Surgery for Multiple Valve Disease *

Surgery for Multiple Valve Disease *

ALBERT STARR, M.D., COLIN W. MCCORD, M.D., JAMES WOOD, M.D.RODNEY HERR, M.D., M. LOWELL EDWARDS, B.S.

From the Department of Surgery, University of Oregon Medical School,Portland, Oregon

SUFFICIENT PROGRESS has been made inthe surgical treatment of isolated valve dis-ease so that attention may now be directedto the vast number of potential surgicalcandidates with multivalvular involvement.This report is based upon 27 such patientsall of whom had combined aortic and mitralsurgery. As with isolated valve disease, suc-cess is related to the proper application ofreplacement and reparative procedures.Some preliminary observations regardingmultiple replacement have been previouslydescribed." With increasing experience therisk of such procedures has been greatly re-duced and the late clinical and hemody-namic results more clearly defined.

The Prosthesis

Since the first mitral replacement opera-tion performed in September, 1960 12 ourexperience with replacement procedureshas been confined to the ball valve pros-thesis both mitral 8, 9 and aortic 3,10 de-veloped in this laboratory (Fig. 1). Theseare used in exactly the same manner as inisolated replacement. The septal portion ofthe mitral prosthesis is in the usual sub-aortic position and there is no impingementof one prosthesis upon the other. Bothprostheses have undergone gradual im-provement in design and this has beenpertinent to the problem of multiple re-placement. The smaller size prostheses are

used more often in multiple valve diseaseso that attention has been directed to anappraisal of function of these sizes. Nomajor changes have been required in theaortic series since even with the 8A pros-theses, the smallest made for adult implan-tation, there is no significant pressuregradient following proper implantation.There is a small mean diastolic gradientand end diastolic gradient across the oldstyle mitral prosthesis, however, andchanges have been made in internal geom-etry of this valve to improve hydraulicfunction. These involve a more streamlinedinflow face, a larger diameter for flowwithout increase in external diameter,thinner struts, and a more compressiblemargin due to the cushion-like effect of thesilicone foam rubber insert in the sewingring (Fig. 2, 3). These changes were of suf-ficient value as determined by late cathe-

FIG. 1A. Current aortic prosthesis size 8A. Notethe small ball to orifice ratio. B. The current mitralprosthesis size 2M as revised in October, 1963.

596

* Presented before the American Surgical As-sociation, Hot Springs, Virginia, April 1-3, 1964.

This study was supported by Program ProjectGrant HE 06336-03 of the USPHS.

Volume 160Number 4

FIG. 2. This demon-strates the progressivechanges made in themitral prosthesis since itsfirst clinical use in Sep-tember, 1960. Stage 4and 5 have a siliconerubber foam insert insewing margin.

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terization studies so that they were sub-sequently applied to all sizes of the mitralprosthesis for isolated as well as for mul-tiple replacement.

Clinical MaterialIn June, 1962, the first patient in this

series with known severe aortic and mitraldisease underwent a double replacementprocedure. Since then 27 such patientshave been operated upon, 18 of whom hadreplacement of two or more valves. Sevenpatients had aortic replacement and repairof the mitral valve. Two patients had mitralreplacement and repair of the aortic valve(Table 1). All were severely incapacitateddespite the most extreme medical measures.All had a history of past episodes of con-gestive failure and seven were in a terminalstate with treatment-resistant congestion atthe time of operation. Despite prolongedpreoperative bed-rest these patients hadhepatomegaly, peripheral edema, and inthree instances persistent ascites. Six pa-tients, including the two patients withtriple replacement, had previous cardiacsurgery.

Important elements of the preoperativework-up included fluoroscopy for valve cal-

cification, right and left heart catheteriza-tion, and careful evaluation of hepatic,renal, and pulmonary function. The preop-erative hemodynamic data is shown inTable 2. Six patients are sufficiently remotefrom surgery so that both pre- and post-operative studies have been completed andare available for comparison (Table 3). Nopatient was denied surgery on the basis ofcatheterization findings. However, suchstudies were crucial in defining multiplevalve disease in patients who from clinicalevaluation alone had isolated aortic or

FIG. 3. Starr-Edwards mitral valve size 1M pressuregradient-steady state flow with water.

STARR AND OTHERS Annals of SurgeryOctober 1964

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TABLE 2. Surgery for Multivalvular Disease Preoperative Hemodynamics Data(Average Pressures (mm. Hg.))

Index 1/RA PA LA LV Aorta meter2/min.

Pt. M V ED S DM M V ED S ED S D Rest Ex.

A. Multiple Valve Replacements

11 2

17 10

2+1 -3

0 -1

4 32

5

33

1

2

40/24 25 34 2048/20 29 19 23 17

27 38 2425/10 14 14 18 1130/10 17 11 12 1231/10 18 12 16 932/15 23 12 18 542/18 26 14 18 960/28 (40) 34 50 2050/32 38 28 42 (wedge)34/13 20 13 25 12

19 27 1623 26 18

29/10 17 10 11 635/15 21 15 23 1336/18 24 17 19(wedge)41/18 30 24 34 2750/18 35 25 35 18

B. Open Mitral Repair + Aortic Replacement

19 3 6 24/9 12 2320 3 3 2 54/26 38 18 30 1221 4 27/14 24 15 23 822 3 30/3(rt. ventricle) 10 21 823 3 3 2 56/24 36 16 21 1024 4 35/10 17 10 17 525 3 8 48/22 35 19 40 8

C. Aortic Repair + Mitral Replacement

26 2.5 4 1 56/15 3027 20 25 11 88/28 52

148/6

114/5232/10112/10205/10120/9160/7

146/10142/12123/3140/11

88/9204/896/8156/68188/5210/20

123/63 (BA)156/56(BA)90/68104/54(BA)100/60(BA)140/48(BA)108/60116/64 (BA)180/52118/10120/7098/5696/64128/60(BA)136/64(BA)122/6100/68150/65

140/40 (BA)216/44(BA)114/60 (BA)160/68 (BA)100/5695/40124/62

24 37 19 230/0 110/6026 48 18 140/2 104/56

2.112.71 2.861.882.32 2.293.64 3.953.26 4.423.22 3.442.75 3.722.254.15 3.011.992.742.363.11 4.352.3 3.43.66 4.422.943.53

2.072.802.57 4.121.04 1.72.023.12.2

3.381.24

mitral involvement. Some patients had rela-tively mild valve disease as determined bypressure gradients and intracardiac pres-

sures. However, with double valve diseasethe combination of valvular abnormalitiesresulted in marked restriction of perform-ance as determined by cardiac output andarterial venous oxygen difference with restand exercise.

Contrast visualization of the ascendingaorta was performed in most patients andwas helpful in assessing the magnitude ofaortic regurgitation. Coronary visualiza-tion was not performed if hemodynamicdata revealed serious valve disease as a

cause of symptoms. A second injection inthe abdominal aorta allowed evaluation ofthis region as a perfusion pathway andassessment of the degree of atherosclerosisin elderly patients.While no patient was denied the opera-

tion on the basis of the severity of cardiacdisability as determined clinically or byhemodynamic studies, some patients withserious associated diseases such as alcoholiccirrhosis, chronic renal failure, and pul-monary fibrosis and emphysema were notconsidered suitable candidates for multiplevalve surgery. Severe pulmonary hyper-tension was not in itself felt to be a con-

600

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6313311006

53104413

Volume 160Number 4

SURGERY FOR MULTIPLE VALVE DISEASE 601TABLE 3. Pre- and Postoperative Catheterization Data on Patients uith Muitiple Valve Surgery

Brachial CardiacRA PA LA LV Artery Index

Pt. M V ED S D M M V ED S ED S D Rest Ex.

Double Replacement

4 Pre- (3) - - 25/10 (14) (14) 18 11 104/54 2.32 2.29Post- (4) 6 3 25/10 (17) (9) 11 5(wedge) 130/5 115/75 2.56 3.56

5 Pre- (1) 30/10 (17) (11) 12 12 148/6 100/60 3.64 3.95Post- (4) 5 1 25/10 (16) (9) 13 8 130/6 130/80 2.56 3.74

7 Pre- (0) 1 -3 32/15 (23) (12) 18 5 108/60 3.22 3.44Post- (5) 9 1 22/6 (13) (7) 12 4 115/4 120/75 2.78 3.42

12 Pre- (3) 4 3 40/3 (RV pressure) (19) 27 16 120/9 98/56* 2.74Post- (3) 4 2 28/10 (18) (8) 13 5 115/8 125/75 2.66 3.55

13 Pre- (1) - 2 50/3 (23) 26 18 166/8 80/62* 2.36Post- 21/5 (13) (5) 5 3 120/7 115/72 2.01 3.96

Arotic Replacement; Mitral Annuloplasty

19 Pre- (3) 6 24/9 (12) (12) 23 88/9 140/40 2.07Post- (2) 28/7 (12) (4) 8 3 102/4 100/63 2.29 3.85

* Aortic.M: Mean pressure; ED: End diastolic pressure; S: Systolic pressure; D: Diastolic pressure.

traindication to operation. Patients over 60years of age have not thus far been ac-cepted for multiple valve surgery althoughmany patients in this age have had a spec-tacular result following correction of iso-lated valve disease.

Patients accepted for surgery were ad-mitted to the hospital one to six weeksprior to operation to be certain that themaximum benefit of medical therapy hadbeen obtained. Advantage was taken inthis period of preoperative preparation tocontrol the patient's staphylococcal floraand search for foci of infection. Thus ifdental examination and x-rays were notpart of the initial workup these studies wereperformed and followed by appropriatetreatment prior to operation. Urine cultureswere performed routinely and surgery wasnot done in the presence of a positive cul-ture. Culture of the external nares provideduseful information regarding the presenceof coagulase + hemolytic staphylococci. Allpatients whether their nasal cultures were

positive or negative were started soon afterhospital admission on a rigid program ofprophylaxis with daily installation of 5 percent ammoniated mercury ointment intothe nasal vestibule, showers or bed bathswith surgical soap twice daily, and shampooevery other day.

Patients not allergic to penicillin weregiven methylcillin, 4 Gm. daily, beginningon the day before operation. The remainderwere treated prophylactically with Chloro-mycetin and Erythromycin in a similarmanner.

Operative Findings

All patients in this series had rheumaticheart disease except Patient 25 who hadcystic medial necrosis of the aorta with re-sultant aneurysmal dilatation of the sinusesof Valsalva and aortic regurgitation. Mitralregurgitation in this case was due to rup-tured chordae tendinae.

Repair rather than replacement of theaortic valve was possible in only two pa-

602 STARR AND OTHERS

FIG. 4. This preoperative chest film on Patient17 shows calcification of the aortic and mitralvalves as a unit involving intervening tissue.

tients in this series. These (Patients 26, 27)had pure aortic stenosis with fusion of thecommissures and only mild thickening ofthe leaflets. Both were in severe failure atthe time of operation and it was felt thatpalliative surgery was justified. The aorticpathology in the remaining cases were quitesimilar. There were varying degrees offusion of the commissures, loss of leafletsubstance, and thickening of the leaflets,especially at the attached margins. Massivecalcification of the aortic valve was uncom-

mon in this group of patients occurringonly in Patients 13, 17 and 24. Of great in-terest is that when this occurred the cal-cification involved the aortic and mitralvalves as a single unit, as if the rheumaticprocess extended from one valve to theother without regard for functional bound-aries (Fig. 4). Once this concept of rheu-

matic involvement of the aortico-mitral

Annals of SurgeryOctober 1964

complex as a unit was appreciated it be-came apparent even in the absence of sig-nificant calcification that the inflammatoryprocess in most cases involved the interven-ing tissue between the aortic and mitralvalves, a point of some significance in thetechnic of resection.Most of the patients having mitral resec-

tion had a mixed lesion, massive calcifica-tion, or both (Fig. 5). The remainder ful-filled other criteria for mitral resection atthis clinic.4 Patient 9 had pure mitral re-gurgitation with normal sized annulus andPatient 12 had pure stenosis without cal-cification but with irreparable subvalvularfusion. Thus, in only seven of the patientsin this series was it possible to adequatelyrepair the mitral valve. The type of repairis described in Table 1. The decision forrepair in these cases was made within afew seconds after seeing the valve and itwas determined by no other considerationthan the anatomic findings. Open com-missurotomy was performed only for flexi-ble uncalcified valves with a good sub-valvular mechanism. Annuloplasty was per-formed only in the presence of a dilatedannulus. Leaflet plication procedures wereperformed only for flexible leaflets withacquired clefts or flail free margin due toruptured or stretched chordae tendinae.

In no case in this series was the mitraldisease simple dilatation of the annulus asthe result of left ventricular failure. Whilewe have operated upon many such patients,none in our experience required mitralvalve surgery. The mitral regurgitation insuch cases along with the elevated leftatrial pressure disappears following aorticvalve surgery alone.

Operative TechnicThe technic of isolated mitral and aortic

valve replacement has been previously de-scribed. Attention is directed here to thosefeatures peculiar to multiple valve surgeryconcerning 1) operative approach; 2)technic of prolonged cardiopulmonary by-


pass; 3) protection of the myocardium dur-ing aortic cross-clamping; and 4) sequence

of implantation.All patients were operated upon with

midline sternotomy incision. Heparin isgiven in the amount of 3 mg./Kg. andboth cavae are cannulated for a venous re-

turn. The left external iliac artery is isolatedfor inflow and the patient is placed on

cardiopulmonary bypass at an initial flowof 2.5 L./m.2 of body surface/min.The extracorporeal circuit consists of a

rotating disc oxygenator and roller pumps

adjusted to complete occlusion. Hemodilu-tion technics are not used, the prime con-

sisting of heparinized blood drawn 18hours prior to surgery. Mannitol is addedto the pump prime in a 20 per cent solu-tion at a dose of 2 Gm./Kg.5. Additionalheparin is given after three hours of perfu-sion if bypass will continue beyond 31/)hours. Light fluothane anesthesia is admin-istered during perfusion and relaxants are

used to prevent muscular activity duringelectrical defibrillation. Shortly after theonset of bypass the patient is cooled to300 C. and when this temperature isreached flow is reduced to 1.8 L./m.2 ofbody surface/min. provided that perfusionpressures remain 65 mm. Hg or above.While cooling is in progress pericardial

adhesions over the ventricles are dividedso that the apex may be elevated for in-sertion of a left ventricular vent. Attentionis directed first to the mitral valve. Ex-posure is facilitated by a long left atriotomy,decompression of the aortic root, and re-

laxation of the myocardium. The pericardialreflection between the inferior vena cava

and the right inferior pulmonary vein isdivided. The posterior interatrial sulcus iswidely opened by sharp and blunt dissec-tion and the right atrium and inferior cava

retracted sharply to the left. A small stabincision is then made in the exposed an-

terior wall of the left atrium and the mitralvalve palpated in the beating heart. Theascending aorta is cross-clamped and the

M iTuz>rhu -

FIG. 5. Operative specimen of Patient 3. Notethe advance mitral pathology with massive cal-cification. There is marked loss of leaflet sub-stance of the tricuspid valve.

left atrial incision extended downward be-tween the inferior cava and the right in-ferior pulmonary vein to reach the back ofthe heart. It is then possible to extend theincision around the posterior wall of theleft atrium to reach the left inferior pul-monary vein if necessary for adequate ex-

posure. As the heart relaxes the mitral valvecomes into view. Momentary release of theaorta clamp provides an indication of thedegree of aortic regurgitation. Decompres-sion of the aortic root during mitral sur-

gery is achieved by intermittent cross-

clamping of the aorta if aortic regurgitationis not too severe. This was possible in 11 ofthe 18 multiple replacement procedures andin four of the combined replacement andreparative procedures. In the remaindercontinuous cross-clamping was necessary

because of loss of perfusion pressure or

flooding of the operative field with bloodupon release of the aortic clamp. Underthese circumstances the myocardium is pro-

tected by intermittent coronary perfusionwith cold blood. This is obtained from theoxygenating chamber, passed through a

heat exchanger with circulating ice waterand delivered to the coronary ostia by a

foot pedal control pump at a combinedflow of 350 to 400 cc./min. After fiveminutes of perfusion the cannulae are re-

moved and mitral surgery is continued.Coronary perfusion is repeated for three

Volume 160Number 4 603


FIG. 6. A. Left ven-tricular view of the mitraland aortic prosthesis. Themitral prosthesis is toolarge and its sewing mar-gin appears to narrow theleft ventricular outflowtract (Patient 6). B. Thisdemonstrates the proper

positioning of both mitraland aortic prostheses (Pa-tient 2).

minutes every 15 to 20 minutes. Myocardialtemperature is thereby reduced to 80 C.and a maximum drift upward during theperiod without perfusion is 0.50 C./min.Iced Ringer's solution is not used in thepericardium.

With intermittent coronary perfusionthere is sufficient myocardial relaxation so

that retraction is possible without injuryto the heart. A useful maneuver is to placea traction suture in the mitral valve or an-

nulus to help pull this area close to theleft atrial incision. If resection is necessary

care must be taken to excise the septalleaflet as close as possible to the aorticroot. A stump of thickened leaflet if leftbehind will impinge upon the limited space

available for the two prostheses. Follow-ing resection of the mitral valve and divi-sion of the chordae tendinae sutures may be

placed in the liberated mitral annulus withsurprising ease.

Special care must be devoted to theselection of a proper size mitral prosthesisin patients with combined aortic and mitraldisease (Fig. 6). With aortic stenosis con-

centric hypertrophy may encroach upon

the left ventricular cavity diminishing avail-able space for the cage. Septal hypertrophymay also diminish the space available forthe fixation ring of the mitral prosthesiswhich occupies a subaortic position. Forthese reasons the smaller sized mitral pros-

theses have been used in the majority ofcases.

Following mitral surgery the left atriot-omy is partially closed and aortic replace-ment is performed exactly as in isolatedaortic disease. In one patient (Patient 2)the aortic valve was replaced before the

604

Aft

dL.,


mitral. Subsequent exposure of the mitralvalve was quite difficult and this error insequence was never repeated. A transverseaortotomy is used to avoid narrowing theaorta by closure of a longitudinal incision.This insures the largest possible area forflow around the ball, a critical factor foroptimal prosthetic function. After removalof the aorta clamp while rewarming is tak-ing place the left atrium is closed. Theleft ventricular vent is placed on passivedrainage and following removal of all airfrom the heart electrical defibrillation isperformed. The left ventricular vent is notremoved until it is apparent by palpationof the closure clicks that both prosthesesare functioning.

Attention is then directed to the tricuspidvalve. In Patients 3 and 11 severe tricuspidregurgitation was present as a result ofmarked loss of leaflet surface area ratherthan passive right ventricular dilatation(Fig. 5). Tricuspid annuloplasty was per-

formed but both patients were unable tomaintain adequate systemic pressures. Pal-pation of the tricuspid valves and pressure

tracings revealed massive residual regurgi-tation. Bypass was resumed and tricuspidreplacement performed with the mitralprosthesis. Care must be taken to avoidheartblock by placing the sutures in theseptal area through leaflet tissue ratherthan through annulus. In both cases it wasthen possible to discontinue perfusion with-out progressive deterioration of the circula-tion and with evidence that tricuspid func-tion was significantly improved. In twopatients (7, 13) tricuspid regurgitation was

present but this was not sufficiently severe

to warrant correction. One patient (27)had tight tricuspid stenosis treated by com-

missurotomy. There was considerable resid-ual tricuspid regurgitation but again thiswas well tolerated and nothing further was

done.The bypass time in this series of patients

varied from two hours and six minutes tofive hours and eight minutes with a mean

of three hours and 17 minutes for all cases.

This was significantly less for the combinedreplacement and repair group. However, no

consideration was given to perfusion timeas a cause of mortality or morbidity andpatients were given extended periods ofpump support following the establishmentof a satisfactory rhythm.

Results

Of the 27 patients operated upon formultiple valve disease at this clinic 20 are

still alive and in good condition, a totalmortality of 26 per cent. If one excludesthe first three patients, in 24 subsequentconsecutive cases there were four deaths-a total mortality of 12 per cent.

Pertinent data concerning morbidity andmortality is shown in Table 1. Patient 1could not be resuscitated in the operatingroom. While autopsy disclosed serious coro-

nary artery disease there was also some

leak around the aortic prosthesis requiringreopening of the aortotomy. Patient 2 was

about to be discharged from the hospitalthree weeks after surgery when he sud-denly developed coma, jaundice, and diedwithin 48 hours. Autopsy revealed acuteyellow atrophy of the liver. Patient 6 hada technically perfect operation and was re-

turned to the recovery room in good condi-tion. During the second postoperative dayshe complained of shortness of breath andexpired shortly after tracheostomy thatnight. In retrospect the earlier use of arti-ficial ventilation in this patient may have

changed the outcome. Patients 9 and 11 re-

quired vasopressor drugs in the operatingroom and despite all supportive therapy in-cluding prophylactic tracheostomy and arti-ficial ventilation expired on the third post-operative day of progressive low cardiacoutput. Both patients were 52 years of ageand were in congestive failure at the timeof operation. Patient 22, a 54-year-old ladywith massive aortic regurgitation andmarked dilatation of the left ventricle, also

Volume 160Number 4 605

606 STARR AND OTHERS

died of progressive low output despite eighthours of left atrial to iliac artery bypassperformed 36 hours following valve im-plantation. Patient 26, the second patientoperated upon in this series, died of asupraventricular tachycardia not respond-ing to all medical measures on the night ofoperation. She had been subject to theseattacks frequently prior to operation.Noteworthy is that all of the deaths oc-

curred in patients over 45 years of age andwith one exception (Patient 6) the patientwas in functional Class IV. The seven pa-tients in congestive failure at the time ofoperation accounted for four of the sevendeaths.

Complications were common in the earlycases surviving multiple valve replacement.Patient 3 required exploration for tampon-ade on the first postoperative day and dur-ing the first week had multiple attacks ofventricular fibrillation. Reoperation for leakaround the mitral and tricuspid prostheseswas successfully performed eight monthsfollowing implantation. Patient 4 requiredreoperation for late cardiac tamponade onthe tenth postoperative day. She also de-veloped febrile splenomegaly with abnor-mal lymphocytosis and fever.6 However,she was never in serious difficulty and leftthe hospital six weeks after operation inexcellent condition. Patient 5 had transientaphasia on the 14th postoperative day withgood recovery of function. Patient 10 wasslow in awakening and was suspected ofhaving mild air embolism. He posed nocardiac problems, however, and was dis-charged four weeks after operation. Patient12 developed sudden ventricular fibrillationon the eighth postoperative day and wassuccessfully defibrillated. She recoveredcompletely and had an excellent result.This episode occurred while the patientwas out of bed for mealtime. In subsequentpatients overexertion during this periodhas been carefully avoided.

There were no late deaths in this seriesand no infections.


Postperfusion Status

Within a few hours after return to therecovery room most patients had easilypalpable peripheral pulses, warm extrem-ities, and excellent color. Indeed, if thiswere not the case a careful search wasmade for the cause. An intravenous dripof epinephrin or noradrenalin was usedwithout hesitation to buy time until bloodvolume deficits could be corrected or digi-talis dose regulated.Most of the patients had a variety of

rhythm disturbances requiring constant at-tention. Nodal rhythm with atrial ventricu-lar dissociation was the most common ar-rhythmia occurring in about half the pa-tients. Isuprel by intravenous drip provedmost effective in the management of thisproblem. Frequent ventricular ectopic beatswere common and usually disappearedwithout definitive therapy. If not, smalldoses of Pronestyl, provided the blood pres-sure was normal, were of value in theircontrol. Some patients in sinus rhythm pre-operatively developed atrial fibrillation.This did not seriously alter their cardiacstatus clinically and usually would revertto sinus rhythm spontaneously or with alittle help from Quinidine during the thirdor fourth week after operation. Heartblockdid not occur in this group of patients.

Prophylactic tracheostomy and artificialventilation with a volume cycled respiratorwas used in three-fourths of the patientsand maintained for seven to ten days afteroperation. The importance of this type ofsupport cannot be overemphasized. Therewere no complications from this treat-ment. No patients had postoperative pneu-monia and in only one case was bronchos-copy required for removal of bronchialplugs.Serum hemoglobin measured immediately

after bypass varied from 44 milligrams percent in Patient 13 to 560 mg.% in Patient1 who was given pump support for tenhours. The mean value was 117 milligrams

Volume 160Number 4

FIG. 7. Pre- and post-operative chest films onPatient 4.


per cent. Hemoglobinuria was common,but urine output on the day of surgery wasat least 60 to 75 cc./hr. and this was usedas an index of the adequacy of cardiac out-put. Temporary decrease in urine flowresponded always to blood transfusion orDigitalis or both except in the four patientsdying of the low cardiac output syndromein this series.Many patients became slightly jaundiced

after surgery and all had elevation of theserum transaminase. The height of the risein serum bilirubin correlated best withevidence of hepatic dysfunction prior tooperation and with the duration of cardio-pulmonary bypass. Except for one patientdying of acute yellow atrophy jaundicesubsided in all patients and did not presenta significant clinical problem. The relativerole of prolonged anesthesia, prolongedperfusion, hemolysis, and pre-existing liverdisease remains to be determined.

607_ -

Perhaps most striking in the immediatepostperfusion period was the mental clarityof all but one of the patients. This wasdespite a mean pump time of three hoursand 19 minutes. Psychosis occurred later inthe postoperative period, usually after thethird postoperative day, and was alwaysfollowed by complete recovery prior todischarge from the hospital.' This was acommon complication, occurring in morethan one-half the patients.

Late Results

Within a few months following operationmost surviving patients noted improvementin their exercise tolerance. These over fourmonths postoperatively have had no cardiacsymptoms despite full activity and normaldiet. There have been a few exceptions.Patient 24 has a small leak around theaortic prosthesis and murmurs at the apex

STARR AND OTHERS608

7.-...:U.'.

. A

of residual mitral valve disease. The dia-stolic pressure is normal and the murmurof aortic regurgitation is short so that adecision for reoperation has not yet beenmade. Her activities have been limited toavoid increasing the leak until firm heal-ing has taken place. The patient with triplevalve replacement is normally active with-out cardiac symptoms but remains on amoderate low salt diet and Digitalis. Hecontinues to improve and an excellent re-sult is anticipated. The chest x-ray in allpatients shows a decrease in pulmonarycongestion and if cardiomegaly was presentbefore operation, a decrease in heart size(Fig. 7, 8). Phonocardiogram shows thefindings of combined aortic and mitral re-placement with an ejection click of theaortic prosthesis followed by a short systolicejection murmur (Fig. 9). The openingsnap of the mitral prosthesis occurs be-tween 0.08 and 0.10 seconds after thepulmonic closure. No diastolic murmurs are


FIG. 8. Pre- and post-operative chest films onPatient 3.

present. The patient following triple re-placement shows a split first sound withtricuspid closure preceding the mitral clo-sure. A double opening snap is present.One patient (3) in this group developed

severe hemolytic anemia in the postopera-tive period requiring multiple transfusions,and corticosteroid therapy. After manymonths of such treatments steroids werediscontinued and hemoglobin and hemato-crit were well maintained at normal levels.The mechanism for hemolysis followingvalve replacement is not clear but it hasoccurred sporadically in patients followingisolated aortic valve replacement and re-sponds to medical management as out-lined.

Six patients are sufficiently remote fromsurgery so that postoperative cardiac cathe-terization has been performed. A compari-son of these findings with the preoperativecatheterization data is shown in Table 3.Those patients with pulmonary hyperten-


FIG. 9. MC-Mitralclosure; TC-Tricuspidclosure; EC-Aortic ejec-tion click; MOS-Mitralopening snap; TOS-Tri-cuspid opening snap.

sion prior to operation demonstrated a fallin pulmonary artery pressure and in allcases there was a profound fall in the meanleft atrial pressure. The end diastolic pres-

sure in the left atrium following replace-ment was universally normal at rest despitethe fact that in most patients the smallersized mitral prostheses were used. Leftventricular and brachial artery or aorticpressures reveal no significant gradientacross the aortic prosthesis (Fig. 10). Car-diac outputs at rest fell into the normalrange for this laboratory and each patientwas able to increase his cardiac output withexercise in a normal manner. These findingsare similar to postoperative studies per-

formed after isolated valve replacement.2

AORTIC AND MITRAL VALVE REPLACEMENTPt. G.Y. # 2 mitral valve, # 8 aortic valve

2010_Simultaneous left ventricular and left atrial pressure

100-

Simultaneous left ventricular and brachial artery pressure

Cardiac output 4.42 liters (2.66 L/M2)

Mean diostolic mitral gradient 3mmHg

No systolic gradient across aortic volveCo/cu/aofed mitral volve areo..... /.6 cm,2

FIGURE 10.

V'olume 160Number 4 609

STARR AND OTHERS

Anticoagulant Therapy

All patients except the wife of an itiner-ant farm worker are receiving long-termanticoagulant medication. This was initi-ated on the seventh postoperative day withthe use of heparin given deep subcutane-ously every eight hours. During the secondor third postoperative week heparin is dis-continued as long term oral anticoagulanttreatment is started.Only one patient in this series had an

embolus and this occurred on the fourteenthpostoperative day while the patient was re-

ceiving heparin. There have been no lateemboli in this group of patients.

Discussion

In many patients the need for surgicalexposure of both valves is obvious. In otherswith severe aortic disease serious mitraldisease might be completely missed unlesscareful hemodynamic studies are per-

formed. In such cases mitral surgery mustbe done at the time of aortic replacementif the patient is to survive operation. Amore difficult problem in surgical judge-ment is posed by the patient with obviousmitral disease associated with mild aorticstenosis or regurgitation. In such cases theaortic systolic gradient may be only 10 to15 mm. Hg. If aortic regurgitation is pres-

ent it may be associated with a normalperipheral arterial pressure tracing. Onemay be tempted to ignore the aortic dis-ease in the hope that significant palliationmay be obtained by mitral surgery alone.While occasionally successful, this limitedapproach to multiple valve disease may bedangerous. Aortic regurgitation interfereswith operative exposure during open mitralsurgery. Should the patient survive opera-

tion the late functional result may be poor.

It is our experience that even small degreesof aortic regurgitation are poorly toleratedby patients following mitral replacement.It has been known for some time that mildaortic stenosis may assume real significanceafter mitral surgery. At the time of explora-

tion of such valves one may be surprised bythe far advanced pathology associated withhemodynamically mild aortic stenosis. Tohave any gradient at all across the aorticvalve there must be a critically small orifice.Once this size orifice is reached smallchanges in anatomy may be reflected invery large changes in pressure studies. Theonly late death in our series of isolatedmitral valve replacements occurred in a pa-

tient who died suddenly with aortic stenosisone year after operation. At the time ofsurgery there was no significant gradientacross the aortic valve but aortic stenosiswas noted on the angiocardiogram. Thus toachieve a good long term result careful con-

sideration must be given to the anatomicdeformity of the aortic lesion as well as tothe hemodynamic deficit it imposes upon

the circulation (Fig. 11). In general it isbest to be prepared to expose both theaortic and mitral valves in patients withmultivalvular disease and to replace thesevalves if necessary.

The decision for replacement versus re-

pair is based upon the same principles as

in isolated valve disease. Replacement isperformed when it is apparent, uisually im-mediately after exposure of the valve, thatlong term function cannot be restored by a

reparative procedure. The emphasis isplaced upon a projection of anticipatedlate results and not upon considerations ofother features such as operating time or

short term improvement. The late resultsof isolated valve replacement remains suf-ficiently good so that in marginal situationswhen one cannot be sure of the late resultsof reparative surgery replacement is done.In most cases the decision is easy to make.Of 57 valves operated upon in this series,47, or 82 per cent, were replaced.

SummaryMultiple valve surgery has been per-

formed on 27 patients, 16 of whom have hadaortic and mitral replacement. Two hadtriple replacement and nine had combinedreplacement and repair.

610 Annals of SurgeryOctober 1964

V'olume 160Number 4


FIG. 11. Preoperativesupravalvular angiocardi-ogram and postoperativechest film of Patient 8demonstrating incompleteopening of aortic valveand aortic regurgitationof mild degree. This pa-tient had no gradientacross the aortic valveprior to operation but atsurgery had significantaortic stenosis associatedwith severe valvular de-formity and aortic re-

gtirgitation.

The replacement procedures were per-

formed with the ball valve prostheses as

designed for isolated replacement exceptthat the smaller sizes are more frequentlyused. Essential features of operative tech-nic are: 1) sternal-splitting incision; 2) re-

placement of the mitral valve before theaortic valve; and 3) myocardial protectionduring aortic cross-clamping by intermittentcoronary perfusion with ice cold blood.The over-all mortality in this series con-

sisting of our total experience with multiplevalve surgery is 26 per cent. Twelve of the16 patients undergoing mitral and aorticreplacement survived operation and one pa-

tient undergoing triple replacement has hada dramatic restoration in normal activity.Seven of the nine patients undergoing com-

bined replacement and repair survived op-

eration. The first three patients operatedupon account for three deaths in this series,and 24 subsequent patients were operatedupon with four deaths, a mortality of 12per cent. The last seven consecutive pa-

tients with double replacement survivedoperation and are doing well. The latehemodynamic results in those patients suf-ficiently remote from surgery to have suchstudies have been presented and documentthe remarkable improvement obtained clini-cally.Thus with increasing experience the risk

of surgery for multiple valve disease has

approached that of surgery for isolatedvalve disease and patients are selected forsurgery on the same basis.

611

I

612 STARR AND OTHERS Annals of Surgery612 ~~~~~~~~~~~~~~~~~~~~~~~~~~October1964Addendum

Since submission of this paper 13 addi-tional patients have undergone surgery formultiple valve disease including three triplereplacements, eight combined mitral andaortic replacements, one aortic replacementwith open mitral commissurotomy, and onemitral replacement with aortic commis-surotomy, with no deaths. Thus, in the mul-tiple replacement group there has been nomortality in the last 18 patients. Morelengthy follow up on previously reportedcases has revealed no late death or sig-nificant complications in our entire series.

AcknowledgmentThe authors are indebted to the engineer-

ing department of Edwards Laboratories,Santa Ana, California, for their collabora-tion in valve design and testing.

References1. Blachly, P. H.: Post-Cardiotomy Delirium.

Am. J. Psychiatry. To be published in 1964.2. Bristow, J. D., C. McCord, A. Starr, L. Ritz-

man and H. E. Griswold: Clinical and Hemo-dynamic Results of Aortic Valve Replace-ment with a Ball Valve Prosthesis. Supple-ment to Circulation, April, 1964.

3. McCord, C., A. Lui, M. L. Edwards and A.Starr: Aortic Valve Replacement: The Semi-rigid Self-Sealing Ball Valve Prosthesis. Sur-

gical Forum, American College of Surgeons,13:213, 1962.

4. McCord, C. W. and A. Starr: Treatment ofMitral Insufficiency by Reparative and Re-placement Methods. Trans. XIV Congress ofthe International College of Surgeons, May1964, pp. 177-186.

5. Porter, G., D. W. Sutherland, C. McCord, A.Starr and H. E. Griswold: The Prevention ofExcess Hemolysis During CardiopulmonaryBypass by the Use of Mannitol. Circulation,27:824, 1963.

6. Seaman, A. J. and A. Starr: Febrile Postcar-diotomy Lymphocytic Splenomegaly: A NewEntity. Ann. Surg., 156:956, 1962.

7. Starr, A., M. Edwards and H. E. Griswold:Mitral Replacement: Late Results with aBall Valve Prosthesis. Progress in Cardio-vascular Diseases, 5:298, 1962.

8. Starr, A.: Total Mitral Valve Replacement:Fixation and Thrombosis. Surgical Forum,11:258, 1960.

9. Starr, A. and M. L. Edwards: Mitral Replace-ment: The Shielded Ball Valve Prosthesis. J.Thorac. Cardiovasc. Surg., 42:673, 1961.

10. Starr, A., M. L. Edwards, C. McCord and H.E. Griswold: Aortic Replacement: Experi-ence with a Semirigid Ball Valve Prosthesis.Circulation, 27:779, 1963.

11. Starr, A., M. L. Edwards, C. W. McCord, J.Wood, R. Herr and H. E. Griswold: MultipleValve Replacement. Circulation, 29:30, 1964.Supplement, April.

12. Starr, A. and M. L. Edwards: Mitral Replace-ment: Clinical Experience with a Ball ValveProsthesis. Ann. Surg., 154:726, 1961.

DISCUSSION

DR. JOHN W. KIRKLIN (Rochester, Minnesota):We are indebted to Dr. Starr for his usual mag-nificent presentation and for his truly pioneeringcontributions to the surgery of acquired heart dis-ease.

I would like to emphasize merely one point inthe surgical management of patients with severeaortic valve disease who appear to have moderateincompetence of the mitral valve but who may notrequire any operative procedure on the mitralvalve. Preoperatively these patients are those whohave symptoms of pulmonary venous hyperten-sion. That is, they have dyspnea and orthopnea,and have full-blown evidence of severe disease ofthe aortic valve and clinical evidence of apparentmoderate incompetence of the mitral valve in theform of some modest enlargement of the leftatrium; an apical systolic murmur and on angio-cardiography the passage of some dye from theleft ventricle to the left atrium. If one measures

left atrial pressure at surgery in such patients itmay be found to be severely elevated and with amarkedly accentuated V-wave. It is well to bearin mind, however, that these patients with severeaortic valve disease can have markedly elevatedleft atrial pressures and very high V-waves with-out any incompetence of the mitral valve at all.

We have had the experience in the last fewyears of leaving alone the mitral valve in some ofthese patients with severe aortic valve disease anda mitral valve which has by palpation no intrinsicdisease but is modestly incompetent and postrepairand postoperatively have had evidences of thisincompetence completely disappearing. There isno apical systolic murmur, and the long-term andresult is good. So, merely a word of caution aboutthose patients with obviously severe aortic valvedisease and evidence of only moderate incompe-tence of the mitral valve.

This does not detract, certainly, from Dr.Starr's results, which are excellent. I would quoteour own material to support his view that patients

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Surgery for Multiple Valve Disease *