversible, suggesting the benefits of earlier intervention [37]. Surgical intervention is indicated for symptomatic patients with severe primary TR, or in asymptomatic patients with worsening RV dysfunction. Similarly, ESC guidelines recommend early consideration of surgical intervention in patients with symptomatic TR or mildly symptomatic severe TR with RV dilation [38]. However, surgical correction has significant surgery-related morbidity and mortality. Transcatheter Tricuspid Valve Interventions (TTVI) aimed at poor surgical candidates are undoing research and development and include direct annuloplasty, leaflet approximation or valve replacement. TTVIs have shown improvement in RV performance and hemodynamics up to 6 months post-procedure, as well as improvement in HF rehospitalizations and survival up to 1-year post-procedure. An expected complication of TTVIs is heart block, though this has not been a widely report complication in preliminary reports [39, 40]. As the TTVI experience improves, it may become an effective strategy to treat pacemaker-induced TR (Section 5.5).
