Chinese Journal of Physiology 59(1): 1-8, 2016 1 DOI: 10.4077/CJP.2016.BAE364 Review Article A Heart too Drunk to Drive; AV Block following Acute Alcohol Intoxication Arthur H. van Stigt1, #, Ruben J. Overduin1, #, Liza C. Staats1, #, Vera Loen1, #, and Marcel A.G. van der Heyden2 1Participant in the Honours Program CRU2006 Bachelor, University Medical Center Utrecht, Heidelberglaan 100, 3584 CM, Utrecht, and 2Department of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Yalelaan 50, 3584 CM Utrecht, The Netherlands Abstract Acute excessive alcohol consumption is associated with heart rhythm disorders like atrial fibrilla- tion but also premature ventricular contractions, collectively known as the “holiday heart syndrome”. More rarely but clinically significant are reports of atrioventricular (AV) conduction disturbances in binge drinkers with no underlying heart disease or chronic alcohol consumption. To obtain better insights into common denominators and the potential underlying mechanisms we collected and com- pared individual case reports of AV block following acute alcohol intoxication in otherwise healthy people. By screening PubMed, Google Scholar, Scopus and JSTOR, fifteen cases were found of which eight were sufficiently documented for full analysis. Blood alcohol levels ranged from 90 to 958 mg/dl (19 to 205 mM). Second and third degree AV block was observed most (6/8) albeit that in two of these patients a vagal stimulus led to deterioration from first into higher order AV block. In all cases, patients reverted to normal sinus rhythm upon becoming sober again. Mildly lowered body temperature (35.9 ± 0.5°C) was observed but can be excluded as a major cause of conduction blockade. We hypothesize that ethanol induced partial inhibition of calcium and potentially also sodium currents in conductive tissue structures may be one of the mechanisms of conduction slowing and block that may become exaggerated upon increased vagal tone. An impairment of gap junction function cannot be excluded as a contributing factor. In conclusion, cases of documented alcohol induced AV block are very rare but events can occur at relatively low serum alcohol levels which should prompt to awareness of this phenomenon in alcohol intoxicated patients. Key Words: alcohol, AV block, conduction, ECG, heart, intoxication, ion channel Introduction junctions (allowing direct ion flow from cell to cell) and connective tissue strands (producing an optimal The atrioventricular (AV) conduction system is source-sink relationship) (29). All four components essential for an optimal cardiac performance in which are subjected to tight regulation by numerous signal- timing of atrial contraction is tuned to its ventricular ing pathways of which some can adapt very rapidly counterpart. The speed of impulse propagation is de- to encounter the ever changing physiological demands, pendent on the amounts of depolarizing currents (cal- e.g. the sympathetic and parasympathetic pathways. cium and sodium currents determining action potential Many environmental substances can influence the AV upstroke), repolarizing potassium currents (determining conduction pathway by addressing one or more of the action potential duration and refractory period), gap above mentioned players. For example, grayanotoxins Corresponding author: Dr. Marcel A.G. van der Heyden, Department of Medical Physiology, Division of Heart & Lungs, Yalelaan 50, 3584 CM Utrecht, The Netherlands. Tel: +31 30 2538901, Fax: +31 30 2539064, E-mail: [email protected] #These authors contributed equally. Received: March 13, 2015; Revised (Final Version): May 21, 2015; Accepted: June 2, 2015. 2016 by The Chinese Physiological Society and Airiti Press Inc. ISSN : 0304-4920. http://www.cps.org.tw 2 van Stigt, Overduin, Staats, Loen and van der Heyden present in honey produced from the flowers of several marize the common denominators in individual cases family members of Ericaceae plants have strong vagal of alcohol induced acute AV block in otherwise healthy effects resulting in severe cases of conduction block individuals to gain better insights into the clinical course (26). Perturbation of AV conduction is classified in and etiology of this potentially dangerous condition. several categories. Whereas normal human PR intervals on the electrocardiography (ECG) are between 120 and Materials and Methods 200 ms, first-degree AV block is characterized by sinus rhythm with lengthening of PR times beyond 200 ms. PubMed, Google Scholar, Scopus and JSTOR Second-degree block shows both conducted and non- were screened for case reports published until No- conducted impulses in three different constitutions vember 2014, using combinations of the following (Mobitz type I and II, and 2:1/3:1 block). Third-degree search terms: ‘AV block’, ‘atrioventricular block’, AV block occurs when none of the atrial electrical ‘alcohol’, ‘ethanol’, ‘intoxication’, ‘PR prolongation’ activity is conducted to the ventricles (8). and ‘holiday heart syndrome’. French and German Alcohol is a well-known environmental factor equivalents of these search terms were also used to affecting heart function, structure and electrophysi- screen the above mentioned databases. References in ology. Chronic alcohol consumption (at least > 90 primary case-reports were used to retrieve additional g/day for five years or more) can result in alcoholic cases. A Chinese native speaker screened Chinese cardiomyopathy that is characterized by cardiac dys- literature bases with similar search terms. function, left ventricular dilation, normal or reduced left ventricular wall thickness, increased left ventricu- Results lar mass and normal ejection fraction to the point of severe alcoholic cardiomyopathy (14, 31). Atrial fibril- Cases of Acute AV Block following Alcohol Intake lation is one of the most common arrhythmias asso- ciated with severe chronic alcohol intake (14), whereas We found ten articles presenting a total of 15 ventricular arrhythmias and sudden cardiac death are cases. Upon further scrutiny three articles were less frequently observed (45). Furthermore, cardiac excluded from further analysis for the following conduction disturbances and even complete AV block reasons. In two articles (6 cases) the ECG param- have also been observed in heavy drinkers (32). In eters and clinical symptoms of the multiplex of 1978, Ettinger was the first to describe the relation- cases were described too briefly and with too little ship between acute excessive alcohol consumption and clinical details to allow any comparison with other cardiac (particularly supraventricular tachy-) ar- cases (23, 33). The third excluded article (1 case) rhythmias in allegedly healthy subjects under the was considered a semi-acute alcohol intoxication in name ‘holiday heart syndrome’ (18). The incidence which consumption of large quantities of whiskey of binge drinking (more than 5 alcoholic beverages had taken place since several weeks prior to AV block in one occasion) in adolescent and young adults re- (21). The remaining seven case reports describing mains at a high level in the last decade.1 The most 8 individual cases on non-chronic alcohol intake commonly seen arrhythmia after binge drinking in followed by an AV block in humans were used in the Ettinger study is atrial fibrillation, followed by our analysis. A short description of the individual atrial flutter, isolated ventricular premature beats, cases is presented and additional numerical data isolated atrial premature complexes and paroxysmal and key information are presented in Table 1. atrial tachycardia. Most of the included patients were Abdelazis et al. (2) (case 1): a 14-year-old boy however heavy periodical drinkers and the holiday was admitted with acute alcohol ingestion. On admis- heart syndrome was therefore initially considered sion, bradycardia (53 bpm) was noted. Saline infusion to be linked to chronic alcohol consumption. In ad- was given in view of hypotension. ECG showed second- dition to a case described by Ettinger, several other degree AV block (Mobitz type I with Wenkebach phe- studies showed cardiac arrhythmias after binge nomenon). Urine did not show any trace of other drugs drinking in non-alcoholic healthy subjects (17, 41), besides alcohol. The next day a repeated ECG was hinting at a true relationship between acute alcohol normal, as well as a twenty-four hours ambulatory intake and cardiac arrhythmias. Moreover, cases of ECG and an echocardiography. incidental excessive alcohol intake leading to acute Abdelazis et al. (2) (case 2): a 15-year-old girl was AV block have been reported as well, but this phe- admitted with acute alcohol ingestion. ECG showed nomenon is rather rare and data are scattered. It was, a first-degree AV block. Except for a slow heart rate therefore, the purpose of this short review to sum- (60 bpm), cardiorespiratory observations showed no 1Substance Abuse and Mental Health Services Administration, Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-48, HHS Publication No. (SMA) 14-4863. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2014. Table 1. Overview of acute ethanol intoxication cases with occurrence of any type of AV block Age Sex Origin of Serum Alcohol Type AV Block Clinical Signs Body Core Treatment Outcome Reference (y) Case Report Ethanol Level Source Temperature (mg/dl) (°C) 14 M United Unknown Unknown 2dAVB (Mobitz I Bradycardia (HR