CPC #6  17yr female 2 years s/p orthotopic heart transplant  New onset SOB, chest pain, incontinence, weakness of arms and legs  Decreased ventricular function  Normal troponin I on admission  Elevated pro-BNP

Ventricular Dysfunction s/p Heart Transplantation  Early graft dysfunction  Late graft dysfunction

Early Graft Dysfunction  Hyperacute rejection  Reperfusion injury  Suboptimal donor

Late Graft dysfunction (our differential diagnosis)  Original disease process  Myocarditis  Humoral rejection  Cellular rejection  Acclerated graft atherosclerosis

Dextrocardia with situs inversus  Congenital heart disease incidence similar to that of the general population  “He does not seem to be left handed more than his fellows. He is apt to live his life unmarked by any peculiarity and die of the same disease that carry off the rest of mankind……” Cleveland 1926

Dextrocardia with situs inversus  Biliary atresia  Kartagener syndrome

Mirror Image Dextrocardia

Polysplenia  Multiple small spleens –frequently functionally asplenia  More commonly seen in patients with heterotaxy (i.e dextrocardia with situs solitus) than dextrocardia with situs inversus

Recurrence of original disease  Amyloidosis  Sarcoidosis  Hereditary hemochromatosis

Our Differential Diagnosis  X -Recurrence of original disease process  Myocarditis  Humoral rejection  Cellular rejection  Accelerated graft atherosclerosis

Myocarditis in Pediatric Heart Transplants  Viruses –CMV,EBV, varicella-zoster, respiratory viruses, herpes simplex  Bacteria – mycobacteria, gram positive, gram negative  Toxoplasmosis  Pneumocystis

Myocarditis in our patient-unlikely  No viral prodrome  Afebrile  WBC 8500  Troponin I <0.06  Not found on biopsy  Does have a history of CMV  Is sexually active  No longer on Bactrim prophylaxis

Myocarditis-treatment  IVIG  Antivirals/antibiotics  Support

Our differential diagnosis  X-Original disease process  X-Myocarditis  Humoral rejection  Cellular rejection  Accelerated graft atherosclerosis

Humoral rejection  Antibody directed against donor antigens located on the endothelial surface of the allograft coronary microvasculature

Humoral rejection  More common early after transplant but has been reported late  More common in a sensitized patient

Humoral rejection Treatment  Plasmapheresis  Cytogam

Our differential diagnosis  X-Original disease process  X-Myocarditis  X-Humoral rejection  Cellular rejection  Accelerated graft atherosclerosis

Cellular rejection  Mononuclear inflammatory response, predominantly lymphocytic, directed against the cardiac allograft

ISHLT Biopsy Grades

Cellular Rejection- treatment 1R- no treatment 2R-steriod bolus 3R-steriods and antithymocyte globulin

Cellular rejection Clinical manifestations  Constitutional symptoms- malaise,fever,myalgias, flu-like symptoms  Cardiac irritation-rub, arrhythmia  Symptoms of low cardiac output- dyspnea,syncope,orthopnea

Cellular rejection in our patient- possible  Shortness of breath  Tachycardia  Initially hypertensive then hypotensive  Not seen on biopsy but this does not eliminate it entirely  Risk factors-female,teenager,CMV, African-American,?induction

Our differential diagnosis  X-Original disease  X-Myocarditis  X-Humoral rejection  ?-Cellular rejection  Accelerated graft atherosclerosis

Accelerated Graft Atherosclerosis  Concentric narrowing or focal obstruction of the coronary arteries in the transplanted heart  Leading cause of death in long term follow up  Progression very variable

Accelerated Graft Atherosclerosis- detected by coronary angiography  10% during first year  20% by the second year  50% by the fifth year (only 10% severe enough to cause graft loss)

Accelerated Graft atherosclerosis by IVUS  25% by 1 year by single vessel IVUS;60% by 3 vessel IVUS  40% by 3 years by single vessel IVUS;70% by 3 vessel IVUS

Risk factors for AGA  Rejection  CMV  Black recipient  Male donor  Older recipient or donor

Clinical presentation  Discovered on routine surveillance  Acute onset heart failure  Arrhythmias  Syncope  Dyspnea  Anginal-like chest pain uncommon  Abdominal pain

Our patient  African American  History CMV  Dyspnea  Abdominal pain/chest pain  Borderline ecg  Troponin I <0.06 on admission

Rejection vs Infarction  Acute episode on floor- normal troponin I on admission  No significant cellular rejection on biopsy  Chest pain/ jaw pain

Diagnosis  Accelerated graft atherosclerosis with acute infarction