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Dog Model Holds Promise for Early Mechanical Unloading in Patients With Acute Myocardial Infarction

2018; Lippincott Williams & Wilkins; Volume: 11; Issue: 5 Linguagem: Inglês

10.1161/circheartfailure.118.004972

1941-3297

Cesar Guerrero-Miranda, Shelley A. Hall,

Cardiovascular Function and Risk Factors

HomeCirculation: Heart FailureVol. 11, No. 5Dog Model Holds Promise for Early Mechanical Unloading in Patients With Acute Myocardial Infarction Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBDog Model Holds Promise for Early Mechanical Unloading in Patients With Acute Myocardial Infarction Cesar Y. Guerrero-Miranda, MD and Shelley A. Hall, MD Cesar Y. Guerrero-MirandaCesar Y. Guerrero-Miranda Division of Cardiology, Department of Internal Medicine, Baylor University Medical Center, Dallas, TX. and Shelley A. HallShelley A. Hall Division of Cardiology, Department of Internal Medicine, Baylor University Medical Center, Dallas, TX. Originally published18 Jun 2018https://doi.org/10.1161/CIRCHEARTFAILURE.118.004972Circulation: Heart Failure. 2018;11:e004972See Article by Saku et alMyocardial infarction (MI) and ischemic heart disease are leading causes of morbidity and mortality. Globally, 110 million people live with ischemic heart disease,1 and >8 million per year die secondary to ischemic heart disease.2 As for MI, the 2018 Heart and Disease Stroke Statistics update of the American Heart Association reported a prevalence of 7.9 million adults in the United States alone. In 2015, >110 000 patients died because of MI, with 30-day in-hospital mortality of 15%.3 Both of these conditions combine as the most common cause of heart failure (HF), either from chronic ischemia or from resultant injury after MI. Up to 40% of individuals with MI develop left ventricular (LV) dysfunction.4 The infarct size with resultant adverse ventricular remodeling is directly associated with the development of HF after MI.4 Cardiogenic shock, the worst expression of HF, in the setting of acute myocardial dysfunction is preceded by myocardial contractile dysfunction, which leads to inadequate tissue perfusion and, in turn, can result in multiorgan failure. Although the prevalence of cardiogenic shock among patients with MI is relatively low (5%–10%),5 cardiogenic shock has historically had an early mortality rate as high as 80%, whereas recent studies have suggested a decline in mortality to ≈40%,6 which is nevertheless still too high.Traditionally, coronary artery reperfusion using percutaneous intervention has been the cornerstone therapy to reduce myocardial damage and subsequent HF. Moreover, early percutaneous coronary intervention, using the latest generation of drug-eluted stents and novel antithrombotics and pharmacological therapies, has significantly reduced mortality in MI-related cardiogenic shock.7 However, the use of inotropes in the management of MI progressing to cardiogenic shock can be associated with tachycardia, increased myocardial oxygen demand, and arrhythmias with associated higher mortality.Over the past decade, the use of temporary mechanical cardiac support (TCS) has increased rapidly in the treatment of patients with refractory cardiogenic shock and is associated with reduced hospital costs and, in some cases, reduced in-hospital mortality.8 TCS devices intend to restore systemic perfusion and prevent further end-organ damage until the insult that resulted in cardiogenic shock is addressed. This is accomplished by augmenting cardiac output, unloading the LV, decreasing filling pressures, and improving coronary perfusion.9 Essentially, 4 primary TCS devices are currently available for hemodynamic support. These include the intra-aortic balloon pump, the Tandem-Heart percutaneous ventricular assist device (TandemLife, Pittsburgh, PA), veno-arterial centrifugally driven extracorporeal membrane oxygenation, and Impella pumps (Abiomed, Inc, Danvers, MA).10The 2 available percutaneous TCS devices able to produce mechanical LV volume unloading are Tandem-Heart and Impella. The Impella system, used in the study by Saku et al in this issue of Circulation: Heart Failure,11 has a caged blood flow inlet placed retrograde into the LV. A pump aspirates blood from the LV, which is then ejected by means of a microaxial pump into the ascending aorta. The Impella system may be implanted via the femoral or axillary approach. The Impella platform consists of 3 commercially available left-sided pumps (Impella 2.5, Impella CP, and Impella 5.0) providing various degrees of hemodynamic support. Specifically, the Impella 5.0 offers full systemic circulatory support (up to 5 L/min), direct LV unloading, and minimally invasive implantation without sternotomy.12 An increase in patient survival, an increase in cardiac output, and a reduction in the use of inotropes and vasopressors as early as 24 hours after intervention were demonstrated by the Detroit Cardiogenic Shock Initiative using early implantation of the Impella device in patients with acute MI and cardiogenic shock.13 Moreover, Remmelink et al, in a small cohort of MI patients, showed the benefit of LV unloading by a decrease in end-diastolic LV wall stress.14 This may diminish early myocardial remodeling and decrease the myocardial oxygen demand, thus potentially reducing infarct size.A vexing question thus becomes: Can infarct size be further reduced by even more aggressive mechanical support? There are few studies in the literature showing potential benefit of early use of LV unloading in MI. In a canine model, Achour et al15 demonstrated that a significant reduction in the infarct size occurred only when mechanical LV unloading was started before coronary reperfusion.In this issue of Circulation: Heart Failure, Saku et al11 report the impact of LV mechanical unloading on both infarct size and preservation of LV function after induced anterior wall MI by ligation of the left anterior descending artery for 180 minutes in dogs. An Impella CP was implanted from 60 minutes after the onset of ischemia to 60 minutes after reperfusion with the idea of imitating real-world management of MI. Importantly, the investigators compared the use of total LV unloading (where the hemodynamics are fully supported by the device, ie, the LV no longer ejects) and partial LV unloading (with the Impella flow equal to half the arterial pulse pressure) in relation to the resulting infarct size and subsequent development of HF. They found that the use of total LV unloading had the greater effect in reducing LV end-diastolic pressure, increasing LV end-systolic elastance, and decreasing NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels as evidence of maximal LV function preservation.Their findings achieved in dogs were impressive and indeed promising: a reduction of up to 80% in the infarct size, found 4 weeks after the ischemia, would undoubtedly correspond to a substantially reduced incidence of HF. Therefore, let us evaluate what it would take to replicate these results in humans. First, we must look at timing. Can we realistically implant unloading mechanical devices in patients within 60 minutes of onset of an infarction? Or would we have to settle on the earliest possible? When is it too late? Do we extrapolate from our percutaneous coronary intervention data and attempt to get under 90 minutes from presentation? Second, let us compare flow relationships. Keeping in mind that the cardiac output in the mongrel dog is substantially lower than that in human, total LV unloading in humans would require generating a flow of 6 to 8 L/min to achieve comparable results. Although flows of this magnitude are currently not feasible with available TCS devices, these findings support the notion that higher flows may be of invaluable benefit to infarct patients and to patients with acute or chronic HF. However, we must also be cautious and learn the lessons from durable mechanical support. What will the longer-term impact on end-organ function be with the loss of pulsatile cardiac flow, if we moved toward complete LV unloading during an infarction, even if only for a few hours? Would the smaller infarct size outweigh potential other complications? Finally, we cannot ignore the cost of such devices. If applied to all MI patients going to the cath lab, how would our already overextended, inflated healthcare system absorb such expense? Only a prospective trial in humans, using technology that still needs to be developed, could answer these questions. Thus, we hope that such devices will become available in the future.Saku et al provide data that introduce a whole new paradigm to infarct reduction, both simplistic in thought and elegant in execution. These modern mechanical LV unloading devices have gained more popularity in the management of cardiogenic shock in both the MI setting and even in various forms of acute decompensated HF. Despite the hemodynamic benefits, perceived barriers to their utilization remain, as large randomized trials have yet to demonstrate a mortality benefit, the associated costs are high, and there is a risk for complications. The new results obtained in the canine model presented in this issue, however, provide a renewed impetus to seeking higher-capacity TCS devices for human application with the hope that early deployment and potentially more aggressive unloading can truly result in resting the insulted ventricle.DisclosuresDr Hall is a consultant for Abiomed, Inc. The other author reports no conflicts.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.http://circheartfailure.ahajournals.orgCesar Y. Guerrero-Miranda, MD, Center for Advanced Heart and Lung Disease, Baylor University Medical Center, 3410 Worth St, Suite 250, Dallas, TX 75246. E-mail [email protected]References1. 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