Infarction-Related Cardiogenic Shock— Diagnosis, Monitoring and Therapy

A German-Austrian S3 guideline

Background: The second edition of the German-Austrian S3 guideline contains updated evidence-based recommendations for the treatment of patients with infarction-related cardiogenic shock (ICS), whose mortality is several times higher than that of patients with a hemodynamically stable myocardial infarction (1).

Methods: In five consensus conferences, the experts developed 95 recommendations—including two statements—and seven algorithms with concrete instructions.

Results: Recanalization of the coronary vessel whose occlusion led to the infarction is crucial for the survival of patients with ICS. The recommended method of choice is primary percutaneous coronary intervention (pPCI) with the implantation of a drug-eluting stent (DES). If multiple coronary vessels are diseased, only the infarct artery (the “culprit lesion”) should be stented at first. For cardiovascular pharmacotherapy—primarily with dobutamine and norepinephrine—the recommended hemodynamic target range for mean arterial blood pressure is 65–75 mmHg, with a cardiac index (CI) above 2.2 L/min/m². For optimal treatment in intensive care, recommendations are given regarding the type of ventilation (invasive rather than non-invasive, lung-protective), nutrition (no nutritional intake in uncontrolled shock, no glutamine supplementation), thromboembolism prophylaxis (intravenous heparin rather than subcutaneous prophylaxis), und further topics. In case of pump failure, an intra-aortic balloon pump is not recommended; temporary mechanical support systems (Impella pumps, veno-arterial extracorporeal membrane oxygenation [VA-ECMO], and others) are hemodynamically more effective, but have not yet been convincingly shown to improve survival.

Conclusion: Combined cardiological and intensive-care treatment is crucial for the survival of patients with ICS. Coronary treatment for ICS seems to have little potential for further improvement, while intensive-care methods can still be optimized.

In the German FITT-STEMI trial on 12 675 patients with ST segment elevation myocardial infarction (STEMI) who were treated with percutaneous coronary intervention (PCI) following emergency medical service transportation to hospital, mortality among hemodynamically stable myocardial infarction (MI) patients (85%) and non-resuscitated MI patients with infarction-related cardiogenic shock (ICS) (5.5%) was 2.7% and 39%, respectively (1). Successful coronary revascularization alone does not seem to ensure a favorable outcome in ICS patients, since the primary factor responsible for their unfavorable prognosis is the shock-related dramatic drop in perfusion of vital organs and the subsequent development of multiple organ dysfunction syndrome (MODS), even after revascularization of the infarction-related coronary artery. Hence, ICS patients require not only interventional cardiology care as in uncomplicated myocardial infarction, but also optimum intensive care treatment.

In light of the complexity of the condition, the first ICS-specific guideline was developed (2). In the now available updated second edition of this guideline, these two components of the management of ICS—cardiology and intensive care treatment—are given adequate consideration; in contrast, the European ICS recommendations (3), which have recently been published, largely focus on the cardiological aspects.

Since only few of the recommendations are supported by high-quality data from randomized controlled trials (RCTs) on ICS patients, it was necessary to review the evidence for critically ill patients and for patients with myocardial infarction in respect to its applicability to ICS patients and, if applicable, to use these findings to make expert-consensus recommendations.

The 95 recommendations (including two statements) and seven algorithms enable clinicians to treat their ICS patients in the prehospital setting, in the cardiac catheterization laboratory, in the intensive care unit, and in the rehabilitation clinic based on the currently available evidence.

Methods

Guideline design and development

The recommendations of the guideline group (eBox 1) were developed in five sessions, using nominal group processes; details are provided in the guideline report (4). The guideline is valid until 31 January 2024.

eBox 1

Composition of the guideline group (collaborators)

The aim of the guideline and who the guideline is for

The aim of this S3 guideline is to implement evidence-based recommendations on best quality of care for patients with ICS. The guideline is for all clinicians responsible for treating patients with myocardial infarction and cardiogenic shock, mainly cardiologists, internists, intensive care physicians, cardiac surgeons, anesthesiologists, physicians in emergency departments and chest pain units, emergency physicians, and rehabilitation physicians. Specific guideline information is also relevant for nursing staff.

Data acquisition

For the second edition of the guideline, again a primary literature search (PubMed, search terms: “myocardial infarction and cardiogenic shock“) was conducted, covering the period following the literature search for the first edition (until 30 September 2009) from 1 October 2009 to 31 January 2019 (3668 hits) (eFigure). For the supporting text, publications from 2019–2021 known to the guideline group were also used; however, these papers did not influence the consensus recommendations.

eFigure

Literature search and selection for clinical practice (S3) guideline

Grades of recommendation

The grades of recommendations are detailed in Box 1.

Box 1

Grades of recommendation

Results

Box 2 shows selected recommendations. In particular, new and modified recommendations of the updated guideline are presented below (Box 3).

Box 2

Selection of recommendations*1 of the German-Austrian S3 guideline “Infarction-related Cardiogenic Shock—Diagnosis, Monitoring and Therapy“, focusing on new or revised recommendations

Box 3

Diagnosis, monitoring and therapy of infarction-related cardiogenic shock—alterations in the 2nd edition

Initial management

Every minute counts! In no other group of patients with myocardial infarction, the length of time between diagnosis and PCI is as critical for patient survival as it is in the ICS patient group (1). Therefore, the emergency physician must establish the suspected diagnosis of “ICS“ quickly in the prehospital setting (↑↑): the diagnosis “myocardial infarction” (ST/non-ST segment elevation myocardial infarction[STEMI/NSTEMI]) based on clinical presentation, ECG and, in the further course, laboratory results; the diagnosis “shock“ typically based on systolic blood pressure (BPsys) <90 mm Hg sustained for 30 min in conjunction with signs of reduced organ perfusion (cold extremities, oliguria, mental alterations). Invasively established shock criteria (cardiac index [CI] <2.2 L/min/m², pulmonary artery occlusion pressure [PAOP] >15 mm Hg) are not required for diagnosis.

Revascularization

Rapid restoration of interrupted coronary blood flow in the infarction-related artery is critical for prognosis (↑↑)— whenever possible by means of primary percutaneous coronary intervention (pPCI) and implantation of a drug-eluting stent (DES) (↑)—in case of initial ICS within 90 min (↑) and in case of delayed occurrence of ICS as early as possible (↑↑)—;in few selected cases by means of coronary artery bypass graft surgery (CABG) and, if pPCI is not available in time, by means of systemic fibrinolysis.

The superiority of the invasive strategy (mainly pPCI) was established in the SHOCK trial published 20 years ago and improvements in long-term survival of 20% have been shown in RCTs (relative risk 0.82; 95% confidence interval [0.69; 0.97]) (5). A significant reduction in hospital mortality was shown by a propensity registry, both in STEMI-ICS patients (odds ratio [OR]: 0.37 [0.34; 0.40], p <0.0001) and in NSTEMI-ICS patients (OR 0.47 [0.43; 0.51], p<0.0001) (6).

In patients with multivessel coronary artery disease, only the infarction-related coronary artery (“culprit lesion”) shall be dilated in the acute stage (Box 2, ↑↑), with a 16% lower 30-day mortality compared to multivessel PCI (7).

In patients with complex coronary pathology, immediate revascularization shall be sought in consultation with cardiologists and cardiac surgeons, either as pPCI or as CABG and in case of unsuccessfully attempted pPCI as CABG (↑↑). Mortality of acute CABG is reported to be not higher than mortality of pPCI (8).

The further pPCI procedure in patients with ICS (vascular access, co-medication, same level of success in men and women as well as in diabetic patients) follows the procedure for patients with STEMI/NSTEMI. Likewise, in patients aged >75 years, early revascularization should be considered based on an individual evaluation of positive components, such as mobility, autonomy and social integration, as well as negative components, such as frailty, immobility and need of nursing care (↑). An increase in mortality of 32% in ICS patients aged <65 years to 56% in patients >85 years was reported in the absence of a higher rate of bleeding complications (9).

Resuscitation in patients with infarction-related cardiogenic shock

One in two ICS patients initially experiences cardiac arrest (7, 10). Successfully resuscitated ICS patients show an increase in mortality by about 20% compared to ICS patients without cardiac arrest (11). In these patients, too, early cardiac catheterization (CC)/pPCI should be considered based on an individual benefit-risk evaluation (Box 2, ↑); however, the decision for pPCI must be made without assessment of the neurological prognosis as this can only be performed later in the course of treatment.

Targeted temperature management (TTM) with lowering of body temperature to 32 – 36 °C for at least 24 hours is recommended for all resuscitated comatose ICS patients (↑). Until valid data is available, the decision on the use of extracorporeal cardiopulmonary resuscitation (eCPR) in ICS patients has to be made on an individual basis (12, 13).

Persistent shock after revascularization: monitoring and drug therapy

In patients with persistent signs and symptoms of shock after revascularization, the goals of hemodynamic treatment control (Figure) are: to stabilize blood pressure and to ensure adequate perfusion to vital organs. Here, it is recommended to repeatedly measure cardiac output (CO) (Box 2, ↑↑) with a target pressure-flow corridor (Figure): “mean arterial pressure” (MAP) >65 to <75 mm Hg, and a cardiac index (CI) >2.2 L/min/m² or a cardiac power index (CPI; product of CI and MAP × 0.0022 in W/m²) of >0.4, with low-dose catecholamine administration and a heart rate of <100/min with sinus rhythm and <110/min with atrial fibrillation.

Figure

Hemodynamic shock therapy in patients with infarction- related cardiogenic shock

Furthermore, dobutamine is the inotropic agent of choice (↑) and, if MAP is <65 mm Hg, norepinephrine the vasopressor of choice (↑). In comparison to norepinephrine administration, lactate levels are higher with epinephrine administration in ICS patients and the rate of patients with refractory shock is increased (14). In patients refractory to catecholamines, levosimendan should be preferred over phosphodiesterase III inhibitors (↑). In light of potentially serious adverse events, caution is required with regard to catecholamine administration; especially in clinically “marginally” stable ICS patients (Figure), catecholamine administration is not generally required.

Not convincing yet: mechanical cardiovascular support

Until a few years ago, the intra-aortic balloon pump (IABP) was part of the standard treatment armamentarium, with a class I recommendation in the European and US guidelines and an implantation frequency in Germany of about 10 000/year; however, its effectiveness was not proven in RCTs. The small randomized IABP-SHOCK study on 40 ICS patients was the first to provide evidence conflicting with this “standard” treatment strategy as it found that the use of IABP did neither result in an improvement of hemodynamics (no significant increase in CI) nor of MODS severity measured using the APACHE II score (15, 16). In the subsequent IABP-SHOCK II study on 600 ICS patients treated with pPCI (95.8%) in 37 centers in Germany, the use of IABP did neither reduce mortality after 30 days (39.7% [IABP] versus 41.3%; relative risk [RR]: 0.96 [0.79; 1.17], p = 0.69) (10) nor after 12 months, nor after six years. A subsequent Cochrane analysis (17)—seven studies with 790 ICS patients—did not show a mortality-reducing effect of IABP either.

Based on these results, an IABP should not be implanted in patients with ICS due to pump failure and PCI as the primary treatment. (Box 2, ↓). IABP may be used in patients who develop mechanical complications after myocardial infarction (↔).

Temporary mechanical circulatory support (TMCS) devices include percutaneous (left) ventricular assist devices (p[L]VAD), such as Impella pumps and TandemHeart, as well as venoarterial extracorporeal membrane oxygenation (VA-ECMO)/extracorporeal life support (ECLS). These TMCS devices achieve a cardiac output of up to 5 L/min and 7 L/min (pLVAD and ECLS, respectively). Despite the considerable increase in cardiac output, no reduction in mortality has yet been demonstrated for TMCS in registries and small meta-analyses, neither for pLVADs (18, 19) nor for ECLS (20. 21). Until results from meanwhile initiated RCTs are available, it is recommended that TMCS “may” be used under strict precautions (Box 2, ↔).

Mechanical MI complications—a task for the cardiac care team

ICS patients with shock due to mechanical MI complications (0.2–6.9%) (22) shall be treated by a cardiac care team consisting of a cardiac surgeon and a cardiologist with experience in intensive care medicine (↑↑). In patients with post-infarction ventricular septal defect and ICS, interventional (↑) (23) closure is a treatment option besides surgical repair (↑). In case of rupture of a free ventricular wall, immediate surgical repair shall be attempted (↑↑). In patients developing hemodynamically relevant acute mitral regurgitation, immediate surgical repair shall be performed (↑↑).

Management of organ dysfunction

The IABP-SHOCK study showed that in ICS patients a developing multiple organ dysfunction syndrome (MODS)—measured by APACHE II scoring—is a stronger predictor of mortality than the cardiac index (CI) (15). The guideline describes the treatment options for supporting the impaired function of the shock organs (lungs, kidneys, liver, gastrointestinal tract, endocrine system, nervous system, and brain).

Respiratory failure

In ICS patients requiring mechanical ventilation, invasive ventilation—arterial oxygen saturation (SaO₂) 94–98% (↑)—should be given preference over non-invasive ventilation (Box 2, ↑) (24). The reasons behind this recommendation include continuously stable ventilation conditions, relief from the breathing effort with large cardiac output portion and prevention of psychomotor agitation and exhaustion of ICS patients.

The benefits of lung-protective ventilation (maximum plateau pressure ≤ 30 mbar, tidal volume target (V_T) of 6–8 mL/kg predicted body weight [see legend in Box 2]; positive end-expiratory pressure [PEEP] of 5–15 mbar) should be harnessed as early as possible (Box 2, ↑), since it has increasingly shown beneficial, albeit weaker effects in non-ARDS patients, too (24, 25). Semi-recumbent position proposed for the prevention or treatment of impaired pulmonary function should, however, not exceed 30 degrees in ICS patients because of the risk of hypotension. Continuous lateral rotation (“kinetic therapy”) showed favorable results in ventilated patients with cardiogenic shock: lower rate of ventilation-induced pneumonia and pressure ulcers and reduction in one-year mortality (26).

For analgesia, opioid-based treatment should primarily be used (↑) and benzodiazepines should be used for long-term sedation (>72 h; mandate holder of the Austrian Society for Internal and General Intensive Care and Emergency Medicine (ÖGIAIN, Österreichische Gesellschaft für Internistische und Allgemeine Intensivmedizin und Notfallmedizin): from day 7) (↑), while the mandate holders of the German Society of Anesthesiology and Intensive Care Medicine (DGAI, Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin) recommend propofol as treatment of first choice for long-term sedation, provided adequate experience. Weaning (27), which is critical especially in ICS patients, should start immediately after hemodynamic and respiratory stabilization (↑) according to a weaning protocol (↑).

Acute kidney failure

Acute kidney failure (28) should be treated with one of the two renal replacement therapies—continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD)—(↑), whereas the mandate holders of ÖGIAIN clearly recommend the use of continuous renal replacement therapy in hemodynamically unstable ICS patients.

Cardiovascular autonomic dysfunction

ICU patients with shock, MODS and sepsis—including ICS patients—are characterized by an inadequately high heart rate (≥ 90–95/min) and restricted heart rate variability. A study reported significant heart rate reduction using esmolol, an intravenous beta blocker, in patients with septic shock, and two further studies with the pacemaker channel blocker (If blocker) ivabradin, both in MODS patients and in ICS patient (29). However, no treatment recommendation for ICS patients can be derived from these findings.

Hypoxic hepatitis, gastrointestinal dysfunction, endocrine dysfunction (CIRCI), CIP and CIM

See eBox 2 for details.

eBox 2

Supplementary material: Management of organ dysfunction

General ICU and prophylactic measures

The two key nutritional recommendations are (Box 2): no nutritional support in patients with uncontrolled shock (↓) and no glutamine supplementation (↓). Blood sugar levels should be <150 mg/100 mL/<8.3 mmol/L (Box 2, ↑). The restrictive transfusion strategy in patients with anemia is described in Box 2. In ICS patients in the shock state, unfractionated heparin (10 000–15 000 I.E./24 h) should be used for thromboembolism prophylaxis and administered intravenously (↑↑) , given the unreliability of subcutaneous (↓) absorption (Box 2). The stress ulcer prophylaxis recommendation for ICS patients remains at “shall” level (Box 2, ↑↑), despite the skepticism about general stress ulcer prophylaxis for all ICU patients. Supplementary information about ICU and prophylactic measures in general is provided in eBox 3.

eBox 3

Supplementary material: General ICU and prophylactic measures

Recommendations for aftercare/rehabilitation

A rehabilitation program (30) shall be offered to all ICS patients (Box 2, ↑↑), with subsequent enrollment in a heart failure/post-ICU outpatient clinic and 6-monthly to annual follow-up examinations by one of the treating physicians.

The quality of life of ICS patients who underwent acute revascularization was rated for the majority of these patients as moderate to good, even after 6 years—this is comparable to the quality of life in the general population (31).

Discussion

Urgent need for research

Many recommendation of this clinical practice (S3) guideline are based on expert opinions, because higher grade evidence was not available.

Temporary percutaneous support devices

In no other group of myocardial infarction patients, the timing of prehospital treatment is as critical as in the group of ICS patients (1). Today, earliest possible successful revascularization of the occluded coronary vessel is achieved in more than 90% of ICS patients; thus, this component of treatment with implantation of a DES and limitation of revascularization to the “culprit lesion“ (6, 7) appears to be exhausted for now. Consequently, efforts to reduce ICS mortality currently focus “only” on timely improvement of impaired cardiac output and optimization of intensive care treatment; based on the current body of evidence, little is to be expected of new inotropic and vasoactive substances. Thus, the key question is whether TMCS devices, such as Impella pumps or VA-ECMOs, with pumping capacities of up to 7 L/min are capable of increasing blood flow to vital organs timely enough to prevent the development of MODS. The small studies and meta-analyses available to date, which were not designed to evaluate mortality, are, however, not promising. This makes it all the more important to wait for the results of the initiated RCTs which are designed to assess mortality reduction. As expected—but not based on evidence—the use of VA-ECMO in Germany has increased from 500 in 2012 to 3000 in 2014 (32).

Lung-protective ventilation

Up to 80% (7, 33) of ICS patients require mechanical ventilation. The expert opinion-supported recommendation of lung-protective ventilation (Box 2, ↑) is based on its favorable effect—with good evidence for mortality reduction—among ARDS and sepsis patients as well as ICU patients without ARDS in need of ventilation; however, the evidence for the latter patient group is weaker (24, 25, 34). The effectiveness of lung-protective ventilation has yet to be proven in RCTs.

Weaknesses and limitations of the guideline

Only 6 of 95 recommendations are based high-quality evidence from studies. It is encouraging to note that since the first publication of this guideline two large studies—the IABP-SHOCK II study (10) and the CULPRIT-SHOCK study (7)—have provided conclusive evidence in support of two important treatments for ICS patients: the proof of lack of benefit of IABP in patients with ICS due to pump failure; and the recommendation to primarily only treat the “culprit lesion” using pPCI in patients with multivessel coronary artery disease (Box 2).

Acknowledgement

Our sincere thanks go to all mandate holders involved in the development of this guideline and their medical societies as well as to Prof. Dr. med. Ina Kopp (AWMF) for methodological consulting and her support in the development of this guideline.

Conflict of interest

Prof. Werdan received fees for his function as Chairman of the Heart Failure Think Tank of Novartis. He is a research associate of a preclinical, BMBF-sponsored research project on the development of a cardiac support system.

Prof. Buerke received fees for his participation in the scientific advisory board of Boehringer Ingelheim. He maintains personal relationships related to the subject and received lecture fees from Orion, Abiomed, Draeger, AstraZeneca, Daichi, Novartis, Bayer, Boehringer Ingelheim, and Pfizer.

Univ.-Doz. Dr. Geppert received lecture fees from Maquet and Abiomed.

Dr. Ruß received authorship/co-authorship fees for a publication related to the topic from Elsevier.

Prof. Thiele and Prof. Zwissler declare no conflict of interest.

Manuscript received on 26 August 2020; revised version accepted on
27 October 2020

Clinical guidelines are not peer-reviewed in Deutsches Ärzteblatt, as well as in many other journals, because clinical (S3) guidelines are texts which have already been repeatedly evaluated, discussed and broadly consented by experts (peers).

Translated from the original German by Ralf Thoene, MD.

Corresponding author
Prof. Dr. med. Karl Werdan
Universitätsklinik und Poliklinik für Innere Medizin III
Universitätsklinikum Halle (Saale) der
Martin-Luther-Universität Halle-Wittenberg
Ernst-Grube-Straße 40
06120 Halle (Saale), Germany

Cite this as:
Werdan K, Buerke M, Geppert A, Thiele H,
Zwissler B, Ruß M, on behalf of the guideline group:
Clinical practice guideline: Infarction-related cardiogenic shock—
diagnosis, monitoring and therapy. A German-Austrian S3 guideline. Dtsch Arztebl Int 2021; 118: 88–95.
DOI: 10.3238/arztebl.m2021.0012

►Supplementary material

eFigure and eBoxes:
www.aerzteblatt-international.de/m2021.0012

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