IJCA-18534; No of Pages 2 International Journal of Cardiology xxx (2014) xxx–xxx

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Letter to the Editor

Chronic obstructive pulmonary disease and hypertrophic obstructive cardiomyopathy: Two antagonistic obstructions Eftychios Siniorakis a, Spyridon Arvanitakis a,⁎, Theodoros Pavlouros a, Theodora Batila a, Ioannis Ntanos b, Elias Rentoukas a a b

Department of Cardiology, Sotiria Chest Diseases Hospital, Athens, Greece 9th Department of Pneumonology, Sotiria Chest Diseases Hospital, Athens, Greece

a r t i c l e

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Article history: Received 30 June 2014 Accepted 27 July 2014 Available online xxxx Keywords: Hypertrophic obstructive cardiomyopathy Chronic obstructive pulmonary disease Ipratropium bromide Side-effects

Coexistence of chronic obstructive pulmonary disease (COPD) and hypertrophic obstructive cardiomyopathy (HOCM) poses several therapeutic dilemmas. HOCM usually requires the use of beta1-antagonists, which despite their cardioselectivity can exacerbate COPD, increasing bronchospasm and wheezing. On the other hand, there is sparse information concerning the deleterious effect of inhaled bronchodilators, especially beta2-agonists, on aggravating the left ventricular outflow tract (LVOT) obstruction in patients with HOCM [1]. Here we describe the paradoxical effect that a nebulized anticholinergic bronchodilator exerted in a patient with COPD and HOCM. A 46-year-old man with known COPD and HOCM was admitted because of a respiratory infection with bronchospasm. For his COPD, the patient was under irregular and rather empiric use of inhaled steroids. Four syncopal episodes attributed to HOCM had occurred in the past, while he was being treated with 240 mg of verapamil twice daily. These phenomena were abolished when 5 mg of bisoprolol was added to verapamil. Wheezing was mildly aggravated by bisoprolol, but this had been well tolerated by the patient. While he was admitted to our unit, the verapamil–bisoprolol regimen was maintained and antibiotics, nebulized steroids and ipratropium bromide were prescribed. On day 2, a routine echocardiogram (ECHO) was performed to reevaluate HOCM. During the echocardiographic assessment, a dose of

⁎ Corresponding author at: 10 Evrou Street, Ampelokipi, Athens 11528, Greece. E-mail address: [email protected] (S. Arvanitakis).

ipratropium bromide nebulizer (500 μg/2 ml) was administered, as per schedule. Then, the following paradox was recorded: the LVOT obstruction previously registered as a systolic gradient of 72 mm Hg was suddenly raised to 160 mm Hg, corresponding to a 122% increase (Fig. 1). This effect lasted almost 15 min after discontinuation of the inhalation. During all these observations, the patient did not show any clinical deterioration and his heart rate and blood pressure remained stable (65 bpm and 120/70 mm Hg, respectively). The following day, when a new ECHO was repeated, accompanied by a programmed ipratropium inhalation, the same phenomenon reoccurred. The patient was informed about the effect ipratropium bromide exerted on his heart. His pneumonologist was similarly informed. Bronchodilator therapy was continued based solely on inhaled steroids until discharge. Ipratropium is an atropine derivative with nonselective antimuscarinic and anti-cholinergic effects [2,3]. Muscarinic receptors are activated by acetylcholine released from postganglionic fibers in the parasympathetic nervous system [4,5]. Human bronchi contain the M3 muscarinic subtype, which provokes bronchospasm if activated. This effect is abolished when ipratropium is inhaled [6]. The human heart is rich in M2 muscarinic receptors which exert a negative chronotropic and inotropic ventricular effect [7,8]. Ipratropium, with its anti-muscarinic properties, is expected to reverse the cardioinhibitory effect of M2 receptors, leading to enhanced ventricular contractility [9]. This is the mechanism we propose in order to interpret the dramatic increase in LVOT obstruction, observed in the case described here. Although the dose of ipratropium inhaled was able to abolish the negative inotropic action of M2 cholinergic receptors in our patient, it was ineffective in reversing his mild bradycardia. At least some explanation could be offered concerning this issue. Chronic treatment with bisoprolol exerted a negative chronotropic effect on beta1 adrenoceptors in the heart, which was unaffected by the anti-muscarinic properties of ipratropium. On the other hand, verapamil, also chronically administered, possesses some intriguing properties, apart from its calcium channel blocking action [10]. It has been proven to protect M2 muscarinic receptors from being attacked by atropine and atropine-like drugs on a dose-dependent regimen [11]. Atropine in low doses is unable to influence the inhibitory chronotropic effect of M2 receptors. Contrarily, by stimulating other muscarinic heart receptors, atropine derivatives may paradoxically sustain bradycardia, rather than producing tachycardia [12]. It seems that the dose of ipratropium administered to our patient was high enough to reverse the M2 negative inotropic action, although

http://dx.doi.org/10.1016/j.ijcard.2014.07.215 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.

Please cite this article as: Siniorakis E, et al, Chronic obstructive pulmonary disease and hypertrophic obstructive cardiomyopathy: Two antagonistic obstructions, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.07.215

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E. Siniorakis et al. / International Journal of Cardiology xxx (2014) xxx–xxx

further validated by other observations, a new complication is to be added to the constellation of ipratropium-related cardiovascular sideeffects [13,14]. Conflict of interest There is no reported conflict of interest. Acknowledgment The authors of this manuscript have certified that they comply with the principles of ethical publishing in the International Journal of Cardiology. No external grant has been received for this article. References

Fig. 1. Gradient in left ventricular outflow tract was 72 mm Hg (A) and raised to 160 mm Hg after ipratropium inhalation (B).

not so high to overcome the inhibitory chronotropic effect of these receptors. In summary, this case focused on a patient with COPD coexisting with HOCM. Inhaled ipratropium resulted in a significant, although reversible and asymptomatic, increase of LVOT obstruction. We cannot predict potential haemodynamic and clinical derangement under different conditions of preload and afterload. Should similar phenomena be

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Please cite this article as: Siniorakis E, et al, Chronic obstructive pulmonary disease and hypertrophic obstructive cardiomyopathy: Two antagonistic obstructions, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.07.215

Chronic obstructive pulmonary disease and hypertrophic obstructive cardiomyopathy: two antagonistic obstructions.

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