Evidence-based Cardiology – part 9 pptx

The presence of CAD, its site and severity can be estimated only by selective coronary angiography, which should be performed in all patients 35 years of age or older who are being consi

stenosis; these patients should be considered as having

severe stenosis Since gradients are frequently measured

ini-tially by Doppler ultrasound, a suggested conservative

guideline for relating Doppler ultrasound gradient to

sever-ity of aortic stenosis (AS) in adults with normal cardiac

out-put and normal average heart rate is shown in Table 53.3

A suggested grading of the degree of aortic stenosis is

given in Table 53.4

Natural history

The duration of the asymptomatic period after the

develop-ment of severe aortic stenosis is uncertain In a study of

asymptomatic patients with varying degrees of severity

of aortic stenosis, 21% of 143 patients18with a mean age of 72

years required valve replacement within 3 months of

evalu-ation at a referral center At 2 years the mortality was 10%

and the event rate (death/valve replacement) in the

remain-ing patients was 26% Moreover, it is important to recognize

that most patients in this study had only moderate aortic

stenosis In another study of 123 asymptomatic adults,7also

with varying grades of severity of aortic stenosis aged

6316 years, only the actuarial probability of death or

aor-tic valve surgery is provided It was 75% at 1 year, 388%

at 3 years and 7410% at 5 years The event rate at 2 years

for aortic jet velocity by Doppler ultrasound of 4·0 m/s

(peak gradient by Doppler ultrasound 64 mmHg) was

7918%, for a velocity of 3·0–4·0 m/s (peak gradient

36–64 mmHg) was 6613%, and for a velocity of 3·0 m/s

(peak gradient of 36 mmHg) was 1616%.7 Aortic jetvelocity is influenced by the same parameters as aortic valvegradient (see above) Thus, the duration of the asympto-matic period, particularly in those aged 60 years, is proba-bly very short.19,20

Paul Dudley White in 195121 credited the first recorded occurrence of sudden death to T Bonet in 1679.22

In the past 70 years the reported incidence of sudden death in eight series has ranged from 1 to 21% Ross andBraunwald,13after reviewing seven autopsy series publishedbefore 1955, concluded the incidence was 3–5% The inci-dence in asymptomatic adult patients has been 33% (one inthree)23and 30% (three of ten).14This information is diffi-cult to use in clinical decision making because importantdata are not available – that is, the incidence by actuarialanalysis of sudden death in a significant number of asympto-matic patients with severe stenosis It is reasonable to con-clude that the true incidence of sudden death in adults withsevere aortic valve stenosis is unknown and that suddendeath usually occurs after the onset of symptoms, howeverminor or minimal the symptoms may be The incidence ofsudden death is believed to be higher in children

The development of symptoms of angina, syncope, orheart failure, changes the prognosis of the patient with aor-tic valve stenosis Average survival after the onset of symp-toms is 2–3 years Nearly 80% of asymptomatic patientswith peak aortic valve velocity measured by Dopplerechocardiography 4m/s develop symptoms within

3 years, and therefore careful clinical monitoring for the opment of symptoms and progressive disease is indicated

devel-Management

Patients with valvular heart disease need antibiotic laxis against infective endocarditis; those with rheumaticvalves need additional antibiotic prophylaxis against recur-rences of rheumatic fever.24

prophy-Surgery is recommended in those with severe valvestenosis and is the only specific and direct therapy for mostadults with severe aortic stenosis Rarely, in young patients,the aortic valve is suitable for balloon or surgical valvotomy

In most adults, surgery for aortic stenosis means valvereplacement.24,25

The operative mortality of valve replacement is 5%.25–27In those without associated coronary artery dis-ease, heart failure or other comorbid conditions, it is 2%

in experienced and skilled centers.28 Aortic valve ment in conjunction with coronary artery bypass carries asurgical mortality of about 7%.27The operative mortality inthose 70 years and in octogenarians is much higher, aver-aging 8% for valve replacement and 13% for those undergo-ing valve replacement and associated coronary bypasssurgery;25however, operative mortality in these patients isalso dependent on the associated factors listed above.29

replace-Grade B

Grade A

Table 53.3 Doppler ultrasound gradient as an

indica-tor of severe aortic stenosis (AS)

Peak gradient Mean gradient AS severe

60–79 mmHg 50–69 mmHg Probable

From Rahimtoola, 15 with permission

Table 53.4 Grading of stenosis by aortic valve area

a Patients with AVAs that are at borderline values between

the moderate and severe grades (0·9–1·1 cm 2 ; 0·55–

0·65 cm2/m2) should be individually considered.

From Rahimtoola 15 with permission

Patients with associated coronary artery disease (CAD)

should have coronary bypass surgery at the same time as

valve replacement, because it results in a lower operative

mortality (4·0% v 9·4%) and better 10 year survival (49% v

36%).28This was in spite of the fact that those who

under-went coronary bypass surgery had more CAD (34% had three

vessel disease, 11% had left main artery disease, and 38% had

single vessel disease) than those who did not undergo

coro-nary bypass surgery (13% had three vessel disease, 1% had

left main disease, and 65% had single vessel disease).28

Although this approach to CAD is generally approved, there

are no randomized trials to support these recommendations

The presence of CAD, its site and severity can be estimated

only by selective coronary angiography, which should be

performed in all patients 35 years of age or older who are

being considered for aortic valve surgery, and in those aged

35 years if they have left ventricular dysfunction, symptoms

or signs suggesting CAD, or they have two or more risk tors for premature CAD (excluding gender).25The incidence

fac-of associated CAD will vary considerably depending on theprevalence of CAD in the population;15,24in general, in per-sons 50 years of age or older it is about 50%.25

In severe aortic stenosis, valve replacement results in animprovement of survival (Figure 53.1) even if they have nor-mal left ventricular function preoperatively.14,30

Normal preoperative left ventricular function remainsnormal postoperatively if perioperative myocardial damagehas not occurred.31Left ventricular hypertrophy regressestoward normal;31,32after 2 years, the regression continues

at a slower rate up to 10 years after valve replacement.32

In patients with excessive preoperative left ventricularhypertrophy,33 the hypertrophy may regress slowly or not

40 60

80

Time (years) BSA

Figure 53.1 There are no prospective randomized trials of aortic valve replacement in severe aortic stenosis (AS), and there are unlikely to be any in the near future Two studies have compared the results of aortic valve replacement with medical treatment in their own center during the same time period in symptomatic patients with normal left ventricular systolic pump function (A) Patients who had valve replacement (closed circles) had a much better survival than those treated medically (open circles) (From Schwarz

et al 30 with permission.) (B) Patients who were treated with valve replacement (BSA) had a better survival than those treated medically (NH) (From Horstkotte and Loogen 14 with permission.) These differences in survival between those treated medically and surgically are so large that there is a great deal of confidence that aortic valve replacement significantly improves the survival of

those with severe aortic stenosis Grade A

at all Preoperatively, these patients have a small left

ventricu-lar cavity, severe increase in wall thickness, and

“super-normal” ejection fraction; this occurs in 42% of women and

14% of men in those aged 60 years.33After valve

replace-ment their clinical picture often resembles that of

hyper-trophic cardiomyopathy without outflow obstruction, which

is a difficult clinical condition to treat, both in the early

post-operative period and after hospital discharge;33therefore,

sur-gery should be performed prior to development of excessive

hypertrophy Surviving patients are functionally improved.25

After valve replacement, the 10 year survival is 60%

and 15 year survival is about 45%.25,34One half or more of

the late deaths are not related to the prosthesis but to

associ-ated cardiac abnormalities and other comorbid conditions.34

Thus, the late survival will vary in different subgroups of

patients The older patients (60 years) have a 12 year

actu-arial survival of 60%.35Relative survival refers to survival

of patients compared to age- and gender-matched people in

the population The relative 10 year survival after surgery is

significantly better in those aged 65 than in those aged

65 years (94% v 81% respectively, Figure 53.2);36the 94%

relative survival is not significantly different from the 100%

relative survival Thus, surgery should not be denied to those

60–65 years old and should be performed early.25,35–37

Patients who present with heart failure related to aortic

valve stenosis should undergo surgery as soon as possible

Medical treatment in hospital prior to surgery is reasonable

but ACE inhibitors should be used with great caution in

such patients, and in such a dosage that hypotension and

significant fall of blood pressure is avoided They should not

be used if the patient is hypotensive If heart failure does not

respond satisfactorily and rapidly to medical therapy, surgery

becomes a matter of considerable urgency.25 Catheter

balloon valvuloplasty has a very limited role in adults with

calcific aortic stenosis and carries a risk of 10% In

addition, restenosis and clinical deterioration occur within

6 to 12 months In adults with aortic stenosis, balloon

valvuloplasty is not a substitute for valve replacement but

can be a bridge procedure in selected patients.38It usually

improves patients’ hemodynamics and may make them

better candidates for valve replacement

The operative mortality for patients with heart failure has

declined: 25 years ago the operative mortality was 20%,39

but in the current era it is 10%.40Although this is higher

than in patients without heart failure, the risk is justified,

because late survival in those who survive the operation is

excellent and is far superior to that which can be expected

with medical therapy The 7 year survival of patients who

survive operation is 84%.41 The 5 year survival in those

without associated CAD is greater than in those with CAD

(69% v 39%, P 0·02).40Left ventricular function improves

in most patients provided there has been no perioperative

myocardial damage and becomes normal in two thirds of

the patients, unless there was irreversible preoperative

myocardial damage (Figure 53.3).39,40In addition, the ative survivors are functionally much improved.39,40 Leftventricular hypertrophy and left ventricular dilation, if pres-ent preoperatively, regress toward normal.39 Despite theexcellent results of valve replacement in patients withsevere aortic stenosis who are in heart failure, these resultsare not as good as for those who are not in heart failure;therefore, it is important to recognize that surgery shouldnot be delayed until heart failure develops

oper-Six per cent of older patients with aortic stenosis present incardiogenic shock.38The hospital mortality in such patients isnear 50% The subsequent mortality is also very high if the patients have not had their aortic stenosis relieved.38Thus, these patients need to be managed aggressively byemergency surgery with or without catheter balloon valvu-loplasty as a “bridge” procedure.38

Grade B

100 90 80

65 years They have examined the relative survival – compared the survival of the patient who has undergone aortic valve replacement with another age and sex matched person in the same population Actuarial survival 95% confidence interval is shown Patients under the age of 65 had a relative survival of 81% which is significantly lower than 100%, and is also lower than that of those aged 65 years On the other hand, patients who underwent valve replacement at age 65 had a relative sur- vival of 94% at the end of 10 years and this was not significantly different from 100% These data indicate that survival following valve replacement for aortic stenosis in patients aged 65 is not significantly different from age- and sex-matched individuals in the population without aortic stenosis; and the late relative sur- vival of patients aged 65 years is much better than that of patients aged 65 (From Lindblom et al 36 with permission.)

Boxes 53.1 and 53.2 summarize the results of valvereplacement in those with severe aortic stenosis and the fac-tors predictive of a worse postoperative survival, less recov-ery of left ventricular function, and less improvement ofsymptoms in those with severe aortic stenosis and preopera-tive left ventricular systolic dysfunction.15,25,29–32,34–36,39–41

Patients with severe left ventricular dysfunction, low aorticvalve gradient, and small calculated aortic valve area repre-sent a difficult patient population There is controversy regard-ing the best management of these patients, in part related tothe difficulty differentiating patients with true severe aorticvalve stenosis from patients with moderate aortic valve steno-sis and severe left ventricular dysfunction Differentiatingthese two patient groups may have an important impact onthe management decision and the operative outcome Thus,patients with low gradient aortic valve stenosis should not bedenied aortic valve replacement A recent series confirms that

Box 53.1 Results of valve replacement in patients with severe aortic valve stenosis

● Improved symptoms and survival in symptomatic patients, especially in those with left ventricular systolic dysfunction, clinical heart failure, and in those aged 65 years

● Improvement in left ventricular systolic dysfunction, which normalizes in two thirds of patients

● Regression of left ventricular hypertrophy

● Improvement in functional class, more marked in those with severe symptoms preoperatively

Box 53.2 Factors predictive of a less favorable outcome

● Extent and severity of associated comorbid conditions

● Presence and severity of clinical heart failure preoperatively

● Severe associated coronary artery disease

● Severity of depression of preoperative left ventricular ejection fraction

● Duration of preoperative left ventricular systolic function

dys-● Extent of preoperative irreversible myocardial damage

● Skill and experience of operating and other associated professional teams

● Extent of perioperative myocardial damage

● Complications of a prosthetic heart valve

Figure 53.3 Examination of changes in LVEF in each

individ-ual patient among those who had left ventricular systolic

dys-function and clinical heart failure After valve replacement the

LVEF improved from 0·34 to 0·63 All but one patient showed

an improvement in LVEF; the only patient who showed

deterio-ration in ejection fraction suffered a perioperative myocardial

infarction and had a complete heart block; and the only patient

who showed only a small increase in ejection fraction had

had a myocardial infarct prior to valve replacement Note that

the surgical mortality is high and late survival lower than

expected Importantly however, most survivors experienced

improvement in functional class and ejection fraction.42

A small gradient across the valve may be associated with

a small calculated aortic valve area that would be in a range

indicating severe aortic stenosis There are at least two

pos-sible causes for this clinical circumstance First, there is a

small or reduced stroke volume and a normal or near

nor-mal systolic ejection time; thus, the gradient is snor-mall and the

calculated aortic valve area correctly indicates severe aortic

stenosis The second consideration is that the stroke volume

is reduced, and thus the valve needs to open only to a small

extent to allow the left ventricle to eject the small stroke

volume The calculated aortic valve area accurately reflects

the extent to which the valve has opened but overestimates

the severity of aortic stenosis Use of a provocative test using

an inotropic agent, such as dobutamine,43,44,45 may allow

one to make the correct differentiation between the two

Dobutamine increases systolic flow per second owing to

increases in stroke volume or shortening of ejection time or

both In the first circumstance described above, dobutamine

will result in an increase in gradient but the calculated valve

area remains more or less unchanged On the other hand, in

the second circumstance described above, the gradient may

or may not increase with dobutamine but the calculated

valve area increases significantly, indicating that the stenosis

is not severe When the dobutamine test is used, it is

impor-tant to measure cardiac output and simultaneous left

ventric-ular and aortic pressures both before and during dobutamine

infusion Alternatively, the gradient and valve area may be

assessed by echocardiography/Doppler during dobutamine

infusion; however, one needs to be certain that cardiac

out-put has increased significantly with dobutamine

Surgery should be advised for the symptomatic patient

who has severe aortic stenosis In young patients, if the

valve is pliable and mobile, simple balloon valvuloplasty or

surgical commissurotomy may be feasible Older patients

and even young patients with calcified, rigid valves will

require valve replacement

In view of the dismal natural history of symptomatic

patients with severe aortic stenosis, the excellent outcome

after surgery, and the uncertain natural history of the

asymptomatic patient, it is reasonable to recommend aortic

valve replacement in select asymptomatic patients in centers

with the appropriate skill and experience The combined risk

of surgery and late complications of a valve prosthesis must

be weighed against the risk of sudden death There is no

con-sensus about valve replacement in the truly asymptomatic

patient Clearly, if the patient has left ventricular dysfunction,

obstructive CAD or other valve disease that needs surgery,

and has severe aortic stenosis, then aortic valve replacement

should be performed Some would recommend valve

replacement in all asymptomatic patients with severe aortic

stenosis, while others would recommend it in all those with

or down sloping ST segment depression of 1mm in men or

2mm in women, or an up sloping ST segment depression of

3mm in men, measured 0·08seconds after the J point Theexercise test was also considered positive if precordial chestpain or near syncope occurred, if the ECG showed a complexventricular arrhythmia, or if systolic blood pressure failed torise by 20mmHg during exercise compared with baseline

It must be emphasized that this is a controversialissue Some cardiologists advise against exercise testing in anypatient with severe aortic valve stenosis, especially when theextent of coronary artery disease is not known

Recommendations: aortic valve replacement/repair in severe aortic stenosis 1

● Asymptomatic patients with:

● associated significantly obstructed I CAD needing surgery

● other valve or aortic disease needing I surgery

● left ventricular systolic dysfunction IIa

● abnormal response to exercise IIa

● severe left ventricular hypertrophy IIb (15 mm)

● significant arrhythmias IIb

● left ventricular dysfunction on exercise IIb

● Prevention of sudden death III

in asymptomatic patients CAD, coronary artery disease Class I: Conditions for which there is evidence and/or gen- eral agreement that a given procedure or treatment is useful and effective.

Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefullness/effi- cacy of a procedure or treatment.

IIa: Weight of evidence or opinion is in favor of ness/efficacy.

usefull-IIb: Usefullness/efficacy is less well established by dence/opinion.

evi-Class III: Conditions for which there is evidence and/or eral agreement that the procedure/treatment is not useful, and in some cases, may be harmful.

gen-Grade B

Chronic aortic valve regurgitation

Etiology

The causes of chronic aortic regurgitation are:46

● aortic root/annular dilation

● congenital bicuspid valve

● previous infective endocarditis

● rheumatic

● in association with other diseases

In developed countries, aortic root/annular dilation and

congenital bicuspid valve are the commonest causes of

severe chronic aortic regurgitation

Natural history

During the first world war, Sir Thomas Lewis and his

col-leagues47 at Hampstead and Colchester Military Hospitals

reported to the Medical Research Council highlighting the

inadequacy of the knowledge of heart disease, especially

from the standpoint of prognosis Sir Thomas Lewis

pro-posed a system,48 subsequently called “after histories”,48

which was a prospective follow up of patients All patients

in RT Grant’s “after histories”48had valvular heart disease –

most had aortic regurgitation – in which the patient

charac-teristics were defined and described in detail, particularly by

the degree of cardiac enlargement and the grade of cardiac

failure This probably was the start of databases or registries

in cardiovascular medicine

Chronic aortic valve regurgitation is a condition of

com-bined volume and pressure overload With progression of

the disease, compensatory hypertrophy and recruitment of

preload reserve permit the left ventricle to maintain a

nor-mal ejection performance despite the elevated afterload

The majority of patients remain asymptomatic throughout

the compensated phase, which may last decades The

natural history of chronic aortic valve regurgitation can be

considered by three different eras: the era of syphilis, the

era of rheumatic fever/carditis, and the current era of

non-invasive quantification of left ventricular function

Era of syphilis

The data are from the 1930s and 1940s, and thus largely prior

to availability of antibiotics.49The duration from syphilis

infec-tion to death was 20 years The durainfec-tion of the asymptomatic

period after aortic regurgitation was 5 years in 60% of

patients; and the 5 year survival was 95% Once symptoms

had developed, the 10 year survival ranged from 40 to 60%

Heart failure was associated with a 1 year survival of 30–50%,

and 10 year survival of 6% In a study of 161 patients reported

in 1935, the 10 year survival after heart failure had developed

was 34% but was 66% in those treated with arsenic.49Syphilis

still occurs, but current therapy of syphilis is cheap and

efficacious if diagnosed early Syphilitic aortic regurgitation is

not common, and the outcome in syphilitic aortic tion may be more benign in the current era

regurgita-Era of rheumatic fever/carditis

Although the incidence of rheumatic valve disease is low indeveloped countries, rheumatic heart disease remains themost common form of valve disease in many parts of theworld Moreover, some people now domiciled in the devel-oped world have had their initial attack(s) of acute rheu-matic fever whilst living in less developed countries.The detection of a murmur after the episode of acuterheumatic fever averages 10 years.49 The average intervalfrom detection of murmur to development of symptoms is

10 years and the percentage of patients remaining free 10 years after detection of the murmur is 50%.49

symptom-In 1971, Spagnuolo and coworkers50reported the 15 yearactuarial follow up of 174 young people who had a medianfollow up of 10 years Patients were considered to be in acumulative high-risk group if they had systolic blood pressure

140 mmHg and/or diastolic blood pressure 40 mmHg,moderate or marked left ventricular enlargement on chestradiography, and two of three ECG abnormalities (S in V2R

in V5 51 mm, ST segment depression or T wave inversion

in left ventricular leads) The group’s findings are rized in Table 53.5

summa-Evidence-based Cardiology

Table 53.5 Reported outcome in 174 young people followed for a mean of 10 years after an episode of rheumatic fever

Current era

In the current era, patients have been followed after

non-invasive tests (echocardiography/Doppler ultrasound,

radionuclide LVEF) or after invasive studies (cardiac

catheterization or angiography) Reported outcomes are

shown in Table 53.7

As outlined in Table 53.7,52–58,64 the natural history of

patients with chronic aortic valve regurgitation depends on

the presence or absence of symptoms and on the status of

the left ventricle In asymptomatic patients with normal left

ventricular function, data would suggest the progression to

symptoms and or left ventricular systolic dysfunction in

approximately 4% per year Sudden death occurs very rarely,

0·1% per year, and asymptomatic left ventricular

dysfunc-tion occurs at a rate of 1–3% per year, depending on the

fre-quency of follow up

There are limited data on asymptomatic patients with

reduced left ventricular systolic function However,

avail-able data would suggest that most of these patients will

develop symptoms warranting surgery within two to three

years, at an average rate of 25% per year

Limited data are available on the natural history of

symp-tomatic patients with severe aortic valve regurgitation

These patients have a poor prognosis despite medical

ther-apy, with reported mortality rates of 10 and 20% per year in

patients with angina and heart failure, respectively

Important limitations of some of the studies in the

litera-ture must be kept in mind For example, the “natural

his-tory” group in one study was composed of several subsets of

patients53 and 36% of this group were on medications for

symptoms Another concern is the true rate of the

develop-ment of asymptomatic left ventricular dysfunction.54At least

25% of patients who develop left ventricular systolic

dys-function do so before they have symptoms, thus emphasizing

the need for quantitative assessment of left ventricular systolicfunction at follow up in asymptomatic patients with severeaortic regurgitation and normal left ventricular systolic func-tion More recent studies indicate a poor outcome of symp-tomatic patients with medical therapy, even among thosewith preserved systolic function (Table 53.8).57,65

Sir William Broadbent66stated 100 years ago that “The

age of the patient at the time when the lesion is acquired is

Table 53.6 Asymptomatic period observed in 126

patients following an episode of rheumatic fever

Age group (years) Patients symptomatic

a Symptoms were those of dyspnea, fatigue and, less

fre-quently, chest pain and palpitations Patients deteriorated

from NYHA functional Class I to Classes II, III, or IV.

From Goldschlager et al 50

Table 53.7 Outcomes of patients with severe aortic regurgitation

Asymptomatic patients with normal left venticular systolic function52–59 progression to symptoms 2·4–5·7% per year and/or left ventricular (average 3·8% systolic dysfunction per year) progression to

asymptomatic left ventricular dysfunction:

follow up at 12 month

follow up at 6 month

Asymptomatic patients with left ventricular systolic dysfunction60–61 progression to cardiac

Symptomatic patients50,62–64

10% per year

a See text for details.

Table 53.8 Likelihood of symptoms or left ventricular dysfunction or death

● Left ventricular end-diastolic dimension

the most important consideration in prognosis …” In

asymptomatic patients with normal left ventricular systolic

function, the independent predictors of symptoms, left

ven-tricular systolic dysfunction, and death by multivariate

analysis were: older age, decreasing resting LVEF, and left

ventricular dimension on M-mode echocardiography.54

However, in many of these patients, M-mode images were

not obtained from two dimensionally directed

echocardio-grams Very importantly, most of these dimensions were

obtained in the United States, and US women have smaller

left ventricular dimensions than men, even when they

become symptomatic.67Thus, it is unlikely that the above

criteria apply to women and almost certainly will not be

applicable to populations of smaller body size, for example,

Asians, Latin Americans, sub-Saharan Africans, and Orientals

The left ventricular dimension should be corrected to body

surface area.68Patients also develop symptoms and/or left

ventricular systolic dysfunction at a faster rate if their initial

left ventricular end-diastolic volume is 150 ml/m2 when

compared to those with volumes 150 ml/m2.53Older age

also appears to increase the annual mortality.68

Patients with severe ventricular dilation when exercised

have shown mean pulmonary artery wedge pressure

20 mmHg and/or exercise ejection fraction 0·50, and

such patients have demonstrated reduced exercise capacity,

with reduced maximum VO2.69,70

Patients who present with ventricular tachycardia,

ven-tricular fibrillation or syncope and have inducible

ventricu-lar tachycardia on electrophysiologic studies have an 80%

probability of a serious arrhythmic event up to 4 years of

follow up, versus 47% in those in whom ventricular

tachy-cardia could not be induced (P 0·005).71

Acute severe aortic valve regurgitation usually causes

sudden severe symptoms of heart failure or cardiogenic

shock The sudden large regurgitant volume load is imposed

on a normal size left ventricle causing marked elevation in left

ventricular end-diastolic pressure and left atrial pressure

Echocardiography is invaluable in determining the severity

and etiology of aortic valve regurgitation.10The etiology of

acute aortic valve regurgitation may have an important

impact on the treatment, which is usually emergency surgery

Management options

Angina is a result of a relative reduction of myocardial blood

flow because of an increased need or associated obstructive

CAD or both.25It does not respond to nitrates as well as in

aortic stenosis The options are to reduce the amount of

aor-tic regurgitation and/or to revascularize the myocardium by

coronary bypass surgery or by percutaneous catheter

tech-niques Clinical heart failure is treated with the traditional

first-line triple therapy, that is, digitalis, diuretics, and ACE

inhibitors Parenteral inotropic and vasodilator therapy may

be needed for those in severe heart failure.72 The only

direct method(s) to reduce the amount of regurgitation is byarterial dilators73and valve surgery – that is, valve replace-ment or valve repair

Arterial dilators

In chronic aortic valve regurgitation, therapy with ing agents is designed to improve forward stroke volumeand reduce regurgitant volume These effects should trans-late into reductions in left ventricular end-diastolic volume,wall stress, and afterload, resulting in preservation of leftventricular systolic function and reduction in left ventricularmass These effects have been observed in small numbers ofpatients receiving hydralazine.73 In a trial of 80 patientsover 2 years74in which 36% of patients were symptomatic(NYHA class II) and were being treated with digitalis anddiuretics, hydralazine produced very minor improvements

vasodilat-of left ventricular size and function.74Side effects associatedwith long-term use of hydralazine seriously impaired com-pliance and only 46% of the patients completed the trial.Hydralazine is rarely used currently Occasionally it is usedfor a short period of time, to tide the patient over an acutereversible complication or in preparation for elective surgery

in selected patients with left ventricular dysfunction Lessconsistent results have been reported with ACE inhibitors,depending on the degree of reduction in arterial pressureand end-diastolic volume In an acute study in the catheter-ization laboratory, 20 patients were randomized to eitheroral nifedipine or oral captopril.75 Nifedipine produced

a reduction of regurgitant fraction but captopril did not Nifedipine produced a greater increase of forwardstroke volume and cardiac output and a greater fall of systemic vascular resistance This study showed that,acutely, nifedipine was superior to an ACE inhibitor A short-term 6 month randomized trial of a small number ofpatients showed that the results with captopril were similar

to placebo – that is, there were no significant changes in M-mode echocardiographic left ventricular dimensions.76

A randomized trial of 72 patients for 12 months of acting nifedipine showed statistically significant reductions

long-of left ventricular end-diastolic volume index and left tricular mass, and increase of LVEF.58The role of long-acting

ven-nifedipine on patient outcome has been evaluated in a

prospective, randomized trial of 143 asymptomatic patientswith chronic, severe aortic valve regurgitation, and normalleft ventricular systolic function; 69 patients were random-ized to long-acting nifedipine and 74 patients to digoxin.The patients were evaluated at 6 month intervals for med-ication complication and had a history, physical examina-tion, ECG, chest radiograph, and echocardiographic/Doppler study Two independent blinded observers readeach echocardiographic/Doppler study Criteria for valvereplacement were established prior to the start of the study

If left ventricular dysfunction developed, this had to be

Evidence-based Cardiology

confirmed by a repeat echocardiographic/Doppler study at

1 month and by preoperative left ventricular angiographic

study At 6 years, the need for valve replacement was

346% in the digoxin-treated group and 153% in the

nifedipine-group, P 0·001 (Figure 53.4).58Thus, for every

100 patients treated with nifedipine, 19 fewer valve

replacements were needed at the end of 6 years; note that

even after 6 years, the curves are not parallel and do not

converge (see Figure 53.4) Compared to the digoxin group,

the nifedipine-treated group demonstrated a reduction in

left ventricular volume and mass Ejection fraction increased

in the digoxin arm of the trial, and left ventricular volumes

and mass increased After aortic valve replacement, 12 of 16

patients (75%) in the digoxin group and all six patients in the

nifedipine group who had an abnormal LVEF before surgery

had a normal ejection fraction Eighty-five per cent of

patients in the digoxin arm of the trial, who underwent valve

replacement, developed an abnormal ejection fraction and

only three patients had valve replacement for symptoms

Moreover, patients in the digoxin arm of the trial had an

out-come similar to that reported in the natural history studies

Long-acting nifedipine is the drug of choice for

asympto-matic patients with severe chronic aortic valve regurgitation

and normal left ventricular systolic function unless there is a

contraindication to its use.25The goal of vasodilator therapy

is to reduce systolic blood pressure The dose should be

increased until there is a measurable decrease in blood

pressure or side effects Vasodilator therapy is not indicated

in patients with normal left ventricular dimension and/ornormal blood pressure ACE inhibitors are not of provenbenefit in asymptomatic patients with severe chronic aortic valve regurgitation and normal left ventricular systolicfunction

Valve surgery (replacement/repair)

Surgery for aortic valve regurgitation should only be considered when the degree of regurgitation is severe.However, the presence of severe aortic valve regurgitationdoes not mandate surgery The critical issue is to choose thebest time for surgical intervention Aortic valve repair orreplacement should be performed in most symptomaticpatients irrespective of the degree of left ventricular dys-function Postoperative survival is better after valve replace-ment in symptomatic patients with normal or mildlyimpaired left ventricular systolic function (ejection fraction[EF] 0·45) than in those with greater impairment of leftventricular systolic function (EF 0·45).77 In one study,patients with preoperative left ventricular EF of 0·60 had

a better survival than those with left ventricular EF of

0·60.78 Extreme left ventricular dilation (end-diastolicdimension 80) associated with aortic valve regurgitationoccurs primarily in men and is often associated with leftventricular dysfunction Extreme left ventricular dilation,however, is not a marker of irreversible left ventricular dys-function Operative risk and late postoperative survival areacceptable in these patients.79In the setting of severe leftventricular dysfunction (EF0·25), the risk of aortic valvesurgery increases and potential benefits decline, since leftventricular dysfunction may be on the basis of irreversiblemyocardial damage However, even in the highest riskpatients, the risk of surgery and postoperative medical ther-apy for heart failure are usually less than the risk of long-term medical management alone

Aortic valve surgery for asymptomatic patients is morecontroversial but is indicated in the setting of left ventriculardysfunction with an EF0·50 and in the setting of severeleft ventricular dilation (end-diastolic dimension 75 mm orend systolic dimension 55 mm), even if the ejection frac-tion is normal The threshold values of end-diastolic and end-systolic dimension recommended for aortic valve replacement

in asymptomatic patients may need to be adjusted to bodysurface area In one series, it was noted that a left ventricularend-systolic dimension corrected for body surface area(LVS/BSA) of 25 mm/m2 was associated with increasedmortality when followed conservatively.1,68,79

After valve replacement, patients with normal tive left ventricular systolic function have reductions of leftventricular volumes and hypertrophy.80 In the majority ofpatients with normal preoperative left ventricular function,there is an increase in EF after valve replacement, presum-ably because of a reduction of myocardial stress.31,81 Left

preopera-Grade B Grade A

20

10

0

Figure 53.4 The role of long term, long acting nifedipine

ther-apy in asymptomatic patients with severe aortic regurgitation

and normal left ventricular systolic pump function was evaluated

in 143 asymptomatic patients in a prospective randomized trial.

By actuarial analysis, at 6 years, 34  6% of patients in the

digoxin group underwent valve replacement versus 15  3% of

those in the nifedipine group (P  0·001) This randomized trial

demonstrates that long term arteriolar dilator therapy with long

acting nifedipine reduces and/or delays the need for aortic

valve replacement in asymptomatic patients with severe aortic

regurgitation and normal left ventricular systolic pump function.

(From Scognamiglio et al 52 with permission.)

ventricular hypertrophy continues to decline for up to 5–8

years in those with normal preoperative left ventricular

sys-tolic function, but at a slower rate after 18–24 months.31,81

Most patients are symptomatically improved and are in

NYHA class I.25

After valve replacement in those with abnormal

preoper-ative left ventricular systolic function (EF 0·25–0·49), there

is a reduction of heart size and left ventricular end-diastolic

pressure, end-diastolic and end-systolic volumes and

hyper-trophy.77Left ventricular EF improves or normalizes only if

the EF was abnormal for 12 months prior to surgery.81

Very early after valve replacement, there may be a reduction

in EF The left ventricular end-diastolic volume has not yet

decreased but the regurgitant volume has been eliminated;

this causes a decline in EF An early decrease in left

ventric-ular end-diastolic dimension is a good indicator of functional

success of aortic valve replacement as the magnitude of

reduction in end-diastolic dimension after operation

corre-lates with the magnitude of late increase in EF.1Moreover,

unless there is a perioperative complication, most patients are

symptomatically improved and are in NYHA class I or II.25

In those with severe symptoms and severe reduction of EF

or severe left ventricular dilation preoperatively, survival aswell as the beneficial effects on left ventricular function andfunctional class are less marked.80,82

Boxes 54.3 and 54.4 summarize the results of valvereplacement in those with severe chronic aortic valve regur-gitation and the factors predictive of a worse postoperativesurvival, less recovery of left ventricular function, and lessimprovement in symptomatic state in those with severeregurgitation and preoperative left ventricular systolic dysfunction

There are two controversial questions regarding patientswith severe aortic valve regurgitation First, when does thesymptomatic patient become inoperable? Second, whenshould one operate on asymptomatic patients with severeaortic valve regurgitation (assuming that associated co-morbid conditions do not make the patient inoperable or athigh risk for surgery)?

Severe left ventricular systolic dysfunction is the majorfactor that makes the patient with severe aortic valve regur-gitation inoperable In the published study of left ventriculardysfunction in which the patient and left ventricular func-tion improved after valve replacement, the patients had an

EF of 0·25–0·49.77,80 Personal experience indicates thatwith skilled and experienced surgery, patients with an EF of0·18–0·24 are improved with operation There are limiteddata on the results of valve replacement in patients withsevere aortic valve regurgitation and severe left ventricularsystolic dysfunction with a left ventricular EF of 0·18,these patients are very high risk for conventional valve sur-gery and many would consider such patients inoperable.The asymptomatic patient with severe aortic valve regur-gitation poses a challenging clinical dilemma If patientshave developed left ventricular systolic dysfunction, thentheir outcome is poor without surgery, and left ventriculardysfunction, if present for 12 months or longer, does notnormalize after surgery;81 therefore, surgery is advisable.Patients who need surgery for associated conditions, forexample, obstructive CAD, thoracic aortic disease, such as

an aortic aneurysm, or another valve lesion, should havesurgery for the severe aortic regurgitation Patients whohave developed severe left ventricular dilation are on theedge of developing symptoms at a high rate One could waitfor symptoms to develop and follow these patients very care-fully at frequent intervals Asymptomatic patients who donot have severe left ventricular dilation and those who donot have left ventricular dysfunction at rest or exerciseshould not have surgery for chronic aortic valve regurgita-tion The current status of aortic valve repair prevents rec-ommending this as an early prophylactic procedure It isdifficult to determine which aortic valves will be amenable

to repair In addition, the current rate of reoperation is at alevel that prevents regular use of this procedure in asympto-matic patients with minimal left ventricular enlargement.83

Evidence-based Cardiology

Box 53.3 Results of valve replacement in patients with

severe chronic aortic valve regurgitation

● Improved survival in those with mild to moderate

impair-ment of left ventricular systolic function and in those

with severe left ventricular enlargement irrespective of

their symptomatic status

● Improvement in left ventricular systolic dysfunction;

function normalizes if the dysfunction is of 12 months’

duration preoperatively

● Regression of left ventricular hypertrophy

● Improvement in functional class, particularly in those

with preoperative mild to moderate impairment and in

those with preoperative left ventricular dysfunction

Box 53.4 Factors predictive of a less favorable

outcome

● Extent and severity of associated comorbid conditions

● Severe obstructive coronary artery disease

● Presence and severity of clinical heart failure

preoperatively

● Severity of depression of preoperative LVEF

● Duration of preoperative left ventricular systolic

dysfunction

● Extent of preoperative irreversible myocardial damage

● Severity of increase in left ventricular end-diastolic and

systolic size (left ventricular diastolic and

end-systolic volumes of 210 and 110 ml/m 2 ,

respec-tively, or end-diastolic and end-systolic dimensions of

80 mm and 60 mm, respectively)

● Skill and experience of operating and associated

profes-sional teams, for example, anesthetists

● Extent of perioperative myocardial damage

● Complications of a prosthetic heart valve

Recommendations: aortic valve replacement/repair in

severe chronic aortic regurgitation

● Symptomatic patients with:

● NYHA class III or IV symptoms and

normal LV systolic function (LVEF  0·5) I

● NYHA class II symptoms, preserved

systolic function (LVEF  0·5) but with

progressive LV dilation or declining EF

at rest, or declining exercise capacity on

● Canadian Heart Association class II or

greater angina with or without CAD I

● NYHA class II symptoms with preserved

LV systolic function (LVEF  0·5) with

stable LV size and systolic function on

serial studies and stable exercise

● normal LV function and:

● associated severe obstructive CAD

● other valve or thoracic aortic disease

● severe LV dilation with EDD 70 mm or

ESD 55 mm and normal LV systolic

function (LVEF 0·50) IIb

● normal systolic function at

rest (LVEF 0·5) but decline in

EF ( 0·50) on exercise radionuclide

● normal systolic function at

rest (LVEF 0·5) but decline in

EF ( 0·50) on stress echocardiography III

● LV dilation is not severe (EDD 70 mm,

Abbreviations: NYHA, New York Heart Association; EDD,

end-diastolic dimension; ESD, end-systolic dimension; LVEF,

left ventricular ejection fraction; EF, ejection fraction; LV, left

ventricular

For definition of classes, see p 773

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Balloon valvuloplasty: aortic valve

Daniel J Diver, Jeffrey A Breall

Aortic stenosis: natural history and prognosis

There are three major etiologies for valvular

aortic stenosis in the adult patient: rheumatic aortic

steno-sis; congenital bicuspid aortic stenosis with secondary

calci-fication; and senile calcific or degenerative aortic stenosis In

rheumatic aortic stenosis the major pathologic feature is

commissural fusion, with associated thickening and fibrosis

of the valve leaflets Symptoms may not occur until the

age of 50 or 60 and are often accompanied by evidence

of other valvular disease, usually mitral Patients with

con-genital bicuspid aortic stenosis develop progressive

narrow-ing and calcification of the aortic valve over time, with

symptoms often present by age 40–50 Degenerative calcific

(senile) aortic stenosis appears to result from years of normal

mechanical stress on the aortic valve, with progressive

immobilization of cusps secondary to calcium accumulation

in the pockets of the aortic cusps, and eventual fibrosis

Degenerative calcific aortic stenosis is now the most

com-mon cause of aortic stenosis in patients presenting for aortic

valve replacement.1

Most data regarding the natural history of aortic stenosis

are derived from clinical experience during the presurgical

era The natural history of aortic stenosis is characterized by

a long latent period marked by slowly increasing obstruction

and adaptive myocardial hypertrophy The majority of

patients are free of cardiovascular symptoms until relatively

late in the course of the disease However, once patients

with aortic stenosis develop symptoms of angina, syncope or

heart failure, survival with medical therapy is dismal, with

death occurring within 2–5 years in most patients following

the development of symptoms (Figure 54.1) Average

survival in patients with aortic stenosis and angina or

syn-cope is 2–3 years, and may be as short as 1·5 years in

patients with aortic stenosis who develop heart failure.2

Concomitant atrial fibrillation decreases survival in all

symp-tom groups

Asymptomatic patients with aortic stenosis have an

excel-lent prognosis and rarely die without premonitory

symp-toms A study by Pellikka et al4showed that mortality was

slightly higher in asymptomatic patients treated with

“pro-phylactic” valve replacement than in patients not operated

on until symptoms develop A recent study by Otto and

col-leagues reported follow up of 123 patients with

asympto-matic aortic stenosis During the 2·5 year, follow up period

Grade A

there were no sudden cardiac deaths This study suggestedthat the rate of hemodynamic progression and clinical out-come in adults with asymptomatic aortic stenosis may bepredicted by echocardiographic aortic jet velocity Of thosepatients who entered the study with a peak aortic jet veloc-ity 4 m/s only 21% were alive and free of valve replace-ment 2 years later.5

The timing of aortic valve replacement in patients withaortic stenosis is predicated on the development of symp-toms or deterioration in left ventricular performance, ratherthan severity of valve gradient or reduction in valve orificearea Carabello6has proposed a definition of “critical” aorticstenosis as that valve area small enough to cause the symp-toms of aortic stenosis that often presage sudden death:

a “critical” situation indicating the need for aortic valvereplacement The aortic valve area associated with suchsymptom development varies significantly from patient topatient

Aortic stenosis: natural history and prognosis

● Long latent period without symptoms

● Poor prognosis following symptom development withdeath in 2–5 years

● Prognosis significantly improved by valve replacementsurgery

54

100

Onset severe symptoms

Angina Syncope Failure

Av Survival (yr) Average death Age ( )

6

Latent period (increasing obstruction, myocardial overload

80 60 40 20

opera-Surgery for aortic stenosis

The initial surgical approach to treatment of

aor-tic stenosis involved surgical valvuloplasty In contrast to the

situation with pulmonary and mitral stenosis, the stenotic

aortic valve did not respond favorably to surgical

valvulo-plasty techniques Closed aortic commissurotomy was

asso-ciated with a high incidence of acute aortic regurgitation

and operative mortality, and was abandoned after the

devel-opment of open aortic valve surgical techniques Surgical

valvuloplasty under direct vision for aortic stenosis was first

described in 1956, but was limited by a high rate of

resteno-sis leading to subsequent aortic valve replacement, as well

as a significant incidence of complications, including aortic

regurgitation, infective endocarditis and systemic

emboliza-tion.7 Although ultrasonic decalcification and careful

surgi-cal sculpting procedures carried out under direct vision are

initially effective in some patients, restenosis remains a

seri-ous problem.8However, open surgical valvulotomy remains

an important treatment for infants and children with critical

aortic stenosis, a situation where initial prosthetic valve

replacement is undesirable

The development and refinement of surgical aortic valve

replacement significantly improved morbidity and mortality

in patients with symptomatic aortic stenosis Although there

is no prospective randomized controlled study comparing

aor-tic valve replacement with medical therapy in such patients,

long-term follow up in high-quality case series has

convinc-ingly demonstrated the long-term benefits of aortic valve

replacement, including hemodynamic improvement,

regres-sion of left ventricular hypertrophy, improvement of left

ventricular function and improved survival.9–11 Operative

mortality for aortic valve replacement ranges from 2 to 8%,

but may be as low as 1% in patients less than 70 years of age

without significant comorbidity

Aortic valve replacement, however, is associated with

increased morbidity and mortality in certain subgroups.10,12–15

Aortic valve replacement in the presence of left ventricular

failure may be associated with perioperative mortality as

high as 10–25%, and the need for emergency aortic valve

replacement with operative mortality as high as 40%

Surgical risk is increased in the elderly patient, and may be

increased severalfold with the need for concomitant bypass

or multiple valve surgery Although advanced age remains a

strong predictor of operative death for aortic valve

replace-ment even in recent studies, age alone is not a

contraindica-tion to aortic valve replacement in patients with aortic

stenosis.16 The Society of Thoracic Surgeons National

Cardiac Surgery Database identified risk factors in nearly

50 000 patients who had valve surgery between 1994 and

1997: for patients with isolated aortic valve replacement,

age was not a strong predictor of risk.17 Fremes and

col-leagues18at the University of Toronto described the result of

valve surgery in 469 consecutive patients over 70 years of

Grade B

age, and found that the predicted probability of operativemortality ranged from 0·9 to 76%, depending on the pres-ence of other risk factors, including urgent operation, dou-ble valve surgery, coronary artery disease, female genderand left ventricular dysfunction The authors suggested thatelderly patients in good risk categories should be offered sur-gical intervention for the correction of valvular lesions,whereas alternative therapy might be indicated in patientswith multiple risk factors in whom surgical mortalitywas prohibitively high Levinson and colleagues at theMassachusetts General Hospital reported on aortic valvereplacement for aortic stenosis in octogenarians.19In theircohort of 64 patients, serious comorbid non-cardiac condi-tions were infrequent In-hospital mortality was 9·4% Anadditional 10% of patients had permanent severe neurologicdeficits and an additional 38% had a “complicated” course,marked by temporary encephalopathy, discharge to a reha-bilitation facility or some combination thereof, albeit withultimately good results Although most survivors were ulti-mately free of cardiac symptoms, there was a high price topay in terms of perioperative mortality and morbidity toachieve these results However, recent series suggest thatsurgical results may be improving in very elderly patients.Rosengart and colleagues20compared results in 100 consec-utive patients age 85 years or older who underwent openheart surgery between 1994 and 1997 with results obtained

in the prior decade, and noted improvement in 30 day tality and risk of major complications

mor-Therefore, while surgical aortic valve replacement hasclearly improved the outcome in most patients with criticalaortic stenosis, the higher risk in some patient subgroups,including the elderly, often leads to physician or patientdeferral of aortic valve replacement In an attempt to definethe natural history of such patients, O’Keefe and colleagues21

at the Mayo Clinic performed a case comparison study of 50patients with severe, symptomatic aortic stenosis in whom

surgery was declined by the patient (n 28) or the physician

(n 22) The actuarial survival at 1, 2 and 3 years was

57, 37 and 25%, respectively The survival of age- and matched control subjects was 93, 85 and 77%, respectively

sex-(P 0 · 0001 at each 1 year interval) (Figure 54.2) Thisstudy suggested that the natural history of untreated aorticstenosis remains dismal and has not improved in the modernera, and confirmed the necessity of evaluating alternativenon-surgical therapy, such as balloon aortic valvuloplasty, inpatients likely to decline aortic valve replacement, or forwhom surgery is not an option

Development of balloon aortic valvuloplasty

Children and adolescents with congenital aorticstenosis generally have non-calcified valves with commissuralfusion Because aortic valve replacement is not desirable in

Grade C

Evidence-based Cardiology

this age group, commissural incision under direct vision is

the preferred surgical procedure, and has been shown to

confer significant hemodynamic improvement at low risk.22

The contribution of commissural fusion to the etiology of

valvular stenosis and mechanism of surgical improvement in

this patient group led to the consideration of balloon aortic

valvuloplasty as an alternative, non-surgical therapy

In 1984 Lababidi and colleagues23reported the first series

of 23 children and young adults with congenital aortic

steno-sis treated with percutaneous balloon aortic valvuloplasty

The patients ranged in age from 2 to 17 years Balloon

valvu-loplasty was performed by the retrograde approach from the

femoral artery, utilizing balloons of 10–20 mm in diameter

Percutaneous balloon dilation resulted in a decrease in the

peak aortic valve gradient from 113 to 32 mmHg, with no

change in cardiac output The excellent initial results of

percutaneous balloon valvuloplasty for aortic valve stenosis

were confirmed by Rosenfeld and colleagues in young

adults with congenital aortic stenosis Long-term follow-up

appeared to be excellent, with a 58% event-free rate at mean

follow-up of 38 months,24 although a recent multicenter

study from Japan reported that progressive aortic insuffiency

and recurrence of pressure gradient was not uncommon by

4 years after balloon valvuloplasty.25

The excellent results of balloon valvuloplasty in pediatric

patients with congenital aortic stenosis led to consideration

of this technique in adult patients with acquired calcific

aor-tic stenosis Two reports in 1986 described the first

success-ful balloon valvuloplasty procedures in adult patients

Cribier and colleagues in France performed percutaneous

balloon dilation in three elderly patients with calcific aortic

stenosis.26The peak aortic gradient decreased from 75 to

33 mmHg, with an increase in calculated aortic valve areafrom 0·5 to 0·8 cm2 All patients had symptomatic improve-ment McKay and colleagues27 at the Beth Israel Hospital

in Boston described two elderly patients (aged 93 and

85 years) with calcific aortic stenosis treated with balloonvalvuloplasty with 12–18 mm balloons This report likewisedescribed a substantial reduction in the transaortic pressuregradient and a significant increase in aortic valve area, withsymptomatic improvement in both patients and significantimprovement in left ventricular function in one Despite ini-tial concern regarding the possibility of valve disruption orembolization in the calcific valves present in adult patients,

no patient in either report developed emboli or a significantincrease in aortic regurgitation

Mechanism of balloon aortic valvuloplasty

To assess the safety, efficacy and mechanism ofballoon aortic valvuloplasty, Safian and colleagues28 per-formed balloon dilation of stenotic aortic valves in 33 post-mortem specimens and in six patients undergoing aorticvalve replacement, prior to removal of the stenotic valve.The cause of aortic stenosis was degenerative nodular calci-fication in 28 cases, calcific bicuspid aortic stenosis in eightcases, and rheumatic heart disease in three The distribution

of the etiology of aortic stenosis in this report is in dance with the observation that degenerative calcific aorticstenosis is now the most common cause of aortic stenosis inadults presenting for aortic valve replacement.1

concor-Safian and colleagues performed balloon dilation with15–25 mm balloons in the postmortem specimens, and with18–20 mm balloons in the surgical patients Balloon dilationresulted in increased leaflet mobility and increased valve ori-fice dimensions in all patients The mechanism of successfuldilation included fracture of calcified nodules within theleaflets in 16 valves, separation of fused commissures in fivevalves, both in six valves, and “grossly inapparent microfrac-tures” (or stretching) in 12 valves Liberation of calcificdebris, valve ring disruption and midleaflet tears did not occur

in any valve, although valve leaflet avulsion was produced inone postmortem specimen after inflation with a clearly over-sized balloon The authors concluded that there were severalmechanisms for successful balloon aortic valvuloplasty, withthe predominant mechanism in a given patient depending onthe etiology of the stenosis Furthermore, it appeared thatembolic phenomena and acute regurgitation were not likely

to be frequent complications following valvuloplasty.The study by Safian and colleagues suggested that themost common etiology of aortic stenosis in the balloon valvu-loplasty population is degenerative nodular calcification,and that the predominant mechanism of valve dilation isfracture of calcified nodules within leaflets and leaflet

Years

3 Aortic stenosis

Figure 54.2 Survival among 50 patients with severe aortic

stenosis who did not undergo surgical treatment, in comparison

with an age- and sex-matched control group from the US

popu-lation Asterisks denote significant differences (P  0.0001)

between the two groups Standard errors are shown as vertical

lines (Reproduced with permission from O’Keefe et al 21 )

stretching Considered in conjunction with the

disappoint-ing surgical experience when stenotic aortic valves were

dilated or cracked, the results of this mechanistic study

pre-dicted that there might be only mild improvement in aortic

valve orifice area in patients treated with balloon aortic

valvuloplasty, and that any such improvement might be

short-lived As will be seen, these implications were

subse-quently borne out in clinical trials

Technical aspects

In the original reports by Cribier26 and McKay,27 balloon

valvuloplasty was performed via the retrograde femoral

approach The most common balloon size used with the

single-balloon retrograde approach is 20 mm, although

smaller balloons can be used initially in small or frail patients

If no waist is produced in the inflated balloon, or if the aortic

valve gradient is not sufficiently decreased by a given balloon

size, a larger balloon may produce a better result

Several modifications of the percutaneous retrograde

femoral approach have been described Block and Palacios29

described an antegrade transseptal technique which they

advocated for patients with severe iliac occlusive disease,

tortuous iliac vessels or abdominal aortic aneurysm This

approach has recently been reported using the Inoue

bal-loon, which may provide a greater increase in aortic valve

area than conventional balloons30 and which allows

com-bined mitral and aortic valvuloplasty using a single catheter

and access site.31A retrograde brachial approach may also

be useful in such situations, although care must be taken to

avoid injury to the brachial artery by the large valvuloplasty

balloon Dorros and colleagues32described a double-balloon

technique, using both femoral arteries or a combined

brachial and femoral approach The combined diameter of

the balloons used in this approach usually exceeds the

diam-eter of the largest balloon used with single-balloon

tech-niques While initial results with double-balloon aortic

valvuloplasty showed a greater enlargement of aortic valve

area, follow-up studies showed no reduction in subsequent

restenosis compared to single-balloon valvuloplasty.33 An

important recent technical advance is management of the

femoral access site with preloaded suture closure devices,

which may significantly reduce the incidence of vascularcomplications following balloon valvuloplasty.34,35

Initial results of balloon aortic valvuloplasty

Single center studies

Within several years of the initial reports of loon valvuloplasty in adult patients with aortic stenosis, sev-eral centers reported large single-center experiences.36–39

bal-Cribier et al36reported their initial experience with 92 adultpatients with symptomatic aortic stenosis and a mean age of

75 years The aortic valve gradient was reduced from 75 to

30 mmHg, with an increase in calculated aortic valve areafrom 0·5 to 0·9 cm2 The left ventricular ejection fractionrose from 48% at baseline to 51% immediately following theprocedure The majority of patients had marked sympto-matic improvement There were three in-hospital deaths andeight late deaths

Safian et al37reported their initial experience with loon aortic valvuloplasty in 170 consecutive patients treated

bal-at the Beth Israel Hospital in Boston The procedure wascompleted successfully in 168 patients and resulted in sig-nificant increases in mean aortic valve area (0·6–0·9 cm2)and cardiac output (4·6–4·8 l/min) and a significantdecrease in aortic valve pressure gradient (71–36 mmHg)

(P 0·01 for all comparisons) There were six in-hospitaldeaths and five patients required early aortic valve replace-ment The majority of patients had marked symptomaticimprovement following the procedure The most commoncomplication was vascular, involving the femoral access site:

40 patients required transfusion and 17 required surgicalrepair Transient dysrhythmias, most commonly left bundlebranch block, occurred in 28 patients Left ventricularperforation and tamponade occurred in three patients,

a marked increase in aortic regurgitation in two patients,and a non-Q wave myocardial infarction in one patient Nopatient suffered a stroke

The hemodynamic results and complications of balloonaortic valvuloplasty in several large single-center studies aresummarized in Tables 54.1 and 54.2, respectively Theresults are remarkable for their similarity across study sites

Evidence-based Cardiology

In general, balloon aortic valvuloplasty resulted in a 50–70%

decrease in aortic valve gradient and a 50–70% increase in

aortic valve area, resulting in early symptomatic

improve-ment in most patients The most common complication was

vascular at the access site; there was a low incidence of

life-threatening procedural complications Death during the

periprocedural period occurred in about 6% of patients

Multicenter studies

Two large multicenter studies reported the initial

results of balloon valvuloplasty in adult patients with

symp-tomatic aortic stenosis.40,41 The Mansfield Balloon Aortic

Valvuloplasty Registry40 evaluated data from 27 clinical

centers in the United States and included 492 patients

treated with balloon aortic valvuloplasty between December

1986 and October 1987 The mean age of patients was

79 years All had severe symptoms, with 92% reporting

congestive heart failure Balloon aortic valvuloplasty was

performed via the femoral approach in 92% of patients,

by the brachial approach in 6%, and by the transseptal

approach in 2% A single-balloon technique was used in

72% of patients The largest balloon size was 20 mm in over

half of patients

In the Mansfield Registry, balloon aortic valvuloplasty

resulted in a decrease in mean aortic valve gradient from

60 to 30 mmHg, an increase in cardiac output from 3·9

to 4·0 l/min and an increase in aortic valve area from 0·5

to 0·8 cm2 Most patients had significant symptomatic

improvement Death occurred during the procedure in

4·9% of patients, and within 7 days of the procedure in an

additional 2·6% The most common complication (11%)

was local vascular injury, requiring surgical repair in 5·7% of

patients Embolic complications, ventricular perforation

resulting in tamponade, and significant increase in aortic

insufficiency each occurred in 1–2% of patients, and

signifi-cant arrhythmia or myocardial infarction in less than 1%

Emergency aortic valve replacement was required in 1% of

patients following balloon valvuloplasty

The National Heart Lung and Blood Institute (NHLBI)

Balloon Valvuloplasty Registry enrolled 674 elderly (average

Grade B

age 78 years) patients at 24 centers between November

1987 and November 1989.41 Heart failure was the mostcommon presenting symptom, occurring in 92% of patients;45% of patients had angina and 35% had syncope A single-balloon retrograde valvuloplasty technique was used in 94%

of patients; the largest balloon used was 20 mm in over half.The mean gradient decreased from 55 to 29 mmHg and theaortic valve area increased from 0·5 to 0·8 cm2, associatedwith symptomatic improvement in most patients Proceduralmortality was 3%; other major complications associated withthe valvuloplasty procedure included cardiac arrest (5%),emergency aortic valve replacement (1%), left ventriculartamponade (2%), cerebral vascular accident (1%), systemicembolus (1%), emergency temporary pacing (5%), and ven-tricular arrhythmia requiring countershock (3%)

In summary, the initial results of the multicenter studieswere similar to each other, and to the results of the previouslydescribed single-center studies, and suggested that balloon aor-tic valvuloplasty resulted in modest hemodynamic improve-ment and significant symptomatic improvement in manypatients considered to be at high risk for aortic valve surgery

Left ventricular function

Aortic valve replacement has been shown toimprove left ventricular function in many patients withaortic stenosis and left ventricular dysfunction.9–11 Safianand colleagues42at Beth Israel Hospital examined the effect

of balloon aortic valvuloplasty on left ventricular ance in 28 patients with a low left ventricular ejectionfraction (mean 37%), severe aortic stenosis and a mean age

perform-of 79 years Balloon valvuloplasty resulted in significantincreases in aortic valve area (0·5–0·9 cm2), systolic pressure(120–135 mmHg), and cardiac output (4·2–4·8 l/min)

(P 0·01 for all comparisons), and significant decreases intransaortic pressure gradient (69–35 mmHg) and pulmonary

capillary wedge pressure (24–20 mmHg) (P 0·01 for bothcomparisons) All patients were symptomatically improved atthe time of discharge

Serial radionuclide ventriculography showed an increase

in left ventricular ejection fraction from 37% prior to

Grade B

Table 54.2 Complications of balloon aortic valvuloplasty

Author Patients (n) Complications (%)

valvuloplasty to 44% 48 hours post procedure and 49% at

3 month follow up However, there was substantial

hetero-geneity of response, with 13 patients showing progressive

increases in left ventricular ejection fraction (34% to 49% to

58%, P 0 · 001), whereas 15 patients showed no

signifi-cant change in ejection fraction (41% to 40% to 41%,

P NS) over 3 months There was no difference between

the groups with respect to age, extent of coronary disease,

history of myocardial infarction, or baseline or

postproce-dure aortic valve area However, peak systolic wall stress

and left ventricular dimensions were higher in those

patients who showed no improvement in ejection fraction

It may be that the failure to increase ejection fraction in this

group is due to irreversible impairment in myocardial

con-tractile function, secondary to previous infarction or

long-standing aortic stenosis Davidson and colleagues at Duke

University also found that fewer than half of patients with a

baseline left ventricular ejection fraction less than 45%

showed sustained improvement following percutaneous

bal-loon aortic valvuloplasty, even at short-term follow up.43

Follow up

Despite the moderate hemodynamic

improve-ment and significant symptomatic improveimprove-ment initially

achieved in most patients with aortic stenosis following

per-cutaneous balloon valvuloplasty, this technique is severely

limited by the high incidence of restenosis The Beth Israel

group reported follow-up results in 170 patients (mean age

77 years) with symptomatic aortic stenosis who underwent

balloon aortic valvuloplasty between October 1985 and

April 1988.37The procedure was completed successfully in

168 patients, with significant improvement in aortic valve

area and gradient There were six in-hospital deaths and five

patients required early aortic valve replacement Follow up

averaging 9·1 months was available for all 157 patients

discharged from the hospital after successful valvuloplasty

In 44 patients (28%), recurrent symptoms developed a

mean of 7·5 months after the procedure: 16 were treated by

repeat valvuloplasty, 17 by aortic valve replacement and 11

with medical therapy Two patients had a second restenosis,

treated by aortic valve replacement in one case and by a

third valvuloplasty procedure in the other At latest follow

up 103 patients (66%) were symptomatically improved,

including 15 with restenosis who successfully underwent

redilation Twenty-five patients died after discharge, a mean

of 6 months after balloon valvuloplasty The most common

cause of death was progressive congestive heart failure

Repeat cardiac catheterization was performed in 35

patients in the Beth Israel follow-up cohort, including 21 with

recurrent symptoms, a mean of 6 months after valvuloplasty

Significant aortic valve restenosis was found in all 21 patients

with recurrent symptoms, and in eight of the 14 patients

Grade B

without symptoms If restenosis was assumed to haveoccurred in all 25 patients who died, and in all 44 patientswith recurrent symptoms, then the “clinical” rate of resteno-sis following valvuloplasty was 44% at only 9 months Theprobability of survival at 1 year was 74% for the entire studypopulation However, if both recurrent symptoms and deathwere considered as events, the probability of event-freesurvival at 1 year was only 50%

Similarly poor long-term results with high rates of earlyrestenosis were reported by both of the multicenter studies

of balloon aortic valvuloplasty Among the 492 patientstreated with balloon valvuloplasty in the Mansfield Registrythe 1 year survival rate was 64%, with an event-free survivalrate of only 43%.44 Among the 674 patients reported inthe National Heart, Lung and Blood Institute BalloonValvuloplasty Registry, survival at 1, 2 and 3 years was 55,

35 and 23%, respectively.45 Lieberman and colleagues46reported long-term follow up in 165 patients undergoingballoon aortic valvuloplasty The median duration of follow

up was 3·9 years, with follow up achieved in 99% ofpatients Ninety-three per cent of patients died or under-went aortic valve replacement, and 60% died of cardiac-related causes The probability of event-free survival,defined as freedom from death, aortic valve replacement orrepeat balloon aortic valvuloplasty at 1, 2 and 3 years afterballoon valvuloplasty, was 40%, 19% and 6%, respectively

By contrast, the probability of survival 3 years after balloonaortic valvuloplasty in a subset of 42 patients who under-went subsequent aortic valve replacement was 84%

of inflammatory response, compared to the slowly ing valvular calcification that initially led to the aortic stenosis, may explain the relatively rapid progression tosymptomatic restenosis following initially successful balloonvalvuloplasty

develop-predictors of event-free survival included pulmonary lary wedge and pulmonary artery pressures Although thepre- and postvalvuloplasty aortic valve area and aortic valvegradient were not associated with event-free survival, theper cent reduction in the peak aortic valve gradient was astrong predictor of long-term event-free survival Forpatients with a left ventricular ejection fraction of less than40% at baseline, improvement in the ejection fraction wasalso directly associated with event-free survival Notably,when patients aged 80 or older were analyzed as a sub-group, univariate analysis indicated that the predictors oflong-term event-free survival were the same in elderlypatients as in the entire patient cohort.

capil-In the stepwise multivariate analysis the only ent predictors of event-free survival following balloon aorticvalvuloplasty were the baseline aortic systolic pressure,the baseline pulmonary capillary wedge pressure (inverselyrelated), and the per cent reduction in the peak aorticvalve gradient A baseline aortic systolic pressure less than

independ-110 mmHg was associated with a relative risk of late events

of 2·03, and a baseline pulmonary capillary wedge pressuregreater than 25 mmHg was associated with a relative risk of1·73, compared to the risk in patients with a baseline aorticsystolic pressure greater than or equal to 140 mmHg and

a pulmonary capillary wedge pressure less than 18 mmHg,respectively Furthermore, a reduction of less than 40% inthe peak aortic valve gradient was associated with a relativerisk of late events of 1·75, compared to the risk in patients

in whom valvuloplasty produced a reduction of 55% ormore in the peak aortic valve gradient

To facilitate prediction of outcome following aortic

valvu-loplasty, using only information available prior to the

proce-dure, Kuntz and colleagues utilized the two independentbaseline hemodynamic predictors in the Cox model, andestimated the probability of event-free survival at 6, 12, 18and 24 months for all patients (Table 54.3) According tothis two-variable predictive model, patients with baselinepulmonary capillary wedge pressure less than 18 mmHg andaortic systolic pressure greater than or equal to 140 mmHg(the most favorable patient subgroup) had event-free sur-vival rates of 65% at 1 year and 41% at 2 years On the otherhand, patients with baseline pulmonary capillary wedgepressure greater than 25 mmHg and aortic systolic pressureless than 110 mmHg had event-free survival rates of only23% at 1 year and 4% at 2 years

In summary, Kuntz and colleagues found that the mostimportant predictors of event-free survival following balloonaortic valvuloplasty were factors related to baseline leftventricular performance, a finding confirmed by analysis oflong-term outcome in both large multicenter balloon aorticvalvuloplasty registries.44,45 The best long-term results fol-lowing valvuloplasty were observed in patients who wouldalso have been expected to have excellent long-term resultsafter aortic valve replacement In fact, comparison with the

Evidence-based Cardiology

Results of balloon aortic valvuloplasty

● Initial hemodynamic and symptomatic improvement

● Early restenosis, with recurrent symptoms

● No improvement in long-term survival or event-free

survival

Predictors of outcome following balloon

aortic valvuloplasty

Following recognition of the high incidence of

restenosis after balloon aortic valvuloplasty, attempts were

made to identify patient subsets more likely to derive

long-term benefit Kuntz and colleagues50 analyzed event-free

survival in 205 patients who underwent balloon

valvulo-plasty for symptomatic critical aortic stenosis They

evalu-ated 40 demographic and hemodynamic variables as

univariate predictors of event-free survival by Cox

regres-sion analysis, and attempted to identify independent

predic-tors of event-free survival by stepwise multivariate analysis

The rate of event-free survival, defined as survival without

recurrent symptoms, repeat balloon valvuloplasty or

sub-sequent aortic valve replacement, was 18% over a mean

fol-low-up period of 24 months (Figure 54.3) Direct predictors

of long-term event-free survival in the univariate analysis

included female gender, left ventricular ejection fraction,

and left ventricular and aortic systolic pressure Inverse

Grade B

Actuarial survival of unselected octogenarians

Actuarial survival after AVR

Actuarial survival after BAV Event-free survival

after BAV

0 6 12 18 24

Months Event-free

Figure 54.3 Actuarial total and event-free survival among

205 patients treated by balloon aortic valvuloplasty (BAV).

Shown for comparison are the actuarial survival rates among

unselected octogenarians in the United States and among

octogenarians who undergo aortic-valve replacement (AVR).

The numbers below the figure show how many patients were

alive or alive without an event at each follow-up (Reproduced

with permission from Kuntz et al 50 )

surgical data on aortic valve replacement in octogenarians

suggests that patients with good hemodynamic performance

have better survival after aortic valve replacement than after

balloon aortic valvuloplasty.19Among patients with poor left

ventricular performance or advanced heart failure,

event-free survival following balloon aortic valvuloplasty was

dismal and did not appear to improve the natural history

of untreated aortic stenosis.21 Therefore, even in elderly

patients with advanced heart failure and higher

periopera-tive risk,13aortic valve replacement may increase the

likeli-hood of long-term survival compared to balloon aortic

valvuloplasty In such high-risk patients, however, balloon

aortic valvuloplasty may have a role in providing transient

hemodynamic improvement, perhaps decreasing the risk of

subsequent aortic valve replacement

Repeat balloon aortic valvuloplasty

In patients who are not candidates for surgery

the development of restenosis following balloon aortic

valvu-loplasty can be managed with a repeat procedure Studies of

repeat valvuloplasty have shown that the absolute aortic

valve area tends to be slightly smaller both before and after

the repeat valvuloplasty, even when larger balloons or

balloon combinations are used.51 The incidence of repeat

restenosis remains high: follow up of the 47 patients in the

Mansfield Registry who underwent repeat valvuloplasty

showed that 66% of patients had died, undergone

sub-sequent valve replacement or required a third valvuloplasty

at a mean follow up of 5 months.52 Histologic study of

valves treated with balloon valvuloplasty, and excised prior

to subsequent surgery or examined at autopsy, has shown

active cellular proliferation within the splits in calcified

nod-ules, as well as foci of ossification.48These findings suggest

Grade B/C

an active scarring process in response to balloon plasty, which may explain the failure to achieve betterresults with the use of larger balloons, and raises the possi-bility that balloon-induced injury to the aortic valve mayaccelerate the natural history of aortic stenosis

valvulo-Aortic valve surgery after balloon aortic valvuloplasty

Most surviving patients who have undergoneballoon aortic valvuloplasty develop clinically significantrestenosis within 1–2 years of the procedure Many of thesepatients are subsequently treated with aortic valve replace-ment Johnson and colleagues at the Beth Israel Hospitalreported 45 patients (25% of the initial balloon valvuloplastycohort) subsequently treated with aortic valve replace-ment.53Three patients required emergency operation imme-diately after unsuccessful valvuloplasty, and the remaining

42 had an elective operation at a mean of 8 months ing valvuloplasty, primarily for the development of sympto-matic restenosis Despite the fact that the majority of thesepatients had initially undergone balloon valvuloplastybecause they were considered to be at high risk for surgery,there were only four hospital deaths among the 45 patients.Three additional patients died a mean of 11 months follow-ing surgery All surviving patients had persistent sympto-matic improvement following surgery

follow-Lieberman and colleagues at Duke reported 40 patients(24% of the initial balloon valvuloplasty treatment group)who subsequently underwent aortic valve replacement.54Only one patient (2·5%) suffered a perioperative death.The probability of survival 3 years from the date of the lastmechanical intervention was 75% for patients treatedwith balloon valvuloplasty and subsequent aortic valve

replacement, compared to only 20% for patients whose

restenosis was treated with repeat balloon valvuloplasty, and

13% for patients who had no further mechanical

interven-tion after developing restenosis The majority of surgically

treated patients remained asymptomatic at last follow up It

is important to note that this study is not a randomized

com-parison of treatment strategies for restenosis, and the results

must be interpreted in light of the probable selection bias

with regard to choice of management strategy for aortic

valve restenosis Nevertheless, it appears that in this group

of patients initially felt to be at high risk for aortic valve

replacement, surgery could be performed with an

accept-able operative risk Furthermore, as opposed to balloon

valvuloplasty, aortic valve replacement appears to offer a

reasonable chance of long-term freedom from symptoms

Although these reports do not specifically address potential

reduction in the risk of subsequent surgery by prior

per-formance of balloon valvuloplasty, a beneficial effect cannot

be excluded

Balloon aortic valvuloplasty v aortic

valve surgery

There are no randomized trials comparing

bal-loon aortic valvuloplasty with aortic valve replacement in

adult patients with critical aortic stenosis However, Bernard

and colleagues in France compared two non-randomized

matched series of patients with aortic stenosis treated with

either balloon aortic valvuloplasty or aortic valve

replace-ment at the same institution between January 1986 and

March 1989.55Forty-six patients were treated with balloon

aortic valvuloplasty and 23 with aortic valve replacement

with a bioprosthesis Baseline clinical and hemodynamic

parameters were similar in both groups; all patients were at

least 75 years old Follow-up was 22 months for the aortic

valvuloplasty patients and 28 months for those having

sur-gery Among patients treated with balloon aortic

valvulo-plasty, three patients (6·5%) died within 5 days of the

procedure, and an additional 24 (42%) died during

sub-sequent follow up, with 16 deaths being due to recurrent

heart failure Sixteen patients (35%) underwent subsequent

aortic valve replacement at a mean of 16 months following

balloon valvuloplasty At last follow up, only three

valvulo-plasty patients (6·5%) remained alive without subsequent

aortic valve replacement Of the patients treated with initial

aortic valve replacement, two (8·7%) died in the

periopera-tive period and an additional three (13%) died during the

follow up period All remaining patients (78%) were alive

and in New York Heart Association functional class I or II at

last follow up The overall survival rate following balloon

valvuloplasty was 75% at 1 year, 47% at 2 years and 33% at

5 years By contrast, survival following surgery was 83% at

1 and 2 years and 75% at 3 and 4 years Although selection

Grade B

bias cannot be excluded in this non-randomized case parison study, nevertheless the results strongly suggest thatpercutaneous balloon aortic valvuloplasty does not comparefavorably with aortic valve surgery in elderly patients withaortic stenosis

com-Specific indications for balloon valvuloplasty

Aortic valvuloplasty prior to non-cardiac surgery

Patients with severe aortic stenosis are atincreased risk for significant cardiac complications duringnon-cardiac surgery.56Three studies described the role of bal-loon aortic valvuloplasty in the management of patients withcritical aortic stenosis requiring major non-cardiac sur-gery.57–59 In these studies, 29 patients with critical aorticstenosis underwent balloon aortic valvuloplasty which wascomplicated by procedural death due to ventricular perfora-tion and tamponade in one patient Valvuloplasty resulted in

a significant improvement in aortic valve gradient and aorticvalve area Twenty-eight of the 29 patients underwent theplanned surgical procedure under general or epidural anes-thesia All but one patient had uncomplicated non-cardiacsurgery, with no significant congestive heart failure, hypoten-sion, myocardial infarction, arrhythmia or conduction abnor-mality either during or immediately after surgery Onepatient developed marked hypotension requiring transientintravenous pressor support during surgery for bowel carci-noma, resulting in interruption of surgery This patient subse-quently underwent aortic valve replacement and coronaryartery bypass graft surgery, followed by repeat bowel resec-tion Procedures performed successfully following palliativeballoon aortic valvuloplasty included aortic aneurysm repair,repair of hip fracture, exploratory laparotomy and thoraco-tomy However, the cited reports are not randomized orcase–control comparisons of preoperative balloon aorticvalvuloplasty versus aortic valve replacement or medicaltherapy, and do not test the hypothesis that routine balloonvalvuloplasty reduces the risk of non-cardiac surgery inpatients with critical aortic stenosis O’Keefe and col-leagues60 at the Mayo Clinic described 48 patients withsevere aortic stenosis who underwent non-cardiac surgery(including vascular, orthopedic and abdominal procedures)without preoperative balloon valvuloplasty There were nomajor perioperative complications in this group, who weremanaged with careful monitoring of systemic and pulmonaryartery pressure during anesthesia Therefore, the availableevidence suggests that balloon valvuloplasty prior to urgentnon-cardiac surgery may have greatest benefit in thosepatients with critical aortic stenosis and poor ventricular func-tion, heart failure or hypotension, in whom transient hemo-dynamic improvement may decrease the risk of perioperativecomplications

Grade B/C

Evidence-based Cardiology

Aortic valvuloplasty as a bridge to

aortic valve replacement

As noted earlier, many patients treated with

balloon aortic valvuloplasty subsequently undergo aortic

valve replacement Early series of such patients demonstrated

an acceptable operative risk and excellent surgical outcome,

with long-term freedom from symptoms in most

sur-vivors.53,54In contrast, recent reports of cardiac surgery in

octogenarians identified previous percutaneous aortic

valvu-loplasty as an independent predictor of hospital death

fol-lowing valve replacement.61,62 However, in most patients

undergoing surgery in these studies, valve replacement was

performed because of failure of the initial balloon aortic

valvuloplasty, which was not specifically used to stabilize

the patient for subsequent surgery

Smedira and colleagues63 studied critically ill patients

with aortic stenosis in whom balloon aortic valvuloplasty

was specifically used as a bridge to aortic valve replacement

They reported five patients with severe aortic stenosis,

mul-tiple organ failure and severe hemodynamic compromise

who were judged to be at excessive risk for aortic valve

sur-gery Balloon aortic valvuloplasty was used in these patients

to provide transient hemodynamic improvement, to improve

organ function, and to decrease the risk of subsequent

defin-itive surgical correction Following successful balloon aortic

valvuloplasty and clinical stabilization, subsequent elective

valve replacement was performed in all patients without

complications This report suggests that balloon aortic

valvu-loplasty may have a role as a bridge to subsequent aortic

valve replacement for patients in whom heart failure or

hypotension is so severe that the risk of primary aortic valve

surgery is unacceptable

Aortic valvuloplasty in cardiogenic shock

Of the 674 patients in the multicenter NHLBI

Balloon Valvuloplasty Registry, 39 (6%) had cardiogenic

shock The largest reported series specifically describing the

role of balloon aortic valvuloplasty in cardiogenic shock is

that of Moreno and colleagues from the Massachusetts

General Hospital

Moreno64studied 21 patients with critical aortic stenosis

and cardiogenic shock treated with balloon aortic

valvulo-plasty All patients had major associated comorbid conditions

precluding the use of emergency aortic valve replacement

The hemodynamic results were excellent, with an increase

in systolic aortic pressure from 77 to 116 mmHg and an

increase in aortic valve area from 0·5 to 0·8 cm2

(P 0·0001 for both comparisons) Cardiac index increased

from 1·84 to 2·24 l/min/m2 (P 0·06) Nine treated

patients died in hospital, two during the procedure and

seven following successful valvuloplasty Procedural

compli-cations were frequent, with five patients suffering vascular

complications and one patient each developing stroke,

Grade C

Grade B/C

cholesterol embolus and aortic regurgitation requiring aortic valve replacement Twelve patients (57%) survivedand were discharged from the hospital During follow up of

15 months, five additional patients died Actuarial survivalwas 38% at 27 months The only predictor of improved survival was the postprocedure cardiac index

In summary, the limited published data suggest thatemergency percutaneous balloon aortic valvuloplasty can besuccessfully performed in patients with critical aortic steno-sis and cardiogenic shock Morbidity and mortality remainhigh even after hemodynamically successful procedures.Given the poor long-term outcome in patients treated withballoon aortic valvuloplasty, its use in patients with cardio-genic shock should be considered a bridge to subsequentaortic valve replacement in those patients who improvesufficiently to undergo surgery at reasonable risk

Aortic valvuloplasty in patients with low output, low gradient

Patients with left ventricular dysfunction andaortic stenosis in the presence of low cardiac output and lowaortic valve gradient present a complex diagnostic and ther-apeutic challenge Aortic valve surgery is associated withincreased morbidity and mortality in such patients, a subset

of whom have irreversible myocardial dysfunction.10–12Balloon aortic valvuloplasty has been proposed as a diagnostictool in patients with aortic stenosis and low-output low-gradient hemodynamics, to distinguish those with reversiblemyocardial dysfunction due to abnormal loading conditionsfrom those with irreversible myocardial dysfunction It hasbeen suggested that patients with low-output low-gradienthemodynamics who have a significant improvement ineither ventricular function or symptoms following success-ful balloon aortic valvuloplasty are more likely to improvefollowing aortic valve replacement than those patients inwhom the former produces no significant benefit

Safian and colleagues studied 28 patients with a low leftventricular ejection fraction (mean 37%) and severe aorticstenosis who underwent balloon aortic valvuloplasty.42Onthe basis of response to balloon valvuloplasty they were able

to separate patients into a subset with progressive ment in left ventricular ejection fraction, and a subset whichshowed no significant change in left ventricular function.Nishimura and colleagues, utilizing data from the multicenterMansfield Aortic Valvuloplasty Registry, compared 67 patientswith low-output low-gradient hemodynamics against

improve-200 patients with a low cardiac index but not a low aorticvalve gradient.65 Patients with low-output low-gradienthemodynamics had less of a decrease in aortic valve gradi-ent after valvuloplasty, but a similar improvement in esti-mated aortic valve area However, actuarial survival at

12 months was 46% for these patients, as against 64% in the

comparison cohort (P 0·05) Furthermore, patients with

Grade B

Evidence-based Cardiology

low-gradient hemodynamics were less likely to show

sus-tained symptomatic improvement Therefore, as

long-term outcome after balloon valvuloplasty is poor in these

patients aortic valve replacement may be indicated

in those in whom balloon aortic valvuloplasty produces an

initial favorable response Although these reports suggest

that it may be possible to identify a subset of patients with

aortic stenosis and low-output low-gradient hemodynamics

likely to benefit from subsequent aortic valve replacement,

the hypothesis that response to aortic valvuloplasty predicts

subsequent outcome following surgery has not been tested

Other indications

Case reports have described the use of balloon

aortic valvuloplasty for the management of critical aortic

stenosis in pregnancy, documenting its safe performance

during pregnancy with subsequent normal births.66 Given

their age range, pregnant patients are more likely to have

congenital or rheumatic aortic stenosis and therefore to

have valve stenosis due to commissural fusion, which

responds more favorably to balloon dilation than does the

more frequently encountered degenerative calcific valvular

disease Use of balloon aortic valvuloplasty as a bridge to

subsequent cardiac transplant in a patient with aortic

steno-sis and end-stage heart failure has also been described.67

Indications for balloon aortic valvuloplasty

● Symptomatic critical aortic stenosis in patients who are

not candidates for aortic valve replacement

● Bridge to aortic valve replacement in patients with severe

hemodynamic compromise

● Prior to urgent non-cardiac surgery

● Aortic stenosis with low-output low-gradient

hemodynamics

Conclusions

The development and analysis of balloon aortic valvuloplasty

as a treatment strategy for adult patients with critical aortic

stenosis offers a paradigm for the investigation of new

thera-peutic techniques The initial enthusiasm for new treatment

modalities, often based on arguments of physiology, first

principles or small case series, is often replaced by a sobering

realization of limitations and complications, revealed by

care-ful prospective multicenter clinical trials, ultimately resulting

in the development of appropriate clinical indications for the

new treatment strategy The development and investigation

of balloon aortic valvuloplasty for aortic stenosis followed

just such a course and illustrates the impact of careful, early

prospective clinical trial data on the evolution and rapid

development of appropriate indications for new therapeutic

techniques

Grade C

Although valve replacement clearly improves morbidityand mortality in patients with symptomatic aortic stenosis,concern regarding the higher morbidity in high-risk subgroupsled to the investigation of balloon aortic valvuloplasty as analternative Early evidence from both single- and multicenterseries showing hemodynamic and symptomatic improvement

in most patients treated with balloon valvuloplasty, led to tial widespread enthusiasm for this new technique However,this enthusiasm was quickly tempered as subsequent follow

ini-up in these high-quality case series demonstrated a high rate

of hemodynamic and clinical restenosis, and failure of balloonvalvuloplasty to improve long-term or event-free survival.Critical evaluation of the data from these large case seriesprovided further understanding of the appropriate role ofballoon valvuloplasty in the management of patients withaortic stenosis When patients were stratified by the inde-pendent predictors of event-free survival, it became clearthat those who did best with balloon aortic valvuloplastywere acceptable candidates for valve surgery and had aneven better event-free survival following surgery On theother hand, patients with baseline profiles that indicated ahigh risk for surgery also did extremely poorly with balloonvalvuloplasty, with event-free survival that did not appear todiffer from the natural history of untreated aortic stenosis.The rapid accumulation and careful analysis of clinical trialdata on patients treated with balloon valvuloplasty quicklyestablished that the treatment of choice for adult patientswith symptomatic aortic stenosis is valve replacement, withballoon valvuloplasty being reserved for those in whom sur-gery is not possible or practical Further refinement of theappropriate therapeutic niche for balloon aortic valvulo-plasty has been aided by small case series targeted at specificindications for non-surgical therapy of aortic stenosis.The following guidelines on appropriate utilization ofballoon aortic valvuloplasty in adult patients with sympto-matic critical aortic stenosis are based on case series andcase–control studies, and therefore should be considered asGrade B recommendations

Based on the available evidence, balloon aortic plasty should be considered:

valvulo-1 For patients with symptomatic aortic stenosis whoare not operable, or who are poor candidates foraortic valve replacement owing to severe comorbidillness or advanced age in the presence of other sig-nificant predictors of surgical risk It should be empha-sized that advanced age alone in a patient withoutother significant surgical risk factors is not a contraindi-cation to aortic valve replacement It must be furtherstressed that the goal of balloon aortic valvuloplasty

in this patient group is transient symptomatic relief, asthere is no evidence that valvuloplasty improves sur-vival or provides long-term freedom from symptoms

Grade B

2 As a bridge to subsequent aortic valve replacement in

patients with advanced heart failure, hypotension or

cardiogenic shock, when clinical presentation suggests

excessive risk for an initial surgical strategy The goal of

balloon aortic valvuloplasty in this cohort is transient

hemodynamic improvement, leading to stabilization of

the patient for subsequent aortic valve replacement,

the only treatment shown to ultimately improve

long-term survival

3 For patients with critical aortic stenosis and poor

vent-ricular function, heart failure or hypotension who

require urgent or emergency non-cardiac surgery The

goal of balloon aortic valvuloplasty in this patient

subset is successful completion of the required

non-cardiac surgical procedure, with subsequent aortic

valve replacement for the underlying aortic stenosis

4 For patients with aortic stenosis, diminished left

ven-tricular function and low-output low-gradient

hemody-namics, in whom the response to initial “diagnostic”

balloon valvuloplasty may help identify those likely

to benefit from subsequent aortic valve replacement

Given the disparity in outcome between aortic valve

replacement and balloon aortic valvuloplasty in large

high-quality case series and non-randomized case–control

stud-ies, it is unreasonable to pursue randomized clinical trials

comparing these treatment strategies However, the

high-quality case series rapidly performed and reported in

patients treated with balloon aortic valvuloplasty not only

established the appropriate role for balloon valvuloplasty

in the treatment of aortic stenosis, but also confirmed

the value of prompt clinical investigation in the rapid

devel-opment of appropriate indications for new therapeutic

techniques When the goal of therapy is long-term or

symptom-free survival, the available clinical trial data clearly

support valve replacement as the treatment of choice for

aortic stenosis However, in patients who are not candidates

for or who refuse surgery, the trial data have demonstrated a

role for balloon aortic valvuloplasty, albeit with the more

limited goal of transient, palliative symptomatic relief,

with-out improvement in survival or long-term symptomatic

benefit

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Introduction

Percutaneous balloon mitral valvuloplasty is the latest

technique in an evolution that began with Elliot Cutler

advancing a knife retrograde through the apex of the left

ventricle of a beating heart in 1923.1Neither he nor Henry

Suttar, who performed a similar procedure in England two

years later received the expected accol ades,2and there has

been continuing dispute about the relative role of mitral

obstruction in defining the spectrum of mitral stenosis Sir

Thomas Lewis’ statement that valvotomy was based on an

erroneous idea, namely that the valve is the chief source of

the trouble3 has few proponents in the modern era and

relieving mitral obstruction is the de facto standard of care.

After a 20 year hiatus, the battlefield experience with

closed heart procedures in the second world war led to the

application of these techniques outside the trauma arena

Although early results were confounded by significant

mor-bidity and mortality, closed mitral valvotomy became a

rou-tine procedure for severe mitral stenosis, and is still the

treatment of choice in many parts of the world where the

dis-ease is endemic and medical facilities limited Large series4,5

have claimed good long-term results, but lack of systematic

follow up or comprehensive objective data obscure the actual

restenosis rate and survival In a Mayo Clinic retrospective

analysis6there was 79% 10 year and 55% 20 year survival rate

with reoperation in 34% by 10 years; however nearly a

quar-ter of patients were lost to follow up and severity of disease at

baseline could only be estimated Open commissurotomy

with the potential advantages of direct vision has supplanted

closed procedures in industrialized nations Controversy

remains as to its superiority7–9with the advantages of direct

vision favoring cases where thrombus is present

The percutaneous approach

A pediatric cardiac surgeon, Kanji Inoue, developed a

double lumen atrial septostomy balloon catheter made

of latex, with a mesh weave used to constrain the

bal-loon during inflation into the classic wishbone shape

depicted in Figure 55.1.10 He then adapted the device for

percutaneous balloon mitral valvuloplasty, demonstrated

under direct vision in the operating room its ability to split

fused mitral commissures11and performed the first procedure

in 1982.12

Mechanisms of valvuloplasty

The mechanisms responsible for the benefits of balloonmitral valvuloplasty13arise from the substantial radial forceexerted by the enlarging balloon.14This stretches the mitralannulus, has the capacity to split fused commissures, andoccasionally results in the cracking of calcifications Thestretching mechanism has been observed intraoperatively,15whereas the splitting of commissures16 and cracking of

Balloon valvuloplasty: mitral valve

Zoltan G Turi

Figure 55.1 The Inoue balloon during staged deployment.

From top to bottom: distal inflation with pullback against the valve; proximal inflation; full deployment (Reprinted with per- mission of the American Heart Association, Inc 38 )

calcifications have been demonstrated by direct observation

in excised valves.17The largely successful nature of balloon

mitral valvuloplasty is derived from commissural splitting;

bal-loon dilatation procedures where the other two mechanisms

predominate, such as balloon valvuloplasty for calcific aortic

stenosis, have less impressive short- and long-term results

Preprocedure evaluation

The most common reason for exclusion of patients is

unsuitable valve anatomy Specific relevant physical

exami-nation findings are diminution of the first heart sound (often

indicative of extensive subvalvular disease) and a

hyper-dynamic ventricle, suggestive of volume loading secondary

to mitral or aortic regurgitation, both of which are relative

contraindications to the procedure

Non-invasive methods

The echocardiographic findings of greatest predictive

value have been debated at length The standard,18 the

Wilkins-Weyman score, incorporates a scoring system for

mitral valve leaflet thickening, mobility and calcification, and

severity of subvalvular disease (Table 55.1), with a score of

8 described as an “ideal” patient population, and echo

scores over 12 potentially predicting poorer results The

correlation between this echo score and initial as well as

long-term results is only fair, perhaps because it is a

semi-quantitative system based on partly subjective assessments

and because other factors not included in the system havepredictive value Thus studies have alternately confirmed19–21

or refuted the predictive value of the Wilkins-Weymanscore.22–25One element of the score, leaflet mobility, corre-

lates more strongly with outcome (r value 0·67) than thecomplete score,26while another element, severe calcification

of the valve,27alone predicts a fourfold increase in cardiaccomplications and a 26% increase in 6 year mortality Inaddition important anatomic features that predict outcome,such as eccentricity of commissural fusion and a funnelshaped subvalvular apparatus28 (both negative predictors)are not included Neither are presence of moderate or severemitral regurgitation or left atrial thrombus, both relative con-traindications In univariate analysis, the scoring system doespredict long-term results,20but so do age, presence of atrialfibrillation,27and severity of stenosis before and after the pro-cedure.29 Further, multivariate analyses that included the

echo score but not its individual components, failed to

demonstrate a single preprocedure predictor of event freesurvival.30 Multivariate analysis that includes commissural

calcification did reveal this to be a strong predictor of death,restenosis, and mitral valve replacement.31Perhaps the mostcompelling reason for routinely deriving the echo score is toallow for comparison with known data; most mitral valvulo-plasty trials incorporate this or similar scoring systems.However, no absolute predictors of short- and long-term out-come have been developed

Routine, preprocedure, transesophageal echocardiographyhas been recommended because of its superiority for detec-tion of left atrial thrombus,32 as well as other structural

Table 55.1 Grading of mitral valve characteristics from the echocardiographic examination

1 Highly mobile valve with Minimal thickening just Leaflets near normal in A single area of increased

only leaflet tips restricted below the mitral leaflets thickness (4–5 mm) echo brightness

2 Leaflet mid and base Thickening of chordal Midleaflets normal, Scattered areas of

portions have normal structures extending up considerable thickening brightness confined to mobility to one third of the of margins (5–8 mm) leaflet margins

chordal length

3 Valve continues to move Thickening extending to Thickening extending Brightness extending into

forward in diastole, the distal third of the through the entire the midportion of the

4 No or minimal forward Extensive thickening and Considerable thickening Extensive brightness

movement of the leaflets shortening of all chordal of all leaflet tissue throughout much of the

in diastole structures extending ( 8–10 mm) leaflet tissue

down to the papillary muscles

Note The total echocardiographic score was derived from an analysis of mitral leaflet mobility, valvar and subvalvar thickening, and calcification which were graded from 0 to 4 according to the above criteria The total possible score ranges from 0 to 16.

Reprinted with permission from Wilkins GT, Weyman AE, Abascal VM et al Percutaneous balloon dilation of the mitral valve: an analysis of echocardiographic variables related to outcome and the mechanism of dilation Br Heart J 60:299–309 © 1988 by the BMJ Publishing Group 18

abnormalities including vegetations or ruptured chordae.

The case is most compelling in patients predisposed to clot

formation such as those with spontaneous echo contrast

(“smoke”) on surface echocardiography and those with atrial

fibrillation The former was an independent predictor of left

atrial thrombus in a prospective study of 100 patients.33

Cardiac catheterization

Cardiac catheterization prior to balloon commissurotomy is

rarely necessary in young patients, but can be beneficial to

exclude coronary artery disease in older subjects The

gradi-ent alone is a poor proxy for assessmgradi-ent of severity of

disease pre-valvuloplasty since it can lead to overestimation

of disease with poor heart rate control or underestimation

in patients who have not had fluids for many hours prior

to catheterization

Contraindications

While the usually cited contraindications are left atrial

thrombus, greater than mild mitral regurgitation and severe

calcification or subvalvular disease, these were largely

empirically derived and can be challenged

Thrombus

Hung34 and others have described at least three series

exceeding 90 patients total with apparent organized left

atrial appendage clot who underwent uncomplicated balloon

commissurotomy However, valvuloplasty is not attempted

when there is left atrial thrombus along the septum, free in

the cavity, or on the surface of the valve Using the

conserva-tive approach preferred by most interventionalists, Kang

reports successful resolution of left atrial thrombi with

warfarin therapy followed by balloon commissurotomy.35

Mitral regurgitation

The general presumption that valvuloplasty in patients with

moderate or greater mitral regurgitation carried a high risk has

not been prospectively tested; however, there have been two

retrospective evaluations A comparison of 25 patients with

moderate mitral regurgitation and 25 age and gender matched

patients with mild or no regurgitation did indeed demonstrate

an increase in severe insufficiency post procedure; however,

these patients had much higher echo scores and twice as

fre-quently had severe calcification.36Further, while 20% of those

with initially moderate mitral regurgitation developed severe

regurgitation, hemodynamic improvement overall was similar,

as was the incidence of post procedure mitral valve

replace-ment Similarly, patients with mild mitral regurgitation also

had less favorable anatomy at baseline and had lower event

free survival but a similar success rate.37Thus, the evidencesuggests that balloon commissurotomy can still be consideredfor these patients if they are poor risks for heart surgery.Nevertheless, a theoretical disadvantage is additional volumeloading of the left ventricle when antegrade flow is improvedafter balloon commissurotomy, a concern in the presence ofaortic regurgitation as well

Severe calcification

Patients with symmetrical severe calcification may notrespond at all to balloon commissurotomy;22,38those withasymmetric calcification are prone to leaflet tearing or rupture.28While high echo score alone does not predict theoccurrence of severe mitral regurgitation,39one component,severe calcification, does.40Nevertheless, when the risk ofsurgery is prohibitive, growing experience with predomi-nantly elderly patients with high echo scores and poor overall morphology has shown moderate improvement

in hemodynamics and palliation of symptoms at the cost ofhigh morbidity and mortality.41

Procedure

Antegrade v retrograde approaches

The predominant approach to percutaneous balloon mitralvalvuloplasty is the antegrade transseptal approach Thetechniques include single cylindrical balloon, Inoue, doubleand trefoil balloons, as well as monorail and metal valvulo-tomes Inoue and the double cylindrical balloon methodsaccount for virtually all mitral valvuloplasties performed.The procedure has also been performed retrograde.42–44Theadvantages include avoidance of transseptal puncture; how-ever large devices are introduced into the femoral artery andballoons are passed across the submitral apparatus withoutballoon flotation (increasing the risk of catheter entrap-ment) There are no direct comparison studies betweenantegrade and retrograde techniques

Inoue technique

The Inoue balloon’s principal features are: a modifiable distaltip with reduced profile for transseptal passage, a nylon meshcovering that allows the balloon to straddle the mitral valve,and a compliance curve that allows the balloon to dilate over

at least a 4 mm range of sizes (Figure 55.1) A stepwiseapproach involves evaluating the patient, typically by echocar-diography, between each balloon inflation to assess forimprovement and detect presence of increasing mitral regur-gitation If improvement is suboptimal and regurgitation hasnot occurred/increased, the size is typically increased by 1 mmincrements In reviewing 19 series reporting results of Inoue

Evidence-based Cardiology

valvuloplasty, we noted a reported early success rate of 93%

in a total of 7091 patients.45,46Success was variably defined

and in some reports overlapped with severe mitral

regurgita-tion, atrial septal defect or embolic events, but included a

doubling of the valve area in most studies

Cylindrical balloon techniques

The cylindrical balloon technique, introduced in 1985,47

did not uniformly result in adequate gradient reduction and

gave way to a double balloon method.48A stepwise dilation

technique is also used with progressively larger balloons

placed side by side until adequate gradient reduction is

obtained or an increase in mitral regurgitation is noted The

results of 12 studies incorporating 1864 patients reported

a 90% overall success rate

Long-term follow up

In an extraordinary series of 4832 patients across 120

cen-ters in China, Chen and colleagues have claimed that 98·8%

of patients were in NYHA functional class I or II at a mean 32

months follow up, 99·3% success rate, and virtually no

com-plications.49Restenosis was reported as 5·2% over a mean

32 months follow up While there were likely problems with

data gathering, the evidence from multiple studies of high

success and low complication rates in patients with favorable

anatomy is consistent.20,50 Less favorable long-term results

were reported by Cohen et al51for 145 patients followed for

a mean of 3 years Their 5 year event free survival was only51% (freedom from mitral valve replacement, redilation, ordeath); however, a high percentage of their patients had unfa-vorable anatomic features In general, these descriptive serieshave suffered from incomplete follow up, non-overlappingend points, and lack of serial hemodynamic measurementsfor assessing hemodynamics and restenosis

Single v double cylindrical balloons

The disadvantages of single balloons are related to the drum of a round balloon in an elliptical orifice – resulting inlower gradient reduction Although no randomized compar-isons were made, and much of the data are from sequentialindividual operator series, or sequential inflations with singlefollowed by double balloons, the latter appears to be superior

conun-in retrospective comparisons (Figure 55.2)52–54as well as in

an in vitro study.55The increased lateral force exerted by twoballoons is one presumed mechanism for the superior split-ting of the laterally directed commissures However, a com-parison of effective balloon dilating area to body surface areashowed that a large single balloon could have similar hemo-dynamic benefits as two smaller balloons Thus, geometry isnot the sole determinant

mmHg

0

Figure 55.2 Single v double balloon mitral valvotomy Note the initial modest reduction of gradient from baseline (A) after single

balloon commissurotomy (B), with near complete resolution of gradient after double balloon inflation (C) (Reprinted with permission

of the American Heart Association, Inc 115 )

Evidence-based Cardiology

Inoue v double balloon (Table 55.2)

The Inoue technique’s principal advantages are simplicity

and short procedure times The Inoue balloon differs from

cylindrical single balloons because of the unique balloon

design The slenderizing feature that facilitates septal

pas-sage and the dumb-bell shape of the inflated balloon have

been reported by some to result in a lower incidence of

atrial septal defect ( 2·5% v up to 10% for the double

balloon technique)56and a much lower likelihood of

cata-strophic apical perforation

In a prospective randomized comparison between Inoue

and double balloon valvotomy, no significant differences

were noted in immediate results, including complications.57

A trend toward fewer atrial septal defects with the Inoue

balloon was not significant Because of a lack of other

prospective randomized comparisons by physicians equally

experienced at both techniques, questions remain

unan-swered It is likely that an easier procedure with lower

com-plication rates (the Inoue technique) is a trade off for slightly

greater mitral regurgitation,25,58possibly because the distal

portion of the balloon is oversized and may traumatize the

subvalvular apparatus There are also suggestive data that

the double balloon technique, by virtue of the lateralization

of forces, is advantageous in less favorable anatomy One

example is the result of dilation of asymmetrically fused

commissures – where the Inoue technique has been used

this led to significant risk of severe mitral regurgitation,59

whereas with double balloon technique use this appeared to

be less of a problem.60The disadvantages of the two balloon

technique include longer procedure times, and higher risk

of left ventricular apical perforation61–64although the higher

complication rates reported61,65 may also reflect operatorexperience with this more complex procedure

Other techniques

Percutaneous metal mitral commissurotomy is a promisingnew technique being adopted primarily in a number of developing countries; a series of 153 patients was described byits inventor, Alain Cribier.66The device, essentially a Tubbsdilator mounted on a cable, is introduced via the right femoralvenous approach and can be opened to a maximum of 40 mm.Initial results are encouraging; in particular, what appear to berelatively high postprocedure valve areas (2·20·4cm2)and low rates of mitral regurgitation (severe mitral regurgi-tation in 1%) Randomized trials comparing this technique

to balloon dilatation have not yet been published althoughseveral smaller studies have been completed The metal-lic head of the device, the most expensive component, is theoretically resterilizable by autoclaving: a potential advan-tage in parts of the world where mitral stenosis is endemicand the cost of disposables prohibitive

Additional data on the retrograde non-transseptal nique previously described by Stefanadis and colleagueshave been reported67for the first time from multiple investi-gational sites Long-term (up to 9 years) results are relativelycomparable to antegrade techniques However, significantrates of severe mitral regurgitation (3·4%) and of femoralartery injury (1·1%), as well as a relatively modest successrate (88%) in the setting of favorable echocardiographyscores (7·7 2·0), suggest that this procedure might best

tech-be reserved for patients where transseptal puncture has

Grade B Grade B

Table 55.2 Comparative results of valvuloplasty techniques

a Study by Park et al was randomized

Abbreviation: MVA, mitral valve area in cm2

unique contraindications Because of the learning curve

associated with this procedure, and the fact that most

patients are amenable to the antegrade approach, the

long-term role of this technique is uncertain Similarly, a series of

antegrade Inoue balloon valvuloplasties via a jugular venous

route had a significant associated complication rate, but

rep-resents another alternative approach.68 Finally, Bonhoeffer

and colleagues have described a monorail double balloon

technique that has potential cost advantages and simplifies

the standard double balloon technique; no formal

compari-son to other techniques has been performed.69

Intraprocedural transesophageal

echocardiography

Use of transesophageal echocardiography during balloon

mitral valvuloplasty has been recommended for early

detec-tion of major complicadetec-tions (severe mitral regurgitadetec-tion,

tamponade, and large atrial septal defect).70 In addition,

transesophageal echo can confirm needle location during

transseptal puncture.71 Finally, decreased procedure time,

mitral regurgitation, and residual atrial septal defects have

been described in a randomized study of fluoroscopy plus

transesophageal echo versus fluoroscopy without echo during

balloon commissurotomy.72The evidence provided by these

three studies is not compelling The latter included a 60% rate

of major complications in the non-echo group, suggesting

lim-ited experience Surface two-dimensional echocardiography is

sensitive enough to detect increasing mitral regurgitation in

most patients, and is an excellent tool for early appreciation of

tamponade Atrial septal defects are becoming substantially

less common and are largely limited to 5 mm or smaller and

resolve post procedure Finally, transseptal puncture in

experi-enced hands has limited risk; arguably the procedure should

not be performed by those who need transesophageal echo

guidance Intracardiac echo using a transducer placed via the

femoral vein may be an alternative but has not yet been tested

systematically in this setting

Complications

The learning curve is steep, which has had a major effect

both on success and complication rates,73as well as skewing

data in the literature.56 The National Heart Lung Blood

Institute (NHLBI) registry reported substantially lower rates

of all major complications except acute mitral regurgitation

at centers performing more than 25 cases and in the second

year that sites enrolled patients; a willingness to attempt

bal-loon commissurotomy in higher-risk subsets in the second

year may explain the mitral regurgitation A recent report

compares the first 100 cases of Inoue balloon dilatation

ver-sus a subsequent 133 cases, all by the same high volume

operator with extensive prior double balloon experience.The postprocedure valve area, overall success rate and complication rates were significantly improved beyond

100 cases.74 It is likely that the best interests of patientsundergoing the procedure would be served by having relatively few centers perform higher volumes

Overall mortality has been approximately 1%, most commonly related to tamponade not only from transseptalcatheterization75but also from fenestration of the left ventric-ular apex, in particular by the cylindrical balloon technique.The incidence of tamponade has ranged from 2% to 4%,severe mitral regurgitation from 1% to 6%, and cerebral vascular accident and/or thromboembolism in up to 4%.Disturbingly, magnetic resonance imaging detected newhyperintensitivity foci suggestive of cerebral infarcts in 11 of

27 patients.76All had been evaluated before their procedure

by transesophageal echocardiography without detection ofclot Thus, embolization may be common even if not clinicallyapparent The probable sources are intracavitary clot, catheterinduced thrombus formation and showers of calcium

Atrial septal defects were a significant source of earlycomplications,76arising from transseptal tearing secondary

to inadvertent proximal deployment of cylindrical balloons,withdrawal of winged balloons retrograde, or trauma to theseptum from 5 or 8 mm balloons used to dilate the septum.Theoretically these problems should be avoidable by use of

a dilator and a shorter balloon system, both features of theInoue technique, and indeed this has been the finding.77Itshould be noted that decompression of the left atrium by asignificant sized post procedure atrial septal defect may haveinfluenced the results of some balloon valvuloplasty seriesand may lead operators to overestimate the mitral valve areapost procedure.78

Predictors of outcome

Predictors of outcome were addressed in a number of randomized prospective and retrospective analyses Factorspredicting poorer functional class, hemodynamics, overalland event free survival were found to include age, presence ofatrial fibrillation, valvular calcification, and postprocedureresults, with event free survival at 6–7 years ranging from 15%(unfavorable baseline anatomy) to 83%.79–81Although thesestudies were not randomized, they incorporate a broaderspectrum of patients with mitral stenosis than the random-ized trials, and may represent a more “real world” assessment

non-of results to be expected in the overall population

Additional attention was focused on predictors of adverseoutcome, in particular mitral regurgitation Age and severity

of mitral stenosis,82 and degree of anterior leaflet tion83 correlated with postprocedure insufficiency Thenature of pre- and postprocedure mitral regurgitation wascarefully studied in 50 patients.84 As previously noted,

retrac-described a 10-fold increase in restenosis rates at 5 years forpatients with prior commissurotomy100 (both to approxi-mately 20%) Most significant is the finding by Jang and colleagues that stratification by echo score resulted in

nearly superimposable results for de novo and repeat

commissurotomy procedures, suggesting that results aredefined by valve morphology rather than history of priorcommissurotomy.98

Bioprosthesis

Several case reports have described successful balloondilatation of bioprosthetic mitral valves, although both thehemodynamic and longer term benefits were obscure in allbut one.101–103However, bioprosthetic valves are typicallysimilar histologically to those seen in calcific aortic stenosis:severe leaflet thickening, immobility and calcification, with-out commissural fusion.104,105 Thus, a formalintraoperative study, examining the morphology of severelystenosed bioprosthetic valves before and after balloon dila-tion, revealed “completely ineffectual” dilation106with sub-stantial leaflet tearing and cuspal perforation Although theneed for a percutaneous approach to the problem is great,the data do not support bioprosthetic mitral valve dilation

Balloon v surgical commissurotomy

Randomized trials comparing balloon and surgical surotomy were begun early in the development phase of thepercutaneous technique Because both use blind dilation ofthe valve with blunt instruments, and because closed com-missurotomy was the predominant procedure in countrieswhere mitral stenosis was prevalent, the early randomizedtrials compared balloon and closed commissurotomy Inthese studies, surgeons were typically more experiencedthan the operators performing balloon valvuloplasty In

commis-1988 we randomized 40 patients with relatively idealanatomy and severe mitral stenosis;107these patients havebeen followed with serial catheterization and echocardiogra-phy over a 7 year period; there were similar hemodynamicimprovements in both groups, sustained through 7 years(Figure 55.3), with one late death in each group and need forrepeat commissurotomy in 20%.108 The actual restenosisrate (26% in the balloon group and 35% in the surgicalgroup) as defined by a 50% loss of the gain and a valve area 1·5 cm2 is significantly higher than the repeat commissurotomy rate because restenosis and functionalclass do not correlate strongly Thus it is likely that resteno-sis rates in trials that have not done formal follow up hemo-dynamics underestimated the true severity of disease duringfollow up Two other studies have compared balloon andclosed commissurotomy with shorter, non-invasive follow

Grade B Grade B

Evidence-based Cardiology

severe mitral regurgitation is typically due to leaflet tearing,

while most new mitral regurgitation is typically

pericommis-sural in origin In addition to anatomic predictors, the steep

compliance curve of the Inoue balloon was reported as a

likely culprit for severe mitral regurgitation.85Use of balloon

sizes in the upper portion of the pressure-volume curve was

associated with increased mitral regurgitation; whether this

finding, based on retrospective observation, is truly causal is

unproven, but has been the subject of numerous anecdotal

reports and several abstracts Previous observations that

patients with prior surgical commissurotomy have

satisfac-tory but inferior results were again confirmed.86,87

Perhaps the most comprehensive analysis of outcome

was a recently published follow up of up to 15 years in

879 patients Severe postprocedure mitral regurgitation,

echo score 8, age, prior surgical commissurotomy, NYHA

functional class IV, moderate preprocedure mitral

regurgita-tion, and elevated pulmonary artery pressures

postproce-dure were identified as independent predictors of adverse

events at long-term follow up.88

Valvuloplasty for mild mitral stenosis

Several studies have looked retrospectively at the results

of balloon valvuloplasty for patients with valve areas of

1·3–1·5 cm2.89,90 While historical comparisons suggest

greater valve area increase than in patients with severe

mitral stenosis, there is no evidence that the risk of

occa-sional mortality, need for mitral valve replacement or other

major morbidity warrants this approach The possibility that

early commissurotomy may adversely affect the course of

the disease, including progression to pulmonary

hyperten-sion, atrial fibrillation and stroke remains a hypothesis in

need of prospective investigation.91

Pregnancy

There have been multiple reports of successful balloon

com-missurotomy during pregnancy.92–94The procedure has been

performed with echo guidance and without fluoroscopy95to

avoid radiation exposure to the fetus

Dilation for restenosis

Reoperation for mitral valve stenosis has long been

associ-ated with increased morbidity and mortality.96Several large

balloon commissurotomy series have reported inferior

over-all results compared to de novo dilatation Davidson reported

less symptomatic improvement97while Jang described a 20%

lower success rate (only 51% having valve area 1·5 cm2)

and nearly 20% requiring mitral valve replacement by

4 years.98Cohen described twice the frequency99and Medina

Grade B Grade C

up only; these have demonstrated balloon results superior

to73 or similar to closed commissurotomy.109 However

closed commissurotomy in the former study resulted in only

a 1·3 cm2 mean valve area, suggesting relatively

unaggres-sive dilation Finally, a randomized comparison by Ben

Farhat and colleagues described superior acute results

(2·2 0·4 cm2 v 1·6 0·4 cm2) for balloon valvuloplasty

and 4 year restenosis rate of 7% v 37%.110 Thus balloon

commissurotomy is at least equal and probably superior to

closed surgical commissurotomy Grade A

Figure 55.3 Mitral valves areas at baseline and each follow up

interval over 3 1 years in patients randomized to percutaneous

balloon or surgical closed mitral commissurotomy 108 Asterisk

denotes P  0·001 compared with baseline.

Open commissurotomy v balloon

The hypothesis that open commissurotomy would be

supe-rior to balloon valvuloplasty was based on the potential

benefits of direct vision, including surgical splitting and

remodeling of the subvalvular apparatus, neither of which

are features of closed or balloon commissurotomy A

pro-spective series of 100 open commissurotomy patients

gathered data specifically for historical comparison to the

then reported results of balloon valvuloplasty and concluded

that open commissurotomy was distinctly superior.111The

results of surgery, mean valve area 2·9 cm2, exceeds

expec-tations and may be related to technique of measurement112

or patient selection, while mitral regurgitation was absent in

all but eight cases (where it was reported to be mild), results

also testimony to great operator skill but in excess of prior

reports.8 On the contrary, the more compelling

evidence from prospective randomized studies is for similar

or superior results with balloon commissurotomy In 1989

we randomized 60 patients to a prospective comparison of

balloon versus open commissurotomy.113Patients had near

identical baseline hemodynamics but those undergoing

bal-loon commissurotomy had superior mitral valve areas at 3

years (Figure 55.4) A possible explanation for superior

results in balloon commissurotomy patients is the direct and

Grade A

continuous feedback to the operator of hemodynamics during catheterization laboratory procedures, which evenwith the advent of transesophageal monitoring in the operating room is not available to the same degree to thesurgeon

In the trial referred to earlier, Ben Farhat and colleaguesreport a three-way randomized comparison of balloon,closed and open surgical commissurotomy in 90 patients.110Most of the objective information is through 6 month follow

up, although clinical status/events and valve areas aredescribed through 7 years Their results, which include anabsence of mortality, NYHA class I function in 90% of theballoon and open mitral commissurotomy (OMC) patients,and residual valve area of 1·8 cm2 in these two groups at

7 years with only 7% restenosis, are exceptionally optimistic.The results of closed commissurotomy were distinctly inferior Because functional class correlates poorly withhemodynamics in mitral stenosis and because planimetry,the technique used here for mitral valve area assessmentbeyond 6 months, is subjective when the commissures areopen (and was not performed by blinded investigators), thefindings of this study need to be confirmed Less optimisticdata, utilizing hemodynamics and blinded interpretation, sug-gest that restenosis rates may be 25% by 7 years even inpatients with relatively ideal valve anatomy preprocedure.114Nevertheless, this paper confirms that balloon valvuloplasty

is at least as effective as open commissurotomy for patientswith severe mitral stenosis and ideal valve anatomy

outcome, balloon commissurotomy, at the cost of higher risk

in patients with unfavorable anatomy, still has the potentialfor palliation The safety and efficacy of Inoue and doubleballoon valvuloplasty are not compellingly different in expe-rienced hands and the selection of techniques should bebased on operator preference, experience, and equipmentavailability Low cost, avoidance of thoracotomy scar and dis-comfort, shorter hospitalization and excellent follow upresults to date mandate consideration of balloon valvulo-plasty in most patients with rheumatic mitral valve stenosiswithout significant contraindications Since balloon as well

as surgical commissurotomy are largely palliative procedures,percutaneous balloon valvuloplasty has the added benefit ofdelaying the time until eventual thoracotomy

In summary, percutaneous balloon mitral valvuloplasty is asuperior alternative to surgical commissurotomy for a signifi-cant subset of patients with rheumatic mitral stenosis Carefulcase selection and performance of the procedure by experi-enced teams will have a significant impact on outcome Bothclinical and financial considerations suggest that balloonvalvuloplasty is the procedure of choice for rheumatic mitralstenosis in patients with suitable anatomy

Key points

● Ideal patients have severe mitral stenosis without:

mild mitral regurgitation, severe subvalvular disease,

or severe calcification eccentric commissural fusion, clot in left atrium, volume loaded left ventricle

● Procedure may be of benefit in:

critical mitral stenosis, but evidence for favorable long-term risk–benefit ratio is lacking

patients with unfavorable anatomy, including moderate mitral regurgitation, but with less favorable results and higher morbidity/mortality

patients with mitral restenosis, dependent on anatomic features

pregnant patients

● Balloon valvuloplasty is superior to closed tomy and is equivalent or superior to open commissuro- tomy in ideal patients

4.John S, Bashi VV, Jairaj PS et al Closed mitral valvotomy: early

results and long-term follow-up of 3724 consecutive patients.

Circulation 1983;68:891–6.

Grade A Grade A

Evidence-based Cardiology

The study’s optimistic findings may perhaps in part be due to

a distinguishing feature of all of the randomized comparisons

of balloon versus surgical commissurotomy: single site

stud-ies that depend to a significant degree on individual

physi-cian practices and small patient populations

Cost

Although formal cost comparison studies have not been

reported, charges and costs at hospitals in India and in the

United States have been estimated Lau and Ruiz described

cost to a United States hospital of $3000 for balloon

valvu-loplasty and $6000 for closed commissurotomy (assuming a

hospital could be found that still performs this procedure)

We published 1991 charges for balloon and closed

commis-surotomy in the United States and India (Figure 55.5) and

demonstrated a sixfold greater expense for balloon

valvulo-plasty in India However, our calculations did not include

the extensive reuse of disposables in developing countries,

where balloons can account for a much higher portion of the

charges than physicians’ fees or operating room billings

Percutaneous metallic commissurotomy, as referred to earlier,

may also have a significant impact on cost considerations

The results of the randomized trials offer compelling

evi-dence that balloon valvuloplasty is an effective alternative to

surgery for patients with good valve anatomy Even with

a number of anatomic features predicting less favorable

Grade A

India

Room charges ICU

Cath lab/

operating room

Physician’s fee

Anesthesia

Disposables 14

Figure 55.5 Charges for percutaneous balloon mitral

valvulo-plasty (PBMV) and closed surgical commissurotomy (CMC) at

the Nizam’s Institute of Medical Sciences in Hyderabad, India

and at Harper Hospital in Detroit, MI in 1991 With the

exten-sive reuse of disposables in developing countries, the cost of

balloon valvuloplasty more closely approximates that for closed

commissurotomy (© 1993, F.A Davis Co Reprinted with

permission 116 )

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