Given the tremendous progress in interventional cardiology over the last decade, a growing number of older patients, who have more comorbidities and more complex coronary artery disease, are being considered for technically challenging and high-risk percutaneous coronary interventions (PCI). The success of performing such complex PCI is increasingly dependent on the availability and improvement of mechanical circulatory support (MCS) devices, which aim to provide hemodynamic support and left ventricular (LV) unloading to enable safe and successful coronary revascularization. MCS as an adjunct to high-risk PCI may, therefore, be an important component for improvement in clinical outcomes. MCS devices in this setting can be used for two main clinical conditions: patients who present with cardiogenic shock complicating acute myocardial infarction (AMI) and those undergoing technically complex and high-risk PCI without having overt cardiogenic shock. The current article reviews the advancement in the use of various devices in both AMI complicated by cardiogenic shock and complex high-risk PCI, highlights the available hemodynamic and clinical data associated with the use of MCS devices, and presents suggestive management strategies focusing on appropriate patient selection and optimal timing and support to potentially increase the clinical benefit from utilizing these devices during PCI in this high-risk group of patients. Recent advances in percutaneous coronary intervention (PCI) technologies, including mechanical circulatory support (MCS) devices, have facilitated treatment of high-risk patients with complex coronary artery disease (CAD) and low left ventricular (LV) systolic function as well as patients with acute myocardial infarction (AMI) complicated by cardiogenic shock. These high-risk patients would otherwise be poor candidates for coronary artery bypass grafting (CABG) due to high surgical morbidity and mortality risks, and the ability to provide adequate hemodynamic support using MCS devices would potentially enable safer PCI and improve outcomes as compared to unprotected PCI strategy, surgical revascularization, or medical therapy alone . HoweverIn light of the development of new generation MCS devices with greater hemodynamic support and lower device-associated complications combined with careful planning and optimal timing of device utilization, a growing body of data is suggestive of improvement in procedural success and clinical outcomes ,8, and tOver the last few decades, there has been a tremendous progression in coronary interventional techniques that enables performance of PCI in complex coronary lesions  that would previously not have been amenable to intervention. This includes improved guide catheters and wires, mother-child guide catheters, low-profile balloons, coronary atherectomy devices, dedicated chronic total occlusion devices and algorithms, and superior stent designs that enhance deliverability to achieve complete multivessel revascularization including those involving chronic totally occluded coronary vessels. However, each aspect of PCI, beginning from guide catheter engagement and ending with balloon inflation and stent deployment, is associated with potential risk of vascular damage and impairment of myocardial perfusion. For instance, patients at advanced age, with increased comorbidities, and underlying left ventricular dysfunction, may pose a clinical challenge, as complex PCI among these patients may incur a substantial risk that overweighs any benefit achieved from revascularization . On the Among high-risk patients with active ischemia, the need and the type of revascularization should be discussed by Heart Team in an individual base. The recommendation with respect to the type of revascularization (PCI versus CABG) should be generally guided by important criteria including the predicted surgical mortality (based on the Society of Thoracic Surgeons (STS) score), the anatomical complexity of CAD (based on the SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score), and the anticipated completeness of revascularization. The risks of periprocedural complications should be weighed up against the anticipated improvement in quality of life and long-term freedom from death, MI, and repeat vascularization for electing whether conservative therapy, PCI, or CABG is the recommended strategy. According to the current ESC guidelines , when suAs high-risk PCI is associated with increased risk of myocardial ischemia and hemodynamic compromise that may lead to circulatory collapse, the purpose of MCS is to diminish myocardial oxygen consumption and provide adequate cardiac output and myocardial perfusion during the procedure. Use of appropriate MCS devices allows adequate time to safely perform complex PCI with optimal results in these high-risk patients who would not otherwise tolerate complete revascularization . It is c2 with hemodynamic support or <1.8 L/min/m2 without support, pulmonary capillary wedge pressure (PCWP) >15 mmHg, and evidence of end-organ damage  .,18.11,18Several percutaneous MCS devices are currently available to assist interventional cardiologists during high-risk PCIs both for patients undergoing a complex PCI and for those requiring PCI in the setting of cardiogenic sock complicating AMI. Types of available percutaneous MCS devices and comparisons of their characteristics and hemodynamic impact are presented in Since its introduction in the 1960s, IABP remains the most widely used device for temporary support in hemodynamically unstable patients due to its greater availability and ease of insertion as compared to other temporary devices . It is tThe complications associated with IABP use are mainly vascular, including limb ischemia, vascular injury, and stroke . AlthougThe Impella pumps are continuous nonpulsatile microaxial flow devices that are deployed into the LV across the aortic valve and unload the LV by pumping blood from the LV cavity to the ascending aorta. The Impella 2.5 and CP pumps  can be placed percutaneously and provide maximal flow rates of 2.5 and 3.0–4.0 L/min, respectively, while the Impella 5.0 and Impella LD  devices are larger LV assist axial-flow pumps that require surgical cutdown and provide up to 5.0 L/min of cardiac output ,37,38. SUnlike IABP, Impella (as other percutaneous ventricular assist devices) functions independently of the remaining LV function and does not require synchronization with the cardiac cycle. Therefore, Impella devices are more helpful than IABP in patients with severely depressed LV function who present with significant arrhythmias. Impella results in effective LV unloading thus resulting in decreased LV filling pressures (LVEDP) and myocardial oxygen consumption, while improving cardiac output, mean arterial pressure, and coronary perfusion . All theDespite the improvement in hemodynamic parameters, device-related complications are not rare and can be clinically meaningful, thereby contradicting the potential hemodynamic benefits that can be achieved with the use of Impella devices in some cases. As with any mechanical support device, common complications associated with Impella include vascular trauma, limb ischemia, and bleeding requiring blood transfusion. Moreover, hemolysis is frequently encountered during Impella support due to mechanical erythrocyte shearing, but usually improves after repositioning the device. Based on the Impella EUROSHOCK Registry , utilizaImpella should not be used in patients with a mechanical aortic valve or LV thrombus as well as in those with severe peripheral arterial disease or who cannot tolerate systemic anticoagulation therapy. Although severe aortic stenosis and regurgitation are considered relative contraindication, the use of Impella in this setting has been shown to be feasible and may be considered in selected high-risk patients with severe aortic stenosis and cardiogenic shock or those with severe LV dysfunction and CAD who require high-risk PCI and/or balloon aortic valvuloplasty as well as in selected patients who develop hemodynamic collapse during transcatheter aortic valve replacement (TAVR) .The TandemHeart (CardiacAssist) system is an extracorporeal, centrifugal, continuous flow pump, which is available on the market for left, right, and biventricular failure. For LV support, TandemHeart device is percutaneously inserted to pump blood extracorporeally from the left atrium through a transseptal cannula back into the femoral/iliac artery through an arterial cannula using a centrifugal pump that provides 3 to 5 L/min of continuous flow at 3000 to 7500 rpm, respectively ,37. The By propelling blood from the left atrium directly to the arterial system, TandemHeart results in a significantly reduced LV preload, filling pressures, and myocardial oxygen demand, while cardiac output and mean arterial pressures are improved. However, because LV output through the aortic valve competes with the retrograde flow from the device, LV afterload increases as the device support is augmented, which may ultimately result in aortic valve closure requiring LV venting ,45.Similar to other percutaneous MCS devices, TandemHeart use may infrequently cause limb ischemia and vascular injury . AdditioBased on the Extracorporeal Life Support Organization (ELSO) registry data, the number of ECMO devices and the number of centers utilizing ECMO are markedly increasing ,48. VA-EVA-ECMO support results in a remarkable increase in cardiac output and mean arterial pressure. However, its use is limited by retrograde blood flow leading to LV afterload mismatch, inadequate LV decompression, and high myocardial oxygen demand. The concurrent use of IABP or Impella can add further support by direct unloading of the LV and reducing ventricular wall stress ,52. ReceOne of the recent advancements in the percutaneous extracorporeal life support (ECLS) technology is the development of the Lifebridge B2T “bridge to therapy” system , which is a miniaturized and portable heart-lung support system similar in design to standard ECMO systems with an ability to provide cardiovascular stabilization and sufficient end-organ perfusion immediately after circulatory arrest. The Lifebridge system enables rapid application within 5 min due to its automated set-up and portable design in addition to less cumbersome transportation of the patient than standard ECMO equipment due to its smaller size and suitcase configuration. Other technical features include a battery life of 2 h, an overall weight of 18 kg (39.6 lb.), and a maximal blood flow of 6 L/min. Real-world clinical data of the German Lifebridge Registry involving 444 patients from 60 tertiary cardiovascular centers has been recently published  showing Adverse events related to VA-ECMO include bleeding (with excessive anticoagulation), thromboembolic events in the circuit or systemically (if anticoagulation is inadequate), cannula-induced vascular injuries, infection, stroke (ischemic or hemorrhagic), hemolysis, and limb ischemia . To reduPercutaneous LV MCS pumps under investigation include the pulsatile iVAC 2L , which has been recently evaluated prospectively in a pilot study of 14 patients undergoing high-risk PCI demonstrating 100% angiographic success . The AorApart from LV support, RV failure refractory to medical therapy is increasingly becoming a clinical challenge, thereby prompting the development of devices to specifically provide RV support. Large inferior AMI may cause predominant RV failure with cardiogenic shock with or without severe LV dysfunction. When cardiogenic shock is persistent despite maximal medical therapy, the options for MCS in this setting include VA-ECMO, surgical implantation of RVAD or total artificial heart (TAH), and heart transplantation . The recThe most recent clinical practice guidelines regarding the use of percutaneous MCS for PCI and management of ACS recommend consideration of the use of these devices in the setting of high-risk PCI and AMI complicated by cardiogenic shock . HoweverIn the setting of PCI with cardiogenic shock complicating AMI, a previous retrospective study has suggested a potential benefit with early IABP support placed prior to PCI showing decreased rates of in-hospital mortality and cardiac adverse events compared with IABP placed only following PCI . In a meAmong patients undergoing PCI without evident cardiogenic shock, IABP use was tested in the CRISP-AMI  trial ; a 30-ceGiven these conflicting results and the controversy surrounding its benefit, the use of IABP in the setting of STEMI complicated with cardiogenic shock is decreasing and its routine use has been recently downgraded to class III (harm) by the ESC  and to cp = 0.01) and 6-month  mortality [There are currently limited available data to establish a significant clinical benefit of Impella use in patients with cardiogenic shock undergoing PCI. Impella devices provide greater hemodynamic support with a more pronounced cardiac output augmentation and LV unloading than IABP. In 2008, the ISAR-SHOCK (Impella LP 2.5 versus IABP in Cardiogenic SHOCK) trial  was the ortality . More reortality . There wortality . Finallyortality . It is iThe effectiveness and safety of Impella support for planned high-risk coronary interventions have been investigated in small studies showing encouraging results. In the AMC MAC1 study , 19 consp = 0.227 in the intention-to-treat population, and 34.3% versus 42.2%, p = 0.092 in the per-protocol population). Impella did provide greater hemodynamic support and at 90-day follow-up there was a trend towards a decreased incidence of adverse events with Impella in the intention-to-treat population  and significantly decreased events in the per-protocol population  [The largest prospective randomized clinical study to examine the effect of hemodynamic support with Impella in patients undergoing high-risk PCI was the PROTECT II trial . In this= 0.023) . A more = 0.023) . Interes2), PCWP (decreased from 31 to 17 mmHg), and mixed venous oxygen saturation (increased from 49 to 69%), as well as improvement in kidney function (urine output increased from 70 to 1200 mL/day and creatinine decreased from 1.5 to 1.2 mg/dL) and lactic acid level (decreased from 11 to 1.5 mg/dL). However, overall mortality (40.2% at 30 days and 45.3% at 6 months) and bleeding complications remained high [Small studies have shown a significant improvement in hemodynamics with TandemHeart use, but were underpowered to show improvement in survival. In an observational study by Kar et al. , TandemHned high . In a smned high . Similarned high .Data on the use of TandemHeart in high-risk PCI is limited to observational studies. A study from the Mayo Clinic summarized data on 54 consecutive patients undergoing high-risk PCI using a TandemHeart device for support, demonstrating feasibility and safety of this device to allow performance of high-risk and complex intervention . All patWhile ECMO provides excellent cardiopulmonary support with a relative ease of implementation, its use in the setting of AMI and shock is limited by the need for specialized perfusion expertise and nursing as well as the possibility for increased LV stroke work and myocardial oxygen demand, which can precipitate further myocardial ischemia. Additionally, there is need for large bore cannulas and aggressive antithrombotic therapy which increase the risk of bleeding. A recent single-center study  reportedA suggested algorithmic approach to MCS use during PCI for cardiogenic shock complicating AMI and high-risk PCI without cardiogenic shock is depicted in For prophylactic percutaneous MCS use in the setting of high-risk PCI, great emphasis should be on identifying the patient’s anatomic, hemodynamic, and procedural features that indicate adjunctive MCS support may be necessary and also determine the optimal device to utilize . The curThe majority of studies involving the new MCS devices for cardiogenic shock and high risk PCI have demonstrated superior hemodynamic improvement as compared to IABP but these studies were largely underpowered to find mortality benefit and therefore should be regarded as feasibility trials and a basis for larger clinical trials in the future. The DanGer Shock study  is an onDespite the lack of current evidence, we believe that advanced MCS devices may improve clinical outcomes, including survival, in a selected group of patients and in specific circumstances. Future studies should largely focus on three major considerations when examining the clinical benefit of MCS. First, the optimal MCS device design and amount of support needed to achieve hemodynamic as well as metabolic improvement is unclear. For instance, in the IMPRESS in Severe Shock trial, one third of the patients died due to refractory cardiogenic shock and lactate levels remained high in many patients while being on Impella CP support, suggesting that the actual level of support was not sufficient ,73. SecoThird, the timing of MCS device insertion in relation to primary PCI among patients with AMI and cardiogenic shock can be critical to achieve survival benefit and future studies should focus on determining the optimal timing of MCS, which remains elusive. Recent studies have shown in an animal model that mechanical support with LV unloading reduces infarct size and favorably mediates key biological pathways associated with inflammation and maladaptive cardiac remodeling when mechanical support is initiated prior to coronary reperfusion compared with early reperfusion without support ,97,98,99Based on these promising retrospective data, and after the FDA’s approval of Impella for cardiogenic shock complicating AMI, investigators have organized the construct of a multicenter national shock protocol now referred to as the “National Cardiogenic Shock Initiative” (NCSI) emphasizing invasive hemodynamic monitoring and rapid initiation of percutaneous MCS support. The analysis of the first 171 patients enrolled in NCSI was recently published .Another field of future research is the percutaneous LV unloading strategy using Impella in combination with VA-ECMO (ECMELLA) to improve outcomes in patients with refractory cardiogenic shock ,104. In The use of MCS devices is expanding and several MCS devices are currently available and can provide varying magnitude of hemodynamic support during high-risk and complex PCIs. Small randomized controlled trials have provided conflicting results regarding survival benefit using these devices despite substantial hemodynamic and metabolic benefit. However, given the high morbidity and mortality burden among patients undergoing high-risk and complex PCI, detailed hemodynamic assessment and careful patient selection is mandatory to achieve incremental benefit over early revascularization and pharmacologic therapy with utilizing these devices. Furthermore, the optimal timing and magnitude of hemodynamic support during PCI as well as prevention of device-related complications are all important considerations in future research in this field. Until adequate data supporting MCS use in a broader patient population is available, MCS devices during PCI should be individualized based on multiple factors with a recommended use in patients with the greatest potential benefit and a relatively low risk of device-related complications.