Clinical communications

The effect of preoperative systemic blood pressure on closed mitral valvuloplasty

A study of 1,630 patients with up to 15 year follow-up

Herbert Benson, M.D. Laurence B. Ellis, M.D.* Dwight E. Harken, M.D.

Boston, Mass.

I n patients undergoing closed mitral valvuloplasty for mitral stenosis, the

presence of preoperative mitral valve calcification and mitral insufficiency have an adverse influence upon progn0sis.i The importance of preoperative systemic hypertension, however, as a poor prog- nostic sign in such patients has not been generahy recognized. Our recent experience suggested that hypertensive patients had a higher mortality than did others with similar degrees of mitral valve disease. Therefore, a review was carried out in a large group of patients who had undergone mitral valvuloplasty to determine the effect of hypertension upon operative mortality and late results.

Methodology

A review was made of 1,630 consecutive patients with predominant mitral stenosis who underwent closed mitral valvulo- plasty between Sept. 26, 1951, and April 30, 1966. These 1,630 patients did not include the first 100 consecutive cases of

the series previously reported because of the considerably higher operative mor- tality rate in this gr0up.l Fifty-two pa- tients aged 60 or over at the time of oper- ation were also excluded. Preoperative blood pressures were not available, largely due to misplacement of records, in 3.5 of these 1,630 patients, and the remaining 1,595 cases (97.8 per cent) formed the basis of this study. The patients were fol- lowed from 1 to 1.5 years postoperatively.

The preoperative blood pressures were taken almost exclusively from hospital records. The admitting hospital blood pressures recorded by a physician were used, except in a very few instances when such were not available and the pressures from nurses’ admitting notes or from pre- operative office visits immediately pre- ceding the operation were taken. The pa- tients were divided into the three arbitrary categories of noymotensive (less than 140 mm. Hg systolic and 90 mm. Hg diastolic), borderline hypertensive, (either 140 to 159 mm. Hg systolic or 90 to 94 mm. Hg di-

From the Thorndike Memorial Laboratory, Second and Fourth (Harvard) Medical Services, Boston City Hospital, The Surgical Service, Peter Bent Briglmm Hospital, The Thoracic Surgical Service, Mount Auburn Hospital, Cam- bridge, Mass., and The Departments of Medicine and Surgery, Harvard Medical School.

This study was supported in part by grants 2 RO 1 HE 00442, 1 PO 1 HE 10539, 5 T 1 HE 5244, HE 8698 from the National Heart Institute, National Institutes of Health, United States Public Health Service.

Received for publication April 26, 196?. *Address: Heart Station, Boston City Hospital, 818 Harrison Avenue, Boston, Mass, 02118.

439

440 Benson, Ellis, and Hwken

astolic), and hypertensive (over 159 systolic or 94 diastolic). The patients were further subdivided into two age groups: less than age 4Q (658 patients) and age 40 to 59 (93 7 patients).

All deaths during operation and after operation, but before hospital discharge, were classed as “operative deaths.” The follow-up method has been previously described.2 The patients were contacted annually by questionnaires and their sub- jective postoperative status and their ability to carry out daily activities were assessed. Records of complications and of the amount of cardiac therapy required were also obtained. Furthermore, in many instances personal follow-up examinations were carried out and physicians’ reports and hospital records were assessed. Pa- tients who were moderately or markedly better by improving one or more categories in the New York Heart Association Classi- fication were classed as &r@oved. Patients were considered f&mproved if they were slightly improved, unchanged, or worse.

An analysis was made of the postopera- tive results at 5 and 10 years. Survival curves were calculated according to the method of Berkson and Gage.3 In the calculation of the survival curves, patients reoperated upon were dropped from the analysis as lost to follow-up at the time of reoperation. The validity of including or excluding patients reoperated upon in the survival calculations has been dis- cussed previous1y.l The slight discrepancy between the number of dead noted in the analysis at 5 and 10 years postoperatively

Table I. Distribution of blood pyesswe

and the number of dead noted by the survival curve analysis at the 5 and 10 year points was due to the difference in the statistical analytical methods em- ployed. The analysis at 5 and 10 years took into account only those patients who were operated upon at least 5 and 10 years ago whereas the survival curves embraced all patients regardless of the date of operation. Also: the patients re- operated upon were included in the 5 and 10 year results, but dropped from the survival curves.

In the 1,595 cases, there were 90 opera- tive deaths. Autopsies were obtained in 64 of these operative deaths (71 per cent). XIo attempt was made to assess autopsy data on those who died in the follow-up period, because of the paucity of autopsies in these patients and the fact that these autopsies were performed in different hospitals with different autopsy protocols.

Results

Prevalence of hypedension. In the younger age group, there were 24 hypertensive and 49 borderline hypertensive patients, repre- senting only 3.7 and 7.4 per cent of the total, respectively. In the older age group, there were 100 hypertensive patients and 157 borderline hypertensive patients repre- senting 10.7 and 16.7 per cent of the total, respectively. Combining both age groups there were 124 or 7.8 per cent hypertensive patients and 206 or 12.9 per cent borderline hypertensive patients (Table I).

Operative mortality rates. In the younger age ww, the operative mortality rate

I

Age < 40 I

Age N-59 ~ Totals ~-

Blood pressure 1

I No. ~ Per cent 1 No. ~ Pw cent No. T-i’irzt-

Xormotensive patients* 585 88.9 680 72.6 la26S 79.3 Borderline hypertensive patientst 49 7.4 1.57 16.7 206 12.9 Hypertensive patients1 24 3.7 100 10.7 124 7.8

-- - -- Totals 6.58 100 937 100 1,595 100

*Less than 140 mm. Hg systolic amI 90 mm. Hg diastolic. tEither 140 to 159 mm. Hg systolic ov 90 to 94 mm. Hg diastolic. IGreater than 159 mm. Hg systolic or 94 mm. Hg diastolic.

Effect of @eoperutive systemic blood presswe 441

was markedly increased in the hyperten- sive and the borderline hypertensive pa- tients when compared to the normotensive control patients. There was a 20.8, 10.2, and 3.1 per cent mortality rate in the hypertensive, borderline hypertensive, and normotensive patients, respectively. These differences were highly significant (p = 0.0001). In the older age group, the opera- tive mortality appeared less affected by the hypertension (Fig. 1, Table I I).

Status of survivors of operation at 5 years postoperatively. A total of 536 patients in

TOTAL NO. IN GROUP

TOTAL NO. IN GROUP

the younger and 673 in the older age group were followed 5 years. Patients who died in the interim or who were reoperated upon were included (Fig. 2). The follow- up was relatively complete in both age groups, only 19 patients, or 3.5 per cent, of the younger and 34, or 5.0 per cent, of the older age group were lost to fol- low-up.

In the hypertensive patients less than 40 years old, a lesser percentage were im- proved than among the normotensive and borderline hypertensive patients of the

AGE LESS THAN 40

NORM~TENS~VE BORDERLINE HYPERTENSIVE PA,TlENTS HYPERTENSIVE PATIENTS

PATlENT$

585 49 - 24 - -

AGE 40- 59

NORMOTENSIVE BORDERLINE HYPERTENSIVE PATIENTS HYPERTENSIVE PATIENTS

PATIENTS 660 - I57 - IO0 -

Fig. 1. The relationship of preoperative systemic blood pressure to hospital mortality rate of patients under- going mitral \Talvuloplasty.

< MJ Normotensive patients* ss!s Borderline hypertensive patients? 49

Hypertensive patients1 24

Total a3

40-59 Normotensive patients* 680 Borderline hypertensive patientst 157 Hypertensive patientst 100

Total 937

Grand totals 1,595

18 5 5

- 28

40 1.5

7 - 62

- 90

3.1 10.2 20.8

4.2

5.9 9.5 7.0

6.6

5.6

*Less than 140 mm. Hg systolic and 90 mm. Hg diastolic. TEither 140 to 1.59 mm. Hg systolic or 90 to 94 nun. Hg diastolic. IGreater than 159 mm. Hg systolic or 94 mm. Hg diastolic,

AGE -=40 AGE 40-53

TOTAL NO. s IN GROUP

LOST TO I5 FOLLOW UP -

B ,*.-.a3 . . . ‘.a.*.’ I.:.:.’ *.*:

-

u

F :& . . . ‘.a:. :.:.I*’ . . .’ ,:.*. ‘.*.*.a :.*: . . .

-

Fig. 2. The relationship of preoperative systemic blood pressure to the status of patients 5 years postoperatively.

Vohme 7.5 Number 4

PER CENT

40

20

AGE c40

TOTAL NO. 316 IN GROUP -

LOST TO FOLLOW UP

?l?

Effect of preoperative systemic blood presswe 443

AGE 40-59

22 -

. . . . . ,.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . :.*::, . . . . .

2 “- $ Sk= OLU!! ECLI- gg2

69 -

2 -

REOPERATED

IMPROVED

Fig. 3. The relationship of preoperative systemic blood pressure to the status of patients IO years postopera- tively.

same age group. These differences were not statistically significant (Fig. 2).

In the hypertensive patients of the 40 to 59 age group there was a lower percent- age improved and a higher percentage of deaths, reoperations, and unimproved than in the normotensive and borderline hyper- tensive patients. These differences were statistically significant (p = 0.05) (Fig. 2).

Status of survivors of operation at 10 years postoperatively. A total of 3.58 patients in the younger and 380 patients in the older age group were followed 10 years. Patients who died in the interim or who were reoperated upon were also included (Fig. 3). In the younger age group, 43, or 12.0 per cent, and in the older age group, 2.5, or 6.6 per cent, were lost to follow-up.

In the less than 40 age group, sizable and statistically significant differences ap- peared when normotensive and borderline hypertensive patients were compared to the hypertensive patients. The hyper- tensive patients had a lower percentage improved, a higher percentage of re- operations and unimproved, and a mark- edly higher percentage dead (p = 0.05) (Fig. 3).

In the 40 to 59 age group, a similar distribution was noted with the hyper- tensive patients having a lower percentage improved and a higher percentage dead than did the normotensive and borderline hypertensive patients. These differences, however, were not statistically significant (Fig. 3).

444 Benson, Ellis, and Hurken

6C

5C

4c

30

20

IO

0

- NORMOTENStVE PATIENTS . ..v.......+.... EORDERLINE HYPERTENSIVE PATIENTS

. . . . ..s.. HYPERTENSIVE PATIENTS

II 11, , , , , , , l23456?

I I 1 8 9 IO II I2 I3 I4 I5

YEARS AFTER LEAVING HOSPITAL

Fig. 4. The relationship of preoperative systemic blood pressure to the survival rates of patients 40 to 59 years- old undergoing mitral valvuloplasty. The vertical lines represent k 2 standard ert-ors.

Swuivd Curves years, and 63 per cent survived 15 years. There were too few patients with border- Borderline hypertensive patients up to

line hypertension or with hypertension in 12 years follow-up fared better than the the younger age group who survived the hypertensive patients, but worse than the operation to calculate survival curves. normotensive patients. From 12 to 15

In the older age group, the hypertensive years, no deaths occurred in the borderline patients had a lower per cent survival hypertensive group and their per cent throughout all the 15 years of follow-up survival exceeded that of the normotensive (Fig. 4). Seventy-nine per cent of the hy- group (Fig. 4). pertensive patients survived 5 years, 60 Autopsy Duta per cent survived 10 years, and 40 per No consistent relationship w-as observed cent survived 15 years. In contrast, 91 in the 64 autopsy cases between increased per cent of the normotensive patients blood pressure in either age group and the survived 5 years, 74 per cent survived 10 presence of macro- or microscopic renal

Efect of @eoperative systemic blood pressure 44.5

Table III. Analysis of blood pressure in relation to renal infarction in 64 autopsied cases

Blood pressure

Xormotensive patients* 7 11 18 8 18 26 44 Borderline hypertensive patientst 1 7 8 1 1 2 10 Hypertensive patients3 2 1 3 2 5 7 10

- - - - - - Totals 10 19 29 11 24 35 64

*Less than 140 mm. Hg systolic and 90 mm. Hg diastolic, tEither 140 to 159 mm. Hg systolic w 90 to 94 mm, Hg diastolic, ZGreater than 159 mm. Hg systolic w 94 mm. Hg diastolic.

Table IV. Anulysis of atrial jibrdlatiox in relation to renal infarction in 64 autopsied cases

Renal &far&on No renal &far&on

Rhythm

~ I

& < 40

6 1

i

d-?SJ ~ T&d 1 :%I 1 d?9 ~ Total “‘a’s

18 24 ? 20 27 51 4 5 5 3 8 13

- - - - - 22 29 12 23 35 64

infarction, nor was there any consistent relationship between the presence of atria1 fibrillation and the presence of renal in- farction (Tables III and IV).

Discussion

The major objectives of this study were to ascertain in a retrospective fashion whether elevations in blood pressure in- fluence operative results and long-term follow-up of patients undergoing mitral valvuloplasty and also to review the litera- ture concerning elevated blood pressure and mitral stenosis. The admitting hospital blood pressure was used to divide arbitrar- ily the patients into three categories of blood pressure. It is recognized that there are objections to the use of a single, pre- operative, hospital blood pressure taken by different observers for analysis. Anxiety of a patient before an operation, anxiety of a patient in a hospital, and observer

variation may all produce spurious eleva- tions or errors in blood pressure determi- nation. Some objective support for the validity of the elevated blood pressures in this series was gained by relating nephro- sclerosis at autopsy to the level of pre- operative blood pressure (Table V). The presence or absence of nephrosclerosis was noted in 60 of the 64 autopsied cases. In the normotensive patients there were fewer patients with nephrosclerosis than without nephrosclerosis. In the hyperten- sive patients, there were more patients with nephrosclerosis. These differences were statistically significant (p = 0.05).

There have been conflicting reports concerning the prevalence of hypertension in mitral stenosis. Gibson* in 1909 and subsequently others5-* claimed that the prevalence of hypertension in mitral ste- nosis exceeded that in normal controls. Othersg-l1 found little difference in blood

446 Benson, Ellis, and Harken

Table V. The relationship of nephrosclerosis to blood pressure

Blood pressure

Normotensive patients* Borderline hypertensive

patients? Hypertensive patients$

Totals

iVe~hmsc1e~osi.s No nephroscleqosis ~~

IAge < 4O~AgeRL.59~ Total page < #~Age40-59~ Total

3 11 14 9 18 27

1 4 5 1 4 .5 2 5 7 1 1 2

- - - - 6 20 26 11 23 34

Totals

41

10 9

- 60

*Less than 140 mm. Hg systolic a& 90 nun. Hg diastolic. tEither 140 to 159 nun. Hg systolic o? 90 to 94 mm. Hg diastolic. :Greater than 159 mm Hg systolic w 94 mm. Hg diastolic.

pressure between patients with mitral stenosis and controls. Evidence has also been presented that hypertension is rela- tively uncommon in mitral stenosis.lz-l4 The data from the various series are dif- ficult to compare because of various defi- nitions of hypertension, of inadequate controls in several instances, and of t.he great span of more than SO years over which the different studies were conducted.

Our data do not clarify these discrepant opinions concerning the prevalence of hypertension in mitral stenosis. Since our analysis was confined to patients with mitral stenosis requiring operation, it dealt only with a selected population of patients and was not necessarily repre- sentative of the entire population of pa- tients with mitral stenosis.

It was noted by Keith and associate@ in 1963 in their series of 94 patients, that systemic blood pressure was greater than 140/90 in 6 patients. The outcome of mitral valvuloplasty in these 6 patients was not good since 3 patients died at operation, 2 had poor results, and only 1 had a good result. Our data indicates that in younger patients an elevation in blood pressure carries a markedly increased risk of operative mortality. In the older age group, this added risk is not evident-

In a study of 389 patients followed 5 to 12 years following mitral commissurotz- omy, Gialloreto and Tardif16 found that preoperative arterial hypertension (the levels were not defined) occurred in 1 per cent of those with excellent results, in 0.5

per cent of those with good results, and 3 per cent of those with fair results. To our knowledge, there are no other studies commenting upon the effect of hyperten- sion on the postoperative prognosis of mitral commissurotomy.

Our data indicate that preoperative hypertension as defined, has a definite adverse effect on the postoperative course of patients undergoing mitral valvulo- plasty. Hypertensive patients had, in gen- eral, a higher percentage mortality and lower percentage of sustained improve- ment than did normotensive and border- line hypertensive patients at 5 and 10 years postoperaCvely. These differences, although not, consistently statistically sig- nificant, were such as to suggest an ad- verse effect of hypertension.

The survival curves further strengthen the prospect of an adverse prognosis with preoperative hypertension. In follow-up studies up to 12 years, the per cent survival was consistently less in hypertensive pa- tients when compared to the normotensive controls. The borderline hypertensive pa- tients were between these two extremes. It may be argued that the survival curve of the hypertensive patients reflects the older age of such patients and not an ad- verse effect of hypertension. The survival curves were calculated in an age group encompassing 19 years (ages 40 to 59). Because of this 19 year age spread, it is conceivable that there was a large number of hypertensive cases who were relatively old (55 to 59) and a small number who were

Effect of preoperative systemic blood @yessure 447

relatively young (40 to 44). However, the number of cases of hypertension was evenly distributed with regard to age. Furthermore, the number of cases of borderline hypertension was also evenly distributed. There was, however, an un- even distribution of the normotensive group with a relatively large number of younger cases. To what extent this in- fluenced the normotensive survival curve when compared to the other two is not known. There remains, however, a large difference in per cent survival between the borderline hypertensive patients and the hypertensive patients which supports the concept of an adverse effect of hyper- tension.

Our data do not support previous find- ings of an association of hypertension and renal infarction nor of an association of atria1 fibrillation and renal infarction.8 As noted by others,8JzJ7 we also found a high degree of association between hyper- tension and atria1 fibrillation in both age groups (p = 0%0007 and p = 0.0003). This however does not prove a causal relation- ship between atria1 fibrillation and hyper- tension. The meaning of this association is unclear.

We found a highly significant relation- ship between increased cardiac limitation and hypertension in the older age group (p = O.OOOl), and it could be argued that the hypertension was, in part, secondary to large numbers of patients with conges- tive heart failure and its attendant in- creased peripheral resistance in this cate- gory. Increased peripheral resistance may well be a factor contributing to the pres- ence of hypertension in some cases, but congestive heart failure often leads to decreased blood pressure in spite of this increased peripheral resistance. Further- more, it could be speculated that hyper- tension is a primary factor causing in- creased cardiac limitation.

We therefore may only hypothesize on the pathogenesis of hypertension in mitral stenosis. Although in some cases it may be due to renal embolization secondary to atria1 fibrillation, our data do not sup- port such a consistent over-all causal relationship. It may also be due in some instances to the presence of congestive heart failure and its secondary increased

peripheral resistance. On the other hand, it may be completely independent of the associated mitral valve disease.

It has been widely believed that hyper- tension improves the prognosis in un- operated mitral stenosis.7 The hypertension was thought to lead to left ventricular dilatation that in turn would stretch the atrioventricular ring and open the stenotic mitral orifice. Another rationale offered for this hypothetical advantage of hyper- tension was that there was right ventricular overload in mitral stenosis leading to an imbalance of the two ventricles. By im- posing a load on the left ventricle with 1 rypertension, this imbalance was cor- rected.’ Alternatively, others found no appreciable change in the life expectancy in the presence of mitral stenosis un- operated upon when the hypertensive patients were compared to normotensive patient+ while still others found that hypertension in mitral stenosis without operation was a bad prognostic sign.12

The pathogenetic mechanism of the adverse effect of preoperative hypertension in mitral stenosis is also unclear. It may be that, in hypertensive patients, otherwise mild degrees of mitral insufficiency follow- ing valvuloplasty become more pronounced because of increased left ventricular pres- sures. Alternatively, this adverse effect may be due to the volume overloading, after the relief of mitral stenosis, of a left ventricle already working against increased pressure. It may also be argued that there is a general, nonspecific, adverse effect of hypertension on patients undergoing any surgery and that our series reflects this general adverse effect. This latter possibility may indeed be valid, but it cannot be verified in this present study.

It has been well established that the presence of preoperative findings such as mitral insufficiency and mitral valve calci- fication have an adverse influence upon the prognosis following mitral valvulo- plasty. The presence of preoperative hyper- tension is another such adverse factor and should also be considered when selecting patients for closed mitral valvuloplasty.

Summary

A total of 1,630 consecutive patients with predominant mitral stenosis who under-

448 Benson, Ellis, and Harken.

went closed mitral valvuloplasty have been reviewed. Preoperative blood pres- sures were used to classify the patients into three categories: normotensive, border- line hypertensive, and hypertensive pa- tients. In terms of operative mortality rate, late improvement, reoperations, and survival, preoperative hypertension, in general, carried a poor prognosis. No meaningful association between the pres- ence of hypertension and postmortem renal infarction or between the presence of atria1 fibrillation and postmortem renal infarction could be found. It was felt that preoperative hypertension should be con- sidered as another, hitherto largely un- recognized, adverse prognostic factor in selecting patients for mitral valvuloplasty.

We are indebted to Dr. Hugo Muench of the Department of Bio-Statistics, Lernuel Shattuck Hospital, Jamaica Plain, Mass. for his aid with the statistical aspect of this material,

REFERENCES 1. Ellis, L. B., and Harken, D. E.: Closed valvulo-

plasty for mitral stenosis. A twelve-year follow- up study of 1571 patients, New England J. Med. 270:643, 1964.

2. Ellis, L. B., Harken, D. E., and Black, H.: A clinical study of 1,000 consecutive cases of mitral stenosis two to nine years after mitral valvuloplasty, Circulation 19:803, 19.59.

3. Berkson, J., and Gage, R. P.: Calculation of survival rates for cancer, Proc. Staff 1Meet. Mayo Clin. 25:270, 1950.

4. Gibson, G. A.: Diseases of the mitral valve ,in Albutt’s System of medicine, London, 1909, Macmillan and Co., vol. 6: p. 360.

5. Cowan, J., and Fleming, G. B.: The associa- tion between mitral stenosis and renal fibrosis, Quart. J. Med. 5:309, 1912.

6. Boas, E. P., and Fineberg, M. H.: Hyperten- sion in its relationship to mitral stenosis and aortic insufficiency, Am. J. M. SC., 172:648, 1926.

7. Levine, S. A., and Fulton, M. N.: The relation of hypertension to mitral stenosis, Am. J. M. SC. 176:465, 1928.

8. Obeyeskere, H. I., Dulake, M., Demerdask, H., and Hollister, R.: Systemic hypertension and mitral valve disease, Brit. M. J. 5459:441, 1965.

9. Horns, H. L.: Association of hypertension and mitral stenosis, AM. HEART J. 28:435, 1944.

10. Roseman, M. D., and Wasserman, F.: The incidence of hypertension in mitral stenosis, New England J: Med. 245:450,1951.

11. Grav. I, R.: Mitral stenosis and hvoertension. Bri< ‘Heart J. 16:165, 19.54. ‘-

12. Brumm, H. J., and Smith, H. L.: Hypertension associated with mitral stenosis, Rep-o& of forty four cases, Minnesota Med. 24:664, 1941.

13. Wood, P. H.: Diseases of the heart and circu- !ation, London, 19.56, Eyre and Spottiswoode, p. 547.

14. Bechgaard, P. Arterial hypertension. A follow- up study of one thousand hypertonics, Acta med. scandinav. 126: Suppl. 172, 1946.

15. Keith, T. A., Fowler, N. O., Helmsworth, J. A4., and Gralnick, H.: The course of surgically modified mitral stenosis. A study of 94 patients with emphasis on the problem of restenosis, &4m. J. Med. 34:308, 1963.

16. Gialloreto, O., and Tardif, B.: Observations on the value of mitral commissurotomy: An analysis of long-term results, Canad. M.A.J. 89589, 1963.

17. Gronath, A.: Mitral valvuloplasty. A clinical and hemodynamic pre- and postoperative study, Acta med. scandinav. 178: Suppl. 433, 196.5.