Acute Rheumatic Fever

By: Dr.Zena A. (Assistant professor of IM, Echo-Technician)

 Acute rheumatic fever (ARF)
 Acute rheumatic fever is a multisystem disease
resulting from an autoimmune reaction to infection
with group A streptococcus.
 Although many parts of the body may be affected,
almost all of the manifestations resolve completely.
 The major exception is cardiac valvular damage
(rheumatic heart disease [RHD]), which may persist
after the other features have disappeared.
 GLOBAL CONSIDERATIONS

 ARF and RHD are diseases of poverty.

 They were common in all countries until the early
twentieth century, when their incidence began to
decline in industrialized nations.
 This decline was largely attributable to improved
living conditions—particularly less crowded housing
and better hygiene—which resulted in reduced
transmission of group A streptococci
 The introduction of antibiotics and improved systems
of medical care had a supplemental effect.
 Cont.
 The virtual disappearance of ARF and reduction in the
incidence of RHD in industrialized countries during the
twentieth century unfortunately was not replicated in
developing countries, where these diseases continue
unabated.
 RHD is the most common cause of heart disease in
children in developing countries and is a major cause of
mortality and morbidity in adults as well
 It has been estimated that between 15 and19 million
people worldwide are affected by RHD, with
approximately one-quarter of a million deaths occurring
each year.
 Cont.
 95% of ARF cases and RHD deaths now occur in
developing countries, with particularly high rates in
sub-Saharan Africa, Pacific nations, Australasia, and
South and Central Asia
 The pathogenetic pathway from exposure to group A
streptococcus followed by pharyngeal infection and
subsequent development of ARF
 ARF recurrences, and development of RHD and its
complications is associated with a range of risk
factors and, therefore, potential interventions at
each point
 Cont.
 In affluent countries, many of these risk factors are well
controlled, and interventions are in place.
 Unfortunately, the greatest burden of disease is found in
developing countries, most of which do not have the
resources, capacity, and/or interest to tackle this
multifaceted disease.
 In particular, almost none of the developing countries has a
coordinated, register-based RHD control program, which is
proven to be cost-effective in reducing the burden of RHD.
 Enhancing awareness of RHD and mobilizing resources for
its control in developing countries are issues requiring
international attention.
 EPIDEMIOLOGY

 ARF is mainly a disease of children, age 5–14 years

 Initial episodes become less common in older
adolescents and young adults and are rare in persons
aged >30 years.
 By contrast, recurrent episodes of ARF remain
relatively common in adolescents and young adults.
 This pattern contrasts with the prevalence of RHD,
which peaks between 25 and 40 years.
 There is no clear gender association for ARF, but RHD
more commonly affects females, sometimes up to
twice as frequently as males.
Cont.
Cont.
 ORGANISM FACTORS

 Based on currently available evidence, ARF is exclusively

caused by infection of the upper respiratory tract with
group A streptococci
 Although classically, certain M-serotypes (particularly
types 1, 3, 5, 6, 14, 18, 19, 24, 27, and 29) were
associated with ARF, in high-incidence regions, it is now
thought that any strain of group A streptococcus has
the potential to cause ARF.
 The potential role of skin infection and of groups C and
G streptococci is currently being investigated.
 HOST FACTORS

 Approximately 3–6% of any population may be

susceptible to ARF
 Findings of familial clustering of cases and
concordance in mono-zygotic twins—particularly for
chorea—confirm that susceptibility to ARF is an
inherited characteristic
• With 44% concordance in mono-zygotic twins
compared to 12% in dizygotic twins, and heritability
more recently estimated at 60%.
 Most evidence for host factors focuses on
immunologic determinants.
 Cont.
 Some human leukocyte antigen (HLA) class II alleles,
particularly HLA-DR7 and HLA-DR4, appear to be
associated with susceptibility
• Whereas other class II alleles have been associated
with protection (HLA-DR5, HLA-DR6, HLA-DR51, HLA-
DR52, and HLA-DQ).
 Associations have also been described with
polymorphisms at the TNF α locus (TNF-α-308 and
TNF-α-238), high levels of circulating mannose-
binding lectin, and Toll-like receptors.
 THE IMMUNE RESPONSE
 The most widely accepted theory of rheumatic fever
pathogenesis is based on the concept of molecular mimicry
• Whereby an immune response targeted at streptococcal
antigens (the M protein and the NAGA of group A
streptococcal carbohydrate) also recognizes human tissues.
 In this model, cross-reactive antibodies bind to endothelial
cells on the heart valve, leading to activation of the
adhesion molecule VCAM-1
• With resulting recruitment of activated lymphocytes and
lysis of endothelial cells in the presence of complement.
 Cont.
 The latter leads to release of peptides including
laminin, keratin, and tropomyosin, which, in turn,
activates cross-reactive T cells that invade the
heart, amplifying the damage
 An alternative hypothesis proposes that the initial
damage is due to streptococcal invasion of
epithelial surfaces, with binding of M protein to
type IV collagen allowing it to become
immunogenic, but not through the mechanism of
molecular mimicry.
 CLINICAL FEATURES

 There is a latent period of ~3 weeks (1–5 weeks) between

the precipitating group A streptococcal infection and the
appearance of the clinical features of ARF.
 The exceptions are chorea and indolent carditis, which
may follow prolonged latent periods lasting up to 6
months.
 Although many patients report a prior sore throat, the
preceding group A streptococcal infection is commonly
subclinical;
• In these cases, it can only be confirmed using
streptococcal antibody testing.
 Cont.
 The most common clinical features are
polyarthritis (present in 60–75% of cases) and
carditis (50–60%).
 The prevalence of chorea in ARF varies
substantially between populations, ranging
from <2 to 30%.
 Erythema marginatum and subcutaneous
nodules are now rare, being found in <5% of
cases.
 HEART INVOLVEMENT

 Up to 60% of patients with ARF progress to RHD.

 The endocardium, pericardium, or myocardium may
be affected.
 Valvular damage is the hallmark of rheumatic carditis.
 The mitral valve is almost always affected, sometimes
together with the aortic valve; isolated aortic valve
involvement is rare.
 Damage to the pulmonary or tricuspid valves is
usually secondary to increased pulmonary pressures
resulting from left-sided valvular disease.
 Cont.
 Early valvular damage leads to regurgitation.
 Over ensuing years, usually as a result of recurrent
episodes,
• Leaflet thickening,
• Scarring,
• Calcification, and
• Valvular stenosis may develop
 Therefore, the characteristic manifestation of carditis
in previously unaffected individuals is mitral
regurgitation, sometimes accompanied by aortic
regurgitation.
 Cont.
 Myocardial inflammation may affect electrical
conduction pathways, leading to P-R interval
prolongation (1st degree AV block or rarely higher level
block) and softening of the first heart sound.
 People with RHD are often asymptomatic for many
years before their valvular disease progresses to cause
cardiac failure.
 Moreover, particularly in resource-poor settings, the
diagnosis of ARF is often not made, so children,
adolescents, and young adults may have RHD but not
know it.
 Cont.
 These cases can be diagnosed using echocardiography;
auscultation is poorly sensitive and specific for RHD
diagnosis in asymptomatic patients.
 Echocardiographic screening of school-aged children in
populations with high rates of RHD is becoming more
widespread.
 A diagnosis of definite RHD on screening
echocardiography should lead to commencement of
secondary prophylaxis
 JOINT INVOLVEMENT

 The most common form of joint involvement in ARF is

arthritis
• Such that objective evidence of inflammation, with hot,
swollen, red, and/or tender joints, and involvement of
more than one joint (i.e., polyarthritis).
 Polyarthritis is typically migratory, moving from one joint to
another over a period of hours.
 ARF almost always affects the large joints—most commonly
the knees, ankles, hips, and elbows—and is asymmetric.
 The pain is severe and usually disabling until anti-
inflammatory medication is commenced.
 Cont.
 Less severe joint involvement is also relatively
common and has been recognized as a potential
major manifestation in high-risk populations in the
most recent revision of the Jones criteria.
 Arthralgia without objective joint inflammation
usually affects large joints in the same migratory
pattern as polyarthritis.
 In some populations, aseptic monoarthritis may be a
presenting feature of ARF, which may, in turn, result
from early medication use before the typical
migratory pattern is established.
 Cont.
 The joint manifestations of ARF are highly responsive
to salicylates and other NSAIDs.
 Indeed, joint involvement that persists for more than
1 or 2 days after starting salicylates is unlikely to be
due to ARF.
 CHOREA

 Sydenham’s chorea commonly occurs in the

absence of other manifestations, follows a
prolonged latent period, and is found mainly in
females.
 The choreiform movements affect particularly the
head (causing characteristic darting movements
of the tongue) and the upper limbs
 They may be generalized or restricted to one side
of the body (hemi-chorea).
 Cont.
 In mild cases, chorea may be evident only on careful
examination, whereas in the most severe cases, the
affected individuals are unable to perform activities
of daily living.
 There is often associated emotional lability or
obsessive-compulsive traits, which may last longer
than the choreiform movements (which usually
resolve within 6 weeks but sometimes may take up
to 6 months).
 SKIN MANIFESTATIONS

 The classic rash of ARF is erythema marginatum ,

which begins as pink macules that clear centrally,
leaving a serpiginous, spreading edge.
 The rash is evanescent, appearing and disappearing
before the examiner’s eyes.
 It occurs usually on the trunk, sometimes on the
limbs, but almost never on the face.
 Cont.
 Subcutaneous nodules occur as painless, small (0.5–2
cm), mobile lumps beneath the skin overlying bony
prominences, particularly of the hands, feet, elbows,
occiput, and occasionally the vertebrae.
• They are a delayed manifestation, appearing 2–3
weeks after the onset of disease
• Last for just a few days up to 3 weeks
• They are commonly associated with carditis.
 Other features

 Fever occurs in most cases of ARF, although rarely in

cases of pure chorea.
 Although high-grade fever (≥39°C) is the rule, lower
grade temperature elevations are not uncommon.
 Elevated acute-phase reactants are also present in
most cases.
 EVIDENCE OF A PRECEDING GROUP A STREPTOCOCCAL INFECTION

 With the exception of chorea and low-grade carditis,

both of which may become manifest many months
later, evidence of a preceding group A streptococcal
infection is essential in making the diagnosis of ARF.
 Because most cases do not have a positive throat
swab culture or rapid antigen test, serologic evidence
is usually needed.
 The most common serologic tests are the anti-
streptolysin O (ASO) and anti-DNase B (ADB) titers.
 Age-specific reference ranges should be
determined
 CONFIRMING THE DIAGNOSIS
 Because there is no definitive test, the diagnosis of
ARF relies on the presence of a combination of typical
clinical features together with evidence of the
precipitating group A streptococcal infection, and the
exclusion of other diagnoses.
 This uncertainty led to develop a set of criteria (Jones
criteria) to aid in the diagnosis
 High or moderate risk (more sensitive criteria) vs low-
risk criteria
Cont.
Cont.
 Treatment of Acute Rheumatic Fever

 Patients with possible ARF should be followed closely to

ensure that the diagnosis is confirmed, treatment of
heart failure and other symptoms is undertaken, and
preventive measures including commencement of
secondary prophylaxis, inclusion on an ARF registry, and
health education are commenced.
 Echocardiography should be performed on all possible
cases to aid in making the diagnosis and to determine
the severity at baseline of any carditis.
 There is no treatment for ARF that has been proven to
alter the likelihood of developing, or the severity of RHD.
 ANTIBIOTICS

 All patients with ARF should receive antibiotics

sufficient to treat the precipitating group A
streptococcal infection
 Penicillin is the drug of choice and can be given orally
PO twice daily for 10 days) or as a single dose of 1.2
million units (600,000 units for children ≤27 kg) IM
benzathine penicillin G.
 SALICYLATES AND NSAIDs
 These may be used for the treatment of arthritis,
arthralgia, and fever, once the diagnosis is confirmed.
 Cont.

 They are of no proven value in the treatment of

carditis or chorea.
 Aspirin is the drug of choice, delivered at a dose of
50–60 mg/kg per day, up to a maximum of 80–100
mg/kg per day (4–8 g/d in adults) in 4–5 divided doses
 At higher doses, the patient should be monitored for
symptoms of salicylate toxicity
• such as nausea, vomiting, or tinnitus; if symptoms
appear, lower doses should be used.
 Cont.
 When the acute symptoms are substantially resolved,
usually within the first 2 weeks, patients on higher
doses can have the dose reduced to 50–60 mg/kg per
day for a further 2–4 weeks.
 Fever, joint manifestations, and elevate APR
sometimes recur up to 3 wks after the discontinuation
 This does not indicate a recurrence and can be
managed by giving salicylates again for a brief period.
 Naproxen is a suitable alternative to aspirin
 Heart failure
 Many clinicians treat cases of severe carditis (causing
heart failure) with glucocorticoids in the belief that
they may reduce the acute inflammation and result in
more rapid resolution of failure.
 However, the potential benefits of this treatment
should be balanced against the possible adverse
effects.
 If used, prednisone or prednisolone is recommended
at a dose of 1–2 mg/kg per day (maximum, 80 mg),
usually for a few days or up to a maximum of 3 weeks.
 Cont.
 BED REST
 Traditional recommendations for long-term bed
rest, are no longer widely practiced.
 Instead, bed rest should be prescribed as needed
while arthritis and arthralgia are present and for
patients with heart failure.
 Once symptoms are well controlled, gradual
mobilization can commence as tolerated
 Medications to control the abnormal movements do
not alter the duration or outcome of chorea.
 CHOREA
 Milder cases can usually be managed by providing a
calm environment.
 In patients with severe chorea, carbamazepine or
sodium valproate is preferred to haloperidol.
 A response may not be seen for 1–2 weeks
 And medication should be continued for 1–2 weeks
after symptoms subside.
 There is recent evidence that steroids are effective
and lead to more rapid symptom reduction
 They should be considered in severe or refractory
cases.
 PROGNOSIS

 Untreated, ARF lasts on average 12 weeks.

 With treatment, patients are usually discharged from
hospital within 1–2 weeks.
 Inflammatory markers should be monitored every 1–2
weeks until they have normalized (usually within 4–6
weeks)
 An echocardiogram should be performed after 1
month to determine if there has been progression of
carditis.
 Cases with more severe carditis need close clinical and
echocardiographic monitoring in the longer term.
 Cont.
 Once the acute episode has resolved, ensure long-
term clinical follow-up and adherence to a regimen of
secondary prophylaxis.
 Patients and their families should also be educated
about their disease, emphasizing the importance of
adherence to secondary prophylaxis.
 PREVENTION OF PRIMARY PREVENTION

 Ideally, primary prevention would entail elimination

of the major risk factors for streptococcal infection,
particularly overcrowded housing.
 This is difficult to achieve in most places where ARF is
common.
 Therefore, the mainstay of primary prevention for
ARF remains primary prophylaxis (i.e., the timely and
complete treatment of group A streptococcal sore
throat with antibiotics).
 Cont.
 If commenced within 9 days of sore throat
onset, a course of penicillin will prevent almost
all cases
 In settings where ARF and RHD are common,
often recommend that all patients with sore
throat be treated with penicillin or, alternatively
 A clinical algorithm be used to identify patients
with a higher likelihood of group A S.coccal
pharyngitis if there is no confirmatory test
 SECONDARY PREVENTION

 The mainstay of controlling ARF and RHD is

secondary prevention.
 Because patients with ARF are at dramatically
higher risk than the general population of
developing a further episode of ARF after a group A
streptococcal infection, they should receive long-
term penicillin prophylaxis to prevent recurrences.
 The best antibiotic for secondary prophylaxis is
benzathine penicillin G (1.2 million units, or 600,000
units if ≤27 kg) delivered every 4 weeks.
 Cont.
 It can be given every 3 weeks, or even every 2 weeks,
to persons considered to be at particularly high risk
 Oral penicillin V (250 mg) can be given twice daily
instead but is less effective than benzathine penicillin
G.
 Penicillin-allergic patients can receive erythromycin
(250 mg) twice daily.
 Cont.
 The duration of secondary prophylaxis is determined
by many factors
• The duration since the last episode of ARF
(recurrences become less likely with increasing time)
• Age (recurrences are less likely with increasing age),
and
• The severity of RHD (if severe, it may be prudent to
avoid even a very small risk of recurrence because of
the potentially serious consequences)
 Secondary prophylaxis is best delivered as part of a
coordinated RHD control program
Cont.
 Valvular diseases

By: Dr.Zena A. (Assistant professor of IM, Echo-Technician)

 MITRAL STENOSIS
 ETIOLOGY AND PATHOLOGY
 Rheumatic fever is the leading cause of MS
 Other less common etiologies of obstruction to left
ventricular inflow include
• Congenital mitral valve stenosis,
• Cor triatriatum,
• MAC with extension onto the leaflets,
• Systemic lupus erythematosus,
• Rheumatoid arthritis,
• Left atrial myxoma, and
• Infective endocarditis with large vegetations
 Cont.
 Pure or predominant MS occurs in approximately 40%
of all patients with RHD and a history of RF
 In other patients with RHD, lesser degrees of MS may
accompany MR and aortic AV disease.
 With reductions in the incidence of acute RF in
developed countries, the incidence of MS has
declined
 However, it remains a major problem in developing
nations
 Cont.
 In rheumatic MS, chronic inflammation leads to diffuse
thickening of the valve leaflets with formation of fibrous
tissue and/or calcific deposits.
 The mitral commissures fuse, the chordae tendineae fuse
and shorten, the valvular cusps become rigid
• These changes, in turn, lead to narrowing at the apex of the
funnel-shaped (“fish-mouth”) valve.
 Calcification of the stenotic mitral valve immobilizes the
leaflets and narrows the orifice further.
 Thrombus formation and arterial embolization may arise
from the calcific valve itself
• But in patients with AF, thrombi arise more frequently from
the dilated LA, particularly in the LA appendage.
 PATHOPHYSIOLOGY

 In normal adults, the area of the MV orifice is 4–6cm2.

 In the presence of significant obstruction, i.e., when
the orifice area is reduced to < ~2 cm2, blood can flow
from the LA to the LV only if propelled by an
abnormally elevated left AVP gradient
• It the hemodynamic hallmark of MS
 When the MV opening is reduced to <1.5 cm2,
referred to as “severe” MS, an LA pressure of ~25
mmHg is required to maintain a normal CO.
 The elevated PV and PAWP reduce pulmonary
compliance, contributing to exertional dyspnea.
 Cont.

 The 1st bouts of dyspnea are usually precipitated by clinical

events that increase the rate of BF across the mitral orifice
 To assess the severity of obstruction hemodynamically,
both the TVPG and the flow rate must be measured
 The latter depends not only on the CO but on the heart
rate, as well.
 An increase in heart rate shortens diastole proportionately
more than systole and diminishes the time available for
flow across the mitral valve
 Therefore, at any given level of CO, tachycardia, including
that associated with rapid AF, augments the TVPG and
elevates further the LA pressure.
 Cont.
 The LVDP and EF are normal in isolated MS.
 In MS and sinus rhythm, the elevated LA and PA
wedge pressures exhibit a prominent atrial
contraction pattern (a wave)
 In severe MS and whenever pulmonary vascular
resistance is significantly increased, the PA pressure is
elevated at rest and rises further during exercise,
often causing secondary elevations of RVEDP and
volume.
 Cont.
 Cardiac Output In patients with severe MS (mitral
valve orifice 1–1.5 cm2), the CO is normal or almost
so at rest, but rises subnormally during exertion.
 In patients with very severe MS (valve area <1 cm2),
particularly those in whom pulmonary vascular
resistance is markedly elevated, the CO is subnormal
at rest and may fail to rise or may even decline
during activity.
 Pulmonary Hypertension
 Pulmonary hypertension results from:
• Passive backward transmission of the elevated LA
pressure;
• Pulmonary arteriolar constriction (the socalled “second
stenosis”), which presumably is triggered by LA and
PVHTN (reactive PHTN);
• Interstitial edema in the walls of the small pulmonary
vessels; and
• At end stage, organic obliterative changes in the
pulmonary vascular bed.
 Severe pulmonary hypertension results in
• RV enlargement, Secondary TR and PR, as well as RHF.
 SYMPTOMS
 In temperate climates, the latent period between the
initial attack of rheumatic carditis and the
development of symptoms due to MS is generally
about two decades
• Most patients begin to experience disability in the
fourth decade of life.
 Studies carried out before the development of mitral
valvotomy revealed that once a patient with MS
became seriously symptomatic, the disease
progressed inexorably to death within 2–5 years
 Cont.
 In patients whose mitral orifices are large enough to
accommodate a normal blood flow with only mild
elevations of LA pressure, marked elevations of this
pressure leading to dyspnea and cough may be
precipitated by sudden changes in the heart rate,
volume status, or CO
• For example, with severe exertion, excitement, fever,
severe anemia, paroxysmal AF and other tachycardias,
sexual intercourse, pregnancy, and thyrotoxicosis
 As MS progresses, lesser degrees of stress precipitate
dyspnea, the patient becomes limited in daily activities,
and orthopnea and PND develop.
 Hemoptysis

 Results from rupture of pulmonary-bronchial venous

connections secondary to pulmonary venous
hypertension.
 It occurs most frequently in patients who have elevated
LA pressures without markedly elevated pulmonary
vascular resistances and is rarely fatal
 Recurrent pulmonary emboli , sometimes with
infarction, are an important cause of morbidity and
mortality late in the course of MS.
 Pulmonary infections commonly complicate untreated
MS, especially during the winter months
 Cont.
 Pulmonary Changes in the pulmonary vascular
bed, fibrous thickening of the walls of the alveoli
and pulmonary capillaries occurs commonly in
MS.
 The vital capacity, total lung capacity, maximal
breathing capacity, and oxygen uptake per unit of
ventilation are reduced.
 Pulmonary compliance falls further as pulmonary
capillary pressure rises during exercise.
 Thrombi and Emboli
 Thrombi may form in the left atria, particularly within
the enlarged atrial appendages of patients with MS.
 Systemic embolization, the incidence of which is 10–
20%, occurs more frequently in patients with AF, in
patients >65 years of age, and in those with a
reduced CO.
 However, systemic embolization may be the
presenting feature in otherwise asymptomatic
patients with only mild MS
 Inspection and Palpation
 In patients with severe MS, there may be a malar flush
with pinched and blue facies.
 In patients with sinus rhythm and severe pulmonary
hypertension or associated tricuspid stenosis (TS), the
jugular venous pulse reveals prominent a waves due to
vigorous right atrial systole.
 The systemic arterial pressure is usually normal or
slightly low.
 An RV tap along the left sternal border signifies an
enlarged RV.
 A diastolic thrill may rarely be present at the cardiac
apex, with the patient in the LA recumbent position.
 Auscultation
 S1 is usually accentuated in the early stages of the
disease and slightly delayed.
 P2 also is often accentuated with elevated PA
pressures, and the two components of the second
heart sound (S2) are closely split.
 The opening snap (OS) of the mitral valve is most
readily audible in expiration at, or just medial to, the
cardiac apex.
 This sound generally follows the sound of aortic valve
closure (A2) by 0.05–0.12 s
 The time interval between A2 and OS varies inversely
with the severity of the MS.
 Cont.
 The OS is followed by a low-pitched, rumbling,
diastolic murmur, heard best at the apex with the
patient in the left lateral recumbent position.
 it is accentuated by mild exercise (e.g., a few rapid
sit-ups) carried out just before auscultation.
 In general, the duration of this murmur correlates
with the severity of the stenosis in patients with
preserved CO
 In patients with sinus rhythm, the murmur often
reappears or becomes louder during atrial systole
(presystolic accentuation).
 Cont.
 Soft, grade I or II/VI systolic murmurs are commonly
heard at the apex or along the left sternal border in
patients with pure MS and do not necessarily signify
the presence of MR.
 Hepatomegaly, ankle edema, ascites, and pleural
effusion, particularly in the right pleural cavity, may
occur in patients with MS and RV failure.
 Associated Lesions
 With severe pulmonary hypertension, a pansystolic
murmur produced by functional TR may be audible
along the left sternal border.
 This murmur is usually louder during inspiration and
diminishes during forced expiration (Carvallo’s sign).
 When the CO is markedly reduced in MS, the typical
auscultatory findings, including the diastolic rumbling
murmur, may not be detectable (silent MS), but they
may reappear as compensation is restored.
 Cont.
 The Graham Steell murmur of PR, a high-pitched,
diastolic, decrescendo blowing murmur along the
left sternal border, results from dilation of the
pulmonary valve ring and occurs in patients with
mitral valve disease and severe pulmonary
hypertension.
 This murmur may be indistinguishable from the
more common murmur produced by aortic
regurgitation (AR), although it may increase in
intensity with inspiration and is accompanied by a
loud and often palpable P
 ECG
 In MS and sinus rhythm, the P wave usually suggests
LA enlargement .
 It may become tall and peaked in lead II and upright
in lead V1 when severe pulmonary hypertension or
TS complicates MS and right atrial (RA) enlargement
occurs.
 The QRS complex is usually normal. However, with
severe pulmonary hypertension, right axis deviation
and RV hypertrophy are often present.
 Chest X-Ray
 The earliest changes are straightening of the upper
left border of the cardiac silhouette, prominence of
the main PAs, dilation of the upper lobe pulmonary
veins, and posterior displacement of the esophagus
by an enlarged LA.
 Kerley B lines are fine, dense, opaque, horizontal
lines that are most prominent in the lower and
midlung fields and that result from distention of
interlobular septae and lymphatics with edema when
the resting mean LA pressure exceeds approximately
20 mmHg.
 Mitral annular calcification
 Mitral annular calcification (MAC) develops from
progressive calcium deposition along and beneath the
mitral valve annulus
 MAC generally follows the C-shape of the mitral
annulus so the base of the anterior mitral leaflet is
generally (but not always ) spared.
 MAC is most commonly identified by echocardiography
as an echodense shelf-like structure involving the mitral
valve annulus with associated acoustic shadowing
 The calcification frequently has an irregular, lumpy
appearance.
 Cont.
 Although mitral valve leaflets and chordae tendinae are
generally not involved, calcification may progressively
accumulate in the subvalvular region beneath the
posterior leaflet with encroachment on the leaflet.
 Usual sparing of the leaflet commissures and anterior
leaflet distinguishes MAC from rheumatic mitral
involvement
 CLINICAL ASSOCIATIONS —MAC is generally an
incidental finding associated with aging although it is
occasionally associated with significant mitral
regurgitation and can rarely cause symptomatic mitral
stenosis.
 Cont.
 The presence of MAC is also associated with
increased risk of atrial fibrillation, conduction system
disease, atherosclerotic disease, and adverse
cardiovascular events, including stroke and mortality.
 Medical Treatment of Mitral Stenosis
 The medical management of MS is directed primarily
toward the following:
(1) Prevention of recurrent rheumatic fever;
(2) Prevention and treatment of complications of MS;
and
(3)Monitoring disease progression to allow intervention
at the optimal time point.
 Penicillin prophylaxis of group A β-hemolytic
streptococcal infections for secondary prevention of
rheumatic fever is important for at-risk patients with
rheumatic MS.
 Cont.
 Recommendations for infective endocarditis prophylaxis are
similar to those for other valve lesions and are restricted to
patients at high risk for complications from infection,
including patients with a history of endocarditis.
 In symptomatic patients, some improvement usually occurs
with restriction of sodium intake and small doses of oral
diuretics
 Beta blockers, nondihydropyridine calcium channel blockers
(e.g., verapamil or diltiazem), and digitalis glycosides are
useful in slowing the ventricular rate of patients with AF.
 Cont.
 Warfarin therapy targeted to an international normalized
ratio (INR) of 2–3 should be administered indefinitely to
patients with MS who have AF or a history of
thromboembolism.
 The routine use of warfarin in patients in sinus rhythm with
LA enlargement (maximal dimension>5.5 cm) with or
without spontaneous echo contrast is more controversial
 The novel oral anticoagulants are not approved for use in
patients with significant valvular heart disease
 If AF is of relatively recent onset in a patient whose MS is not
severe enough to warrant PMBV or surgical commissurotomy,
reversion to sinus rhythm pharmacologically or by means of
electrical countershock is indicated.
 Cont.
Usually, cardioversion should be undertaken after
the patient has had at least 3 consecutive weeks
of anticoagulant treatment to a therapeutic INR.
If cardioversion is indicated more urgently, then
intravenous heparin should be provided and TEE
performed to exclude the presence of LA
thrombus before the procedure.
Conversion to sinus rhythm is rarely successful or
sustained in patients with severe MS, particularly
those in whom the LA is especially enlarged or in
whom AF has been present for more than 1 year.
Surgical treatment of mitral stenosis
 MITRAL REGURGITATION

 ETIOLOGY
 MR may result from an abnormality or disease
process that affects any one or more of the five
functional components of the mitral valve apparatus
• Leaflets, annulus, chordae tendineae, papillary
muscles, and subjacent myocardium
 Acute MR can occur in the setting of
• Acute myocardial infarction (MI) with papillary
muscle rupture
• Following blunt chest wall trauma, or
• During the course of infective endocarditis.
 Cont.
 With acute MI, the posteromedial papillary muscle
is involved much more frequently than the
anterolateral papillary muscle because of its singular
blood supply.
 Transient, acute MR can occur during periods of
active ischemia and bouts of angina pectoris.
 Rupture of chordae tendineae can result in “acute-
on-chronic MR” in patients with myxomatous
degeneration of the valve apparatus.
 Cont.
 Chronic MR can result from
• Rheumatic disease,
• Mitral valve prolapse (MVP),
• Extensive mitral annular calcification,
• Congenital valve defects,
• Hypertrophic obstructive cardiomyopathy (HOCM),
and
• Dilated cardiomyopathy
Cont.
 Cont.
 Distinction also should be drawn between primary
(degenerative, organic) MR, in which the leaflets and/or
chordae tendineae are primarily responsible for
abnormal valve function, and
 Functional (secondary) MR, in which the leaflets and
chordae tendineae are structurally normal but the
regurgitation is caused by annular enlargement, papillary
muscle displacement, leaflet tethering, or their
combination
 The rheumatic process produces rigidity, deformity, and
retraction of the valve cusps and commissural fusion, as
well as shortening, contraction, and fusion of the
chordae tendineae.
 Cont.
 The MR associated with both MVP and HOCM is
usually dynamic in nature.
 MR in HOCM occurs as a consequence of anterior
papillary muscle displacement and systolic anterior
motion of the anterior mitral valve leaflet into the
narrowed LV outflow tract.
 Annular calcification is especially prevalent among
patients with advanced renal disease and is
commonly observed in women >65 years of age with
hypertension and diabetes.
 Cont.
 Irrespective of cause, chronic severe MR is often
progressive, because enlargement of the LA places
tension on the posterior mitral leaflet, pulling it away
from the mitral orifice and thereby aggravating the
valvular dysfunction.
 Similarly, LV dilation increases the regurgitation,
which, in turn, enlarges the LA and LV further,
resulting in a vicious circle; hence the aphorism,
“mitral regurgitation begets mitral regurgitation.”
 PATHOPHYSIOLOGY

 The resistance to LV emptying (LV after load) is reduced in

patients with MR.
 As a consequence, the LV is decompressed into the LA during
ejection, and with the reduction in LV size during systole, there
is a rapid decline in LV tension.
 The initial compensation to MR is more complete LV emptying.
 However, LV volume increases progressively with time as the
severity of the regurgitation increases and as LV contractile
function deteriorates.
 This increase in LV volume is often accompanied by a reduced
forward CO
 Cont.
 LV compliance is often increased, and thus, LV
diastolic pressure does not increase until late in the
course.
 The regurgitant volume varies directly with the LV
systolic pressure and the size of the regurgitant
orifice; the latter, in turn, is influenced by the extent
of LV and mitral annular dilation.
 Because EF rises in severe MR in the presence of
normal LV function, even a modest reduction in this
parameter (<60%) reflects significant dysfunction.
 SYMPTOMS

 Patients with chronic mild-to-moderate, isolated MR are

usually asymptomatic.
 Fatigue, exertional dyspnea, and orthopnea are the most
prominent complaints in patients with chronic severe
MR.
 Palpitations are common and may signify the onset of AF.
 Right-sided heart failure, with painful hepatic congestion,
ankle edema, distended neck veins, ascites, and
secondary TR, occurs in patients with MR who have
associated pulmonary vascular disease and PHN
 Acute pulmonary edema is common in patients with
acute severe MR.
 PHYSICAL FINDINGS

 In patients with chronic severe MR, the arterial

pressure is usually normal, although the carotid arterial
pulse may show a sharp, low-volume upstroke owing to
the reduced forward CO.
 A systolic thrill is often palpable at the cardiac apex, the
LV is hyperdynamic with a brisk systolic impulse and a
palpable rapid-filling wave (S3), and the apex beat is
often displaced laterally.
 In patients with acute severe MR, the arterial pressure
may be reduced with a narrow pulse pressure, the JVP
and wave forms may be normal or increased and
exaggerated, the apical impulse is not displaced, and
signs of pulmonary congestion are prominent
 Auscultation
 S1 is generally absent, soft, or buried in the
holosystolic murmur of chronic, severe MR.
 In patients with severe MR, the aortic valve may close
prematurely, resulting in wide but physiologic
splitting of S2.
 A low-pitched S3 occurring 0.12–0.17 s after the
aortic valve closure sound
 A fourth heart sound is often audible in patients with
acute severe MR who are in sinus rhythm.
 A presystolic murmur is not ordinarily heard with
isolated MR.
 Cont.
 A systolic murmur of at least grade III/VI intensity is
the most characteristic auscultatory finding in chronic
severe MR.
 It is usually holosystolic, but as previously noted, it is
decrescendo and ceases in mid to late systole in
patients with acute severe MR.
 The systolic murmur of chronic MR is usually most
prominent at the apex and radiates to the axilla
 LABORATORY EXAMINATION

 ECG In patients with sinus rhythm, there is evidence of

LA enlargement, but RA enlargement also may be
present when pulmonary hypertension is significant
and affects RV function.
 Chronic severe MR is frequently associated with AF.
 In many patients, there is no clear-cut ECG evidence of
enlargement of either ventricle.
 In others, the signs of eccentric LV hypertrophy are
present on Echocardiogram.
 TTE is indicated to assess the mechanism of the MR
and its hemodynamic severity.
 Cont.
 LV function can be assessed from LV end-diastolic and
end-systolic volumes and EF.
 Observations can be made regarding leaflet structure
and function, chordal integrity, LA and LV size, annular
calcification, and regional and global LV systolic function.
 Doppler imaging should demonstrate the width
 The LA and LV are the dominant chambers in chronic MR
on CXR.
 Late in the course of the disease, the LA may be
massively enlarged and forms the right border of the
cardiac silhouette.
 Cont.
 Pulmonary venous congestion, interstitial edema, and
Kerley B lines are sometimes noted.
 Marked calcification of the mitral leaflets occurs
commonly in patients with long-standing, combined
rheumatic MR and MS.
 Calcification of the mitral annulus may be visualized,
particularly on the lateral view of the chest.
 Patients with acute severe MR may have asymmetric
pulmonary edema if the regurgitant jet is directed
predominantly to the orifice of an upper lobe pulmonary
vein
 Cont..
 DEFINITION OF SEVERE MR — Corrective surgery is
indicated only in selected patients with severe chronic MR
 Which is usually defined by Doppler echocardiography
 The following findings, in order of priority, are consistent
with severe MR
• A vena contracta width ≥7 mm
• A regurgitant orifice area ≥0.40 cm2
• A regurgitant volume ≥60 mL
• A regurgitant fraction ≥50 percent
• A jet area >40 percent of left atrial area, but this is not so
reproducible
 TREATMENT Mitral Regurgitation

 MEDICAL TREATMENT
 The management of chronic severe MR depends to
some degree on its cause.
 Anticoagulation with either warfarin or a direct oral
agent (e.g., apixaban, rivaroxaban) should be provided
if AF intervenes, as guided by the CHA2DS2-VAS score.
 The direct oral anticoagulants should not be used if
rheumatic MS is also present; they are also not
approved for use in patients with mechanical PHV
 Cardioversion should be considered depending on the
clinical context, AF chronicity, LA size.
 Cont.
 In contrast to the acute setting, there are no large,
long-term prospective studies to substantiate the use
of vasodilators for the treatment of chronic, isolated
severe MR with HFpEF in the absence of HTN
 The severity of MR in the setting of an ischemic or
nonischemic DCMP may diminish with aggressive
guideline directed treatment of heart failure including
the use of diuretics, beta blockers, ACE inhibitors,
digitalis, and biventricular pacing (CRT) when
otherwise indicated.
 Cont.
 Patients with acute severe MR require urgent
stabilization and preparation for surgery
 Diuretics, intravenous vasodilators, and even IAB
counterpulsation may be needed for patients with
post-MI papillary muscle rupture or other forms of
acute severe MR
Surgical management of MR
 AORTIC STENOSIS

 Aortic stenosis (AS) occurs in about one-fourth of all

patients with chronic valvular heart disease
 Approximately 80% of adult patients with
symptomatic, valvular AS are male.
 ETIOLOGY AND PATHOGENESIS

 AS in adults is due to degenerative calcification of the

aortic cusps and occurs most commonly on a substrate
of congenital disease (BAV), chronic (trileaflet)
deterioration, or previous rheumatic inflammation.
 A pathologic study of specimens removed at the time of
aortic valve replacement for AS in adults showed that
53% were bicuspid and 4% unicuspid
 The process of aortic valve deterioration and
calcification is not a passive one,
 Cont..
 But rather one that shares many features with vascular
atherosclerosis,
• Including endothelial dysfunction, lipid accumulation,
inflammatory cell activation, cytokine release, and up
regulation of several signaling pathways
 Eventually, a fibrocalcific response is established where
in collagen is deposited and valvular myofibroblasts
differentiate phenotypically into osteoblasts and
actively produce bone matrix proteins that allow for the
deposition of calcium hydroxyapatite crystals
 Cont.
 Genetic polymorphisms involving the vitamin D
receptor, the estrogen receptor in postmenopausal
women, interleukin 10, and apolipoprotein E4 have
been linked to the development of calcific AS,
• And a strong familial clustering of cases has been
reported from western France.
 Several traditional atherosclerotic risk factors have
also been associated with the development and
progression of calcific AS, including LDL cholesterol,
Lp[a], DM, smoking, CKD , and the metabolic
syndrome.
 Cont.
 The presence of aortic valve sclerosis (focal thickening
and calcification of the leaflets not severe enough to
cause obstruction) is associated with an excess risk of
cardiovascular death and myocardial infarction (MI)
among persons aged >65.
 Approximately 30% of persons aged >65 years exhibit
some degree of aortic valve sclerosis. Rate and extent
of progression to valve obstruction (stenosis) vary
among individual patients.
 Rheumatic disease of the aortic leaflets produces
commissural fusion, sometimes resulting in a bicuspid-
appearing valve.
 Cont.
 This condition, in turn, makes the leaflets more susceptible
to trauma and ultimately leads to fibrosis, calcification, and
further narrowing.
 By the time obstruction to left ventricular (LV) outflow
causes serious clinical disability, the valve is usually a rigid
calcified mass, and careful examination may make it difficult
or even impossible to determine the etiology of the
underlying process
 Rheumatic AS is almost always associated with involvement
of the mitral valve and with aortic regurgitation (AR).
 Mediastinal radiation can also result in late scarring, fibrosis,
and calcification of the leaflets with AS.
 Cont..

 In addition to valvular AS, three other lesions may be

responsible for obstruction to LV outflow: hypertrophic
obstructive cardiomyopathy, discrete
fibromuscular/membranous subaortic stenosis, and
supravalvular AS
 The causes of LV outflow obstruction can be differentiated
on the basis of the cardiac examination and Doppler
echocardiographic findings.
 PATHOPHYSIOLOGY
 The obstruction to LV outflow produces a systolic pressure
gradient between the LV and aorta.
 When severe obstruction is suddenly produced experimentally,
the LV responds by dilation and reduction of stroke volume.
 However, in some patients, the obstruction may be present at
birth and/or increase gradually over the course of many years,
and LV contractile performance is maintained by the presence
of concentric LV hypertrophy.
 Initially, this serves as an adaptive mechanism because it
reduces toward normal the systolic stress developed by the
myocardium, as predicted by the Laplace relation (S = Pr/h,
where S = systolic wall stress, P = pressure, r = radius, and h =
wall thickness).
 Cont.

 A large transaortic valve pressure gradient may exist

for many years without a reduction in cardiac output
(CO) or the development of LV dilation.
 Ultimately, however, excessive hypertrophy becomes
maladaptive, LV systolic function declines because of
afterload mismatch, abnormalities of diastolic function
progress, and irreversible myocardial fibrosis develops
 A mean systolic pressure gradient >40 mmHg with a
normal CO or an effective aortic orifice area of ~<1 cm2
(or ~<0.6 cm2/m2 body surface area in a normal-sized
adult)—i.e., less than approximately one-third of the
normal orifice area—is generally considered to
represent severe obstruction to LV outflow.
 Cont.
 The elevated LVEDP observed in many patients with
severe AS and preserved EF signifies the presence of
diminished compliance of the hypertrophied LV.
 Although the CO at rest is within normal limits in most
patients with severe AS, it usually fails to rise normally
during exercise.
 Loss of an appropriately timed, vigorous atrial
contraction, as occurs in AF or AV dissociation, may cause
rapid progression of symptoms.
 Late in the course, contractile function deteriorates
because of afterload excess, the CO and LV–aortic
pressure gradient decline, and the mean LA, PA, and RV
pressures rise.
 Cont.
 LV performance can be further compromised by
superimposed epicardial coronary artery disease (CAD).
 Stroke volume (and thus CO) can also be reduced in
patients with significant hypertrophy and a small LV cavity
despite a normal EF.
 Low-flow, low-gradient AS (with either reduced or normal
LV systolic function) is both a diagnostic and therapeutic
challenge.
 The hypertrophied LV causes an increase in myocardial
oxygen requirements.
 In addition, even in the absence of obstructive CAD,
coronary blood flow is impaired to the extent that ischemia
can be precipitated under conditions of excess demand.
 Cont.
 Capillary density is reduced relative to wall thickness,
compressive forces are increased, and the elevated LV
end-diastolic pressure reduces the coronary driving
pressure.
 The subendocardium is especially vulnerable to
ischemia by this mechanism.
 SYMPTOMS

 AS is rarely of clinical importance until the valve orifice has

narrowed to ~1 cm2.
 Even severe AS may exist for many years without producing
any symptoms because of the ability of the hypertrophied LV
to generate the elevated intraventricular pressures required
to maintain a normal stroke volume.
 Once symptoms occur, valve replacement is indicated.
 Most patients with pure or predominant AS have gradually
increasing obstruction over years but do not become
symptomatic until the sixth to eighth decades
 Adult patients with BAV disease, however, develop significant
valve dysfunction and symptoms one to two decades sooner.
 Cont.
 Exertional dyspnea, angina pectoris, and syncope are the
three cardinal symptoms.
 Often, there is a history of insidious progression of fatigue
and dyspnea associated with gradual curtailment of
activities and reduced effort tolerance
 Dyspnea results primarily from elevation of the pulmonary
capillary pressure caused by elevations of LV diastolic
pressures secondary to impaired relaxation and reduced LV
compliance.
 Angina pectoris usually develops somewhat later and
reflects an imbalance between the augmented myocardial
oxygen requirements and reduced oxygen availability.
 CAD may or may not be present, although its coexistence is
common among AS patients age >65.
 Cont.
 Exertional syncope may result from a decline in arterial
pressure caused by vasodilation in the exercising muscles and
inadequate vasoconstriction in nonexercising muscles in the
face of a fixed CO, or from a sudden fall in CO produced by an
arrhythmia.
 Because the CO at rest is usually well maintained until late in
the course, marked fatigability, weakness, peripheral cyanosis,
cachexia, and other clinical manifestations of a low CO are
usually not prominent until this stage is reached.
 Orthopnea, paroxysmal nocturnal dyspnea, and pulmonary
edema, i.e., symptoms of LV failure, also occur only in the
advanced stages of the disease.
 Severe PHTN leading to RV failure and systemic venous HTN,
hepatomegaly, AF, and TR are usually late findings in patients
with isolated severe AS.
 Cont.
 When AS and mitral stenosis (MS) coexist, the
reduction in flow (CO) induced by MS lowers the
pressure gradient across the aortic valve and,
thereby, masks many of the clinical findings produced
by AS.
 The transaortic pressure gradient can be increased in
patients with concomitant AR due to higher aortic
valve flow rates.
 PHYSICAL FINDINGS
 The rhythm is generally regular until late in the course; at
other times, AF should suggest the possibility of associated
mitral valve disease.
 Hypertension occurs commonly among older adults with AS.
 In the late stages, however, when stroke volume declines,
the systolic pressure may fall and the pulse pressure narrow.
 The carotid arterial pulse rises slowly to a delayed peak
(pulsus parvus et tardus).
 A thrill or anacrotic “shudder” may be palpable over the
carotid arteries, more commonly the left.
 In the elderly, the stiffening of the arterial wall may mask
this important physical sign.
 Cont.
 In many patients, the a wave in the jugular venous pulse is
accentuated.
 This results from the diminished distensibility of the RV
cavity caused by the bulging, hypertrophied
interventricular septum.
 The LV impulse is sometimes displaced laterally in the later
stages of the disease.
 A double apical impulse (with a palpable S4) may be
recognized, particularly with the patient in the left lateral
recumbent position.
 A systolic thrill may be present at the base of the heart to
the right of the sternum when leaning forward or in the
suprasternal notch.
 Cont.
 Auscultation An early systolic ejection sound is frequently
audible in children, adolescents, and young adults with
congenital BAV disease.
 This sound usually disappears when the valve becomes
calcified and rigid.
 As AS increases in severity, LV systole may become
prolonged so that the AV closure sound no longer
precedes the PV closure sound, and the two components
may become synchronous, or aortic valve closure may
even follow PV closure, causing paradoxical splitting of S2
 The sound of aortic valve closure can be heard most
frequently in patients with AS who have pliable valves,
and calcification diminishes the intensity of this sound.
 Cont.
 Frequently, an S4 is audible at the apex and reflects
the presence of LV hypertrophy and an elevated LV
end-diastolic pressure; an S3 generally occurs late in
the course, when the LV dilates and its systolic
function becomes severely compromised.
 The murmur of AS is characteristically an ejection
(mid) systolic murmur that commences shortly after
the S1, increases in intensity to reach a peak toward
the middle of ejection, and ends just before aortic
valve closure.
 It is characteristically low-pitched, rough and rasping
in character, and loudest at the base of the heart,
most commonly in the second right intercostal space.
 Cont.
 It is transmitted upward along the
carotid arteries.
 Occasionally it is transmitted
downward and to the apex, where it may
be confused with the systolic murmur
of MR (Gallavardin effect).
 In almost all patients with severe obstruction and
preserved CO, the murmur is at least grade III/ VI
 In patients with mild degrees of obstruction or in those
with severe stenosis with heart failure and low CO in
whom the stroke volume and, therefore, the
transvalvular flow rate are reduced, the murmur may be
 LABORATORY EXAMINATION

 ECG
 In most patients with severe AS, there is LVH
 In advanced cases, ST-segment depression and T-wave
inversion (LV “strain”) in standard leads I and aVL and in
the left precordial leads are evident.
 However, there is no close correlation between the ECG
and the hemodynamic severity of obstruction, and the
absence of ECG signs of LV hypertrophy does not
exclude severe obstruction.
 Systemic hypertension can coexist and also contribute to
the development of hypertrophy.
 Cont.
 Echocardiography
 The key findings on TTE are thickening, calcification,
and reduced systolic opening of the valve leaflets and
LV hypertrophy.
 Eccentric closure of the aortic valve cusps is
characteristic of congenitally bicuspid valves.
 TEE imaging can display the obstructed orifice
extremely well, but it is not routinely required for
accurate characterization of AS.
 The valve gradient and aortic valve area can be
estimated by Doppler measurement of the transaortic
velocity.
 Cont.

 Severe AS is defined by a valve area <1 cm2, whereas

moderate AS is defined by a valve area of 1–1.5 cm2 and
mild AS by a valve area of 1.5–2 cm2.
 Aortic valve sclerosis, conversely, is accompanied by a jet
velocity of <2.5 m/s (peak gradient <25 mmHg).
 LV dilation and reduced systolic shortening reflect
impairment of LV function.
 There is increasing experience with the use of
longitudinal strain and strain rate to characterize earlier
changes in LV systolic function, well before a decline in
EF can be appreciated.
 Doppler indices of impaired diastolic function are
frequently seen.
 Cont.
 It is useful for identifying coexisting valvular abnormalities,
differentiating valvular AS from other forms of LVOO, and
measuring the aortic root and proximal AA dimensions.
 These aortic measurements are particularly important for
patients with BAV disease
 Dobutamine stress echo is useful for the evaluation of patients
with AS and severe LV systolic dysfunction (low-flow, low-
gradient, severe AS with reduced EF), in whom the severity of
the AS can often be difficult to judge.
 Patients with severe AS (i.e., valve area <1 cm2) with a
relatively low mean gradient (<40 mmHg) despite a normal EF
(low-flow, low-gradient, severe AS with normal EF) are often
hypertensive, and efforts to control their systemic BP should
be optimized before Doppler echo is repeated.
 Cont.
 The use of dobutamine stress echocardiography in
this setting is under investigation.
 When there is continued uncertainty regarding the
severity of AS in patients with reduced CO,
quantitative analysis of the amount of aortic valve
calcium with chest CT may be helpful.
 There is increasing use of chest CT to assess aortic
valve morphology and function.
 It has become the imaging method of choice to plan
for transcatheter aortic valve replacement.
 Cont.
 Chest X-Ray
 It may show no or little overall cardiac enlargement for many
years.
 Hypertrophy without dilation may produce some rounding of
the cardiac apex in the frontal projection and slight backward
displacement in the lateral view.
 A dilated proximal ascending aorta may be seen along the
upper right heart border in the frontal view
 AV calcification may be discernible in the lateral view, but it is
usually readily apparent on fluoroscopic examination or by
echo; the absence of valvular calcification on fluoroscopy in an
adult suggests that severe valvular AS is not present.
 In later stages of the disease, as the LV dilates, there is
increasing roentgenographic evidence of LV enlargement,
pulmonary congestion, and enlargement of the LA, PA, and right
heart chambers.
 NATURAL HISTORY

 Death in patients with severe AS occurs most commonly

in the seventh and eighth decades.
 Based on data obtained at postmortem examination in
patients before surgical treatment became widely
available, the average time to death after the onset of
various symptoms was as follows:
• Angina pectoris, 3 years;
• Syncope, 3 years;
• Dyspnea, 2 years;
• Congestive heart failure, 1.5–2 years.
 Moreover, in >80% of patients who died with AS,
symptoms had existed for <4 years.
 Cont.
 Among adults dying with valvular AS, sudden death,
which presumably resulted from an arrhythmia,
occurred in 10–20%; however, most sudden deaths
occurred in patients who had previously been
symptomatic.
 Sudden death as the first manifestation of severe AS is
very uncommon (~1% per year) in asymptomatic adult
patients.
 Calcific AS is a progressive disease, with an annual
reduction in valve area averaging 0.1 cm2 and annual
increases in the peak jet velocity and mean valve
gradient averaging 0.3 m/s and 7 mmHg, respectively
 MEDICAL TREATMENT
 In patients with severe AS (valve area <1 cm2), strenuous
physical activity and competitive sports should be
avoided, even in the asymptomatic stage.
 Care must be taken to avoid dehydration and hypovolemia
to protect against a significant reduction in CO.
 Medications used for the treatment of HTN or CAD,
including beta blockers and ACE inhibitors, are generally
safe for asymptomatic patients with HFpEF
 Nitroglycerin is helpful in relieving angina pectoris in
patients with CAD.
 Studies suggested that patients with degenerative calcific
AS who receive statins exhibit slower progression of
leaflet calcification and AVA reduction than those who do
not.
 Cont.
 However, randomized prospective studies with either
high-dose atorvastatin or combination
simvastatin/ezetimibe have failed to show a
measurable effect on valve-related outcomes
 The use of statin medications should be driven by
considerations regarding primary and secondary
prevention of ASCVD events.
 ACE inhibitors have not been studied prospectively for
AS-related outcomes.
 The need for endocarditis prophylaxis is restricted to
AS patients with a prior history of endocarditis.
Cont.
 Aortic Regurgitation
ETIOLOGY

 Aortic regurgitation may be caused by primary valve

disease, aortic root disease or their combination.
 Primary Valve Disease
 Rheumatic disease results in thickening, deformity,
and shortening of the individual aortic valve cusps,
changes that prevent their proper opening during
systole and closure during diastole.
 A rheumatic origin is much less common in patients
with isolated AR who do not have associated
rheumatic mitral valve disease.
Cont.
 Cont.
 Patients with congenital bicuspid aortic valve (BAV) disease
may develop predominant AR, and ~20% of these patients
will require aortic valve surgery between 10 and 40 years
of age.
 Congenital fenestrations of the aortic valve occasionally
produce mild AR.
 Membranous subaortic stenosis results in a high velocity
systolic jet that often leads to thickening and scarring of
the aortic valve leaflets and secondary AR
 Prolapse of an aortic cusp, resulting in progressive chronic
AR, occurs in ~15% of patients with ventricular septal
defect, but may also occur as an isolated phenomenon or
as a consequence of myxomatous degeneration sometimes
associated with mitral and/or tricuspid valve involvement.
 Cont.
 AR may result from IE, which can develop on a valve previously
affected by RHD, a congenitally deformed valve, or on a
normal aortic valve, and may lead to perforation or erosion of
one or more leaflets.
 The AV leaflets may become scarred and retracted during the
course of syphilis or ankylosing spondylitis and contribute
further to the AR that derives primarily from the associated
root disease
 Although traumatic rupture or avulsion of an aortic cusp is an
uncommon cause of acute AR, it represents the most frequent
serious lesion in patients surviving nonpenetrating cardiac
injuries.
 The coexistence of hemodynamically significant AS with AR
usually excludes all the rarer forms of AR because it occurs
almost exclusively in patients with rheumatic or congenital AR.
 Cont.
 In patients with AR due to primary valvular disease, dilation
of the aortic annulus may occur secondarily and lead to
worsening regurgitation
 Primary Aortic Root Disease
 AR also may be due entirely to marked aortic annular
dilation, i.e., aortic root disease, without primary
involvement of the valve leaflets; widening of the aortic
annulus and lack of diastolic coaptation of the aortic leaflets
are responsible for the AR
 Medial degeneration of the AA, which may or may not be
associated with other manifestations of Marfan syndrome;
idiopathic dilation of the aorta; annuloaortic ectasia;
osteogenesis imperfecta; and severe, chronic HTN may all
widen the aortic annulus and lead to progressive AR.
 Cont.
 Occasionally AR is caused by retrograde dissection of
the aorta involving the aortic annulus
 Syphilis and ankylosing spondylitis, both of which may
also affect the aortic leaflets, may be associated with
cellular infiltration and scarring of the media of the
thoracic aorta, leading to aortic dilation, aneurysm
formation, and severe regurgitation.
 In syphilis of the aorta , now a very rare condition, the
involvement of the intima may narrow the coronary
ostia, which in turn may be responsible for myocardial
ischemia.
 Takayasu’s aortitis and giant cell aortitis can also result
in aneurysm formation and secondary AR.
 PATHOPHYSIOLOGY

 The total stroke volume ejected by the left ventricle (LV)

(i.e., the sum of the effective forward stroke volume
and the volume of blood that regurgitates back into the
LV) is increased in patients with AR.
 In patients with severe AR, the volume of regurgitant
flow may equal the effective forward stroke volume.
 In contrast to MR, in which a portion of the LV stroke
volume is delivered into the low-pressure left atrium
(LA), in AR the entire LV stroke volume is ejected into a
high-pressure zone, the aorta.
 An increase in the LV end-diastolic volume (increased
preload) constitutes the major hemodynamic
compensation for AR.
 Cont.
 The dilation and eccentric LLVH of the LV allow this
chamber to eject a larger SV without requiring any
increase in the relative shortening of each myofibril
 Therefore, severe AR may occur with a normal effective
forward stroke volume and a normal LV EF (LVEF, total
[forward plus regurgitant] SV/LVEDV), together with an
elevated LV end-diastolic pressure and volume.
 However, through the operation of Laplace’s law, LV
dilation increases the LV systolic tension required to
develop any given level of systolic pressure.
 Chronic AR is, thus, a state in which LV preload and
afterload are both increased.
 Cont.
 Ultimately, these adaptive measures fail.
 As LV function deteriorates, the end-diastolic volume rises
further and the forward stroke volume and EF decline.
 Deterioration of LV function often precedes the
development of symptoms.
 Considerable thickening of the LV wall also occurs with
chronic AR, and at autopsy, the hearts of these patients may
be among the largest encountered, sometimes weighing
>1000 g.
 The reverse pressure gradient from aorta to LV, which drives
the AR flow, falls progressively during diastole, accounting
for the decrescendo nature of the diastolic murmur.
 Equilibration between aortic and LV pressures may occur
toward the end of diastole in patients with chronic severe
 Cont.
 In patients with acute severe AR, the LV is unprepared
for the regurgitant volume load.
 LV compliance is normal or reduced, and LV diastolic
pressures rise rapidly, occasionally to levels >40 mmHg
 The LV pressure may exceed the LA pressure toward
the end of diastole, and this reversed pressure
gradient closes the mitral valve prematurely.
 In patients with chronic severe AR, the effective
forward cardiac output (CO) usually is normal or only
slightly reduced at rest, but often it fails to rise
normally during exercise.
 An early sign of LV dysfunction is a reduction in the EF.
 Cont.
 In advanced stages, there may be considerable elevation of
the LA, PA wedge, PA, and RV pressures and lowering of
the forward CO at rest.
 Myocardial ischemia may occur in patients with AR
because myocardial oxygen requirements are elevated by
LV dilation, hypertrophy, and elevated LV systolic tension,
and coronary blood flow may be compromised.
 A large fraction of coronary blood flow occurs during
diastole, when arterial pressure is low, thereby reducing
coronary perfusion or driving pressure.
 This combination of increased oxygen demand and
reduced supply may cause myocardial ischemia,
particularly of the subendocardium, even in the absence of
epicardial CAD.
 HISTORY

 Approximately 3/4th of patients with pure or predominant

valvular AR are men; women predominate among patients
with primary valvular AR who have associated RVHD.
 A history compatible with IE may sometimes be elicited
from patients with rheumatic or congenital involvement of
the aortic valve, and the infection often precipitates or
seriously aggravates preexisting symptoms
 In patients with acute severe AR, as may occur in IE, aortic
dissection, or trauma, the LV cannot dilate sufficiently to
maintain stroke volume, and LV diastolic pressure rises
rapidly with associated marked elevations of LA and PA
wedge pressures.
 Pulmonary edema and/or cardiogenic shock may develop
rapidly.
 Cont.

 Chronic severe AR may have a long latent period, and

patients may remain relatively asymptomatic for as long as
10–15 years.
 Uncomfortable awareness of the heartbeat, especially on
lying down, may be an early complaint.
 Sinus tachycardia, during exertion or with emotion, or
premature ventricular contractions may produce particularly
uncomfortable palpitations as well as head pounding.
 These complaints may persist for many years before the
development of exertional dyspnea, usually the first
symptom of diminished cardiac reserve.
 The dyspnea is followed by orthopnea, PND, and excessive
diaphoresis.
 Anginal chest pain even in the absence of CAD may occur in
patients with severe AR, even in younger patients
 Cont.
 Anginal pain may develop at rest as well as during
exertion.
 Nocturnal angina may be a particularly troublesome
symptom, and it may be accompanied by marked
diaphoresis
 The anginal episodes can be prolonged and often do
not respond satisfactorily to sublingual nitroglycerin
 Systemic fluid accumulation, including congestive
hepatomegaly and ankle edema, may develop late in
the course of the disease.
 PHYSICAL FINDINGS

 In chronic severe AR, the jarring of the entire body and the
bobbing motion of the head with each systole can be
appreciated, and the abrupt distention and collapse of the
larger arteries are easily visible.
 The examination should be directed toward the detection of
conditions predisposing to AR, such as bicuspid valve, IE, Marfan
syndrome, or ankylosing spondylitis.
 Arterial Pulse
 A rapidly rising “water-hammer” pulse, which collapses
suddenly as arterial pressure falls rapidly during late systole and
diastole (Corrigan’s pulse), and capillary pulsations, an alternate
flushing and paling of the skin at the root of the nail while
pressure is applied to the tip of the nail (Quincke’s pulse), are
characteristic of chronic severe AR.
 Cont.
 A booming “pistol-shot” sound can be heard over the
femoral arteries (Traube’s sign), and a to-and-fro murmur
(Duroziez’s sign) is audible if the femoral artery is lightly
compressed with a stethoscope.
 The arterial pulse pressure is widened as a result of both
systolic hypertension and a lowering of the diastolic
pressure.
 The measurement of arterial diastolic pressure with a
sphygmomanometer may be complicated by the fact that
systolic sounds are frequently heard with the cuff completely
deflated
 However, the level of cuff pressure at the time of muffling of
the Korotkoff sounds (phase IV) generally corresponds fairly
closely to the true intraarterial diastolic pressure.
 Cont.
 As the disease progresses and the LV end-diastolic pressure
rises, the arterial diastolic pressure may actually rise as well,
because the aortic diastolic pressure cannot fall below the LV
end-diastolic pressure.
 For the same reason, acute severe AR may also be
accompanied by only a slight widening of the pulse pressure.
 Such patients are invariably tachycardic as the heart rate
increases in an attempt to preserve the CO.
 Palpation
 In patients with chronic severe AR, the LV impulse is heaving
and displaced laterally and inferiorly.
 The systolic expansion and diastolic retraction of the apex
are prominent.
 Cont.
 A diastolic thrill may be palpable along the left sternal border
in thin-chested individuals, and a prominent systolic thrill may
be palpable in the suprasternal notch and transmitted upward
along the carotid arteries. This systolic thrill and the
accompanying murmur do not necessarily signify the
coexistence of aortic stenosis (AS).
 In some patients with AR or with combined AS and AR, the
carotid arterial pulse may be bisferiens, i.e., with two systolic
waves separated by a trough
 Auscultation
 In patients with severe AR, the aortic valve closure sound (A2)
is usually absent.
 A systolic ejection sound is audible in patients with BAV
disease, and occasionally an S4 also may be heard.
 Cont.
 The murmur of chronic AR is typically a high-pitched,
blowing, decrescendo diastolic murmur, heard best in
the third intercostal space along the left sternal border
 In patients with mild AR, this murmur is brief, but as the
severity increases, it generally becomes louder and
longer, indeed holodiastolic.
 When the murmur is soft, it can be heard best with the
diaphragm of the stethoscope and with the patient
sitting up, leaning forward, and with the breath held in
forced expiration.
 In patients in whom the AR is caused by primary
valvular disease, the diastolic murmur is usually louder
along the left than the right sternal border
 Cont.
 However, when the murmur is louder along the right sternal
border, it suggests that the AR is caused by aneurysmal dilation
of the aortic root.
 “Cooing” or musical diastolic murmurs suggest eversion of an
aortic cusp vibrating in the regurgitant stream.
 A MSM is frequently audible in isolated AR.
 It is generally heard best at the base of the heart and is
transmitted along the carotid arteries
 This murmur may be quite loud without signifying aortic
obstruction
 A 3rd murmur sometimes heard in patients with severe AR is the
AFM, a soft, low-pitched, rumbling mid-to-late diastolic murmur.
 It is probably produced by the diastolic displacement of the AL
of the MV by the AR stream and is not associated with
hemodynamically significant mitral obstruction.
 Cont.
 The auscultatory features of AR are intensified by
strenuous and sustained handgrip, which augments
systemic vascular resistance.
 In acute severe AR, the elevation of LV end-diastolic
pressure may lead to early closure of the mitral valve,
a soft S1, a pulse pressure that is not particularly
wide, and a soft, short, early diastolic murmur of AR.
 LABORATORY EXAMINATION

 ECG
 In patients with chronic severe AR, the ECG signs of LV
hypertrophy are common
 In addition, these patients frequently exhibit ST-segment
depression and T-wave inversion in leads I, aVL, V5, and V6
(“LV strain”).
 Left-axis deviation and/or QRS prolongation denote diffuse
myocardial disease, generally associated with patchy
fibrosis, and usually signify a poor prognosis
 Echocardiogram
 LV size is increased in chronic AR and systolic function is
normal or even supernormal until myocardial contractility
declines, as signaled by a decrease in EF or increase in the
end-systolic dimension.
 Cont.
 A rapid, high-frequency diastolic fluttering of the anterior
mitral leaflet produced by the impact of the regurgitant jet
is a characteristic finding.
 The echocardiogram is also useful in determining the cause
of AR, by detecting dilation of the aortic annulus and root,
aortic dissection, or primary leaflet pathology).
 With severe AR, the central jet width assessed by color flow
Doppler imaging exceeds 65% of the LV outflow tract, the
regurgitant volume is ≥60 mL/beat, the regurgitant fraction
is ≥50%, and there is diastolic flow reversal in the proximal
descending thoracic aorta.
 The continuous-wave Doppler profile of the AR jet shows a
rapid deceleration time in patients with acute severe AR,
due to the rapid increase in LV diastolic pressure.
 Cont.
 Surveillance TTE forms the cornerstone of longitudinal
follow-up and allows for the early detection of changes in
LV size and/or function.
 For patients in whom TTE is limited by poor acoustical
windows or inadequate characterization of LV function or
the severity of the regurgitation, CMR imaging can be
performed. This modality also allows for accurate
assessment of aortic size and contour
 TEE can also provide detailed anatomic assessment of the
valve, root, and portions of the aorta.
 There is increasing experience with the use of 3D
echocardiography to measure LV volumes.
 Cont.
 Chest X-Ray
 In chronic severe AR, the apex is displaced downward and
to the left in the frontal projection.
 In the left anterior oblique and lateral projections, the LV
is displaced posteriorly and encroaches on the spine
 AR is caused by primary disease of the aortic root,
aneurysmal dilation of the aorta may be noted, and the
aorta may fill the retrosternal space in the lateral view.
 Echocardiography, cardiac MRI, and chest CT angiography
are more sensitive than the chest x-ray for the detection
of root and ascending aortic enlargement.
 Cont.
 Cardiac Catheterization and Angiography
 When needed, right and left heart catheterization
with contrast aortography can provide confirmation
of the magnitude of regurgitation and the status of LV
function.
 Coronary angiography is performed routinely in
appropriate patients prior to surgery.
 Management of Aortic Regurgitation

 ACUTE AORTIC REGURGITATION

 Patients with acute severe AR may respond to
intravenous diuretics and vasodilators (such as sodium
nitroprusside), but stabilization is usually short-lived and
operation is indicated urgently.
 Intraaortic balloon counterpulsation is contraindicated.
Beta blockers are also best avoided so as not to reduce
the CO further or slow the heart rate, thus allowing more
time for diastolic filling of the LV.
 Surgery is the treatment of choice and is usually
necessary within 24 h of diagnosis.
 Cont.
 CHRONIC AORTIC REGURGITATION
 Early symptoms of dyspnea and effort intolerance
respond to treatment with diuretics; vasodilators (ACE
inhibitors, dihydropyridine calcium channel blockers, or
hydralazine) may be useful as well.
 Surgery can then be performed in a more controlled
setting
 The use of vasodilators to extend the compensated phase
of chronic severe AR before the onset of symptoms or the
development of LV dysfunction is more controversial and
less well established
 Systolic blood pressure should be controlled (goal <140
mmHg) in patients with chronic AR, and vasodilators are
 Cont.
 It is often difficult to achieve adequate control because of the
increased stroke volume that accompanies severe AR
 Cardiac arrhythmias and systemic infections are poorly
tolerated in patients with severe AR and must be treated
promptly and vigorously.
 Although nitroglycerin and long-acting nitrates are not as
helpful in relieving anginal pain as they are in patients with
ischemic heart disease, they are worth a trial.
 Patients with syphilitic aortitis should receive a full course of
penicillin therapy
 Beta blockers and ARB losartan may be useful to retard the rate
of aortic root enlargement in young patients with Marfan
syndrome and aortic root dilation.
 A randomized controlled trial showed no difference in efficacy
between atenolol and losartan for this indication
 Cont.
 Whether BBS or ARBs is useful in retarding the rate of growth
of aortic aneurysms in other patient subsets (e.g., BAV with
aortopathy, Takaysu’s disease) have not been demonstrated
 BBs in patients with valvular AR were previously considered
relatively contraindicated due to concerns that the resulting
slowing of the HR would allow more time for diastolic AR
 Observational reports, however, have suggested that BBs may
provide functional benefit in some patients with chronic AR
 BBs can sometimes provide incremental blood pressure
lowering in patients with chronic AR and HTN.
 They can also lessen the sense of forceful heart action that
many patients find uncomfortable.
 Patients with severe AR, particularly those with an associated
aortopathy, should avoid isometric exercises.
Surgical treatment of AR
 .

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