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Three cases of electrical storm in fulminant myocarditis treated by extracorporeal membrane oxygenation
Three Cases of Electrical Storm in Fulminant Myocarditis Treated by Extracorporeal Membrane Oxygenation Weihang Hu M.D, Lan Chen M.D, Changwen Liu M.D, Wei Hu M.D, Jun Lu M.D, Yin Zhu M.D, Jianrong Wang M.D, Bingwei Liu M.D PII: DOI: Reference:
S0735-6757(14)00759-1 doi: 10.1016/j.ajem.2014.10.025 YAJEM 54575
To appear in:
American Journal of Emergency Medicine
Received date: Accepted date:
5 October 2014 11 October 2014
Please cite this article as: Hu Weihang, Chen Lan, Liu Changwen, Hu Wei, Lu Jun, Zhu Yin, Wang Jianrong, Liu Bingwei, Three Cases of Electrical Storm in Fulminant Myocarditis Treated by Extracorporeal Membrane Oxygenation, American Journal of Emergency Medicine (2014), doi: 10.1016/j.ajem.2014.10.025
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ACCEPTED MANUSCRIPT Three Cases of Electrical Storm in Fulminant Myocarditis Treated by Extracorporeal Membrane Oxygenation 2
Lan Chen, M.D.,
Lu, M.D., 1Yin Zhu, M.D.,
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Changwen Liu*, M.D.,
1
Wei Hu, M.D., 1Jun
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Weihang Hu, M.D.,
1
Jianrong Wang, M.D.,
1
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1
Bingwei Liu, M.D.
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Affiliations:
Department of ICU, Hangzhou First People’s Hospital, Hangzhou 310006, China.
2
Department of Electrocardiography, Hangzhou First People’s Hospital, Hangzhou
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1
310006, China.
Running title: Electrical Storm in Fulminant Myocarditis treated by ECMO
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Email: [email protected]
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Corresponding author: Changwen Liu, M.D.
Phone/Fax: +86 13957161977/+86 571 87914773
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China.
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Address: Department of ICU, Hangzhou First People’s Hospital, Hangzhou 310006,
* Weihang Hu and Lan Chen
contributed equally to this paper.
Authors’ contributions: Changwen Liu designed the study. Wei Hu, Jun Lu and Yin Zhu carried out the experiments and collected data. Jianrong Wang and Bingwei Liu analyzed the data and interpreted the results. Weihang Hu, Lan Chen and Changwen Liu discussed analyses, interpretation, and wrote the paper. All authors have contributed to, seen and approved the manuscript. Conflicts of interests: The authors declare having no conflicts of interest regarding the design or outcomes of this study.
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Abstract:
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Background: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO)
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provides effective circulation support for patients with fulminant myocarditis (FM),
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and there are very few reports of electrical storm (ES) occurring in FM patients due to inadequate left ventricular unloading during ECMO support.
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Methods: We report the treatment and outcomes of five FM patients who were enrolled in our study and treated with V-A ECMO support in our intensive care unit from September 2009 to May 2013.
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Results: All five FM patients (mean age 19.40 ± 4.80 years) were found to have inadequate left ventricular unloading and significantly reduced myocardial
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contractility. Electrical storms experienced in three patients were successfully treated
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with urgent medical attention and electric cardioversion or in combination with an
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intra-aortic balloon pump. Conclusions: The risk of ES during V-A ECMO support in FM patients should be highlighted, and especially during the period of inadequate LV unloading and reduced myocardial contractility at the peak phase of myocardial edema. Administration of β-blockers is critical for managing ES, and an intra-aortic balloon pump can be employed when necessary.
ACCEPTED MANUSCRIPT Introduction:
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Myocarditis is an inflammatory disease of the myocardium, and is often considered a
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precursor of dilated cardiomyopathy and chronic heart failure (1), which is the most common reason for heart transplantation. Myocarditis accounts for ~ 10% of patients
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with new-onset cardiac dysfunction who subsequently undergo endomyocardial
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biopsy (2), and 8.6%-12% of sudden death cases in young adults (3). Most cases of myocarditis are caused by viral infections, followed by bacterial and protozoan infections, and other triggers such as post-viral immune-mediated responses or other systemic illnesses including systemic lupus erythematosus, polymyositis, scleroderma,
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sarcoidosis, Whipple’s disease, and sprue (4). Fulminant myocarditis (FM) is an
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unusual type of myocarditis which initially occurs in the myocardium and then rapidly
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progresses to cause acute-onset heart failure and cardiogenic shock (4). While no robust data exist which adequately define the incidence of FM, its estimated
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prevalences are 10% among patients with biopsy-proven myocarditis and 0.9% among patients with new-onset heart failure (5). FM patients typically present with rapidly deteriorating hemodynamic parameters, which are associated with the disorder’s high rates of mortality and morbidity (6). However, patients who survive the initial acute episode have a better prognosis compared to those with more insidious disease (7). The long-term prognosis for FM survivors is good, with a near 100% chance of survival with normal cardiac function without transplantation at 12 years following diagnosis (6,8).
ACCEPTED MANUSCRIPT As a self-resolving entity, and because no well-established therapies are available to improve recovery, current treatments for the acute episode of FM are
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mostly supportive (9). While left ventricular assist devices are used as supportive therapy in FM refractory to usual resuscitative therapies such as vasopressors and
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intra-aortic balloon pumps (IABPs), they are complicated by the need for bulky and invasive procedures (10). In contrast, use of veno-arterial (V-A) extracorporeal
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membrane oxygenation (ECMO) provides time for recovery of organ function, and has been well validated in FM complicated by cardiogenic shock or cardiac arrest (9, 11). Additionally, compared with other supportive treatments, ECMO is a more
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readily accessible and reversible intervention, and has advantages of simplicity and
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economic benefits (6). A previous study reported that patients who survive with ECMO support can usually be weaned in < 7 days (12). It has also been deemed that
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ECMO should be viewed as a mechanical bridge leading to myocardial recovery
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rather than an intervention prior to transplantation (8). As an increasingly common life-threatening emergency, electrical storm (ES) is defined as three or more separate episodes of ventricular arrhythmia which occur during a single 24 h time period, and lead to use of an implantable cardioverter defibrillator (ICD) (13,14). ES is associated with a particularly high risk of mortality, and even the consequent therapy for ventricular arrhythmias, may lead to substantial impairment of quality of life and a poor prognosis (13). The current strategies used to treat ES are complex and unsatisfactory, because they require simultaneous administration of several medications and do not favorably influence the long-term
ACCEPTED MANUSCRIPT outcome (15). Therefore, more appropriate support and treatment methodologies need to be identified. The occurrence of ES is associated with a multitude of factors,
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including acute ischemia, structural heart disorders (nonischemic and ischemic cardiomyopathies), and inherited channelopathies (15). ES can also occur in FM
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patients due to their unstable cardiac electrical activity and compromised hemodynamics (16). In theory, ECMO support should merely provide favorable
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conditions for recovery of cardiac function and hemodynamics in FM patients. However, in actual practice, ECMO significantly contributes to the termination of ES when medicinal therapies are unsuccessful, and is also useful for supporting patients
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with severe heart failure (17, 18). Very few studies have reported ES in patients with
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ECMO support, and there is only one reported case of ES occurring during veno-venous (V-V) ECMO support in a child with influenza A-associated myocarditis
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Methods
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(19). Here, we report three cases of ES in five FM patients treated by V-A ECMO.
General information
The protocol for this study was reviewed and approved by the local ethics committee of Hangzhou First People’s Hospital, and all participants provided a signed informed consent prior to enrollment. This study enrolled five FM patients (3 males and 2 females; mean age 19.40 ± 4.80 y) who were admitted to our Intensive Care Unit (ICU) and received ECMO therapy during September 2009 to May 2013. All five patients had experienced symptoms of upper respiratory infection including fever,
ACCEPTED MANUSCRIPT pharyngalgia, chest distress, dyspnea, and muscular soreness within one week prior to admission, and their symptoms had increased in severity. Blood analyses showed
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elevated levels of aspartate aminotransferase (AST), creatine kinase (CK), CK-MB, troponin (TNI), and lactic dehydrogenase (LDH), and results of electrocardiograms
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were abnormal. However, cardiac ultrasonography results did not show immediate heart chamber dilation, and the cardio-thoracic proportion in each of the five patients
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was normal. Based on these test results, the patients were diagnosed as viral myocarditis (2).
Due to their disease progress, all five patients were supported with mechanically
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assisted breathing and administrated immunoglobulin (i.v., 0.40 g/kg) plus
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methylprednisolone (i.v., 40 mg) bid. One 27-week pregnant patient (No. 3) continued receiving bedside hemopurification due to her reduced urine volume and elevated
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levels of creatinine and lactic acid. However, regardless of their therapeutic support,
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all five patients showed unsatisfactory clinical progress. Three patients (No. 1, 2, 3) were provided ECMO support due to their compromised hemodynamics and unstable cardiac electrophysiologic functions. The other two patients (No. 4, 5) suffered sudden cardiac arrest and were treated with ECMO cannulation during cardiopulmonary resuscitation (ECPR) (Table 1).
Extracorporeal membrane oxygenation
Four patients (No. 1, 2, 3, 4) received an indwelled catheter via the arteria femoralis and femoral vein under general anesthesia. The other patient (No. 5) underwent an
ACCEPTED MANUSCRIPT urgent catheterization to initiate V-A ECMO. Both the ECMO system and cannulas (arterial and venous) were heparin coated. Ultrasound was used to detect whether the
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cannulas were indwelled from the femoral vein into the ingress of the inferior vena cava, and from the femoral artery into the crotch common iliac artery, respectively.
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Heparin (1 mg/kg) was administered prior to placement of the cannulas. During ECMO support, heparin infusion was initiated with an activated clotting time (ACT)
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of 160-220 seconds. ECMO was initiated with a flow of 80-100 mL/kg, and oxygen flow was controlled to maintain a ratio of ventilation to blood flow (V/Q ratio) of 0.8. After paying off oxygen debt, ECMO was continued with a flow of 70 mL/kg. When
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the patient’s condition stabilized, the ECMO flow was decreased to 20 mL/kg (at least
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1 L/min), and maintained at that level for 2-4 hours prior to withdrawal. ECMO support was provided using a small total volume, low pressure, and low frequency to
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control airway pressure as a means of preventing barotrauma and volutrauma caused
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by mechanical ventilation.
Results
Two patients (No. 4, 5) were administrated lidocaine (4 mg/h) plus amiodarone (2 mg/h) in conjunction with ECMO support, and recovered sinus rhythm 12 h later. These patients received metoprolol (12.5 mg, bid) via nasal administration while lidocaine and amiodarone were gradually being tapered and finally eliminated. The other three patients (No. 1, 2, 3), did not receive the above-mentioned drugs because they were
suspected
of
having
atrioventricular
dissociation
or
complete
ACCEPTED MANUSCRIPT atrioventricular block, and their electrocardiograms showed signs of improvement (Figure 1 A-C). After 12 h of ECMO support, the doses of vasopressor agents were
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significantly reduced (dopamine ≤ 5 ug/kg/min), while hemodynamic parameters and cardiac function became stabilized. However, 66.67 ± 58.52 h after terminating
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ECMO support, all three patients (No. 1, 2, 3) experienced ES (Figure 2 A-C, Table 2), and common causes such as hypokalemia and acidosis were excluded.
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One patient (No.1) suffered ES three times within 24 hours and a burst of ventricular tachycardia at 11:45 on July 17, 2009. In that case, isoprenaline (0.12 mg) was given intravenously and a micro-pump was used to maintain a steady flow of
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drug. Sinus rhythm was recovered after one minute. However, ventricular fibrillation
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occurred at 13:27; after which, adrenaline (0.5 mg) plus lidocaine (50 mg) and chest compression were administered simultaneously. The patient recovered sinus rhythm
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after 3 minutes and was maintained with lidocaine (2 mg/h). Ventricular tachycardia
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occurred again at 16:00, and administration of lidocaine (50 mg) plus amiodarone (30 mg) failed to produce a curative effect. Adrenaline (0.5 mg), electric defibrillation (monophase 120 J) and chest compression were employed to recover sinus rhythm. A bedside echocardiography showed a normal left heat size and a left ventricular ejection fraction (LVEF) of 27%. However, asynergic movement in the left ventricular wall and decreased diffuse movement were also detected. The patient was treated with combined lidocaine and amiodarone (2 mg/h), and ES did not re-occur. After receiving ECMO support for 140 h, the patient’s pressure difference returned to normal pulse with a LVEF > 40%, and a central venous oxygen saturation > 70%;
ACCEPTED MANUSCRIPT ECMO support was then withdrawn. The patient was discharged without complications at 21 days after admission, and displayed a normal sized heart chamber
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and a properly functioning valve.. A followup visit showed no detrimental effect on the patient’s growth and development, and no recurrence of ES was detected. Another
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patient (No. 2) suffered four occurrences of ES and a burst of ventricular tachycardia at 4:50 on June 14, 2012. Lidocaine (50 mg) plus amiodarone (150 mg) was given
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intravenously and sinus rhythm was recovered. Afterwards, a micro-pump was used to maintain a steady flow of drugs [lidocaine (4 mg/h) and amiodarone (2 mg/h)]. Later, two episodes of ES occurred at 12:38 and 12:42 respectively, and amiodarone (1 mg/h)
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plus electric defibrillation (monophase 120 J) were used to recover sinus rhythm.
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However, ventricular tachycardia was detected by ECG at 12:45, and esmolol (100 mg) was used to help recover sinus rhythm. The patient showed a pulse pressure
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difference < 10 mmHg (97/92 mmHg). A bedside electrocardiogram revealed an
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enlarged left ventricle with a spontaneous echo. The interventricular septum was 1.2 cm deep, and local apical bulging was detected. The left ventricular wall displayed decreased diffuse movement with a LVEF of 20%. ECG monitoring detected repeated attacks of ventricular tachycardia. Because the patient exhibited weak myocardial contraction, and the reverse blood flow of V-A ECMO had significantly increased cardiac afterload, an intra-aortic balloon pump (IABP) was immediately implanted. Following IABP implantation, the patient’s pulse pressure difference was > 20 mmHg and the arrhythmia disappeared. A re-examination at the 24-48 h time interval revealed improved left ventricular contractions with no ES relapse. After 134 h of
ACCEPTED MANUSCRIPT support, the patient’s condition returned to normal and the ECMO and IABP were weaned two days later. The patient was discharged 21 days after admission, and
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presented with normal heart function with no relapse of ES at the 2-year follow-up visit.
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One patient (No. 3) suffered three episodes of ES and was treated with electric defibrillation (monophase 120 J) and lidocaine (4 mg/h). Ventricular tachycardia,
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atrioventricular block, and ventricular escape were detected by ECG. Invasive blood pressure monitoring suggested continuous nonpulsatile flow perfusion, which was considered related to ventricular escape. A bedside ultrasound guided temporary
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pacemaker with frequency of 100 times per minute and initial output current of 5 mA
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was used for cardiac pacing; however, the pulse pressure difference was < 5 mmHg. A bedside echocardiography revealed asynergic movement in the left ventricular wall,
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with anteroposterior diameters of 5.0 cm in end-diastolic phase and 4.3 cm in systole
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phase, and a flat, low amplitude. The patient’s LVEF was estimated to be 20% and blood pressure was 90/69 mmHg, suggesting a decrease in heart afterload. Although ES did not re-occur, ECG examinations consistently showed grade III atrioventricular block. The patient developed a catheter-related blood borne infection, continued to show unsatisfactory recovery of LVEF, and died from multiple organ failure after receiving ECMO support for 431 h. Three patients (NO. 1, 2, 3) recovered sinus rhythm or pacing rhythm after treatment of ES; however, their pulse pressure differences decreased during continuous nonpulsatile flow perfusion, while their blood lactate levels increased. Echocardiography examinations detected flat and low
ACCEPTED MANUSCRIPT amplitudes in movements of the left ventricular wall and ventricular septum, accompanied by decreases in LVEF and no significant changes in myocardial
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enzymes. V-A ECMO support and IABP supplementation were used to steadily elevate the afterload and LVEF. The clinical manifestations in these three FM patients
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suggested myocardial stunning (Figure 3).
Two patients (No. 4, 5) who had been maintained with ECMO support for 57.50
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± 17.68 h were found to have decreased pulse pressure differences. Echocardiography examinations helped to rule out hydropericardium, but indicated enlargement of the left ventricle, and decreased diffuse movement of the left ventricular wall of each
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patient, accompanied by a significant decrease in LVEF. Chest films suggested
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increased effusion in the lungs. When taken together, these manifestations strongly indicated a decline in left ventricular function caused by ECMO support (Table 3).
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These patients received metoprolol (12.5 mg, bid, via nasal feeding) to adjust their
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activated clotting times (ACTs) to 220-240 s; after which they showed increased LVEF, a steady decrease in lung effusion, and no relapse of ventricular tachycardia or ventricular fibrillation. Both patients were withdrawn form ECMO support (148 h ECMO for No. 4, 187 h ECMO for No. 5) and discharged without complications. During their respective followup visits, the two patients exhibited normal heart chambers, normal cardiac valve function, normal intelligence, and showed no evidence of ES relapse. Additionally, both patients showed a LVEF > 65%.
ACCEPTED MANUSCRIPT Discussion
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Here, we reported three cases of ES in five FM patients treated by ECMO. These
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cases highlight the need to be aware of inadequate LV unloading and reduced myocardial contractility during the peak phase of myocardial edema. Oda et al (19)
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reported a case of ES which occurred during V-V ECMO support of a child diagnosed
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as myocarditis. Interestingly, both cardioversion and medication were ineffective in treating the electrical storm, while a switch from V-V ECMO to V-A ECMO successfully maintained systemic flow, and terminated the ES (19). To the best of our knowledge, that was the first report of ES occurring during V-A ECMO support of an
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FM patient.
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Although FM is associated with rapid circulatory collapse and a high mortality
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rate, patients may have an excellent recovery if they are aggressively supported in a timely manner (5). Maximum pharmacologic therapy may not be effective in some
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cases, and a clinical strategy employing optimal mechanical circulatory support (e.g., ECMO) may be the treatment of last resort to save a critically ill patient. Additionally, an FM patient who receives full supportive care often benefits from significant improvement in their left ventricular function (4). Because FM is potentially reversible, it is reasonable to deploy ECMO to bridge patients until recovery or transplantation (20). ECMO support provides sufficient coronary perfusion for myocardium as well as adequate blood and oxygen for other important organs. These effects create favorable conditions for recovery of injured cells, including myocardial cells. Compared to use of a ventricular assist device (VAD), ECMO has advantages of
ACCEPTED MANUSCRIPT fewer complications, easier application, and the ability to provide biventricular support. It has therefore been considered as the first-line mechanical support treatment
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for FM complicated with profound shock, when intra-aortic balloon pumping is inadequate or infeasible (21).
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It is extremely important to maintain an optimal balance between flow support and left ventricular (LV) afterload when employing ECMO in support of FM patients
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(6). The drawback of ECMO is that it may not adequately alleviate left ventricular (LV) afterload, and thus increase LV wall stress and pressurize the systemic arterial circuit. In the absence of adequate left atrial decompression, the compromised LV
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may lack sufficient contractility to open the aortic valve, resulting in elevated LV
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cavity pressure, pulmonary venous hypertension, pulmonary vascular injury, and acute respiratory distress syndrome (22). As a result, ECMO has been associated with
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both patient and mechanical complications; including stroke (8%), brain death (6%),
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hemorrhage (cannula, 27%; pulmonary, 10%), infection (15%), and a need for dialysis (16%) (23). Therefore, in actual clinical practice, a maximum ECMO flow should not be maintained because the resulting high afterload may further aggravate an already severely deteriorated heart. In our cases, we continued to regulate ECMO flow to rates of 80-100 mL/kg to 70 mL/kg, and 20 mL/kg (1L/min), based on the progress of the disease. The correlation between ES and ECMO support is unclear and complicated. All five cases in our study showed inadequate LV unloading and significantly reduced myocardial contractility. These problems became especially obvious after 24 h of
ACCEPTED MANUSCRIPT ECMO support, which correlated with the peak period of myocardial injury and edema. On the other hand, ECMO support is a supplementary approach and has no
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direct therapeutic effect on the infective virus or the patient’s autoimmune response; therefore, myocardial injury and edema are not avoided. Moreover, an increase in LV
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afterload resulting from ECMO plus myocardial diffuse edema may subsequently contribute to excessive myocardial tensile strength and remodeling (24). Heart failure
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and myocardial remodeling can alter myocardial ion channels, increase dispersion of repolarization, increase the autorhythmicity of Purkinje fibers, and create new electrical circuits. Such pathological changes in electrophysiology tend to trigger
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receiving ECMO support.
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ventricular tachycardia and fibrillation, which may be precursors of ES in FM patients
The current drugs used to treat ES are often prescribed empirically and
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demonstrate moderate efficacy. Most drug treatment strategies seek to produce a
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sympathetic blockade by use of a β-blocker, or induce left stellate ganglion denervation (25). Arya et al (26) reported that β-blockers and angiotensin-converting enzyme (ACE) inhibitors could reduce ES severity in patients with an implantable cardioverter defibrillator (ICD). Similarly, Flores-Ocampo et al (27) found that failure to include treatment with β-receptor blockers was a strong predictor for ES in ICD patients. Accordingly, our study indicated that β-blockers might help prevent ES in FM patients receiving ECMO support. In our study, three patients (No. 1, 2, 3) experienced ES while receiving ECMO support, while ES did not occur in the remaining two patients (No. 4, 5), who were treated with only amiodarone and
ACCEPTED MANUSCRIPT metoprolol. These results suggest β-receptor blockers as a therapeutic choice to prevent myocardial remodeling and ES in patients receiving ECMO support. This
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may especially apply when treating ES in patients with inadequate LV unloading and significantly reduced myocardial contractility.
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An organized approach for managing ES, including pharmacological and/or non-pharmacological interventions, has been previously proposed (28). We found that
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the urgent and timely use of drugs and electric cardioversion can terminate ES in FM patients receiving ECMO support. Additionally, the pulsatile blood flow produced by an IABP can effectively reduce LV afterload, resulting in increased myocardial
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oxygen supply (22). Adequate myocardial unloading and improved myocardial
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metabolism would certainly reduce a patient’s risk for ES. Therefore, we believe that
myocardium.
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combined use of an IABP and ECMO would greatly benefit the recovery of stunned
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In conclusion, physicians need to be aware of the risk for ES in FM patients receiving V-A ECMO support, and especially in patients who exhibit inadequate LV unloading and reduced myocardial contractility during the peak phase of myocardial edema. Moreover, we found that β-receptor blockers might help prevent ES in FM patients receiving V-A ECMO support, and that pulsatile perfusion by an IABP facilitated myocardial unloading in seriously ill patients. Nevertheless, this was a single center study, which included a small number of patients. Large multicenter studies are required to verify our findings.
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ACKNOWLEDGEMENT
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We thank Medjaden Bioscience Limited for assisting in the preparation of this
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manuscript
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Figure Legends Figure 1. Electrocardiograms of three fulminant myocarditis patients (No. 1, 2, 3)
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prior to electrical storm. A: Patient No.1, sinus tachycardia; B: Patient No. 2, sinus tachycardia, complete right bundle branch block; C: Patient No. 3, sinus tachycardia,
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complete atrioventricular block, accelerated idioventricular rhythm.
Figure 2. Electrical storm in three fulminant myocarditis patients during
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venous-arterial extracorporeal membrane oxygenation support. A: No. 1; B: No. 2; C: No. 3.
Figure 3. Echocardiography of cardiac stunning after an electrical storm within the
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preceding 24 hours.
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3
CR I
4
5
Female
Male
Male
21
18
21
3.00
7
5
Bidirectional ventricular
Sinus tachycardia,
Sinus tachycardia;
onal tachycardia;
tachycardia;
V1-V3 ST segment
Complete atrioventricular
tachycardia;
Endotracheal
Endotracheal intubation;
elevation; Endotracheal
block; Accelerated
Endotracheal intubation
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Table 1. Clinical characteristics of five patients with fulminant myocarditis.
intubation
Hemopurification
intubation
idioventricular rhythm;
Sinus tachycardia;
Sinus tachycardia;
1
2
Gender
Male
Female
Year (y)
12
25
4.00
2.00
Admission to
Sinus tachycardia;
Atrioventricular juncti
intensive care
Paroxysmal ventricular
unit
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No.
MA
Prodromal
AC
TE
D
phase (d)
Endotracheal intubation
ECMO
Sinus tachycardia;
support
Atrioventricular
Complete
interference dissociation;
atrioventricular block
block; Ventricular
Bidirectional ventricular
Accelerated
escape-ventricular
tachycardia
idioventricular
premature beat bigeminy
Sudden cardiac arrest;
Sudden cardiac arrest;
Complete atrioventricular external cardiopulmonary external cardiopulmonary resuscitation
resuscitation
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rhythm;
CR I
Duration
84.20
95.50
0.50
Dopamine (15.00) +
Dopamine (20.00) +
Adrenaline (2.00)
Adrenaline (2.00)
dobutamine (30.00)
dobutamine (40.00) +
hospital
31.00
30.50
Vasoactive
Dopamine (20.00) +
drugs
dobutamine (40.00)
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between
admission and
TE
D
MA
ECMO (h)
400.00
179.00
185.00
172.00
2780.00
CK (U/L)
997.00
235.00
704.00
165.00
1294.00
CK-MB（U/L）
42.00
99.00
56.00
24.00
205.00
TNI (ug/L)
42.10
12.70
12.40
0.90
43.90
LDH (U/L)
620.00
403.00
560.00
283.00
4700.00
Cr (ummol/L)
92.00
169.00
191.00
164.00
242.00
Lac (mmol/L)
3.90
7.10
5.20
2.90
13.10
Cardiothoracic
0.45
0.42
0.52
0.42
0.40
AC
AST (U/L)
adrenaline (2.00)
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(ug/kg/min)
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0.25
TE
D
MA
NU S
CR I
0.28
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0.33
AC
LVEF
PT
ratio
－
－
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Table 2. Clinical characteristics of three fulminant myocarditis patients who experienced electrical storm. 1
Duration between hospital
3.50
2
3
3.00
9.50
28.00
134.00
Dopamine (3.00) + nitroglycerin (1.0)
Dopamine (3.00) + nitroglycerin (0.5)
CR I
No.
NU S
admission and electrical storm (d) 38.00
MA
Duration between ECMO and electrical storm (d)
Dopamine (3.00) + nitroglycerin (0.8)
D
Vasoactive agent
TE
(ug/kg/min)
Pre-
Storming
24-48 h later
Pre-
Storming
24-48 h later
95/
95/
97/
105/
90/
103/
90/
70/
78/
92/
78/
76/
103/
69/
78
84
94
87
80
103
76
330.00
330.00
120.00
118.00
117.00
133.00
141.00
126.00
285.00
247.00
139.00
183.00
144.00
141.00
98.00
98.00
78.00
CK-MB（U/L）
16.00
11.00
10.00
19.00
19.00
14.00
5.00
10.00
3.00
TNI (ug/L)
2.21
2.44
2.03
1.70
1.34
1.19
0.53
0.67
0.57
Storming
Systolic pressure /
98/
86/
Diastolic pressure /
78/
80/
Blood pressure (mmHg)
85
83
AST (U/L)
320.00
CK (U/L)
24-48 h later
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Pre-
AC
Phase
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788.00
788.00
254.00
Lac (mmol/L)
1.50
4.50
2.00
0.97
K+ (mmol/L)
4.40
4.10
4.7O
4.20
LVEF
0.36
0.27
0.40
0.40
NU S MA
D TE CE P AC
226.00
190.00
457.00
632.00
423.00
1.19
0.85
3.30
4.50
2.60
4.50
4.70
4.50
4.00
4.20
0.20
0.36
0.31
0.20
0.30
PT
689.00
CR I
LDH (U/L)
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Table 3. Clinical characteristics of two patients with minimum left ventricular ejection fraction (LVEF) 4
CR I
No.
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Duration between admission and LVEF 7.00 (d) 70.00
Vasoactive agent (ug/kg/min)
Dopamine (2.00) + nitroglycerin (1.2) 24 h previous
Minimum
24 h afterwards
2.50
45.00 Dopamine (1.00) + nitroglycerin (1.5) 24 h previous
Minimum LVEF
24 afterwards
D
Phase
MA
Duration between ECMO and LVEF (h)
5
104/
Diastolic pressure /
70/
Blood pressure (mmHg)
81
LVEF
0.29
98/
98/
90/
105/
84/
70/
73/
75/
79/
87
79
81
80
88
0.23
0.28
0.29
0.20
0.30
95/
AC
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Systolic pressure /
TE
LVEF
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T
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CE
PT
Fig. 1
Fig. 2
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CE
PT
ED
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T
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Fig. 3
S0735-6757(14)00759-1 doi: 10.1016/j.ajem.2014.10.025 YAJEM 54575
To appear in:
American Journal of Emergency Medicine
Received date: Accepted date:
5 October 2014 11 October 2014
Please cite this article as: Hu Weihang, Chen Lan, Liu Changwen, Hu Wei, Lu Jun, Zhu Yin, Wang Jianrong, Liu Bingwei, Three Cases of Electrical Storm in Fulminant Myocarditis Treated by Extracorporeal Membrane Oxygenation, American Journal of Emergency Medicine (2014), doi: 10.1016/j.ajem.2014.10.025
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Three Cases of Electrical Storm in Fulminant Myocarditis Treated by Extracorporeal Membrane Oxygenation 2
Lan Chen, M.D.,
Lu, M.D., 1Yin Zhu, M.D.,
1
Changwen Liu*, M.D.,
1
Wei Hu, M.D., 1Jun
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Weihang Hu, M.D.,
1
Jianrong Wang, M.D.,
1
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1
Bingwei Liu, M.D.
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Affiliations:
Department of ICU, Hangzhou First People’s Hospital, Hangzhou 310006, China.
2
Department of Electrocardiography, Hangzhou First People’s Hospital, Hangzhou
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1
310006, China.
Running title: Electrical Storm in Fulminant Myocarditis treated by ECMO
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Email: [email protected]
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Corresponding author: Changwen Liu, M.D.
Phone/Fax: +86 13957161977/+86 571 87914773
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China.
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Address: Department of ICU, Hangzhou First People’s Hospital, Hangzhou 310006,
* Weihang Hu and Lan Chen
contributed equally to this paper.
Authors’ contributions: Changwen Liu designed the study. Wei Hu, Jun Lu and Yin Zhu carried out the experiments and collected data. Jianrong Wang and Bingwei Liu analyzed the data and interpreted the results. Weihang Hu, Lan Chen and Changwen Liu discussed analyses, interpretation, and wrote the paper. All authors have contributed to, seen and approved the manuscript. Conflicts of interests: The authors declare having no conflicts of interest regarding the design or outcomes of this study.
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Abstract:
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Background: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO)
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provides effective circulation support for patients with fulminant myocarditis (FM),
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and there are very few reports of electrical storm (ES) occurring in FM patients due to inadequate left ventricular unloading during ECMO support.
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Methods: We report the treatment and outcomes of five FM patients who were enrolled in our study and treated with V-A ECMO support in our intensive care unit from September 2009 to May 2013.
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Results: All five FM patients (mean age 19.40 ± 4.80 years) were found to have inadequate left ventricular unloading and significantly reduced myocardial
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contractility. Electrical storms experienced in three patients were successfully treated
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with urgent medical attention and electric cardioversion or in combination with an
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intra-aortic balloon pump. Conclusions: The risk of ES during V-A ECMO support in FM patients should be highlighted, and especially during the period of inadequate LV unloading and reduced myocardial contractility at the peak phase of myocardial edema. Administration of β-blockers is critical for managing ES, and an intra-aortic balloon pump can be employed when necessary.
ACCEPTED MANUSCRIPT Introduction:
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Myocarditis is an inflammatory disease of the myocardium, and is often considered a
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precursor of dilated cardiomyopathy and chronic heart failure (1), which is the most common reason for heart transplantation. Myocarditis accounts for ~ 10% of patients
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with new-onset cardiac dysfunction who subsequently undergo endomyocardial
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biopsy (2), and 8.6%-12% of sudden death cases in young adults (3). Most cases of myocarditis are caused by viral infections, followed by bacterial and protozoan infections, and other triggers such as post-viral immune-mediated responses or other systemic illnesses including systemic lupus erythematosus, polymyositis, scleroderma,
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sarcoidosis, Whipple’s disease, and sprue (4). Fulminant myocarditis (FM) is an
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unusual type of myocarditis which initially occurs in the myocardium and then rapidly
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progresses to cause acute-onset heart failure and cardiogenic shock (4). While no robust data exist which adequately define the incidence of FM, its estimated
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prevalences are 10% among patients with biopsy-proven myocarditis and 0.9% among patients with new-onset heart failure (5). FM patients typically present with rapidly deteriorating hemodynamic parameters, which are associated with the disorder’s high rates of mortality and morbidity (6). However, patients who survive the initial acute episode have a better prognosis compared to those with more insidious disease (7). The long-term prognosis for FM survivors is good, with a near 100% chance of survival with normal cardiac function without transplantation at 12 years following diagnosis (6,8).
ACCEPTED MANUSCRIPT As a self-resolving entity, and because no well-established therapies are available to improve recovery, current treatments for the acute episode of FM are
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mostly supportive (9). While left ventricular assist devices are used as supportive therapy in FM refractory to usual resuscitative therapies such as vasopressors and
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intra-aortic balloon pumps (IABPs), they are complicated by the need for bulky and invasive procedures (10). In contrast, use of veno-arterial (V-A) extracorporeal
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membrane oxygenation (ECMO) provides time for recovery of organ function, and has been well validated in FM complicated by cardiogenic shock or cardiac arrest (9, 11). Additionally, compared with other supportive treatments, ECMO is a more
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readily accessible and reversible intervention, and has advantages of simplicity and
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economic benefits (6). A previous study reported that patients who survive with ECMO support can usually be weaned in < 7 days (12). It has also been deemed that
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ECMO should be viewed as a mechanical bridge leading to myocardial recovery
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rather than an intervention prior to transplantation (8). As an increasingly common life-threatening emergency, electrical storm (ES) is defined as three or more separate episodes of ventricular arrhythmia which occur during a single 24 h time period, and lead to use of an implantable cardioverter defibrillator (ICD) (13,14). ES is associated with a particularly high risk of mortality, and even the consequent therapy for ventricular arrhythmias, may lead to substantial impairment of quality of life and a poor prognosis (13). The current strategies used to treat ES are complex and unsatisfactory, because they require simultaneous administration of several medications and do not favorably influence the long-term
ACCEPTED MANUSCRIPT outcome (15). Therefore, more appropriate support and treatment methodologies need to be identified. The occurrence of ES is associated with a multitude of factors,
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including acute ischemia, structural heart disorders (nonischemic and ischemic cardiomyopathies), and inherited channelopathies (15). ES can also occur in FM
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patients due to their unstable cardiac electrical activity and compromised hemodynamics (16). In theory, ECMO support should merely provide favorable
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conditions for recovery of cardiac function and hemodynamics in FM patients. However, in actual practice, ECMO significantly contributes to the termination of ES when medicinal therapies are unsuccessful, and is also useful for supporting patients
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with severe heart failure (17, 18). Very few studies have reported ES in patients with
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ECMO support, and there is only one reported case of ES occurring during veno-venous (V-V) ECMO support in a child with influenza A-associated myocarditis
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Methods
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(19). Here, we report three cases of ES in five FM patients treated by V-A ECMO.
General information
The protocol for this study was reviewed and approved by the local ethics committee of Hangzhou First People’s Hospital, and all participants provided a signed informed consent prior to enrollment. This study enrolled five FM patients (3 males and 2 females; mean age 19.40 ± 4.80 y) who were admitted to our Intensive Care Unit (ICU) and received ECMO therapy during September 2009 to May 2013. All five patients had experienced symptoms of upper respiratory infection including fever,
ACCEPTED MANUSCRIPT pharyngalgia, chest distress, dyspnea, and muscular soreness within one week prior to admission, and their symptoms had increased in severity. Blood analyses showed
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elevated levels of aspartate aminotransferase (AST), creatine kinase (CK), CK-MB, troponin (TNI), and lactic dehydrogenase (LDH), and results of electrocardiograms
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were abnormal. However, cardiac ultrasonography results did not show immediate heart chamber dilation, and the cardio-thoracic proportion in each of the five patients
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was normal. Based on these test results, the patients were diagnosed as viral myocarditis (2).
Due to their disease progress, all five patients were supported with mechanically
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assisted breathing and administrated immunoglobulin (i.v., 0.40 g/kg) plus
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methylprednisolone (i.v., 40 mg) bid. One 27-week pregnant patient (No. 3) continued receiving bedside hemopurification due to her reduced urine volume and elevated
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levels of creatinine and lactic acid. However, regardless of their therapeutic support,
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all five patients showed unsatisfactory clinical progress. Three patients (No. 1, 2, 3) were provided ECMO support due to their compromised hemodynamics and unstable cardiac electrophysiologic functions. The other two patients (No. 4, 5) suffered sudden cardiac arrest and were treated with ECMO cannulation during cardiopulmonary resuscitation (ECPR) (Table 1).
Extracorporeal membrane oxygenation
Four patients (No. 1, 2, 3, 4) received an indwelled catheter via the arteria femoralis and femoral vein under general anesthesia. The other patient (No. 5) underwent an
ACCEPTED MANUSCRIPT urgent catheterization to initiate V-A ECMO. Both the ECMO system and cannulas (arterial and venous) were heparin coated. Ultrasound was used to detect whether the
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cannulas were indwelled from the femoral vein into the ingress of the inferior vena cava, and from the femoral artery into the crotch common iliac artery, respectively.
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Heparin (1 mg/kg) was administered prior to placement of the cannulas. During ECMO support, heparin infusion was initiated with an activated clotting time (ACT)
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of 160-220 seconds. ECMO was initiated with a flow of 80-100 mL/kg, and oxygen flow was controlled to maintain a ratio of ventilation to blood flow (V/Q ratio) of 0.8. After paying off oxygen debt, ECMO was continued with a flow of 70 mL/kg. When
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the patient’s condition stabilized, the ECMO flow was decreased to 20 mL/kg (at least
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1 L/min), and maintained at that level for 2-4 hours prior to withdrawal. ECMO support was provided using a small total volume, low pressure, and low frequency to
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control airway pressure as a means of preventing barotrauma and volutrauma caused
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by mechanical ventilation.
Results
Two patients (No. 4, 5) were administrated lidocaine (4 mg/h) plus amiodarone (2 mg/h) in conjunction with ECMO support, and recovered sinus rhythm 12 h later. These patients received metoprolol (12.5 mg, bid) via nasal administration while lidocaine and amiodarone were gradually being tapered and finally eliminated. The other three patients (No. 1, 2, 3), did not receive the above-mentioned drugs because they were
suspected
of
having
atrioventricular
dissociation
or
complete
ACCEPTED MANUSCRIPT atrioventricular block, and their electrocardiograms showed signs of improvement (Figure 1 A-C). After 12 h of ECMO support, the doses of vasopressor agents were
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significantly reduced (dopamine ≤ 5 ug/kg/min), while hemodynamic parameters and cardiac function became stabilized. However, 66.67 ± 58.52 h after terminating
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ECMO support, all three patients (No. 1, 2, 3) experienced ES (Figure 2 A-C, Table 2), and common causes such as hypokalemia and acidosis were excluded.
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One patient (No.1) suffered ES three times within 24 hours and a burst of ventricular tachycardia at 11:45 on July 17, 2009. In that case, isoprenaline (0.12 mg) was given intravenously and a micro-pump was used to maintain a steady flow of
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drug. Sinus rhythm was recovered after one minute. However, ventricular fibrillation
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occurred at 13:27; after which, adrenaline (0.5 mg) plus lidocaine (50 mg) and chest compression were administered simultaneously. The patient recovered sinus rhythm
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after 3 minutes and was maintained with lidocaine (2 mg/h). Ventricular tachycardia
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occurred again at 16:00, and administration of lidocaine (50 mg) plus amiodarone (30 mg) failed to produce a curative effect. Adrenaline (0.5 mg), electric defibrillation (monophase 120 J) and chest compression were employed to recover sinus rhythm. A bedside echocardiography showed a normal left heat size and a left ventricular ejection fraction (LVEF) of 27%. However, asynergic movement in the left ventricular wall and decreased diffuse movement were also detected. The patient was treated with combined lidocaine and amiodarone (2 mg/h), and ES did not re-occur. After receiving ECMO support for 140 h, the patient’s pressure difference returned to normal pulse with a LVEF > 40%, and a central venous oxygen saturation > 70%;
ACCEPTED MANUSCRIPT ECMO support was then withdrawn. The patient was discharged without complications at 21 days after admission, and displayed a normal sized heart chamber
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and a properly functioning valve.. A followup visit showed no detrimental effect on the patient’s growth and development, and no recurrence of ES was detected. Another
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patient (No. 2) suffered four occurrences of ES and a burst of ventricular tachycardia at 4:50 on June 14, 2012. Lidocaine (50 mg) plus amiodarone (150 mg) was given
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intravenously and sinus rhythm was recovered. Afterwards, a micro-pump was used to maintain a steady flow of drugs [lidocaine (4 mg/h) and amiodarone (2 mg/h)]. Later, two episodes of ES occurred at 12:38 and 12:42 respectively, and amiodarone (1 mg/h)
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plus electric defibrillation (monophase 120 J) were used to recover sinus rhythm.
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However, ventricular tachycardia was detected by ECG at 12:45, and esmolol (100 mg) was used to help recover sinus rhythm. The patient showed a pulse pressure
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difference < 10 mmHg (97/92 mmHg). A bedside electrocardiogram revealed an
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enlarged left ventricle with a spontaneous echo. The interventricular septum was 1.2 cm deep, and local apical bulging was detected. The left ventricular wall displayed decreased diffuse movement with a LVEF of 20%. ECG monitoring detected repeated attacks of ventricular tachycardia. Because the patient exhibited weak myocardial contraction, and the reverse blood flow of V-A ECMO had significantly increased cardiac afterload, an intra-aortic balloon pump (IABP) was immediately implanted. Following IABP implantation, the patient’s pulse pressure difference was > 20 mmHg and the arrhythmia disappeared. A re-examination at the 24-48 h time interval revealed improved left ventricular contractions with no ES relapse. After 134 h of
ACCEPTED MANUSCRIPT support, the patient’s condition returned to normal and the ECMO and IABP were weaned two days later. The patient was discharged 21 days after admission, and
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presented with normal heart function with no relapse of ES at the 2-year follow-up visit.
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One patient (No. 3) suffered three episodes of ES and was treated with electric defibrillation (monophase 120 J) and lidocaine (4 mg/h). Ventricular tachycardia,
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atrioventricular block, and ventricular escape were detected by ECG. Invasive blood pressure monitoring suggested continuous nonpulsatile flow perfusion, which was considered related to ventricular escape. A bedside ultrasound guided temporary
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pacemaker with frequency of 100 times per minute and initial output current of 5 mA
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was used for cardiac pacing; however, the pulse pressure difference was < 5 mmHg. A bedside echocardiography revealed asynergic movement in the left ventricular wall,
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with anteroposterior diameters of 5.0 cm in end-diastolic phase and 4.3 cm in systole
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phase, and a flat, low amplitude. The patient’s LVEF was estimated to be 20% and blood pressure was 90/69 mmHg, suggesting a decrease in heart afterload. Although ES did not re-occur, ECG examinations consistently showed grade III atrioventricular block. The patient developed a catheter-related blood borne infection, continued to show unsatisfactory recovery of LVEF, and died from multiple organ failure after receiving ECMO support for 431 h. Three patients (NO. 1, 2, 3) recovered sinus rhythm or pacing rhythm after treatment of ES; however, their pulse pressure differences decreased during continuous nonpulsatile flow perfusion, while their blood lactate levels increased. Echocardiography examinations detected flat and low
ACCEPTED MANUSCRIPT amplitudes in movements of the left ventricular wall and ventricular septum, accompanied by decreases in LVEF and no significant changes in myocardial
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enzymes. V-A ECMO support and IABP supplementation were used to steadily elevate the afterload and LVEF. The clinical manifestations in these three FM patients
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suggested myocardial stunning (Figure 3).
Two patients (No. 4, 5) who had been maintained with ECMO support for 57.50
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± 17.68 h were found to have decreased pulse pressure differences. Echocardiography examinations helped to rule out hydropericardium, but indicated enlargement of the left ventricle, and decreased diffuse movement of the left ventricular wall of each
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patient, accompanied by a significant decrease in LVEF. Chest films suggested
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increased effusion in the lungs. When taken together, these manifestations strongly indicated a decline in left ventricular function caused by ECMO support (Table 3).
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These patients received metoprolol (12.5 mg, bid, via nasal feeding) to adjust their
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activated clotting times (ACTs) to 220-240 s; after which they showed increased LVEF, a steady decrease in lung effusion, and no relapse of ventricular tachycardia or ventricular fibrillation. Both patients were withdrawn form ECMO support (148 h ECMO for No. 4, 187 h ECMO for No. 5) and discharged without complications. During their respective followup visits, the two patients exhibited normal heart chambers, normal cardiac valve function, normal intelligence, and showed no evidence of ES relapse. Additionally, both patients showed a LVEF > 65%.
ACCEPTED MANUSCRIPT Discussion
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Here, we reported three cases of ES in five FM patients treated by ECMO. These
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cases highlight the need to be aware of inadequate LV unloading and reduced myocardial contractility during the peak phase of myocardial edema. Oda et al (19)
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reported a case of ES which occurred during V-V ECMO support of a child diagnosed
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as myocarditis. Interestingly, both cardioversion and medication were ineffective in treating the electrical storm, while a switch from V-V ECMO to V-A ECMO successfully maintained systemic flow, and terminated the ES (19). To the best of our knowledge, that was the first report of ES occurring during V-A ECMO support of an
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FM patient.
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Although FM is associated with rapid circulatory collapse and a high mortality
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rate, patients may have an excellent recovery if they are aggressively supported in a timely manner (5). Maximum pharmacologic therapy may not be effective in some
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cases, and a clinical strategy employing optimal mechanical circulatory support (e.g., ECMO) may be the treatment of last resort to save a critically ill patient. Additionally, an FM patient who receives full supportive care often benefits from significant improvement in their left ventricular function (4). Because FM is potentially reversible, it is reasonable to deploy ECMO to bridge patients until recovery or transplantation (20). ECMO support provides sufficient coronary perfusion for myocardium as well as adequate blood and oxygen for other important organs. These effects create favorable conditions for recovery of injured cells, including myocardial cells. Compared to use of a ventricular assist device (VAD), ECMO has advantages of
ACCEPTED MANUSCRIPT fewer complications, easier application, and the ability to provide biventricular support. It has therefore been considered as the first-line mechanical support treatment
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for FM complicated with profound shock, when intra-aortic balloon pumping is inadequate or infeasible (21).
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It is extremely important to maintain an optimal balance between flow support and left ventricular (LV) afterload when employing ECMO in support of FM patients
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(6). The drawback of ECMO is that it may not adequately alleviate left ventricular (LV) afterload, and thus increase LV wall stress and pressurize the systemic arterial circuit. In the absence of adequate left atrial decompression, the compromised LV
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may lack sufficient contractility to open the aortic valve, resulting in elevated LV
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cavity pressure, pulmonary venous hypertension, pulmonary vascular injury, and acute respiratory distress syndrome (22). As a result, ECMO has been associated with
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both patient and mechanical complications; including stroke (8%), brain death (6%),
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hemorrhage (cannula, 27%; pulmonary, 10%), infection (15%), and a need for dialysis (16%) (23). Therefore, in actual clinical practice, a maximum ECMO flow should not be maintained because the resulting high afterload may further aggravate an already severely deteriorated heart. In our cases, we continued to regulate ECMO flow to rates of 80-100 mL/kg to 70 mL/kg, and 20 mL/kg (1L/min), based on the progress of the disease. The correlation between ES and ECMO support is unclear and complicated. All five cases in our study showed inadequate LV unloading and significantly reduced myocardial contractility. These problems became especially obvious after 24 h of
ACCEPTED MANUSCRIPT ECMO support, which correlated with the peak period of myocardial injury and edema. On the other hand, ECMO support is a supplementary approach and has no
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direct therapeutic effect on the infective virus or the patient’s autoimmune response; therefore, myocardial injury and edema are not avoided. Moreover, an increase in LV
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afterload resulting from ECMO plus myocardial diffuse edema may subsequently contribute to excessive myocardial tensile strength and remodeling (24). Heart failure
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and myocardial remodeling can alter myocardial ion channels, increase dispersion of repolarization, increase the autorhythmicity of Purkinje fibers, and create new electrical circuits. Such pathological changes in electrophysiology tend to trigger
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receiving ECMO support.
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ventricular tachycardia and fibrillation, which may be precursors of ES in FM patients
The current drugs used to treat ES are often prescribed empirically and
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demonstrate moderate efficacy. Most drug treatment strategies seek to produce a
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sympathetic blockade by use of a β-blocker, or induce left stellate ganglion denervation (25). Arya et al (26) reported that β-blockers and angiotensin-converting enzyme (ACE) inhibitors could reduce ES severity in patients with an implantable cardioverter defibrillator (ICD). Similarly, Flores-Ocampo et al (27) found that failure to include treatment with β-receptor blockers was a strong predictor for ES in ICD patients. Accordingly, our study indicated that β-blockers might help prevent ES in FM patients receiving ECMO support. In our study, three patients (No. 1, 2, 3) experienced ES while receiving ECMO support, while ES did not occur in the remaining two patients (No. 4, 5), who were treated with only amiodarone and
ACCEPTED MANUSCRIPT metoprolol. These results suggest β-receptor blockers as a therapeutic choice to prevent myocardial remodeling and ES in patients receiving ECMO support. This
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may especially apply when treating ES in patients with inadequate LV unloading and significantly reduced myocardial contractility.
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An organized approach for managing ES, including pharmacological and/or non-pharmacological interventions, has been previously proposed (28). We found that
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the urgent and timely use of drugs and electric cardioversion can terminate ES in FM patients receiving ECMO support. Additionally, the pulsatile blood flow produced by an IABP can effectively reduce LV afterload, resulting in increased myocardial
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oxygen supply (22). Adequate myocardial unloading and improved myocardial
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metabolism would certainly reduce a patient’s risk for ES. Therefore, we believe that
myocardium.
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combined use of an IABP and ECMO would greatly benefit the recovery of stunned
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In conclusion, physicians need to be aware of the risk for ES in FM patients receiving V-A ECMO support, and especially in patients who exhibit inadequate LV unloading and reduced myocardial contractility during the peak phase of myocardial edema. Moreover, we found that β-receptor blockers might help prevent ES in FM patients receiving V-A ECMO support, and that pulsatile perfusion by an IABP facilitated myocardial unloading in seriously ill patients. Nevertheless, this was a single center study, which included a small number of patients. Large multicenter studies are required to verify our findings.
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ACKNOWLEDGEMENT
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We thank Medjaden Bioscience Limited for assisting in the preparation of this
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manuscript
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Figure Legends Figure 1. Electrocardiograms of three fulminant myocarditis patients (No. 1, 2, 3)
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prior to electrical storm. A: Patient No.1, sinus tachycardia; B: Patient No. 2, sinus tachycardia, complete right bundle branch block; C: Patient No. 3, sinus tachycardia,
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complete atrioventricular block, accelerated idioventricular rhythm.
Figure 2. Electrical storm in three fulminant myocarditis patients during
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venous-arterial extracorporeal membrane oxygenation support. A: No. 1; B: No. 2; C: No. 3.
Figure 3. Echocardiography of cardiac stunning after an electrical storm within the
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preceding 24 hours.
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3
CR I
4
5
Female
Male
Male
21
18
21
3.00
7
5
Bidirectional ventricular
Sinus tachycardia,
Sinus tachycardia;
onal tachycardia;
tachycardia;
V1-V3 ST segment
Complete atrioventricular
tachycardia;
Endotracheal
Endotracheal intubation;
elevation; Endotracheal
block; Accelerated
Endotracheal intubation
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Table 1. Clinical characteristics of five patients with fulminant myocarditis.
intubation
Hemopurification
intubation
idioventricular rhythm;
Sinus tachycardia;
Sinus tachycardia;
1
2
Gender
Male
Female
Year (y)
12
25
4.00
2.00
Admission to
Sinus tachycardia;
Atrioventricular juncti
intensive care
Paroxysmal ventricular
unit
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No.
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Prodromal
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TE
D
phase (d)
Endotracheal intubation
ECMO
Sinus tachycardia;
support
Atrioventricular
Complete
interference dissociation;
atrioventricular block
block; Ventricular
Bidirectional ventricular
Accelerated
escape-ventricular
tachycardia
idioventricular
premature beat bigeminy
Sudden cardiac arrest;
Sudden cardiac arrest;
Complete atrioventricular external cardiopulmonary external cardiopulmonary resuscitation
resuscitation
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rhythm;
CR I
Duration
84.20
95.50
0.50
Dopamine (15.00) +
Dopamine (20.00) +
Adrenaline (2.00)
Adrenaline (2.00)
dobutamine (30.00)
dobutamine (40.00) +
hospital
31.00
30.50
Vasoactive
Dopamine (20.00) +
drugs
dobutamine (40.00)
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between
admission and
TE
D
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ECMO (h)
400.00
179.00
185.00
172.00
2780.00
CK (U/L)
997.00
235.00
704.00
165.00
1294.00
CK-MB（U/L）
42.00
99.00
56.00
24.00
205.00
TNI (ug/L)
42.10
12.70
12.40
0.90
43.90
LDH (U/L)
620.00
403.00
560.00
283.00
4700.00
Cr (ummol/L)
92.00
169.00
191.00
164.00
242.00
Lac (mmol/L)
3.90
7.10
5.20
2.90
13.10
Cardiothoracic
0.45
0.42
0.52
0.42
0.40
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AST (U/L)
adrenaline (2.00)
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(ug/kg/min)
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TE
D
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NU S
CR I
0.28
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0.33
AC
LVEF
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ratio
－
－
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Table 2. Clinical characteristics of three fulminant myocarditis patients who experienced electrical storm. 1
Duration between hospital
3.50
2
3
3.00
9.50
28.00
134.00
Dopamine (3.00) + nitroglycerin (1.0)
Dopamine (3.00) + nitroglycerin (0.5)
CR I
No.
NU S
admission and electrical storm (d) 38.00
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Duration between ECMO and electrical storm (d)
Dopamine (3.00) + nitroglycerin (0.8)
D
Vasoactive agent
TE
(ug/kg/min)
Pre-
Storming
24-48 h later
Pre-
Storming
24-48 h later
95/
95/
97/
105/
90/
103/
90/
70/
78/
92/
78/
76/
103/
69/
78
84
94
87
80
103
76
330.00
330.00
120.00
118.00
117.00
133.00
141.00
126.00
285.00
247.00
139.00
183.00
144.00
141.00
98.00
98.00
78.00
CK-MB（U/L）
16.00
11.00
10.00
19.00
19.00
14.00
5.00
10.00
3.00
TNI (ug/L)
2.21
2.44
2.03
1.70
1.34
1.19
0.53
0.67
0.57
Storming
Systolic pressure /
98/
86/
Diastolic pressure /
78/
80/
Blood pressure (mmHg)
85
83
AST (U/L)
320.00
CK (U/L)
24-48 h later
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Pre-
AC
Phase
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788.00
788.00
254.00
Lac (mmol/L)
1.50
4.50
2.00
0.97
K+ (mmol/L)
4.40
4.10
4.7O
4.20
LVEF
0.36
0.27
0.40
0.40
NU S MA
D TE CE P AC
226.00
190.00
457.00
632.00
423.00
1.19
0.85
3.30
4.50
2.60
4.50
4.70
4.50
4.00
4.20
0.20
0.36
0.31
0.20
0.30
PT
689.00
CR I
LDH (U/L)
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Table 3. Clinical characteristics of two patients with minimum left ventricular ejection fraction (LVEF) 4
CR I
No.
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Duration between admission and LVEF 7.00 (d) 70.00
Vasoactive agent (ug/kg/min)
Dopamine (2.00) + nitroglycerin (1.2) 24 h previous
Minimum
24 h afterwards
2.50
45.00 Dopamine (1.00) + nitroglycerin (1.5) 24 h previous
Minimum LVEF
24 afterwards
D
Phase
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Duration between ECMO and LVEF (h)
5
104/
Diastolic pressure /
70/
Blood pressure (mmHg)
81
LVEF
0.29
98/
98/
90/
105/
84/
70/
73/
75/
79/
87
79
81
80
88
0.23
0.28
0.29
0.20
0.30
95/
AC
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Systolic pressure /
TE
LVEF
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Fig. 1
Fig. 2
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Fig. 3