CARDIAC CYCLE

•A single cycle of cardiac activity can be divided into two basic phases -
diastole and systole.
•Diastole represents the period of time when the ventricles are relaxed (not
contracting).Throughout most of this period, blood is passively flowing from the left atrium
(LA) and right atrium (RA) into the left ventricle (LV) and right ventricle (RV), respectively
(see figure at right). The blood flows through atrioventricular valves (mitral and tricuspid)
that separate the atria from the ventricles. The RA receives venous blood from the body
through the superior vena cava (SVC) and inferior vena cava (IVC). The LA receives
oxygenated blood from lungs through four pulmonary veins that enter the LA. At the end
of diastole, both atria contract, which propels an additional amount of blood into the
ventricles.
•Systole represents the time during which the left and right ventricles contract and eject
blood into the aorta and pulmonary artery, respectively. During systole, the aortic and
pulmonic valves open to permit ejection into the aorta and pulmonary artery. The
atrioventricular valves are closed during systole, therefore no blood is entering the
ventricles; however, blood continues to enter the atria though the vena cavae and
pulmonary veins.
•The cardiac cycle diagram shown to the right depicts changes in aortic pressure (AP), left
ventricular pressure (LVP), left atrial pressure (LAP), left ventricular volume (LV Vol), and
heart sounds during a single cycle of cardiac contraction and relaxation. These changes are
related in time to the electrocardiogram. An online video and tutorial of the cardiac cycle
from the Health Education Assets Library is available: cardiac cycle video.
•Aortic pressure is measured by inserting a pressure catheter into the aorta from a
peripheral artery, and the left ventricular pressure is obtained by placing a pressure
catheter inside the left ventricle and measuring changes in intraventricular pressure as the
heart beats. Left atrial pressure is not usually measured directly, except in investigational
procedures; however, left atrial pressure can be estimated by recording the pulmonary
capillary wedge pressure. Ventricular volume changes can be assessed in real time using
echocardiography or radionuclide imaging, or by using a special volume conductance
catheter placed within the ventricle.
•To analyze systole and diastole in more detail, the cardiac cycle is usually divided into
seven phases. The first phase begins with the P wave of the electrocardiogram, which
represents atrial depolarization, and is the last phase of diastole. Phases 2-4 represent
systole, and phases 5-7 represent early and mid-diastole. The last phase of the cardiac
cycle ends with the appearance of the next P wave, which begins a new cycle.
PHASE 1: A-V Valves Open; Semilunar Valves Closed
• This is the first phase of the cardiac cycle because it is initiated by the p wave of the
electrocardiogram (ECG), which represents electrical depolarization of the atria.
Atrial depolarization then causes contraction of the atrial musculature. As the atria
contract, the pressure within the atrial chambers increases, which forces more
blood flow across the open atrioventricular (AV) valves, leading to a rapid flow of
blood into the ventricles. Blood does not flow back into the vena cava because of
inertial effects of the venous return and because the wave of contraction through
the atria moves toward the AV valve thereby having a "milking effect." However,
atrial contraction does produce a small increase in venous pressure that can be
noted as the "a-wave" of the left atrial pressure (LAP). Just following the peak of
the a wave is the x-descent.
• Atrial contraction normally accounts for about 10% of left ventricular filling when a
person is at rest because most of ventricular filling occurs prior to atrial contraction
as blood passively flows from the pulmonary veins, into the left atrium, then into
the left ventricle through the open mitral valve.
• At high heart rates, however, the atrial contraction may account for up to 40% of
ventricular filling. This is sometimes referred to as the "atrial kick." The atrial
contribution to ventricular filling varies inversely with duration of ventricular
diastole and directly with atrial contractility.
• After atrial contraction is complete, the atrial pressure begins to fall causing a
pressure gradient reversal across the AV valves. This causes the valves to float
upward (pre-position) before closure. At this time, the ventricular volumes are
maximal, which is termed the end-diastolic volume (EDV). The left ventricular EDV
(LVEDV), which is typically about 120 ml, represents the ventricular preload and is
associated with end-diastolic pressures of 8-12 mmHg and 3-6 mmHg in the left and
right ventricles, respectively.
• A heart sound is sometimes noted during atrial contraction (fourth heart sound,
S4). This sound is caused by vibration of the ventricular wall during atrial
contraction. Generally, it is noted when theventricle compliance is reduced ("stiff"
ventricle) as occurs in ventricular hypertrophy and in many older individuals.
PHASE 2: All Valves Closed
• This phase of the cardiac cycle begins with the appearance of the QRS complex of
the ECG, which represents ventricular depolarization. This triggersexcitation-
contraction coupling, myocyte contraction and a rapid increase in intraventricular
pressure. Early in this phase, the rate of pressure development becomes
maximal. This is referred to as maximal dP/dt.
• The AV valves to close as intraventricular pressure exceeds atrial
pressure. Ventricular contraction also triggers contraction of the papillary
muscles with their attached chordae tendineae that prevent the AV valve leaflets
from bulging back into the atria and becoming incompetent (i.e.,
“leaky”). Closure of the AV valves results in the first heart sound (S1). This sound
is normally split (~0.04 sec) because mitral valve closure precedes tricuspid
closure.
• During the time period between the closure of the AV valves and the opening of
the aortic and pulmonic valves, ventricular pressure rises rapidly without a
change in ventricular volume (i.e., no ejection occurs). Ventricular volume does
not change because all valves are closed during this phase. Contraction,
therefore, is said to be "isovolumic" or "isovolumetric." Individual myocyte
contraction, however, is not necessarily isometric because individual myocyte are
undergoing length changes. Individual fibers contract isotonically (i.e.,
concentric, shortening contraction), while others contract isometrically (i.e., no
change in length) or eccentrically (i.e., lengthening contraction). Therefore,
ventricular chamber geometry changes considerably as the heart becomes more
spheroid in shape; circumference increases and atrial base-to-apex length
decreases.
• The rate of pressure increase in the ventricles is determined by the rate of
contraction of the muscle fibers, which is determine by mechanisms
governingexcitation-contraction coupling.
• The "c-wave" noted in the LAP may be due to bulging of mitral valve leaflets back
into left atrium. Just after the peak of the c wave is the x'-descent.
PHASE 3: Aortic and Pulmonic Valves Open; AV Valves Remain Closed
• This phase represents the initial and rapid ejection of blood into the aorta and
pulmonary arteries from the left and right ventricles, respectively. Ejection begins
when the intraventricular pressures exceed the pressures within the aorta and
pulmonary artery, which causes the aortic and pulmonic valves to open. Blood is
ejected because the total energy of the blood within the ventricle exceeds
the total energy of blood within the aorta. In other words, there is an energy
gradient to propel blood into the aorta and pulmonary artery from their
respective ventricles. During this phase, ventricular pressure normally exceeds
outflow tract pressure by a few mmHg. This pressure gradient across the valve is
ordinarily low because of the relatively large valve opening (i.e., low resistance).
Maximal outflow velocity is reached early in the ejection phase, and maximal
(systolic) aortic and pulmonary artery pressures are achieved.
• No heart sounds are ordinarily noted during ejection because the opening of
healthy valves is silent. The presence of sounds during ejection (i.e.,
ejectionmurmurs) indicate valve disease or intracardiac shunts.
• Left atrial pressure initially decreases as the atrial base is pulled downward,
expanding the atrial chamber. Blood continues to flow into the atria from their
respective venous inflow tracts and the atrial pressures begin to rise, and
continue to rise until the AV valves open at the end of phase 5.
PHASE 4: Aortic and Pulmonic Valves Open; AV Valves Remain Closed
• Approximately 200 msec after the QRS and the beginning of ventricular
contraction, ventricular repolarization occurs as shown by the T-wave of the
electrocardiogram. Repolarization leads to a decline in ventricular active tension
and therefore the rate of ejection (ventricular emptying) falls. Ventricular
pressure falls slightly below outflow tract pressure; however, outward flow still
occurs due to kinetic (or inertial) energy of the blood.
• Left atrial and right atrial pressures gradually rise due to continued venous return
from the lungs and from the systemic circulation, respectively.
PHASE 5: All Valves Closed
• When the intraventricular pressures fall sufficiently at the end of phase 4, the aortic
and pulmonic valves abruptly close (aortic precedes pulmonic) causing the second
heart sound (S2) and the beginning of isovolumetric relaxation. Valve closure is
associated with a small backflow of blood into the ventricles and a characteristic
notch (incisura or dicrotic notch) in the aortic and pulmonary artery pressure
tracings.
• After valve closure, the aortic and pulmonary artery pressures rise slightly (dicrotic
wave) following by a slow decline in pressure.
• The rate of pressure decline in the ventricles is determined by the rate of relaxation
of the muscle fibers, which is termed lusitropy. This relaxation is regulated largely by
the sarcoplasmic reticulum that are responsible for rapidly re-sequestering calcium
following contraction (see excitation-contraction coupling).
• Although ventricular pressures decrease during this phase, volumes remain constant
because all valves are closed. The volume of blood that remains in a ventricle is
called the end-systolic volume and is ~50 ml in the left ventricle. The difference
between the end-diastolic volume and the end-systolic volume is ~70 ml and
represents the stroke volume.
• Left atrial pressure (LAP) continues to rise because of venous return from the lungs.
The peak LAP at the end of this phase is termed the v-wave.
PHASE 6: A-V Valves Open
• As the ventricles continue to relax at the end of phase 5, the intraventricular
pressures will at some point fall below their respective atrial pressures. When this
occurs, the AV valves rapidly open and ventricular filling begins. Despite the inflow of
blood from the atria, intraventricular pressure continues to briefly fall because the
ventricles are still undergoing relaxation. Once the ventricles are completely relaxed,
their pressures will slowly rise as they fill with blood from the atria.
• The opening of the mitral valve causes a rapid fall in LAP. The peak of the LAP just
before the valve opens is the "v-wave." This is followed by the y-descent of the
LAP. A similar wave and descent are found in the right atrium and in the jugular vein.
• Ventricular filling is normally silent. When a third heart sound (S3) is audible, it may
represent tensing of chordae tendineae and AV ring during ventricular relaxation and
filling. This heart sound is normal in children; but is often pathological in adults and
caused by ventricular dilation.
PHASE 7: A-V Valves Open
• As the ventricles continue to fill with blood and expand, they become less
compliant and the intraventricular pressures rise. This reduces the pressure
gradient across the AV valves so that the rate of filling falls.
• In normal, resting hearts, the ventricle is about 90% filled by the end of this
phase. In other words, about 90% of ventricular filling occurs before atrial
contraction (phase 1).
• Aortic pressure and pulmonary arterial pressures continue to fall during this
period.
PRESSURE VOLUME LOOP
The cycle can be divided into four basic phases: ventricular filling (phase a; diastole), isovolumetric contraction (phase b; systole) ,
ejection (phase c; systole), and isovolumetric relaxation (phase d; diastole) . Point 1 on the PV loop is the pressure and volume at the end
of ventricular filling (diastole), and therefore represents the end-diastolic pressure and end-diastolic volume (EDV) for the ventricle. As
the ventricle begins to contract isovolumetrically (phase b), the mitral valve closes and the LVP increases, but the LV volume remains the
same, therefore resulting in a vertical line (all valves are closed). Once LVP exceeds aortic diastolic pressure, the aortic valve opens (point
2) and ejection (phase c) begins. During this phase the LV volume decreases as LVP increases to a peak value (peak systolic pressure) and
then decreases as the ventricle begins to relax. When the aortic valve closes (point 3), ejection ceases and the ventricle relaxes
isovolumetrically - that is, the LVP falls but the LV volume remains unchanged, therefore the line is vertical (all valves are closed). The LV
volume at this time is the end-systolic (i.e., residual) volume (ESV). When the LVP falls below left atrial pressure, the mitral valve opens
(point 4) and the ventricle begins to fill. Initially, the LVP continues to fall as the ventricle fills because the ventricle is still relaxing.
However, once the ventricle is fully relaxed, the LVP gradually increases as the LV volume increases. The width of the loop represents the
difference between EDV and ESV, which is by definition the stroke volume (SV). The area within the loop is the ventricular stroke work.
The filling phase moves along the end-diastolic pressure-volume relationship (EDPVR), or passive filling curve for the ventricle. The slope
of the EDPVR is the reciprocal of ventricular compliance. The maximal pressure that can be developed by the ventricle at any given left
ventricular volume is defined by the end-systolic pressure-volume relationship (ESPVR), which represents the inotropic state of the
ventricle. The pressure-volume loop, therefore, cannot cross over the ESPVR because that relationship defines the maximal pressure that
can be generated under a given inotropic state. The end-diastolic and end-systolic pressure-volume relationships are analogous to
the passive and total tension curves used to analyze muscle function.
 VALVE DEFECTS
STENOSIS REGURGITATION
• Stenosis of either atrioventricular valves • Valvular insufficiency results from
(tricuspid, mitral) or outflow tract valves valve leaflets not completely sealing
(pulmonic, aortic) leads to an elevated when a valve is closed so
pressure gradient across the valve as that regurgitation of blood occurs
blood is flowing through the valve (backward flow of blood) into the
opening. This increased pressure gradient proximal cardiac chamber.
is expressed as an increase in the • Regurgitation results in turbulence
pressure proximal to the valve and a small and the generation of characteristic
fall in pressure distal to the valve. The heart murmurs.
magnitude of the pressure gradient
depends on the severity of the stenosis
and the flow rate across the valve. A
narrowed valve also results in an increase
in the velocity of the blood as it travels
across the valve, and this increases the
probability of turbulence, which leads to
a heart murmur.
MITRAL VALVE STENOSIS
• results from a narrowing of the opened mitral valve orifice so that it is more difficult
for blood to flow from the left atrium (LA) into the left ventricle (LV) during
ventricular diastole (see figure at right). The high resistance across the stenotic
mitral valve causes blood to back up into the left atrium, thereby increasing LA
pressure, which in this example is 25 mmHg (normally ~10 mmHg). This results in
the LA pressure being much greater than the LV pressure during diastolic filling. If
left ventricular maximal filled volume (end-diastolic volume) is reduced despite the
elevated left atrial pressure, then the left ventricular end-diastolic pressure will be
reduced as shown in the figure (6 mmHg compared to 10 mmHg in the normal
heart). The left atrium enlarges (hypertrophies) over time because it has to generate
higher than normal pressures when it contracts against the high resistance of the
stenotic valve. The reduced ventricular filling (decreasedpreload) decreases
ventricular stroke volume by the Frank-Starling mechanism. If stroke volume falls
significantly, the reduced cardiac output may result in a reduction in aortic
pressure (AP; 115/80 mmHg in this example), although compensatory mechanisms
(e.g., systemic vasoconstriction) will attempt to maintain normal arterial pressure.
Mitral valve stenosis is associated with a diastolic murmur because
of turbulence that occurs as blood flows across the stenotic valve.
• The figure to the right shows how mitral stenosis affects left atrial pressure (LAP),
aortic pressure (AP) and left ventricular pressure (LVP) during the cardiac cycle. The
shaded area separating the LAP from the LVP during diastole represents the
elevated pressure gradient that is characteristic of mitral stenosis. The gradient is
highest during early diastole when the the flow across the valve is highest. Normally,
the pressure gradient across the valve is very small (a few mmHg); however, the
pressure gradient can become quite high during severe stenosis (10-30 mmHg). The
increase in LA pressure can cause pulmonary congestion and edema because of
increased pulmonary capillary hydrostatic pressure.
• The changes in ventricular pressures and volumes that result from mitral stenosis
are best illustrated using pressure-volume loops.
• Tricuspid valve stenosis is similar to mitral valve stenosis except that the pressure
and volume changes occur on the right side of the heart.
•AORTIC VALVE STENOSIS is characterized by the left ventricular pressure being much
greater than aortic pressure during left ventricular (LV) ejection (see figure at right). In
this example, LV peak systolic pressure during ejection is 200 mmHg (normally ~120
mmHg) and the aortic pressure is slightly reduced to from 120 to 110 mmHg. Normally,
the pressure gradient across the aortic valve during ejection is very small (a few mmHg);
however, the pressure gradient can become quite high during severe stenosis (>100
mmHg). The high pressure gradient across the stenotic valve results from both
increased resistance (related to narrowing of the valve opening) and turbulence distal to
the valve. The magnitude of the pressure gradient is determined by the severity of the
stenosis and the flow rate across the valve.
•Aortic stenosis can reduce ventricular stroke volume due to increased afterload (which
decreases ejection velocity). The reduced stroke volume decreases the aortic pulse
pressure, and the mean aortic pressure will fall if the reduced cardiac output is not offset
by an increase in systemic vascular resistance.
•Because the ventricle is required to generate greater pressures, this leads to
ventricular hypertrophy (thickening of the muscular walls) and diastolic
dysfunction (impaired filling). The hypertrophied ventricle has less compliance and
therefore has a higher filling pressure at any given end-diastolic volume (the end-diastolic
pressure is 25 mmHg in this example). Elevated left ventricular end-diastolic pressure
causes blood to back up into the left atrium and pulmonary veins, which increases left
atrial pressure (and pulmonary capillary wedge pressure). This enlarges the left atrium
and results in hypertrophy of the atrial wall because the left atrium has to generate
increased pressure when it contracts in order to complete ventricular filling. Aortic valve
stenosis is associated with a mid-systolic systolic murmur because of turbulence that
occurs as blood flows across the stenotic valve.
•The figure to the right shows how aortic stenosis affects left ventricular pressure (LVP),
aortic pressure (AP) and left atrial pressure (LAP) during the cardiac cycle. The shaded
area separating the LVP from the AP during systole represents the elevated pressure
gradient that is characteristic of aortic stenosis. Note that the gradient only occurs during
the time that blood is being ejected across the stenotic valve. Such measurements of LVP
and AP by cardiac catheterization provide a quantitative, hemodynamic assessment of
the severity of stenosis.
•Pulmonic valve stenosis is analogous to aortic valve stenosis except that the changes in
pressure are on the right side of the heart. A pressure gradient occurs across the
pulmonic valve during right ventricular ejection. Compensatory increases in right
ventricular end-diastolic pressure as well as right atrial pressure and volume occur.
•AORTIC REGURGITATION occurs when the aortic valve fails to close completely and blood
flows back from the aorta (Ao) into the left ventricle after ejection into the aorta is
complete and during the time that the left ventricle (LV) is also being filled from the left
atrium (LA) (see figure at right). Because the ventricle is being filled from two sources
(aorta and LA), this leads to much greater LV filling; therefore, LV end-diastolic volume is
increased as well as LV end-diastolic pressure (20 mmHg in this example). The increased
ventricular end-diastolic volume (preload) leads to an increase in the force of contraction
through the Frank-Starling mechanism, which causes a greater than normal stroke
volume into the aorta. This elevates aortic systolic pressure (160 mmHg in this example);
however, the aortic diastolic pressure (60 mmHg in this example) is much lower than
normal because blood more rapidly leaves the aorta due to regurgitation back into the
ventricle. Therefore, a defining characteristic of aortic regurgitation is an increase in
aorticpulse pressure (systolic minus diastolic pressure). The elevation in LV end-diastolic
pressure causes blood to back up into the left atrium and pulmonary veins, which leads
to an increase in left atrial pressure and pulmonary capillary wedge pressure, which can
result in pulmonary congestion and edema. The backward flow of blood into the
ventricular chamber during diastole results in a diastolic murmur.
•The figure at the right shows the changes in aortic pressure (AP), left ventricular pressure
(LVP) and left atrial pressure (LAP) that can be observed during the cardiac cycle with
aortic regurgitation. These pressures differ from those that normally occur (compare with
normal cardiac cycle) in that the aortic pulse pressure is greatly increased because of a
lower diastolic pressure and elevated systolic pressure. Furthermore, the LAP and LVP
pressures are elevated during ventricular filling because of the increased ventricular
volume.
•Early in the course of regurgitant aortic valve disease, there is a large increase in left
ventricular end-diastolic pressure and left atrial pressure. The ventricle and atria function
on a stiffer portion of theircompliance curves so that the increased volume results in a
large rise in pressure. With long-standing regurgitation and volume overload of the
chambers, the ventricles and atria dilate so that the increased volume does not result in
an exceptionally large increase in pressure. In other words, remodeling of the chambers
results in increased chamber compliance and more normal filling pressures.
•The changes in ventricular pressures and volumes during aortic regurgitation are best
illustrated using ventricularpressure-volume loops.
•Pulmonary valve regurgitation has a similar hemodynamic basis as aortic regurgitation
except that the changes in pressures and volumes are noted on the right side of the heart
(pulmonary artery, right ventricle, and right atrium).
MITRAL VALVE REGURGITATION
•occurs when the mitral valve fails to close completely during ventricular systole, which
causes blood to flow back (regurgitate) into the left atrium (LA) as the left ventricle (LV)
contracts (see figure at right). This causes the left atrium to be become engorged with
blood because blood is entering the LA from the LV during ventricular systole as well as
from the pulmonary veins. This causes LA pressure to increase (25 mmHg in this
example). During LV filling, the higher pressure and volume of the LA leads to an increase
in LV end-diastolic pressure (25 mmHg in this example) and LV end-diastolic volume. This
increase in LVpreload causes the LV to contract more forcefully (Frank-Starling
mechanism), which enables it to increase its stroke volume. Although the LV stroke
volume (end-diastolic minus end-systolic volume) is increased, the net amount of blood
ejected into the aorta is reduced because part of the LV stroke volume (regurgitant
fraction) is also ejected into the LA. If the volume of blood ejected into the aorta is
sufficiently reduced, then aortic pressure may fall (110/75 mmHg in this example). In
acute mitral regurgitation (e.g., after sudden rupture of the chordae tendineae), the atrial
pressure can become very elevated. In long-standing or chronic mitral regurgitation, the
left atrium adapts to the larger volume by dilating, which increases its compliance. The LV
also undergoes anatomic dilation. This remodeling helps to limit the increases in LA and
LV pressures. The backward flow of blood into the LA during ventricular systole results in
a holosystolic murmur.
•The figure at the right shows how mitral valve regurgitation affects aortic pressure (AP),
left ventricular pressure (LVP) and left atrial pressure (LAP) during the cardiac cycle.
Because the left atrium now receives blood from the ventricle as well as from the
pulmonary veins, there is a large increase in atrial pressure throughout the cardiac cycle,
which is most apparent at the end of ventricular systole where a very tall v-wave is
observed. LV pressure during diastole are elevated because of the elevated LA
pressure. The increased left atrial pressure can lead to pulmonary congestion and edema.
•Then changes in left ventricular pressure and volume that occur in response to mitral
valve regurgitation are best illustrated bypressure-volume loops.
•Tricuspid valve regurgitation has a similar hemodynamic basis as mitral regurgitation
except that the changes in pressures and volumes are noted on the right side of the heart
(pulmonary artery, right ventricle, and right atrium).
•