New Study Sheds Light on Cardiac Arrhythmia Risk

Two new basic animal studies have shed light on alcohol consumption and the heart. The first study may help explain why excessive drinking can sometimes cause arrhythmias and how to prevent it. The second study investigated why alcohol may negatively affect heart function in women taking estrogen replacement therapy. Both studies are preliminary research for posters presented at the American Heart Association's 2024 Basic Cardiovascular Science Scientific Sessions. The conference will be held in Chicago from July 22-25, 2024, and will offer the latest research on innovations and discoveries in cardiovascular science.

Excessive alcohol consumption (5 drinks within 2 hours for men and 4 drinks within 2 hours for women) is common worldwide. Recent studies also show that the incidence of atrial fibrillation (AFib), the most common type of arrhythmia, continues to rise.

“The holiday season brings with it a short period of celebration that often involves heavy drinking. Unfortunately, this can send people with no previous heart problems to the hospital with a racing or abnormally beating heart,” said Saugat Kanal, PhD, lead author of the study and a postdoctoral researcher in the Department of Physiology and Cell Biology at The Ohio State University College of Medicine in Columbus, Ohio. “In our mouse study, we investigated the mechanism of alcohol-induced arrhythmia and possible ways to prevent it in the future.”

“Repeated heavy drinking can lead to serious arrhythmias, including atrial fibrillation, the most common type of arrhythmia,” Canal said.

Atrial fibrillation can increase the risk of stroke and heart failure. Approximately one-third of new diagnoses of atrial fibrillation are related to alcohol use. People who habitually drink excessively often have recurrent atrial fibrillation. The link between repeated heavy drinking during celebrations and arrhythmia is so well-known that medical experts call it Holiday Heart Syndrome, which is caused by excessive drinking during the holidays.

Saugat Kanal, postdoctoral researcher in the Department of Physiology and Cell Biology at The Ohio State University College of Medicine, Columbus

Previous animal studies by the research team found that arrhythmias linked to heavy drinking are caused by an increase in the stress-induced protein JNK2, which can cause heart cells to misprocess calcium and malfunction, causing the heart to beat too fast or irregularly. The new study is the first to suggest that the molecule Alda-1 may prevent the activation of JNK2 that causes atrial fibrillation.

As a result of the investigation, the following was discovered:

• In the study, more than 70 percent of mice given alcohol to mimic binge drinking developed atrial fibrillation, whereas mice that were also given the investigational cardioprotectant Alda-1 did not develop atrial fibrillation.
• Exposure to excessive levels of alcohol doubled JNK2 activity levels compared to a control group that did not mimic binge drinking, and this activated JNK2 increased AFib susceptibility in a mouse model that mimicked binge drinking.
• In cardiac cells from mice treated with Alda-1, both JNK2 enzyme activity and calcium handling remained normal.

“abstinence “Abstaining from alcohol can prevent most alcohol-related risks of atrial fibrillation. Unfortunately, despite national awareness campaigns, excessive drinking continues to increase across all age groups. Our findings suggest that the development of new medications, including Alda-1 and other JNK2-specific inhibitors, may be an effective approach to atrial fibrillation in patients with Holiday Heart Syndrome,” said Khanal.

The study was limited because the researchers used a mouse model to replicate Holiday Heart Syndrome in humans, and although the mouse model showed promising results, it may not have fully captured the complexity of excessive drinking in humans and its associated effects on the cardiovascular system.

“Studies using larger animals will be the future direction to translate our exciting findings into clinical applications,” Canal said.

Research background and details:

• The mice used in the study were split into three groups: the Holiday Heart Syndrome group consumed alcohol four times on alternate days, mimicking binge drinking on holidays in humans; the Alda-1 group received the cardioprotectant Aldi-1 in addition to the alcohol regimen; and the control group received saline (no alcohol) or Alda-1 exposure.
• Outcome measures were obtained 24 hours after the last alcohol intake. Measures used included:
• Burst pacing-induced atrial arrhythmias were evaluated by electrophysiological testing.
• In calcium imaging studies, we investigated the effect of Alda-1 on JNK2-dependent calcium mishandling.
• Biochemical assays were used to examine the effects of alcohol on ALDH2 expression and the apoptosis signaling pathway.

Co-authors, their disclosures, and funding sources are listed in the abstract.

The hormone estrogen helps keep blood vessels open and flexible, and is generally thought to protect women from heart disease. Premenopausal women have higher estrogen levels, which means they may have fewer heart attacks and strokes than men of the same age. But exposure to alcohol worsens cardiovascular function in women more than in men, the researchers said. And previous animal studies have confirmed that alcohol worsens heart function more in animals with the highest estrogen levels.

The study investigated whether regular alcohol exposure led to differences in several measures of heart function and the proteins that control it in female rats who were given a hormone to supplement their estrogen supply and those who were not.

The eight-week study involved female rats whose ovaries had been removed to simulate menopause (the period when the ovaries produce virtually no estrogen). The researchers compared menopausal rats that were regularly exposed to alcohol (5% ethanol mixed into their liquid diet) with rats that were given alcohol and estrogen replacement.

In this study, menopausal rats treated with estrogen replacement and alcohol, compared to those who consumed alcohol alone, showed:

• Both positive (weight gain and fat mass loss) and negative (increased blood pressure and heart rate) changes in indicators related to heart health.
• A decrease in the heart's ejection fraction (the heart's ability to pump oxygen-rich blood to the rest of the body) and two other indicators of impaired pumping function that can eventually lead to heart failure.
• Disruption of circadian clock proteins, known to regulate cardiac and other bodily functions, increased both oxidative stress in heart cells (which can lead to plaque buildup in arteries) and ferroptosis (a type of cell death caused by iron overload).

“Estrogen is known to have cardioprotective effects, so we were surprised to see its significant effect on alcohol-induced cardiac dysfunction. Pre- and perimenopausal women taking hormone replacement therapy should be careful because alcohol consumption may be a contributing factor in cardiac dysfunction,” said Saeed Anees Ahmed, PhD, a postdoctoral research fellow in pharmacology and toxicology at the Brody School of Medicine at East Carolina University in Greenville, North Carolina, and lead author of the study.

The findings are limited by the short duration of the study and the use of an animal model. The study was conducted on rats, so it may not fully represent the long-term effects of estrogen intake and regular alcohol consumption in menopausal women as they age.

The American Heart Association recommends moderate alcohol intake for optimal cardiovascular health. If you don't drink alcohol already, don't start. If you drink alcohol, talk to your doctor about the benefits and risks of drinking in moderation. Some people should not drink alcohol at all, including women who are pregnant or planning to become pregnant, people under the age of 21, and people with certain health conditions. The Association does not recommend drinking wine or other alcohol to obtain potential health benefits. Instead, take steps to lower cholesterol, control high blood pressure, manage your weight, get enough exercise, get enough sleep, avoid tobacco, and eat a healthy diet, as detailed in the Association's “Eight Essential Things to Do in Life” recommendations.