The cough reflex is an airway defensive process that can be modulated by afferent inputs from organs located also out of the respiratory system. A bidirectional relationship between cough and heart dysfunctions are presented in the article, with the special insights into an arrhythmia-triggered cough. Albeit rare, cough induced by cardiac pathologies (mainly arrhythmias) seems to be an interesting and underestimated phenomenon. This condition is usually associated with the presence of abnormal heart rhythms and ceases with successful treatment of arrhythmia either by pharmacotherapy or by radiofrequency ablation of arrhythmogenic substrate. The two main hypotheses on cough-heart relationships - reflex and hemodynamic - are discussed in the review, including the authors' perspective based on the experiences with an arrhythmia-triggered cough.

Department of Internal Medicine Pulmonary Diseases and Allergy University Clinical Centre Medical University of Warsaw Poland

See more in PubMed

ALIYEV F, KILIÇKESMEZ KO, ÇELIKER C, TÜRKOĞLU C. Cough-induced sinus arrest resulting in recurrent episodes of syncope: is it really transient? J Cardiovasc Med (Hagerstown) 2012;13:468–470. doi: 10.2459/jcm.0b013e32833892c4. PubMed DOI

American Heart Association. Cough CPR. [Accessed 22 September 2019]. https://www.heart.org/en/health-topics/cardiac-arrest/emergency-treatment-of-cardiac-arrest/cough-cpr .

BARON SB, HUANG SK. Cough syncope presenting as Mobitz type II atrioventricular block--an electrophysiologic correlation. Pacing Clin Electrophysiol. 1978;10:65–69. doi: 10.1111/j.1540-8159.1987.tb05925.x. PubMed DOI

BENDITT DG, SAMNIAH N, PHAM S, SAKAGUCHI S, LU F, LURIE KG, ERMIS C. Effect of cough on heart rate and blood pressure in patients with “cough syncope”. Heart Rhythm. 2005;2:807–813. doi: 10.1016/j.hrthm.2005.04.022. PubMed DOI

BRANDIMORE AE, TROCHE MS, HUBER JE, HEGLAND KW. Respiratory kinematic and airflow differences between reflex and voluntary cough in healthy young adults. Front Physiol. 2015;6:284. doi: 10.3389/fphys.2015.00284. PubMed DOI PMC

BRANDON N. Premature atrial contraction as an etiology for cough. Chest. 2008;133:828. doi: 10.1378/chest.07-2059. PubMed DOI

BRIGNOLE M, MOYA A, DE LANGE FJ, DEHARO JC, ELLIOTT PM, FANCIULLI A, FEDOROWSKI A, FURLAN R, KENNY RA, MARTÍN A, PROBST V, REED MJ, RICE CP, SUTTON R, UNGAR A, van DIJK JG ESC Scientific Document Group. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J. 2018;39:1883–1948. doi: 10.5603/kp.2018.0161. PubMed DOI

BUDAY T, BROZMANOVA M, BIRINGEROVA Z, GAVLIAKOVA S, POLIACEK I, CALKOVSKY V, SHETTHALLI MV, PLEVKOVA J. Modulation of cough response by sensory inputs from the nose - role of trigeminal TRPA1 versus TRPM8 channels. Cough. 2012;8:11. doi: 10.1186/1745-9974-8-11. PubMed DOI PMC

CANNING BJ, MORI N, MAZZONE SB. Vagal afferent nerves regulating the cough reflex. Respir Physiol Neurobiol. 2006;152:223–242. doi: 10.1016/j.resp.2006.03.001. PubMed DOI

CANNING BJ, CHOU YL. Cough sensors. I. Physiological and pharmacological properties of the afferent nerves regulating cough. Handb Exp Pharmacol. 2009;187:23–47. doi: 10.1007/978-3-540-79842-2_2. PubMed DOI

CANNING BJ. Afferent nerves regulating the cough reflex: mechanisms and mediators of cough in disease. Otolaryngol Clin North Am. 2010;43:15–25. doi: 10.1016/j.otc.2009.11.012. PubMed DOI PMC

CANNING BJ, CHANG AB, BOLSER DC, SMITH JA, MAZZONE SB, MCGARVEY L CHEST EXPERT COUGH PANEL. Anatomy and neurophysiology of cough: CHEST Guideline and Expert Panel report. Chest. 2014;146:1633–1648. doi: 10.1016/j.chest.2016.03.014. PubMed DOI PMC

CHOI YS, KIM JJ, OH BH, PARK YB, SEO JD, LEE YW. Cough syncope caused by sinus arrest in a patient with sick sinus syndrome. Pacing Clin Electrophysiol. 1989;12:883–886. doi: 10.1111/j.1540-8159.1989.tb05024.x. PubMed DOI

DAVENPORT PW. Clinical cough I: the urge-to-cough: a respiratory sensation. Handb Exp Pharmacol. 2009;187:263–276. PubMed

DICPINIGAITIS PV, LIM L, FARMAKIDIS C. Cough syncope. Respir Med. 2014;108:244–251. PubMed

DICPINIGAITIS PV, KANTAR A, ENILARI O, PARAVATI F. Prevalence of Arnold nerve reflex in adults and children with chronic cough. Chest. 2018;153:675–679. doi: 10.1016/j.chest.2017.11.019. PubMed DOI

FERASIN L, LINNEY C. Coughing in dogs: what is the evidence for and against a cardiac cough? J Small Anim Pract. 2019;60:139–145. doi: 10.1111/jsap.12976. PubMed DOI

GANDEVIA SC, BUTLER JE, TAYLOR JL, CRAWFORD MR. Absence of viscerosomatic inhibition with injections of lobeline designed to activate human pulmonary C fibers. J Physiol. 1998;511:289–300. doi: 10.1111/j.1469-7793.1998.289bi.x. PubMed DOI PMC

GIRSKY MJ, CIRLEY JM. Images in cardiovascular medicine. Cough cardiopulmonary resuscitation revisited. Circulation. 2006;114:e530–e531. doi: 10.1161/circulationaha.106.620773. PubMed DOI

HARGREAVES M, CHANNON K. Mechanism of pacemaker induced cough. Br Heart J. 1994;71:484–486. doi: 10.1136/hrt.71.5.484. PubMed DOI PMC

HART G, OLDERSHAW PJ, CULL RE, HUMPHREY P, WARD D. Syncope caused by cough-induced complete atrioventricular block. Pacing Clin Electrophysiol. 1982;5:564–566. doi: 10.1111/j.1540-8159.1982.tb02279.x. PubMed DOI

HASDEMIR C, MUSAYEV O, KEHRIBAR DY, KARTAL Y, CAN LH. Chronic cough and tachycardia-induced cardiomyopathy in a patient with idiopathic frequent, monomorphic premature ventricular contractions. Pacing Clin Electrophysiol. 2013;36:e156–e158. doi: 10.1111/j.1540-8159.2011.03236.x. PubMed DOI

IRANI F, SANCHIS J. Inspiration- and cough-induced atrioventricular block. Can Med Assoc J. 1971;105:735–756. PubMed PMC

IRWIN RS, FRENCH CL, CHANG AB, ALTMAN KW. CHEST Expert cough panel classification of cough as a symptom in adults and management algorithms: CHEST guideline and expert panel report. Chest. 2018;153:196–209. doi: 10.1016/j.chest.2016.03.014. PubMed DOI PMC

JAVORKOVA N, VARECHOVA S, PECOVA R, TATAR M, BALAZ D, DEMETER M, HYRDEL R, KOLLARIK M. Acidification of the esophagus acutely increases the cough sensitivity in patients with gastrooesophageal reflux and chronic cough. Neurogastroenterol Motil. 2008;20:119–124. doi: 10.1111/j.1365-2982.2007.01020.x. PubMed DOI

KALLA M, HERRING N, PATERSON DJ. Cardiac sympatho-vagal balance and ventricular arrhythmia. Auton Neurosci. 2016;199:29–37. doi: 10.1016/j.autneu.2016.08.016. PubMed DOI PMC

KARDOS P, BERCK H, FUCHS KH, GILLISSEN A, KLIMEK L, MORR H, PFEIFFER-KASCHA D, SCHULTZE-WERNINGHAUS G, SITTER H, VOSHAAR T, WORTH H. German Respiratory Society for diagnosis and treatment of adults suffering from acute or chronic cough. Guidelines of the German Respiratory Society for diagnosis and treatment of adults suffering from acute or chronic cough. Pneumologie. 2010;64:701–711. doi: 10.1055/s-0030-1255526. PubMed DOI

KOLLARIK M, BROZMANOVA M. Cough and gastroesophageal reflux: insights from animal models. Pulm Pharmacol Ther. 2009;22:130–134. doi: 10.1016/j.pupt.2008.12.017. PubMed DOI PMC

KOLLARIK M, RU F, BROZMANOVA M. Vagal afferent nerves with the properties of nociceptors. Auton Neurosci. 2010;153:12–20. doi: 10.1016/j.autneu.2009.08.001. PubMed DOI PMC

KRYŃSKI T, STEC S, MAKOWSKA E, SWIATKOWSKI M, SZYMOT J, KUŁAKOWSKI P. Atrial infarction or ischaemia as the cause of atrial pacing failure in a patient with acute myocardial infarction. Kardiol Pol. 2007;65:1381–1383. PubMed

LAI K, SHEN H, ZHOU X, QIU Z, CAI S, HUANG K, WANG Q, WANG C, LIN J, HAO C, KONG L, ZHANG S, CHEN Y, LUO W, JIANG M, XIE J, ZHONG N. Clinical practice guidelines for diagnosis and management of cough-Chinese Thoracic Society (CTS) Asthma Consortium. J Thorac Dis. 2018;10:6314–6351. doi: 10.21037/jtd.2018.09.153. PubMed DOI PMC

LEE D, BELDNER S, POLLARO F, JADONATH R, MACCARO P, GOLDNER B. Cough-induced heart block. Pacing Clin Electrophysiol. 1999;22:1270–1271. doi: 10.1111/j.1540-8159.1999.tb00615.x. PubMed DOI

LEE LY, PISARRI TE. Afferent properties and reflex functions of bronchopulmonary C-fibers. Respir Physiol. 2001;125:47–65. doi: 10.1016/s0034-5687(00)00204-8. PubMed DOI

LO MAURO A, ALIVERTI A. Blood shift during cough: negligible or significant? Front Physiol. 2018;9:501. doi: 10.3389/fphys.2018.00501. PubMed DOI PMC

MAZZONE SB. An overview of the sensory receptors regulating cough. Cough. 2005;1:2. doi: 10.1186/1745-9974-1-2. PubMed DOI PMC

McLACHLAN CS, YOW SZ, AL-ANAZI M, EL OAKLEY RM. Letter by McLachlan et al regarding article, “Cough cardiopulmonary resuscitation revisited”. Circulation. 2007;115:e460. doi: 10.1161/circulationaha.106.672204. PubMed DOI

NIIMI A, KIHARA Y, SUMITA Y, OKANO Y, TAMBARA K, FUJITA M. Cough reflex by ventricular premature contractions. Int Heart J. 2005;46:923–926. doi: 10.1536/ihj.46.923. PubMed DOI

ODEH M, OLIVEN A. A man who coughed for 15 years before a doctor took his pulse. Lancet. 1996;348:378. doi: 10.1016/s0140-6736(96)03432-0. PubMed DOI

OMORI I, YAMADA C, INOUE D, KATSUME H, IJICHI H. Tachyarrhythmia provoked by coughing and other stimuli. Chest. 1984;86:797–799. doi: 10.1378/chest.86.5.797. PubMed DOI

OZTURK S, YETKIN E. An innocent etiology of chronic cough: premature atrial contraction. Int J Cardiovasc Res. 2016;5:6. doi: 10.4172/2324-8602.1000290. DOI

PACHON JC, PACHON EI, PACHON JC, LOBO TJ, PACHON MZ, VARGAS RN, JATENE AD. “Cardioneuroablation”--new treatment for neurocardiogenic syncope, functional AV block and sinus dysfunction using catheter RF-ablation. Europace. 2005;7:1–13. doi: 10.1016/j.eupc.2004.10.003. PubMed DOI

PATBERG KW, de GROOT JR, REESINK HJ, SNIJDERS D, STERK PJ, BEL EHD. Cardiac arrhythmia induced cough: demonstrable but not clinically significant in chronic cough. Am J Respir Crit Care Med. 2012;185:A5847. doi: 10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a5847. DOI

PONIKOWSKI P, VOORS AA, ANKER SD, BUENO H, CLELAND JG, COATS AJ, FALK V, GONZÁLEZ-JUANATEY JR, HARJOLA VP, JANKOWSKA EA, JESSUP M, LINDE C, NIHOYANNOPOULOS P, PARISSIS JT, PIESKE B, RILEY JP, ROSANO GM, RUILOPE LM, RUSCHITZKA F, RUTTEN FH, van der MEER P. Authors/Task Force Members, Document Reviewers: 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 J Heart Fail. 2016;18:891–975. doi: 10.1002/ejhf.592. PubMed DOI

RAJ H, SINGH VK, ANAND A, PAINTAL AS. Sensory origin of lobeline-induced sensations: a correlative study in man and cat. J Physiol. 1995;482(Pt 1):235–246. doi: 10.1113/jphysiol.1995.sp020513. PubMed DOI PMC

REISIN L, BLAER Y, JAFARI J, MANOACH M. Cough-induced nonsustained ventricular tachycardia. Chest. 1994;105:1583–1584. doi: 10.1378/chest.105.5.1583. PubMed DOI

RESUSCITATION COUNCIL (UK) Statement on cough CPR. [Accessed 22 September 2019]. https://www.resus.org.uk/cpr/statement-on-cough-cpr .

RUCKDESCHEL ES, WOLFEL E, NGUYEN DT. A Case of cough-induced ventricular tachycardia in a patient with a left ventricular assist device. Card Electrophysiol Clin. 2016;8:165–167. doi: 10.1016/j.ccep.2015.10.019. PubMed DOI

RYBAK IA, O’CONNOR R, ROSS A, SHEVTSOVA NA, NUDING SC, SEGERS LS, SHANNON R, DICK TE, DUNIN-BARKOWSKI WL, OREM JM, SOLOMON IC, MORRIS KF, LINDSEY BG. Reconfiguration of the pontomedullary respiratory network: a computational modeling study with coordinated in vivo experiments. J Neurophysiol. 2008;100:1770–1799. doi: 10.1152/jn.90416.2008. PubMed DOI PMC

SACHER F, MONAHAN KH, THOMAS SP, DAVIDSON N, ADRAGAO P, SANDERS P, HOCINI M, TAKAHASHI Y, ROTTER M, ROSTOCK T, HSU LF, CLÉMENTY J, HAÏSSAGUERRE M, ROSS DL, PACKER DL, JAÏS P. Phrenic nerve injury after atrial fibrillation catheter ablation: characterization and outcome in a multicenter study. J Am Coll Cardiol. 2006;47:2498–2503. doi: 10.1016/j.jacc.2006.02.050. PubMed DOI

SAITO D, MATSUNO S, MATSUSHITA K, TAKEDA H, HYODO T, HARAOKA S, WATANABE A, NAGASHIMA H. Cough syncope due to atrio-ventricular conduction block. Jpn Heart J. 1982;23:1015–1020. doi: 10.1536/ihj.23.1015. PubMed DOI

SAKIHARA E, KURIYAMA A, OKABE K, IKEGAMI T. An unexpected cause of chronic cough in a young woman: Tachycardia-induced cardiomyopathy. Am J Emerg Med. 2019;37:563.e5–563.e7. doi: 10.1016/j.ajem.2018.12.014. PubMed DOI

SELLICK H, WIDDICOMBE JG. The activity of lung irritant receptors during pneumothorax, hyperpnoea and pulmonary vascular congestion. J Physiol. 1969;203:359–381. doi: 10.1113/jphysiol.1969.sp008868. PubMed DOI PMC

SHARPEY-SCHAFER EP. Effects of coughing on intrathoracic pressure, arterial pressure and peripheral blood flow. J Physiol. 1953;122:351–357. doi: 10.1113/jphysiol.1953.sp005004. PubMed DOI PMC

SHEN WK, SHELDON RS, BENDITT DG, COHEN MI, FORMAN DE, GOLDBERGER ZD, GRUBB BP, HAMDAN MH, KRAHN AD, LINK MS, OLSHANSKY B, RAJ SR, SANDHU RK, SORAJJA D, SUN BC, YANCY CW. 2017 ACC/AHA/HRS Guideline for the evaluation and management of patients with syncope: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2017;70:620–663. doi: 10.1161/cir.0000000000000498. PubMed DOI

SHEPHERD JT. The lungs as receptor sites for cardiovascular regulation. Circulation. 1981;63:1–10. doi: 10.1161/01.cir.63.1.1. PubMed DOI

SHEPHERD JT. The heart as a sensory organ. J Am Coll Cardiol. 1985;5(6 Suppl):83B–87B. doi: 10.1016/s0735-1097(85)80533-7. PubMed DOI

SHIVKUMAR K, AJIJOLA OA, ANAND I, ARMOUR JA, CHEN PS, ESLER M, DE FERRARI GM, FISHBEIN MC, GOLDBERGER JJ, HARPER RM, JOYNER MJ, KHALSA SS, KUMAR R, LANE R, MAHAJAN A, PO S, SCHWARTZ PJ, SOMERS VK, VALDERRABANO M, VASEGHI M, ZIPES DP. Clinical neurocardiology defining the value of neuroscience-based cardiovascular therapeutics. J Physiol. 2016;594:3911–3954. doi: 10.1113/jp271870. PubMed DOI PMC

STEC S, DABROWSKA M, ZABORSKA B, BIELICKI P, MASKEY-WARZECHOWSKA M, TARNOWSKI W, CHAZAN R, KULAKOWSKI P. Premature ventricular complex-induced chronic cough and cough syncope. Eur Respir J. 2007;30:391–394. doi: 10.1183/09031936.00062606. PubMed DOI

STEC SM, GRABCZAK EM, BIELICKI P, ZABORSKA B, KRENKE R, KRYŃSKI T, DĄBROWSKA M, DOMAGAŁA-KULAWIK J, DOMERACKA-KOŁODZIEJ A, SIKORSKA A, KUŁAKOWSKI P, CHAZAN R. Diagnosis and management of premature ventricular complexes-associated chronic cough. Chest. 2009;135:1535–1541. doi: 10.1378/chest.08-1814. PubMed DOI

TAKAZAWA T, IKEDA K, KANO O, KABUKI T, KAWABE K, IWASAKI Y. A case of sinus arrest and post-hiccup cough syncope in medullary infarction. J Stroke Cerebrovasc Dis. 2014;23:566–571. doi: 10.1016/j.jstrokecerebrovasdis.2013.04.016. PubMed DOI

TRETHEWEY SP. ‘Cough CPR’: Misinformation perpetuated by social media. Resuscitation. 2018;133:e7–e8. doi: 10.1016/j.resuscitation.2018.10.003. PubMed DOI

WALDMANN V, COMBES N, NARAYANAN K, SHARIFZADEHGAN A, BOUZEMAN A, BEGANTON F, COMBES S, ALBENQUE JP, BOVEDA S, MARIJON E. Cough Syncope. Am J Med. 2017;130:e295–e296. doi: 10.1016/j.amjmed.2017.01.050. PubMed DOI

WANG X, LI Z, WANG J, HE B. The application of catheter ablation in a rare case with coughing-induced supraventricular tachyarrhythmias. Clinical Case Rep. 2017;5:2133–2135. doi: 10.1002/ccr3.1078. PubMed DOI PMC

WEI JY, GREENE HL, WEISFELDT ML. Cough-facilitated conversion of ventricular tachycardia. Am J Cardiol. 1980;45:174–176. doi: 10.1016/0002-9149(80)90235-0. PubMed DOI

WEI JY, HARRIS WS. Heart rate response to cough. J Appl Physiol Respir Environ Exerc Physiol. 1982;53:1039–1043. doi: 10.1152/jappl.1982.53.4.1039. PubMed DOI

WEI JY, ROWE JW, KESTENBAUM AD, BEN HAIM S. Post-cough heart rate response: influence of age, sex, and basal blood pressure. Am J Physiol. 1983;245:R18–R24. doi: 10.1152/ajpregu.1983.245.1.r18. PubMed DOI

WIDDICOMBE JG. Neurophysiology of the cough reflex. Eur Respir J. 1995;8:1193–1202. doi: 10.1183/09031936.95.08071193. PubMed DOI

Legacy of Prof. Juraj Korpáš: International Impact of Slovak School of Experimental Respirology