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Anaesthesia and cardiac contractility modulation

Huschak, G.*; Schmidt-Runke, H.*; Rüffert, H.*

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European Journal of Anaesthesiology: October 2007 - Volume 24 - Issue 10 - p 819-825
doi: 10.1017/S0265021507000853
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Despite the development of pharmacological strategies to improve cardiac function, including angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, β-adrenergic blockers and aldosterone receptor antagonists, there are a number of patients with chronic heart failure who require further non-pharmacologic therapy [1]. Medical device therapy for heart failure includes implantable cardioverter defibrillators (ICDs) and cardiac resynchronization systems [2]. The development of therapies that improve heart function, relieve symptoms, reduce hospitalization and improve survival remains a challenge for the future.

Future demographic changes will lead to a growing number of patients with chronic heart failure. The perioperative management of these patients aims at preventing myocardial ischaemia and deterioration of the pre-existing impairment of cardiac function [3]. A phase III trial is currently evaluating a promising new electric therapy in patients with severe chronic heart failure (cardiac contractility modulation, CCM).1 As patient recruitment progresses, a number of the patients with CCM will require non-cardiac surgery. No literature on the anaesthesiological management of patients with implanted CCM devices is currently available. This review intends to close this gap. The case reported in the Appendix section describes our first experiences with CCM during emergency surgery.

Rationale of cardiac contractility modulation

Poor contractility in patients with chronic congestive heart failure is believed to result from defects in Ca2+ handling. Cardiac myocytes in the chronically failing heart show a pattern of decreased intracellular Ca2+-mediating proteins [4-7], while proteins mediating extracellular Ca2+ transport are increased [8-11]. These changes are considered to fit the pattern of ‘reversion to fetal phenotype’ of excitation-contraction coupling, with a poorly developed sarcoplasmic reticulum and a shift from an intracellular to an extracellular Ca2+ cycle [12]. The result of these changes in the cardiac myocyte is a decreased amount of Ca2+ delivered to the myofilaments during each beat.

Medical strategies to improve inotropy consist of increasing intracellular Ca2+ concentration or Ca2+ sensitization of myofilaments. Repeated or prolonged treatment with inotropic agents increases mortality and is not recommended in chronic heart failure [2]. Nevertheless, intravenous (i.v.) inotropic support is frequently used in patients with an unstable circulation [13]. CCM is a novel, non-pharmacological approach to improve Ca2+ action on cardiac myofilaments through the use of electric current.

Inotropic effects of cardiac contractility modulation using electric currents

The purpose of CCM is to modulate the impaired Ca2+ cycle in patients with chronic heart failure. Electric currents are used to affect the magnitude and duration of the action potential of cardiac myocytes [12]. As shown in vitro, CCM signals timed before peak myocardial tension exert an inotropic effect that is maintained during the entire cardiac cycle [14]. Intracellular recordings show that CCM signals induce an increase in action potential duration that correlate with CCM amplitude. The increased duration of the action potential allows an increased peak tension induced by an influx of Ca2+ [15,16].

The CCM system records an intra-cardiac electrocardiogram (ECG). Shortly after sensing the intra-cardiac ECG action, a biphasic impulse (20 ms; 7-10 V) is applied. In contrast to pacemakers, CCM does not initiate a cardiac contraction. Non-excitatory electric currents are delivered during the action potential plateau as shown in Figure 1. It is important that the signal be applied during the absolute refractory period, since malignant arrhythmias might otherwise be induced. As intracellular currents cannot be delivered in the intact heart muscle cell, myocardial field stimulation via two electrodes is used [12]. In the setting of chronic heart failure, CCM positively influences impaired calcium homoeostasis resulting in improved systolic function [17]. The improvement in systolic function followed by an increase in cardiac output can be seen as increased systolic pressure in the arterial pressure trace (Fig. 2) as well as in transoesophageal echocardiography [18].

Figure 1.
Figure 1.:
(a) Surface ECG illustrating cardiac contractility modulation (CCM) using ‘pacemaker modus’ (monitor's filter algorithm disabled). CCM impulses appear as ECG artifacts. (b) The lower part shows the action potential of a cardiac myocyte corresponding to the surface ECG shown in the upper part. The CCM biphasic impulse (Symbol) is applied 20msec after sensing a regular intra-cardiac ECG action during the absolute refractory period. The grey area represents the total refractory period (Symbol).
Figure 2.
Figure 2.:
Schematic arterial pressure recording without (Symbol) and with (Symbol) cardiac contractility modulation (CCM). Systolic contractility improvement results in an increased area under the curve (AUC) representing an increased cardiac output.

Practical use of cardiac contractility modulation

The CCM system currently used (OPTIMIZER™ III, Impulse Dynamics, Orangeburg, NY, USA) consists of a subcutaneously implanted pulse generator connected to three electrodes. The electrodes are introduced via the vena cava. The first electrode is placed in the right atrium and senses the intra-cardiac ECG. Two further electrodes are located in the right ventricular septum (Fig. 3). The leads are commercially available and already in use for pacemakers and ICDs.

Figure 3.
Figure 3.:
Chest radiograph in the antero-posterior view showing the positions of the three leads and the CCM pulse generator.

The system monitors electrical activity in both the right atrium and the interventricular septum, recognizing local activation and automatically delivering CCM impulses. The CCM signal is similar to a pacing signal in that it is characterized by delay, duration and amplitude. In contrast to a pacing signal, the CCM signal is multiphasic with a wider pulse duration (two biphasic square-wave pulses with a total duration of 20 ms) and a higher amplitude (7-10 V). An implemented safety algorithm ensures non-excitatory stimulation within a precise time window of local refractoriness (30-60 ms after detection of local electric myocardial activation) [19]. The safety algorithm inhibits CCM stimulation when irregular activation (e.g. ectopic beats) is detected and restarts after three consecutive normal beats.

Programming and interrogation is conducted telemetrically. The battery integrated into the generator is charged regularly by induction using a waistcoat (up to weekly rechargings). Because of heat generation during charging, the body surface temperature above the generator is monitored. CCM requires significantly more energy than ICDs/pacemakers. Currently, implanted CCM devices are programmed to stimulate 7 h day−1 during the daytime (e.g. 9.00a.m. to 4.00p.m.) to improve quality of life. At present, it is not clear if the interruption is necessary to preserve the effect of CCM. Although there are no data on the i.v. use of sympathomimetics, one might assume that less inotropic or vasopressor support would be required for elective surgery during the CCM stimulation period.

Potential risks associated with cardiac contractility modulation

Potential risks associated with CCM are still being discussed. The ongoing phase III trial ‘Evaluation of the Safety and Effectiveness of the OPTIMIZER System in Subjects With Heart Failure: FIX-HF-5’ will yield data concerning the safety of CCM.1

As with other electrical cardiac devices (e.g. pacemakers, ICDs), periprocedural complications include pneumothorax, asystole, complete heart block, haemopericardium, bleeding, diaphragm/phrenic nerve stimulation and pocket infection of the implantation site. Postimplantation complications include induction of arrhythmias, malfunctioning of the device, lead dislocation/breakage, improper sensing, infection, battery depletion/malfunction, etc.

The risk of inducing arrhythmias requires special attention. The safety algorithm described above is aimed at preventing such complications. Analysis of serial Holter ECG recordings of 13 patients during the pilot study revealed no increase in the frequency of premature ventricular or supraventricular ECG complexes: the authors report a decrease in non-sustained ventricular tachycardias. No significant changes in the duration of the QRS or QT intervals were observed [19]. However, these findings need to be confirmed by further studies. A recent randomized, double-blind, pilot study investigated 49 New York Heart Association (NYHA) III or IV patients with normal QRS complexes and an implanted CCM device (25 with active CCM, 24 with deactivated CCM). Twenty-four hour Holter recordings showed no significant changes between groups. Interestingly, study endpoints (6-min walk, anaerobic threshold, NYHA class, Minnesota Living with Heart Failure Questionnaire score, left ventricular ejection fraction) showed an improvement in both groups but were neither clinically relevant nor statistically significant [20].

Anaesthetics are known to affect the absolute refractory period of the heart. They mainly increase QTC-time in patients without congenital long QT syndrome [21,22]. No data are available regarding the interactions of anaesthetics and CCM devices. The non-excitatory impulses are delivered during a time window 30-60 ms after the detection of local electric myocardial activation. From a theoretical point of view, an interaction between anaesthetics and CCM is not anticipated. The overall action potential duration of cardiac myocytes is approximately 200-400 ms depending on heart rate and localization of the cell. As illustrated in Figure 1, the wide safety margin from the end of CCM stimulation to the end of the absolute refractory period implies that a prolongation of QTC-time by anaesthetics and even a shortening, e.g. by digitoxin should not induce interactions between anaesthetics and CCM.

Perioperative management of patients with implanted CCM devices

Anaesthesiologists will possibly encounter patients with implanted CCM devices in the following situations: management of elective surgery, postoperative care in the ICU and emergency management. There are currently no guidelines on the perioperative management of patients with CCM devices. Neither anaesthesiologists nor cardiologists will be able to draw on experience or offer relevant advice if they are not part of the ongoing phase III trial. After the phase III trial and assuming that the CCM device is approved by the authorities (e.g. the FDA) for routine use, a steep increase in the number of patients may occur. Issues that need to be addressed include minimum preoperative assessment, guidance on the identification of normal and abnormal device function and the recognition and avoidance of potential hazards in the medical environment.

The following considerations and our own experience of anaesthetic CCM management may support the idea of using pacemaker and cardioverter/defibrillator guidelines for CCM patients supplemented by author's recommendations. Table 1 summarizes key points for the intraoperative and perioperative management of patients with implanted CCM devices.

Table 1
Table 1:
Key commendations for the intraoperative and perioperative management of patients with implanted CCM devices.

Evaluation for anaesthesia

Patients with CCM devices are likely to have relevant co-morbidity. CCM devices should be interrogated prior to elective surgery by the person or institution that implanted the device to assure and document proper functioning and adequate battery charge, and a copy of the interrogation protocol should be obtained. Furthermore, the implanting instance (e.g. cardiologist) should decide whether further optimization of the medical treatment is warranted.

The integrity and position of the leads should be confirmed preoperatively by a chest X-ray. Additional radiographic information may include signs of cardiac decompensation (e.g. pleural effusion) and the identification of the central vein used for lead placement. This information may be useful when selecting the optimal site for central venous cannulation if necessary.

A baseline chest lead ECG should be obtained. It is not recommended to evaluate the magnet switch-off function preoperatively unless absolutely necessary. As stated on the identification card, placing a magnet over the device for 3-5 s switches the OPTIMIZER™ into the off mode [23].

Intraoperative management

Routine monitoring includes ECG, pulse oximetry and temperature. A magnet should be available. Since patients eligible for CCM device implantation are classified as NYHA class III with a left ventricular ejection fraction under 35% that has not changed in spite of at least three months with three of the medications at maximum tolerable doses (digoxin, diuretics, β-blockers, angiotensin-converting enzyme inhibitor) the anaesthesiologist should expect relevant chronic congestive heart failure [19]. The authors therefore recommend the use of invasive arterial pressure if the use of i.v. catecholamines is expected [24]. If required, central venous cannulation should be performed with caution because of the possibility of lead dislodgement. The use of a pulmonary artery catheter should be avoided if possible, since reliable information on cardiac output can be obtained by non-invasive methods [25].

The management of intraoperative deterioration of cardiac pump function is similar to that in patients without CCM. No data are available on the concomitant use of CCM and i.v. inotropic support (e.g. norepinephrine, dobutamine), but the authors believe that in the event of acute cardiac failure, the anaesthesiologist will have no choice but to use i.v. inotropic drugs. Furthermore, the effects of mechanical ventilation in CCM patients have not been assessed.

As cardiac pacemaker and defibrillator devices do not require antimicrobial prophylaxis apart from the perioperative situation [26], patients with CCM devices should also not receive routine antimicrobial prophylaxis unless otherwise indicated.

It is important to be aware of the potential adverse interactions between electrical/magnetic activity and CCM function that may occur during the operative period. These interactions result from electric current generated by electrocautery or cardioversion, as well as the impact of metabolic derangements, antiarrhythmic agents and anaesthetic agents on pacing and sensing thresholds.

Electrical devices generating electromagnetic fields should be placed at least 15 cm from the CCM generator. The CCM generator has a built-in magnetic ‘OFF’ switch. It deactivates the generator within 3-5 s of exposure to a magnetic field. The CCM generator may be damaged by high-frequency ablation, medical diathermia, external cardioversion/ or defibrillation, radiotherapy, magnetic resonance imaging (MRI) and therapeutic ultrasound [23]. If electromagnetic fields such as electrocautery are essential for surgery, the authors recommend turning the CCM device off, even for short procedures.

At present, there are no guidelines on intraoperative malfunctioning of the CCM device. If malfunctioning (e.g. after electrosurgery) is suspected, the magnet should be used to switch the device off. As the CCM is not considered a life saving device, deactivation should not constitute a further risk [23].

If emergent cardioversion is required, the paddles should be placed as far from the implanted device as possible and in a position assumed to be perpendicular to the orientation of the device leads (i.e. anterior-posterior paddle position is preferred).

Post-anaesthetic evaluation

Postoperatively, the patient should be transferred to an ICU. Cardiac output monitoring should be continued if necessary. After cardiac stabilization and complete reversal of muscle relaxation the normothermic patient may be extubated. It should be remembered that the CCM device is currently deactivated during the night. Alternatively, the CCM generator needs to be read out postoperatively. If a prolonged hospital stay is expected the recharging ‘waistcoat’ device might be useful for confirming the proper battery status.


As far as we know at present, CCM therapy is safe and feasible. This new treatment has not been seen to have pro-arrhythmic effects while improving systolic function. The technique may be promising as an additive treatment for severe HF. Perioperative and intraoperative management should follow cardiac pacemaker/ICD guidelines.


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Cited Here


A 71-yr-old, 70-kg man underwent emergency surgery for intra-abdominal bleeding after ascites drainage. Concurrent diseases were liver cirrhosis with ascites, ischaemic cardiomyopathy after multiple myocardial infarctions treated with angioplasty, stents, and coronary artery bypass surgery, mitral valve replacement, pulmonary hypertension and chronic renal failure. Initial haemoglobin was 3.7 mmol L−1. The patient was graded ASA IV. At this time it was known that the patient had an implanted ‘unknown cardiac device’ called ‘Optimizer’. No device identity card was available. None of the doctors in the hospital had heard of cardiac ‘optimizing’. Because of the bleeding there was no time for further telephone/Internet evaluation of the device.

General anaesthesia was induced with etomidate and alfentanil, and intubation of the trachea was facilitated with rocuronium (rapid sequence induction). During this procedure systolic arterial pressure fell to a minimum value of 50 mmHg. Norepinephrine (0.12 μg kg−1 min−1) and dobutamine (15 μg kg−1 min−1) were given continuously via a central venous catheter line for haemodynamic stabilization. The surgeon refused to operate without monopolar electrocautery. Surgery was performed and a total of 4800 ml of ascites and blood were evacuated. During the procedure a total of five units of packed red blood cells and three units of fresh frozen plasma were administered. Due to circulatory instability, the patient was transferred to the ICU (internal medicine department) and sedation and ventilation were continued. The situation stabilized and the trachea was extubated after three hours. After extubation neither vasopressor support nor other interventions were necessary.

During surgery, standard patient monitoring (Siemens, Infinity, SC 9000 XL) detected no pacemaker activity. During the operation, intra-arterial pressure registering showed an unusual second systolic wave. At first, a ‘kind of intra-aortic balloon pump’ was considered. A postanaesthetic evaluation of the case revealed that a CCM device had been implanted in the context of a phase III trial. At the time of surgery (8.00p.m.) the device was in standby mode. The abnormal pulse wave is now thought to be an artifact. The CCM device had been programmed to give impulses for seven hours during the daytime, when the patient's activity was normally greater.



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