Shortness of breath

The patient is a 73-year-old African American woman with rheumatoid arthritis, ANA-positivity, hypertension, dyslipidemia, diabetes mellitus, and interstitial lung disease admitted to Johns Hopkins Hospital with worsening shortness of breath.

Over the last eleven years, the patient's rheumatologic disease was described to be unchanged and quiescent. She had occasional episodes of synovitis, particularly in the right wrist that were treated with NSAID medications. There were no changes in her medical regimen recently. Prior to plaquenil, the patient had been on methotrexate, which was discontinued 10 years ago. It was around that time that she had developed radiographic interstitial lung disease, and it was unclear whether it was related to methotrexate treatment or her underlying disease. She never had a lung biopsy or bronchoscopy.

Her last pulmonary function tests two years ago demonstrated:

FEV1	1.1 L	(48%)
FVC	1.5 L	(48%)
TLC	3.1 L	(61%)
FRC	2.1 L	(65%)
DLCO	11.9	(65%)

The patient reports that prior to the recent worsening, her respiratory status was unchanged. She has dyspnea on exertion with 1-2 flights of stairs. She has no history of hypoxemia at rest. The patient described experiencing palpitations up to three times weekly that had worsened recently. A transthoracic echocardiogram 6 months prior to admission revealed an ejection fraction of 35-40% with global hypokinesis of the left ventricle and a RVSP of 42 mmHg. There were no focal wall motion deficits.

The patient presented to The Johns Hopkins Hospital Emergency Department with the chief complaint of increasing shortness of breath over the course of three weeks. She now was unable to climb stairs without dyspnea, and had shortness of breath at rest. She also noted a non-productive cough with subjective fevers. There was no wheezing. The dyspnea was not accompanied by any chest pain. She complained of worsening orthopnea but no paroxysmal nocturnal dyspnea. She also reported intermittent nausea and vomiting over the last three weeks. There was no melena, hematemesis, or abdominal pain.

Rheumatoid arthritis; Interstitial lung disease; Diabetes mellitus; Hypertension; Glaucoma; Cerebrovascular accident 12 years ago.

Negative for rheumatologic disease, otherwise non-contributory.

The patient is a retired, divorced mother living in her own home. Social support includes a daughter who lives nearby. While the patient stopped smoking 12 years ago, she has an 80-pack-year history of smoking. The patient denies ethanol or illicit drug use.

Lipitor, Metformin, Plaquenil 400 mg daily, hydrochlorothiazide, verapamil, aspirin, potassium, Timolol eye drops

No known drug allergies

Mild rhinorrhea x 2-3 weeks, 25 lb weight loss over 3 months.

• VS: Weight: 70.4 kg T: 96.2 BP: 146/82 HR: 62 RR 20
• General: African American female consistent with stated age. AAO x 3. No acute distress.
• HEENT: Sclera anicteric. EOM intact. Mucous membranes moist, oropharynx clear.
• Neck: Soft, supple. No lymphadenopathy. JVP 12 cm at 45 degrees.
• CV: RRR S1S2, +S3, no S4, no murmurs
• Lungs: Inspiratory crackles anterior and posterior, three-quarters up the lung fields, no wheezing. No accessory muscle use.
• Abdomen: Normoactive bowel sounds. Soft non-tender, non-distended
• Extremities: No LE edema.

• Na 138; K 3.5; Cl 98; BUN 21; Cr 1.1; Glucose 79; Calcium 10; TP 7.9; Albumin 4; TBili 1.9; AST 68; ALT 25; Alk Phos 100
• WBC 7.1; RBC 4.63; Hemoglobin 14.1; Hct 42.1; MCV 90.9; Platelet 370
• Pro-BNP 7371

• Chest X-ray (on admission): Increased lung markings both lower lobes compatible with interstitial edema or fibrosis. Cardiomegaly [Image 1 (frontal) and Image 2 (lateral)].

One day after admission: Sinus bradycardia, biatrial enlargement, rightward axis, cannot rule out anterior infarct (age undetermined), prolonged QT interval or TU fusion.

Workup in the emergency department included a chest radiograph with increased lung markings, suggestive of edema or fibrosis (see above). Laboratory studies demonstrated cardiac enzymes negative for myocardial infarction. A pro-BNP was 7371. The patient was admitted to a monitored medical floor for an exacerbation of congestive heart failure. Approximately 8 hours later, the patient had an episode of atrial fibrillation with left bundle branch block followed by asystolic cardiac arrest. Initially, the patient was resuscitated using CPR and three rounds of epinephrine. She was subsequently transferred to the critical care unit where she had another episode of asystole requiring transcutaneous pacing. The patient was taken emergently to the cardiac catheterization laboratory where a transvenous pacemaker wire was placed. Additionally, an intraaortic balloon pump was inserted. Coronary angiography at the time showed non-critical disease. The patient had progressive and irreversible cardiogenic shock, despite pressor and intraaortic balloon pump support. Over the next few hours, she developed multi-system organ failure and disseminated intravascular coagulation, and subsequently died approximately 45 hours after presenting to the emergency department.

What is in the differential diagnosis of this patient's dyspnea?
What is the most likely cause of her recent clinical deterioration and her cardiac demise?