(Circulation. 2000;102:IV-24.)
© 2000 American Heart Association, Inc.
Special Anniversary Issue |
From the Griffith Center, Division of Cardiology, Department of Medicine, Los Angeles County and University of Southern California Medical Center, Keck School of Medicine of the University of Southern California; and the Division of Cardiology, Department of Internal Medicine, Mayo Clinic and Foundation, Mayo Medical School, Rochester, Minn.
Science is about the systematic collection of data and the interpretation of that data. Dr Stanley B. Prusiner 1997 Nobel Laureate in Physiology/Medicine
Era Before 1950
In 1950, rheumatic valvular heart disease (VHD) was the most common cause of VHD. The link between streptococcal infection and rheumatic fever was established, and a successful trial of penicillin prophylaxis against rheumatic fever was reported.1 In 1944, Jones published a seminal article on diagnosis of rheumatic fever.2 The American Heart Association (AHA) and Circulation played an important role in communicating the importance of (1) penicillin prophylaxis, which resulted in a dramatic reduction of rheumatic fever and rheumatic VHD, and (2) diagnosis of rheumatic fever, by revising the Jones criteria in 1956, 1965, 1984, and most recently in 1992.3
It was well recognized that the mitral valve was the valve most commonly affected in rheumatic heart disease. As a consequence, closed-chest mitral commissurotomy for mitral stenosis (MS) was the most common early and successful cardiac surgical intervention. 1950 was the first year of Circulation, and one of the articles published that year described the surgical experience in 8 patients.4
The etiology of mitral regurgitation (MR) in 1950 was rheumatic carditis; mitral valve prolapse (MVP) was not even recognized. As late as 1958, the following quote reflects the lack of recognition of MVP: "mid- and late systolic clicks are commonly produced by the tensing of pleuropericardial adhesions"; thus, MVP was considered to be of extracardiac origin.5
Circulation in 1950 had a smaller number of articles regarding VHD than one might expect. Some of the articles are of interest: (1) There were several articles on subacute bacterial endocarditis. One of these included the Lewis Conner Lecture by Bloomfield, "The Present Status of Treatment of SBE."6 (2) Levinson et al7 discussed the "Increasing Bacterial Resistance to the Antibiotics ... ," a recurring theme in todays literature.7 (3) The absence of noninvasive diagnostic imaging and hemodynamic assessment of VHD is striking. Also, the limitations in surgical therapy of congenital VHD before the development of open-heart surgery are obvious. An example of these 1950 realities is provided by Engle and Taussigs article,8 which includes the early use of cardiac catheterization and angiocardiography to differentiate between tetralogy of Fallot and valvular pulmonary stenosis in other settings. This represented a critical distinction in those days before open-heart surgery. The former was treated with a Blalock-Taussig anastomosis, and the latter was treated with closed pulmonary valvotomy. (4) There were several articles on cardiac catheterization and other efforts to enhance diagnosis of VHD. These included one of the first articles on left heart catheterization via the retrograde crossing of the aortic valve.9 (5) There was a study of the electrokymograph in analysis of aortic and pulmonary valve regurgitation.
A common cause of isolated severe aortic regurgitation (AR) in 1950 was tertiary syphilis.10
In summary, the state of knowledge in 1950 included (1) detailed and remarkably accurate bedside clinical descriptions and increasing understanding of the natural history of VHD; (2) an understanding of the pathogenesis of rheumatic fever, its diagnosis, and effective prophylaxis of rheumatic heart disease; and (3) recognition of the need to improve diagnostic precision in anticipation of the future development of open-heart surgery. In fact, it is the successful implementation of open-heart surgery that forced improvements and refinements in all aspects of cardiovascular medicine and surgery.
Era 1950 to 2000
Julius Comroe Jr emphasized that breakthroughs in
medicine are a culmination of advances in many different areas
(Figure 1
).11
Thus, it is our goal to "walk through" succinctly how we have
arrived in 2000 at a very advanced state in treatment of
VHD.
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Prophylaxis for Recurrences of Rheumatic
Fever
A randomized trial of 405 children was started in 1954
in Irvington
House12 ; the final
6-year data are shown in Table 1
. The recommendations of the AHA for
prophylaxis of recurrences of rheumatic fever are the standard of
practice in the United States
(Table 2
).13
The AHA has also contributed in a major way by continuously providing
updated educational materials and also by continued revisions of the
recommendations for prophylaxis against bacterial
endocarditis.14
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Invasive Studies
In a seminal article, Gorlin and
Gorlin15 used
information derived from hydraulic systems to derive the following
equations:
![]() |
The MVA equation was revised by
Gorlin16 :
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These equations have stood the test of time and are the standard for assessment of severity of valve stenosis.
This led to a series of attempts to measure left atrial and left ventricular (LV) pressures directly. The transseptal technique developed by Ross17 (subsequently an editor in chief of Circulation, 1988 to 1992) is still in use, particularly in patients with MS undergoing catheter balloon commissurotomy (CBC) and in selected patients with aortic stenosis (AS) and mitral/aortic prosthetic valves. The use of a systemic arterial site for retrograde entry into the LV, accelerated by percutaneous entry into a systemic artery (Seldinger technique),18 facilitated the performance of aortic and LV angiography, which was essential for assessment of AR/MR and calculation of LV volumes and ejection fraction (EF).19 The percutaneous technique later led to the development of the Judkins technique20 for coronary arteriography, which largely replaced the pioneering Sones technique,21 which had used the cut-down technique for arterial entry.
These diagnostic invasive techniques are still the bedrock for assessment of severity of VHD in many patients and assessment of extent and severity of associated coronary artery disease.
Valve Surgery
In 1951, Bailey reported closed transventricular aortic
valve commissurotomy for
AS.22 This produced
significant AR and was abandoned altogether after heart valve
replacement (VR) was developed.
After Baileys and Harkens efforts at closed mitral commissurotomy in the late 1940s, transatrial and transventricular dilation in the 1950s improved the results that were obtained.
In 1954, John Gibbon, Jr described the use of total
cardiopulmonary bypass for intracardiac
surgery23
(Figure 2
), which had an enormous impact on and
completely changed the performance of valve surgery.
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In 1956, Lillehei performed successful open mitral commissurotomy. With experienced and skilled operators, the long-term results of closed and open mitral commissurotomy in appropriate patients are similar when the baseline patient characteristics are the same.24
Also in 1956, Lillehei and associates performed open annuloplasty for severe MR.25 However, largely because of the report of Carpentier in 1971,26 mitral valve repair revolutionized the surgical management of many patients with severe MR.
1960 was the start of heart VR. Two major classes of valves
for heart VR are (1) mechanical prosthetic valves and (2) biological
(tissue) valves, which include autograft, homograft (allograft), and
bioprosthesis (xenograft). Mechanical heart valves were first used in
1960 by Harken et
al27 and Starr and
Edwards
(Figure 3
).28
The use of homografts was first described by
Ross29 and by
Barratt-Boyes30 in
1962 and 1964, respectively. Heterografts (xenografts) were first used
by Carpentier in
196531 ; in 1971,
Carpentier used the term bioprosthesis for heterografts
(Figure 4
).32
Ross described the use of autografts in
1967.33
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It was Starrs initial results that changed the
scene.28 Of his
first 8 patients (all were in NYHA functional class IV), 6 survived and
left the hospital, and several returned shortly thereafter to an active
life. The longest known survival of these 8 patients is 31 years. In
the 1950s, Starr thought that he would have no chance of obtaining
research funds from national agencies and organizations because he was
young and without a track record and because the feasibility of his
proposed techniques being successful was unproven. Therefore, he turned
to the Oregon Affiliate of the AHA for funding of his initial
research.34 Of
Starrs series, the known maximal follow-up for aortic valve
replacement (AVR) is 35 years and for mitral valve replacement (MVR) is
34 years
(Table 3
).
|
By the mid-1970s, it was recognized that the major clinical
problem with mechanical valves was thromboembolism and that with
bioprostheses was limited durability because of valve degeneration. To
evaluate differences in patient outcome between these 2 types of
prosthetic heart valves, the VA Randomized Trial was initiated. The
principal long-term findings (average follow-up 15 years) of this
randomized trial35
are as follows. (1) Use of a mechanical valve resulted in a lower
mortality rate (66% versus 79%, P=0.02) and a
lower reoperation rate after AVR
(Figure 5
). (2) The mortality rate after MVR was
similar with use of 2 prosthetic-valve types. (3) There were virtually
no primary valve failures with use of a mechanical valve. (4) Primary
valve failure after AVR and MVR occurred more frequently in patients
with a bioprosthetic valve, especially in patients <65 years old (AVR
26% versus 0%, P<0.001, and MVR 44% versus
4%, P=0.0001). (5) The primary valve failure rate
between bioprosthesis and mechanical valve for AVR was not
significantly different in those
65 years old
(Table 4
). (6) Use of a bioprosthetic valve
resulted in a lower bleeding rate. (7) There were no significant
differences between the 2 valve types with regard to other
valve-related complications, including thromboembolism, and all
complications.
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Future studies will need to delineate (1) the optimal timing of valve surgery in asymptomatic and minimally symptomatic patients, (2) improvements in valve repair and VR devices, (3) optimal matching of an appropriate valve surgery procedure/device to an individual patient, (4) the ideal minimally invasive surgery, (5) percutaneous implantation of prosthetic valves, and (6) the proper role of robotic surgery.
Echocardiography: Doppler
The use of high-frequency ultrasound to assess cardiac
structure and function is one of the great advances in the past 50
years; it has greatly enhanced our ability to safely and accurately
make cardiac diagnoses noninvasively. Edler and
Hertz36 first
recorded movements of cardiac structures with ultrasound. M-mode
studies had particular success in diagnosing the presence and severity
of MS. Early efforts by
Joyner37 and
Feigenbaum38 led to
the rapid development of echocardiography in clinical cardiology in the
United States. These initial recordings of ultrasound reflections from
cardiac structures provided only an "ice-pick" view of the heart.
The development of 2D sector scanning allowed real-time tomographic
images of cardiac morphology and function
(Figures 6
, 7
).39
In the late 1970s, the addition of Doppler echocardiography allowed
noninvasive hemodynamic assessment of VHD
(Figure 8
) and reduced the need for cardiac
catheterization to obtain the hemodynamics of VHD, particularly in
patients with mild to moderate valve lesions. Intracardiac pressure
gradients, when obtained with meticulous care with Doppler (initially
pioneered by
Hatle40 ), were
demonstrated to be reasonably accurate on the basis of careful
comparison with simultaneously measured gradients at the time of
cardiac
catheterization.41
Widespread application of these techniques now allows assessment not
only of VHD but also of LV systolic and diastolic function.
Transesophageal echocardiography represents a further enhancement of
echocardiographic study, which now has wide application, including
intraoperative imaging, which has contributed importantly to enhancing
surgical repair of valvular
regurgitation42 and
in diagnosis of infective endocarditis involving both native and
prosthetic valves. Future important research includes improving methods
for quantification of valvular regurgitation and simplification
of technology to allow easy bedside application of ultrasound imaging
of the heart and role 3D echocardiography. The major accomplishments
since 1950 are summarized in Table 5
.
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Aortic Stenosis
Calcific AS in the older patient is now the most common
cause for VR, which will continue to increase because of the marked
increase of life span of the population. Major advances have occurred:
1.0
cm2 (
0.60
cm2/m2).13 43
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All patients with severe AS have been shown to benefit from AVR unless they have a very serious noncardiac condition that severely restricts their life span.
Vasodilator Therapy in VHD
In 1953, Kelley, a Research Fellow of the Washington,
DC, affiliate of the AHA, used intravenous (IV) hexamethonium in 2
patients with VHD out of a total of 14 patients with heart
failure.52 In 1956,
IV hydralazine produced marked improvements in cardiac hemodynamics and
renal function.53 In
1973, Chatterjee and
coworkers54
documented the marked beneficial effects in hemodynamics and cardiac
function in patients with acute valve regurgitation treated with IV
nitroprusside
(Figure 11
).
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Subsequent studies showed beneficial effects of oral hydralazine both at rest and on exercise in symptomatic patients with severe AR55 ; the mechanism is arteriolar dilatation, which increases forward flow and reduces regurgitant flow.56 However, results of long-term use of hydralazine were disappointing.57
Subsequently, a randomized
trial58 in
asymptomatic patients with severe AR and normal LVEF showed that at the
end of 6 years, of patients assigned to long-acting nifedipine, 15%
needed AVR, compared with 34% in those assigned to digoxin
(Figure 12
). All patients in the nifedipine group
needed AVR because of LV dysfunction; 85% of patients in the digoxin
group needed AVR because of development of LV dysfunction. Digitalis
has never been shown to produce LV dysfunction. Moreover, after AVR,
all patients on nifedipine normalized LVEF, but 25% of those in the
digoxin group did not do so. This observation is compatible with the
hypothesis that digoxin therapy masked early LV dysfunction that, when
detected, had already progressed to beyond the stage of afterload
mismatch, so that after AVR, recovery of LV function was incomplete.
This trial shows that all asymptomatic patients with chronic severe AR
and normal LV systolic function (1) should be treated with long-acting
nifedipine unless there is a contraindication to its use and (2)
should not be given digitalis therapy.
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Natural History of Chronic Severe Aortic
Regurgitation
Up until the early 1980s, it was claimed that
asymptomatic patients with severe AR and normal LV systolic function
frequently developed LV systolic dysfunction while they were still
asymptomatic. The seminal natural history study by Bonow et
al59 from the
NHLBI showed that in younger patients (average age 36 years), the event
rate was low
(Figure 13
). Dujardin and
coworkers60 have
shown that in older asymptomatic patients (56±19 years old) with LVEF
55%, the annual mortality was 2% per year
(Figure 14
). This was not significantly different
(P=0.81) from that of age- and sex-matched
people, suggesting that the mortality is related to older age and/or
associated comorbid conditions. These studies have played an important
role in the decision not to recommend premature AVR in such
patients.
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Mitral Stenosis
In a seminal article in 1954,
Wood61 described the
clinical features and pathophysiology of MS; in another seminal
article, Heath and Edwards described the 6 grades of structural changes
in the pulmonary arteries in patients with pulmonary
hypertension.62
Roy and Gopinaths
study63 from India
showed that in comparable patients, surgical commissurotomy was
associated with a better survival than medical therapy in patients with
class II symptoms as well as in those with class III and IV symptoms
(Figure 15
). In less developed countries, excellent
results have been reported in a very high percentage of young patients
for up to 25
years.64
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CBC for MS was first used by Inoue in
Japan.65 Al Zaibag
in Saudi Arabia developed the double-balloon technique for
CBC.66 The immediate
and 30-day hemodynamic and clinical results of CBC are comparable to
those obtained by surgical
commissurotomy.13 67
The mitral valve area increases from a mean of 1.0 to 2.0
cm2.67
The reductions of left atrial and pulmonary arterial pressures at rest
are more marked on
exercise,68 and
there is an increase of exercise
capacity.68 The
immediate results of CBC are greatly influenced by the characteristics
of the valve and its supporting apparatus, which are best determined by
2D echocardiography (transthoracic and/or
transesophageal).69
Echocardiographic scores of
8 or of 0 to 1 determined by the 2
different methods provide a clue to the best early results. After CBC,
the long-term outcome was best predicted by the post-CBC mitral valve
area (
1.5 cm2) and mean pulmonary arterial
wedge pressure (
18 mm Hg); the 7-year event-free survival was
90±6%
(Figure 16
).70
In the appropriate patient and in centers with skilled and experienced
staff, CBC is the procedure of first choice for relief of severe
MS.
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Mitral Valve Prolapse/Mitral
Regurgitation
Recognition of MVP as the cause of midsystolic clicks
followed by a late systolic murmur is credited to
Barlow,71 who made
his initial observations at autopsy. MVP is now the most common valve
disorder in developed countries. Criley and
colleagues72 defined
the clinical and angiographic features of MVP in the mid-1960s, and a
voluminous literature has evolved over the subsequent years. Some have
suggested a genetic basis for
MVP,73 and there is
a wide range of abnormalities of mitral valve function, ranging from
minor prolapse to severe thickening and redundancy of the
valve74 and finally
flail leaflets.75
The importance of recognition of MVP relates to planning subacute
bacterial endocarditis prophylaxis and maintaining surveillance
in those with MR. There is growing evidence from observational studies
that early repair of mitral valves with severe MR associated with
prolapse or flail leaflets may help preserve LV function. The
importance of recognition of MVP and myxomatous degeneration of the
mitral valve is reflected in the fact that this spectrum of pathology
is now the most common basis of MR, at least in those areas of the
world in which rheumatic fever has been controlled. The observational
data supporting early intervention in repair of severe MR need
confirmation in properly controlled clinical trials, and this
represents an important area of future research. In 1997, Connolly and
coworkers described the occurrence of VHD in patients taking anorectic
drugs.76 The precise
prevalence and progression of valve disease with use of these drugs and
regression after discontinuation of these drugs is being
evaluated.
Footnotes
Reprint requests to Shahbudin H. Rahimtoola, MD, Distinguished Professor, Keck School of Medicine of the University of Southern California, 2025 Zonal Ave, Los Angeles, CA 90033.
References
This article has been cited by other articles:
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J. M. Pass, Y. Zheng, W. B. Wead, J. Zhang, R. C. X. Li, R. Bolli, and P. Ping PKC{epsilon} activation induces dichotomous cardiac phenotypes and modulates PKC{epsilon}-RACK interactions and RACK expression Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H946 - H955. [Abstract] [Full Text] [PDF] |
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