Typification of atrial organization in electrogram recordings

of blood ejected during resting conditions is approximately 5 l/min, with a
heart rate of about 70 bpm and a stroke volume of about 70 ml; these number
can vary greatly so that the amount of blood pumped could reach values close
to, or even exceeding 15 l/min, satisfying the increased metabolic requests
of the body under stress conditions.
1.1 The atria
The atria represent a crucial element of the normal circulatory functions and
regulation. Often atrial dysfunctions precede the onset of AF, so that a
better understanding of atrial function and dysfunction is relevant to clinical
management of AF and can guide the research on new algorithms which
are able to detect, describe and discriminate between different types of the
pathology.
Even though much progress has been made during the last few decades
in understanding the electrophysiology and hemodynamics, atrial contrac-
tile function pre-onset and in paroxysmal (non persistent) AF (PAF) is still
poorly understood. AF trigger mechanisms are elusive and in some cases
unknown, even if both an underlying etiology and an apparently proper pre-
cipitating cause are present.
1.1.1 Anatomy
The atria are thin-walled and are mainly constituted of muscular tissue, with
longitudinally oriented fibers. The right atrium is connected to the venae
cavae and is separated from the right ventricle by the tricuspid valve, while
the left atrium is connected to the pulmonary veins and divided from the left
ventricle by the mitral valve. Both atria have attached appendages named
auricles: in particular the left auricle shows a very narrow and elongated
structure that, likely, favours thrombus formation if non contracting.
The thin structure of atrial walls and the organization of the muscular fibers
suggest the atria to be low-pressure chambers: stretch receptors are in fact
present as well, with granules releasing a peptide (ANP, atrial natriuretic
peptide) that represents a feedback control stadium for volume and pressure
overload.
Moreover, a specialised conduction tissue is present in the SA and AV nodes
in the internodal pathways: both SA and AV nodes are influenced by auto-
nomic nerve endings, suggesting some possibilities for neural mechanisms to
play a role in the genesis and maintenance of AF.
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1.1.2 Functions
Atria have different functions: hemodynamic and electrical functions are
relevant when studying AF.
Hemodynamically the atria work as collection and suction chambers dur-
ing diastole and as booster pumps during systole favouring a more complete
filling of the ventricles, depending on their compliance and on the force ex-
erted by atrial wall contraction. Left ventricular filling pressure is also reg-
ulated via ventricular suction by the left atrium during diastole, so that an
optimal timing for closure of the mitral valve is achieved. As stated in the
Guyton model, atrial filling pressure is a fundamental parameter that regu-
lates the function of the cardiac pump: the atrial manometer function makes
use of stretch receptors and ANP secretion and contributes to blood volume
homeostasis by restoring atrial pressure and volume conditions and it also
functions as a first line defense mechanism in case of congestive heart failure
before other neurohormonal systems could act.
Electrically the atria, in particular the right atrium, work as impulse gen-
erators via the SA node and current distributors via internodal conduction:
the impulse is conducted in the atria via longitudinally oriented muscular
fibers. The lack of a specialized conduction system make atrial conduction
vulnerable to pathology: by applying a proper stimulus, it is in fact relatively
easy to induce different types of fibrillatory rhythms into the normal heart.
1.2 Pathology and failure of the atria
A number of pathologic conditions can afflict the atria: they could be of a
primary or secondary type (caused by underlying ventricular pathologies).
Between primary pathologies atrial infarction, infection or septal aneurysm
or degenerations can be sometimes responsible of cases of AF while in old
age atrial amyloidosis could also lead to mechanical failure of contraction.
Atrial dilatation is common in many cardiac pathologies, as for example in
the late stages of hypertensive heart disease: it can have several consequences,
involving sluggish blood flow, and favour the onset and maintenance of AF
(over a critical atrial size).
Dysfunction of the atria can lead to several consequences: from an hemo-
dynamic point of view sluggish atrial blood flow can lead to thrombus for-
mation and is an accepted risk factor for thromboembolic complications,
while loss of the atrial contribution to stroke volume is a detrimental fac-
tor in patient with diastolic ventricular filling problems, due to, for example,
scarce compliance. Atrial enlargement can induce further modification of the
5
anatomical and conduction properties of the tissue, according to a mecha-
nism called mechano-electric feedback: experimental and clinical studies have
demonstrated that changes in the mechanical loading condition can modify
both electrophysiological and anatomical properties of the atrial tissue.
6
Chapter 2
Atrial Fibrillation
2.1 An overview
AF is the most common sustained cardiac arrhythmia in clinical practice and
leads to twice the mortality of that among people in sinus rhythm: although
it can occur at any age, its prevalence tends to increase with age and affects
men slightly more often than women.
Causes Certain risk factors predispose patients to AF and progression to
chronic AF:
• tachycardia or faster atrial rates;
• rheumatic valvular disease;
• other structural heart disease;
• cardiac failure;
• hypertensive heart disease;
• pericarditis;
• left-atrial enlargement;
• increased thickness of the left ventricular wall;
• lower than normal left-ventricular shortening.
AF can also occur as a secondary event: for example, a trigger mechanism
such as a premature atrial contraction has been associated with the initiation
of AF in some patients; other arrhythmias such as atrial tachycardia and
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atrial flutter may also be initiated from a single region of either atria and
subsequently degenerate into AF. Several non-cardiac disorders increase the
risk of AF, including diabetes mellitus, alcohol ingestion, thyrotoxicosis, and
increased vagal or sympathetic tone in susceptible individuals.
AF with no identifiable cause or associated abnormalities of the cardiac
muscle is defined as loneAF .
In the broadest sense, AF represents the loss of synchronization between
the atria and the ventricles.
For many years, AF was believed to be a completely chaotic event with
unorganized electrical impulses bouncing around the atria randomly. Moe [2]
in 1962 suggested that AF might be the result of multiple, migrant wavelets
of activation. Such a hypothesis is nowadays generally accepted: if it really
describes the physiology of AF reentrant activation, together with possible
values for refractory period and conduction velocity, it must provide some
constraints to the activation process.
Therefore AF could not be a random process and its organization could be
strongly influenced by such parameters.
2.1.1 Different clinical classification
AF was classified in paroxysmal or persistent according to its frequency of
occurrence and duration:
• paroxysmal AF occurs intermittently and varies in frequency and du-
ration from a few seconds to several hours or even days.
• persistent AF is the primary heart rhythm and is usually unresponsive
to medical therapy or other non-pharmacologic interventions such as
electrical cardioversion.
While both lone and paroxysmal AF tend to be seen more often in younger
people, persistent AF is normally seen in an older population.
An imbalance in the nervous system regulation of the heart can cause
neurogenic AFs:
• vagal AF occurs in conjunction with enhanced parasympathetic re-
sponse from the vagus nerve so that the heart rate slows down and
the refractory period of the atria shortens. Typically, vagal AF occurs
more frequently at rest or following a meal, and is usually in seen men
who are between 30 and 50 years of age.
8
• adrenergic AF occurs as a result of excessive adrenaline that comes
from sympathetic stimulation; sympathetic effects on the heart include
increased rate and force of contraction. This type of AF is most likely
occurring during the day and may be associated with emotional or
physical stress.
2.1.2 Complications
The tachycardia per se and the associated atrial contraction failure lead to
profound alterations in atrial anatomy and function, establishing two differ-
ent vicious circles sustaining AF and worsening eventual pre-existing heart
failure.
The non contracting atrium may lead to remodeling of the atrial body, in-
creasing atrial size and causing intra-atrial flow velocity to decrease, leading
to sluggish flow and increasing the risk of thrombus formation. AF patients
with a large left atrium are thus threatened with both thromboembolic com-
plications and worsening congestive heart failure.
Cognitive defects increasingly develop in AF even in the absence of clinical
stroke, and may relate to small, silent, deep lacunar and cortical infarcts.
Furthermore, significant deficits in attention, memory, and language have
been reported with no evidence of cerebral ischaemia.
The increased heart rate in AF and the severity of the underlying ven-
tricular disease, determine the overall hemodynamic derangement: hemody-
namically, the loss of atrial transport and the impaired diastolic filling can
reduce resting cardiac output by up to 20% if uncontrolled and long lasting,
the irregular tachycardia may by itself precipitate cardiomyopathy and lead
to congestive heart failure.
Thromboembolic disease and stroke are the most important complica-
tions of AF and their occurrence strikingly increases in both paroxysmal and
chronic AF. However, because of a low rate of stroke among patients with
lone AF, the causal link between AF and stroke has still to be proved.
Complications are also heavily dependent on the effectiveness of the ther-
apy, which strongly varies according to the duration of time since the onset of
AF. As it is normally difficult to isolate AF onset, studies showed that eval-
uation of atrial size may be of some help to assess the approximate duration
of a patients AF [3-4].
2.1.3 Therapy
The initial management of patients with AF should address potential pre-
cipitating illnesses while clinical assessment should moreover address those
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factors that maintain and worsen the patient’s conditions. Therapy should
aim to restore sinus rhythm or to control heart rate to reduce palpitations
and symptoms of heart failure and to decrease consequences due to stroke
and thromboembolism.
Cardioversion to sinus rhythm is the primary goal when patients are
hemodynamically compromised, for acute AF and in patients who lack the
risk factors for disease progression, and it can be performed electrically or
pharmacologically. Cardioversion has a subsequent stroke risk of up to 3%
because of the dislodgement of pre-existing thrombi and should therefore be
preceded and followed by some anticoagulation therapy.
While therapy in permanent AF is limited to the amelioration of symp-
toms by rate control, an important point in other types of AF is whether to
attempt the maintenance of sinus rhythm or to be satisfied with rate con-
trol. Maintenance of sinus rhythm restores physiological heart-rate control
at the cost of immediate therapeutic complications while rate control po-
tentially affords symptom relief at the cost of chronic disease. Surgery can
restore sinus-nodal control of ventricular rhythm in drug-resistant patients
by creating conduction blocks. Implantable atrial defibrillators are becoming
a viable option for termination of recurrent episodes of chronic AF, at the
cost of potentially painful intra-atrial shocks and cost-effectiveness. Invasive
therapy for refractory AF includes catheter-based radiofrequency ablation of
the atrioventricular node to induce a complete atrioventricular block, after
which heart rate is maintained with an adaptive-rate permanent ventricular
pacemaker.
Thrombolytic therapy is important in the prevention of the high risk of
stroke and thromboembolism among patients with paroxysmal and chronic
AF. Warfarin reduces the annual incidence of thrombotic stroke while As-
pirin is useful in patients at risk for non-cardiac emboli, even though it is
generally less effective.
In the following sections the pathophysiology of AF will be discussed in more
detail, pointing out the concepts of mechano-electric feedback and introduc-
ing Moe’s multiple wavelets theory.
Since this work concerns different methods of AF detection and classifica-
tion, a review of the most interesting types of signals, the instrumentation
used and of the Wells’ scheme for AF classification will be also presented: at
that stage the evolution of such methods will be discussed, bringing different
examples of time-domain analysis and comparing the different achievements
of such papers.
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2.2 Trigger mechanisms and
mechano-electric feedback
AF frequently occurs under conditions suggesting a role of mechano-electric
feedback in its genesis. To understand why an individual gets AF it is nec-
essary to try to asses which of the various mechanisms, anatomic, hemo-
dynamic, electric or endocrine, might be responsible: both mechanical and
electrical abnormalities are needed for AF onset and maintenance [5].
Parasympathetic stimulation (acetylcholine) shortens the refractory pe-
riod, facilitating inhomogeneous atrial conduction, refractoriness dispersion
and then AF and atrial flutter, while sympathetic discharge (noradrenaline)
is a more common AF trigger in patients with some underlying heart disease.
The association between atrial dilatation and AF has already been shown
in many clinical studies: atrial enlargement, though, may be both a cause
and a consequence of AF [6].
Mechanical stretch of parts of the atrial wall can be caused by:
• an increase in internal volume and pressure
• an external pressure
• epicardial lesions
• underlying cardiac pathologies
Atrial stretch and dilatation may favour the development of atrial ar-
rhythmias in a wide range of clinical conditions and then modulate electro-
physiological properties of the atria, thus promoting arrhythmogenic events.
Basically two different hypothesis have been proposed:
• abnormal impulse formation
• abnormal impulse conduction with associated re-entry.
Afterdepolarizations of sufficient magnitude to precipitate an extrasystole
or repetitive firing can develop both during (early afterdepolarization, EAD)
or after the process of repolarization (delayed afterdepolarization,DAD). Sev-
eral factors, as a reduction in the normal repolarizing currents, an abnormal
prolongation of inward Na+ or Ca++ currents or an intracellular calcium
overload could trigger such a process.
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