Cardiac Unloading with an Implantable Interatrial Shunt in Heart Failure: Serial Observations in an Ovine Model of Ischemic Cardiomyopathy

ABSTRACT

Background: Patients with dilated cardiomyopathy often have progressive heart failure with systolic dysfunction, ventricular remodeling and clinical decompensation heralded by elevations of filling pressures. Our hypothesis is that an interatrial shunt device can regulate left atrial pressure and stabilize left ventricular function without overloading the right heart.

Methods: Sheep (N = 21) were subjected to repeat coronary microembolization until left ventricular dysfunction with reduced LVEF was documented. After study group assignment, animals were chronically instrumented during thoracotomy. Shunts were implanted in n = 14 and n = 7 were sham controls. Hemodynamic and echocardiographic responses were serially evaluated for 12 weeks.

Results: Comparisons at study termination showed improved outcomes with interatrial shunting (LVEF 46 ± 11% vs. 18 ± 3%; fractional shortening 19 ± 6% vs. 6 ± 1%; ventricular septal thickness 1.2 ± 0.2 cm vs. 1.0 ± 0.3 cm; left atrial pressure 14 ± 3 mmHg vs. 25 ± 5 mmHg; mean pulmonary artery pressure 24 ± 4 mmHg vs. 37 ± 8 mmHg; right atrial pressure 8 ± 4 mmHg vs. 15 ± 4 mmHg; LV dP/dt_max 1515 ± 391 mmHg·s⁻¹ vs. 879 ± 333 mmHg−s⁻¹; LV dP/dt_min −2116 ± 569 mmHg·s⁻¹ vs. −1138 ± 545 mmHg·s⁻¹; p ≤ 0.03 for all comparisons). These findings were supported by gross pathological observations and there was a survival advantage with shunting (13/14 vs. 4/7 at 12 weeks, p = 0.047). Shunts were small with Qp:Qs 1.2 ± 0.1 and all devices were patent at necropsy.

Conclusion: In an animal model of ischemic cardiomyopathy, interatrial shunting selectively unloaded the left-heart leading to sustained reductions in left-atrial pressure, improved left ventricular performance, preserved inotropic and lusitropic function with blunted remodeling. Secondary pulmonary hypertension was absent and right-sided cardiac pressures and function were preserved.

KEYWORDS:

• Animal model
• atrial septum
• cardiomyopathy
• heart failure
• hemodynamics
• shunt prosthesis

Acknowledgments

We thank Yaacov Nitzan and Meni Jacoby for their coordination and performance of this work as V-Wave employees. We also thank Richard Holcomb, PhD, for his biostatistical advice.

Funding

This study was sponsored in part by V-Wave Ltd., Caesarea, Israel.

Disclosure Statement

Dr Eigler is a corporate officer, employee, and has an equity interest in V-Wave Ltd. Dr Shkurovich is also an employee with an equity interest. Drs Keren, Verheye, and Abraham disclose consultancies and equity interests in V-Wave Ltd. The remaining authors report no conflicts.

Additional information

Funding

This study was sponsored in part by V-Wave Ltd., Caesarea, Israel.