Dyspnea is a common symptom with a broad differential diagnosis. Further instrumental examinations should be planned based on the history and clinic. Knowledge of the exact mechanism is the basis for adequate therapy.
Dyspnea is a very common symptom in clinical practice with a broad differential diagnosis. The purpose of this article is to outline the general principles of the evaluation of dyspnea in the outpatient setting, although due to the limited scope, a detailed discussion of individual clinical pictures must be omitted. The workup of acute dyspnea in the emergency department is also not addressed.
Causes of dyspnea
Dyspnea is the sensation of difficult/uncomfortable breathing. The exact mechanisms mediating this sensation are still not known in full detail. However, it is important to realize that dyspnea is subjective and the limitations and pathologies associated with it can vary widely. Table 1 lists some common causes of dyspnea. The key question in the workup is always “Heart or lungs?”. Basic diagnostic modalities are discussed below, with typical patterns for each summarized in Table 1.
Medical history
A careful anamnesis is the indispensable prerequisite for the subsequent selection and prioritization of instrumental examinations. It must be said in advance, however, that history and clinical examination are usually insufficient for a differentiated diagnosis that allows therapy to be determined. On the one hand, the medical history must identify predisposing factors for certain medical conditions potentially associated with dyspnea (e.g., alcohol: cardiomyopathy; nicotine: coronary artery disease, COPD; agriculture: farmer’s lung; anthracycline therapy: cardiomyopathy; tuberculosis: Pneumopathy, but also pericardial constriction, etc.) or detect the presence of previously asymptomatic disease or disease that is symptomatic in another form (e.g., coronary artery disease, previous episodes of atrial fibrillation, known but previously well-controlled COPD, etc.). On the other hand, characteristic aspects of the symptomatology (duration of existence, at rest/under stress, during which stress, associated symptoms/circumstances, triggers, favorable influence, etc.) must be worked out. Dyspnea on exertion and intolerance of performance are leading symptoms of cardiac-related dyspnea (heart failure in the broader sense), but they are nonspecific. Pulmonary dyspnea (e.g., in the setting of interstitial pneumopathy or even obstructive lung disease) or severe anemia may present very similarly. Previous episodes of heart failure and paroxysmal nocturnal dyspnea make heart failure relatively likely. Edema, on the other hand, is nonspecific and may be an expression of heart failure, but also of chronic venous insufficiency or a consequence of drug therapy (e.g., amlodipine). Sputum, whistling breathing, and cyanosis and/or use of auxiliary respiratory muscles observed by relatives are more suggestive of pulmonary disease. Noticeable additional symptoms (diarrhea, weight loss, sweating, black stool, blood in the stool, etc.) must make one think of rarer causes of dyspnea (e.g., hyperthyroidism, anemia). Episodic dyspnea occurring primarily at rest combined with good exercise tolerance is suspicious for an anxiety disorder/hyperventilation. However, a hasty conclusion without an extended history and certain instrumental examinations is dangerous, since, for example, paroxysmal supraventricular tachycardia may not infrequently present as dyspnea and malaise (with or without palpitations) at rest.
Clinical examination
The clinical examination may provide seminal clues, but it may also remain unproductive, which, however, does not exclude a relevant somatic cause of the dyspnea. A third heart sound (reflecting increased left ventricular end-diastolic pressure) and congested jugular veins (increased right atrial pressure) have relatively high specificity for heart failure but are often absent or cannot be identified. Edema alone is a very nonspecific finding and must be evaluated along with the neck veins. In the outpatient setting, patients rarely present with obvious decompensation, and clinical findings are often discrete. Auscultation of the heart and lungs may provide evidence of valvular vitium and various pulmonary pathologies (Table 1) . An absolute arrhythmia usually indicates atrial fibrillation, which is usually an expression of underlying heart disease and does not occur in isolation. Measurement of vital signs (blood pressure on both sides, heart rate, oxygen saturation) is always part of the assessment. Tachypnea, tachycardia, cyanosis, reduced oxygen saturation (caveat: erroneous measurements in nail polish) are always indications of a significant pulmonary or cardiac problem and should be clarified promptly. Arterial hypertension alone does not explain dyspnea, but may dictate further work-up steps (ECG, echocardiography).
ECG
An ECG should be obtained in any patient in whom there is a question of a cardiac problem. A completely normal ECG makes heart failure relatively unlikely, but does not definitely rule it out. A pathologic ECG (Q-spikes, repolarization abnormalities, left bundle branch block, hypertrophy signs, atrial fibrillation) in a symptomatic patient suggests a cardiac cause and should be clarified with echocardiography. Patients with advanced lung disease and/or pulmonary hypertension often also have a pathologic ECG due to right heart strain. In young patients, one must be aware of the norm variations in this age group (e.g., increased ST leakage in chest wall leads in men <40 years).
Chest X-ray
A standing chest radiograph in two planes is also part of the workup for any patient with dyspnea. Signs of pulmonary venous hypertension and/or cardiomegaly strongly support the diagnosis of heart failure. The absence of cardiomegaly reduces the likelihood of heart failure to about one-third, but does not exclude it. The chest radiograph may provide clues to the etiology of heart failure (calcifications of the aortic valve or pericardium). In advanced lung disease, the chest x-ray is always abnormal and will often be supplemented by computed tomography. Pleural effusion can be easily visualized, and the radiograph will often, but not always, provide clues to etiology (heart failure, tumor disease).
Laboratory tests
A set of standard laboratory tests should be drawn on all patients with unexplained dyspnea. Normal levels of hemoglobin, creatinine, and thyroid-stimulating hormone (TSH) can rule out important differential diagnoses. In addition, knowledge of electrolytes, renal and liver function, and blood coagulation/platelet count is a prerequisite for establishing various drug interventions and for performing invasive diagnostics.
Measurement of “B-type natriuretic peptide” (BNP) or N-terminal-proBNP (NT-proBNP) is well established in the evaluation of acute dyspnea in the emergency department. Fewer data are available for ambulatory, less symptomatic patients, but measurement is also recommended by analogy. The great strength of natriuretic peptides is the exclusion of heart failure at very low levels (BNP <35 ng/l, NT-proBNP <125 ng/l; note that the cut-offs are lower than the cut-offs for acute dyspnea in the emergency department) (Fig. 1) [1]. If BNP or NT-proBNP are significantly elevated (BNP >300 ng/l, NT-proBNP >1000 ng/l), some form of heart failure is very likely. Nevertheless, it is then mandatory to perform echocardiography so that the mechanism of heart failure can be detected, as this is crucial for management. It should be noted that BNP is a nonspecific, semiquantitative marker of “cardiac stress” and that BNP may also be elevated, for example, in pulmonary disease with right heart strain and pulmonary hypertension. In addition, several noncardiac factors influence circulating BNP, knowledge of which is important for interpretation (Table 2).
Lung function and blood gas analysis
Spirometry can be performed in many primary care practices. It is the measurement of the so-called dynamic lung volumes, mainly the first-second capacity (FEV1) and the forced vital capacity (FVC). The quotient of FEV1 and FVC, the so-called FEV1/FVC ratio, is also of decisive importance. The latter should generally be more than 70%. Lower values mean evidence of bronchial obstruction with concomitant lowering of FEV1 below 80% of normal. Restrictive ventilatory dysfunction can be suspected, but not diagnosed with certainty, based on restricted FVC. A definitive diagnosis of restriction requires measurement of total lung capacity (TLC), which can be determined by body plethysmography. In addition to diseases of the pulmonary skeleton, the interstitial pneumopathies, a large-volume pleural effusion can also manifest itself in a restrictive ventilatory disorder. Another modality is to test gas exchange by measuring CO diffusion capacity. Deep CO diffusion capacity with concomitant normal spirometry and body plethysmography is typically seen in patients with pulmonary arterial hypertension. Arterial blood gas analysis indicates the severity of a ventilatory and/or diffusion disorder in patients with pulmonary disease and may provide evidence of chronic hyperventilation in unclear cases.
These studies allow basic conclusions to be drawn about the underlying pathology of dyspnea. In combination with performance diagnostics (spiroergometry), specifically selected imaging (primarily computed tomography) or, if necessary, invasive diagnostic methods (bronchoscopy), the diagnosis can thus be made. However, abnormalities in pulmonary function may also occur in patients with cardiac-related dyspnea. Patients with heart failure often show obstruction in pulmonary function due to interstitial edema. In contrast, patients with pleural effusion are expected to have decreased vital and first-second capacities.
Echocardiography
Echocardiography is the key investigation in patients with dyspnea and possible cardiac disease. According to current recommendations, echocardiography should be performed if there is evidence of possible heart failure from history, clinical examination, or ECG (at least somewhat abnormal/suggestive; Fig. 1) . According to current guidelines, echocardiography can be omitted if BNP<35 ng/l or NT-proBNP <125 ng/l. As stated earlier, the role of BNP/NT-proBNP is less well established for the outpatient setting than for acute dyspnea in the emergency department, and echocardiography can be performed directly accordingly. It is important to realize that the diagnosis of “heart failure” cannot be made purely clinically. According to the current definition, apparative evidence of cardiac dysfunction is crucial [1]. Dyspnea in heart failure likely results from increased left atrial pressure with increased “pulmonary artery wedge pressure” (PAWP) and interstitial edema. Figure 2 shows schematically that disturbances/”obstructions” at different levels of the circulation can lead to increased left atrial pressure/PAWP. In the case of severe valvular vitiation and/or severely impaired left ventricular ejection fraction (LVEF) or the classic picture of pulmonary hypertension, the mechanism of dyspnea or the diagnosis of heart failure is relatively obvious. The diagnosis of heart failure with preserved LVEF remains very difficult, because in this constellation it must be proven that left atrial pressure is elevated at rest and/or exercise despite normal LVEF and explains the symptoms [2]. Echocardiography sets the stage for further investigations (coronary angiography, right heart catheterization, cardiac MRI) and the initiation of therapy.
Spiroergometry
Not always do the studies of cardiac and pulmonary function at rest discussed above permit a definite conclusion regarding the mechanism of dyspnea during exercise. Often, abnormal findings are obtained (e.g., diastolic LV function, moderately impaired FEV1) whose functional significance remains unclear, and/or multiple pathologies are present and the leading problem remains unclear. In this situation, spiroergometry is a very helpful examination. In addition to the aspects of “normal ergometry” (ischemia, chronotropic competence, blood pressure behavior), spiroergometry can, roughly speaking, differentiate between ventilatory/gas exchange (pulmonary disease) and cardiocirculatory (cardiac disease, but also lack of exercise) limitation (shown schematically in Figure 3) and thus reveal the mechanism relevant to performance limitation.
For a more detailed discussion, the reader is referred to another article [3]. However, the principle of the examination should be briefly outlined, as it is helpful for pathophysiological considerations: During ergometry, oxygen uptake (VO2) is measured continuously, in parallel with ventilation,CO2 production, heart rate and respiratory rate. Of interest is the performance capacity expressed as maximum VO2 (“peak VO2“), since a lowered value with adequate effort can document that there is effectively an objectifiable performance impairment. “Peak VO2” is the product of cardiac output and the difference in oxygen content between arterial and venous blood, i.e. the amount of oxygen that can be extracted from the blood by the “periphery” (muscles, organs). As shown in Figure 3, oxygen transport and oxygen utilization can be impeded at different levels. A depletion of the respiratory reserve estimated on the basis of FEV1 indicates a ventilatory limitation, a desaturation a form of gas exchange disturbance, a low oxygen pulse (“peak VO2” divided by maximum heart rate) a low stroke volume (thus a cardiac dysfunction) and/or an impaired O2 uptake by the musculature (usually lack of training).
Take-Home Messages
- Dyspnea is a common symptom with a broad differential diagnosis.
- A careful history and clinical examination are the basis for the selection and prioritization of further apparative examinations.
- ECG, chest x-ray, spirometry, and laboratory tests set the stage for more advanced testing (echocardiography, body plethysmography, computed tomography, etc.).
- The purely clinical diagnosis of heart failure or pneumopathy is not correct. Knowledge of the exact mechanism is the basis for adequate therapy.
Literature:
- Ponikowski P, et al.: 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016; 37(27): 2129-2200.
- Maeder MT, et al: Heart failure with preserved left ventricular pump function (HFpEF)-Update diagnosis and therapy. Info@heart+vascular 2017; 7(4): 4-7.
- Maeder MT: Value of spiroergometry in the diagnosis of exertional dyspnea. Therapeutic Review 2009; 66(9): 665-669.
CARDIOVASC 2017; 16(4): 13-20
