Integrative management of atrial fibrillation and natural blood thinning.
AF is a disturbance of the normal conduction of electricity in the heart. The sinoatrial (SA) node is the normal pacemaker of the heart. It is situated in the right atrium of the heart near the junction with the superior vena cava. The SA node releases an impulse of depolarization (electricity) that is conducted through both the right and left atrium, causing them to contract. The impulse makes its way down to the atrioventricular (AV) node at the junction between the atria and the ventricles. The AV node collects this depolarization, holds it for about a fifth of a second, and then releases the electricity down into the ventricles.
The atria and ventricles are electrically isolated from one another. The only way for electricity from the upper rooms of the heart (the atria) to get down to the lower rooms of the heart (the ventricles) is through the AV node and the normal conduction system. The conduction system is the "wiring" of the heart. Its job is to conduct electricity in a rapid and organized fashion from the SA node to the AV node and then down through the lower conduction pathways to the ventricles.
The problem in AF is that the SA node has lost control of the pace of the heart. The atria are beating disorganizedly and rapidly, which is to say fibrillating. Because of this rapid, disorganized beating, electrical impulses are only making it through the AV node and down to the ventricles every so often and with irregular timing. As a result, the systolic ejection of the heart (the pulse) becomes erratic.
There are several methods for classifying AF. While pathological and molecular classifications will play an important role in our clinical strategies, the first decisions to be made in the clinical setting of a case of acute AF typically hinge upon the heart rate (the pulse).
At the most basic, we can classify AF as having a controlled ventricular response or a rapid ventricular response. If the heart rate remains under 110 beats per minute (bpm), we consider the ventricular response to be controlled. If the heart rate is over 110 bpm, we consider the ventricular response to be rapid. (1)
Rapid ventricular response to AF can be immediately life-threatening. The higher the heart rate, the more immediately concerned we are about heart failure. (2) It does not take long, in some cases less than 24 hours, for a heart in a sustained rapid rate to begin failing. The heart simply does not have enough time to fill and eject completely when the rate is so fast for so long. The signs and symptoms of this type of heart failure are typically identical to other types of systolic failure (shortness of breath, orthopnea, pulmonary edema, peripheral edema, fatigue). The difference is simply that the failure is not a result of a weak pump, but rather the result of a pump that is working too fast.
This brings up our first important clinical point: the radial pulse is not a reliable indicator of the heart rate when a patient is in AF. Due to the irregularly irregular timing of the ventricular ejection, not every contraction of the heart causes an equal volume of blood or strength of pulse to reach the periphery. Moreover, because the rate is irregularly irregular, if the pulse per minute is estimated from a 15-or 30-second pulse count, the estimate of the heart rate can be very different from the actual because the number of beats over any period of time is not regular. Therefore, it is of the utmost importance to document the heart rate in AF by listening to the heart and counting the number of beats over a full minute as they occur at the cardiac apex. If this can be done several times over a visit and the pulse from multiple measures averaged, an even better estimate of ventricular response can be ascertained.
For example, a recent patient presented to us in AF. His radial pulse was 60 bpm, by palpation and a finger tip pulse oximeter also read his heart rate as 60 bpm; his oxygen saturation as 99%. When counting his apical pulse by auscultation, the patient's actual heart rate was 90 bpm. The radial pulse was only receiving 66% of the heart's impulses. Moreover, we have a completely different assessment of the patient's rate control and potential for complications when the resting rate is 90 bpm as opposed to 60 bpm.
A rapid ventricular response to AF must be controlled to prevent heart failure. For the majority of CAM providers and midlevel practitioners, AF with rapid ventricular response is a condition that warrants referral to the emergency department, the patient transported there by another person or by EMS. The decision about how to control the rapid heart rate depends upon the heart rate, duration and type of AF with which we are dealing, and the present complications. (3)
The most useful clinical classification of AF (other than the ventricular response) is based on the instances and durations of the arrhythmia. We classify instances and durations as lone, paroxysmal, persistent, or permanent. (4-6)
A lone episode of AF is just that, it is a first-time episode. It is typically treated by returning the heart to a normal sinus rhythm. There may never be another episode of the arrhythmia thereafter or not for many years.
Paroxysmal AF describes an arrhythmia that comes and goes. The episodes (paroxysms) are short, often less than 24 hours and certainly less than 7 days. The heart may be converted back to normal sinus rhythm (NSR) by interventional means, but often returns to NSR spontaneously.
Persistent AF is a circumstance in which the duration of arrhythmic episodes become quite long, usually lasting more than 7 days and sometimes months or years. Persistent AF may still spontaneously convert back to NSR, but as the duration of the episodes becomes longer and their instances more frequent, intervention is more often required to return the heart to normal rhythm.
The saying goes, "AF begets AF," and this is certainly the natural history of the condition. The longer and more often the heart is in AF, the more its anatomy becomes deranged, typically beginning with enlargement of the atria. As the atria enlarge, the conduction system becomes distorted and AF episodes typically begin to occur more frequently and last for longer periods. It becomes progressively more difficult to return the heart to a normal rhythm and the heart does a progressively poorer job of staying out of AF. (7)
Permanent AF is defined by the point at which we accept AF as the new "normal" rhythm of the heart and give up on attempts to return the heart to NSR. Patients can live a long, happy, and otherwise healthy life in permanent AF as long as their two largest risk factors are controlled; namely, those risks are rapid heart rate and thromboembolic risk.
While in AF, the contractions of the atria are disorganized. As a result, the blood within the atria is not moved through them efficiently. Rather, the blood pools, eddies, and becomes stagnant, especially near the walls of the atria. The stagnation of blood greatly increases the probability for a clot to form within the atrium. Along the wall of the atrium (especially within the small alcove of the left atrium called the left atrial appendage) it is possible for very large clots (thrombi) to form. This is the primary underlying etiology for an increased risk of thromboembolic events in AF, especially strokes.
If a clot forms on the left side of the heart, then breaks loose and enters the systemic circulation (an embolism), it will become lodged in the first artery that it reaches that is smaller in caliber than it is itself. If that artery is in the brain it will cause and ischemic stroke, but the clot could become lodged anywhere in the circulatory system.
The risk of thromboembolic events begins to rise within the first 5 hours of an episode of AF and reaches maximum risk within 72 hours. (8), (9) This fact forms the basis of much of the decision making around when, how, and if an attempt to convert the heart back to normal rhythm will occur.
If the heart is returned to normal rhythm, the risk of heart failure and thromboembolic events is dramatically reduced. If the heart cannot be returned to normal rhythm, then it is mandatory that we control the accompanying risk factors. Therefore, we say that the basic management strategy in AF is to (1) convert the rhythm (if possible and safe), (2) control the rate, and (3) prevent thromboembolic events. (10)
Cardioconversion, or cardioversion, is the term for our attempt to return a heart from a state of arrhythmia back to normal sinus rhythm. Cardioversion can be achieved by any of several methods. In AF, the most reliable method of conversion is to use a moderate level (50-200 joules) direct current electrical shock (delivered to the heart while the patient is under sedation) to reset the electrical conduction of the heart. This kind of shock causes all of cells of the heart to depolarize at the same time. Since the SA node (the natural pacemaker of the heart) is the part of the heart that resets the fastest it typically resumes beating first and is thereby able to resume control of the heart rate and rhythm.
This process of electrocardioversion has a high success rate at first, but its success rate decreases as episodes of AF get longer and the left atrium gets larger. It does not prevent the heart from returning to AF or prevent the need for subsequent conversions. (11-14)
Other conventional management techniques are available to attempt to return the heart to a normal rhythm and keep it there. These techniques include procedural, surgical, medical, and device therapies based on individual circumstances; and all of these are the purview of conventional cardiologists, especially electrophysiologists who subspecialize in cardiac dysrhythmias.
Sometimes the very process of bringing the AF rate under control with medication causes rhythm conversion. Most frequently this occurs in the emergency department with delivery of intravenous (IV) rate control drugs such as beta blockers or certain calcium channel blockers, though on occasion we have seen it happen in the outpatient setting with delivery of the same drugs by oral administration.
There are several methods available to attempt to convert the cardiac rhythm using natural interventions and CAM therapies. As a word of caution: conversion is not a process to be undertaken without due consideration. The process of conversion can cause an existing blood clot in the heart to become dislodged and enter circulation, resulting in an embolic event that can be far more serious than the arrhythmia itself. This is why, when the duration of the present episode of AF is unknown, the conventional standard of care requires weeks to months of anticoagulation therapy prior to any attempt at cardioversion. (3)
One natural method for cardioversion by IV nutrient delivery is through the use of a moderately paced IV push of magnesium sulfate. The basic premise is to deliver 0.5 to 2.5 grams of magnesium sulfate (MgSO4) over 20 to 30 minutes. This treatment has largely fallen out of favor in conventional settings due to the higher success rates of treatments such as electrocardioversion and the conflicting evidence regarding its efficacy. (15-18) The largest recent study, a trial of 199 patients in 2005, demonstrated that IV MgSO4 used in conjunction with other rate control therapies was significantly more likely to control rate and convert patients to NSR from AF-RVR. (17) Despite outcomes, the studies generally agree on the safety of the intervention.
All of the normal contraindications to IV Mg apply: the absorption of digoxin, nitrofurantoin, and anti-malarials may be decreased by Mg; Mg may interfere with anticoagulants and quinolone or tetracycline antibiotics; Mg may interfere or have additive effects with beta blockers and calcium channel blockers. Most patients will experience a typical Mg "flush" during the treatment, and many will feel sedated or drowsy following the treatment and should have someone else drive them home. (19)
We often consider attempts to convert patients to a normal rhythm using homeopathy. Natrum muriaticum is the most indicated single or classical remedy for this purpose. (20) We have seen the remedy convert patients from AF to NSR on three occasions, twice in the same patient. More frequently, we use a mixed, low-potency spagyric remedy indicated for tachycardia as a means of cardioversion. We have used it to success in several instances. The success rate is low, but the safety profile is high and the patient stands to lose very little for a trial of the therapy if the conversion circumstance is otherwise safe.
Finally, it is important to consider the potential association of irritation and inflammation in local tissues as a potential etiology of AF and a means by which to achieve its resolution. The most frequent association here is between AF and the sliding type of hiatal hernia. An excellent article was produced by Armaganijan et al. 2012 and published in Expert Reviews in Cardiovascular Therapy in October 2012 on this topic. (21) Visceral manipulation and reduction of the sliding hiatal hernia can cause or help in the conversion of AF to NSR. We have experience with one patient in particular, in whom the association between paroxysms of AF and the position of his hiatal hernia superior to the lower esophageal sphincter appears to be completely unitary. In each instance that we have seen the patient during a paroxysm of AF, reduction/visceral manipulation of his hiatal hernia back to correct anatomical position alleviates his arrhythmia.
Antithrombotic therapy (AT) is a mainstay of treatment in virtually all instances of AF other than a single instance of a lone episode. AT is necessary to address the increased risk of thromboembolic events, especially stroke, which have a relative risk 10-to 20-fold higher or more in AF patients than in the average population. (22) As AF patients age and comorbidities are compiled, they may reach an annual stroke risk over 15%. (23)
Whether antiplatelet therapy, by the use of aspirin (ASA) or anticoagulant therapy is more appropriate for a patient is determined by use of the [CHADS.sub.2] score. The [CHADS.sub.2] score helps predict the annual stroke risk by virtue of the patient's age and comorbidities. According to the [CHADS.sub.2] score, we tally points for the patients risk based on: Congestive heart failure (past or present), Hypertension (controlled or uncontrolled), Age [greater than or equal to]75 years), Diabetes mellitus (controlled or uncontrolled), and Stroke or transient ischemic attack (TIA) history. (24)
The presence of each of the first four (CHAD) are worth 1 point each, whereas a history of stroke or TIA is worth two points ([S.sub.2]). According to the [CHADS.sub.2] score system, 81 to 325 mg ASA/day is appropriate therapy for a score of 0 or 1 point and a score of greater than 2 points requires either warfarin therapy (to a target INR range of 2.0-3.0) or dabigatran, typically 150 mg/twice daily. A score of 2 points presents the managing physician and patient with a clinical decision between ASA therapy or anticoagulation with warfarin or dabigatran.
More recent modifications to the [CHADS.sub.2] score have resulted in the development of the [CHA.sub.2][DS.sub.2]-VASc score for AF. The [CHA.sub.2][DS.sub.2]-VASc score (sometimes referred to simply as "ChadsVasc" score) helps us get a more precise assessment of the relative risk of vascular events, thus providing more clarity on the necessary level of AT intervention for a given patient. By contrast, the risk of the patient having a bleeding event while on AT is predicted utilizing the "HAS BLED" score. (25), (26)
Many patients come to our practice seeking an alternative to pharmaceutical management of stroke risk. Many excellent natural therapies exist that may help to modify stroke risk and conventional AT. The greatest challenges with "natural blood thinning" (NBT) therapies are: (1) monitoring them and (2) educating patients that there is insufficient evidence of their efficacy to rely on them to prevent thromboembolic events without accompanying pharmaceutical stroke prophylaxis.
In order to monitor nontraditional blood thinning treatments (NBT), we use the Surgicutt Bleeding Time (BT) test. The bleeding time test has several different forms including: Ivy method, Duke method, template method, in vitro method, and the device methods including the Surgicutt and the Simplate (which is no longer available). The evidence surrounding BT for measuring primary hemostasis (ability to form a clot) is relatively robust. (27-35) It is that indication which most concerns us as we are trying to create an iatrogenic disorder of primary hemostasis in order to lower stroke risk.
The test is widely criticized for the potential variability and (seemingly) subjective interpretation of its results. However, within individuals there is little biological variability, and most of the difference over time is due to observer variability. (27) Despite criticism, it is still widely used in research as a measure of platelet function.
The strength of the BT is the same as its weakness: it is completely nonspecific. This is of great value to us when using NBTs because they achieve their effects by several different mechanisms. While several NBTs can interfere with or alter the INR, none are reliably measured by it. Moreover, the effects of conventional AT on the BT are exceptionally variable. With the BT we are measuring the furthest downstream effects on all aspects of hemostasis, the formation of a clot.
Warfarin therapy is monitored by the PT/INR test, but this makes it the exception rather than the rule among conventional ATs, which typically undergo no monitoring at all and have few reliable or cost-effective monitoring test options. Moreover, other than ASA, antiplatelet therapy is not used in the conventional management of AF. Yet, platelet aggregation and dysfunction, as well as blood viscosity, are as important in thrombus formation as are the factors of the clotting cascade antagonized by warfarin and dabigatran.
We believe that monitoring and optimization of the BT test in AF is an important element of integrative AF management. It is also important to monitor scrupulously for changes in the INR, for drug/herb/nutrient/ metabolism interactions and for signs or symptoms of increased bleeding when combing conventional AT with NBTs.
We utilize several different therapies to optimize platelet function and bleeding time. We typically begin with optimization of polyunsaturated fatty acid (PUFA) intake. PUFAs exert several important effects on platelet function, blood thinning, AF, and cardiovascular function. They are well-tolerated, essential nutrients, which are inexpensive and easy to incorporate into the daily regimen for most patients.
The essential omega-3 (n-3) PUFAs, EPA and DHA, appear to increase the BT in a dose-dependent manner, but results of studies are mixed on its AT effects and are far from conclusive. (36-39) In addition, PUFAs have important effects on cardiovascular conditions that are often concomitant to AF such as high blood pressure and poor lipid profiles. (40-49)
PUFAs can exert an antiarrhythmic effect in AF. This point is hotly contested throughout the medical literature, and the studies which analyze these effects vary substantially in the type of AF that is scrutinized, the sample sizes, the doses used, and the ratio of n-3 PUFAs used. (50-55) However, in the studies of patients with permanent AF taking 6 grams or more of n-3 PUFAs daily, antiarrhythmic properties have been reliably demonstrated. (50), (51)
We typically begin by recommending that patients get 4 to 8 tablespoons per day of ground flax seeds and 2 to 4 tablespoons per day of ground chia seeds. Additional PUFA support comes by way of vegetarian or fish-oil supplementation based on the other indications present in a particular case and the BT.
Our second-line intervention to optimize BT is a nattokinase supplement that has been analyzed after manufacture for its fibrinolytic activity. The product that we use has 2000 FU (fibrinolytic units) per capsule, and we initiate therapy at 1 cap once or twice daily; we may escalate to as much as 4 caps twice daily, but we never exceed this amount based on safety and cost.
The nattokinase research is also controversial, but studies have shown fibrinolytic activity as well as an upregulation in the endogenous activity of tissue plasminogen activator (tPA) by the vascular endothelial cells, decreased red blood cell aggregation, and low-shear blood viscosity. (56-59) One compelling prospective study of 186 patients taking a proprietary combination of nattokinase and Pycnogenol before air travel demonstrated that no thrombotic events occurred in the treatment group while the control group demonstrated five instances of deep vein thrombus and two of superficial venous thrombus. (57) Nattokinase has also shown side benefits on concomitant cardiovascular conditions such as high blood pressure. (60)
We use a sustained-release grape-seed extract as our third-line intervention to optimize BT. Several small studies show that grape-seed extract may have very potent antiplatelet activity. (61-68) This evidence, too, is conflicting; however, we have seen its use routine raise BT in our practice. In one particular patient, her BT remains suboptimal at 7 minutes on PUFA and nattokinase therapy; the addition of sustained-release grape-seed extract reliably elevates her bleeding time over 12 minutes and its removal returns the BT to 7 minutes. Like those above, grape-seed extract has cardiovascular side benefits, including effects on blood pressure. (69) It is rich in polyphenols, especially anthocyanidins, and has demonstrated compelling effects on many systems outside of the cardiovascular system.
Finally, we do not hesitate to use 81 to 325 mg of ASA therapy to achieve optimal platelet function and BT when necessary and appropriate. To be sure, there are many patients who come to us because they cannot use ASA due salicylate sensitivity, medication interactions, or gastrointestinal bleeding events; and in these, as well as others, ASA may not be appropriate. In the instance of a stubborn bleeding time or suboptimal platelet function in the absence of contraindications, however, it can be just the extra push that is needed. Moreover, the research surrounding its ability to prevent a first instance of heart attack in men or a first instance of stroke in women is virtually absolute.
Atrial fibrillation is a complex management scenario. Depending on AF type and duration, as well as on patient comorbidities and preferences, there are many opportunities for the improvement of patient health via the integration of CAM therapies with conventional management. In this and in previous articles in this journal, we have discussed CAM protocols to improve patient arrhythmias and endothelial function. Certain CAM therapies can be effective in conversion of arrhythmias back to normal rhythm, when appropriate. Finally, the optimization and monitoring of platelet function and bleeding time in AF patients may be one of the most important contributions that CAM can make to conventional management of this common arrhythmia.
Dr. Jeremy Mikolai
Heart & Lung Wellness Program
Center for Natural Medicine Inc.
1330 SE Cesar E Chavez Blvd.
Portland, Oregon 97214
This author has no financial conflicts of interest to declare.
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by Jeremy Mikolai, ND
Jeremy Mikolai, ND, is professor of cardiology in the naturopathic medicine program in the School of Health Sciences at Universidad del Turabo in Gurabo, Puerto Rico, and cofounder of the Naturopathic Institute of Cardiovascular and Pulmonary Medicine (NICVM). He is the attending physician in cardiovascular and pulmonary medicine at the National College of Natural Medicine (NCNM) and co-attending physician in the Heart & Lung Wellness program at the Center for Natural Medicine (CNM), both in Portland, OR. Dr. Mikolai is in his third year as the Heart & Lung Resident and is the Chief Resident for 2012-2013 at NCNM. He is also an adjunct faculty member in the Masters of Science in Integrative Medicine Research (MSiMR) program at the Helfgott Research Institute at NCNM. He is actively working to create the first ND fellowship in cardiology.
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|Date:||May 1, 2013|
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