Diagnostic Puzzlers: A case of new-onset wheezing during pregnancy

A 24-year-old Korean woman, who was 20 weeks' pregnant, was referred to an allergist for an elimination diet and evaluation of the risk of allergies to her unborn child. She had a several-year history of perennial allergic rhinitis with seasonal exacerbations.

One year earlier, she had undergone skin testing; the results were positive for allergy to animal dander, dust mite, and pollens. She took loratadine/pseudoephedrine for 4 months, with good results. Results of skin tests were also positive for allergy to milk and soy, and she had nonbloody diarrhea after ingestion of these foods.

Before her office visit, she discontinued loratadine and reported nonproductive nocturnal cough and wheezing. She denied a history of cardiac problems, asthma, and other lung diseases. She also denied shortness of breath, rhinorrhea, fever, pain, vomiting, rashes, and ankle swelling. She was receiving regular prenatal care and vitamins.

The patient was a nonsmoker, worked as a data entry coordinator, and had a pet rat. Her family history was unknown because she was adopted. Her past medical history revealed mild depression and an allergic reaction to penicillin.

On physical examination, the patient's respiration rate was 16 breaths per minute; heart rate, 93 beats per minute; and blood pressure, 127/81 mm Hg. She was in no distress. Her nasal mucosa was pale, and there was no swelling. She had good respiratory effort, with bilateral lower lobe wheezing on expiration. There were no rales.

Findings from the cardiac examination were normal, and there was no clubbing, cyanosis, or edema. Her abdomen was round and nontender, with normal bowel sounds and no ascites.

Spirometric results were normal: forced vital capacity (FVC) was 81% of predicted; forced expiratory volume in 1 second (FEV₁), 84% of predicted; and forced expiratory flow between 25% and 75% of vital capacity (FEF_25%-75%), 76% of predicted. After the patient had received 0.5 mg of nebulized albuterol, the FEV₁ increased to 87% of predicted and the FEF_25%-75% increased by 21%. By the time auscultation was repeated, the wheezing had resolved. Chest radiography was deferred because of pregnancy.

A presumptive diagnosis of asthma was made. She was given 400 µg of budesonide twice daily via a dry-powder inhaler and albuterol, as needed.

At a follow-up visit after 8 weeks, the patient reported mild symptoms of a viral upper respiratory tract infection with cough but no wheezing. Her FEV₁ was 88% of predicted. She continued taking budesonide and albuterol (as needed) for 8 weeks. At her follow-up visit, she denied nocturnal cough and wheezing and reported that she had not taken albuterol. This time, her FEV₁ was 85% of predicted.

The patient was instructed to continue taking the same medications and to return for follow-up after delivery. One week later (37 weeks' gestation), she presented to her obstetrician, complaining about progressive shortness of breath over the past 4 days, which had not been relieved by taking albuterol. The patient was admitted to the hospital.

On admission, the patient appeared to be in respiratory distress. Her blood pressure was 137/98 mm Hg; pulse rate, 124 beats per minute; and respiration rate, 48 breaths per minute. She had trace peripheral edema. Her lungs were clear to auscultation.

Figure 1 is the patient's preadmission chest radiograph.

What do you suspect? How would you proceed?

Making the diagnosis

The patient's chest radiograph showed a mildly enlarged heart, a small right pleural effusion, and pulmonary vascular congestion. An echocardiogram revealed a mildly enlarged left ventricle with severe systolic dysfunction, normal wall thickness, and a left ventricular (LV) ejection fraction of 0.20 to 0.25. There was moderate mitral regurgitation, mild tricuspid regurgitation, and mild pulmonary hypertension with a pulmonary arterial systolic pressure of 38 mm Hg. The patient's ECG revealed sinus tachycardia, LV hypertrophy, possible left atrial enlargement, and nonspecific ST- segment abnormalities.

A helical CT scan of the chest was performed to evaluate for pulmonary embolism. Findings included alveolar infiltrates, a moderate-sized right pleural effusion, a mildly enlarged heart with thickening of the papillary muscles within the left ventricle, and a small amount of pericardial fluid (Figure 2). However, there were no filling defects to suggest pulmonary embolism.

Spirometric results suggested a restrictive ventilatory abnormality. FVC was 49% of predicted; FEV₁, 53% of predicted; and FEV₁:FVC, 86%. FEF_25%-75% was 58% of predicted. There was no improvement with the use of albuter- ol. Results of further examination were negative for thyroid disease, coagulopathy, preeclampsia, and myocardial infarction. The findings from prenatal laboratory studies were unremarkable.

Discussion

This is a case of a patient with cardiomyopathy who presented with new-onset wheezing during pregnancy. The patient presented in the mid-second trimester with findings suggestive, but not diagnostic, of asthma. Asthma occurs in 4% of gravid women and is the most common obstructive pulmonary disease seen in pregnancy. It is frequently associated with allergies, and patients typically present with wheezing, cough, shortness of breath, or chest tightness, or any combination of these symptoms.

Our patient had bilateral wheezing that improved with use of a short-acting ß₂-agonist, but reversible airway obstruction or bronchial hyperreactivity was not confirmed. Her signs and symptoms may have been early evidence of cardiac failure with pulmonary edema, but they were initially overlooked.

Peripartum cardiomyopathy is strictly defined by the NIH consensus conference as cardiac failure with unexplained LV systolic dysfunction occurring in the last month of pregnancy or up to 5 months postpartum. The prevalence is unknown, but it is estimated to be between 1 in 1400 and 1 in 15,000 live births. Risk factors for peripartum cardiomyopathy include black race, advanced maternal age, and multiple gestations.¹ Our patient had none of these risk factors.

Reported mortality rates for peripartum cardiomyopathy are about 25% to 50%.² Mortality occurs mainly in the first year postpartum.³ It is controversial whether women with peripartum cardiomyopathy are at increased risk for morbidity and mortality in subsequent pregnancies, and there is no consensus as to whether patients should become pregnant again. A further decrease in LV function has been shown to occur in subsequent pregnancies,⁴ and reduced LV function with the first pregnancy is associated with a worse outcome.⁵

Peripartum cardiomyopathy rarely causes cardiac failure during pregnancy, but it must be considered in patients who have signs of respiratory distress or cardiac dysfunction. In our patient, wheezing may have been the first sign and heart failure was masquerading as asthma. It is less likely that she had an unidentified trigger of dilated cardiomyopathy during pregnancy and simultaneously had mild asthma associated with pregnancy. In either instance, this case emphasizes the importance of considering cardiac causes of respiratory symptoms in pregnant women.

Other sources of cardiac dysfunction, such as valvular anomalies, need to be excluded. Other causes of cardiomyopathy during pregnancy include hypertrophic or hypertensive disease, thyroid disease, congenital heart disease, HIV infection, diabetes, and connective tissue disease.^6-9 Possible causes of heart failure are shown in Table 1.

The usual presentation of peripartum cardiomyopathy includes typical signs and symptoms of heart failure, such as cough, dyspnea, chest pain, pulmonary edema, or ascites.¹⁰ Wheezing is not a common finding. Several causes of wheezing during pregnancy are listed in Table 2.¹¹

The diagnosis of peripartum cardiomyopathy is made by identifying clinical signs of cardiac failure and may involve chest radiography, electrocardiography, or echocardiography. A chest radiograph may show cardiomegaly and/or pulmonary edema. ECG findings may include LV hypertrophy, nonspecific ST-segment and T-wave changes, and tachycardia; however, ECG findings may be normal in some patients.¹² The echocardiogram may reveal LV systolic dysfunction, with decreased ejection fraction, and enlarged chambers.¹³

Treatment of peripartum cardiomyopathy consists of diuretics, digoxin, ß-blockers, and angiotensin-converting enzyme inhibitors after delivery. Because of the risk of thromboembolism, anticoagulation with heparin is recommended for patients with low ejection fraction.¹³

Outcome in this case

The patient received digoxin, and she delivered a healthy 3.2-kg (7-lb) girl by an expedited low transverse cesarean section without complications. She was given metoprolol, enalapril, and furosemide, as needed, and she continued taking digoxin. She received enoxaparin as anticoagulant therapy.

The patient had rapid resolution of her symptoms and denied orthopnea and paroxysmal nocturnal dyspnea. On postoperative day 2, she reported mild dyspnea on ambulation, which rapidly resolved.

Seven weeks after delivery, our patient was evaluated in the allergy clinic. She denied any respiratory symptoms, her lungs were clear to auscultation, and her FEV₁ was 83% of predicted. Her asthma medications were reduced gradually and were discontinued within 3 months.

Six months after delivery, an echocardiogram still showed a moderately enlarged left ventricle with moderate dysfunction and a slightly improved ejection fraction of 0.30. Six months after that, an echocardiogram showed normal valvular function and a normal-sized left ventricle, with an ejection fraction of 0.55 to 0.60. An ECG revealed normal sinus rhythm with nonspecific ST-segment and T-wave abnormalities. The patient's furosemide and digoxin were gradually discontinued, but she continues to take metoprolol and enalapril.

References:

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