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Annual Update: The State of the Field in Cardiac Unloading

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Support: The development of this supplement was funded by Abiomed.

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Dr Burkhoff opened the 6th A-CURE symposium by defining ventricular unloading. The 2018 A-CURE consortium defined unloading as “the reduction of total mechanical power expenditure of the ventricle which correlates with reductions in myocardial oxygen consumption and hemodynamic forces that lead to ventricular remodeling”.1

Dr Burkhoff demonstrated this concept using Impella as the means of primary unloading. As the left ventricle is unloaded under Impella support, the pressure–volume loop shifts leftwards, reducing the pressure–volume area and thus the work of the heart. Overall, unloading the ventricle with the Impella device results in decreased total work, with a concomitant reduction in myocardial oxygen consumption. Dr Burkhoff described additional benefits of unloading in hearts under stress conditions, such as in cardiogenic shock. Unloading the heart provides the opportunity to potentially withdraw medications such as inotropes and vasopressors, reducing heart rate and inotropic stimulation while maintaining cardiac output, blood pressure and normal wedge pressure. Weaning of inotropes can further reduce the pressure–volume area and myocardial oxygen consumption. Thus, unloading offers both primary and secondary benefits to the myocardium under stress.

Dr Burkhoff shared a recent review covering the myriad cardioprotective effects of ventricular unloading during myocardial infarction.2 These cardioprotective effects include decreased oxygen consumption, activation of cardioprotective signalling pathways, increased cardiac microvascular perfusion into the infarct zone, haemodynamic stabilisation through reperfusion-dependent arrhythmia, the ability to bridge through reperfusion-induced myocardial stunning and reduced acute infarct size and subsequent scar size.

Dr Burkhoff emphasised a number of milestones reached as a result of the A-CURE initiative and research. These include several ongoing clinical trials, including the seminal pilot study for Door-to-Unload (DTU), the currently enrolling DTU pivotal study, the recent publication of the early feasibility data of the preCardia device, the PROTECT Kidney study, which is examining the effect of mechanical unloading on end organ perfusion (kidney), and the IMPACT trial for the use of unloading in the context of cardiac surgeries.3,4 In addition, he highlighted new uses for mechanical circulatory support as an enabler for other procedures, such as bridging patients with advanced heart failure through non-cardiac surgeries and other high-risk cardiac procedures such as MitraClip. Dr Burkhoff pointed out a number of novel research initiatives also scheduled to begin this year, such as investigating the impact of Impella on microvascular obstruction in ST-elevation MI.

Dr Burkhoff highlighted two recent Nobel Prize-winning scientific investigations and their immediate relevance to the field of unloading. He emphasised the work of Dr Gregg Semenza, who received the 2019 Nobel Prize in Medicine or Physiology for his discovery of hypoxia-inducible factor-1 (HIF-1),5 and pointed out a recent research article demonstrating how unloading prior to revascularisation led to a significant reduction in infarct size, where the HIF-1 pathway was clearly implicated.6 He next highlighted Dr Ardem Patapoutian, who received the 2021 Nobel Prize in Medicine or Physiology for his discovery of PIEZO1/2.7 PIEZO1 is a channel protein on the membrane that changes the entry of calcium into the cell when force is applied, and is another molecular mechanism by which unloading can impact myocardial contractility.

Dr Burkhoff concluded that these fundamental research discoveries are critical to better understanding the biology and physiology of cardiac unloading.

References

  1. Chandrasekaran U, Burkoff D, Ishikawa K, et al. Proceedings of the 3rd annual Acute Cardiac Unloading and REcovery (A-CURE) symposium. BMC Cardiovasc Disord 2019;19(Suppl 2):27.
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  2. Curran J, Burkhoff D, Kloner RA. Beyond reperfusion: acute ventricular unloading and cardioprotection during myocardial infarction. J Cardiovasc Transl Res 2019;12:95–106.
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  3. Kapur NK, Kiernan MS, Gorgoshvili I, et al. Intermittent occlusion of the superior vena cava to improve hemodynamics in patients with acutely decompensated heart failure: the VENUS-HF Early Feasibility study. Circ Heart Fail 2022;15:e008934.
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  4. Kapur NK, Alkhouli MA, DeMartini TJ, et al. Unloading the left ventricle before reperfusion in patients with anterior ST-segment-elevation myocardial infarction. Circulation 2019;139:337–46.
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  5. Spiering MJ. How to catch a HIF – the work of Gregg Semenza’s lab on hypoxia-inducible factor 1. J Biol Chem 2020;295:715–6.
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