Biventricular Assist Device Support for Intractable Arrhythmias From Histiocytoid Cardiomyopathy : ASAIO Journal

Secondary Logo

Journal Logo

Case Reports

Biventricular Assist Device Support for Intractable Arrhythmias From Histiocytoid Cardiomyopathy

Magnetta, Defne A.*; Reichhold, Allison*; Thrush, Philip T.*; Monge, Michael; Webster, Gregory*; Joong, Anna*

Author Information
doi: 10.1097/MAT.0000000000001715



A 13 month old 7 kg girl born at 27 weeks gestational age had known left ventricular (LV) noncompaction with preserved systolic function, a small secundum atrial septal defect, and chronic feeding intolerance requiring a gastrostomy tube. At home, she had 2 days of vomiting and pallor, progressing to lethargy. On arrival to the emergency department, her rhythm was an irregular narrow and wide-complex tachycardia with cycle lengths between 192 and 352 ms (an average of ~ 250 beats per minute during salvos of wide-complex tachycardia; Figure 1). She had poor peripheral perfusion and synchronized cardioversion was attempted with only brief sinus rhythm followed by recurrent tachyarrhythmia. A procainamide bolus and infusion produced chemical conversion to a slow atrial rhythm with Wenckebach conduction. Her perfusion improved in an atrial-driven rhythm.

Figure 1.:
Electrocardiogram demonstrating occasional sinus rhythm with intact atrioventricular conduction, predominantly irregular polymorphic tachycardia with an average rate of 300 beats per minute. aVR, aVL, and aVF are the limb leads of a standard electrocardiogram (along with leads I, II, and III). They stand for "augmented vector right/left/foot" respectively, but these terms are not commonly used in medical practice. Leads V1-V6 (seen on the right half of the ECG) are the precordial leads.

Despite management with multiple anti-arrhythmic medications, including amiodarone (maximum dose 14 mcg/kg/min), procainamide (maximum dose 60 mcg/kg/min), and esmolol (maximum dose 275 mcg/kg/min), rhythm control was transient with breakthrough paroxysmal atrial fibrillation, ventricular tachycardia (VT), and ventricular fibrillation (VF). She retained normal LV size (Figure 2) with mildly depressed systolic function (LV ejection fraction 54%) in sinus rhythm. Her ventricular arrhythmias were incessant and ultimately intractable to chemical and electrical cardioversion. Although we could obtain rate control and adequate perfusion with salvos of VT, sustained rhythm control was not achieved with anti-arrhythmic medications. A percutaneous stellate ganglion block1 was attempted to improve rhythm control, but there was only brief resolution of VT; therefore, biventricular assist device (BiVAD) implantation was pursued to provide adequate cardiac output in the setting of incessant arrhythmias as a bridge to transplantation (BTT).

Figure 2.:
Still images of the patient's echocardiogram on presentation to the cardiac intensive care unit. The echocardiogram demonstrated hypertrabeculated LV (arrows) with normal dimensions in the (A) apical and (B) parasternal long-axis views. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

The patient was initially cannulated onto PediMag BiVAD support (Thoratec Corp, Pleasanton, CA) using an LV-aorta and right atrial-pulmonary artery cannulation strategy. For both the atrial and arterial cannulation, 6 mm Berlin cannulas (Berlin Heart, Inc, The Woodlands, TX) were utilized, and 8 mm extension Dacron grafts were anastomosed to the arteriotomies. Although there was unobstructed left ventricular assist device (LVAD) inflow during VT/VF, her intracardiac wall motion changed during periods of sinus rhythm, creating inflow “suction events” (precipitous drop in flow with negative pressure due to myocardial tissue obstruction of the LVAD inflow cannula) that were refractory to fluid resuscitation or reduction in device speed. In the 24 hours following BiVAD placement, she had periods of asystole, during which LVAD flows were acceptable with evidence of good end-organ perfusion. During periods of sinus rhythm, LVAD flows continued to be difficult to maintain, and there was evidence of elevated central venous pressure, indicating ongoing LVAD inflow obstruction. Therefore, the patient returned to the operating room 6 days later for revision of the LV inflow cannula from an apical to atrial position. In the setting of a small left atrium, a 10 mm ringed Gore-Tex graft (W.L. Gore & Assoc, Flagstaff, AZ) was placed through the left atrial appendage and then connected to a 6 mm arterial Berlin cannula. With cannula repositioning, the suction events resolved and the patient was able to be transitioned from the PediMag to Berlin EXCOR (Berlin Heart Inc, The Woodlands, TX) 10 cc pumps 3 days later. As she was hemodynamically well supported, all anti-arrhythmic agents were discontinued and her rhythm alternated between sinus rhythm, asystole, and VT/VF throughout her BiVAD course. The unchanged arrhythmia burden on BiVAD support led us to conclude that her underlying histiocytoid cardiomyopathy (HICMP), rather than ventricular output/mechanics, was responsible for her arrhythmias. The Berlin EXCOR (Berlin Heart Inc) pumps combined with intrinsic cardiac function were successful at providing adequate cardiac output as evidenced by reassuring perfusion and end-organ function. Additionally, the pumps were susceptible to intermittent pauses (no fill/no eject) in sinus rhythm, which did not occur while in VT/VF (Supplemental Video, The etiology of these pauses differed from the suction events experienced while on PediMag support, as these were pauses in both fill and ejection (whereas suction typically impacts only fill). Thus, these pauses of the pump were felt to be due to competition from native ejection with preserved systolic function during sinus rhythm and fortunately caused no detriment to the patient.

Fibrin burden remained mild on a bivalirudin infusion (activated partial thromboplastin time goals 60–80) and aspirin 17 mg/kg/day (VerifyNow Aspirin result of 449), and she experienced no device-related complications. For the majority of her BiVAD course, she did not require supplemental oxygen or intravenous pharmacologic support of blood pressure or systolic function. She tolerated enteral nutrition. She made significant developmental progress while on the device, learning to crawl, cruise, stand, and take steps with assistance.

The patient had a normal microarray and pediatric cardiomyopathy panel (100 genes, July 2019; GeneDx Inc, Gaithersburg, MD). A myocardial excision from the LV during BiVAD implantation was diagnostic for HICMP, based on an increased size and number of mitochondria, intramitochondrial glycogen and lipid deposition, and vacuolated cristae (Figure 3). Skeletal muscle biopsy was inconclusive, with a mild increase in muscle fiber neutral lipid and increased size and irregular organization of cristae, but no other typical markers of mitochondrial disease. Given her comorbidities, whole exome trio sequencing (which includes analysis of patient and parental blood samples) was sent and returned with variants of unknown significance in two genes: reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 alpha (NDUFA1, de novo variant, heterozygous for p.A24TfsX23) and serine hydroxymethyltransferase-2 (SHMT2, compound heterozygous for p.Y130C and p.R209H). Mitochondrial genome was normal. As the patient did not exhibit other features of NDUFA1-related disorders, this was not felt to adequately explain her phenotype. SHMT2 was classified as a candidate gene associated with mitochondrial respiration defects with insufficient evidence to attribute this gene to the patient’s clinical presentation. Genetic counseling was provided with these results and included a discussion of the remaining uncertainty of her underlying genetic diagnosis.

Figure 3.:
Electron microscopy from myocardial biopsy taken at the time of VAD implantation confirmed HICMP, with increased size/number of mitochondria, intramitochondrial glycogen (†) and lipid (‡) deposition, and vacuolated cristae (§). VAD, ventricular assist device; HICMP, histiocytoid cardiomyopathy.

The patient was supported on mechanical support for a total of 205 days, after which she underwent successful heart transplantation. Her post-transplant course was uneventful, and she was discharged from the hospital 11 days postoperatively. She is now 10 months post-transplant with excellent graft function, somatic growth, and developmental progress.


HICMP is a rare mitochondrial cardiomyopathy associated with intractable, life-threatening ventricular arrhythmias. Additionally, a spectrum of cardiomyopathic phenotypes may be present, including ventricular dilation, hypertrophy, and noncompaction, with variable degrees of systolic dysfunction. There have been three case reports with a total of four patients who received heart transplants for HICMP, and all but one of these patients had severely depressed LV systolic function and advanced heart failure.1–3 One patient, with an left ventricular ejection fraction (LVEF) of 27%, demonstrated multiorgan failure necessitating extracorporeal membrane oxygenation and was ultimately transitioned to Berlin EXCOR (Berlin Heart Inc) LVAD as BTT. However, there have been no prior reports of intractable arrhythmias as an indication for biventricular mechanical support as BTT in this population. Current registry data acquisition does not capture exactly how many pediatric patients have undergone LVAD or BiVAD implantation for primary arrhythmia, although we believe this population to be very small.

Patients on BiVAD support, particularly smaller patients, have worse survival than those on LVAD support.4 However, this inferior survival is thought to be secondary to patient characteristics, rather than device factors.5 In the setting of frequent paroxysmal VT/VF and the risk of associated right ventricle (RV) failure, we chose biventricular mechanical support to bridge our patient to transplantation. In addition to her small size, nondilated LV cavity, and inconsistent rhythm, her prior gastrostomy tube placement dictated a more medial cannula exit site and may have contributed to unfavorable LV cannulation angle and suction events. Additionally, there have been reports of inflow cannula obstruction in patients with LV noncompaction secondary to prominent apical trabeculations, which may not be easily recognizable on cardiopulmonary bypass.6 These suction events resolved with revision to left atrial inflow cannulation, but pump fill and eject was still impacted by rhythm and native ejection.

Stroke complicates 12–30% of paracorporeal LVAD support in children.7–10 Efforts to reduce the incidence of stroke have centered around maintaining precise blood pressure parameters, optimizing the anticoagulation strategy (including avoiding stagnation of flow in the pump and monitoring fibrin/thrombus deposits closely), and clear communication between all team members.10 In line with these recommendations and per our institutional protocol, our patient was maintained on two anti-hypertensive medications with appropriate blood pressures as well as a bivalirudin infusion and therapeutic aspirin. With these maneuvers and despite intermittent pauses in the pump/fill eject, we did not observe any accelerated fibrin deposition or thrombosis over the >200 days of BiVAD support.

In summary, we present a case of HICMP where the arrhythmia burden and myocardial structure/function drove clinical care in three important ways. First, intractable, hemodynamically unstable arrhythmia was an indication for BiVAD and transplantation despite preserved ventricular function. Second, muscular configuration changes between sinus rhythm and ventricular arrhythmia impeded LVAD inflow with apical cannulation. Third, when cannula position was adjusted to avoid inflow occlusion, the combination of intact sinus rhythm and normal ventricular function caused device filling inefficiencies when physiologic ejection was robust. The combination of a nondilated noncompacted LV, preserved systolic function, and fluctuating heart rhythm made this case uniquely challenging and demanded advanced BiVAD management. Ultimately, careful consideration of all these factors yielded the hemodynamic stability necessary for this small child to wait over 6 months for a life-saving donor heart.


1. Boe BA, Webster G, Asher Y, Tsao S, Suresh S, Steinhorn DM: Percutaneous, ultrasound-guided stellate ganglion nerve block suppresses recurrent ventricular fibrillation in an infant awaiting heart transplant. Circ Arrhythm Electrophysiol. 5: e93–e94, 2012.
2. Zangwill SD, Trost BA, Zlotocha J, Tweddell JS, Jaquiss RD, Berger S: Orthotopic heart transplantation in a child with histiocytoid cardiomyopathy. J Heart Lung Transplant. 23: 902–904, 2004.
3. Siehr SL, Bernstein D, Yeh J, Berry GJ, Rosenthal DN, Hollander SA: Orthotopic heart transplantation in two infants with histiocytoid cardiomyopathy and left ventricular non-compaction. Pediatr Transplant. 17: E165–E167, 2013.
4. Zafar F, Jefferies JL, Tjossem CJ, et al.: Biventricular Berlin Heart EXCOR pediatric use across the United States. Ann Thorac Surg. 99: 1328–1334, 2015.
5. Baez Hernandez N, Kirk R, Sutcliffe D, et al.: Utilization and outcomes in biventricular assist device support in pediatrics. J Thorac Cardiovasc Surg. 160: 1301–1308.e2, 2020.
6. Kornberger A, Stock UA, Risteski P, Beiras Fernandez A: Left ventricular non-compaction cardiomyopathy and left ventricular assist device: A word of caution. J Cardiothorac Surg. 11: 108, 2016.
7. Jordan LC, Ichord RN, Reinhartz O, et al.: Neurological complications and outcomes in the Berlin Heart EXCOR® pediatric investigational device exemption trial. J Am Heart Assoc. 4: e001429, 2015.
8. Morales DLS, Adachi I, Peng DM, et al.; Pedimacs Investigators: Fourth annual pediatric interagency registry for mechanical circulatory support (Pedimacs) report. Ann Thorac Surg. 110: 1819–1831, 2020.
9. Zafar F, Conway J, Bleiweis MS, et al.; ACTION Learning Network Investigators: Berlin heart EXCOR and ACTION post-approval surveillance study report. J Heart Lung Transplant. 40: 251–259, 2021.
10. Villa CR, VanderPluym CJ; ACTION Investigators*: ABCs of stroke prevention: Improving stroke outcomes in children supported with a ventricular assist device in a quality improvement network. Circ Cardiovasc Qual Outcomes. 13: e006663, 2020.

arrhythmia; biventricular assist device; cannulation strategy; histiocytoid cardiomyopathy; pediatric

Supplemental Digital Content

Copyright © ASAIO 2022