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Cardiac Recovery: The Best of Times, the Worst of Times


Scott R. Auerbach, MD
Medical Director of Ventricular Assist Device Program
Children's Hospital of Colorado
Aurora, CO, USA
scott.auerbach@childrenscolorado.org

Melanie D. Everitt, MD
Medical Director of Cardiac Transplantation Program
Primary Children's Hospital
Salt Lake City, UT, USA
mdeverit@gmail.com



A Tale of Two Cities comes to mind when I think of 2 recent patients and their potential for cardiac recovery. Both teenagers presented acutely with dilated cardiomyopathy and decompensated heart failure. Both patients were scheduled for elective VAD implant due to progressive deterioration on intravenous inotrope support. "Ana" received an acceptable donor organ 24 hours prior to the scheduled VAD implant. Ana's graft functioned well initially. "Jonathon" deteriorated precipitously prior to the elective VAD and suffered neurologic injury while undergoing VAD implant emergently.

Their stories continue. Ana developed antibody-mediated rejection due to a non-HLA antibody. She died 6 months post-transplant from systemic Aspergillus, a result of aggressive immune suppression to treat the rejection. Perhaps VAD implant prior to heart transplant and a watchful eye for ventricular recovery would have benefited Ana. Jonathon had myocardial recovery despite a diagnosis of familial dilated cardiomyopathy. His VAD was explanted 6 months after initial implant. Unfortunately, the heart failure recurred, and he suffered an additional neurologic insult at the time of the recurrence. Both stories illustrate "the best of times, the worst of times". Both stories leave questions regarding myocardial recovery.

Much has been written about myocardial recovery in the adult literature [1-7]. There is comparatively sparse literature pertaining to recovery in pediatric heart failure [8-9]. How does medical therapy or device therapy impact myocardial recovery in pediatric heart failure? Additionally, is recovery simply a matter of allowing time for recovery to occur in select children? We are likely to identify and treat myocardial insults that lead to heart failure, such as neurohormonal activation, inflammation, hemodynamic derangements such as pressure or volume overload, toxic insults, or myocyte energy impairment. However, identifying who will recover myocardial function long-term or permanently remains an enormous challenge. Are there biochemical markers we can use to predict recovery at diagnosis and/or during medical or device therapy?

Identifying children with the potential for myocardial recovery and supporting the heart to allow for (or even promote) recovery are important topics. Thus far, the durability and safety profile of early generation VADs and the lack of VAD experience at pediatric centers have limited the recommendation for LVAD placement with the intent of supporting a patient through a trial of myocardial recovery (10-11). If an LVAD were to be placed in a patient that was stable on inotropic support and recovery did not occur, LVAD placement could result in significant morbidity or lead to HLA sensitization and potentially worse pre-transplant outcomes. However, devices have improved and results continue to improve as experience is gained. That being said, germane to the topic of VAD placement for myocardial recovery is whether or not destination therapy is an acceptable option for children and young adults who are supported by a VAD but are not a candidate for heart transplant or do not want transplant. This is an important question to answer for children before one advocates for device therapy in an attempt to promote recovery.

How do we define "success" in myocardial recovery with respect to cardiac function and duration of improvement? To date, recovery has been defined in many different ways, including echocardiographic normalization, myocardial recovery, and heart failure remission. To measure cardiac recovery, we need to agree upon a definition of success including end points and duration.

This brings us to a third patient, "Mike". Mike required LVAD placement for acute anthracycline toxicity and inability to wean inotropic support. Seven months post continuous flow LVAD placement, he has shown evidence of myocardial recovery. An exercise test on full LVAD support reported a VO2 indexed of 25 ml/kg/min. An echocardiogram (LVAD turned down to lowest setting) showed low normal qualitative biventricular function with a 6 minute walk of 546 meters. After 4 weeks of decreased LVAD support (LVAD flow average of 1.5L/min) the qualitative echocardiographic function of both his right and left ventricles were mildly depressed, the BNP level increased from 158 to 723. His peak VO2 indexed went from 25 ml/kg/min on full support to 20 ml/kg/min. Clearly these findings raise concern for long term sustained myocardial recovery and many questions arise. What biomarker can best predict success or failure of LVAD explantation? Will unloading the ventricle for a longer period of time promote recovery or has the ability of mechanical support to promote recovery already run its course? Are the currently available adult LVAD weaning protocols predictive of sustained recovery and can they be applied to pediatric patients?

Steps toward understanding cardiac recovery:

  1. Routine, serial assessment for myocardial recovery as part of heart failure management for patients supported by VAD (12).
  2. Innovation of therapies that may uniquely benefit pediatric heart failure rather than extrapolation of adult trials and therapies (13).
  3. Opportunities for discussion and debate on myocardial recovery including thorough review of the success stories, the recurrences, and the treatment failures.
  4. Participation in multi-center studies and registries to find predictors for recovery and indicators of recurrence.
  5. Use of tissue and blood banking studies to better understand recovery on the biochemical, cellular, and molecular level in pediatric heart failure.

To close with another quote by Charles Dickens from A Tale of Two Cities:

"A wonderful fact to reflect upon, that every human creature is constituted to be a profound secret and mystery to every other."

Myocardial recovery may seem a "profound secret and mystery" at present, particularly in children with idiopathic, familial, or other "non-acute" causes of heart failure. Nevertheless, it is worth our effort to study myocardial recovery, look for recovery in children with heart failure, and to identify therapies that promote recovery. One of the best rewards in clinical practice is caring for the child with decompensated heart failure who experiences recovery. ■

Disclosure Statement: Melanie Everitt has no disclosures to report. Scott Auerbach accepted travel funds from HeartWare to attending a training session.


References:

  1. Birks EJ, Tansley PD, Hardy J, et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med 2006:355:1873-84.
  2. Dandel M, Weng Y, Siniawski H, et al. Prediction of cardiac stability after weaning from left ventricular assistance in patients with idiopathic dilated cardiomyopathy. Circulation 2008;1881:S94-S105.
  3. Moon J, Ko Y-G, Chung N, et al. Recovery and recurrence of left ventricular systolic dysfunction in patients with idiopathic dilated cardiomyopathy. Can J Cardiol 2009;25:e147-e150.
  4. Birks EJ, George RS, Hedger M, et al. Reversal of severe heart failure with a continuous-flow left ventricular assist device and pharmacological therapy: a prospective study. Circulation 2011;123:381-90.
  5. Krabatsch T, Schweiger M, Dandel M, et al. Is bridge to recovery more likely with pulsatile left ventricular assist devices than with nonpulsatile flow system? Ann Thorac Surg 2011;91:1335-41.
  6. Basuray A, French B, Ky B, et al. Heart failure with recovered ejection fraction: clinical description, biomarkers, and outcomes. Circulation 2014;129:2380-87.
  7. Segura AM, Dris L, Massin EK, et al. Heart failure in remission for more than 13 years. Tex Heart Inst J 2014:41(4):389-94.
  8. Alexander P, Daubeney P, Nugent A, et al. Long-term outcomes of dilated cardiomyopathy diagnosed during childhood: results from the national population-based study of childhood cardiomyopathy. Circulation 2013;128:2039-46.
  9. Everitt MD, Sleeper LA, Lu M, et al. Recovery of echocardiographic function in children with idiopathic dilated cardiomyopathy: results from the pediatric cardiomyopathy registry. J Am Coll Cardiol 2014;63:1405-13.
  10. Holman WL, Naftel DC, Eckert CE, et al. Durability of left ventricular assist devices: Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) 2006 to 2011. J Thorac Cardiovasc Surg 2013;146:437-41.
  11. Almond CS, Morales DL, Blackstone EH, et al. Berlin Heart EXCOR pediatric ventricular assist device for bridge to heart transplantation in US children. Circulation 2013;127:1702-11.
  12. Kirk R, Dipchand AI, Rosenthal DN, et al. The International Society of Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: Executive summary. J Heart Lung Transplant 2014;33:888-909.
  13. Schranz D, Rupp S, Muller M, et al. Pulmonary artery banding in infants and young children with left ventricular dilated cardiomyopathy: A novel therapeutic strategy before heart transplantation. J Heart Lung Transplant 2013;32:475-81.



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