phonocardiographic manifestations of heterograft valve ...british heartjournal, i972, 34, 93694i....

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 thesystolic

PA.

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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 -

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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.

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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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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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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, 20, I75.

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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