Preoperative factors affecting the outcome of isolated mitral valve replacement: A 10 year review

Preoperative Factors Affecting the Outcome of

Isolated Mitral Valve Replacement: A 10 Year Review

ANTHONY J. DALBY, FCP (SA)’ BRIAN G. FIRTH, MRCP (UK), DPhil

(Oxon) ROBERT FORMAN, FCP (SA), FACC

Cape Town, South Africa

The outcome after mitral valve replacement is influenced not only by the skill and experience of the surgical team and the type of prosthesk used bul also by preoperative factors. This study was performed to assess the effect of such factors on early and late mortallty and the rate of thromboembollsm afler isolated mitral valve replacement In 545 patlents. A Starr-Edwards prosthesis was used In 292 and a porcine heterografl in 253 patients. The overall operative (1 month) mortallty rate was 7 percent. Age at operation (19 or less versus 20 to 54 versus 55 or more years), type of mitral valve lesion, and heart rhythm did not influence operatlve or 3 year survhfal or rate of ttuomboemM km. A large cardkthorack ratk (75 percent or greater) on standard anteroposterkr chest radkgraph was associated with a reduced operatlve survival rate (81 versus 95 percent, p <O.OOS) that was still evident at 3 years (87 versus 84 percent, p <O.OOS) and a higher incidence rate of thKwnboembdk events (90 versus 98 percent thromboembotlsm-free rate, p <0.05) in the perkperatlve period. A large left atrial diameter (12 cm or more) was also associated with a reduced operatlve survival rate (85 versus 95 percent, p <0.05) but did not influence late survival or rate of thromboembolism. Cardiac catheterixatkn was performed in 387 patients. A depressed cardiac index (1.5 Itters/mln per m2 or less), elevated systolic pulmonary arteflal pressure (100 mm Hg 01 greater), putmonary vascular resistance (10 units 0I greater) 0T kft ventrkular end-dfastoUc pressure (20 nun Hg or greater) were not indlvldually associated with an increased mortality or thromboembollsm rate. However, when grouped according to the presence or absence of one or more severely abnormal hemodynamk variables, patients with poor hemodynamics had a reduced operative survival (9 1 versus 97 percent, p <0.02), but survival at 3 years and rate of throm- boemboflsm were not slgnlfkantly different in the two groups.

Thus (1) patients with a large cardlothoracic ratio, large lefl atrlum or poor hemodynamks have a reduced operative survival and should be managed with great care in the perkperatlve period because their late postoperatlve survival is not slgnifkantly different from that of patients without these derangements; and (2) thr omboembdk events after mitral valve replacement are largely unrelated to preoperatlve factors.

From the Cardiac Clinic, Depa&nent of Medlcine, University of Cape Town Medical School and Groote Schuu Hospiil, Obsen/atc+y, Cape Town, South Africa. Manuscxipt received Septaher 23. 1980; revised manuscript received December 3. 1980; accepted December 5, 1980

l Present address: Cardiac Unit. General l-h- pital. Johannesburg, South Africa.

Address for reprints: Secretary, Card&c Clinic, Groote Schuur Hospital, observatory, 7925, South Africa.

The outcome after mitral valve replacement is influenced not only by the skill and experience of the surgical team and the type of prosthesis used but also by preoperative factors.’ The effects of preoperative factors, whether clinical, electrocardiographic, radiographic or hemodynamic, either in isolation or in combination, on both the mortality rate and the rate of thromboembolism after mitral valve replacement have been studied by many investigators .2-22 However, the findings of these different investigators have been conflicting, and conclusions drawn in the early period of mitral valve replacement do not necessarily reflect the present situation.

828 April lW1 The Amerkan Journal 04 CARDtOLOGY Vtaknne 47

In this study actuarial methods are used to analyze the effect of a variety of preoperative factors on both operative and late mortality, as well as the rate of thromboembolism in a large group of patients after mitral valve replacement.

Methods

Patients: The study group comprised all patients who underwent isolated mitral valve replacement for the first time during the 10 year period, March 1969 to February 1979, in the Cardiac Clinic, Cape Town. Patients with mitral valve disease as a result of ischemic or complex congenital heart disease were excluded from this study. The presence of concomitant aortic regurgitation (greater than l+ on a scale of l+ to 4+)23 or aortic stenosis also constituted a criterion for exclusion from the study. Patients who had undergone previous cardiac surgery with cardiopulmonary bypass (mitral anuloplasty or valve replacement) were also excluded. How- ever, patients who had previously undergone closed mitral valvotomy, those who underwent simultaneous mitral valve replacement and tricuspid anuloplasty (58 patients) were included in this analysis. Six hundred eleven patients fulfilled these criteria.

All patients had clinically severe mitral valve disease with dyspnea on mild exertion while on treatment with digitalis and diuretic agents (New York Heart Association24 class III or IV with treatment). The patients’ age and preoperative cardiac rhythm in the electrocardiogram were noted. The cardiothoracic ratio and left atria1 diameter25 were measured on the preoperative 6 foot posteroanterior chest radiograph.

Cardiac catheterization: The minority of patients underwent catheterization during the initial period of the study while almost all patients underwent catheterization during the latter period. Adequate catheterization data were available for analysis in 387 patients. Left and right heart catheterization was performed with either the brachial or femoral approach. Left ventricular end-diastolic pressure was measured from the left ventricular pressure tracing at the trough following the a wave or 50 ms after the onset of the QRS complex. Cardiac output was measured using the computer analysis of the curve (Columbus Instrument Co., Columbus, Indiana) after injection of indocyanine green. Pulmonary vascular resistance was expressed in resistance units (dynes s cm+)/ 80.

The mitral valve lesion was defined as follows: When no end-diastolic gradient was demonstrated on simultaneously recorded pulmonary arterial wedge and left ventricular diastolic pressure tracings and mitral regurgitation was demonstrated by left ventriculography, the lesion was designated “mitral regurgitation. ” “Mitral stenosis” was considered present when a pandiastolic gradient was present across the mitral valve and no more than slight (l+) mitral regurgita- tion23 was evident in the left ventriculogram. Patients with mitral valve disease whose findings did not fall into either of these two categories were regarded as having “mixed mitral valve disease.” In the 224 patients who did not undergo catheterization preoperatively, the mitral valve lesion was classified according to the surgeon’s report on the appearance of the valve at operation.

Surgery: The majority of patients in the initial period of the study received a cloth-covered Starr-Edwards mitral valve prosthesis (model 6300,6310,6320 or 6400). During the last 3 years of the study, Hancock and Carpentier-Edwards glu- taraldehyde-preserved porcine heterografts were used in preference to mechanical prostheses because of the inconvenience of anticoagulant therapy. A small number of patients received a Lillehei-Kaster or Bjplrk-Shiley prosthesis.

Follow-up analysis: Follow-up information was collected during examinations performed every 3 months, except in patients living at a distance from our institution from whom information was obtained by correspondence at yearly intervals. Actuarial methods26 were used to calculate the percent of valves functioning satisfactorily, rates of patient survival and thromboembolism-free period, at the 1st postoperative month and then at yearly intervals to 3 years postoperatively. Satisfactory valve function was determined from the number of patients surviving who had not required reoperation for replacement of a malfunctioning prosthesis. Malfunction was due to thrombosis or excessive tissue ingrowth in the mechanical prostheses and calcification or cusp rupture in the heterograft prostheses. Operative mortality was defined as death occurring at operation or within the 1st postoperative month. Thromboembolic events included valve thrombosis and embolic events associated with a functional deficit, whether transient or permanent.

Statistical analysis: Results are expressed as the mean f standard error of the mean. Student’s t test modified for un- equal variance (Welch t test) was used to test for significant differences in cumulative survival proportions when two variables were compared (for example, sinus rhythm versus atria1 fibrillation). This analysis was preceded by an analysis of variance when more than two variables were compared (for example, stenosis versus regurgitation versus mixed valve disease). Discriminant analysis was also performed on the preoperative factors studied. The significance of the association between factors was then tested by chi-square analysis. A probability (p) value of 0.05 or less was regarded as significant.

Results

Six hundred eleven patients fulfilled the criteria for inclusion during the 10 year period of this study. Sev- enty patients (11.5 percent) were lost to follow-up; the majority of these (56 or 80 percent) lived at a distance from our institution. Twenty-four (4 percent) underwent reoperation. Forty-three patients (7 percent) died at operation or within the 1st postoperative month. Fifty-four late deaths were recorded, and there were 97 documented thromboembolic events.

Type of prosthesis: The mitral valve prostheses used were: Starr-Edwards in 292, porcine heterograft in 253 (42 Hancock and 211 Carpentier-Edwards), Lil- lehei-Kaster in 53 and Bjgrk-Shiley in 13 patients. Owing to the small number of Bjark-Shiley prostheses used, patients with this prosthesis were excluded from the remainder of the study.

Thromboembolism-free period and satisfactory valve function were compared for the porcine heterograft, Starr-Edwards and Lillehei-Kaster prostheses (Fig. 1 and 2). Analysis of data in patients with a porcine heterograft extended only to 2 years postoperatively. This reflects the relatively short period of time that these valves have been used in our institution. Separa- tion of Hancock and Carpentier-Edwards prostheses revealed no significant difference in period of satisfactory valve function or freedom from thromboembolism; these prostheses were thus grouped together for subsequent analyses. The thromboembolism-free periods did not differ significantly among the Starr-Edwards, porcine heterograft or Lillehei-Kaster prostheses (Fig. 1).

PREOPERATIVE FACTORS AND MITRAL VALVE REPLACEMENT-OALBY ET AL.

April 1981 The American Journal of CARDIOLOGY Volume 47 827

LILLEHEI- KASTER

\

STARR - ECWARDS

HETEROGRAFTS

J OU I 1 I

%2 1 2 3

YEARS

FIGURE 1. Actuarial analysis of the percentage of patients with freedom from thromboembolism with isolated Lillehei-Kaster (n = 53) Starr- Edwards (n = 292) or porcine heterograft (n = 253) mitral valve replacement. There was no significant difference among the three types of prosthesis at 2 years, or between Llllehei-Kaster and Starr-Edwards prostheses at 3 years. Vertkal bars represent the standard error of the mean. Analysis of the data in the patients who received a porcine heterograft extended for only 2 years postoperatively because of the relatively short period of time that these valves have been used in our institution.

Satisfactory valve function was not significantly different for Starr-Edwards or porcine heterograft prostheses (Fig. 2). The Lillehei-Kaster prosthesis appeared to function less well than either the porcine heterograft or the Starr-Edwards prostheses (Fig. 2). However, this difference was not significant (Lillehei- Kaster versus Starr-Edwards at 3 years, p = 0.059; Lillehei-Kaster versus heterograft at 2 years, p = 0.055). Because these differences approach the designated level of significance and might distort subsequent data analysis, and because fewer than 10 percent of patients received the Lillehei-Kaster prosthesis, the patients who received this prosthesis were excluded from the remainder of the study. The data on the remaining 545 patients who had either Starr-Edwards or porcine heterograft prostheses were analyzed to determine the effect of certain preoperative factors on perioperative and late survival, and freedom from thromboembolism.

Age at operation: There were no differences in survival when patients were grouped according to age at operation (19 years and below [range 7 to 19, mean 15.3 years]; 20 to 54 years; and 55 years and above [range 55 to 70, mean 58.8 years]) (Table I). Only 11 patients aged 65 to 70 years were operated on in this series, and no patient was more than 70 years old. All 11 patients survived operation; 1 died late, 3 years postoperatively.

PREOPERATIVE FACTORS AND MITRAL VALVE REPLACEMENT-DALBY ET AL.

1 ,

4

0’ I I I 1

‘42 1 2 3 YEARS

FIGURE 2. Actuarial analysis of the percent of valves functioning satisfactorily. Satisfaotory vafve function was determined from the number of patients surviving who had not undergone reoperation for replacement of a malfunctioning prosthesis. Satisfactory valve function was not significantly different for Starr-Edwards (n = 292) or porcine heterograft (n = 253) prostheses. The Lillehei-Kaster (n = 53) prosthesis appeared to function less well than either the porcine heterograft or Starr-Edwards prosthesis. This difference approached significance (Lillehei-Kaster versus Starr-Edwards at 3 years, p = 0.059; Lillehei- Kaster versus heterograft at 2 years, p = 0.055).

Those patients aged 19 years and under had greater freedom from thromboembolism at 3 years than those aged 55 years and older ( p CO.05). This may be a chance finding because this difference was not apparent at 2 years, or at 4 years when, in this instance, the study was extended to that period.

Preexisting mitral valve lesion: The preexisting mitral valve lesion (stenosis in 160, regurgitation in 76 or mixed mitral valve disease in 309 patients) did not influence either survival or the thromboembolism-free period (Table I).

Cardiac rhythm: Preoperative cardiac rhythm (sinus in 174 and atria1 fibrillation or other supraven- tricular rhythm in 371 patients) also had no influence on either survival or thromboembolism-free period (Table I).

Chest radiograph: Preoperative posteroanterior chest radiographs were available in 487 patients (89 percent). The left atria1 diameter could be assessed in 334 (61 percent).

Patients with a markedly increased cardiothoracic ratio (75 percent or greater) had reduced survival when compared with those with a smaller (less than 75 percent), ratio both within the 1st postoperative month (81 versus 95 percent, p CO.005) and at 3 years (67 versus 84 percent, p <0.005) (Fig. 3). The patients with a cardiothoracic ratio of 75 percent or greater had a greater incidence of thromboembolism (90 versus 98 percent

828 April 1881 The American Journal ol CARDlOLDGY Volume 47

PREOPERATIVE FACTORS AND MITRAL VALVE REPLACEMENT-DALEY ET AL.

TABLE I

Relations Among Clinlcal Preoperative Factors and Percent Survival and Freedom From Thromboembollsm After Mitral Valve Replacement

Patients

(n)

Percent Survival Percent Thromboembolism-Free

Operative Late Operative Late (1 mo) (3 yr) (1 mo) (3 yr)

Age 519 20-54 255

Valve lesion Stenosis Regurgitation Mixed

ECG rhythm Sinus AF

LA diameter

3% 90.7 93.6 f f 2.9 1.3 82.1 72.9 f f 5.6 2.4 72 94.4 f 2.7 84.2 f 5.6

160 93.1 f 2.0 83.5 f 3.8

3:: 89.5 94.2 f f 3.5 1.3 80.8 75.5 f f 6.3 2.6

174 94.8 f 1.7 76.6 f 4.2 371 92.5 f 1.4 82.5 f 2.3

<12 cm 268 95.5 f 1.3+ 82.5 f 3.0 112cm 66 84.8 f 4.4+ 77.0 f 6.0

l p CO.05 compared with patients 155 years.+ p <0.05. Other differences not significant. AF = atrial fibrillation; ECG = electrocardiographic: LA = left atrial.

thromboembolism-free rate; p <0.05) only in the 1st A large left atria1 diameter did not influence the postoperative month (Fig. 4). thromboembolism-free period (Table I).

The group of patients with a large left atria1 diameter (12 cm or greater) had reduced operative survival in comparison with the group with a smaller left atrium (85 versus 95 percent, p <0.05), but after this period there was no significant difference in survival (Fig. 5).

Hemodynamic variables: The 387 patients who underwent cardiac catheterization were grouped according to the following variables: Cardiac index greater than 1.5 or equal to or less than 1.5 liters/min per m2, systolic pulmonary arterial pressure less than 100 or 100 or greater mm Hg, pulmonary vascular resistance less than 10 or 10 or more units, and left ventricular end- diastolic pressure less than 20 or equal to or greater than

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FIGURE 3. Actuarial survival curves of patients with mitral valve replacement according to their preoperative cardiicic ratio (C.T.R.). Patients with a markedly increased cardlothoracic ratio (75 percent or greater, n = 69) had reduced survival when compared with those with a smaller (less than 75 percent, n = 418) ratio, both within the 1st postoperative month (p <0.005) and at 3 years (p <O.OOS). However, the effect on 3 year suvival is due to the effect of cardiothoracic ratio on operative survival being carried through.

96.9 f 1.8 89.3 f 4.1’ 97.3 f 0.8 78.2 f 3.0 95.8 f 2.4 73.1 f 7.4

96.9 f 1.4 85.3 f 4.0 98.7 f 1.3 78.1 f 6.9 96.8 f 1.0 77.0 f 3.2

98.3 f 1.0 80.7 f 4.3 96.5 f 1.0 78.4 f 2.9

98.1 f 0.8 78.6 f 3.7 97.0 f 2.1 74.5 f 7.9

1

‘42 1-A

1 2 3 YEARS

FIGURE 4. Actuarial analysis of the percent freedom from thromboembolism according to cardiothoracic ratio (C.T.R.) for patients with mitral valve replacement. Patients with a large cardiothoracic ratio (75 percent or geater. n = 69) had a geater incidence of tfvoMoembolism (p cO.05) than did those with a smaller cardlothoracic ratio (less than 75 percent, n = 418) only in the 1st postoperative month.

April 1991 The Arnerlcan Journal of CARDIOLOGY Volume 47 829

b o-4/ ’ I I

62 1 2 3

YEARS

FIGURE 5. Actuarial survival curves for patients with mitral valve replacement according to preoperative left atrial (L.A.) size on chest radiography. Patients with a large left atrial diameter,( 12 cm or greater, n = 66) had reduced operative survival compared with those with a smaller (less than 12 cm, n = 268) left atrial diameter (p <0.05). There was no difference in survival beyond the 1st operative month.

20 mm Hg. The number of patients in each category, their percent survival and percent freedom from thromboembolism are shown in Table II. None of the abnormal hemodynamic variables individually pre- dicted a reduced early or late survival or reduced thromboembolism-free period. However, when patients were grouped according to the presence or absence of any one severely altered hemodynamic variable, reduced perioperative survival could be demonstrated in that group with poorer hemodynamics (91 versus 97 percent, p CO.021 (Fig. 6). Poorer hemodynamics did not influence survival after the 1st postoperative month, and had no significant influence on the thromboembolism-free period.

Coronary artery disease: Selective coronary arte- riography was performed in 126 patients. Of the 387 patients who underwent cardiac catheterization, 190 were more than 40 years old and coronary arteriograms were performed in 119 (66 percent) of these patients. The coronary arteriograms were abnormal in 12 patients, of whom 11 were more than 40 years old. Coro- nary arterial bypass surgery was performed at the time of mitral valve replacement in seven patients with no associated operative mortality. The remaining five patients did not undergo revascularization at the time of valve replacement. There was one perioperative death in this latter group. Because of the small number of patients with coronary artery disease and the isolated death it is not possible to draw any conclusions from our study concerning the effect of concomitant coronary artery disease on survival in patients undergoing mitral valve replacement.

Discriminant analysis results: The interrelations among the variables were investigated by means of a multiway contingency table analysis, analysis of vari-


ante and tested for significance by chi-square analysis. Significant interrelations (p <O.Ol) were demonstrated among the following variables: cardiothoracic ratio, type of lesion and patient age; cardiothoracic ratio, heart rhythm and patient age; type of valve prosthesis, valve lesion and heart rhythm; cardiac index, pulmonary vascular resistance and left ventricular end-diastolic pressure; pulmonary vascular resistance, cardiac index and pulmonary arterial pressure. It is less statistically valid to emphasize the specific relation responsible for these observations.

However, the following general observations may be made about our population group: A cardiothoracic ratio of 75 percent or more was as common in patients with isolated mitral stenosis as in those with isolated regurgitation, was encountered more frequently in patients less than 19 years of age and more frequently in patients with atria1 fibrillation than might have been expected on the basis of probability; Starr-Edwards valves were used more commonly in patients with preoperative atria1 fibrillation and in those with mitral stenosis; a pulmonary vascular resistance 10 or more units was more prevalent in patients with a cardiac index of 1.5 liters/min per m2 or greater, a left ventricular end-diastolic pressure of 20 mm Hg or greater or a pulmonary arterial pressure of 100 mm Hg or greater-an interrelation that is largely mathematical in nature.

These data are included merely for the sake of com- pleteness but will not be discussed further. The mathematical interrelation of the hemodynamic data is largely predictable and the remaining interrelations, while seeming to characterize our patient group, are not necessarily generally applicable.

Discussion

The factors influencing the outcome of isolated mitral valve replacement have been the subject of many studies.1-22 Roberts1 has suggested that the major factors that determine the outcome are the skill of the surgical team, the type of prosthesis used and the preoperative state of the patient. In the present study op- erations were all performed by the same group of sur- geons in one institution over a 10 year period, and the overall perioperative mortality rate (7 percent) com- pares favorably with mortality data from other major surgical institutions during this period.10J1J3J5Js

Types of prostheses: Hancock and Carpentier- Edwards porcine bioprostheses and Starr-Edwards, Lillehei-Kaster and Bjdrk-Shiley mechanical prostheses were used in this series. Because only 13 patients received a Bjdrk-Shiley prosthesis they were eliminated from subsequent analyses. Other investigators27 have recently reported unsatisfactory results with this prosthesis in the mitral position in a large series of patients.

The rate of thromboembolism did not differ significantly in patients who received a porcine heterograft or mechanical prosthesis (Fig. 1). Patients in the latter group were maintained on long-term anticoagulant therapy, except when this proved impractical or was contraindicated. Patients in the group with a hetero-

830 April 1991 The American Journal of CARMOLOGY Volume 47


graft were treated with an anticoagulant agent for the first 3 months postoperatively, after which the agent was withdrawn, providing sinus rhythm was present, the heart was not greatly enlarged and there was no past history of thromboembolism. Thus, the advantage to patients with a heterograft was that they did not have the inconvenience of oral anticoagulant therapy rather than a reduction in the incidence of thromboembolism.

Despite the favorable hemodynamic characteristics of the Lillehei-Kaster mitral prosthesis,28 we2g have previously reported our unsatisfactory functional results with this prosthesis as a result of valve thrombosis and excessive tissue ingrowth. In the present study, Lille- hei-Kaster prostheses appeared to function less well than either the Starr-Edwards or porcine heterograft prostheses (Fig. 2), although this difference did not attain statistical significance (p = 0.059 and 0.055, re- spectively). Because this difference in prosthetic function might have distorted subsequent data analysis, and because fewer than 10 percent of patients received this prosthesis, patients who received a Lillehei-Kaster prosthesis were eliminated from the remainder of the study.

The different models of the cloth-covered Starr- Edwards prosthesis used in this group of patients have previously been shown 3o to be associated with similar early and late mortality and rate of thromboembolism. They were thus considered as a single group. There was also no demonstrable difference in mortality or rate of thromboembolism between the Hancock or Carpen- tier-Edwards heterograft, and these bioprostheses were similarly grouped for purposes of actuarial analysis.

There was no significant difference in satisfactory prosthetic valve function in patients who received a Starr-Edwards or porcine heterograft prosthesis (Fig.

I \ \

‘\ T

of-++_, 12 2 3

YEARS

FIGURE 6. Actuarial analysis of patients with mitral valve replacement according to the presence of “severe” (n = 159) or “less severe” (n = 204) hemodynamics. Patients with at least one severely altered hemodynamic variable had reduced operative survival (p <0.02) compared with that of the remaining patients. Poorer hemodynamics did not influence survival beyond the 1st postoperative month.

2). However, because the period of follow-up in patients with a porcine heterograft extended only to 2 years, the question of late bioprosthesis malfunction could not be addressed.

Age: Patient age at operation did not influence survival at operation or within the first 3 years (Table I). This finding is at variance with a number of previous reports in which both operative mortality5~s-10JsJ* and late mortalityll,l2,16,20,21 were found to be increased in

TABLE II

Relations Among Preoperative Hemodynamic Factors and Percent Survival and Freedom From Thromboembolism Hemodynamics After Mitral Valve Replacement

Percent Percent Survival Thromboembolism-Free

1. Cardiac index (liters/min per m2)

>1.5 11.5

2<yoy (mm Hg) 2100

3;9”0” (units) 110

4?;\EDP (mm Hg) 220

Severe alteration of 1. 2. 3 or 4

Absent’ _ Present

Patients Operative Late Operative Late (n) (1 mo) (3 yr) (1 mo) (3 yr)

277 95.7 f 1.2 81.4 f 3.4 97.1 f 1.0 76.4 f 4.3 86 89.5 f 3.3 80.6 f 6.7 95.3 f 2.3 76.7 f 7.5

322 95.3 f 1.2 62.3 f 3.4 97.2 f 0.9 77.5 f 4.0 42 65.7 f 5.4 71.7 f 7.9 92.9 f 4.0 72.6 f 10.2

280 95.7 f 1.2 80.0 f 3.9 96.8 f 1.1 74.9 f 4.5 82 69.0 f 3.5 62.9 f 4.7 96.3 f 2.1 62.2 f 6.5

331 94.6 f 1.2 60.5 f 3.4 97.3 f 0.9 77.6 f 3.9 33 90.9 f 5.0 83.8 f 6.7 90.9 f 5.0 68.7 f 11.9

204 97.1 f 1.2’ 81.5 f 4.5 97.1 f 1.2 77.1 f 5.2 159 90.6 f 2.3’ 80.1 f 4.3 96.2 f 1.5 76.6 f 5.4

l Difference significant (p <0.02). Other differences not significant. LVEDP = left ventricular end-diastolic pressure; PVR = pulmonary vascular resistance; SPAP = systolic pulmonary arterial pressure.

April lB81 The American Journal of CARDIOLOGY Volume 47 831

older patients. In our series, the older age group (55 years and older) is similar to that of the other series cited (variously more than 50, 55 or 60 years). Other investigators 13,1g,22 observed no increase in mortality in older patients, even in those over 70 years.17 Hochberg et al.22 found that neither preoperative mitral stenosis nor regurgitation in association with older age (greater than 60 years) adversely affected prognosis, and the change in pulmonary arterial pressure, left ventricular end-diastolic pressure, left atria1 pressure and cardiac index after operation was similar in younger and older patients. The oldest patient in our series was 70 years old. We are thus unable to comment on the outcome of mitral valve replacement in patients older than 70 years.

Mitral valve lesion: The mitral valve lesion did not influence early or late survival in this study. This finding is in agreement with the observations of others.l’-lsJ6 In contrast, Litwak et al.2 found an increased operative mortality in patients with mixed mitral valve disease. Other more recent investigators have found an increased mortality in patients with mitral regurgitation, either early7 la@ or both early and late.18 Chaffin and Daggett18 suggested that this difference in mortality was present even when patients who had mitral regurgitation on the basis of ischemic heart disease were excluded from consideration. The few patients who underwent mitral valve replacement for ischemic mitral regurgitation in our institution were specifically excluded from our series.

Cardiac rhythm: Preoperative atria1 fibrillation did not adversely affect either operative or 3 year survival. This observation is in agreement with the findings of most other investigators,ss11J2J8 although Mary et al.‘O reported an increase in late deaths in patients with preoperative atria1 fibrillation. No attempt was made in our study to analyze the effect of atria1 fibrillation in the postoperative period, but direct current cardio- version was attempted in only a minority of patients postoperatively.

Chest radiograph: cardiothoracic ratio and left atria1 size: Gross cardiomegaly, as indicated by a cardiothoracic ratio in the preoperative chest radiograph of 75 percent or greater, was associated with a 19 percent operative mortality rate compared with a 5 percent operative mortality rate in patients with a smaller ratio (p <O-005) (Fig. 3). This factor was also significant (p <0.005) at 3 years postoperatively (mortality rate 33 percent versus 16 percent). Cardiothoracic ratio did not influence late mortality directly; rather, the effect on operative mortality was carried through and was still evident at 3 years.

It is of interest that we chose a cardiothoracic ratio of 75 percent or greater as a cutoff point because, when a lower ratio was chosen (60 percent or greater), no difference could be demonstrated between the two groups. In a previous study9 a cardiothoracic ratio greater than 50 percent was found not to be associated with a higher operative mortality rate, whereas Si- monsen et al.8 could not relate an increase in “radiographic heart volume” to hospital mortality. Conversely, Kittle et a1.3 found that “left ventricular enlargement”

PREOPERATIVE FACTORS AND MITRAL VALVE REPLACEMENT-DALBY ET AL

was associated with a poor prognosis and Litwak et al.2 found that marked cardiomegaly carried a poor prognosis.

A recent study20 failed to demonstrate a significant relation between survival and angiographically determined left ventricular volumes or ejection fraction in patients with mitral valve disease. However, the inherent problems involved in making these measure- ments in patients with mitral valve disease were not addressed. Specifically, the number of patients with atria1 fibrillation was not indicated and the effect of a varying heart rate on the accuracy with which both ventricular volumes and ejection fraction can be determined was not mentioned. The investigators also did not mention how the problem of gross ventricular distortion, which would negate conventional geometric assumptions in the calculation of ventricular volumes and ejection fraction, was circumvented. In the present retrospective study left ventricular volumes or ejection fractions, or both, were not measured for both practical and theoretical reasons: The majority (two thirds) of patients had atria1 fibrillation; there was frequently gross distortion of ventricular configuration, particu- larly in patients with mitral stenosis; the magnification factor was generally not known; finally, the same ejection fraction in patients with stenosis and regurgitation does not reflect the same degree of ventricular func- tion31 and there does not seem to be any simple way of normalizing the ejection fraction to enable comparison in these two conditions or in patients with varying de- grees of mixed mitral valve disease.

Large left atria1 size has previously been related to both early and late deaths.“j12 In the present study a significant increase (p <0.05) in operative mortality (from 5 to 15 percent) could be demonstrated when left atria1 diameter was 12 cm or greater as measured on the preoperative chest radiograph (Fig. 5). A measurement in excess of 7 cm has been reported to be a reliable in- dicator of left atria1 enlargement in adultsZ5

The discrepancy between the predictive value of left atria1 size and cardiothoracic ratio in the chest radiograph suggests that enlargement of other chambers plays a significant role in determining the outcome. This may, at least in part, reflect the role of left ventricular dilatation and presumed dysfunction, although this may prove difficult to quantitate.

Individual hemodynamic variables: A low cardiac index (generally less than 2.0 liters/min per m2) has been associated with a significantly increased opera- tive2J3J6Js or late mortality16J8,21, or both. However, we could not substantiate these findings in the present study. Although earlier studies2,32 and some later in- vestigationsg suggested prohibitive operative mortality rates in patients with severe pulmonary hypertension, other&Q4 found no significant increase in operative mortality in this group of patients, as was true in our series of patients. Late mortality rate does not appear to be affected by the degree of preoperative pulmonary hypertension either in our study or in the other studies cited.

Pulmonary vascular resistance greater than 10 units (800 dynes s cmm5) was also not associated with a sig-

832 April 1981 The American Journal ol CARDIDLDGY Volume 47


nificant increase in either operative or late mortality in our patients. This finding contrasts with the findings of certain other investigators.sTg,ls Zoner et aL6 suggested that for any given level of pulmonary vascular resistance, operative mortality decreased as pulmonary arterial pressure increased; that is, an elevated pulmonary vascular resistance carries a worse prognosis when it is associated with a low cardiac index rather than merely with a high pulmonary arterial pressure.

An elevated left ventricular end-diastolic pressure was associated with an increased operative and late mortality rate in some studies’fi,‘s but not in others.20 In our study, a left ventricular end-diastolic pressure greater than 20 mm Hg was not associated with a significant increase in either operative or late mortality rate.

Grouped hemodynamic variables: Although abnormality of a single hemodynamic variable (cardiac index, systolic pulmonary artery pressure, pulmonary vascular resistance or left ventricular end-diastolic pressure) was not associated with a significantly increased mortality in our group of patients, it is evident from Table II that for each variable the operative mortality was consistently higher in the group with severely abnormal as compared with less abnormal hemodynamic function. Patients were thus grouped according to the presence or absence of one or more markedly abnormal hemodynamic variables (Fig. 6). With this grouping, the presence of one or more severe alterations in hemodynamics was indeed associated with a significant increase in operative mortality (from 3 to 9 percent) (p <0.02). Pooling all patients with poor hemodynamics has the effect of eliminating from the group with better hemodynamics those patients who would otherwise be included when univariate analysis is performed and increases the confidence limits of the group with poor hemodynamics by increasing the sample size. Thus it is probable that each hemodynamic variable studied does indeed influence operative survival and that our failure to demonstrate the significance of these individually is a product of univariate analysis and population size, albeit apparently large. This may also account for the conflicting results obtained in earlier studies.

Poor preoperative hemodynamics, either individually or as a group, did not adversely affect long-term

survival in our patients. Because elevated pulmonary arterial pressure and vascular resistance and depressed cardiac index generally return to near normal levels within days after mitral valve replacement,““.:34 although hemodynamics may still be abnormal in response to exercise,““,“6 it is not surprising that preoperative hemodynamics did not seem to influence late survival.

Preoperative factors influencing thromboembolic rate: A cardiothoracic ratio of 75 percent or greater was associated with operative but not with late thromboembolic events (Fig. 4). No other variable in our study was associated with either early or late thromboembolic phenomena. In particular, left atria1 size was not associated with either early or late thromboembolic complications in our patients, although Barnhorst et a1.12 found such an association. Patients with atria1 fibrillation preoperatively also did not have an increased thromboembolic rate in our series, in contrast with the findings of some other investigators.lg The major factors determining the rate of thromboembolism postoperatively thus appear to be related to the type of prosthesis and the adequacy of anticoagulant therapy7,’ ‘,I2 rather than to preoperative variables.10~Z~7

Clinical implications: (1) The presence of any one severely abnormal hemodynamic variable in patients undergoing mitral valve replacement is associated with increased operative mortality. However, if these patients survive operation, their late mortality rate is similar to that of patients with less severe hemodynamic abnormality. They should thus be treated with particular care during the perioperative period. (2) Marked cardiomegaly on chest radiography is associated with a considerable increase in operative mortality. (3) Perioperative thromboembolic events are more frequent in patients with marked cardiomegaly, but rates of both early and late thromboembolism appear to be unrelated to any other preoperative factor. Type of prosthetic valve and the adequacy of anticoagulant therapy may thus be more important determinants of thromboembolic events after mitral valve replacement than are preoperative factors.

Acknowledgment

We are indebted to S. G. Reinach, PhD and T. J. v. W. Kotze, PhD for help with the statistical analysis and to Juanita Alexander and Merle Greenblatt for secretarial assistance.

References

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Documents

Preoperative factors affecting the outcome of isolated mitral valve replacement: A 10 year review