**5. Additional benefit of interventional and surgical treatment options after cardiac arrest**

Beside revascularization therapy of all critical coronary artery stenoses or occlusion, further interventional and surgical therapeutic option have become available for patients after cardiac arrest. These advanced therapies reveal two main therapeutic goals:


#### **5.1. Targeted temperature management**

Cerebral and myocardial protection can be achieved by myocardial reperfusion and targeted temperature management (TTM). The TTM may attenuate various signaling pathways leading to cell death by revealing anti-apoptotic and anti-inflammatory effects [37]. Smaller cohort studies demonstrated that invasive treatment after cardiac arrest including TTM and coronary angiography with reperfusion therapy by PCI can reduce myocardial infarction size [38]. In addition, it could have been shown that TTM alone without reperfusion reveals adverse effects because the extent of myocardial infarction was comparable independently of treatment with TTM. TTM plus reperfusion resulted in the best recovery of cardiac function with the lowest myocardial infarction size [39]. This experimental evidence confirms the disadvantage of delayed coronary revascularization and limits the benefit of sole TTM after cardiac arrest.

In contrast, Mooney et al. demonstrated that delayed initiation of TTM in patients with outof-hospital cardiac arrest was associated with a 20% increase of mortality. However, the rate of invasive coronary angiography was 72% with a PCI rate of 40% only [40]. It is well documented from several cohort studies that a combined PCI plus TTM improves survival and neurological outcome in patients with cardiac arrest and persistent coma [6].

TTM consists of controlled intravenous infusion systems (e.g., Bogard XP® Temperature Management System, ZOLL Medical Corporation, Asahi Kasei Corp, Japan) in combination with cool packs. TTM may not be initiated out-of-hospital only in order to achieve potentially best possible prognostic and neurological outcome [41, 42]. The target temperature is aimed between 32 and 36°C, whereas even lower target temperatures were shown to have no additional prognostic or neurological benefit [37, 43, 44]. Regardless of the documented primary arrhythmia, TTM is always recommended for at least 24 h duration in patients with persistent coma [37].

### **5.2. Cardiac assist devices for extracorporeal life support (ECLS)**

Despite successful CPR and consecutive ROSC, there are still 30–40% of patients revealing hemodynamic instability and prolonged cardiogenic shock. In this situation, cardiac ventricular assist devices (VAD) may achieve stabilization or normalization of circulation. Cardiac index may be normalized, myocardial oxygen consumption and perfusion of secondary organs including brain and kidneys will be improved [25]. The presence of the acute emergency, in which post-cardiac arrest patients with prolonged cardiogenic shock are situated, favors minimally invasive or percutaneous VAD. Depending on the device type, each individual VAD increases cardiac output either with left (LV) or right ventricular (RV) mechanical support.

Currently available VAD systems for percutaneous access include the following:


disease [28]. In cardiogenic shock, early coronary revascularization was associated with improved long-term survival compared to drug therapy [29, 30]. However, early PCI in cardiogenic shock or in patients with aborted cardiac arrest is applied in 50–70% of patients only [31], although most of these patients reveal coronary multivessel disease being associated with significantly higher mortality compared to coronary one-vessel disease [32, 33]. Depending on hemodynamic instability and complexity of multivessel coronary disease according to the SYNTAX level, either a PCI or CABG may be the recommended treatment option in cardiogenic shock (Grade I, Level B evidence) [22]. The "CULPRIT-SHOCK" study recently demonstrated a prognostic benefit for a staged PCI of the "culprit lesion" at first in patients with cardiogenic shock and coronary multivessel disease compared to "ad-hoc" multivessel PCI directly at presentation. This prognostic benefit was attributed to fewer amount of contrast use and consecutive fewer rates of renal failure, when the culprit lesion was treated at first presentation and all other critical coronary artery stenoses underwent PCI some days later after hemodynamic recovery [34, 35]. Comparative studies evaluating CABG versus PCI in patients suffering from cardiac arrest or cardiogenic shock are lacking [36]. However, the advantages for immediate PCI consist of a better accessibility of cardiac catheterization laboratories compared to cardiac surgery units, including rapid feasibility of PCI with minimally invasive access. This has led to an almost lower prevalence

of emergency CABG in post-cardiac arrest patients of less than 5% [31].

diac arrest. These advanced therapies reveal two main therapeutic goals:

**2.** restoration of hemodynamic stability in cardiogenic shock.

**options after cardiac arrest**

50 Myocardial Infarction

during cardiac arrest; and

**5.1. Targeted temperature management**

**5. Additional benefit of interventional and surgical treatment** 

Beside revascularization therapy of all critical coronary artery stenoses or occlusion, further interventional and surgical therapeutic option have become available for patients after car-

**1.** cerebral neuroprotection and myocyte protection after episodes of ongoing hypoxemia

Cerebral and myocardial protection can be achieved by myocardial reperfusion and targeted temperature management (TTM). The TTM may attenuate various signaling pathways leading to cell death by revealing anti-apoptotic and anti-inflammatory effects [37]. Smaller cohort studies demonstrated that invasive treatment after cardiac arrest including TTM and coronary angiography with reperfusion therapy by PCI can reduce myocardial infarction size [38]. In addition, it could have been shown that TTM alone without reperfusion reveals adverse effects because the extent of myocardial infarction was comparable independently of treatment with TTM. TTM plus reperfusion resulted in the best recovery

	- Vena cava inferior (VCI) to pulmonary artery (PA): non-pulsatile axial Impella RP® (Abiomed Europe, Aachen, Germany; 3a),

○ RA to PA: TandemHeart® RVAD KIT with 2 cannulas (CardiacAssist, Inc., Pittsburgh, USA; Abb. 3c),

mechanical circulatory support during high-risk PCI [45]. Specifically, for TandemHeart® a transseptal puncture is needed during implantation with trans-septal sheath diameters ranging from diameters of 15–16 French. However, transseptal puncture is rarely performed on a regular basis and only by a smaller number of interventional cardiologists. This makes the application of TandemHeart® limited for a widespread use in clinical practice especially in emergency situations of patients with cardiac arrest and cardiogenic shock [45]. In addition, dislocation of the LA cannula into pulmonary veins or left atrial appendage during relocation maneuvers or during intensive care transports are potential

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Data on VA-ECMO in cardiac arrest or cardiogenic shock patients are based on many smaller cohort studies published in 2006 in cardiac surgery settings. Here, a meta-analysis demonstrated a survival rate of 50% [11]. The abovementioned ELSO registry reports about a survival rate of 27% post cardiac arrest [58]. In 2013, Takayama et al. reported on 50% survival rate for patients with cardiac arrest or cardiogenic shock after implantation of VA-ECMO. Half of these patients needed a permanent surgical VAD at follow-up. Also in this cohort, prolonged duration of CPR was associated with increased mortality despite the

Modern medical technologies have been developed in recent years, which make VAD applicable for percutaneous access in critical and unstable situations. It should be emphasized that mechanical support after cardiac arrest and consecutive cardiogenic shock is not limited to the left heart only. In principle, and always depending on the underlying individual clinical condition, RV support can also be performed by another RVAD at the same time. The femoral access route is usually preferred for implantation of the LVAD. For RVAD, both the femoral and the transjugular access routes are possible. Direct and central unload of the congested heart is always recommended, but depends on technical applicability in each individual clinical situation. In contrast, insertion of cannulas at peripheral femoral vessels will always provide indirect unload for the congested heart because extracorporeal blood re-circulated to peripheral vessels. As a result, contrary effects were recently demonstrated for peripheral assist devices (**Figure 3d**, **e**, **left**; [45]). The increasing amount of peripherally recirculated blood volume automatically raises wall tension in the peripheral arterial system. In turn, this leads to considerable increase of afterload, which may be harmful for the congested, severely impaired LV after cardiac arrest. Therefore, the implantation of peripheral VA-ECMO systems additionally requires the placement of LA transseptal cannulas, which leads to "central unload" at the level of left atrium and the left ventricle (**Figure 3e**, **middle**; [60]). "Central unload" within the LA was more effective compared to RA because LV filling can be reduced from the left atrial level, while at the same time systemic perfusion is maintained more effectively. In contrast, unloading at the right atrium was associated with a significant increase of LV wall tension and LV unloading becomes even less effective [60]. Direct unloading within LA or LV (e.g., in the TandemHeart®) therefore represents the most effective way for mechanical circulatory support by VAD [49]. Additional unloading is usually achieved by an additionally inserted cannula, which is positioned in the LA after transseptal puncture, while it can be integrated into the peripheral VA-ECMO circuit via

complications.

use of VA-ECMO [59].

Y-connectors (**Figure 3e**, **right**).

	- V. femoralis to *A. femoralis* (VA): CARDIOHELP system (MAQUET GETINGE GROUP, Rastatt, Germany) or LIFEBRIDGE® 2.0 Systemccar- dio (ZOLL Medical Deutschland GmbH; Abb. 3e).

Unfortunately, scientific evidence about clinical benefits of the various VAD in patients with cardiogenic shock, aborted cardiac arrest or persistent ventricular tachycardia or fibrillation ("ventricular storming") is still insufficient and not sound [1, 22, 25, 45]. Recommendation for mechanical circulatory support in cardiogenic shock caused by myocardial infarction is based purely on expert opinion (grade of evidence IIb, level of evidence C; [22]). VAD were shown to stabilize patients suffering from hemodynamically unstable ventricular tachycardia. In contrast, VAD may also complicate the therapeutic management in emergency situations because clinical application of VAD demands more members of stuff. Additionally, mechanical assist devices were also shown to alleviate the incidence of ventricular tachycardia by the VAD itself [1].

Combining PCI with IABP was not associated with a significant reduction of infarct size [46]. In particular, IABP was not associated with a reduction of 30-day or 1-year mortality in patients surviving cardiogenic shock due to myocardial infarction [47, 48]. Therefore, the use of IABP is recommended only in case of mechanical complications in order to bridge the patient for cardiac surgery [22, 49].

More and more meta-analyses have recently been published, which conclusively analyzed smaller studies evaluating the benefit of VAD in patients after cardiac arrest or with cardiogenic shock. Ouweneel et al. [50] demonstrated that, after cardiac arrest, the use of VA-ECMO significantly improves both survival and neurological outcome at 30 days compared to patients treated with IABP or Impella® (n = 219). Even after cardiogenic shock, patients treated with VA-ECMO showed a higher survival rate at 30 days compared to patients with IABP or Impella® (n = 151) [50]. In contrast, the direct comparison between IABP and Impella® showed differences of survival in patients with acute myocardial infarction and cardiogenic shock [51, 52]. However, it could have been shown that the earliest possible use of Impella® reveals an independent prognostic factor for improved survival after cardiogenic shock [53–55]. Vase et al. described in a small case series (n = 8) that the use of the Impella® after cardiac arrest and mean CPR duration with "low-flow-time" of about 50 min is associated with a comparable survival rate to cardiogenic shock [56, 57].

Data for VAD between LA and aorta, such as TandemHeart®, are not available for patients surviving cardiac arrest or cardiogenic shock. Therefore, no evidence-based recommendation can be given. However, TandemHeart® was shown as a safe and feasible mechanical circulatory support during high-risk PCI [45]. Specifically, for TandemHeart® a transseptal puncture is needed during implantation with trans-septal sheath diameters ranging from diameters of 15–16 French. However, transseptal puncture is rarely performed on a regular basis and only by a smaller number of interventional cardiologists. This makes the application of TandemHeart® limited for a widespread use in clinical practice especially in emergency situations of patients with cardiac arrest and cardiogenic shock [45]. In addition, dislocation of the LA cannula into pulmonary veins or left atrial appendage during relocation maneuvers or during intensive care transports are potential complications.

○ RA to PA: TandemHeart® RVAD KIT with 2 cannulas (CardiacAssist, Inc., Pittsburgh,

○ RA to PA: TandemHeart® RVAD PROTEKDuo® double lumen cannula (CardiacAssist,

○ V. femoralis to *A. femoralis* (VA): CARDIOHELP system (MAQUET GETINGE GROUP, Rastatt, Germany) or LIFEBRIDGE® 2.0 Systemccar- dio (ZOLL Medical Deutschland

Unfortunately, scientific evidence about clinical benefits of the various VAD in patients with cardiogenic shock, aborted cardiac arrest or persistent ventricular tachycardia or fibrillation ("ventricular storming") is still insufficient and not sound [1, 22, 25, 45]. Recommendation for mechanical circulatory support in cardiogenic shock caused by myocardial infarction is based purely on expert opinion (grade of evidence IIb, level of evidence C; [22]). VAD were shown to stabilize patients suffering from hemodynamically unstable ventricular tachycardia. In contrast, VAD may also complicate the therapeutic management in emergency situations because clinical application of VAD demands more members of stuff. Additionally, mechanical assist devices were also shown to alleviate the incidence of ventricular tachycardia by the

Combining PCI with IABP was not associated with a significant reduction of infarct size [46]. In particular, IABP was not associated with a reduction of 30-day or 1-year mortality in patients surviving cardiogenic shock due to myocardial infarction [47, 48]. Therefore, the use of IABP is recommended only in case of mechanical complications in order to bridge the

More and more meta-analyses have recently been published, which conclusively analyzed smaller studies evaluating the benefit of VAD in patients after cardiac arrest or with cardiogenic shock. Ouweneel et al. [50] demonstrated that, after cardiac arrest, the use of VA-ECMO significantly improves both survival and neurological outcome at 30 days compared to patients treated with IABP or Impella® (n = 219). Even after cardiogenic shock, patients treated with VA-ECMO showed a higher survival rate at 30 days compared to patients with IABP or Impella® (n = 151) [50]. In contrast, the direct comparison between IABP and Impella® showed differences of survival in patients with acute myocardial infarction and cardiogenic shock [51, 52]. However, it could have been shown that the earliest possible use of Impella® reveals an independent prognostic factor for improved survival after cardiogenic shock [53–55]. Vase et al. described in a small case series (n = 8) that the use of the Impella® after cardiac arrest and mean CPR duration with "low-flow-time" of about 50 min is associated with a comparable survival rate to

Data for VAD between LA and aorta, such as TandemHeart®, are not available for patients surviving cardiac arrest or cardiogenic shock. Therefore, no evidence-based recommendation can be given. However, TandemHeart® was shown as a safe and feasible

• Extracorporeal membrane oxygenation (VA [veno-arterial]-ECMO) – peripheral:

USA; Abb. 3c),

52 Myocardial Infarction

GmbH; Abb. 3e).

VAD itself [1].

patient for cardiac surgery [22, 49].

cardiogenic shock [56, 57].

Inc., Pittsburgh, USA; Abb. 3d);

Data on VA-ECMO in cardiac arrest or cardiogenic shock patients are based on many smaller cohort studies published in 2006 in cardiac surgery settings. Here, a meta-analysis demonstrated a survival rate of 50% [11]. The abovementioned ELSO registry reports about a survival rate of 27% post cardiac arrest [58]. In 2013, Takayama et al. reported on 50% survival rate for patients with cardiac arrest or cardiogenic shock after implantation of VA-ECMO. Half of these patients needed a permanent surgical VAD at follow-up. Also in this cohort, prolonged duration of CPR was associated with increased mortality despite the use of VA-ECMO [59].

Modern medical technologies have been developed in recent years, which make VAD applicable for percutaneous access in critical and unstable situations. It should be emphasized that mechanical support after cardiac arrest and consecutive cardiogenic shock is not limited to the left heart only. In principle, and always depending on the underlying individual clinical condition, RV support can also be performed by another RVAD at the same time. The femoral access route is usually preferred for implantation of the LVAD. For RVAD, both the femoral and the transjugular access routes are possible. Direct and central unload of the congested heart is always recommended, but depends on technical applicability in each individual clinical situation. In contrast, insertion of cannulas at peripheral femoral vessels will always provide indirect unload for the congested heart because extracorporeal blood re-circulated to peripheral vessels. As a result, contrary effects were recently demonstrated for peripheral assist devices (**Figure 3d**, **e**, **left**; [45]). The increasing amount of peripherally recirculated blood volume automatically raises wall tension in the peripheral arterial system. In turn, this leads to considerable increase of afterload, which may be harmful for the congested, severely impaired LV after cardiac arrest. Therefore, the implantation of peripheral VA-ECMO systems additionally requires the placement of LA transseptal cannulas, which leads to "central unload" at the level of left atrium and the left ventricle (**Figure 3e**, **middle**; [60]). "Central unload" within the LA was more effective compared to RA because LV filling can be reduced from the left atrial level, while at the same time systemic perfusion is maintained more effectively. In contrast, unloading at the right atrium was associated with a significant increase of LV wall tension and LV unloading becomes even less effective [60]. Direct unloading within LA or LV (e.g., in the TandemHeart®) therefore represents the most effective way for mechanical circulatory support by VAD [49]. Additional unloading is usually achieved by an additionally inserted cannula, which is positioned in the LA after transseptal puncture, while it can be integrated into the peripheral VA-ECMO circuit via Y-connectors (**Figure 3e**, **right**).

**6. Conclusions for daily clinical practice**

infarction (i.e., NSTEMI or STEMI).

further evaluation.

plication is still a long way off.

for providing figures of cardiac assist devices.

\*, Philipp Kuche1

Krozingen, Bad Krozingen, Germany

\*Address all correspondence to: michael.behnes@umm.de

Medicine Mannheim, University of Heidelberg, Germany

**Acknowledgements**

**Author details**

Michael Behnes1

include important prognostic cofactors.

genic shock and coronary multivessel disease.

and RVAD, as well as peripheral ECMO systems.

• The grade of recommendation for early invasive coronary angiography with immediate PCI in post cardiac arrest patients is still based only on non-randomized cohort studies or expert opinions, depending on the pretest probability and on the type of myocardial

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55

• Decision-making for either an interventional-invasive or surgical approach should always

• A staged PCI including emergency PCI of the coronary "culprit lesion" only in the emergency setting was shown to be safer and associated with improved survival compared to "ad-hoc" emergency PCI of all critical coronary stenoses in patients suffering from cardio-

• The benefit of emergency CABG compared to emergency PCI after cardiac arrest requires

• Advanced interventional and operative therapies include targeted temperature management in combination with coronary revascularization and extracorporeal mechanical cardiac support systems, which include intra-aortic counter pulsation (IABP), central LVAD

• Randomized prospective studies comparing the use of VAD in post cardiac arrest patients is lacking. Use of VAD is still limited to specialized centers and a widespread routine ap-

We thank the companies Abiomed Europe (Aachen, Germany), CardiacAssist, Inc. (Pittsburgh, USA), AVIDAL Group (Berlin, Germany) und MAQUET GETINGE GROUP (Rastatt, Germany)

and Kambis Mashayekhi2

, Ibrahim Akin1

2 Division of Cardiology and Angiology II, University Heart Center Freiburg Bad

1 First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of

**Figure 3.** Graphical illustration of different ventricular assist devices (VAD) for extracorporeal life support (ECLS): Central left ventricular assist device (LVAD): (A) LV (left ventricular) to aorta: non-pulsatile axial Impella® 2.5/5.0 (Abiomed Europe, Aachen, Germany). (B) LA (left atrial) to aorta: Tandem Heart® VLAD KIT (Cardiac Assist, Inc., Pittsburgh, USA). Central right ventricular assist device (RVAD): (A) Vena cava inferior (VCI) to PA: nonpulsatile axial Impella RP® (Abiomed Europe, Aachen, Germany). (C) RA (right atrial) to PA (pulmonary artery): Tandem Heart® RVAD KIT with 2 cannulas (Cardiac Assist, Inc., Pittsburgh, USA). (D) RA to PA: Tandem Heart® RVAD PROTEKDuo® dual lumen cannula (Cardiac-Assist, Inc., Pittsburgh, USA). Peripheral ECLS: (E) extracorporeal membrane oxygenation (VA [veno-arterial] - ECMO): peripheral femoral vein to femoral artery (VA) - ECLS: CARDIOHELP System (MAQUET GETINGE GROUP, Rastatt, Germany). (F) Placement of LA cannula (trans-septal) in addition to the VA-ECMO: improved "unload" of the congested heart, the additional cannula can be integrated into the VA-ECMO circuit via Y-connectors. Unfavorable effects on the cardiovascular system due to peripherally placed assist devices can be reduced.
