Setting: office
CC: “I really get out of breath when I walk around.”
VS: BP: 114/72 mm Hg; P: 90 beats/minute; T: 99.8°F; R:14 breaths/minute
HPI: You are visited at your office by a 34-year-old woman with recently diagnosed CREST (calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia) syndrome and with increasing dyspnea especially on exertion that has been slowly progressive over several months. She originally presented last year with triphasic color changes and pain of Raynaud phenomenon. Nifedipine partially controls this. Her skin has been tightening up, but she is still mobile. Her reflux disease is well maintained on omeprazole. She has no cough, fever, or sputum.
PMHx/Medications: as above
PE:
General: thin woman
Chest: no rales; no crepitations; no dullness to percussion
Cardiovascular: loud P2, no murmur
Skin: immobile, sclerodactyly present; few telangiectasia
Initial Orders:
Chest x-ray
Echocardiogram
Oximeter
CBC
Report:
Oximeter: 91% to 92% saturation on room air
Because oxygen saturation is >90% on room air, you do not order supplemental oxygen. Clearly, the patient desaturates when walking around, as oxygen demand increases. Schedule a repeat visit in a few days after the test results are back.
What do you expect to find on the CBC?
a. Increased platelets
b. Hct increased, MCV decreased
c. Hct decreased, MCV decreased
d. Normal
e. WBC count increased
Answer b. Hct increased, MCV decreased
The body’s response to chronic hypoxia is to increase erythropoietin and red blood cell (RBC) production. This decreases MCV. Erythropoietin is produced at the kidney, which is also the site of detection of chronic hypoxia.
What is the physiologic mechanism of a loud P2?
a. Tricuspid stenosis
b. Pulmonic stenosis
c. Pulmonary hypertension
d. Aortic stenosis
e. Atrial septal defect
Answer c. Pulmonary hypertension
The P2 is the second part of the S2 heart sound. When there is pulmonary hypertension, the normal P2 becomes like a “slammed shut door,” and it is a sign of both increased pressure and decreased flow out of the pulmonary valve.
Reports:
Chest x-ray: enlarged right ventricle on lateral x-ray
Echocardiogram: pulmonary hypertension, increased right ventricular wall thickness, and right ventricular hypertrophy
What is the mechanism of pulmonary hypertension in this patient?
a. CREST causes primary pulmonary hypertension with normal lung parenchyma.
b. The patient has pulmonary fibrosis.
c. Hypoxia led to vasoconstriction of the pulmonary vasculature, which led to pulmonary hypertension.
d. Right-to-left shunting through a patent foramen ovale puts desaturated blood in the lungs.
e. Carbon dioxide retention makes the pulmonary vasculature dilate.
Answer a. CREST causes primary pulmonary hypertension with normal lung parenchyma.
CREST syndrome includes primary pulmonary hypertension. It is called “primary” entirely because the lung parenchyma is normal. Anyone with lung fibrosis or COPD has pulmonary hypertension from decreased compliance of the lung and the greater work of the right ventricle. Primary pulmonary hypertension leads to hypoxia. Hypoxia further constricts pulmonary vessels. The origin of the defect, however, is the idiopathic narrowing of the PA.
CREST Pulmonary Hypertension
• Excess prostacyclin
• Excess endothelin
The patient returns in 3 months feeling worsening dyspnea.
PE:
Abdomen: enlarged liver
Extremities: peripheral edema
Pulmonary Hypertension = Decreased RV Filling
Decreased RV Filling = Increased Hydrostatic Venous Pressure
Increased venous hydrostatic pressure transudates edema into tissues.
Orders:
Furosemide orally is started.
Over the next few weeks, the patient continues to have worsening dyspnea on exertion. Oxygen saturation hovers at 89% to 90%. Oxygen is started.
Oxygen vasodilates pulmonary vasculature.
Oxygen decreases pulmonary hypertension.
Progression of dyspnea continues. The patient feels fine at rest on oxygen but quickly desaturates on exertion. The repeat echocardiogram shows worsening PA pressure.
Orders:
Warfarin to INR 2 to 3
Pulmonary consultation
Evaluation for right-sided heart catheterization and vasoreactivity test
Trial of calcium channel blockers
Anticoagulation for:
• Sluggish blood flow +
• Intrapulmonary thrombosis +
• Dilated right side of heart
The patient returns in 2 weeks. There is no significant improvement in symptoms. Right-sided heart catheterization was equivocal for improvement with calcium channel blockers (e.g., diltiazem). Pulmonary consultation, as do all consultations on CCS, does not give specific advice.
Orders:
Continue home oxygen, warfarin, and furosemide.
Begin trial of bosentan (or ambrisentan).
Bosentan or Ambrisentan
• Endothelin-1 antagonists
• Decrease growth of PA
After 2 weeks, on return, the patient is no better. Her oxygen saturation hits 90% on a 3-L nasal canula and her exercise tolerance is deteriorating.
Orders:
Add epoprostenol.
Add sildenafil.
Epoprostenol
• Prostacyclin analogue
• Prostaglandin I2
• Eicosanoid derivative
• Inhibits platelet activation
• Vasodilatory
Sildenafil
• Phosphodiesterase inhibitor
• Cyclic guanosine monophosphate (cGMP) inhibitor
• Prolongs nitric oxide effect
• Vasodilates pulmonary vasculature
Over time, severe pulmonary hypertension may need lung transplantation. The management of primary pulmonary hypertension is extremely difficult. There is no medical therapy to cure or permanently halt the disorder. Most treatment is a matter of trial and error.