P76: Need for an Interlaboratory Study of Mock Circulatory Loops to Evaluate the Performance of Mechanical Circulatory Support Devices

Abstract

Purpose of Study: Mechanical circulatory support (MCS) devices are a surgical therapeutic option for patients with advanced and end-stage heart failure (HF), but predictions of device performance are difficult after implantation and often rely on animal and human studies. There is an unmet need for standardized non-clinical test methods to assess MCS flow performance. Mock circulatory loops (MCLs) can fill this need by simulating healthy and pathophysiologic pressure and flow conditions on the bench. However, test methods and parameters are inconsistent among stakeholders (i.e., test laboratories), and there are no standardized acceptance criteria for using MCLs in the evaluation of MCS devices. Methods: Recognizing the need for a consensus test protocol, the FDA engaged with external partners who are currently using MCLs to develop and evaluate MCS devices. Through these collaborations, we resolved key components and characteristics of MCLs needed for assessing device performance. A test protocol with test parameters and operating conditions was proposed by the FDA and modified based on the input of the external partners for use in an interlaboratory study. Common pathophysiologic hemodynamics were identified through literature review, discussions with clinicians, real-world evidence from post-market studies, and annual reports. For each HF condition, clinically significant cardiac indices such as heart rate, cardiac output (CO), systolic and diastolic pressures (SP and DP), left ventricular (LV) volume, left atrial filling pressure, cardiac cycle time (CCT), and systemic vascular resistance were controlled. Results: An interlaboratory study is underway to evaluate consensus test methods and parameters using MCLs to assess MCS device performance under critical HF conditions. A standardized test protocol, including data acquisition time, fluid properties, and cardiac/device pressures and flows, has been developed to evaluate MCS device operating modes. The study participants are collecting cardiac and MCS device pressure-flow data, utilizing the standardized protocol to simulate patient conditions such as cardiogenic shock, hypertension, LV hypertrophy, coronary artery disease and congenital heart defects. Figure 1 shows the common elements of MCLs, along with pressure and flow waveforms representing cardiogenic shock. Initial results indicate that the differences between the target and simulated hemodynamics range between 3 – 9 mmHg for SP, 2 – 12 mmHg for DP, 0.3 – 1 L/min for CO, and 0.001 – 0.01 s for CCT. This study demonstrates that MCLs can be used as an alternative preclinical method to reliably generate waveforms mimicking healthy and pathophysiologic patient hemodynamics. Summary: This interlaboratory study aims to standardize the use and increase the utility of MCLs in the evaluation of MCS devices. The study results can be incorporated into consensus standards.Figure 1. A) A schematic of the key elements of mock circulatory loops used to evaluate mechanical circulatory support devices; B) Representative pressure waveforms generated by an MCL to simulate cardiogenic shock (simulated CO = 3.4 LPM).