Regional and Global Changes in Cardiac Function After High-Intensity Ultrasound Septal Reduction Therapy for Hypertrophic Cardiomyopathy

Background: Our group has developed a high-intensity ultrasound (HIU) ablation catheter for minimally invasive septal reduction therapy to alleviate left ventricular outflow tract obstruction (LVOTO) and symptoms of hypertrophic cardiomyopathy [1]. In addition to reduction in basal interventricular septal (IVS) thickness, reducing IVS contractility is an important mechanism in translating this therapy from swine to effective LVOTO reduction in humans. In this study we use cardiac magnetic resonance (CMR) to evaluate global and regional changes in left ventricle (LV) contractility after HIU ablation of the IVS in swine. CMR regional strain analysis for non-ischemic lesions is not well described in literature.

Methods: EEleven healthy farm pigs (40-45 kg) underwent HIU catheter ablation via femoral venous access targeting the IVS from the right ventricle. Animals were imaged on a 3T Ingenia CX whole body MRI scanner (Philips, Best, Netherlands) at baseline, immediately post-ablation, and during 1 and 3 months follow up. Ejection fraction (EF), ventricular volumes, global and segmental myocardial strain were assessed using Circle Cardiovascular Imaging (cvi42) software. Regional (circumferential and radial) strain was analyzed at each timepoint in each of the 16 AHA segments (apex was excluded from analysis).

Results: HIU ablation of the IVS was effectively performed in all swine (Figure 1). Global EF decreased from 58.4±4.6% pre-ablation to 47.0±5.5% immediately post-ablation (p=0.0003) but recovered by 1- and 3-months post-procedure (Table 1). Global radial strain (GRS) decreased from 28.0 ± 4.3% at baseline to 21.0 ± 2.1 % immediately after ablation (25% decrease, p=0.0009) with subsequent recovery to 27.7 ± 1.9% by 3 months (p=0.4333) (Table 1). Global circumferential strain (GCS) decreased immediately after ablation from -16.3 ± 1.9% to -13.5 ± 0.9% (p=0.0029) but recovered to 15.6 ± 0.6% by 3 months (p=0.2038). Regional circumferential strain in the ablated region of the heart changed from -14.7±4.1% at baseline to -2.9±14.3% immediately post-ablation and increased back to -14.3±3% at 1-month follow up (Figure 2).

Conclusion: HIU catheter ablation produced deep lesions and might serve as a new modality for IVS reduction in hypertrophic cardiomyopathy. This study demonstrated temporal decrease in the LV contractility, global and regional myocardial strain after septal HIU ablation with subsequent recovery at 3-month follow up.

Table 1. Changes in global ejection fraction, global and regional circumferential, longitudinal and radial strains of the pig’s heart before, immediately after and at one and three months after ultrasound ablation. Data is shown as mean ± standard deviation.

Time point	Global ejection fraction (EF), %	Global LV radial strain, GRS (%)	Global LV circumferential strain, GCS (%)	Global LV longitudinal strain, GLS (%)	Regional RS, ablated segment 2 (%)	Regional RS, non-ablated segment 5 (%)	Regional CS, ablated segment 2 (%)	Regional CS, non-ablated segment 5 (%)
Pre-ablation	58.4±4.6	28.2±4.3	-16.3 ± 1.9	-13.9 ± 2.1	24.2±9.3	33.0±8.9	-14.8 ± 4.1	-18.9 ± 4.3
Post-ablation	47.0±5.5	21.0±2.1	-13.5 ± 0.9	-12.9 ±2.6	18.9±10.3	29.9±5.9	-2.9 ± 14.3	-17.1 ± 1.8
1 month	52.4±3.6	23.9±5.5	-14.6 ± 2.6	-12.6 ±3.5	23.8±9.2	32.7±7.4	-14.3 ± 3.0	-18.3 ± 2.6
3 months	55.1±6.2	27.7±1.9	-15.6 ± 0.6	-12.8 ±1.6	27.9±5.2	22.8±6.9	-12.0 ± 0.5	-13.9 ± 2.9

Figure 1. Representative balanced turbo field echo (bTFE) cine CMR images of the pig’s heart before and after HIU catheter ablation. Arrows point to the area of septal reduction. A-C, short axis images of the heart. D-E, long axis images of the heart.
Figure 2. Changes in the regional myocardial strain (radial and circumferential) in the ablated region of the heart (AHA segment 2) and non-ablated LV wall (AHA segment 5). * marks statistically significant difference between ablated and non-ablated segments of the same slice of the left ventricle (p < 0.05).