-
British HeartJournal, I972, 34, 93694I.
Phonocardiographic manifestations ofheterograft valve
dysfunction in the mitral area
Barry Stimmel, Elliott Stein, Arnold M. Katz, Robert S. Litwak,
andEphraim DonosoFrom the Department of Medicine, Division of
Cardiology, and the Department of Surgery,Division of
Cardiothoracic Surgery, of the Mount Sinai School of Medicine,City
University of New York, New York, U.S.A.
Phonocardiographic and pathological features of mitral porcine
aortic heterograft valve failureare described in 1o patients with
rheumatic valvular disease. Six had isolated mitralporcine
aorticheterograft valve; 3 also had one in the aortic area; one had
this in both mitral and tricuspidareas with an aortic ball valve
prosthesis. Allpatients had systolic murmurs at the apex
indicativeof mitral insufficiency, 8 had prominent third heart
sounds. Five had specific and unusual varia-tions in the systolic
murmurs consisting of (i) conspicuous alternation of systolic
murmur intensitywith heart beat independent ofpreceding cycle
length and/or (2) division of the systolic murmurinto distinct
components. Seven required reoperation with replacement of the
mitral porcine aorticheterograft valve. Commissural separation from
the stent was the major finding in 4; primaryleaflet damage in 3.
Only patients with commissural separationfrom the stent exhibited
these twospecific and unusual variations of the systolic murmur
which thus appear to resultfrom oscillationof the torn commissure.
A systolic murmur consisting of several distinct components
and/orvarying intensity may therefore be presumptive evidencefor
commissural separationfrom the stentof the heterograft valve.
During the past several years, porcine aorticheterograft valves
have been employed atvarious centres as prosthetic devices
inpatients undergoing mitral valve replacement(Carpentier et al.,
I969; Kouchoukos et al.,I969; Litwak et al., I97I). In this
institutionporcine aortic heterograft valves were used inselected
patients during I969 and I970.Review of phonocardiograms taken
in
several of these patients revealed unique find-ings not present
in other forms of mitral re-gurgitation. The purpose of this paper
is toreport the distinctive phonocardiographicfindings and to
attempt to correlate theseresults with pathological examination
ofdefective valves.
MethodsAll I0 of the patients studied had rheumatic
heartdisease. Six patients had primarily mitral valvedisease and
received a heterograft in the mitralarea. Three patients had mitral
and aortic valvedisease and received heterografts in both the
mitraland aortic areas. One patient had disease of the
Received 2I January I972.
aortic, mitral, and tricuspid valve and receivedheterografts in
the mitral valve area and thetricuspid valve area with a Starr
Edwards ballvalve prosthesis in the aortic area. Duringoperation
all mitral infravalvular structures wereremoved. The heterograft
valves used were allformalin fixed porcine aortic valves sewn ontoa
high porosity Dacron cloth-covered stentmachined from a solid piece
of stellite No. 25.Details of the valve preparation and
mountinghave been previously described (Litwak et al.,1971). Seven
of these patients have required re-operation with replacement of
the defectiveheterograft valve with ball valve prosthesis.Three
patients, one with a double heterograft, inspite of clinically
shown valve malfunction arenot sufficiently disabled at the present
time towarrant corrective surgery. All of the reoperatedpatients
had phonocardiograms immediately be-fore operation. The 3 remaining
patients hadphonocardiograms on an ambulatory basis.
Thephonocardiograms were performed on an Elec-tronics for Medicine
DR8 recorder at a paperspeed of 75 mm per second, using crystal
micro-phones, and a standard pulse pick-up for carotidpulse,
jugular venous pulse, and apex motion.Pass ban filters of low,
medium, medium to high,and high frequency types were employed in
thesound recordings.
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Phonocardiographic manifestations of heterograft valve
dysfunction in the mitral area 937
All recordings were made with the breath heldin full expiration.
Measurement of time intervals
-was made from the onset of the Q wave of theelectrocardiogram
to the onset of the major de-flections of the heart sounds or from
the onset ofthe aortic component of the second sound to the
. onset of the third heart sound. Time intervalscorrected for
heart rate were measured in 5 con-secutive cycle lengths with the
mean valuesreported.
ResultsSix of the 7 patients with heterografts in
4mitral valve area were in atrial fibrillation;one had a right
bundle-branch block. All 3patients with heterografts in both aortic
andmitral areas were in normal sinus rhythm.* The first sound was
recorded without diffi-
X culty in all patients. In 2 out of 7 patients withmitral valve
heterografts and one of the 3
, patients with aortic and mitral heterografts,a low frequency
muscular component wasidentified o0o3 to o o4 sec after the Q
waveon the electrocardiogram. Two components%f the first sound were
identified in 3 of the 7patients with mitral heterografts and i of
the3 patients with heterografts in both areas.The first component
(Q-i) appeared betweeno-o6 to o-o8 sec and the second
component(Q-2), when present, appeared o'o8-o-io secafter the Q
wave of the electrocardiogram. ATonsistent variation in intensity
with the firstheart sound as related to previous cycle lengthcould
not be shown; in some instances the in-tensity of Si decreased and
in some instancesit increased after long cycle lengths.An ejection
sound was recorded in 2 of the
7 patients with mitral valve heterografts and2 out of the 3
patients with heterografts inboth valve areas. This sound appeared
O 12e0 O I7 sec after the Q wave of the electro-cardiogram and may
have been related to pul-monary hypertension.The aortic and
pulmonary components of
~ the second sound were identified in all pa-tients. There were
no significant abnormalitiesof this sound.-.A third heart sound was
seen in 6 of the 7patients with mitral valve heterografts and 2
v of the 3 patients with heterografts in bothareas. The interval
between the aortic com-
'ponent of the second sound and the thirdsound (S3) (A2-S3)
varied from O-I2 to o-i8sec.
All the patients had medium-high fre-quency, high intensity
systolic murmurs
A starting with the second component of thefirst sound and
ending shortly before the
m aortic component of the second sound. Twodistinctive features-
were noted in the- systolic
PA.
APEX
CARCIOY
F C Cs -.').. 4
F I G. i The phonocardiogram recordedfromthe apical and
pulmonary (PA) area in Case 9.Normal sinus rhythm is present with a
prema-ture ventricular contraction in cycle 3. Asignificant
difference in intensity exists betweencycle I, 2, and j5. Division
of the murmur intocomponents is also present (CI, C2).
murmur: a variation of intensity and a divisionof the murmur
into components. Four out of7 patients with mitral valve
heterografts and 2of the 3 patients with heterografts in bothvalve
areas had a conspicuous alteration inintensity of the murmur not
related to pre-ceding cycle length in the patients with
atrialfibrillation and present in patients with normalsinus rhythm
(Fig. i and 2). Three patientswith mitral valve heterografts and 2
patientswith mitral and aortic heterografts were also
FIG . 2 The phonocardiogram recorded fromthe apical area in Case
6. Atrial fibrillation ispresent. An alternation in intensity and
dura-tion of murmur is seen between cycles I, 2, and4. A short
diastolic murmur (DM) is alsopresent.
ECG -
MF
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938 Stimmel, Stein, Katz, Litwak, and Donoso
noted to have 2 or 3 distinct components to themurmur giving it
a 'warbling' quality (Fig. i,3, and 4). Neither the alternation nor
the war-bling was affected by respiration.
Diastolic murmurs were observed in 2patients. One patient with a
mitral valveheterograft had a low frequency mid-dias-tolic murmur,
probably representing a mitralflow murmur and ending before the
first heartsound. One patient with aortic and mitralvalve
heterografts had an early high frequencydiastolic murmur which
ended in late dias-tole.The mitral heterograft valves were
exam-
ined in 5 patients with mitral and 2 patientswith mitral and
aortic heterografts after re-operatior, Abnormalities were
classified as(i) leaflet, (2) leaflet separation from the stentat
the commissure and, (3) stent (Table 2).Two of the 5 patients with
mitral hetero-grafts and both patients with both hetero-grafts
exhibited conumissural separation. Fourof 5 patients with mitral
heterografts hadleaflet abnormalities ranging from minor
al-terations such as sagging of the leaflets toinversion and, in
one instance, perforation ofthe cusp. No abnormalities of the stent
werenoted. Correlation of the pathological withthe
phonocardiographic findings revealed thealternation or warbling of
the systolic mur-mur to be present in all cases of
commissuralseparation (Table 3). In the 2 instances withonly
leaflet damage, the distinctive findings inthe systolic murmur were
not seen. Of the 3unoperated patients, alternation was seen
inone.
DiscussionAll patients in this study had mitral insuffici-ency
secondary to failure of the porcineheterograft. Though 3 of the
patients hadinitial replacement of the aortic valve with
aheterograft as well as the mitral valve, and onepatient had a
Starr Edwards aortic prosthesis,at the time of the study their
aortic valveswere functioning normally and, for purposesof
discussion, all patients will be consideredin one group. Gianelly,
Popp, and Hultgren(1970) reported phonocardiographic findingsin
patients with normally functioning aortichomografts in the mitral
valve area andrelated these findings to angiocardiographicand
echocardiographic studies on the samepatients. The first sound was
found to consistof four components: a low frequency muscu-lar
component, two valvular components, anda late ejection sound that
was seen in some,but not all, of the patients. In the presentstudy,
the existence of a low frequency sound
F I G. 3 The phonocardiogram recorded fromthe apex and left
sternal border (LSB) inCase IO. Normal sinus rhythm is present.
Themurmur can be separated into three distinctcomponents (Ci, C2,
C3).
FIG. 4 The phonocardiogram recordedfromapex and left sternal
border in Case 2. Atrialfibrillation with a right bundle-branch
block ispresent. Division of the murmur into two com-ponents is
seen as well as abrupt cessation ofthe murmur oo8 sec before S2 in
cycle 2.
J 1 ~4APEX
CAR I
f:;1
i!
il
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Phonocardiographic manifestations of heterograft valve
dysfunction in the mitral area 939
TABL E I Phonocardiographic findings: heart sounds
pCase Rhythm Valve QRS Q-M Q-I Q-2 Q-ES A2P2 A2S3No.
x Atrial fibrillation MVH2 Atrial fibrillation MVH/TVH/SEA
* 3 Atrial fibrillation MVH4 Atrial fibrillation MVH5 Atrial
fibrillation MVH6 Atrial fibrillation MVH7 Normal sinus rhythm/
MVH
intraventricular conduc-tion defect
8 Normal sinus rhythm BVH9 Normal sinus rhythm BVH
I0 Normal sinus rhythm BVH
o-o80112o0ogo og0.07O-I0010
0-09o-o8o-o9
0-04
0-04
0.070.07o-o6o-o8o-o80-07o-o8
O-00
0O10O-00 0-17
OI2
0-020.040.040.030-020-020-05
o-i6O-I30-I5OI2o-i8O-I70-I5
0*03 o-o6 01*0 012 0°03- o-o8 - - 002 01I2- o*o6 - 0o14 0*02
0*I5
Abbreviations: Q-M = Q wave of electrocardiogram to onset of
initial low frequency component before first sound;Q-i = Q to onset
of first loud component of first sound; Q-2 =Q to onset second loud
component first sound;a-ES = Q to ejection sound; A2P2 = distance
between aortic and pulmonic components of second sound;
A2S3=component of second sound to third heart sound; MVH =
heterograft in mitral area; SEA = Starr Edwards Ballvalve aortic
area; TVH = heterograft in tricuspid area; BVH = heterografts in
both aortic and mitral areas.
after the QRS was seen in only 3 of the I0cases. The reason for
this discrepancy may berelated to a difference in recording
technique.The valvular components of the first sound
were shown by Gianelly et al. (I970) to con-sist of an initial
sound occurring when the,early systolic ballooning of the graft
leafletswas suddenly checked. The second compo-nent occurred at the
time when the leafletswere suddenly jerked back toward the base
ofthe heart at the onset of ventricular ejection.The absence of the
second component in 6 ofI0 patients in our series might be related
toeither technique or to the presence of signifi-cant mitral
regurgitation which obscured thissound. An alternative explanation
is that theconspicuous insufficiency prevents the 'sud-den
acceleration of a mass of blood behind
tensed valve leaflets' which has been proposedas the mechanism
of this sound. A soundoccurring OI2 to 017 sec after the Q wavewas
seen in 4 out of I0 patients. In 2 of thesepatients, coexisting
aortic valve heterograftswere present and the ejection sound
mighthave been related to some abnormalities of theaortic ring or
alternately pulmonary hyper-tension.A third heart sound was noted
in 9 out of
the I0 patients. Two current theories exist asto the origin of
the third heart sound. Themost common relates the sound to the
rapidincrease in left ventricular filling which causesthe
ventricular musculature to check itselfsuddenly when distended,
producing a vibra-tion (Potain, I900; Crevasse et al., I962).Many
investigators, however, feel the third
TABL E 2 Phonocardiographic and pathological findings
Case Systolic murmurs'uNo.
Present Alterna- Compo-tion nents
Diastolic Apex cardiogram Abnormality of heterograft
Leaflet Separationfrom stent
"I + + + o Normal Sagging + /calcification Normal2 + + + +
Prominent rapid Inversion + /calcification Normal
filling wave3 + o o o Prominent rapid Contraction Normal
Normal
filling wave8 4 + + 0 Normal
5 + o o o Normal6 + + + 0 Normal Normal + Normal7 + o o o
Prominent rapid Perforation Normal Normal
filling wave of leaflet8 + o o + Prominent systolic - -
wave9 + + + o Systolic plateau Normal + Normal
I0 + + + 0 Normal Normal + Normal
Abbreviations: + = present; o= absent; -= not known.
Stent
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940 Stimmel, Stein, Katz, Litwak, and Donoso
TABLE 3 Correlation of changes in thesystolic murmur with
pathological findingsat operation
Unknown Leaflet Commissure(only)
Holosystolicmurmur only 3 2 0
Alternation I 0 5Components 0 0 5
sound is subvalvular in origin and representstension of chordae
or papillary muscles duringearly diastole at the end of the rapid
fillingphase (Nixon, I96I; Fleming, I969).
Evidence to support the subvalvular originof this sound has come
from Fleming (i969)who noted the absence of a third sound
inpatients with ball valve prosthesis. However,third heart sounds
have been recorded re-cently in patients with both normally
func-tioning and failing heterografts (Gianelly etal., I970; El
Gamal and Smith, I970). Sincepatients with heterograft replacements
havethe chordae and papillary muscles removed, itis likely that
other factors such as left ventricu-lar wall motion may play a
significant role inthe production of the third sound.The most
interesting findings are the
alternation in intensity and the warblingquality of the systolic
murmur seen in thepatients with commissural separation fromthe
stent. Pathological examination of hetero-graft failures has shown
several types of ab-normalities, the most common being com-missural
separation from the stent. However,leaflet perforation, prolapse,
or sagging of theleaflets, and peripheral leak around the
sewingring have also been described. Separation ofthe leaflet from
the stent was seen in 5 of the7 cases examined, being the sole
abnormalityfound in 3. Leaflet abnormalities were foundin 4 of the
patients, in 2 coexisting withseparation of the commissure from the
stent.
All those patients manifesting separation ofthe commissure
exhibited changes in alterna-tion and division of the systolic
murmur. Themechanism of the production of this uniquemurmur is
unclear. However, it is possible,using the pathological findings,
to hypothesizethe aetiology. The separation from the stentat the
commissural area might result in a ran-dom variation of valve
leaflet position at thebeginning of each cardiac contraction
conse-quently affecting the degree of regurgitantflow and the
intensity of the murmur. Anotherpossibility is that the murmur
results fromtwo different sources, one the turbulence of
the regurgitant blood and the second thevibrations of the
non-attached commissure.The random variation of commissure
positionat the beginning of each contraction maydetermine the
degree and type of vibrationfor that particular cycle. The amount
of re-gurgitant flow need not change if the secondexplanation is
correct.Though 6 of the patients studied were in
atrial fibrillation, which would predispose toa varying volume
of blood ejected with eachcardiac cycle, this finding was present
also inpatients in normal sinus rhythm as well asbeing absent in
those patients with atrialfibrillation and primarily leaflet
abnormalities.It seems, therefore, that the intensity of themurmur
depended not as much on the cyclelength as on the varying position
of the separ-ated commissures.
This variation in leaflet position might alsoresult in a
division of the murmur into com-ponents secondary to the
oscillation of thefree commissural edge with each
cardiaccontraction.
In order to delineate further the origin ofthese changes,
correlation of angiographic andphonographic studies will be carried
out inthe future. It should be noted that Killebrewand Cohn (I97I)
described unusual murmursin patients with heterograft mitral
valvefailures. These murmurs were described ashaving a 'honking'
quality and were associatedwith abnormalities of the valve
leaflets. Onepatient, however, had a 'machine-gun' typemurmur which
had several distinct compo-nents similar to those found in the
presentstudy. At operation, this patient had a separa-tion of his
leaflet from the stent at the com-missural area. This finding
serves to corrobor-ate the association made between the changesin
the systolic murmur and the pathologicalfindings ofthe heterograft
valve abnormalities.
It is suggested that a patient with a mitralvalve heterograft
who has a holosystolic mur-mur, alternating in intensity from beat
to beatand consisting of several components, mayhave an
insufficiency due to commissuralseparation of the valve leaflets
from the stent.
ReferencesCarpentier, A., Lemaigre, G., Robert, L.,
Carpentier,
S., and Dubost, C. (I969). Biological factors affect-ing
long-term results of valvular heterografts.J7ournal of Thoracic and
Cardiovascular Surgery, 58,467.
Crevasse, L., Wheat, M. W., Wilson, J. R., Leeds,R. F., and
Taylor, W. J. (I962). The mechanismof the generation of the third
and fourth heartsounds. Circulation, 25, 635.
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Phonocardiographic manifestations of heterograft valve
dysfunction in the mitral area 941
El Gamal, M., and Smith, D. R. (1970). Occurrenceof a left
ventricular third heart sound in incom-petent mitral heterografts.
British Heart Journal,32, 497.
Fleming, J. S. (I969). Evidence for a mitral valve originof the
left ventricular third heart sound. BritishHeart journal, 31,
I92.
Gianelly, R. E., Popp, R. L., and Hultgren, H. N.(1970). Heart
sounds in patients with homograftreplacement ofthe mitral valve.
Circulation, 42, 309.
Killebrew, E., and Cohn, K. (I97I). Observations onmurmurs
originating from incompetent heterograftmitral valves. American
Heart,Journal, 8I, 490.
Kouchoukos, N. T., Kerr, A. R., Sheppard, L. C.,Ceballase, R.,
and Kirklin, J. W. (I969). Hetero-
graft replacement of the mitral valve. Circulation,39-40, Suppl.
III, I25.
Litwak, R. S., Hancock, W. B., Lukban, S. B., Jurado,R. A., and
Olsen, E. G. J. (I97i). Results of mitralvalve replacement with
formalin fixed porcinexenografts. Presented at American College of
Cardi-ology Meeting, Jan. Io-i2, I971.
Nixon, P. G. F. (I96I). The third heart sound in
mitralregurgitation. British Heartjournal, 23, 677.
Potain, P. C. E. (i9oo). Les bruits de galop. SemaineMidicale,
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Requests for reprints to Dr. Barry Stimmel,Mount Sinai School of
Medicine, I212 FifthAvenue, New York, N.Y. I0029, U.S.A.
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