response to: periop Atr Fib, subclincal AF and future strokes

Geoff,

I enjoyed this submission.  I have been thinking a lot about AF screening recently. I think it is an important issue despite the fact that the most recent AHA AF guidelines do not even mention screening.

ESC recommends “ opportunistic screening”, ie pulse palpation followed by EKG if pulse abnormal/irregular- based on just a few studies.

Many barriers to screening, and you alluded to some of them. With the advent of automatic BP cuffs, many clinician do not routinely  palpate their patient’s pulse.

One solution, which is more commonly used in Europe, is the adoption of “ AF detecting BP cuffs” that assess pulse irregularity and using a fairly reliable algorithm signal if AF is “suspected”.

In several studies these BP cuffs were shown to be as good at correctly diagnosing AF as clinicians reading a 12 lead EKG. We are in the process of bringing these cuffs in to a few of the busier PCP practices and I am contemplating recommending these cuffs for my over 65 yo HTN patients, for home monitoring. I too advise some ( calm) patients to download the cardio app on their smart phone and have advised other ( calm) PAF patients to buy the Kardia device which records and transmits a pretty good single channel EKG.

The product that intrigues and terrifies me is the new AppleWatch.  It tracks steps/activity and HR and “learns” what a normal range of HR is for each individual at each level of activity. If the HR jumps above that range, it signals for the wearer to record an EKG ( with the Kardia watchband). Essentially, it is the first step toward continuous home telemetry. I think this has the potential to diagnose a lot of previously undiagnosed AF and to drive clinicians crazy with all the false positives.

Best,

George

Two related articles on atrial fibrillation (AF), both situations with AF undertreatment and increased stroke risk
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A recent study found that those who had atrial fibrillation following noncardiac, non-obstetrical surgery were at higher risk of thromboembolic events in the future (see afib periop as bad as nonvalv AF jacc2018 in dropbox, or doi.org/10.1016/j.jacc.2018.07.088).

Details:

-- Denmark has extensive and pretty complete national registries documenting: individual level registration; all hospital admissions and outpatient contacts; medicinal product dispensing date, strength, and quantity; and a civil registration system information on vital status, birth date, and sex

-- a retrospective review was done including all patients who developed postoperative atrial fibrillation (POAF) following noncardiac surgery from 1996 to 2015; none had a history of AF, or outpatient diagnosis of AF, or prescription for antiarrhythmic or oral anticoagulant drugs

-- mean age 77, 43% male, comorbidities: 15% ischemic heart disease/14% heart failure/17% thromboembolism/30% hypertension/12% bleeding/12% COPD, meds: 11% statin/25% aspirin/20% NSAIDs

-- POAF patients were matched to patients with nonsurgical, nonvalvular atrial fibrillation (NVAF) in a 1:4 ratio by age, sex, heart failure, hypertension, diabetes, previous thromboembolism, ischemic heart disease, and year of diagnosis.

-- The CHADS₂ and CHA₂DS₂-VASc as well as the HAS-BLED scores were calculated based on the database

    -- CHADS₂: 1.4; CHA₂DS₂-VASc: 3.0; HAS-BLED: 1.9

-- most common surgeries were orthopedic (35%), abdominal (29%) and thoracic/pulmonary (14%). Also 7% had vascular surgery

-- primary outcome was thromboembolism (a composite of ischemic stroke, transient cerebral ischemia, and thrombosis or embolism in peripheral arteries)

-- secondary outcome was AF rehospitalization

Results:

-- 6,048 (0.4%) developed POAF during hospitalization, mostly after thoracic/pulmonary, vascular, and abdominal surgery.

-- 3,830 patients with POAF were matched with 15,320 patients with NVAF

-- oral anticoagulation (OAC) therapy was prescribed within 30 days post-discharge in 24.3% POAC and 41.3% NVAF patients (p <0.001)

-- long-term risk of thromboembolism was similar in patients with POAF and NVAF (31.7 events vs. 29.9 events per 1,000 person-years; HR 0.95; (0.85 to 1.07).

-- Oral anticoagulants (vs none) were associated with a comparably lowered risk of thromboembolic events in patients with POAF, HR 0.52 (0.40 to 0.67) and NVAF, HR 0.56 (0.51 to 0.62)

-- those with POAF had roughly ½ the risk of AF rehospitalization compared to those with NVAF

-- analysis of all-cause mortality showed no difference between those with POAF vs NVAF over 10 years, but only after the 1^st year follow-up (all-cause mortality was almost twice as high in those with POAF during the 1^st year, likely reflecting the underlying indication for surgery)

Commentary:

-- the incidence of new onset POAF in patients undergoing noncardiac surgery historically ranged from 0.3 to 4.1%

-- This study suggests a few things about POAF

    -- it is more common in those undergoing thoracic/pulmonary, vascular, and abdominal surgery

    -- it has a similar risk of thromboembolism as for those with nonvalvular atrial fibrillation

    -- OAC therapy seems to work as well in POAC as NVAF

    -- prior thoughts that POAF may be transient and benign seem to be quite incorrect

    -- and, prescriptions for OAC in those with POAF is pretty strikingly low (<25%), though, it wasn’t great in those with nonvalvular AF (41%)

-- potential mechanisms for POAF include sympathetic activation, systemic inflammation, electrophysiologic disturbances, metabolic disturbances, hypoxia, hypervolemia

-- as an observational study, there are many potential limitations undercutting its generalizability, including confounding by indication (healthier patients receiving OAC, esp in light of the low numbers getting OAC), inadequate recording of transient episodes of POAF resulting in decreased documentation of the diagnosis, and potentially large differences in the background health status of those developing POAF (those receiving noncardiac surgery are likely very different those who just have NVAF)

-- one observation in the study was that there were continuing increases in thromboembolism over the 10 years of follow-up, suggesting that these patients would benefit from long-term OAC therapy.

And, a 2012 study found that subclinical atrial tachyarrhythmias without clinical atrial fibrillation occurred frequently and was associated with an increased risk of ischemic stroke or systemic embolism (see subclinical afib and stroke nejm2012 in dropbox, or Healey JS. N Engl J Med. 2012; 366: 120). 

Major points:

-- 2580 patients 65 years old or older with a history of hypertension and no history of atrial fibrillation or being on anticoagulation, who had a pacemaker recently implanted were followed for 2.5 years (the pacemaker being the means to assess if they had episodes of AF)

    -- mean age 77, 7% male, systolic blood pressure 137 mmHg, BMI 28, 7% prior stroke/5% prior TIA/15% heart failure/25% diabetes/15% prior MI, CHADS₂ score 2.2, 62% on aspirin/36% beta blocker/5% statin

-- subclinical tachyarrhythmias were defined as episodes of atrial rate >190 bpm for more than 6 minutes

-- by 3 months, 261 patients (10.1%) had subclinical atrial tachyarrhythmias on interrogation of their pacemakers. Over the course of the study, an additional 633 patients (24.5%) developed subclinical atrial tachyarrhythmias, for an overall rate of 34.7% of the patients over 2.5 years

-- subclinical tachyarrhythmias did lead to huge increased risk of clinical atrial fibrillation, HR 5.56 (3.78- 8.17), p<0.001

-- ischemic stroke or systemic embolization was also increased in the subclinical atrial tachyarrhythmia group, HR 2.49 (1.28- 4.85), p=0.007

-- of the total of 51 patients who had an ischemic stroke or systemic embolism, 11 had subclinical atrial tachyarrhythmias detected by 3 months, none of whom had clinical atrial fibrillation [of the 11 events in the 1^st 3 months, 10 were ischemic stroke and one systemic embolism]

-- the incidence of both ischemic stroke/systemic embolism and developing clinical atrial tachyarrhythmias continued to increase over the course of the study

-- the population attributable risk of stroke or systemic embolism associated with subclinical atrial tachyarrhythmias was 13%

-- the association between subclinical atrial tachyarrhythmias and stroke remained after adjustment for predictors of stroke, HR 2.50 (1.28- 4.89), p=0.008

-- an RCT embedded in this observational study found that patients randomly assigned to receive continuous atrial overdrive pacing as a means to abort the atrial tachyarrhythmia did not prevent atrial fibrillation, though the actual number of patients who developed atrial fibrillation was low

Commentary:

-- About 15% of strokes are attributable to documented AF, 50 to 60% to documented cerebrovascular disease, but 25% of those with ischemic strokes do not have identified etiologic factors (though are suspected to be related to subclinical atrial fibrillation)

-- implanted pacemakers themselves may well have an increased risk of atrial fibrillation. Unclear reason. Perhaps related to the underlying cardiac condition leading to implantation of the pacemaker. But this risk has been found in one study to be 5.8% of the patients within 4 years of implantation

-- the implications of the study are that:

    -- lots of patients have subclinical atrial tachyarrhythmias

    -- these were associated with an ischemic stroke or systemic embolism, which were largely prevented by OAC therapy

    -- the population-attributable 13% stroke risk for those with subclinical atrial tachyarrhythmias found in the 1^st 3 months after the pacemaker implantation is similar to the attributable risk of stroke found in the Framingham study in those with clinical atrial fibrillation (ie, suggesting that subclinical is as bad as clinical AF)

    -- and 62% were on aspirin/18% were ultimately put on vitamin K antagonists, both of which might have understated the actual stroke risk

-- This study therefore provides a reasonable explanation for the 25% of patients with ”cryptogenic”stroke

--relevant recent blogs:

    --https://blogs.bmj.com/bmjebmspotlight/2015/12/02/primary-care-corner-with-geoffrey-modest-md-atrial-fibrillation-should-we-look-harder-for-it/
reviews an editorial in JAMA which argues that AF is so common, OACs work well to decrease stroke risk (by 2/3) and mortality (by 1/3), is a common cause of stroke (Swedish study finding 1/3 of stroke patients had AF) and likely dementia, and that even a single arterial palpation during a clinical visit has a significant AF pickup.  Comment also on the use of smartphone-based screening (see further comment below)

    -- https://blogs.bmj.com/bmjebmspotlight/2017/04/19/primary-care-corner-with-geoffrey-modest-md-the-elusive-search-for-afib-in-stroke-patients-and-an-app/ , which reviews a German study finding that prolonged Holter monitoring was more useful than standard monitoring for detecting atrial fibrillation in patients who would had had an ischemic stroke (the European Society of Cardiology recommends at least 72 hours of Holter monitoring in these people in order to detect AF and prevent recurrent strokes)

So, what other primary-care takeaways from these articles?

-- Atrial fibrillation is really common, especially with aging, and is associated with many bad outcomes, especially stroke

-- it is clearly better to diagnose and treat the atrial fibrillation prior to the patient getting a stroke

-- it does seem that those with postoperative atrial fibrillation are at increased risk and perhaps should be routinely anticoagulated (this is not a transient and benign condition: strokes can happen at increased rate for years, as with nonvalvular AF). would be beneficial to have a randomized controlled trial on this, given the risks of OAC

-- and, it seems pretty clear from the above that many patients have subclinical atrial tachyarrhythmias and are at higher risk for stroke. But, what is the best way to find these patients, who may well be not just asymptomatic but have very intermittent and short-lived episodes of their tachyarrhythmias?

    -- One potential future option is the use of a smart phone app (eg, Cardiio) which displays one’s pulse and is approved in Europe to diagnose atrial fibrillation (the FDA has not approved the app in the US). Not sure the FDA will ever get to it, but it might be useful to have patients download this app and check their heart rate intermittently, and then do a more prolonged Holter to identify those who might benefit from OAC

geoff

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