Mechanically Regulating Cardiac Preload to Maximize Left Ventricular Unloading with a Trans-Valvular Micro-Axial Flow Pump

All mechanical circulatory support (MCS) devices are preload dependent irrespective of pump type, configuration, or clinical use (1). By sourcing blood from the left ventricle (LV), durable and temporary LV MCS devices transfer rotational energy into the bloodstream and pressurize the systemic vasculature. When LV preload is reduced, MCS devices reduce both LV pressure and volume, which effectively evacuates the LV and uncouples the LV from the systemic circulation, known as ventriculo-arterial (VA)-uncoupling. Both reduced PVA and VA-uncoupling are hemodynamic indicators of LV unloading and associated with reduced myocardial oxygen consumption and wall stress [2].

We hypothesized that mechanically restricting total cardiac preload augments LV unloading in the presence of a trans-valvular microaxial flow pump. To test this hypothesis, adult swine (40–50kg;n=5) underwent balloon occlusion of the left anterior descending artery (LAD) for 90 minutes as previously described [3]. After 90 minutes of LAD occlusion, an Impella CP was deployed into the LV and activated at power levels (P)-3 (low speed) then P8 (high speed) in the presence and absence of SVC occlusion. We employed the preCARDIA system, a venous catheter mounted balloon and console, to mechanically reduce cardiac preload by occluding the superior vena cava (SVC). In the Venus HF early feasibility study, the duration of SVC occlusion was restricted to 5 minutes [4]. In this preclinical study, each condition was recorded after 10 minutes to achieve a steady state. LV and aortic hemodynamics were recorded to quantify LV unloading (Figure). Continuous data are presented as mean±SD. Comparisons between 2 groups used Student’s t-test with unequal variance. A 2-sided P value<0.05 was considered statistically significant. Animal studies and procedures were followed in accordance with institutional guidelines. Data that supports the findings of this study are available from the corresponding author upon reasonable request.

Figure.

Mechanically Reducing Preload to Augment Left Ventricular Unloading

A) Representative pressure-volume loops illustrating reduced left ventricular pressure and volume after activation of the preCARDIA superior vena cava occlusion system in the presence of an Impella CP pump activated, known as PrePella, at P3 or P8 levels of support. B) Pressure-time tracings from the LV (black) and aorta (red) demonstrate reduced aortic pulse pressure and flattening of the tracing during systolic ejection and diastolic filling during PrePella activation. C) Summary of hemodynamic parameters during each condition (n=5 adult swine).

Compared to Impella speeds P3 or P8 with a patent SVC, occlusion of the SVC significantly decreased LV stroke work (LVSW), PVA, LV end-diastolic pressure (LVEDP), and both LV end-systolic and diastolic volumes. LV PVA, LVSW, and LVEDP during Impella P3 support with SVC occlusion were similar to values observed during Impella P8 support with a patent SVC. Systemic mean arterial pressure was unchanged by SVC occlusion during Impella P8 support but was reduced with SVC occlusion during Impella P3 support. Heart rate and Impella flows were unchanged by SVC occlusion. No suction events were observed.

We introduce a novel approach to maximize LV unloading during trans-valvular pump support by mechanically regulating preload using a specialized catheter designed to occlude the SVC. By restricting total cardiac preload, the combination of preCARDIA and Impella, known as PrePella, reduces biventricular volumes and enables more efficient emptying of the LV by a trans-valvular pump. This observation is evident by the flat morphology of the LV tracing during diastole during SVC occlusion.

LV unloading may enable pulmonary and systemic decongestion and may also limit myocardial damage or maladaptive cardiac remodeling in the setting of heart failure or acute myocardial infarction. Clinical causes of reduced preload with LV mechanical support include dehydration, bleeding, right ventricular failure, and cardiac tamponade. The impact of preload on MCS device function can be illustrated during the strain phase of the Valsalva maneuver where total cardiac preload is reduced by increased intra-thoracic pressure and VA-uncoupling can be observed (5). In cardiogenic shock, profound RV failure can also reduce LV preload whereby MCS devices significantly reduce LV pressure until an RV assist device is implanted.

In each of these cases, LV preload is reduced in an unregulated manner, suggesting that controlled reduction of cardiac preload with caval occlusion may enable a MCS device to reduce PVA more effectively and unload the native LV, especially in conditions of systemic congestion. Mechanically regulating preload may also enable lower speed settings on MCS devices, thereby reducing the risk of hemolysis. Smaller bore transvalvular pumps may also achieve similar levels of unloading as larger capacity pumps by virtue of reducing total cardiac preload. Presumably patients with very low cardiac filling pressures, severe RV failure, increased pulmonary vascular resistance, or profound hypotension due to vasodilatory shock may not benefit from the combination of preCARDIA and Impella. Our novel observations introduce a potentially simple and novel approach to achieve maximum LV unloading and require further preclinical and clinical testing.