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Canadian Journal of Cardiology

What Is the Role of Medical Therapy in Cardiogenic Shock in the Era of Mechanical Circulatory Support?

  • Sean van Diepen
    Correspondence
    Corresponding author: Dr Sean van Diepen, 2C2 Cardiology Walter MacKenzie Center, University of Alberta Hospital, 8440-11 St, Edmonton, Alberta T6G 2B7, Canada. Tel.: +1-780-407-6948; fax: +1-780-407-7485.
    Affiliations
    Department of Critical Care Medicine and Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada

    Canadian Vigour Center, University of Alberta, Edmonton, Alberta, Canada
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  • David A. Baran
    Affiliations
    Sentara Heart Hospital, Advanced Heart Failure Center, and Eastern Virginia Medical School, Norfolk, Virginia, USA
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  • Alexandre Mebazaa
    Affiliations
    Université de Paris, U942 Inserm–MASCOT, Paris, France

    APHP, Department of Anesthesia, Burn and Critical Care, Hôpitaux Universitaires, Saint Louis Lariboisière, Paris, France
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Published:November 29, 2019DOI:https://doi.org/10.1016/j.cjca.2019.11.030
      In patients hospitalized with cardiogenic shock (CS), contemporary short-term mortality rates are 30% to 50%.
      • van Diepen S.
      • Katz J.N.
      • Albert N.M.
      • et al.
      Contemporary management of cardiogenic shock: a scientific statement from the American Heart Association.
      To date, the only therapy that has definitively improved survival is revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting in patients with myocardial infarction associated with CS.
      • Hochman J.S.
      • Sleeper L.A.
      • Webb J.G.
      • et al.
      Early revascularization in acute myocardial infarction complicated by cardiogenic shock
      SHOCK investigators: should we emergently revascularize occluded coronaries for cardiogenic shock?.
      Temporary mechanical circulatory support (MCS) devices can potentially increase cardiac output, reduce pulmonary congestion, and help to restore end-organ perfusion in patients with CS.
      • van Diepen S.
      • Katz J.N.
      • Albert N.M.
      • et al.
      Contemporary management of cardiogenic shock: a scientific statement from the American Heart Association.
      ,
      • Seyfarth M.
      • Sibbing D.
      • Bauer I.
      • et al.
      A randomized clinical trial to evaluate the safety and efficacy of a percutaneous left ventricular assist device versus intra-aortic balloon pumping for treatment of cardiogenic shock caused by myocardial infarction.
      ,
      • Weil B.R.
      • Konecny F.
      • Suzuki G.
      • Iyer V.
      • Canty Jr., J.M.
      Comparative hemodynamic effects of contemporary percutaneous mechanical circulatory support devices in a porcine model of acute myocardial infarction.
      In principle, a pump that augments the failing heart ought to be clinically beneficial. These findings have likely fueled and exponential growth in the use of temporary MCS devices, including extracorporeal membrane oxygenation (ECMO) and Impella (Abiomed, Danvers, Massachusetts).
      • Khera R.
      • Cram P.
      • Lu X.
      • et al.
      Trends in the use of percutaneous ventricular assist devices: analysis of national inpatient sample data, 2007 through 2012.
      • Stentz M.J.
      • Kelley M.E.
      • Jabaley C.S.
      • et al.
      Trends in extracorporeal membrane oxygenation growth in the United States, 2011-2014.
      • Stretch R.
      • Sauer C.M.
      • Yuh D.D.
      • Bonde P.
      National trends in the utilization of short-term mechanical circulatory support: incidence, outcomes, and cost analysis.
      This shift in practice is juxtaposed against the potential complications and the scientific uncertainty of whether temporary MCS devices can meaningfully improve such clinical outcomes as mortality or quality of life.
      • Schrage B.
      • Ibrahim K.
      • Loehn T.
      • et al.
      Impella support for acute myocardial infarction complicated by cardiogenic shock.
      ,
      • Amin A.P.
      • Spertus J.A.
      • Curtis J.P.
      • et al.
      The evolving landscape of Impella use in the United States among patients undergoing percutaneous coronary intervention with mechanical circulatory support.
      To date, large high-quality randomized trials are lacking, and most international clinical practice guidelines assign temporary MCS a class IIb (C) recommendation.
      • van Diepen S.
      • Thiele H.
      An overview of international cardiogenic shock guidelines and application in clinical practice.
      Temporary MCS is perhaps the most promising therapeutic technology that could potentially improve CS survival, and 2 pending randomized controlled trials, Danish-German Cardiogenic Shock Trial (DANGER) and Testing the Value of Novel Strategy and Its Cost Efficacy in Order to Improve the Poor Outcomes in Cardiogenic Shock (EUROSHOCK), may help to inform the use of MCS in clinical practice.
      ClinicalTrials.gov
      Danish Cardiogenic Shock Trial (DanShock).
      ,
      ClinicalTrials.gov
      Testing the Value of Novel Strategy and Its Cost Efficacy in Order to Improve the Poor Outcomes in Cardiogenic Shock (EUROSHOCK).
      They may not, however, clearly outline which patients are best suited for medical therapy alone vs MCS. This potential complexity is underscored by 2 recent publications that have helped frame the growing recognition of the hemodynamic and phenotypic diversity of CS. In addition, they may help inform future clinical and research frameworks to identify which patients might benefit from MCS. The American Heart Association (AHA) Scientific Statement of CS, based largely on secondary analyses of the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial, emphasized that although all patients CS share reduced cardiac output, but pulmonary capillary wedge pressures, systemic vascular resistances, and right-ventricle (RV) function can vary.
      • van Diepen S.
      • Katz J.N.
      • Albert N.M.
      • et al.
      Contemporary management of cardiogenic shock: a scientific statement from the American Heart Association.
      In this framework, it is conceivable that patients with vasodilatory CS, caused by either a postinfarction inflammatory or mixed shock state, may—theoretically—be less likely to benefit from temporary MCS if a low systemic vascular resistance (SVR) is the dominant hemodynamic abnormality and/or there is concurrent multifactorial end-organ failure. Similarly, there is growing clinical recognition that in normotensive CS, patients with hypoperfusion—despite normal blood pressure potentially related to large compensatory SVR response—often respond well hemodynamically to inodilators, although definitive evidence on efficacy and safety is lacking. Layered on this diversity is the underlying etiology; although most vasoactive research has been performed in acute myocardial infarction with isolated left ventricular dysfunction, the vasoactive agent selection and hemodynamic goals in patients with CS due to dynamic outflow-tract obstruction, severe mitral stenosis, or isolated RV failure are very different and are based on physiologic principles in the absence of high-quality studies.
      The second study is the Society of Cardiovascular Angiography and Interventions Expert Consensus CS classification.
      • Baran D.A.
      • Grines C.L.
      • Bailey S.
      • et al.
      SCAI clinical expert consensus statement on the classification of cardiogenic shock.
      The document, which was endorsed by the AHA, the American College of Cardiology, the Society of Critical Care Medicine, and the Society of Thoracic Surgeons and was designed to account for the dynamic nature of CS and the heterogeneity in acuity that is not fully captured with pre-existing Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) staging. The taxonomy of (A) At risk, (B) Beginning, (C) Classic, (D) Deteriorating, (E) Extremis was designed to provide a simple clinical communication tool that could be applied by multidisciplinary team members throughout the care continuum (Fig.1). This nomenclature, which has been validated by at least 1 group, could help refine MCS selection in the future.
      • Jentzer J.C.
      • van Diepen S.
      • Barsness G.W.
      • et al.
      Cardiogenic shock classification to predict mortality in the cardiac intensive care unit.
      ,
      • Jentzer J.C.
      • Baran D.A.
      • van Diepen S.
      • et al.
      Admission Society for Cardiovascular Angiography and Intervention shock stage stratifies post-discharge mortality risk in cardiac intensive care unit patients.
      Although CS outcomes are poor, more than 50% of patients in contemporary studies do survive with medical therapy alone.
      • Mebazaa A.
      • Combes A.
      • van Diepen S.
      • et al.
      Management of cardiogenic shock complicating myocardial infarction.
      Thus, it is plausible that a more targeted deployment of temporary MCS in more acute, profound, or refractory CS states that have been appropriately hemodynamically phenotyped could maximize the survival benefits and minimize health care costs. In the schema presented in the Figure, we surmise that the Society for Cardiovascular Angiography and Interventions (SCAI) stage D and E (and selected stage C) patients may be more likely to benefit from temporary MCS and less likely to survive with isolated medical therapy. Thus, stage B and C patients could conceptually receive a trial of medical therapy first, and deteriorating (stage D) would require temporary MCS support. Appropriately selected patients in stage E with ongoing resuscitation would be most suitable for extracorporeal cardiopulmonary resuscitation (eCPR).
      Figure thumbnail gr1
      Figure 1Potential role of medical therapy alone and temporary mechanical circulatory support stratified by stages of cardiogenic shock.
      It should be acknowledged, however, that the evidence supporting a stepwise escalation in MCS therapies is equally sparse as other more broadly proposed principles including door-to-unloading time in CS.
      • Kapur N.K.
      • Alkhouli M.A.
      • DeMartini T.J.
      • et al.
      Unloading the left ventricle before reperfusion in patients with anterior ST-segment elevation myocardial infarction.
      A phase 2 Study of Multistep Pharmacological and Invasive Management for Cardiogenic Shock (ALTSHOCK) of 24 patients in Italy with CS had a protocol driven escalation from inopressor therapy, to intra-aortic balloon pump, to ECMO, if necessary.
      • Morici N.
      • Oliva F.
      • Ajello S.
      • et al.
      Management of cardiogenic shock in acute decompensated chronic heart failure: the ALTSHOCK phase II clinical trial.
      The authors reported an 88% 60-day survival and that 29% improved on medical treatment, 65% underwent ventricular assist device implantation, and 9% underwent transplant. Although these data clearly require replication in larger population, this proof of concept study re-enforces the potential for selective MCS deployment and that some patients can improve on medical therapy alone. Layered on this framework is the potential for early multidisciplinary management in the form of cardiogenic shock teams. Tehrani and colleagues recently reported that, in a single-centre cohort, the early activation of a shock team that included interventional cardiology, advanced heart failure, cardiac surgery, and critical care substantially improved 30-day survival from 47% to 77% over a 3-year period.
      • Tehrani B.N.
      • Truesdell A.G.
      • Sherwood M.W.
      • et al.
      Standardized team-based care for cardiogenic shock.
      Although this study used protocol-driven hemodynamic criteria to guide early MCS therapy, it is impossible to disentangle the potential benefits of more proximal engagement of multispecialty stakeholders. The team-based approach may have plausibly improved therapeutic decisions owing to collective input, the vigilance with which individual patients were followed, and/or the ability escalate therapies when initial strategies were failing.
      In this special Cardiac Support Therapies issue of the Canadian Journal of Cardiology, Kim highlights the unmet expectations for improvement of CS survival following the publication of the SHOCK trial, particularly with the growth of temporary MCS, and proposes the need for more proximal multidisciplinary care and the rapid triage of patients with CS to dedicated CS centres within Canada.
      • Hochman J.S.
      • Sleeper L.A.
      • Webb J.G.
      • et al.
      Early revascularization in acute myocardial infarction complicated by cardiogenic shock
      SHOCK investigators: should we emergently revascularize occluded coronaries for cardiogenic shock?.
      ,
      • Kim D.H.
      Mechanical circulatory support in cardiogenic shock: shock team or bust?.
      In addition, a number of authors highlight our collective understanding of MCS best practices in patients with CS and/or advanced heart failure in either the acute or subacute phases of care. Three reviews provide complementary perspectives on ECMO best practices indications and management, each with unique focuses. Bhatia et al. provides a comprehensive overview of the multimodal and multisystem monitoring requited to care for patients on ECMO; Guihaire et al. discuss the unique impact MCS devices have on hemostasis and hemolysis; and Singh et al. provide a practical and well–thought-out approach to ECMO weaning, all of which I believe are important contributions to the pre-existing body of ECMO review papers.
      • Bhatia M.
      • Katz J.N.
      Contemporary comprehensive monitoring of the veno-arterial extracorporeal membrane oxygenation patients.
      • Guihaire J.
      • Haddad F.
      • Hoppenfeld M.
      • et al.
      Physiology of the assisted circulation in cardiogenic shock: a state of the art perspective.
      • Singh G.
      • Hudson D.
      • Shaw A.
      Medical optimization and liberation of adult patients from VA-ECMO.
      In addition, Alviar et al. outline the physiologic cardiopulmonary interaction in patients with left and right ventricular failure requiring positive pressure ventilation and provide an approachable mechanical ventilation framework for the nonexpert in this tenuous population.
      • Alviar C.L.
      • Rico-Mesa J.S.
      • Morrow D.A.
      • et al.
      Positive pressure ventilation in cardiogenic shock: review of the evidence and practical advice for patients with mechanical circulatory support.
      The review by O'Brien et al. provides a thought-provoking argument that the lactate-pyruvate ratio should be routinely monitored in this population to better delineate the interplay between tissue hypoxia and high-demand state.
      • O’Brien C.
      • Beaubien-Souligny W.
      • Amsallem M.
      • et al.
      Cardiogenic shock: reflections at the crossroad between perfusion, tissue hypoxia, and mitochondrial function.
      The second group of reviews focus on subacute care. Kiamanesh provides an approach to left-ventricular assist device care and complications, which blends accessible language and clinical accuracy that will undoubtedly be appreciated by its nonexpert clinician target audience.
      • Kiamanesh O.
      • Kaan A.
      • Toma M.
      Medical management of left ventricular assist device patients: a practical guide for the nonexpert clinician.
      Finally, Huitema and colleagues discuss therapies in transplant ineligible patients with a focus on how palliative care can reduce symptoms and hospitalizations in this challenging population.
      • Huitema A.A.
      • Harkness K.
      • Malik S.
      • Suskin N.
      • McKelvie R.S.
      Therapies for advanced heart failure patients ineligible for heart transplant: beyond pharmacotherapy.
      The unifying themes among all the reviews is that many of the authors call for team-based care models and were careful to not misrepresent their clinical practice suggestions as standards of care based on high-quality evidence, and many simultaneously acknowledged the pressing needs need for more research in this field.
      In the acute phase of CS, as we work to discover the best temporary MCS and medical treatment strategies, we believe there is a growing recognition that CS is an etiologically, phenotypically, and hemodynamically diverse condition. Although early temporary MCS therapy is the most promising therapeutic technology that could improve the survival of patients with CS, the costs and potential complications together with the yet unproven survival advantage highlights the potential future research need for a more targeted MCS deployment strategy in patients who are the most likely the benefit or, conversely, the least likely to survive with medical therapy alone.

      Funding Sources

      The authors have no funding sources relevant to the contents of this paper to report.

      Disclosures

      D.A.B. has performed consulting work for Abiomed, Abbott, Livanova, and Getinge and has been a speaker for Novartis. A.M. has received speaker's honoraria from Orion, Otsuka, Philips, Roche, and Servier and has received fees as a member of an Advisory Board and/or Steering Committee and/or research grants from 4TEEN4, Adrenomed, Epygon, Neurotronik, Roche, Sanofi, and Sphyngotec. S.v.D. has no conflicts of interest to disclose.

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