Cardiac resynchronisation therapy (CRT) entails the coordinated pacing of the left and right ventricles. Patients with severely impaired left ventricular ejection fraction or malignant ventricular arrhythmias are implanted with devices that allow CRT and defibrillation, which are known as cardiac resynchronisation therapy defibrillators (CRT-D). Patients who have no defibrillation indication receive cardiac resynchronisation therapy pacing via a cardiac resynchronisation pacemaker (CRT-P).

IMPLANT PROCEDURE

Device implants are mostly performed under conscious sedation with local anaesthesia. During implantation, the pulse generator is usually situated in a subcutaneous pocket at the infraclavicular region of the chest. Venous access is obtained via various approaches, such as a cephalic cutdown or a modified seldinger approach through axillary or subclavian veins.

In patients who are not in permanent atrial fibrillation, the system commonly incorporates a right atrial pacing and sensing lead, similar to that of a dual chamber pacemaker. This aids coordination of atrial and ventricular contractions. Left ventricular pacing is achieved by positioning a lead with one or more electrodes in a suitable coronary sinus branch, preferably a lateral branch away from the apex and the septum. Biventricular pacing is accomplished by the implantation of a right ventricular lead endocardially at the right ventricular apex or right ventricular septum.

I. CARDIAC RESYNCHRONISATION THERAPY AND HEART FAILURE

Heart failure is a global pandemic with increasing prevalence that results in significant morbidity and mortality. The past few decades have seen large improvements in the prognosis of patients with cardiac failure, and CRT has established itself as a crucial component of therapy in heart failure therapy in patients with conduction disorders. CRT is often incorporated with a defibrillator in patients with significant left ventricular ejection fraction impairment and with concomitant defibrillator indications.

Cardiac Dyssynchrony
QRS prolongation on electrocardiogram, particularly left bundle branch blocks (LBBB), results in electrical dyssynchrony in heart failure patients (Refer to Figure 3A). This leads to dis-coordinated contraction between the right and left ventricle, and also within the left ventricle itself. There is excessive left ventricular myocardial wall strain and also decreased left ventricular output, attributed to dyssynchronous contraction patterns caused by conduction delay.¹

​CRT functions by restoring synchronicity through stimulation of opposite left ventricular sites (pacing from lateral left ventricular wall and from the right ventricle) to re-establish synchrony, which translates to improved cardiac hemodynamics and reverse remodelling.^2,3 Studies have shown that CRT, compared to optimal medical therapy, is associated with improvements in patients’ New York Heart Association functional class exercise tolerance, quality of life and left ventricular ejection fraction. More importantly, CRT therapy has been shown to reduce heart failure related hospital admissions, and reduce mortality in patients with advanced heart failure.^4-8

Maximising Cardiac Resynchronisation Therapy Benefits
With significant mortality benefits observed with CRT, much effort has been focused on identifying patient factors that predict CRT response, which is generally defined as:

• Improvement in six minute walking distance of at least 25%, left ventricular ejection fraction improvement
• 15% improvement in left ventricular end systolic or diastolic volume or stroke volume

Invariably, 30% of patients undergoing CRT implants, according to standard guideline indications, are unable to benefit much from this modality of therapy.⁹

CRT in LBBB patients
In terms of patients selection, greater benefit of CRT has been demonstrated in females with non-ischemic cardiomyopathy, LBBB and long QRS durations. Current medical literature has shown associations with QRS duration and mortality or hospitalisation for any cause. CRT in patients with longer QRS durations has resulted in greater reduction in morbidity and mortality.

CRT in non-LBBB patients
The role of CRT in patients with non-LBBB patients, comprising right bundle branch block pattern electrocardiograms or intraventricular conduction delay (QRS prolongation that does not fulfil criteria for left or right bundle branch block), is less clear as subgroup analysis of seminal trials has revealed poorer response to CRT in comparison to patients with LBBB.

Analysis has shown most benefit being derived by patients with very broad non-LBBB QRS duration (greater than 180 milliseconds (ms)).

In narrow QRS heart failure patients, implantation of CRT is associated with excess mortality (Refer to Table 1).¹⁰

IMPLANTATION

Left ventricular lead 

With regards to implantation, the left ventricular lead is preferably positioned within a coronary sinus branch at the lateral wall of the left ventricle (Refer to Figure 4). Apical or septal positions were found to be suboptimal.

Further studies have shown that targeting left ventricular lead placement at the site of latest mechanical delay (site of latest electrical activation of the left ventricle) predict increased reverse remodelling and quality of life. This however can be limited by unsuitable coronary sinus anatomy which prevents ideal lead positioning.

Pacing timings
Optimisation of pacing timings between the left and right ventricle to achieve the narrowest QRS duration possible is also an essential component of the post-implant process, with the target QRS duration of less than 140ms being associated with mortality benefits (Refer to Figure 3B).¹¹ Echocardiography has also been used as an adjunct to CRT optimisation.

Biventricular pacing

Maximising biventricular pacing is paramount in CRT management post-implant and on follow-up. Achieving greater than 98.6% biventricular pacing was associated with incremental mortality benefits.12,13 This is achieved by optimal device programming, proprietary device algorithms and also the use of atrioventricular node blocking agents, such as beta blockers or digoxin.

Among patients whom optimal biventricular pacing is not achieved, atrial fibrillation is the most common cause of rapidly conducted ventricular response rate, which precludes biventricular pacing. In such situations, ablation of atrial fibrillation or atrioventricular node ablation can be performed.

Table 1  Cardiac Resynchronisation Guidelines for Heart Failure

II. CARDIAC RESYNCHRONISATION THERAPY IN CONDUCTION DISORDERS

Conventional right ventricular pacing via standard single or dual chamber pacemakers results in ventricular desynchronisation, which potentially leads to pacinginduced cardiomyopathy. Clinical trials have established a relationship between the degree of right ventricular pacing dependence and the risk of heart failure. In the context of patients with underlying heart failure who require frequent ventricular pacing, right ventricular pacing is associated with worsened cardiac hemodynamics.

CRT therapy as compared to conventional right ventricular pacing is associated with improvement in left ventricular reverse remodelling and reduction in left ventricular dyssynchrony, heart failure and hospitalisations. Patients that develop pacing-induced drop in left ventricular ejection fraction (LVEF) from a high degree of right ventricular pacing who subsequently undergo CRT “upgrades” experience improved quality of life, as well as reverse left ventricular remodelling.

Current guidelines recommend CRT in patients with significant ventricular pacing burden due to underlying atrioventricular block and heart failure with reduced ejection fraction (Refer to Table 2).

Table 2  Cardiac Resynchronisation Guidelines for High Ventricular Pacing Requirements

(Adapted from ESC 2016 Heart Failure Guidelines)¹⁴

FUTURE DIRECTIONS

• Multipoint pacing of the left ventricle is currently being studied as a solution to CRT non-response. By utilising a multi-electrode left ventricular lead positioned in the coronary sinus, multisite stimulation can be achieved in the hopes of overcoming underlying anatomical scar that result in slow conduction and late dis-coordinated contraction.


• Left ventricular pacing endocardially, which incorporates a lead being passed from the right heart through a ventricular or atrial septal puncture into the left ventricle, with the lead sited within the left ventricle itself, instead of through the coronary sinus, has experienced renewed interest in CRT non-responders. This facilitates placement of the left ventricular lead at the latest site of left ventricular depolarisation without being limited by coronary sinus anatomy and variations. As a result, studies have reported improved cardiac hemodynamics, at the cost of requiring permanent anticoagulation to prevent strokes, due to thrombogenicity of the lead within the left ventricle.

Future developments include the leadless left ventricular systems utilising a wireless receiver electrode in the left ventricle, paired with standard right ventricular leads, and together with a subcutaneous ultrasound transmitter to coordinate impulse delivery biventricularly.¹⁵

Assistant Professor Paul Lim is a Consultant with the Department of Cardiology at the National Heart Centre Singapore (NHCS) and an Assistant Professor at the Duke-NUS Medical School. He specialises in treatment of heart rhythm disorders with ablation or device-based therapy.

GPs can call for appointments through the GP Appointment Hotline at 6704 2222 for more information.

REFERENCES

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3. St John Sutton M, Ghio S, Plappert T, et al. Cardiac resynchronisation induces major structural and functional reverse remodeling in patients with New York Heart Association class I/II heart failure. Circulation 2009;120:1858-65.
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11. Cleland JG, Abraham WT, Linde C, et al. An individual patient meta-analysis of five randomised trials assessing the effects of cardiac resynchronisation therapy on morbidity and mortality in patients with symptomatic heart failure. European heart journal 2013;34:3547-56.
12. Hayes DL, Boehmer JP, Day JD, et al. Cardiac resynchronisation therapy and the relationship of percent biventricular pacing to symptoms and survival. Heart rhythm 2011;8:1469-75.
13. Padeletti L, Pieragnoli P, Ricciardi G, et al. Acute hemodynamic effect of left ventricular endocardial pacing in cardiac resynchronisation therapy: assessment by pressure-volume loops. Circulation Arrhythmia and electrophysiology 2012;5:460-7. 14. Ponikowski P, Voors AA, Anker SD, et al. [2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure]. Kardiologia polska 2016;74:1037-147.
15. Auricchio A, Delnoy PP, Butter C, et al. Feasibility, safety, and short-term outcome of leadless ultrasound-based endocardial left ventricular resynchronisation in heart failure patients: results of the wireless stimulation endocardially for CRT (WiSE-CRT) study. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2014;16:681-8.