P1594Ventricular fibrosis spatial distribution and quantity is a key mechanistic determinant of ventricular fibrillation mechanisms

• Published in: European heart journal Vol. 40; no. Supplement_1
• Main Authors: Handa, B S, Li, X, Mansfield, C A, Jabbour, R J, Pitcher, D, Chowdhury, R A, Peters, N S, Ng, F S
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01-10-2019
• Subjects: Basic Science - Cardiac Biology and Physiology: Ion Channels, Electrophysiology
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehz748.0353

Abstract
Background
Ventricular fibrosis is known to play a critical role in initiation and maintenance of ventricular fibrillation (VF). Post myocardial infarction the quantity of fibrosis negatively correlates with survival. There is a lack of data on how the quantity and degree of fibrosis influences the mechanisms of VF itself. VF mechanisms remain debated, there are data to support both critical areas sustaining rotational drivers (RDs) and the contrary hypothesis of disorganized myocardial activation driving VF.
Purpose
We hypothesized that the underlying mechanism of VF is influenced by the spatial distribution and quantity of ventricular fibrosis.
Methods
Thirty-five Sprague-Dawley rats underwent permanent left anterior descending (LAD) ligation (n=11), 20mins LAD territory ischaemia-reperfusion (n=13) or in-vivo angiotensin infusion (500ng/kg/min, n=11) to generate compact (CF), patchy (PF) and diffuse fibrosis (DF) models respectively. After a 4-week maturation period, the hearts were explanted, Langendorff perfused and VF induced with burst pacing and 30μM pinacidil. Fibrillation dynamics were quantified using phase analysis, phase singularity (PS) tracking and our novel method of global fibrillation organisation quantification, frequency dominance index (FDI), which is a power ratio of highest amplitude dominant frequency in the frequency spectrum.
Results
Ventricular fibrosis for each group was characterized and quantified (CF: 22.3±3.2%, PF: 18.4±4.2%, DF: 5.8±1.3%, p=0.046). VF was driven predominantly by disorganised activity in CF, PSs were detected 26±7% of time comparative to 51.2±4% in DF and 69.5±8% in PF group (p=0.001). PF stabilised RDs, average maximum rotations for a single RD in PF were 31.6±7.1 comparative to 12.5±1.7 in DF and 6.4±1.1 in CF, p<0.001. The average maximum duration for a single RDs was significantly longer in PF (PF: 1231±365ms, DF: 568±68ms, CF: 363±41ms, p=0.014). Similarly, average rotations per RD were greater in the PF group (PF: 4.5±0.7, DF: 3.3±0.2, CF: 2.41±0.3 rotations, p=0.013). Total number of RDs/second were much greater with PF (PF: 12.4±2.0, DF: 5.4±0.8, CF: 3.1±1.1, p<0.001). VF organisation measured by FDI was higher in PF (PF: 0.61±0.07, DF: 0.47±0.04, CF: 0.33±0.03, p=0.004). RDs in DF showed a greater degree of meander comparative to PF (DF: 12.6±1.4 vs PF: 9.3±0.8 pixels, p=0.024).
Conclusion
VF mechanisms occur along a spectrum between organised activity sustained by discrete drivers and disorganised myocardial activation. The underlying VF mechanism can differ significantly dependent on the quantity and pattern of fibrosis. Patchy fibrosis stabilises RDs with localization to discrete areas and sustains an organised form of VF comparative to CF where VF is largely disorganised. Characterising the degree and pattern of fibrosis in patient groups vulnerable to VF might be beneficial in identifying patients with suitable targets for ablation.
Acknowledgement/Funding
BHF Programme Grant PG/16/17/32069