Answering Clinical Questions by Investigating the Research Evidence: An Acupuncture/Atrial Fibrillation-Based Example

 Atrial fibrillation (AF) has emerged as a nascent global epidemic that poses a growing global disease burden.^1,2 In the United States, AF affects approximately 9% of those aged 65 years or older.³ It is the most common clinically significant arrhythmia and is acknowledged as one of the most difficult to treat.⁴ As the most common heart rhythm disorder worldwide, AF requires our attention in general, and as a cause of increased rates of stroke and systemic embolic events when left untreated, it demands our consideration regarding treatment possibilities. The need to answer clinical questions about treating AF with acupuncture grows along with our awareness of this expanding patient population.

As with many other clinical questions, whether and how to treat AF using acupuncture remains relatively unexplored by clinicians. This is likely due to the fact that researching clinical questions can be a daunting task, particularly when one has not mastered the requisite skills to accomplish it. The purpose of this article is two-fold: first, it elucidates a process for gathering research evidence to answer clinical questions by exploring current research on acupuncture and AF; second, this article summarizes the research to create evidence-based treatment recommendations for AF. In line with accepted convention regarding quality of research evidence, the process gives preference to systematic reviews, followed by narrative reviews and RCTs published in peer-reviewed journals.

Getting Started

To research clinical questions, a way to start is by making a list of information needed. Researching the following will help us learn about AF and acupuncture:

• What is AF and how widespread is it?
• What is the biomedical treatment for AF?
• Is there evidence that acupuncture can successfully treat AF? If so, how do treatment results compare with those of biomedical treatments?
• Can the evidence guide treatment of AF with acupuncture?

There are both narrative and systematic reviews on AF. To research a disease process about which one knows relatively little, a narrative review is an ideal starting place. Although narrative reviews are not as comprehensive as systematic reviews and reflect only the information the authors choose to include, they are generally written by subject matter experts—and good reviews provide reader-friendly background information. In the case of AF, a narrative review is a desirable starting place in order to learn more about risk factors, clinical presentation, and standard medical treatments. The article by Staerk, et al., Atrial Fibrillation: Epidemiology, pathophysiology, and clinical outcomes ⁵, does this and more.

Pathophysiology and epidemiology

What is AF and who develops it?

AF is a cardiac rhythm disturbance in which the atrium receives electrical signals at a faster than normal rate, resulting in uncoordinated atrial contractions coupled with irregular ventricular stimulation.⁵ AF is caused by mis-coordination of the sympathetic and parasympathetic branches of the autonomic nervous system (ANS). When both branches of the cardiac ANS fire simultaneously, the rhythm of the heart is disrupted, leading to atrial fibrillation.⁶ Ultimately, this leads to reduced myocardial and systemic perfusion as well as an increased risk of emboli from pooling of blood.

AF has long been known to be associated with mitral stenosis, and more recently non-valvular links have been discovered. Staerk, et al’s article, focusing on non-valvular AF, presents the current thinking that, due to any of several possible causes, some portion of atrial tissue becomes vulnerable. This vulnerable tissue is called AF substrate or atrial cardiomyopathy and has a number of characteristics that render it subject to the continual rapid firing that characterizes AF.⁵

Risk factors for developing AF include many considered modifiable: sedentary lifestyle, hypertension, obesity, diabetes, and obstructive sleep apnea. In addition, non-modifiable risk factors are family history, increased age, European ancestry, and being male. Once a person has AF, they are at higher risk for stroke, thrombosis, dementia, congestive heart failure, and myocardial infarction.⁵

Clinical presentation and diagnosis

Although some patients with AF are asymptomatic, most present with complaints of one or more symptoms including fatigue, dizziness, abnormal heartbeats (rapid, skipping, fluttering), shortness of breath, chest or abdominal pain, or exercise intolerance. Symptoms result from reduced systemic and coronary blood flow due to limited atrial output. Blood pools in the atrium, leading to thrombus formation. Consequently, patients with AF must take anticoagulants in order to avoid strokes caused by emboli.⁷

Diagnosis of AF is generally straightforward:the patient’s history and clinical picture are confirmed by EKG. In some cases, additional follow-up studies are needed. There are several types of AF, based on duration. Paroxysmal AF stops either spontaneously or with intervention within 7 days of onset; Persistent AF is continuous and sustained for longer than 7 days, and AF that is continuous for longer than 12 months is termed Long-Standing Persistent AF. When AF does not improve despite several trials of medical treatment, it is considered Permanent AF.⁷

Biomedical theory

Long-term biomedical treatment for AF includes drug therapy and a procedure known as cardiac ablation, described below. The optimal treatment for AF is far from a settled matter; ongoing and future clinical trials will attempt to determine how best to manage various types of AF. One long-awaited clinical trial has just begun to generate published results. The CABANA trial (Catheter Ablation Versus Anti-Arrhythmic Drug Therapy for Atrial Fibrillation), with two results papers published in March, 2019,^4,8 is a an example of the large clinical trials being undertaken in our current era of ‘Big Data’. CABANA is an international RCT involving 2204 subjects in 126 centers spread over 10 countries. During the 6.5-year-long trial, patients were randomized to either catheter ablation or drug therapy. While it must be pointed out that current AF literature presents opposing opinions regarding the significance and interpretation of the study, published results indicate that catheter ablation did not significantly reduce the incidence of death, disabling stroke, serious bleeding, or cardiac arrest when compared to drug therapy,⁴ although there were significant improvements in quality of life.⁸

Catheter Ablation Therapy: Using an expert consensus statement to understand complex procedures

In addition to examining review articles and clinical trials, when investigating research on biomedical treatment efficacy one may find consensus statements. These papers are written by large panels of experts representing several institutions and are elicited in searches for review articles. Useful for their reliably accurate background information, these articles generally give more detail than needed for answering clinical questions. However, they provide a thorough understanding of the procedure or treatment in question—which is often useful when trying to explain procedures to patients. One such article on atrial fibrillation and catheter ablation was authored by 60 experts representing 11 organizations and published in 2017.⁹ This 40-page consensus statement provides deep background information about ablation procedures including rationale, indications, techniques, technology, outcomes and complications.

Cardiac ablation is a procedure in which tiny electrodes are placed inside the heart in order to map cardiac electrical impulses and locate the source of the extra beats. These areas are then treated in order to render them inactive. Ablation is done both surgically and via a catheter inserted distally. Surgical ablation is performed concomitantly with other cardiac procedures such as valve replacement or coronary artery bypass graft (CABG). Once the cardiac tissue is accessed, the procedure is similar, regardless of approach. Catheter ablation, being more common,⁹ is considered in this paper.

Complications, when they occur, are often quite serious, but their incidence is low—less than 1% for the vast majority of complications. The two complications with the highest incidence (2-15% and 0-17%, respectively), are of a less serious nature: asymptomatic cerebral emboli and gastric hypomotility.⁹

Drug therapy

Another reliable source of information regarding clinical questions is clinical practice guidelines. Issued by professional associations, practice guidelines resemble review articles in that they are systematically developed by subject matter experts and comprise a synthesis of current research findings. In this case, the product is evidence-based treatment recommendations. Some practice guidelines give detailed background information on a condition’s pathophysiology, epidemiology, diagnosis, etc., while others are more succinct. Guideline summaries are also published and can be quite helpful.

To learn about drug therapy for AF, the authors of this paper turned to the American Academy of Family Physicians’ (AAFP) guideline, Pharmacologic Management of Newly Detected Atrial Fibrillation, published in 2017. The AAFP recommends that first-line therapy be limited to rate control using calcium channel blockers or beta blockers.¹⁰ Both calcium channel blockers and beta blockers inhibit sympathetic nerve signals, causing a decrease in heart rate. These drugs have been in widespread use for a number of years and are generally safe and well-tolerated.

If rate control is insufficient to manage the AF, then rhythm control with antiarrhythmic drugs may be employed. This is second-line therapy due to the significant risks and side effects associated with these drugs, which include amiodarone, sotalol, deslanoside and others. One risk, for example, is that of proarrhythmia—drug-induced exacerbation of existing arrhythmias. Management of the AF as a whole includes risk assessment for stroke and anticoagulants to prevent embolic strokes unless the patient is at low risk.¹⁰

Can acupuncture treat AF?

Exploring evidence about treating AF with acupuncture is similar to answering the broader questions about biomedical evidence, and again, a narrative review is a good choice. The Journal of Thoracic Disease’s 2015 review presents evidence for complementary interventions in AF, including yoga, nutritional supplements, and acupuncture. According to the authors, acupuncture appears to outperform amiodarone in stabilizing AF: 85% of patients in the acupuncture group experienced a return to normal heart rhythm compared to 67.5% of amiodarone group patients.¹¹ In addition, acupuncture may decrease recurrences of AF. In one study, patients receiving acupuncture were 2.766 times less likely to experience AF recurrence than patients in the control group, and the lower risk persisted for one year after the course of treatment.¹² While this is encouraging information, keep in mind that narrative reviews can have a type of selection bias due to author choice of particular studies for inclusion. As systematic reviews are intended to include all the relevant research on a topic, they avoid this problem.

Fortunately for this investigation into acupuncture and AF, a systematic review was published in 2018.¹³ A search of 9 different databases, including Chinese language databases, yielded 9 original research articles on acupuncture and heart rhythm that met the inclusion criteria. The systematic review offered similar conclusions to the narrative review: acupuncture appeared to be as effective as anti-arrhythmic drugs, including amiodarone, and the AF recurrence rate was lower in patients who received acupuncture. Meta-analysis results showed response rates to acupuncture and amiodarone to be virtually identical (RR, 1.09, CI: 0.79-1.49). When compared to the antiarrhythmic deslanoside, patients who received acupuncture intervention had a lower AF recurrence rate for 3 months after treatment. In addition, patients who received acupuncture intervention suffered fewer adverse events than those in the drug intervention groups.¹³

Can evidence guide the acupuncture treatment of AF?

When formulating a clinical course of treatment for AF patients, research should be thoughtfully combined with classical acupuncture theory to ensure the best possible outcome for the patient. Acupuncture and AF review articles guide the clinician in AF treatment in three areas: point selection, needle stimulation, and course of treatment.

Point selection for AF

While most traditionally trained acupuncturists value the individuality of treatments specific to their patient’s pattern, consideration should be given to a few points that stand out as having clinical efficacy in the treatment of AF.

Points near the vagus nerve vs. points on the sympathetic chain

Since AF is caused by a dysfunction between the sympathetic and parasympathetic branches of the ANS, a review of the acupuncture points adjacent to the sympathetic and parasympathetic pathways could inform point selection for the treatment of AF. To affect the sympathetic branch, it is helpful to know that most of the sympathetic signals to the heart travel in the ganglia of the cervical-thoracic region. This includes points near T4-T5, which may explain why UB14 and UB15 are known as the back shu points of the pericardium and heart. Both points are indicated for palpitations and chest pain,¹⁴ and are commonly found in study protocols for AF.¹³

The vagus nerve transmits most of the parasympathetic signals to the heart, therefore points along the vagus nerve may be employed to affect the parasympathetic branch of the ANS. In 2014, da Silva and Dorsher wrote a narrative review on the relationship between acupuncture point indications and vagus nerve stimulation. These authors point out that acupoints along the vagus nerve in the head and neck include points along the skull base, auricular points in the conchae of the ear, and lateral neck points.¹⁵ The skull base points GV16, GB12 and Anmian (M-HN-54) all carry traditional indications for palpitations or heart agitation.¹⁴ The auricular point for the heart (found within the cavum conchae) also is indicated for palpitations and heart disease.¹⁶ Da Silva and Dorsher point out that the right vagus nerve “provides more parasympathetic innervation to the cardiac atria than does left vagus nerve”.¹⁵ Therefore, a consideration when formulating treatments for patients with AF may be a focus on right-sided points along the vagus nerve pathway in the hope that this will enhance the clinical effect.

Unsurprisingly, points along the pericardium meridian are among the most frequently studied in cardiac arrhythmias.¹² In particular, PC6 (nei guan) appears in 25% of the point combinations studied for AF.¹³ In 2012, the journal Acupuncture Medicine published a review article devoted exclusively to the acupoint PC6 and its mechanisms for affecting cardiovascular disorders.¹⁷ Interestingly, PC6, while not located near the sympathetic pathway, appears to reduce the activity of sympathetic neurons. This point’s influence on the cardiovascular system includes lowering blood pressure, increasing heart rate variability, and moderating heart rhythm.¹⁷

Points near deep nerves vs. cutaneous nerves

A narrative review by Longhurst¹⁸ discussed how different types of acupuncture points influence the cardiovascular ANS. In his research, Longhurst found that acupuncture points near deep somatic nerves (PC6, PC5–median nerve, ST36, ST37–deep peroneal nerve) impacted the cardiovascular portion of the ANS, while nearby acupuncture points at superficial cutaneous nerves (LI6, LI7) did not.¹⁸ Sensory fibers of the deep nerves appear to carry the “acupuncture effect” to the heart. The cardiovascular response to acupuncture can be blocked by applying local anesthesia to the acupoint prior to point stimulation.¹⁸

Needle stimulation for AF

Since the cardiovascular action of acupuncture is carried via the sensory nerves, some type of needle stimulation that can be felt by the patient may be needed for optimal results.¹⁸ Both manual needle stimulation and electroacupuncture (EA) stimulation have been used to study the acupuncture effect on AF.

Much of the research into the cardiovascular actions of acupuncture has been performed on hypertensive populations, usually employing EA stimulation. The EA frequency that has the strongest action on the heart (and, indeed, the ANS) is 2 Hz.¹⁸ Some studies use a continual 2 Hz EA stimulation for 30 minutes,¹⁹  while others use bursts of EA for 2 minutes, followed by a 10 minute resting period, repeated for 3 cycles.^20. Both methods appear to successfully modulate the cardiovascular ANS pathways.

Manual acupuncture can also influence the cardiovascular actions of the autonomic nervous system—with a caveat. Manual acupuncture that is similar to EA has an effect, but simple needle insertion and retention (even if de-qi is achieved) does not seem to have the same effect on the heart. That is, if the needle is inserted and manipulated in a lift-and-thrust motion 2 times per second for 2 minutes, then the ANS responds to the acupuncture. The ANS does not seem to respond as robustly if the needle is simply inserted and retained, without the lift-and-thrust motion.²⁰

Course of treatment for AF

A clinician needs to be able to advise the AF patient on the ideal course of treatment to maximize the cardiovascular effects of acupuncture. Here, the research literature can inform one’s course of treatment. In one study, subjects received acupuncture once per week for 10 weeks. This protocol lowered AF recurrence rates well after the treatment period. In fact, at the 12-month follow up, subjects in the acupuncture group continued to demonstrate a lower risk for recurrence.¹²

In a trial of electroacupuncture for hypertension, a similar pattern was noted. The study applied acupuncture once per week for 8 weeks. This course of treatment lowered blood pressure, and it remained low for 4 weeks after treatment ended.²¹ Longhurst noted that repeated application of acupuncture appeared to have a cumulative effect, prolonging the lower blood pressure readings.¹⁸ He proposes that acupuncture’s effect on the cardiovascular ANS is due to stimulation of preproenkephalin expression, which can be increased with repeated interventions. In addition, the increased preproenkephalins can be maintained with monthly or bimonthly acupuncture performed after the initial course of treatment.¹⁸

By reading the studies of acupuncture and blood pressure, one can understand the effect of acupoint stimulation on cardiovascular ANS tissue. The BP reduction is slow, doesn’t start until 2-4 weeks after treatment initiation, and the effects extend after the treatment course concludes. More studies are needed to know if acupuncture’s effect on AF is modulated by the same mechanisms. In the absence of these studies, based on the current literature, acupuncture applied once per week for 8-10 weeks, followed by monthly or bimonthly follow up treatments, is a reasonable course for AF patients.

Take home messages

The following treatment insights were arrived at by a careful review of the acupuncture and AF-related research literature and can therefore be incorporated into treatment plans with some degree of confidence.

• Acupuncture appears to be effective for AF, particularly in patients for whom cardiac ablation is not a viable option
• Acupuncture appears to reduce the recurrence of AF
• Acupuncture points near ANS pathways may be useful in the treatment of AF
• Acupuncture points over deep somatic nerves appear to be more effective in modulating cardiovascular function than points over superficial cutaneous nerves
• 2Hz EA (or manual equivalent) appears to maximize the acupuncture effect on the cardiovascular system
• A course of treatment should include weekly treatments for 8-10 weeks, followed by monthly or bi-monthly acupuncture

Researching clinical questions can be satisfying in many ways. Whether following the process demonstrated in this paper or one you develop on your own, you will find that it becomes easier and more richly rewarding each time you undertake such a project. Not only is your clinical practice enhanced, but you will likely also find new areas of interest that are mentally stimulating!

Anna Smith, DACM

Anna Smith teaches in the Bioscience department at Pacific College of Health and Science. Anna loves teaching and also enjoys walking, her qi-gong practice, learning new skills, gardening, reading and writing.

References

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9. Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: Executive summary. Europace. 2018 Jan;20(1):157-208. doi: 10.1093/europace/eux275. Epub 2017 Sep 15. PubMed PMID: 29016841; PubMed Central PMCID: PMC5892164.
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