Module 3 - Atrial Fibrillation Flashcards
1
Q
Conversion
A
the active process of changing an arrhythmia into sinus rhythm using electrical current or drugs
2
Q
lone atrial fibrillation
A
AF occurring in a patient younger than 60 years who has no clinical or echocardiographic evidence of cardiopulmonary disease
3
Q
MAZE
A
surgical procedure for AF that creates a maze of new electrical pathways
4
Q
Paroxysmal atrial fibrillation
A
AF that typically lasts 7 days or less and that converts spontaneously to sinus rhythm
5
Q
Permanent atrial fibrillation
A
AF that is refractory to cardioversion or that has persisted for longer than 1 year
6
Q
Persistent atrial fibrillation
A
AF that typically lasts longer than 7 days or that requires pharmaco- logic or direct current cardioversion
7
Q
Proarrhythmia
A
a tendency of antiarrhythmic drugs to facilitate emergence of new arrhythmias
8
Q
recurrent atrial fibrillation
A
AF occurring in a patient who has experienced an episode of AF in the past
9
Q
_______ is dependent on the ability of the Av node to conduct impulses.
A
Ventricular rate
10
Q
AF is considered ______ when a patient has two or more episodes.
A
Recurrent
11
Q
_______ of AF incidents require costly hospitaliza- tions.
A
Over Half
12
Q
Atrial fibrillation is estimated to be present in ____________of the general population.
A
Up to 1%
13
Q
The most frequent pathogenetic findings of AF are:
A
Atrial fibrosis and loss of atrial muscle mass.
14
Q
What is to the term for the deposition of a waxy type of protein called amyloid in tissues of the body?
A
Amyloidosis
15
Q
Endomyocardial fibrosis may affect the right and left ventricles, creating _____________, and may be accompanied by atrial fibrillation.
A
Restrictive heart failure
16
Q
Which of the following is a large venous channel in the heart wall that receives blood via the coronary veins and empties into the right atrium?
A
Coronary Sinus
17
Q
The results of some experimental studies suggest that the pulmonary veins are  ______.
A
Capable of sustaining an automatic discharge for an extended period of time.
18
Q
Which of the following is characterized by shortening of atrial refractoriness and develops within a few days of the onset of atrial fibrillation?
A
Electrical remodeling
19
Q
Patients with atrial fibrillation often have other significant cardiovascular morbidities and risk factors, including .
A
ALL of the following a. Congestive heart failure, valvular heart disease, and stroke b.Abnormal mitral or aortic valve disease c. Systemic hypertension
20
Q
A definitive diagnosis of atrial fibrillation requires documentation of the abnormal rhythm via ______ .
A
ECG
21
Q
Up to _______ of episodes are not recognized by the patient.
A
90%
22
Q
In patients who may have concomitant heart disease, the ______ can be useful in assessing the lungs, vasculature, and size of the cardiac shadow to look for signs of congestion in the lungs and cardiac enlargement.
A
Chest x-ray
23
Q
What test is performed by placing the measuring device in the esophagus and behind the heart?
A
Transesophageal echocardiography*
24
Q
Total mortality is _____approximately among people with atrial fibrillation compared with those in normal sinus rhythm.
A
Double
25
According to the findings of the Framingham Study, decreased survival with atrial fibrillation was seen in \_\_\_\_\_\_\_\_.
Men and women and across a wide range of ages
26
A factor that contributes to the increase in mortality among older persons is the \_\_\_\_\_\_\_\_ .
Increased prevalence of diabetes mellitus
27
The \_\_\_\_\_ score can be used to quantify the risk of stroke in patients with atrial fibrillation and may aid in selection of antithrombotic therapy.
CHADS2
28
What are the four key components to Qol measurements?
General health, physical function, social function, and mental health
29
Initial atrial fibrillation management involves a decision-making process regarding \_\_\_\_\_\_\_\_\_\_.
Rate control and rhythm control
30
The  should be individualized for each patient and based on whether the patient has symptoms from uncon- trolled ventricular rates or from atrial fibrillation itself.
Overall treatment strategy
31
3. The timing of attempted cardioversion is influenced by the \_\_\_\_\_\_\_\_\_.
Duration of atrial fibrillation
32
Which of the following are disadvantages of employing a rate control strategy in the treatment of AF? (Choose all that apply.)
Both: Persistence of irregular ventricular response Drugs used to maintain ventricular response may cause very slow heart rates in some patients
33
Which of the following are proven advantages of maintaining sinus rhythm? (Choose all that apply.)
Both: Improved hemodynamics Relief of symptoms
34
One of the strategies for management of patients with atrial fibrillation, which is appropriate in all patients who do not have contraindications for anticoagulation therapy?
Stroke Prevention
35
The primary end point of the \_\_\_\_\_\_\_\_\_\_\_\_trial was a composite of death, cardiopulmonary resuscitation, cerebrovascular event, and systemic embolism
STAF
36
In the AFFIrM study, there was a trend toward increased mortality in the rhythm-control group, which may be explained by differences in the number of \_\_\_\_\_\_\_\_ .
Noncardiovascular deaths
37
Which of the following are elements of the primary end point for the RACE study?
ALL: Death from cardiac causes, heart failure, thromboembolic compli- cations, bleeding The need for a pacemaker Serious adverse effects of the antiarrhythmic agents
38
In the AF-CHF study, which of the following was the primary end point?
Cardiovascular mortality
39
\_\_\_\_\_ % of all strokes occur in people with AF
15%
40
Atrial fibrillation is a cardiac arrhythmia in the category called “supra- ventricular tachyarrhythmias.” Its main features include:
Uncoordinated atrial activation Deterioration of atrial mechanical function
41
Afib causes \_\_\_% of all strokes in patients from 80 to 89 years of age.
Approximately one quarter
42
Patterns of Atrial Fibrilation
The classification scheme proposed in 2006 by the American Heart Association is based on a previous system jointly recommended by three different medical organizations.
43
Epidemiology Statistics
* It is the most common sustained cardiac arrhythmia
* It currently affects over 2.3 million Americans, or 1% of the US population
* It preferentially affects men and the elderly
* The prevalence of AF is expected to increase by at least 2.5-fold by 2050
* The lifetime risk of developing AF is 1 in 4 for men and women aged 40 years or older
44
Independent Risk Factors for AFib from the Framingham study were:
* **Age and gende**r: AF increases with age, doubling in prevalence and incidence with each decade. Men have a 1.5-fold greater risk for developing AF than women (after adjustment for age and predis- posing conditions), but the reason for this difference is unknown.
* **Cardiovascular risk factors**: Of the major cardiovascular risk fac- tors, hypertension and diabetes are significant independent predictors of AF (adjusting for age and other predisposing conditions). Cigarette smoking is a significant risk factor in women, but neither obesity nor alcohol intake appears to be independently associated with risk of AF in either men or women.
* **Thyroid disease**: Hyperthyroidism has been implicated as a condition predisposing to AF. This relationship was firmly established by the Framingham Study and confirmed by the Cardiovascular Health Study of community dwellers aged 65 years or older for whom baseline serum thyroid-stimulating hormone levels were measured.
* **Cardiac structural abnormalities**: Valvular heart disease, enlargement of the left atrial dimension on echocardiogram, and abnormal mitral or aortic valve function are independently associated with increased prevalence and incidence of AF.
45
INCREASING PREVALENCE OF ATRIAL FIBRILLATION
One explanation for the increasing prevalence of AF with age is that there is a higher prevalence of predisposing conditions for AF in older persons today.
Medical conditions such as diabetes, obesity, heart failure, coronary artery disease, valvular heart disease, and past cardiac surgery are known predisposing factors.
They have a greater influence on the incidence of AF than 50 years ago **because people are living longer** with these diseases and thus reaching an age at which AF will occur
46
Abnormalities in Atrial Tissues
The most frequent histological abnormalities observed in atrial tissue in patients with AF are:
* Atrial fibrosis
* Loss of atrial muscle mass
47
RELATIONSHIP BETWEEN ATRIAL FIBROSIS
AND ATRIAL FIBRILLATION
**The theory is that the normal wavefront of depolarization is inter- rupted by nonconducting (fibrotic) tissue, which causes the electri- cal activity in the atria to become disorganized.** This disorganization is characterized by different refractory periods in cells that are near each other, facilitating the development of multiple wavelets of activity.
**Once it starts, AF is propagated by multiple migrating reentrant microwavelets, which rarely complete a circuit because of variation in conduction and refractoriness across the atrium, a phenomenon called spatial heterogeneity.** Through structural remodeling, cardiac cell degeneration, and dilation of the atria, the electrical abnormality persists.
48
In addition to myocardial fibrosis, other atrial pathological findings that have been described in patients with AF include \_\_\_\_\_\_\_\_\_\_\_\_\_.
* amyloidosis,
* hemo-chromatosis,
* and endocardial fibrosis.
49
Amyloidosis
Amyloidosis is the deposition of a waxy type of protein called amyloid in tissues of the body .
50
Hemochromatosis
Hemochromatosis is the result of deposition of hemosiderin and other iron-containing pigments in tissue.
51
Endomyocardial Fibrosis
Endomyocardial fibrosis is a condition characterized by thickening of the inner layer of the heart (endocardium) by fibrous tissue (Figure 3-11). It can affect both the right and left ventricles, creating restrictive heart failure, and may be accompanied by AF.
52
Atrial Dilation
Atrial size (or volume) is a factor that appears to have a codependent relationship with AF.
This relationship is manifested as follows:
* Larger volumes (through atrial stretch, heart failure, or other mecha- nisms) appear to be associated with increased risk for AF
* On the other hand, AF can cause atrial dilation through loss of contractility and increased compliance
53
Loss of Contractility
Once dilation occurs due to AF or associated heart disease, accumu- lation of extracellular matrix and fibrosis are associated with more pro- nounced changes in cardiac muscle cells, including:
* An increase in cell size
* Perinuclear glycogen accumulation
* Loss of sarcoplasmic reticulum
* Breakdown of sarcomeres
54
Automatic Focus Theory
The theory that the AF has a focal origin that if identified could be fixed surgically.
Electrical mapping studies have identified the **pulmonary veins as one of the anatomical locations where rapid atrial impulses most frequently originate**. However, the impulses have also been found in the:
* Superior vena cava, a large vein conveying blood from the head, chest, and upper extremities to the right atrium
* Ligament of Marshall, a neuromuscular bundle situated in the left atrial epicardium that has been associated with the genesis of atrial tachyarrhythmias and AF
* Left posterior free wall, the back or dorsal wall of the left atrium
* Crista terminalis, a vertical crest on the interior wall of the right atri- um that lies to the right of the sinus of the vena cava and separates this area from the remainder of the right atrium
* Coronary sinus, a large venous channel in the heart wall that receives blood via the coronary veins and empties into the right atrium
55
Multiple-wavelet Hypothesis
This hypothesis suggests that **electrical wavefronts are broken up by various structural and electrical factors in the atria, producing a group of self-perpetuating “daughter wavelets.”** The number of wavelets that are moving through atrial tissue at any one time depends on the refractory period, mass, and conduction velocity in different parts of the atria. Greater heterogeneity in the atria supports a larger number of wavelets. Thus, a patient who has large atrial mass (or volume) with short refractory periods and delayed conduction is more likely to have an increased number of wavelets, favoring sustained AF
56
Role of the Pulmonary Veins
Studies have demonstrated that the pulmonary veins are an important source of spontaneous electrical activity that can initiate AF. Rapid focal discharges that persist for hours or days have been observed to drive sustained AF in some patients. Electrical mapping at the time of surgery in patients with chronic AF has identified rapid activity origi- nating in the pulmonary venous region
Electrophysiological studies of the pulmonary veins and the junction between them and the left atrium have revealed conduction delay and conduction block associated with changing myocardial fiber orientation.
57
Atrial remodeling
AF appears to be associated with a process that involves structural changes in the atrium itself. This process has been called atrial remodeling and involves **electrical, structural, and contractile changes**.
58
Electrical Remodeling
Electrical remodeling, characterized by shortening of atrial refractori- ness, develops within a few days of the onset of AF. It is associated with increased susceptibility to AF resulting from shortening of the wavelength of the atrial impulse.
59
Contractile Remodeling
Contractile remodeling of the atria leads to a reduction in atrial trans- port function (which relates to how ionic channels allow contraction) and loss of contractility.26
Contractile modeling was initially recognized through echocardio- graphic studies that revealed that atrial contractile dysfunction corre- lated with the duration of AF and that it could take months before the atrial transport function was fully recovered.
60
Structural Remodeling
Experimental animal studies initially demonstrated that AF can cause alterations in the ultrastructure of atrial muscle cells. After prolonged periods of rapid atrial pacing, histological changes were found in the atria.
Includes:
* Increase in cell size
* Accumulation of glycogen around the nucleus
* Loss of muscle cells around the center of the affected region
* Alterations in connexin expression (connexin is a transmembrane protein that is involved in the structure of the cell)
* Changes in mitochondrial shape
* Fragmentation of sarcoplasmic reticulum (a system of membrane- bound tubules that surrounds muscle fibrils, releasing calcium ions during contraction and absorbing them during relaxation)
* Homogeneous distribution of nuclear chromatin (genetic material)
* Changes in quantity and localization of structural cellular proteins
61
Common Comorbidities that may contribute to AF
* Hypertension
* valvular disorders
* Coronary Artery Disease
* Cardiomyopathy
* Ischemic Heart Disease
62
Atrial Fibrillation and Heart Failure
Heart failure can cause atrial changes that either predispose to or worsen AF. It can also cause a number of neurohormonal alterations. Activation of the RAAS as a result of heart failure can lead to interstitial fibrosis, which may cause further conduction delay.
Essentially, any change that decreases the atrial refractory period slows atrial conduction, or increases heterogeneity of atrial repolarization can propagate AF.
Conversely, AF can lead to HF. The hemodynamic changes that result from AF can lead to further deterioration of cardiac function by reduc- ing stroke volume, cardiac output, and peak oxygen consumption
63
Atrial Fibrillation and Atrial Size
larger atria are more prone to AF. Clinically, as the heart begins to fail, a compensatory mechanism increases the amount of blood in the heart during diastole, causing atrial pressure and volume to increase. Subsequent increases in atrial pressure and volume can cause a “tissue stretch” that may cause the refractory periods in atrial fibers to become altered and more heterogeneous.
64
Characteristics and Comorbidities of Patients Hospitalized with Atrial Fibrillation
65
Typical ECG PResentation
66
Diagnosis made by\_\_\_\_\_
A definitive diagnosis of AF requires documentation of the abnormal rhythm via ECG. Diagnosis can be made with a standard 12-lead ECG or a rhythm strip recorded from a single lead.
In addition, the AHA/ACC and ESC recommend the following when appropriate:
* History and Physical exam
* ECG
* Chest X-ray - to evaluate comorbidities and heart diseases
* Echocardiogram - to evaluate valve disease and hypertrophies and evaluate atrial size
* Assessment for Hyperthyroidism
* Exercise testing
* Electrophysiological Studies - time direction and propagation of impulses
67
Clinical Impacts of Afib
68
Risk for Thromboembolic Stroke
AF is an independent risk factor for stroke, increasing the risk approxi- mately 5-fold, and the proportion increases markedly with age. Additionally, ischemic stroke associated with AF is often more severe than stroke due to other causes.
69
CHADS2
The CHADS2 score can be used to quantify the risk of stroke in patients with AF and may aid in selection of antithrombotic therapy.
C stands for recent congestive heart failure; H for hypertension, A for age 75 years or greater, and D for diabetes mellitus. Each of these is assigned a point value of 1. Two points are assigned to a history of stroke or transient ischemic attack, which is represented by S2. The total score provides a guideline for the risk of stroke and management of each patient assessed.
70
Stroke Risk Without Anticoagulation
The stroke rate per 100 patient-years without antithrombotic therapy increased by a factor of 1.5 for each 1-point increase in the CHADS2 score.
71
Heart Failure and Afib
AF has an important relationship with heart failure. In many patients, heart failure appears for the first time or worsens during treatment for AF. This is believed to occur as a result of three possible causes2:
The progression of underlying cardiac disease
Inadequate control of the ventricular rate when AF recurs Toxicity secondary to antiarrhythmic drugs2
72
Clinical and Economic Impacts
Many patients with AF present with symptoms such as palpitations, chest pain, dyspnea, fatigue, and lightheadedness. Figure 3-28 is a diagrammatic representation of the impact of the three key factors.
73
Impact of Atrial Fibrillation on Quality of Life
There are four key components to QOL measurements —
1. general health,
2. physical function,
3. social function, and
4. mental health.
74
Hospitalizations and Emergency Department Visits
Another phenomenon that affects QOL is the amount of time that persons with AF have to spend in the hospital. Studies have shown that hospitalizations for AF have increased substantially (2- to 3-fold) since 1985.
Moreover, irrespective of the year, the prevalence of hospitalization for AF was higher with increasing age.
US National Hospital Ambulatory Medical Care Survey, 1993 to 2004.55
* During the 12-year period, there were approximately 2.7 million emer- gency department visits for AF in the United States55:
* The absolute number of visits increased 88%, from 300,000 in the period 1993–1994 to 564,000 in the period 2003–2004
* Almost two-thirds of these patients were admitted to the hospital, a rate that remained constant throughout the 12-year period
* Admission rates were significantly lower in the western region of the United States than in the Northeast
* Patient characteristics and emergency department management did not materially differ by admission status
* Congestive heart failure was the only predictor of admission but accounted for only 14% of admissions
75
Management of AF involves three objectives:
1. Rate control
2. Prevention of thromboembolism
3. Correction of the rhythm disturbance
76
Rate Control Approach
Under the rate-control strategy, the ventricular rate is controlled with no commitment to restoring or maintaining sinus rhythm
Regardless of whether the rate-control or rhythm-control strategy is pursued, attention must also be directed to antithrombotic therapy for prevention of thromboembolism.
77
Rythym Control Approach
The rhythm-control strategy attempts restoration and maintenance of sinus rhythm. This strategy also requires attention to rate control
Regardless of whether the rate-control or rhythm-control strategy is pursued, attention must also be directed to antithrombotic therapy for prevention of thromboembolism.
78
The overall management strategy should consider several factors :
* Type and duration of AF
* Severity and type of symptoms
* Associated cardiovascular disease
* Patient age
* Associated medical conditions
* Short- and long-term treatment goals
* Pharmacologic and nonpharmacologic therapeutic options
The treatment strategy (i.e., ventricular rate control or restoration and maintenance of sinus rhythm) should be individualized for each patient and based on whether the patient has symptoms from uncontrolled ventricular rates or from AF itself
79
A patient with newly diagnosed AF should be evaluated for a precipi- tating cause, such as:
* Disease of the thyroid gland
* Mitral stenosis
* Pulmonary blood clots
* Inflammation of the pericardium (pericarditis)
80
How can you tell which patients are likely to convert to sinus rhythm and which ones are likely to stay in sinus rhythm?
**Duration of the arrhythmia**: Studies have indicated that the longer the patient has had AF, the greater the likelihood that he or she will remain in AF because of electrophysiological remodeling, which implies that the heart becomes “rewired” to be susceptible to arrhythmias
**Size of the atria**: Atrial size has been shown to predict the success of cardioversion, with lower success rates for larger atria. In this case, larger size refers to larger internal volume, just as a balloon becomes “larger” when filled with air. However, even having large atria does not appear to be an absolute contraindication to cardioversion
81
TREATMENT OPTIONS FOR ATRIAL FIBRILLATION
82
There are two important reasons to prevent a rapid ventricular rate in patients with AF:
1. Avoidance of hemodynamic instability and/or symptoms such as pal- pitations, heart failure, angina, lightheadedness, and poor exercise capacity
2. Avoidance of a tachycardia-mediated cardiomyopathy (over a longer period of time)
83
How is Rate Control Achieved?
Rate control in AF is usually achieved by slowing AV nodal conduction with a beta-blocker, calcium channel blocker, or digoxin. Amiodarone is also effective, although it is not generally used as a primary therapy for rate control.
Rate control is usually easier to achieve than sinus rhythm main- tenance, but the disadvantage is a persistent irregular ventricular response that does not allow symptomatic relief for many patients.
84
Drawbacks of Rate Control
Although hemodynamic function is improved with rate control, maintenance of sinus rhythm frequently leads to better results. The drugs used to maintain ventricular response (Ca2+ blockers, beta-blockers, and digitalis) may cause very slow heart rates in some patients. These patients may require implantation of a permanent pacemaker.
85
How is Rate Control Assessed?
Rate control is usually assessed both at rest and with exertion. In the AFFIRM trial described in the next section, heart rate targets for the patients in the rate-control arm included the following:
* Resting heart rate of 80 bpm or lower
* 24-hour Holter monitoring average of no more than 100 bpm and heart rate not over 110% of the age-predicted maximum
* Heart rate no higher than 110 bpm in 6-minute walk
* An alternative method that is sometimes used to assess rate control during exercise is submaximal or maximal exercise ECG testing. However, these recommendations may be burdensome to perform in patients in clinical practice.
86
What are the Two Standars for approaching Rythym Control?
1. synchronized external direct current (DC) cardioversion
2. pharmacologic cardioversion.
87
When Should Cardioversion be delayed?
In particular, patients with AF of more than 48 hours’ duration, of unknown duration, or of less than 48 hours’ duration in the presence of mitral stenosis or a history of thromboembolism may have atrial thrombi that can embolize to the brain and other organs.
88
Anticoagulation prior to Cardioversion
cardioversion should be delayed until the patient has been anticoagulated at appropriate levels (an International Normalized Ratio, or INR, of 2.0 to 3.0) for 3 to 4 weeks or shorter-term anticoagulation if screening transesophageal echocardiography has excluded atrial and atrial appendage thrombi.
89
DC cardioversion is indicated in patients who are\_\_\_\_\_\_\_\_
hemodynamically unstable, a setting in which the AF is typically of short duration.
90
What about Cardioversion for Stable Afib pts?
In stable patients in whom spontaneous reversion due to correction of an underlying disease is not likely, either DC or pharmacologic cardioversion can be performed.
Electrical cardioversion is usually preferred because of greater efficacy and a low risk of proarrhythmia.
91
What is the success Rate for Electrical Cardioversion?
The over- all success rate of electrical cardioversion for AF is 75% to 93% and is inversely related both to the duration of AF and to left atrial size
92
What is the success Rate for Pharmacologic Cardioversion?
A number of antiarrhythmic drugs are more effective than placebo, converting 30% to 60% of patients. Evidence of efficacy from ran- domized trials is best established for ibutilide, flecainide, dofetilide, propafenone, and amiodarone.
93
Why is it important to maintain sinus rythym?
Maintenance of sinus rhythm has two proven advantages:
1. Relief of symptoms
2. Improved hemodynamics
In addition, there is the theoretical (but not proven) possibility that maintenance of sinus rhythm leads to a decrease in thromboembolic events and electrical atrial remodeling.
94
Disadvantages of choosing maintenance of sinus rhythm as a treatment option are \_\_\_\_\_\_\_\_\_\_\_\_
The drug (class IC or III, beta-blockers) side effects, which usually are only an annoy- ance but can be life-threatening in a small percentage of patients.
Class IC agents (flecainide and propafenone) can result in ventricular tachycardia, heart failure, and conversion to atrial flutter with rapid conduction through the AV node.
Class III agents (dofetilide and sotalol) can cause bradycardia, heart failure, and torsade de pointes. Additionally, beta-blockers can result in bradycardia and heart block.
95
Nonpharmacologic approaches to maintaining sinus rythym include:
1. MAZE - pulmonary vein isolation
2. Implantable defibrilators
3. Catheter ablation
96
Pharmacologic options for stroke prevention include:
1. Aspirin
2. Warfarin
3. Xarelto
4. Pradaxa
97
STAF Trial
The Strategies of Treatment of Atrial Fibrillation (STAF) trial was a ran- domized multicenter trial that compared rhythm control and rate con- trol for the treatment of 200 patients with persistent AF. **The primary end point was a composite of death, cardiopulmonary resuscitation, cerebrovascular event, and systemic embolism**. Patients were followed for an average of 19.6 months.
**At the end of the study, there was no difference in the primary end point between rhythm control (5.54% per year) and rate control (6.09% per year; P=.99)** (Figure 3-35). Notably, 18 primary end points were reached during AF and only one was reached while a patient was in sinus rhythm (P=.049). These data suggest that results in the rhythm-control group might have been better if sinus rhythm had been maintained in a higher proportion of patients.
98
Framingham Study
Another trial was actually a follow-up of the original Framingham Heart Study cohort.
In this trial:
* Of the 5209 total subjects, 621 — 296 men and 325 women (mean age, 74 and 76 years, respectively) — developed AF
* AF was associated with a 1.5- to 1.9-fold mortality risk after adjustment for preexisting cardiovascular conditions
99
CHF-STAT
A third trial, the Congestive Heart Failure Survival Trial of Antiarrhythmic Therapy (CHF-STAT), demonstrated the following:
* Of 667 patients with heart failure, 103 (15%) had AF at baseline
* AF patients who converted to sinus rhythm (n = 16) had a lower mortality rate (P=.04) than those who did not (n = 35)
100
SOLVD
A fourth trial, Studies of Left Ventricular Dysfunction Prevention and Treatment Trial (SOLVD), was a retrospective analysis that examined the survival advantage of maintaining normal sinus rhythm in patients who present with AF.64
* The trial evaluated whether AF in patients with symptomatic or asymp- tomatic left ventricular dysfunction was associated with increased mortality attributed to progressive heart failure or arrhythmic death
Patients with AF compared to those in sinus rhythm at baseline had greater:
* – All-cause mortality (34% vs. 23%; P\<.001)
* – Death attributed to pump failure (16.7% vs. 9.4%; P\<.001)
* – Composite end point of death or hospitalization for heart failure (45% vs. 33%; P\<.001)
* – Increased risk of death associated with progressive pump failure when AF was associated with either asymptomatic and symptom- atic left ventricular systolic dysfunction
No significant difference in arrhythmic death was seen between the groups when they also had normal ventricular systolic function
**This study provided important evidence in favor of maintaining patients in sinus rhythm after an initial episode of AF **
101
DIAMOND
The Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) study revealed the following65:
* Of 3028 patients with severe congestive heart failure or recent myocardial infarction, 506 (17%) had AF
* Presence of sinus rhythm was associated with a significant reduction in mortality (RR 0.44, 95% CI 0.30–0.64; P\<.0001)
102
What three studies compared the rhythm strategy and rate strategy?
1. AFFIRM
2. RACE
3. AF-CHF
103
What studies assessed the benefits of maintaining sinus rythym?
1. STAF
2. Framinham (Cohort)
3. CHF-STAT
4. SOLVD
5. DIAMOND
104
AFFIRM Study Design
* The AFFIRM study was a randomized, multicenter clinical trial that compared rate- versus rhythm-control treatment strategies in the treatment of AF.66 The key features of this study were as follows58:
* 4,060 patients enrolled (2,027 in the rate-control group, 2,033 in the rhythm-control group) who were at least 65 years of age or who had other risk factors for stroke or death. Both groups were bal- anced according to baseline characteristics
* Patients were followed for 2 to 6 years (mean 3.5 years):
* – Mean age: 69.7 ± 9.0 years
* – 39.3% of participants were women
* – 50.8% had hypertension as the most predominant cardiac diagnosis
* – 38.2% had coronary artery disease
* Over 33% had enrolled after having had a first episode of AF; over 90% had had the qualifying episode within the previous 6 weeks, and the qualifying episode lasted 2 days in over 65%
* In the rhythm-control group, the antiarrhythmic drug used was cho- sen by the treating physician and cardioversion could be used to maintain sinus rhythm
* In the rate-control group, the therapeutic goal was heart rate con- trol in which AV nodal blocking drugs were used. The goal was a heart rate no higher than 80 bpm at rest and no higher than 110 bpm during a 6-minute walk
105
Affirm Primary Endpoint
**The primary end point was mortality from any cause**, and there was no significant difference in mortality (P=.08) between the two groups. The strategy of restoring and maintaining sinus rhythm in patients with AF and risk factors for stroke was comparable to the strategy of controlling the ventricular rate
106
AFFIRM Results
* The primary end point was mortality from any cause, and there was no significant difference in mortality (P=.08) between the two groups. The strategy of restoring and maintaining sinus rhythm in patients with AF and risk factors for stroke was comparable to the strategy of controlling the ventricular rate
* At the 5-year follow-up visit, 34.6% of patients in the rate-control arm were in sinus rhythm, whereas this prevalence was 62.6% for the rhythm-control group
* There was a trend toward increased mortality in the rhythm-control group (P=.08), **which may be explained by differences in the number of noncardiovascular deaths**.
107
AFFIRM and Strokes
Another factor that is believed to have played a role in the outcome of the AFFIRM study was the effect of anticoagulation intensity on the risk for stroke. Over 85% of patients in the rate-control arm were receiving warfarin throughout the study. In the rhythm-control group, warfarin use declined after the first 4 months, leaving these patients without the protection of anticoagulation. Overall, the proportion of patients receiving anticoagulation therapy was about 70% throughout the trial.69
Most strokes in both groups occurred among patients who had dis- continued warfarin or had a subtherapeutic INR. These data suggest that all patients with AF and risk factors for stroke should be receiv- ing anticoagulation therapy, unless contraindicated.
108
AFFIRM and Sinus Rythym
Another factor that was not evaluated in the original publication of the AFFIRM results is the effect of sinus rhythm on outcome, a serious omission from the initial analysis.
The presence of sinus rhythm was associated with a 54% lower risk of death (P\<.0001). Additionally, anticoagulation was associated with better survival.
The association of sinus rhythm — and not antiarrhythmic drugs per se — with improved survival may indicate that currently avail- able options for rhythm control may not be entirely safe or efficacious.
109
RACE Trial Design
The RACE Trial assigned 256 patients to rate control and 266 patients to rhythm control. **The primary end point for this study was a composite of death from cardiac causes, heart failure, thromboembolic complications, bleeding, need for a pacemaker, or serious adverse effects of the antiarrhythmics. It also studied the effects of sinus rhythm on QOL.**
110
RACE Trial Results
* Approximately 22% of patients in the rhythm-control group reached the composite primary end point, as compared with 17% in the rate- control group, suggesting a trend favoring rate control (Figure 3-38)
* Sinus rhythm was difficult to attain; 61% of patients in the rhythm- control arm were in AF at the end of the study compared with 90% in the rate-control group
* The study also demonstrated that the presence of sinus rhythm was associated with improved QOL
* The RACE study analyzed predictors of improved or impaired QOL in patients with persistent AF randomized to rhythm-control (n
* = 177) or rate-control (n = 175) strategies compared with age- matched healthy control subjects71
* At the beginning of the study, QOL was lower for all patients with AF compared with a healthy age-matched control group
111
AF-CHF Trial
The AF-CHF trial was a prospective multicenter study designed to deter- mine whether restoration and maintenance of sinus rhythm reduces car- diovascular mortality, compared with a rate-control approach, in 1,376 patients with AF and comorbid congestive heart failure. Patients were followed for an average of 2 years
## Footnote
**The primary end point was cardiovascular mortality. Secondary end points included total mortality, worsening heart failure, stroke, hospital- ization, QOL, and cost of therapy. **
112
AF-CHF Results
Overall, 445 (32.3%) patients died during a mean follow-up of 27 months. Other major clinical events during the trial included 832 events of worsening heart failure, 133 ventricular tachyarrhythmias, and 77 strokes or emboli. There was no difference in the primary
end point of cardiovascular death between the groups (26.7% of the rhythm-control group vs. 25.2% of the rate-control group; HR 1.06, 95% CI 0.86–1.30, P=NS). There were also no significant differences in total mortality (31.8% vs. 32.9%), stroke (2.6% vs. 3.6%), or worsen- ing heart failure (27.6% vs. 30.8%) between the groups
113
