Direct Assessment of Hemodynamic Function in a Normothermic Ex Situ Full Cardiac Output Model

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Objective: Many DCD and DBD donor hearts are discarded over concerns of hemodynamic dysfunction following transplantation. Normothermic ex situ heart perfusion (NEHP) in full cardiac output (CO) mode provides a unique opportunity for hemodynamic assessment because loading conditions can be completely controlled. Over the last five years, we have developed NEHP protocols that routinely maintain normal heart functions for 24 hours or more. We have since developed system modifications enabling full-CO assessment with pressure-volume loop (PVL) derived measurements of hemodynamic performance. This proof-of-concept study aims to assess the accuracy and reproducibility of full-CO NEHP assessment as a surrogate for determining hemodynamic suitability for transplantation in donor hearts.

Methods: Three porcine hearts (342 ± 24.6 g) were procured and resuscitated using NEHP for 24 hours. Hearts were perfused in Langendorff mode at 0.5-0.6 cc/g of cardiac tissue/min with 22 kDa hemofiltration and electrolyte replacement. Hearts were randomized to one of three graded management protocols: minimal support (MS, no additional treatment), partial support (PS, vasoactive treatment), and full support (FS, vasoactive treatment with serum supplementation). At hours 1, 12, and 24, hearts were assessed utilizing full-CO NEHP with passive preload adjustable left atrial (LA) infusion and afterload adjustable aortic outflow (Ao). At each time point, hearts were exposed to three LA preload pressures (2-4 mmHg, 6-12 mmHg, and 12-22 mmHg) with afterload adjusted to replicate physiologic left ventricular (LV) conditions. Data collection during assessments included continuous flow monitoring (LA, Ao, coronary outflow), continuous chamber pressure monitoring (LA, LV, Ao), and echocardiography.

Results: At 24 h the MS heart displayed gross valvular incompetency with equalization of chamber pressures and converted to an irregular wide-complex arrythmia refractory to intervention. PS and FS hearts maintained functional viability. When compared to MS, there was a trend towards preserved cardiac index (CI) in the PS and FS hearts at hr12. At 24 h the FS heart demonstrated statistically significant improvement in CI in the FS group compared to MS heart at hour 24 (P=0.022) (Figure 1A). Preload recruitable stroke work (PRSW) displayed a trend towards improvement in PS and FS hearts compared to the MS heart (Figure 1B). There was no significant decline in dp/dt-max in any hearts from hour 1 to hour 12 and no significant change in the PS and FS hearts from hour 1 to hour 24 (Figure 1C). At hour 24, the FS heart displayed a statistically significant preservation in dp/dt-max compared to the PS heart at hour 24 (P=0.0413). No statistically significant changes in Tau were observed between groups; however, there was a trend towards improved diastolic preservation in the FS group (Figure 1D).

Conclusions: Donor heart function can be reproducibly stratified using full-CO NEHP. PRSW and Tau are load independent during NEHP and appear to be optimal for stratifying systolic and diastolic donor heart function. This is a proof-of-concept study and was not powered for statistical significance.

Authors
Wyeth Alexander (1), Daniel Drake (2), Alvaro Rojas-Pena (3), Robert Bartlett (2), Takahiro Nakashima (2), Kristopher Urrea (4), Vikramjit Chakrabortty (2), Sydney Maddox (5), Joe Niman (2)
Institutions
(1) University of Michigan Health System, Ann Arbor, MI, (2) University of Michigan, Department of Surgery, Ann Arbor, MI, (3) N/A, Ann Arbor, MI, (4) Michigan Medicine - University of Michigan, Saint Joseph, MI, (5) University of Michigan, Ann Arbor, MI