Impact of airflow limitation in chronic heart failure

Consecutive patients visiting the outpatient HF clinic of the Maastricht University Medical Centre (the Netherlands) were screened for inclusion in this cross-sectional observational study between October 2012 and November 2013 and were asked to participate in this study. Inclusion criteria were documented HF based on prevailing European Society of Cardiology guidelines [16] with left ventricular dysfunction (LVD), irrespective of LVEF, age above 50 years and clinically stable condition for at least one month. Patients who were not able to cooperate or in whom spirometry was clinically contraindicated (detached retina, active tuberculosis, resting pulse >120/min) were excluded. Other exclusion criteria were recent surgery, recent myocardial infarction (<1 month), lower respiratory tract infection or pneumothorax within the last 2 months or stroke within the last 12 months. The study was approved by the local ethics committee. All patients provided written informed consent prior to enrolment.

A total of 586 patients were screened. Of these, 205 HF patients volunteered to participate in this study. Six patients did not complete a lung function test and were excluded for further analysis. Of the remaining 199 patients, 13 patients (7%) had restrictive lung disease and were not analysed further (Fig. 1).

The demographic and clinical characteristics are shown in Table 1. The patients had an overall mean age of 76 years, median LVEF of 44% and approximately 70% of the participants were male. The mean ejection fraction for HFrEF patients was 37%. Thirty percent of the patients had HFpEF. Approximately half of the patients had mild symptoms (NYHA class II) and 50% had an ischaemic aetiology of HF. Other most common causes of HF were dilated cardiomyopathy (19%) and hypertensive heart disease (18%). Most patients were former or non-smokers.

Of the 186 patients without restrictive lung disease, 68 (37%) fulfilled the criteria of COPD. According to the traditional GOLD classification, 29 (15%) patients had mild, 31 (16%) moderate and 8 (4%) severe disease, while no patients had very severe COPD. When the updated GOLD assessment was applied, most COPD patients were categorised as GOLD B (Fig. 1). The prevalence of COPD did not differ between men and women.

Importantly, 43 (63%) patients were previously undiagnosed with COPD, whereas 3 of 118 patients (2.5%) who did not have significant airflow limitation had received the diagnosis of COPD previously. In addition, 8% of the patients used pulmonary medication without a proper diagnosis of COPD.

Patients with COPD had more symptoms of dyspnoea as compared to those having HF only. Systolic blood pressure and saturation differed significantly. The number of co-morbidities was similar in both groups. The proportion of patients with a previous diagnosis of asthma was not significantly different between HF patients with and without COPD. The distance walked during the 6‑MWT did not differ significantly (Table 2).

The medication used in both groups was similar, except for the inhalation therapy at baseline, which was more frequently used in the COPD patients (Table 1).

The difference in the CAT score between HF patients with or without COPD failed to reach statistical significance (Table 2). The overall KCCQ scores were significantly worse in the COPD group (p = 0.005) as summarised in Table 3. The following domains were significantly worse in the COPD group: physical limitation, symptom severity and symptom stability. The other domains did not significantly differ between patients with and without COPD. The ADO and BODE index were significantly different between the two groups (Table 3).

Survival did not differ significantly between HF patients with COPD and without COPD (p = 0.54) (Fig. 2).

In previous studies, the prevalence of COPD varied widely from 9 to 56% in patients with chronic HF, being on average between 20 and 30% [12, 25‐27]. Most studies were retrospective and included decompensated or hospitalised HF patients [8, 11, 12, 25‐27]. Studies in stable chronic HF patients are, however, relatively scarce. Valk et al. [12], reported COPD prevalence of 28% in 106 primary care patients. Boschetto et al. [26] reported a prevalence of 30% in 118 predominantly male, ambulatory HF patients. Masceranhas et al. [27] included 186 HFrEF patients retrospectively and reported a COPD prevalence rate of 40%. The variation in prevalence rates may depend on factors such as population, study design, inclusion criteria and used diagnostics [28]. In particular, most studies did not systematically perform lung function testing and based the diagnosis on medical history alone. In the current study, state of the art spirometry was performed in all HF patients. Given the significant proportion of underdiagnosis of COPD, this very likely explains the somewhat higher prevalence in this study. Moreover, the prevalence of COPD in HF patients increases with age until approximately 75 years [28, 29]. Thus, the mean age of >75 years in this study may have contributed to the observed prevalence.

HF itself can cause a reduction of about 20% in FEV1 and FVC [30]. Therefore, some studies recommend the use of the individual lower limit of normal (LLN), instead of the GOLD classification, to define COPD to prevent overdiagnosis of COPD in the elderly HF patients [31‐33]. However, in stable, not volume overloaded patients, the ratio FEV1/FVC is almost similarly impaired, thus the ratio FEV1/FVC is not affected prominently when spirometry is performed in a stable condition of the disease [30, 33]. This study included only stable HF patients; overdiagnosing COPD by using the fixed FEV1/FVC ratio proposed by GOLD in this study is therefore very unlikely [30, 34, 35]. Furthermore, the current guidelines acknowledge the limitations of the current GOLD-COPD classification, but appropriate alternatives are lacking [18].

Prevalence of COPD in HF patients with HFpEF was reported to be higher in comparison to HF with HFrEF [28]. This study did not confirm such a difference between patients with HFpEF and HFrEF. In fact, patients with preserved ejection fraction even tended to have less concomitant COPD. There are several reasons that could explain this discrepancy. Thus, most of the previous reports were retrospective, did not use proper testing, were predominantly performed in hospitalised patients and cut-off regarding ejection fraction was not uniform [36‐42]. Moreover, inclusion of HFpEF patients who actually have HF is certainly challenging and misdiagnosis exists [43, 44]. Thus, reliable estimates of COPD prevalence in representative stable HFpEF patients are still lacking [28]. Therefore, this study gives important insight in the COPD prevalence in the HFpEF population in comparison to other studies. Given the results of this study, showing that diagnosis of COPD is often missed or performed without proper testing, and the same is true for HFpEF, it may be speculated that some COPD patients may be misdiagnosed as HFpEF (and vice versa) in previous cohorts, highlighting the need for proper diagnostics, particularly in patients with suspicion of HFpEF.

The presence of COPD appears not only to worsen dyspnoea, but also negatively affect cardiac specific quality of life, as seen by the results of the KCCQ. On the other hand, the presence of COPD in HF patients did not negatively affect pulmonary specific health status, as assessed by the CAT questionnaire. Still, there was a strong trend which just failed to reach statistical significance, possibly due to less power as a result of missing values. Unfortunately, there is no specific questionnaire for patients with HF and concomitant COPD. In this regard, there is room to investigate and compare which questionnaire is suited best for such patients, or to develop a new questionnaire that specifically addressing symptoms and quality of life for patients suffering from both HF and COPD.

Despite having more symptoms, the functional status was not different between the two groups as assessed by the 6MWT [20]. This contrast with a previous study and the discrepancy cannot easily be explained. The average distance walked in this study indicates mild to moderate limitation in functional capacity, probably primarily due to HF.

Even though the effect on survival is negligible, current treatment of COPD generates symptom relief and improves quality of life [45, 46]. Therefore, it may be expected that proper treatment of COPD may result in improvement of symptoms and quality of life. Still, it needs to be prospectively tested if this really is the case. On the other hand, up to now it is unknown which specific COPD treatment is the best in HF patients. Advantages of HF medication in comorbid COPD patients on survival are well established, but the other way around is not that well established. Caution is needed with some inhalation therapy in HF patients [47‐49]. Therefore, safety and efficacy of various COPD drugs needs to be tested in appropriate trials. In addition, cessation of unnecessary treatment in patients not having COPD is of utmost importance. In this study, some patients received pulmonary medication without a proper diagnosis. Finally, survival was not adversely affected by COPD in this study. However, the study was too small to address this question sufficiently. Previous reports suggested some impact, but results were not uniform. Again, inhomogeneous criteria for diagnosis and differences in treatment may explain such discrepancies, further stressing the need of prospective testing of best management of these patients in a large prospective trial.