What is the pathophysiology of holiday heart syndrome (HHS)?

Updated: May 30, 2018
  • Author: Lawrence Rosenthal, MD, PhD, FACC, FHRS; Chief Editor: Jose M Dizon, MD  more...
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Answer

Several mechanisms are theorized to be responsible for the arrhythmogenicity of alcohol. They may be characterized into two broad groups: direct effects on the myocardium and alcohol's effect on traditional risk factors for atrial fibrillation.

With regard to direct effects on the atrial myocardium, alcohol causes a autonomic nervous system imbalance. Alcohol increases sympathetic nervous system (SNS) activity (and its related increased secretion of epinephrine and norepinephrine), with resultant effects including an increased release of calcium into the myocytes from the sarcoplasmic reticulum. [3, 10] Increased SNS activity is further evidenced by a marked increase in the incidence of sinus tachycardia and reduced respiratory sinus arrhythmia during acute alcohol intoxication. [11] Consequently, the parasympathetic nervous system (PNS) is activated as well, with an increased intermittent vagal tone, which has been shown to also shorten the atrial refractory period and preciptate atrial fibrillation. [10] Note that the risk of atrial fibrillation persists into the "hangover" and/or withdrawal phase, which corresponds with an increased sympathetic tone. [3]

Other direct effects on the myocardium are perhaps less well studied. They include the effects of alcohol's primary metabolite acetaldehyde, which is associated with local inflammation and oxidative stress. [10]  Alcohol itself can also directly decrease the myocyte sodium current and can affect intracellular pH, ether causing acidosis with low doses or alkalosis with higher doses. Interestingly, these effects may be species specific, with rabbits [12] and humans being similarly affected, whereas canine atria appear unaffected. [13]  Research indicates that cardiac cells exposed to ethanol doses of 0.1% or greater undergo extrusion of magnesium (Mg2+), possibly owing to ethanol oxidation by cytochrome P-450 2E1; whether this contributes to alcoholic cardiomyopathy is not known. [14, 15]

A more recent study revealed that binge alcohol consumption activates the stress kinase JNK (c-Jun N-terminal kinase) (JNK2), which subsequently phosphorylates (and activates) the CaMKII protein, thereby enhancing CaMKII-driven mishandling of sarcoplasmic reticulum calcium—which prompts aberrant calcium waves and enhances susceptibility to atrial arrhythmia. [8] Conversely, CaMKII inhibition eliminates binge alcohol-evoked arrhythmic activities.

In another recent study involving isolated human atrial and murine atrial or ventricular cardiomyocytes, investigators indicated sarcoplasmic reticulum calcium leak as well as disordered excitation-contraction coupling as the basis for the arrhythmogenic and negative inotropic effects (reduced systolic calcium release) of acute ethanol exposure. [16] The investigators noted that production of reactive oxygen species (ROS) via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) and oxidative activation of CaMKII appeared have key roles in the mechanism of action.

Analysis of electrocardiograms (ECGs) performed following the resolution of arrhythmias in patients who have consumed a large quantity of alcohol shows significant prolongation of the PR, QRS, and QT intervals compared to that of patients who experienced arrhythmias in the absence of alcohol consumption. [1, 17]


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