holiday heart: alcohol and atrial fib

 

in the spirit of the upcoming holiday season, there was a recent article finding that even moderate alcohol consumption was associated with atrial fibrillation (“holiday heart”), in a dose-dependent manner (see: alcohol and atrial fib AIM2021 in dropbox, or doi:10.7326/M21-0228) 

               

Details: 

-- 100 consecutive patients at least 21 years old with a history of documented paroxysmal atrial fibrillation (AF) who consumed on average at least one standard alcohol drink per month, recruited from cardiology clinics at UCSF

-- they excluded patients with documented substance use disorder (alcohol or other)

-- mean age 64, 79% male, 85% white/9% Asian/3% Black, smoking: 1% current/23% former/25% never

-- median alcohol drinks: median of 19 drinks (IQR 10-38 drinks) on a median 12 different days (IQR 7-21 days); IQR = intraquartile range, which compares the distance between the 1st and 3rd quartiles to see the variability in the middle half of the data

-- hypertension 24%, diabetes 6%, coronary artery disease 16%, heart failure 6%

-- antiarrhythmics, comparing those not developing AF vs those who did: flecainide 27% vs 9%, dofetilide 14% vs 9%, propafenone 9% vs 5%, rest under 5% [ie, being on antiarrhythmic decreased AF occurrences]

 

--the first 27 participants were fitted with a LifeWatch ambulatory cardiac telemetry unit, to wear for 4 weeks, the remainder of participants were given 2 successive Zio patches for 2 weeks each; these devices accurately record single-lead EKGs to detect episodes of AF

-- alcohol use assessment:

    -- patients were instructed to activate a button on the EKG monitor every time they had a standard alcoholic drink (the equivalent of a glass of wine, 12 ounces of beer, or a shot of spirits), as self-reported drinking events, but not to activate the button other times

    -- participants were also fitted with a transdermal alcohol sensor around the ankle for passive alcohol monitoring: SCRAM (Secure Continuous Remote Alcohol Monitor) which reliably detects alcohol consumption above 2 to 3 drinks per occasion but also detects lower amounts of alcohol

    -- there were in-person visits at 2 and 4 weeks of the study to ensure adherence to the devices and place new devices if needed

    -- a fingerstick blood spot was collected for phosphatidylethanol (PEth), an abnormal phospholipid formed in the blood only after the presence of alcohol use, which is able to detect high-risk consumption of alcohol for a 2-to-4-week period, the half-life being 4 to 10 days (though PEth is detectable at lower levels of alcohol use, including after a single drink)

-- 98% self-reported at least some drinking

-- 60% had at least some transdermal alcohol detection, 71% had a positive PEth result

 

-- Primary outcome: relationship between alcohol ingestion and AF events, timing between alcohol and AF, dose-response between alcohol and AF

-- statistical analysis involved dividing the day into one-hour or two-hour periods, to assess the short-term effects of alcohol intake on AF as per the heart monitor

 

Results: 

-- 56 people had at least one episode of AF

-- alcohol validation: PEth levels correlated with the number of real-time self-reported drinks as recorded when the patient pressed the button on the continuous EKG monitor, as well as events detected by the transdermal alcohol sensor (in the latter case, the odds of AF were 38% greater per 0.1% increase in blood peak alcohol concentration in the past 12 hours)

 

-- AF events in the preceding four hours were associated with:

    -- twofold higher odds of one alcoholic drink: OR 2.02 (1.38-3.17)

    -- threefold higher odds of at least two drinks: OR 3.58 (1.63-7.89)

    --and the events tended to cluster 2-4 hours after drinking:

 

                                             Figure 2. Odds of any real-time, self-reported drinking event before an AF                                                                                     episode, restricted to 2-hour increments 

-- AF episodes we associate with higher odds of peak blood alcohol concentration, OR 1.38 (1.04-1.83) per 0.1% increase in blood alcohol concentration

    -- AF episodes were also associated with the total area under the curve of alcohol exposure, OR 1.14 (1.06-1.22), per a 4.7% increase in alcohol exposure, as inferred from the transdermal ethanol sensor in the preceding 12 hours

 

Commentary:

--AF is really common, >12 million people have it, and so is drinking alcohol. So, this study is important because the old studies mostly were observational ones in heavy drinkers showing up in the emergency room. ?is alcohol and AF just true/true/and unrelated, as can co-occur with 2 common events? or was there a true alcohol causation?

--this study found a few important things not so clear from other studies: that only moderate alcohol consumption was associated with AF, that there was a dose-response relationship, that there was a delay of a few hours until the AF (ie, it was not simply direct alcohol toxicity, either to the heart or perhaps through esophageal irritation), and there was no clear evidence of a threshold effect (the relationship between AF episodes over time was fairly linear)

    -- the finding of increased AF in those with only 1 drink is quite profound, since older studies were observational (either in EDs, or by patient self-report of alcohol consumption, usually having drunk much more alcohol)

    -- also, the finding of cardioprotection  by alcohol (which did not include AF, by the way), has largely been debunked:

        -- likelihood of bias in studies finding moderate alcohol consumption was cardioprotective: http://gmodestmedblogs.blogspot.com/2015/02/moderate-alcohol-and-cardioprotection.html

        -- an interesting mendelian randomization study found no cardioprotective effect of moderate alcohol drinking in risk of stroke or heart disease (included in this blog above)

    -- decreasing alcohol consumption decreases AF recurrences and total AF burden: http://gmodestmedblogs.blogspot.com/2020/03/afib-dec-with-alcohol-abstinence.html

    -- zero alcohol was associated with fewer strokes, including using a genetic analysis: http://gmodestmedblogs.blogspot.com/2019/05/stroke-risk-lowest-if-zero-alcohol.html

    -- and, though alcohol is a known carcinogen, it is currently “acceptable” to allow up to 2 drinks/day for men and 1/d for women, with some recommendations even more generous: 2 drinks for women and no more than 10/week, 3 drinks for men and no more than 15/week.

        -- calculated lifetime risk of cancer is higher with alcohol consumption at the level of one bottle of wine a week: http://gmodestmedblogs.blogspot.com/2019/04/a-bottle-of-wine-week-and-cancer-risk.html

    -- in general, alcohol is the leading risk factor for death in those 15-45yo: http://gmodestmedblogs.blogspot.com/2018/10/alcohol-as-leading-risk-facor-for-death.html

 

-- the findings of this study are more reliable than previous studies (really good methodology, with multiple assessments of alcohol consumption beyond self-reported as in prior studies), has pretty accurate access to timing of drinking (still triggered by participants pushing a button, but that correlated well with a few objective measurements of alcohol consumed), accurate documentation of AF events over a month-long period, ability to compare the timing of events with the timing of drinking in individual patients (they served as their own controls, comparing AF during drinking times vs nondrinking times)

 

-- alcohol has several known effects on the heart including ventricular cardiomyopathy in some patients with excessive drinking, especially an issue for AF since the atria are more prone to fibrosis than ventricles

    -- the Framingham Study found that increased alcohol consumption is associated with a larger atrium (a predictive factor in developing AF), though it should be noted that AF itself is associated with atrial remodeling

    -- and, we know that high doses of intravenous alcohol are used for catheter ablation for AF as well as other sites (e.g. hepatic ablation for liver metastases)...

 

Limitations:

-- all of these participants had paroxysmal AF. Were these people predisposed to AF in ways that are not generalizable to the population overall? Were there other factors involved in their having AF beforehand that separate them from the general population (stress, diet, exercise, hypertension, BMI, sleep apnea, valvular heart disease, hyperthyroidism, metabolic syndrome,…), and that may have increased the likelihood of their having AF in the first place, and then recurrences with even small amounts of alcohol?

-- the study was done on patients in one location and recruited in a cardiology clinic. Is that generalizable?

-- there is not a lot of racial/ethnic diversity in the patients in the study, as well as few women, further limiting generalizability

-- in this study there was only moderate alcohol ingestion, so this did not reflect the breadth of alcohol ingestion in society

-- there was not an associated full-scale Holter monitor, which limits our understanding of the potential mechanism involved: alcohol has been shown to decrease the atrial refractory periods in the pulmonary veins, and it seems likely that alcohol leads to increased premature atrial contractions, perhaps as a segue into AF??? would need have a monitor that revealed the full cardiac rhythm and not just AF to document this

 

So, I bring up this article not because these are new findings (though the goals and methodology of this study adds lots of oomph to the connection between alcohol and AF), but more as a reminder that AF is one of alcohol’s many potential negative effects. Atrial fibrillation, the most common cardiac arrhythmia, of course is also associated with thromboembolism, which can be pretty disastrous. this therefore stresses the importance of asking patients regularly about alcohol (with an emphasis during the holiday seeing, which can lead to increased drinking both because of happiness being around family/friends, or because of distress/depression/anxiety during this time)

 

So enjoy the upcoming holidays, but ‘tis the season to be fibrillating….                                               

 

geoff

 

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