Patient case: 32-year-old male with dilated cardiomyopathy; genetic feature: LMNA

Clinical trial: Reversible Pulmonary Artery Banding as Simplified Management of End-stage Dilated Left Ventriculopathy in Early Life

Summary: The purpose of this study is to: 1) Remodel and restore left ventricular geometry and function. 2) Avoid the need for mechanical circulatory support (MCS) and/or cardiac transplantation (CT). 3) Confirm the outcomes of a pilot study completed in Germany and reported in The Journal of Heart and Lung Transplantation in May 2013.

Detailed description: The study infant will undergo cardiac catheterization and myocardial biopsy before pulmonary artery banding and at appropriate intervals during follow-up surveillance by the interventional cardiologist. Patients will be "listed" for heart transplantation, and rPAB will be applied in lieu of mechanical circulatory support or as an alternative to already existing mechanical circulatory support, in the form of extracorporeal mechanical oxygen (ECMO). Myocardial biopsies will be flash frozen for storage and eventual probing for cell type (mature or stem) as part of a separate study.
  The addition of afterload rPAB to a normal-functioning right ventricle (in the setting of end-stage dilated cardiomyopathy) shifts the inter-ventricular septum toward the midline, thus significantly improving left ventricular geometry and function. It permits the infant or young child to operate from a much improved position on Starling's curve with gradual resolution of congestive heart failure and the potential for lethal ventricular dysrhythmia. An abundance of progenitor myocytes known to exist within the myocardium of this patient age group may then contribute to "permanent" left ventricular restoration.
  A sternotomy incision is used for application of the rPAB. The band is tightened under echocardiographic control until the inter-ventricular septum becomes a midline structure. Myocardial function is augmented with inotropic and vasodilator agents. These agents are weaned off gradually over a period of 2-4 weeks. The infant is separated from mechanical ventilation within the first post-rPAB week, and enteric feeding is resumed. The infant is discharged on oral medications, and is kept under frequent clinical surveillance.
  As the infant grows, the rPAB becomes relatively more obstructive to right ventricular outflow. Based on a finding of increasing right ventricular dilation, onset or worsening tricuspid valve regurgitation, or a gradual late increase in plasma B-type natriuretic peptide (BNP) levels, the band may be loosened in stages as a balloon catheter-based procedure. Band enlargement may be accomplished in stages, ultimately opting for a mild residual right ventricle-main pulmonary artery pressure gradient of 15-30 mmHg.
  The infants' short- and long-term surveillance will include clinical examination, height, weight, cardiac catheterization, electrocardiogram, echocardiogram, chest x-ray, and plasma BNP levels.

Eligibility: Inclusion Criteria:
  1. Age 0-4 years
  2. Isolated, idiopathic left-ventricular end-stage dilated cardiomyopathy or a Left Ventricular End-Diastolic Diameter (LVEDD) Z-score > 4.5; Ejection Fraction (EF) < 30%
  3. Acceptable candidate for mechanical circulatory support and/or cardiac transplantation
  4. Preserved right-ventricular function
  5. Clinical functional status IV (hospitalized)
  6. Parental consent
  Exclusion Criteria:
  1. Biventricular end-stage dilated cardiomyopathy
  2. Proven or suspected myocarditis
  3. Concomitant structural (congenital) heart disease
  4. Moderate-severe tricuspid valve regurgitation
  5. Pulmonary hypertension out of proportion with left-ventricular end-stage cardiomyopathy
  6. Hereditary disease associated with bi-ventricular dysfunction
  7. Age greater than 4 years
  8. No parental consent

Relevance to patient case: not relevant