Misclassification of Both Chronic Obstructive Pulmonary Disease and Heart Failure

Both heart failure (HF) and chronic obstructive pulmonary disease (COPD) are common in the elderly population and are at least partly understood as accelerated aging. They share smoking and systemic inflammation in etiology, with a chronic progressive disease trajectory characterized by exacerbations. Overlap is large in symptoms and signs as well as in chest radiography, electrocardiography, and spirometry results.^1,2

The study by Lawson et al³ used the large Clinical Practice Research Datalink linked to Hospital Episode Statistics between 2002 and 2014. In 2 separate nested case-control studies, patients with HF who developed COPD were compared with those without. The diagnoses of COPD and HF were based on clinical assessment and routinely requested further investigations, ie, echocardiography in those diagnosed with HF. Approximately 40% of patients additionally diagnosed with COPD received spirometry.³

The study showed that in patients diagnosed with HF, the development of COPD and increasing COPD severity were associated with first all-cause hospitalization and all-cause mortality.³ Chronic obstructive pulmonary disease severity was based on medication intensity and forced spirometry. A finding that still holds true if we realize that the diagnostic workup for both COPD and HF were incomplete—very common in routine (primary) care—and may have resulted in some misclassification of either disease. The clinical implications are, however, challenging owing to the overlap of COPD and HF as it relates to diagnosis and potential for misclassification of patients. Misclassification happens in both COPD and HF, notably in primary care.

Spirometry is the most commonly applied examination for COPD⁴ and is readily available in primary care, but it is sensitive to misinterpretation in patients with (undetected) HF.^2,5 Patients with HF should be stable and euvolemic for several months before a spirometry-derived ratio of forced expiratory volume in 1 second (FEV₁) to forced vital capacity less than 0.70 may be considered as obstruction within the small airways and compatible with a diagnosis of COPD.^2,5,6 Overdiagnosis of COPD in HF is common, as HF causes pulmonary congestion and thus external compression of the small airways, resulting in an obstructive spirometric pattern as in true COPD, while in the latter the obstruction is caused by inflammation and phlegm production in the small airways.² Misclassification of COPD in patients with HF may range from 40% to 80% if based on forced spirometry only.^5,7 Moreover, spirometry overestimates the COPD severity based on FEV₁ because HF itself reduces both FEV₁ and forced vital capacity values by 10% to 20%.⁸ If unsure about stability and pulmonary fluid status, it is better to perform body plethysmography to identify COPD, especially in patients with HF.⁵ Because air trapping is not influenced by pulmonary congestion, the ratio of the residual volume to total lung capacity as derived from body plethysmography is not affected and may even be used in patients with HF with clear signs of pulmonary congestion.⁵ However, body plethysmography is not available in primary care. Clinicians should realize that adequate (diuretic) treatment of HF may create an euvolemic state in patients with HF, that is, without pulmonary fluid overload not only relieving the patient’s shortness of breath but also critically reducing the risk of overdiagnosing COPD with spirometry.

Although HF is a clinical syndrome with typical symptoms and signs, a definite diagnosis requires echocardiographic evidence of structural and/or functional cardiac abnormalities. Heart failure is also prone to misclassification, although in general, underdiagnosis may be more common than overdiagnosis.^7,9 Misclassification of HF is related to the tendency of both patients and physicians to more easily attribute respiratory symptoms to an underlying pulmonary than cardiac disease, and because echocardiography is not readily available in primary care. But even with the facility of echocardiography there is a challenge in patients with COPD because echo views are more often of less quality than in those without COPD, and the left ventricular ejection fraction is sensitive to measurement errors of up to ±5%. Even more challenging is classifying HF with preserved ejection fraction in the presence of COPD. There is an ongoing discussion about which combination of echocardiographic structural and functional abnormalities exactly defines diastolic dysfunction and what cut points should be applied to differentiate those abnormalities from changes due to aging. Moreover, because of the large overlap in symptoms and signs seen in COPD and HF, it is not really possible to conclude whether these are due to COPD, HF, or both.¹

Considering the therapeutic management of patients with both HF and COPD, there are realistic concerns about interactions and adverse effects of pulmonary drugs on cardiac function, notably oral prednisolone and short-acting inhaled β-mimetics. Inadequate assumptions about interactions can impede proper management. For example, instructions on drug leaflets still mention that β-blockers are contraindicated in COPD. Interestingly, multiple observational studies all point in the direction of beneficial effects of cardioselective β-blockers on survival and reduction in exacerbations, and recently a large randomized controlled trial started to evaluate metoprolol among 1028 patients with COPD.¹⁰

The study by Lawson et al³ concluded that prescribed COPD medication intensity and FEV₁ levels provide the basis for targeting high-risk groups. Importantly, they also showed that short-acting inhaler only or monotherapy in patients with HF and without COPD was significantly associated with approximately 30% increased risk of all-cause hospitalizations, confirming that we should be careful with short-acting inhaled β-mimetics in HF. Moreover, this finding may also be explained by inadequate management of exacerbations of HF, misinterpreted as COPD symptoms and treated by inhaled β-mimetics instead of up-titration of diuretics.

The results of Lawson et al³ clearly highlighted that concurrent COPD is associated with poor outcome, which is worse in severe cases. How can such clinical record-based prognostic stratification improve our care for patients with HF? We are nowadays challenged not only to provide prognostic information to our patients, but also to give tools that beneficially influence this prognosis. The finding that short-acting inhaled β-mimetics may be deleterious in patients with HF is a crucial finding and in line with literature, and should urge clinicians to refrain from prescribing these drugs that are not obligatory in COPD, but instead use inhaled long-acting β-mimetics and muscarin antagonists. In addition, we need valid diagnoses of both COPD and HF, and notably the diagnosis in the presence of the other is a challenge, even when a patient receives all noninvasive diagnostic tests available for such cases.

Published: December 14, 2018. doi:10.1001/jamanetworkopen.2018.5486

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2018 Rutten FH et al. JAMA Network Open.

Corresponding Author: Frans H. Rutten, MD, PhD, Julius Center for Health Sciences and Primary Care, Department of General Practice, University Medical Center Utrecht, Utrecht University, Stratenum 6.106, PO Box 85500, 3508 GA Utrecht, the Netherlands (f.h.rutten@umcutrecht.nl).

Conflict of Interest Disclosures: None reported.