Direct Mechanical Ventricular Actuation of the Acutely Failing Rabbit Heart Attenuates Maladaptive Remodeling

B. A. Schmitt¹, M. P. Anstadt^2
1LifeBridge Technologies, LLC, Fairfield, Ohio ²Miami Valley Heart & Lung Surgeons, LLC, Dayton, Ohio

Purpose: Mechanical circulatory support in pediatric populations is limited to ECMO and repurposed adult VAD’s. Major complications largely result from blood contact. The purpose of this study was to evaluate the efficacy of the next-generation, non-blood contacting direct mechanical ventricular actuation (DMVA) during support of pediatric-sized hearts.

Methods: New Zealand white rabbits (n = 56, 4.33 ± 0.07 kg) were anesthetized, instrumented for hemodynamic monitoring, and transesophageal echocardiography (ECHO). Esmolol was titrated to induce heart failure (HF) at 50% baseline output. Animals were randomly divided into SHAM control (n = 6), HF-only (n = 22), and DMVA (n = 28) groups. Both the HF-only and DMVA groups were divided into 30 min, 60 min, and 120 min esmolol-infusion periods. DMVA was periodically disengaged to assess underlying function and adjust esmolol infusion. These HF periods served as controls as well as HF-only animals for comparison with DMVA support. LV volumes and wall strain metrics throughout the cardiac cycle were assessed for a 2-chamber 2D ECHO image as well as an array of stress biomarkers collected from tissue samples taken after esmolol cessation. One-way ANOVA with post-hoc Tukey’s HSD was used to assess statistical differences (p < 0.05) for all comparisons.

Results: All animals remained in sinus rhythm throughout these experiments. Average DMVA EDV (4.25 ± 0.04) and SV (1.69 ± 0.03) were improved compared to HF after device removal (EDV: 4.48 ± 0.06, p=0.0036, SV:1.19 ± 0.04, p< 0.0001) toward baseline values (EDV: 3.86 ± 0.04, p< 0.0001, SV:1.63 ± 0.03, p = 0.5136). Average strain metrics during DMVA (Strain: 16.9 ± 0.4 %, Systolic Strain Rates: -2.96 ± 0.06 1/s, Diastolic Strain Rates: 3.00 ± 0.05) were improved compared to HF after device removal (9.9 ± 0.3, p< 0.0001, -1.46 ± 0.04, p< 0.0001, 1.65 ± 0.05, p< 0.0001) and at least equivalent to baseline (16.9 ± 0.4, p = 0.0079, -2.53 ± 0.06, p< 0.0001, 2.76 ± 0.07, p = 0.0201). Recovery (after esmolol infusion ceased) peak systolic and diastolic strain rates were amplified in DMVA support animals compared to control animals after equivalent HF periods (Figure 1). Notable improvements in diastolic strain rates suggest the effectiveness of DMVA’s unique diastolic mechanism. LV and RV biomarkers were compared between DMVA and HF-only animals (see Table 1). LV TNFR, Caspase-8, HSP-70, and SOD were decreased during DMVA by 120 mins while no differences between RV values were observed.

Conclusion: This study demonstrated DMVA support promoted superior cardiac mechanics (more toward baseline) in an acute esmolol-induced HF model. DMVA’s unique ability to augment diastole is a critical component of this augmentation. Notably, the neonatal-sized DMVA is a direct miniaturization of adult DMVA, that avoids problems associated with miniaturizing adult devices for pediatric use, without loss of efficacy. The stress biomarker results corroborate past experiments suggesting improvements to wall dynamics were achieved without any obvious damage to the myocardium. This next-generation DMVA technology offers a new therapy to address the shortage of effective pediatric support.

Identify the source of the funding for this research project: Funded in part from DoD Grant W81XWH-08-1-0484T.