Shortness of breath, chest pain, incontinence, weakness/parasthesias of arms and legs

The patient is a 17 year-old African-American female with a history of congenital biliary atresia, situs inversus totalis, and polysplenia syndrome. At age 2 years she underwent liver transplantion. As a child she was diagnosed with a dilated cardiomyopathy of uncertain etiology.

Because of worsening cardiac function despite medical therapy, at age 15 years she received a cardiac transplant. She has been hospitalized multiple times since then for management of infections secondary to post-transplant immunosuppression.

The patient was in her usual state of health until the morning of admission when she experienced incontinence, and weakness and tingling in the arms and legs. She denied syncope, slurred speech, or gait disturbance. She arrived at the emergency room where she was found to be short of breath and tachycardic with muffled heart sounds. Emergency room work-up included ECG showing borderline changes and chest x-ray showing mildly enlarged heart and left lower lobe atelectasis.

Cardiac rejection was suspected. Echocardiography showed depressed ventricular function and moderate tricuspid valve regurgitation. She was taken for cardiac catheterization and endomyocardial biopsy. Following this, she was given pulse dose solumedrol and admitted to the floor.

Congenital - Situs inversus with dextrocardia (situs inversus totalis) and associated polysplenia syndrome
Liver - Biliary atresia diagnosed at 1 month of age; unsuccessful Kasai procedure at 3 months of age; orthotopic liver transplant at age 2; multiple hospitalizations for elevated liver function tests, fevers, epigastric pain
Heart - Dilated cardiomyopathy diagnosed at 1 year of age; orthotopic heart transplant at age 15; superior vena cava stent at age 16; persistent mild acute cellular rejection (International Society of Heart and Lung Transplant [ISHLT] grade 1A) on multiple cardiac biopsies
Iatrogenic - Several problems felt related to chronic immunosuppressive/steroid use including avascular necrosis of hip and feet (surgically treated at age 15), chronic renal insufficiency, hypertension, secondary hyperparathyroidism, chronic CMV infection, Shigella gastroenteritis

See above

Non-contributory

The patient is currently in the eleventh grade and is being home-schooled. She denies drug or alcohol use. She has been recently sexually active.

Tacrolimus 1 mg QD
Mycophenolate mofetil 250 mg BID
Prednisone 10 mg QD
Enalapril 5 mg QD
Sodium bicarbonate
Iron
Vitamin D
Caltrate

NKDA

See HPI/PMH

• Vital signs: T = 36.2, HR=133, RR=22, BP=132/91
• Head and Neck: Neck supple, mild Cushingoid appearance, no other abnormalities
• Lungs: Decreased breath sounds at left base, no crackles or wheezes.
• Cardiovascular: Tachycardic with muffled heart sounds. No murmurs, rubs, or gallops heard.
• Abdomen: Surgical scars. Bowel sounds present.
• Extremities: Normal.
• Neuro: CN II-XII intact, strength 5/5 in all major muscle groups, no paresthesias identified

Na 136, K 5.8, HCO3 18, Cl 106, BUN 56, creatinine 2.5, glucose 1.7, ALT/AST 50/39, Alk Phos 108, Troponin I <0.06, HCG neg, Pro-BNP 7255, Tacrolimus 4.7, WBC 8500, Hct 35%, Plt 235, 000. Arterial blood gas: 7.39/33/54.

Image 1: Age 15, prior to heart transplant: Dextrocardia and right-sided stomach. Pacemaker in place.
Image 2: Age 15, 1 week post-transplant: Note NG tube in right-sided stomach, heart situs now normal.
Image 3: Age 16, clinical follow-up: Transplant normal in appearance, normal lungs.
Image 4: Age 17, 1 month prior to death: clinical follow - up, stable.
Image 5: Age 17, in PICU, immediately prior to death.

Initial cardiac biopsy did not show increased cellular rejection, though it did show changes suggestive of ischemic injury or humoral rejection. Cardiac catheterization showed severely elevated right atrial pressure and a moderately elevated pulmonary capillary wedge pressure. Overnight on the floor, the patient developed increased shortness of breath, hypoxia, and hypotension. She was found unresponsive the next morning but was eventually aroused with complaints of chest and jaw pain. After transfer to the PICU, a second cardiac biopsy was performed, this time demonstrating humoral rejection per immunofluoresence. Over the following day the patient's respiratory status continued to worsen, eventually requiring intubation. Complicating her respiratory statues was the development of methemoglobinemia of unclear origin, treated with methylene blue. The next morning she again became hypotensive and twice went into cardiac arrest, both times quickly revived with CPR and epinephrine. An echocardiogram revealed severe left ventricular dysfunction. ECMO was suggested but declined. Resuscitation was initiated for a third cardiac arrest but was withdrawn at the mother's request and the patient expired.

What was the cause of the patient's left ventricular dysfunction?
What is the cause of the patient's demise?