Approach to the Patient with Chronic Dyspnea Case File

Approach to the Patient with Chronic Dyspnea Case File

Eugene C. Toy, Md, Michael d . Faulx, Md

A 55- year -old woman presents for evaluation of gradually progressive exertional dyspnea. She reports that for the past 2 years she has experienced a sensation of “heavy breathing ” with exertion. She describes feeling noticeably winded after walking continuously for more than 5 minutes at a normal pace or when climbing one flight of stairs. She denies overt cardiac symptoms, and her review of systems is normal except for a 50-lb weight gain since menopause 3 years ago and excessive sleepiness and difficulty concentrating during the day. Her husband reports that she snores loudly an occasionally gasps for air during sleep. Her lifestyle is sedentary . Her medical history is noteworthy for hypertension, osteoarthritis of the knees, and cholecystitis requiring cholecystectomy 1 year ago. She is a married cashier at a local diner who has never been a smoker and drinks alcohol only rarely . She has no drug allergies, and her medications include chlorthalidone 25 mg daily, losartan 25 mg daily, and a daily multivitamin.

Her vital signs are as follows: blood pressure 125/72 mmHg , pulse 86 bpm, respiratory ate 18 breaths/min, and room air O2 saturation 98%. She is 61 in (155 cm) tall and weighs 221 lb (100 kg ). Her examination is remarkable for morbid obesity and soft but audible heart sounds without murmurs. Her chest is clear. Her neck veins are difficult to evaluate because of obesity, but she has warm legs with no pitting edema.

• What is the most likely diagnosis?
• What is the best next diagnostic step?
• What is the best next step in treatment?

Answer to Case 23:

Approach to the Patient with Chronic Dyspnea

Summary: This 55-year-old morbidly obese (BMI 42 mg/m2) woman reports the insidious onset and progression of exertional dyspnea that correlates with a period of significant weight gain. Her history does not strongly suggest the presence of a direct cardiovascular or pulmonary cause for her symptoms, although she does endorse symptoms suggestive of obstructive sleep apnea. Her physical examination is limited by her obesity, but it does not suggest an obvious diagnosis other than morbid obesity. Her resting ECG is normal.

• Most likely diagnosis: Chronic dyspnea, likely due to obesity and deconditioning.
• Next diagnostic step: Basic laboratory assessment, chest x-ray, echocardiogram, and pulmonary function studies.
• Best next step in treatment: Regular aerobic exercise and dietary modification for weight loss.

ANALYSIS

Objectives

1. Understand the physiologic mechanisms that produce dyspnea.
2. Become familiar with the most common causes of chronic dyspnea in adults.
3. Review the basic approach to the evaluation of a patient with chronic dyspnea.

Considerations

This patient has several potential reasons for her dyspnea, including risk factors for ischemic heart disease, obesity, and deconditioning. Of these, cardiovascular problems (ischemic heart disease, structural heart disease, and pulmonary hypertension) carry the gravest prognosis and often receive the greatest attention. Dyspnea is one of the more common reasons for outpatient referral to a cardiologist. Dyspnea is often distressing to both the patient and the caregiver as it is not uncommon to encounter patients who report rather limiting dyspnea despite a paucity of objective findings to indicate a cause. Although the initial history and physical examination will indicate a cause in a majority of patients, there are still plenty of patients like ours who appear to have no obvious cardiac or pulmonary pathology.

Approach To:

Dyspnea

DEFINITIONS

DYSPNEA: The subjective sensation of uncomfortable or abnormal breathing. Dyspnea may be described by patients in several ways using terms such as “breathlessness,” “ air hunger,” “hard breathing,” or the inability to take in a deep breath.

ORTHOPNEA: Dyspnea caused by supine or flat posture. Orthopnea is a common feature of heart failure with pulmonary congestion, but it can also occur in obese patients or patients with pulmonary disease.

PAROXYSMAL NOCTURNAL DYSPNEA (PND): Episodic dyspnea occurring during sleep, often waking the patient from sleep.

B-TYPE NATRIURETIC PEPTIDE (BNP): Active natriuretic hormone produced by cardiac tissues (predominantly ventricular tissue) in response to stretch. BNP is created by cleavage of a pro-molecule (pro-BNP) into BNP and an inert peptide, namely, N-terminal pro-BMP. Both BNP and NT pro-BNP assays are used to rule heart failure out or in as a cause of dyspnea.

CARDIOPULMONARY EXERCISE TEST (CPET): Comprehensive exercise study that measures several parameters including oxygen consumption and carbon dioxide production in addition to standard exercise data. Useful for differentiating the causes of dyspnea, such as heart failure, pulmonary disease, muscle weakness, and general deconditioning.

PEAK OXYGEN CONSUMPTION (VO2): Estimate of cardiopulmonary fitness measured via cardiopulmonary exercise testing, measured in milliliters per kilogram per minute (mL/kg/min).

METABOLIC EQU IVALENTS (METs): Commonly used metric of exercise capacity; 1 MET equals an oxygen consumption of 3.5 mL/kg/min. VO2 can be converted to METs by dividing peak VO2 by 3.5 mL/kg/min.

CLINICAL APPROACH

Overview

The pathophysiology of dyspnea is complex and incompletely understood. There is a great deal of afferent nerve traffic traveling to the brain to provide information regarding the adequacy of ventilation. Specialized chemoreceptors in the carotid arteries and brainstem provide information regarding the relative levels of oxygen, carbon dioxide, and hydrogen ions in the blood. Mechanoreceptors in the alveoli, bronchi, and chest wall provide information regarding alveolar stretch, airflow, and muscle tension. Higher-level cortical afferents provide neurologic feedback resulting from cognitive and emotional stimuli. The sensory data acquired from the frontal cortex and periphery are processed by the brain in areas such as the anterior right insula, amygdala, and the anterior and posterior cingulated cortices, influencing the efferent output to the diaphragms and chest wall musculature in order to regulate the

frequency and depth of breathing. The sensation of dyspnea is assumed to arise when there is some imbalance between the afferent stimuli and the efferent response.

Acute dyspnea is dyspnea that occurs over a period of minutes to hours. Unlike chronic dyspnea, which has a broad differential diagnosis, there are relatively few causes of acute dyspnea (Table 23-1). Most of the causes of acute dyspnea can be determined via the initial history and exam; evaluation and management is often performed in the hospital setting given the serious implications of most of the diagnoses on the differential.

Chronic dyspnea is dyspnea that has been present for several weeks or longer. The most common causes of chronic dyspnea are pulmonary disorders (asthma, COPD, and interstitial lung disease), cardiovascular disorders (ischemic heart disease, heart failure, valvular dysfunction), and obesity/deconditioning. It is difficult to determine the cause of dyspnea entirely on the basis of its subjective description; however, certain clinical features may help you establish a cause (Table 23-2).

Dyspnea that has clear environmental triggers such as smoke, cold air, or pet dander is likely to be due to asthma. In a patient with a smoking history, seasonal dyspnea associated with a cough productive of nonpurulent sputum is suggestive of chronic bronchitis. Dyspnea accompanied by wheezing is suggestive of obstructive lung disease, whereas dyspnea in the setting of pulmonary rales, leg edema, or a gallop rhythm is probably due to heart failure.

Initial Evaluation

The initial history and physical examination can establish a diagnosis for approximately two-thirds of patients presenting with chronic dyspnea. Beyond the H&P there are a few routine studies that can further narrow the differential diagnosis. Laboratory assessment should include a basic metabolic panel and a complete blood count; these tests can exclude disorders such as chronic kidney disease, metabolic abnormalities, anemia, and leukocytosis if infection is suspected. If thyroid disease is suspected on clinical grounds, then a thyroid-stimulating hormone (TSH) level should be obtained.

Another laboratory assay that may be helpful in the assessment of patients with chronic dyspnea is B-type natriuretic peptide (BNP). BNP is a molecule produced by ventricular myocytes. Elevated BNP levels are indicative of increased ventricular stretch or strain; this is most commonly seen in patients with left ventricular heart failure, although several conditions can increase ventricular strain, including myocardial ischemia, hypertensive heart disease, and pulmonary embolism with right ventricular strain. Additionally, patients with chronic systolic heart failure may have increased BNP even in the absence of acute decompensation. In a patient with dyspnea a normal BNP level (<100 pg/mL) reasonably excludes the diagnosis of heart failure, provided that the patient is not morbidly obese. Obesity has been shown to attenuate BNP levels for reasons that are not entirely clear, so a normal level does not exclude heart failure or some other cardiovascular cause.

Substantially elevated BNP levels (>400 pg/mL) strongly suggest the diagnosis of heart failure. Values between 100 and 400 pg/mL are fairly nonspecific for heart failure and may be due to any number of cardiac or pulmonary conditions such as myocardial ischemia or cor pulmonale.

The initial evaluation of the patient with dyspnea should also include a surface ECG, a posteroanterior (PA) x-ray, a lateral chest x-ray, and spirometry. The surface ECG can reveal evidence of cardiac disease such as prior myocardial infarction, active myocardial ischemia, arrhythmia, and atrial or ventricular hypertrophy. The chest x-ray might suggest diagnoses such as emphysema, pleural effusion, or interstitial lung disease. Spirometry is also helpful in the early assessment of dyspnea as it allows one to assess for abnormalities with pulmonary mechanics that might narrow the differential diagnosis such as fixed extrathoracic airflow obstruction (tracheal stenosis, large goiter), dynamic airways obstruction (asthma, COPD), and restrictive pattern (interstitial lung disease, obesity). Patients are commonly assessed with ambulatory pulse oximetry at the same time. In the setting of abnormal spirometry or ambulatory hypoxemia, one may perform more extensive pulmonary function testing to assess for total lung capacity, diffusion capacity, and testing of inspiratory force to better differentiate between restrictive lung disease and severe airway obstruction and to assess for respiratory muscle weakness. In cases where clinical, x-ray or spirometry findings strongly suggest interstitial lung disease, a CT of the chest may be helpful to confirm the diagnosis; routine use of CT scanning in the evaluation of dyspnea is rarely performed because of the risk of radiation exposure and cost.

Echocardiography is another useful tool in the assessment of the patient with chronic dyspnea. An echocardiogram can confirm a cardiac diagnosis that is suspected on the basis of the history and physical examination. It may also be useful in excluding occult cardiac causes of dyspnea in patients who do not have a clear diagnosis following basic investigation. Echocardiography allows for a noninvasive comprehensive assessment of cardiac function. With two and three-dimensional (2D and 3D) imaging and Doppler assessment, an echocardiogram can provide diagnostic information regarding ventricular systolic and diastolic function, ventricular filling pressures, pericardial disease, and pulmonary artery pressure.

Cardiopulmonary exercise testing (CPET) is typically arranged for patients who continue to report dyspnea without an obvious cardiovascular or pulmonary cause or when the degree of dyspnea is out of proportion to objective findings. The feature that distinguishes CPET from other forms of exercise testing is the direct measurement of respiratory gas exchange as a means to quantify energy expenditure. In standard stress tests energy expenditure, reported as metabolic equivalents (METs), is coarsely estimated from the duration and intensity of exercise. METs levels can be estimated by correlation with activities in daily life (Table 23-3). CPET allows for a more direct way to quantify exercise capacity from measurement of gas exchange. In addition to the standard monitoring of blood pressure, heart rate, and electrocardiography, during CPET the exercising patient breathes into a closed circuit of plastic tubing attached to an analyzer that measures ventilatory volumes and the fractions of oxygen and carbon dioxide in expired air. These primary data allow for the calculation of the minute ventilation (VE), oxygen consumption (VO2), and carbon

*Metabolic equivalents.

dioxide output (VCO2). Of these, the VO2 provides the best estimate of aerobic performance and is the most widely used measure to discriminate between patients with obesity or deconditioning (normal VO2) and those with cardiopulmonary disease (reduced VO2). The exercise protocols used for CPET all employ gradual increases in treadmill speed and degree of incline to provide a uniformly sustained effort and to accommodate for a broad range of physical abilities. For subjects with reduced VO2 the data obtained from a CPET can be used to estimate anaerobic threshold and respiratory reserve, allowing further differentiation between cardiac and pulmonary causes of dyspnea.

CASE CORRELATION

• See also Case 1 (acute coronary syndrome/STEMI), Case 2 (acute coronary syndrome/NSTEMI), Case 3 (cardiogenic shock), Case 6 (acute valvular regurgitation), Case 8 (hypertrophic obstructive cardiomyopathy), Case 10 (valvular stenosis), Case 11 (atrial fibrillation and flutter), Case 16 (acute heart failure), Case 17 (advanced heart failure), and Case 19 (chronic heart failure).

COMPREHENSION QUESTIONS

23.1 An 85-year-old woman presents for evaluation of her 1-year complaint of gradually increasing exertional dyspnea. She presently reports significant breathlessness after walking one block or climbing one flight of stairs. She also reports a general decrease in exercise tolerance over the past year with occasional episodes of near-syncope after more strenuous activities such as carrying a laundry basket from the basement. Her medical history is remarkable only for osteoporosis, for which she takes vitamin D and calcium. She has never been a smoker. Her physical examination is remarkable for a harsh III/VI latepeaking systolic murmur at the right upper sternal border that obscures the second heart sound and radiates to the base of the neck. Her carotid pulses are reduced in volume and amplitude bilaterally. Her ECG reveals sinus rhythm with voltage evidence of left ventricular hypertrophy. Basic chemistries, complete blood count, and chest x-ray have been performed and are normal.

Which of the following is the most appropriate next test?

A. Spirometry

B. Cardiopulmonary exercise testing

C. Echocardiography

D. B-type natriuretic peptide assay

E. Carotid artery ultrasonography

23.2 A 65-year-old man is referred to you for assessment of his complaint of 6 months of progressive exertional dyspnea with activities of daily living. His history is remarkable for hypertension, peptic ulcer disease, and active smoking of one pack per day with >100 packs per year in total. He denies chest pain, orthopnea, PND, or productive cough, but he does report moderate weight loss over the past year. His examination reveals a thin man in no distress who smells of smoke. He is afebrile and normotensive with a room air saturation of 92%. He has diffuse end expiratory wheezing and distant heart sounds without murmurs. His legs are warm and without edema. His ECG is remarkable for sinus rhythm with low QRS voltage and slight right-axis deviation. His labs are all within normal limits, including a B-type natriuretic peptide level. From what you know about this patient right now, in addition to smoking cessation counseling, what would you recommend next?

A. Furosemide

B. Inhaled ipratropium bromide and albuterol

C. Azithromycin

D. Metoprolol

E. Heparin

23.3 A 58-year-old man presents to your office for evaluation of his 6-month complaint of exertional dyspnea. He currently becomes winded after climbing one flight of stairs, but he denies any other symptoms. He does not see a doctor regularly and takes no medications on a regular basis. He is a truck driver who was a one-pack/day smoker for 25 years until he quit 5 years ago after his brother was diagnosed with smoking-related lung cancer. On physical examination his vitals are as follows: BP 165/105 mmHg, pulse 80 bpm, respirations 16/minute, room air saturation 98%, and BMI 28 kg/m². His cardiopulmonary examination is normal aside from trace ankle edema and an estimated jugular venous pressure of 9 cm H2O. His ECG reveals sinus rhythm with voltage criteria for left ventricular hypertrophy. His basic laboratory data are normal with the exception of a BNP level of 305 pg/mL. His chest x-ray reveals a borderline enlarged cardiac shadow and normal lungs. You have him return after spirometry and an echocardiogram; the spirometry demonstrated mildly reduced FEV1 and forced vital capacity (FVC) with a normal ratio, and his echocardiogram was normal aside from stage 2 diastolic dysfunction.

What is the most appropriate next step?

A. Arrange for a CT scan of the chest to exclude interstitial lung disease

B. Begin treatment with an ACE inhibitor and a thiazide-type diuretic for hypertensive heart disease

C. Begin inhaled albuterol and ipratropium bromide in combination for COPD

D. Arrange for a cardiopulmonary exercise test to further assess his dyspnea

E. Arrange for a pharmacologic myocardial perfusion imaging study to rule out coronary artery disease

ANSWERS

23.1 C. Echocardiography. This patient has a history and clinical examination that is classic for severe aortic stenosis; an echocardiogram would confirm this diagnosis, and this would be the appropriate next step. Spirometry would most likely be normal or reveal a mildly restrictive pattern, which is common in patients with left atrial hypertension caused by left-sided heart disease. Cardiopulmonary stress testing would almost certainly demonstrate reduced VO2 secondary to her valvular heart disease and would not add any additional information. A BNP in her case would likely fall into the nondiagnostic range and would not facilitate the diagnosis. Her carotid artery findings are due to her aortic stenosis; isolated carotid stenosis would not be expected to cause dyspnea.

23.2 B. This patient almost certainly has emphysema caused by cigarette smoking, a diagnosis that is supported by his history and physical examination. Smoking cessation is of utmost importance for this patient, but inhaled bronchodilator therapy would also be appropriate. There is little in his history or physical exam to suggest the presence of heart failure, ischemic heart disease, pulmonary embolism, or pneumonia.

23.3 B. Treat for hypertensive heart disease. This patient presents with stage 2 hypertension with evidence of end-organ involvement (left ventricular hypertrophy) and increased left atrial pressure (stage 2 diastolic dysfunction). Although he does not have overt heart failure, a dual-agent antihypertensive treatment regimen that includes a diuretic would be the most appropriate next step. With a normal chest film and lung examination, there would be no clear role for a CT scan of the chest. For similar reasons and with no obstruction on spirometry, there would be no indication for COPD treatment with inhaled bronchodilators. A cardiopulmonary exercise test seems unnecessary as the patient’s hypertensive heart disease appears to explain his dyspnea. Although this patient does have risk factors for coronary disease, and myocardial ischemia can cause dyspnea, he does not report chest pain, and his overall clinic picture is more consistent with hypertensive heart disease.

CLINICAL PEARLS

• The cause of chronic dyspnea can be determine from the history and physical examination in approximately two-thirds of cases.
• For the diagnosis of heart failure in nonobese patients, BNP values <100 pg /mL or >400 pg/mL have excellent negative and positive predictive value, respectively .
• A normal transthoracic echocardiogram can confidently exclude a number of cardiovascular conditions associated with dyspnea.
• Cardiopulmonary exercise testing can be extremely helpful in finding a diagnosis in patients with dyspnea who do not have an obvious cause after primary investigation.

References

Maisel AS. B-Type natriuretic peptide levels: diagnostic and prognostic in congestive heart failure. What’s next? Circulation. 2002;105:2328–2331. 

Milani RV, Lavie CJ, Mehra MR, Ventura HO. Understanding the basics of cardiopulmonary exercise testing. Mayo Clin Proc. 2006;81(12):1603–1611. 

Nishino T. Dyspnoea: underlying mechanisms and treatment. Br J Anaesth. 2011;106(4):463–474. 

Pratter MR, Curley FJ, Dubois J, Irwin RS. Cause and evaluation of chronic dyspnea in a pulmonary disease clinic. Arch Intern Med. 1989;149(10):2277.

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