Science of left ventricular unloading

Abstract

The concept of left ventricular unloading has its foundation in heart physiology. In fact, the left ventricular mechanics and energetics represent the cornerstone of this approach. The novel sophisticated therapies for acute heart failure, particularly mechanical circulatory supports, strongly impact on the mechanical functioning and energy consuption of the heart, ultimately affecting left ventricle loading. Notably, extracorporeal circulatory life support which is implemented for life-threatening conditions, may even overload the left heart, requiring additional unloading strategies. As a consequence, the understanding of ventricular overload, and the associated potential unloading strategies, founds its utility in several aspects of day-by-day clinical practice. Emerging clinical and pre-clinical research on left ventricular unloading and its benefits in heart failure and recovery has been conducted, providing meaningful insights for therapeutical interventions. Here, we review the current knowledge on left ventricular unloading, from physiology and molecular biology to its application in heart failure and recovery.

Keywords: cardiogenic shock; impella; infarct size; intra-aortic balloon pump; left ventricular unloading; myocardial oxygen consumption; pressure-volume loops; renal unloading; veno arterial extra-corporeal membrane oxygenation; ventriculo-arterial coupling.

Figure 1.

Normal pressure-volume (PV) loop of the left ventricle. On the x-axis, ventricular volume. On the y-axis, ventricular pressure. See text for details. ESV, end-systolic volume; EDV, end-diastolic volume; SV, stroke volume; EDPVR, end-diastolic pressure-volume relationship; ESPVR, end-systolic pressure-volume relationship; ESP, end-systolic pressure; Ea, arterial elastance.

Figure 2.

Left ventricular energetics. On the x-axis, ventricular volume. On the y-axis, ventricular pressure. See text for details. SW, stroke work; PE, potential energy; ESV, end-systolic volume; EDV, end-diastolic volume; EDPVR, end-diastolic pressure-volume relationship; ESPVR, end-systolic pressure-volume relationship; ESP, end-systolic pressure.

Figure 3.

Pressure-volume loop during cardiogenic shock. The change of the slope of the end-systolic pressure-volume relationship (ESPVR) line from 1 to 3 and its rightward shift indicate a reduction of LV contractility, associated with a reduction of the stroke volume and with an increase of left ventricular end-diastolic pressure. SV, stroke volume; EDV, end-diastolic volume; EDPVR, end-diastolic pressure-volume relationship; ESPVR, end-systolic pressure-volume relationship. Adapted from: Nir Uriel et al, Mechanical unloading in heart failure. J Am Coll Cardiol. 2018 Jul 31;72(5):569-580.

Figure 4.

Unloading during cardiogenic shock. V-A-ECMO leads to an upward and rightward shift of the PV loop due to an increased afterload (dark red curve). The combined application of LV unloading techniques, such as TandemHeart (blu curve), IABP (green curve) or Impella (red curve), determine a leftward shift of the PV loop. See text for details. IABP, intra-aortic balloon pump; CS, cardiogenic shock; V-A-ECMO, veno-arterial extra-corporeal membrane oxygenator. Adapted from: Donker, DW, et al., Left ventricular unloading during veno-arterial ECMO: a review of percutaneous and surgical unloading interventions. Perfusion. 2019 Mar;34(2):98-105; and Kapur, NK, et al., From bedside to bench and back again: translational studies of mechanical unloading of the left ventricle to promote recovery after acute myocardial infarction. F1000Res. 2018 Nov 27;7:F1000 Faculty Rev-1852.

Figure 5.

Unloading under V-A-ECMO. Combined application of V-A-ECMO and IMPELLA (blue curve) or pulmonary artery cannula (green curve) as unloading techniques. CS (black curve), cardiogenic shock; PA, pulmonary artery; V-A-ECMO, veno-arterial extracorporeal membrane oxygenator. Adapted from: Meani, P., et al., Transaortic or Pulmonary Artery Drainage for Left Ventricular Unloading in Venoarterial Extracorporeal Life Support: A Porcine Cardiogenic Shock Model. Semin Thorac Cardiovasc Surg, 2021. 33(3): p. 724-732. and Mlcek, M., et al., Atrial Septostomy for Left Ventricular Unloading During Extracorporeal Membrane Oxygenation for Cardiogenic Shock: Animal Model. JACC Cardiovasc Interv, 2021. 14(24): p. 2698-2707.

Figure 6.

Effects of LV unloading on infarct size and myocardial remodelling. Increased afterload leads to higher myocardial workload, causing an oxygen supply-demand imbalance. The result is tissue ischemia, followed by the activation of the inflammation cascade, fibrosis and ultimately myocardial remodelling. LV unloading, reducing stroke work and therefore oxygen consumption, may interfere in these pathological mechanisms. See text for details.