Update on the management of cardiogenic shock

PURPOSE OF REVIEW: Cardiogenic shock is a life-threatening emergency that occurs frequently with acute coronary syndromes. If rapid myocardial reperfusion following acute myocardial infarction is not obtained, either with thrombolytics or by revascularization, cardiogenic shock frequently develops and the mortality rate is high. This review summarizes recent advances in the pathophysiology, incidence and treatment of cardiogenic shock. Particular attention is given to pharmacologic advances. RECENT FINDINGS: Cardiogenic shock continues to occur in 5-10% of patients who suffer a myocardial infarction and the mortality remains over 50% in most studies. Treatment preference is referral to a cardiac center capable of reperfusion using multiple therapies. While no delay in reperfusion is acceptable, emphasis on implementing supportive treatment such as vasopressors, inotropes, and fluids remains critical. There is a wide variance in treatment standards despite established guidelines. Overall mortality from cardiogenic shock has decreased but the incidence remains unchanged. SUMMARY: Emerging pharmacological interventions designed to counteract the underlying proinflammatory pathophysiologic mechanisms may, in combination with early revascularization, result in improved patient outcomes, but there is no magic bullet on the horizon. Attention to the timeliness of transport and treatment of patients with a focus on revascularization is required for cardiogenic shock patients.     

Cardiogenic shock: treatment

The treatment of cardiogenic shock complicating the acute coronary syndromes consists of medical therapy, percutaneous revascularization procedures, cardiac surgery, and the implantation of devices. Medical therapy is limited to different positive inotropic and vasoactive drugs, without any firm evidence of survival benefit using these drugs. Several new pharmacologic compounds are at different stages of clinical research, but are not yet routinely approved for the treatment of cardiogenic shock. The only evidence-based therapy with proven survival benefit is timely revascularization. Intra-aortic balloon pump counterpulsation maintains its central role as supportive treatment in cardiogenic shock patients. Anecdotal evidence is available about the use of ventricular assist devices, cardiac resynchronization therapy, and emergent heart transplantation.     

Plasma concentrations of interleukin-6, organ failure, vasopressor support, and successful coronary revascularization in predicting 30-day mortality of patients with cardiogenic shock complicating acute myocardial infarction

OBJECTIVE: Inflammation may play an important role in the pathogenesis, persistence, and prognosis of cardiogenic shock. We analyzed whether elevated plasma concentrations of inflammatory markers are independently associated with an adverse prognosis (increased 30-day mortality rate) in patients with cardiogenic shock. DESIGN: Retrospective study. SETTING: Single-center study, eight-bed intensive care unit at a university hospital. PATIENTS: Retrospective study on stored plasma samples from 38 patients with cardiogenic shock complicating acute myocardial infarction. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-day nonsurvivors (n = 23, 61%) had been less frequently successfully revascularized, exhibited more frequently renal failure, needed higher vasopressor doses, and presented with significantly higher interleukin-6 plasma concentrations on intensive care unit admission than 30-day survivors. Univariate hazard ratios (95% confidence interval) for 30-day mortality were 1.49 (1.24-1.80) for every 50 pg/mL increase in the interleukin-6 plasma concentration (p = .00003), 1.06 (1.02-1.10) for every 0.1 microg x kg x min increase in the total vasopressor dose (p = .007), 1.14 (1.04-1.25) for every mmol/L increase in serum lactate (p = .006), 2.47 (1.06-5.73) for acute renal failure (p = .036), and 0.34 (0.14-0.82) for successful revascularization (p = .016). However, interleukin-6 plasma concentrations were correlated with vasopressor need and were significantly higher in patients with acute renal failure and in patients without or unsuccessful revascularization. In a multivariate Cox-proportional hazard model, interleukin-6 was the only significant predictor of 30-day mortality with a hazard ratio of 1.42 (1.12-1.80, p = .004). Accordingly, interleukin-6 concentrations > or =200 pg/mL (the point of maximum interest by receiver operating characteristic analysis with a specificity of 87% and a sensitivity of 74%) were associated with a significantly increased 30-day mortality rate in both patients with and patients without successful revascularization. CONCLUSIONS: Interleukin-6 concentrations are an independent predictor of 30-day mortality in patients with acute myocardial infarction complicated by cardiogenic shock.     

主动脉内球囊反搏在急性心肌梗死并发心源性休克中的应用

目的　评价主动脉内球囊反搏 (IABP)对急性心肌梗死合并心源性休克患者在不同血管再通治疗中的疗效和短期生存的影响。方法　回顾性分析了 10 8例接受IABP治疗的急性心肌梗死合并心源性休克患者 ,分别分析了溶栓治疗组、介入治疗组和冠脉搭桥 (CABG)手术治疗组患者的基本特征和血流动力学情况 ,并比较IABP治疗对住院病死率和 30d病死率的影响。结果　患者的基本特征包括年龄、冠心病的危险因子等在各组间差异无显著性意义 (P >0 0 5 ) ,但手术治疗组的男性患者显著少于其它两组 (P <0 0 5 ) ;IABP治疗前血流动力学状态各组间也无显著性意义 ,住院病死率和 30d病死率手术治疗组均显著低于溶栓组和介入组 ,分别为 18 9%、 6 2 8%和 6 0 7% ,16 2 %、 6 0 5 %和 6 0 7% ,P值均 <0 0 0 1。结论　IABP支持下进行CABG治疗可显著减低心肌梗死合并心源性休克患者的近期死亡率 ,且显著优于溶栓治疗和介入治疗     

Clinical experience with intra-aortic balloon counterpulsation over 10 years: a retrospective cohort study of 459 patients

OBJECTIVE: The objective of this study was to identify prognostic predictors for the patients experiencing cardiogenic shock who required the institution of intra-aortic balloon counterpulsation (IABP). DESIGN, SETTING, AND PATIENTS: Patients with cardiogenic shock were retrieved from the clinical information system in National Taiwan University Hospital and classified according to their etiology: acute coronary syndrome (ACS), ST segment elevation myocardial infarction (STEMI), congestive heart failure (CHF), hemodynamic instability after post-coronary bypass graft operation (post-CABG) or after percutaneous intervention (post-PCI), and out-of-hospital cardiac arrest (OHCA) victims. MEASUREMENTS: Kaplan-Meier curves and Cox regression model were applied to evaluate the factors associated with survival. MAIN RESULTS: A total of 459 patients were found to belong to one of six etiology categories between 1995 and 2004. The 30-day mortality was highest in the OHCA group, followed by the STEMI, CHF, ACS, post-PCI, and post-CABG groups in a decreasing frequency (log rank p<0.001). Peak troponin I level was negatively associated with survival, and its effect largely paralleled with underlying etiology. Age and renal impairment were significant prognostic predictors for 30-day mortality (hazard ratio=1.031, p<0.001 and hazard ratio=1.266, p<0.001). Comparing to those manifested as OHCA who had the worst outcome, patients in the other etiology groups had significantly better survival. CONCLUSIONS: This study has illustrated that age, renal function, and etiology-related cardiac injury are predictors for in-hospital course and mortality in those who experienced cardiogenic shock with IABP. The optimal strategy for revascularization in this high-risk group needs further validation.     

Nitric oxide inhibition rapidly increases blood pressure with no change in outcome in cardiogenic shock: the TRIUMPH trial

The TRIUMPH study, recently published in Journal of the American Medical Association, was a prospective randomized placebo-controlled trial testing the hypothesis that tilarginine (a non-specific inhibitor of nitric oxide synthase), when compared with placebo, would reduce 30-day mortality by 25% in patients with myocardial infarction complicated by refractory cardiogenic shock despite successful revascularization of the infarct-related artery. Patients received an intravenous bolus of the drug followed by 5 hours of intravenous infusion of the drug or a matching placebo. Although tilarginine increased systolic blood pressure by 5 mmHg at 2 hours, no effect on mortality was observed at 30 days. There was, however, a 6% absolute increase in 30-day mortality in the tilarginine group (48%, versus 42% in the placebo). This definitive trial gave strong indications for stopping any further trial using non-specific inhibitors of nitric oxide synthase in cardiogenic shock and possibly also in any other cardiovascular area.     

急性心肌梗死合并心源性休克的血运重建策略

尽管早期血运重建的广泛开展,急性心肌梗死合并心源性休克仍是治疗的重点和难点。另外,急性心肌梗死伴心源性休克患者往往合并多支血管病变,其最佳血运重建策略尚无定论。本文就心源性休克定义及病因,急性心肌梗死合并心源性休克早期血运重建的重要性及血运重建策略选择方面做一综述。     

Prise en charge du choc cardiogénique d’origine ischémique : mise au point

Cardiogenic shock complicating myocardial infarction still remains a clinical challenge. Early revascularization represented the last major improvement aiming at the mortality reduction; however, despite optimal pharmacological treatments, mortality still exceeds 40%. Treatment with catecholamines is limited by arrhythmia, increases myocardial oxygen consumption, and is associated with worsened prognosis. Due to multiple beneficial hemodynamic and systemic effects, therapeutic hypothermia seems a promising tool. At least, life support aims to ensure adequate coronary and systemic circulation to limit multi-organ failure while preserving the myocardium and reducing the risk of ischemia. While intra-aortic balloon pump has been questioned recently in a large randomized controlled trial, other circulatory support devices have proved their effectiveness on early hemodynamic parameters without improving mortality, except for refractory shock. Large randomized trials are required to define the exact role of these devices according to patient’s hemodynamic status. Early diagnosis, coupled with the intensive management of shock based on effective reperfusion and adequate circulatory support, is the only way to limit or even better prevent multi-organ failure occurrence and thus improve outcome.     

Intra-aortic balloon pump in patients with acute myocardial infarction complicated by cardiogenic shock: results of the ALKK-PCI registry

Aims

The recommendation for the use of the intra-aortic balloon pump (IABP) as adjunct in patients with cardiogenic shock undergoing primary PCI in current guidelines is controversial. We sought to investigate the use and impact of the outcome of IABP in current practice of percutaneous coronary interventions in Germany.

Methods and results

Between January 2006 and December 2011, a total of 55,008 consecutive patients with acute coronary syndromes undergoing PCI in 41 hospitals were enrolled into the prospective Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte registry. Of these, 22,039 had STEMI and 32,969 had NSTEMI, and cardiogenic shock was observed in 1,435 (6.5 %) and 478 (1.4 %), respectively. Of the total of 1,913 patients with shock, 487 (25.5 %) were treated with IABP. In-hospital mortality with and without IABP was 43.5 and 37.4 %. In the multivariate analysis, the use of IABP was associated with a strong trend for an increased mortality (odds ratio 1.45, 95 % CI 1.15–1.84).

Conclusion

In the current clinical practice in Germany, IABP is used only in one quarter of patients with cardiogenic shock treated with primary PCI. We observed no benefit of IABP on outcome, which supports the findings of the randomized IABP-Shock II trial.     

Aortic counterpulsation in cardiogenic shock during acute myocardial infarction

Intra-aortic balloon counterpulsation is the most widely used form of mechanical hemodynamic support in the setting of cardiogenic shock due to ST-segment elevation myocardial infarction (STEMI). Intra-aortic balloon pump (IABP) is also strongly recommended (class 1b) in the current European guidelines for treatment of STEMI. The evidence of a possible benefit of IABP in this setting is based mainly on registry data and a few randomized trials. Cardiogenic shock and subsequent death due to STEMI result from three factors: hemodynamic deterioration, occurrence of multiorgan dysfunction and systemic inflammatory response. IABP does not cause an immediate improvement in blood pressure, but the recent SHOCK II trial shows positive effects on multiorgan dysfunction. Some experimental and clinical studies have indicated that IABP results in hemodynamic benefits as a result of afterload reduction and diastolic augmentation with improvement of coronary perfusion. However, the effect on cardiac output is modest and may not be sufficient to reduce mortality. Furthermore we can say that the use of IABP before coronary revascularization in the setting of STEMI complicated with cardiogenic shock may make the interventional procedure safer by improving left ventricular unloading. The purpose of the present review is to clarify the state of the art on this topic.     

Cardiogenic shock.

Mortality rates in patients with cardiogenic shock remain frustratingly high. Its pathophysiology involves a downward spiral in which ischemia causes myocardial dysfunction, which in turn worsens ischemia. Areas of viable but nonfunctional myocardium can contribute to the development of cardiogenic shock. Rapid diagnosis and prompt initiation of supportive therapy to maintain blood pressure and cardiac output, followed by expeditious coronary revascularization, are crucial. The SHOCK multicenter randomized trial has provided important new data that support a strategy of emergent cardiac catheterization and revascularization with angioplasty or coronary surgery when feasible. This strategy can improve survival and represents standard therapy at this time. In hospitals without direct angioplasty capability, stabilization with IABP and thrombolysis followed by transfer to a tertiary care facility may be the best option.     

Effect of diabetes on the mortality risk of cardiogenic shock in a community-based population

OBJECTIVE: To examine the mortality of diabetic vs nondiabetic patients with anterior myocardial infarction (AMI) among the subsets of this population who did and did not develop cardiogenic shock. PATIENTS AND METHODS: The study population consisted of a consecutive series of 1263 Olmsted County, Minnesota, patients admitted to the coronary care unit at the Mayo Clinic in Rochester, Minn, between January 1, 1988, and July 31, 2000. Of these patients, 73 met the criteria for cardiogenic shock during their hospitalization. In-hospital and postadmission mortality were compared between diabetic and nondiabetic patients within the cardiogenic shock and nonshock patient groups, respectively. RESULTS: In patients with AMI and cardiogenic shock, diabetes was associated with a trend for increased in-hospital mortality (odds ratio, 2.82; 95% confidence interval [CI], 0.90-9.92; P = .08). In 73 patients with cardiogenic shock, estimated survival at 1, 3, and 5 years was 25%, 17%, and 17%, respectively, for diabetic patients, and 50%, 44%, and 36%, respectively, for nondiabetic patients (P = .046). The association between diabetic patients and increased long-term mortality was stronger in patients with cardiogenic shock than in patients without cardiogenic shock (adjusted relative risk, 2.08; 95% CI, 1.11-3.90; P = .02). In diabetic patients without cardiogenic shock, estimated survival at 1, 3, and 5 years was low, at 75%, 61%, and 45%, respectively, compared with 83%, 76%, and 69%, respectively, for nondiabetic patients (adjusted relative risk, 1.29; 95% CI, 1.02-1.62; P = .03). CONCLUSION: The presence of diabetes as a comorbidity in patients with AMI appears to be associated with increased mortality compared with nondiabetic patients, and this relationship may be potentially magnified in patients who develop cardiogenic shock.     

The Best Bypass Surgery Trial: rationale and design of a randomized clinical trial with blinded outcome assessment of conventional versus off-pump coronary artery bypass grafting

BACKGROUND: Recent trials suggest that off-pump coronary artery bypass grafting (OPCAB) reduces the risk of mortality and morbidity compared with conventional coronary artery bypass grafting (CCAB) using cardiopulmonary bypass. Patients with a moderate- to high-risk of complications after CCAB may have additional benefit from OPCAB. METHODS: The Best Bypass Surgery Trial is a randomized, single center trial comparing the effects of OPCAB versus CCAB. The inclusion criteria are 3 vessel coronary heart disease affecting one of the marginal arteries, age>54 years, and EuroSCORE>or=5. The primary composite outcome measure consists of all-cause mortality, myocardial infarction, stroke, cardiac arrest, cardiogenic shock, and cardiac revascularization procedure. Follow up involves collection of data of mortality and morbidity via linkage to public registers, quality of life assessment at 3 and 12 months postoperatively and angiographic control at 12 months. The sample size of 330 patients was based on an estimated 75% one-year event free rate of the primary outcome measure in the OPCAB arm and 60% in the control arm with alpha=.05 and beta=.20. Accordingly, the trial will be able to detect an absolute risk reduction of 15% or a relative risk reduction of 37.5%. The median follow-up time is scheduled to 3 years. RESULTS: Enrollment started in April 2002 and ended March 2006. CONCLUSION: The results may have implications on the treatment modality of moderate- to high-risk patients scheduled for coronary artery bypass grafting.     

床边紧急置入主动脉内球囊反搏治疗心源性休克的围术期护理

目的总结床边紧急置入主动脉内球囊反搏（IABP）辅助治疗急性心肌梗死合并心源性休克的围术期护理。方法对15例急性心肌梗死合并心源性休克患者床边置入IABP的围术期护理要点进行总结,包括术前准备,术中配合,术后生命体征、尿量、心电图、球囊导管、反搏压力、并发症等的监测。结果患者在应用IABP辅助治疗后,血流动力学趋于稳定,表现为心率减慢,舒张压、平均动脉压、尿量明显增加,血管活性药物剂量明显减少（P〈0.01）;住院期间存活11例,死亡4例。结论对于急性心肌梗死合并心源性休克早期床旁应用IABP的患者,积极的术中配合和有效的术后监护能为冠脉血运重建提供稳定的血流动力学支持,提高救治成功率。     

Acute myocardial infarction complicated by cardiogenic shock: role of mechanical circulatory support

Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is the leading cause of in-hospital death for patients admitted with acute coronary syndromes. Expert guidelines for the care of AMI-CS patients recommend early revascularization with intra-aortic balloon pump support. Ventricular assist devices (VADs) offer the advantages of providing greater and longer-term cardiac support than an intra-aortic balloon pump and may improve outcomes when inserted early after heart failure symptoms begin. Pulsatile VADs are versatile and can provide biventricular support but are associated with a higher incidence of serious complications. The newer percutaneous VADs can normalize cardiac index and can be implanted without surgery. Therefore, early implementation of percutaneous VADs and early revascularization may reduce the high mortality of AMI-CS. However, access to revascularization and VAD support, including percutaneous VADs, is currently limited and must improve to more effectively treat AMI-CS patients.     

Acute myocardial infarction complicated by cardiogenic shock: role of mechanical circulatory support

Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is the leading cause of in-hospital death for patients admitted with acute coronary syndromes. Expert guidelines for the care of AMI-CS patients recommend early revascularization with intra-aortic balloon pump support. Ventricular assist devices (VADs) offer the advantages of providing greater and longer-term cardiac support than an intra-aortic balloon pump and may improve outcomes when inserted early after heart failure symptoms begin. Pulsatile VADs are versatile and can provide biventricular support but are associated with a higher incidence of serious complications. The newer percutaneous VADs can normalize cardiac index and can be implanted without surgery. Therefore, early implementation of percutaneous VADs and early revascularization may reduce the high mortality of AMI-CS. However, access to revascularization and VAD support, including percutaneous VADs, is currently limited and must improve to more effectively treat AMI-CS patients.     

Clinical outcomes of complete revascularization using either angiography-guided or fractional flow reserve-guided drug-eluting stent implantation in non-culprit vessels in ST elevation myocardial infarction patients: insights from a study based on a systematic review and meta-analysis

Current guidelines recommend that percutaneous coronary intervention (PCI) should be restricted to the culprit vessel in ST elevation myocardial infarction (STEMI) patients with multi-vessel disease (MVD) and without cardiogenic shock. However, newer data suggests that performing complete revascularization (CR) in MVD patients may lead to better outcomes compared to intervention in the culprit vessel only. The aim of this meta-analysis is to examine the available data to determine if CR (using either angio- or fractional flow reserve guidance—FFR) following primary PCI in STEMI patients without cardiogenic shock impacts clinical outcomes. Meta-analysis was performed by conducting a literature search of PubMed from January 2004 to July 2017. Pooled estimates of outcomes, presented as odds ratios (OR) [95% confidence intervals], were generated using random-effect models. A total of 9 studies (3317 patients) were included. CR showed a significant MACE reduction (OR 0.49, 95% CI 0.36–0.66, p?<?0.001); All-cause mortality (OR 0.69, 95% CI 0.48–0.98, p?=?0.04) and repeat revascularization (OR 0.38, 95% CI 0.28–0.51, p?<?0.001) at?≥?12 months follow-up. The FFR-guiding CR group presented a MACE reduction (odds ratio 0.52, 95% CI 0.30–0.90, p?=?0.02) due to a decrease of repeat revascularization (OR 0.41, 95% CI 0.21–0.80, p?=?0.009). Overall, performing complete revascularization in STEMI patients showed a MACE reduction, all-cause death and repeat revascularization. Compared to culprit-only revascularization, treating multi-vessel disease in STEMI patients using FFR guidance is associated with decreased incidence of MACE, due to a decreased rate of revascularization.     

Prehospital clinical presentation in patients with acute coronary syndrome complicated by cardiogenic shock: A single center study

BackgroundThe development of cardiogenic shock remains the most important factor affecting the prognosis of patients with acute coronary syndrome. Despite significant advances in treatment, achieved in the last two decades, the mortality rate is still very high. The development of knowledge about the pathophysiology of cardiogenic shock, necessitates a thorough and comprehensive assessment of its progress at all stages of medical care.ObjectivesThe aim of the study was to assess the prehospital clinical presentation in patients with acute coronary syndrome complicated by cardiogenic shock.MethodsThe population of our study consisted of 40 patients with acute coronary syndrome complicated by cardiogenic shock who were transported to the Intensive Cardiac Therapy Clinic by ambulances directly from place of the event in order to implement primary coronary intervention. The control group was selected among age, gender and infarct location-matched patients with acute coronary syndrome uncomplicated by shock. The clinical presentation in investigated patients was assessed on the basis of the data contained in the medical records of Emergency Medical Services teams.ResultsIn univariate logistic regression analysis eight prehospital clinical symptoms proved to be statistically significant predictors of the development of cardiogenic shock: fainting and/or impaired consciousness, pale skin, cold skin, clammy skin, dyspnea, pulmonary congestion, peripheral cyanosis and hyperglycemia >11,1 mmol/l. In the multivariate model significant predictors of cardiogenic shock development were: pale skin and hyperglycemia >11.1 mmol/l. A risk prediction model was constructed. It proved to differentiate patients from study and control group highly significantly (p < 0.001).ConclusionsPatients with acute coronary syndrome who develop cardiogenic shock, present a different clinical symptoms at the moment of the first medical contact. The proposed 4S Scale can be used for quick assessment of risk in patients with acute coronary syndrome before the development of a fully-blown cardiogenic shock with severe, long-lasting hypotonia.     

Acute myocardial infarction. Treatment in the coronary care unit

Management of the patient with acute myocardial infarction is in flux. In the current "reperfusion era," many patients receive intravenous thrombolytic therapy and aspirin before admission to the coronary care unit. Appropriate use of drugs limits expansion of the infarct and reduces mortality rates in patients with uncomplicated myocardial infarction. Percutaneous transluminal coronary angioplasty may be necessary in those who are not candidates for drug treatment or who show recurrent ischemia after thrombolysis, while cardiac transplantation may be the only hope for patients with multivessel disease who are in cardiogenic shock. The "cocktail era," in which polypharmacy is both acceptable and effective, will likely be the next stage in management of acute myocardial infarction.     

Short-term mechanical circulatory support by veno-arterial extracorporeal membrane oxygenation in the management of cardiogenic shock and end-stage heart failure

Despite modern treatment modalities, cardiogenic shock is associated with a very high risk of mortality and morbidity. The short- and long-term survival in patients with cardiogenic shock or end-stage heart failure has improved considerably by recent technological advances in short and long-term mechanical circulatory support devices. For short-term mechanical support, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been increasingly used as bridge-to-decision and bridge-to-recovery in cardiogenic shock patients. Long-term mechanical circulatory support devices such as left ventricular assist devices (LVADs) are widely available and play a central role in bridge-to-transplantation in those eligible for heart transplantation (HTX) and as destination therapy (DT) in those not eligible for heart transplantation. Nevertheless, patients with critical cardiogenic shock show a deleterious outcome after LVAD-implantation or HTX with higher mortality, more complications and higher burden on financial resources. These considerations underscore the importance of optimal timing and appropriate patient selection for eventual LVAD therapy. The current report will focus on the immediate management of patients with cardiogenic shock with inotropes, discuss the use of IABP and focus mainly on pivotal choices to be made in the period spanned by short term mechanical circulatory support in patients with refractory cardiogenic shock.