Multi site left ventricular pacing for CRT nonresponders

Multi-site Left Ventricular (LV) pacing is an advanced evolution of Cardiac Resynchronization Therapy (CRT). While standard CRT uses a single lead in a tributary of the coronary sinus to pace the LV, multi-site pacing involves stimulating the left ventricle from two or more distinct locations. The goal is to achieve more near-simultaneous depolarization of the LV, especially in patients who have large areas of scarred tissue or slow conduction (fragmented QRS).

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Mechanisms of Action

The primary objective is to reduce the LV total activation time (LVTAT). By initiating the electrical impulse from multiple points, the wavefronts converge faster than they would from a single point, which:

• Reduces intra-ventricular dyssynchrony.
• Increases the dP/dt_max (the rate of pressure rise in the LV), improving contractility.
• Overcomes “dead zones” or areas of myocardial scar that might block a single pacing wavefront.

Technical Approaches

There are two primary ways to achieve multi-site LV pacing:

A. Multi-pole (Quadripolar) Leads

This is the most common clinical method. Using a single lead with four electrodes (quadripolar), the device is programmed to pace from two different electrodes on that same lead (e.g., Distal 1 and Proximal 4). This has been called Multipoint Pacing (MPP).

• Pros: Requires only one lead; reduces the risk of phrenic nerve stimulation by allowing multiple vector options.
• Cons: The pacing sites are limited to the anatomical path of that specific vein.

B. Multiple LV Leads

Two separate leads are placed into different branches of the coronary sinus (e.g., one in the posterolateral vein and one in the anterolateral vein). Using two leads in separate coronary veins has been called multizone pacing (MZP).

• Pros: Provides true spatial separation of pacing sites, which can be significantly more effective for wide-spread dyssynchrony.
• Cons: Higher procedural complexity, longer fluoroscopy time, and increased risk of lead dislodgement or venous complications.

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Clinical Indications & “Non-Responders”

Multi-site pacing is rarely the first-line approach. It is typically reserved for:

1. CRT Non-Responders: Approximately 30% of patients do not improve with standard CRT. Multi-site pacing is a “rescue” strategy for these individuals.
2. Significant LV Dilatation: In very large hearts, a single pacing site may be insufficient to synchronize the entire chamber.
3. Extensive Myocardial Scar: If the standard pacing site is near an old infarct, multi-site pacing can help “bypass” the slow-conducting scar tissue.

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MORE-CRT MPP randomized trial

MORE-CRT MPP randomized trial results were published in Europace in June 2025. Aim of the study was to check whether multipoint pacing (MPP) was associated with improved clinical outcomes in CRT non-responders. CRT patients were treated with conventional biventricular pacing for 6 months. Non-responders with less than 15% relative reduction in left ventricular end systolic volume were randomized to either conventional biventricular pacing or multipoint pacing and followed up for 6 months. The trial report concluded that multipoint pacing was associated with significant reduction of all-cause mortality or heart failure hospitalization in prior non-responders to conventional biventricular pacing. The devices used in this study allowed sequential pacing pulses to be delivered from two sites on the same LV lead.

MSP-Max: from 4 dipoles of 2 LV leads!

Acute hemodynamic effect of a novel dual vein multisite biventricular pacing has been reported in JACC: Clinical Electrophysiology. Left ventricular hemodynamics was evaluated using micromanometer-tipped catheter. Configurations tried were single lead conventional biventricular pacing, single lead multipoint pacing, three point pacing from distal dipoles of two LV leads and maximum multisite pacing (MSP-Max) from four dipoles of two LV leads. Twenty patients with nonischemic dilated cardiomyopathy and left bundle branch block were investigated during routine CRT implant procedure. Mean LV ejection fraction was 27% and native QRS 171 ms. Significant increase in LVdP/dT_Max compared to conventional biventricular pacing (P = 0.041) was noted in MSP-Max but no other multisite pacing options.