Disease and drug-induced arrhythmias : the example of obstructive pulmonary disease

Notwithstanding the clinical importance of cardiac arrhythmias, relevant information about the background risk and the exact underlying mechanisms of cardiac arrhythmias in patients with obstructive pulmonary disease (asthma and chronic obstructive pulmonary disease [COPD]) is still lacking. The overall aim of this thesis hence was to gain more insight in the risks for cardiac arrhythmias in patients with obstructive pulmonary disease, and to evaluate how arrhythmias in patients suffering from obstructive pulmonary disease can be prevented. The results of this thesis show that patients with COPD and asthma more often have electrocardiographic (ECG) abnormalities, than those without these diseases. For example, patients with COPD have a higher resting heart rate, and patients with asthma have an increased risk of tachycardia, than those without these diseases. A separate analyses showed that an increased resting heart rate is a strong and independent risk factor for all-cause mortality in elderly patients with COPD, although resting heart rate did not result in non-fatal pulmonary complications. Obstructive pulmonary disease is also associated with a 40% increased risk of ECG-confirmed sudden cardiac arrest, and patients with obstructive pulmonary disease have lower survival rates after sudden cardiac arrest than patients without this disease. Finally, we focused on the prevention of cardiac arrhythmias in patients with obstructive pulmonary disease. The results a systematic review made clear that in COPD patients, pharmacological therapy combined with behavioural counselling is more effective than each strategy separately. In order to manage the risk of drug-induced arrhythmias in daily clinical practice, the drug label plays a central role. The drug label forms the basis of information for health care professionals on how to use the specific product safely and effectively, also regarding information on arrhythmogenic properties of drugs.Inconsistencies in drug labelling may hamper the usefulness of the information and jeopardize risk minimization strategies. In our study we found that the extent and content of information on QT prolongation varied considerably between drug labels, and that many drug labels did not provide a clear message on whether the drug does or does not prolong the QT interval. Furthermore, there are quite some inconsistencies between the American and European drug labels with respect to how QT prolonging effects are described In a separate analysis we looked at how the recommendations concerning preventive measures for drug-induced arrhythmias are followed in routine care. We found that compliance of general practitioners to ECG monitoring recommendations stated in the label of the QT prolonging drug haloperidol was extremely low (1.8%). Although it is impossible to fully disentangle the effects of the disease (COPD and asthma) and the treatment for the disease (β2-agonists and anticholinergics), current evidence shows that patients with obstructive pulmonary disease have an increased risk of cardiac arrhythmias, especially patients with COPD. For patients with COPD, but also in selected patients with asthma, integrated pulmonary and cardiovascular care with special attention to previously unrecognized cardiovascular disease, is preferable