(Circulation. 1995;92:137-142.)
© 1995 American Heart Association, Inc.
Articles |
Long-term Outcome of Cardiac Surgery in Patients With Mitral Stenosis and Severe Pulmonary Hypertension
Presented in part at the 67th Scientific Sessions of the American Heart Association, Dallas, Tex, November 17, 1994.
From the University of Pennsylvania Medical Center, Philadelphia.
Correspondence to Howard C. Herrmann, MD, Director, Interventional Cardiology, University of Pennsylvania Medical Center, 3400 Spruce St, 9 Founders Pavilion, Philadelphia, PA 19104.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background Pulmonary hypertension increases perioperative risk in patients having mitral valve replacement, but most studies have included patients with mixed mitral valve disease and have not examined long-term outcome.
Methods and Results We retrospectively examined the results and
predictors of outcome of cardiac surgery in 43 patients (age, 62±13
years [mean±SD]; 81% women) with a primary diagnosis of
mitral
stenosis and severe pulmonary hypertension
(pulmonary artery systolic pressure 
60 mm Hg or mean
pressure 50 mm Hg). Patients with more than mild mitral
regurgitation were excluded. Thirty-eight patients
(88%) were in NYHA functional class III or IV, and 11 patients (26%)
had an acute presentation requiring urgent surgery.
Preoperative hemodynamics demonstrated a mean mitral
valve area of 0.7±0.3 cm2, mean pulmonary
artery pressure of 50±9 mm Hg, and pulmonary artery
systolic pressure of 81±18 mm Hg. Other characteristics
included right ventricular failure (18 patients),
coronary artery disease (16 patients), and critical aortic
stenosis (11 patients). Forty patients underwent mitral valve
replacement with St Jude prostheses; 3 had open commissurotomy.
Additional surgical procedures included aortic valve replacement
(42%), coronary artery bypass graft surgery (26%), and
tricuspid valvuloplasty (16%). There were 5
perioperative deaths (11.6%), and 7 other patients
(16%) had major complications, including reoperation for
hemorrhage, stroke, respiratory failure, myocardial infarction,
or a >30-day hospitalization. Univariate analysis
of demographic, hemodynamic, and operative
characteristics identified the following predictors of
perioperative death (P<.05): acute
presentation, clinical evidence of right
ventricular failure, impaired left ventricular
ejection fraction, and increased left ventricular
diastolic pressure. Predictors of complications
(P<.05) were acute presentation, ECG evidence
of right ventricular hypertrophy, and elevated
right ventricular systolic pressure.
Multivariate analysis showed only acute
presentation and right ventricular
hypertrophy as predictors of perioperative
death or major complications, respectively. Five- and 10-year actuarial
survivals were 80% and 64%, respectively. The only predictor of
long-term mortality was advanced age. Functional NYHA status was
improved by one grade or more in 76% of survivors.
Conclusions Patients referred to a tertiary care hospital in the United States with mitral stenosis and severe pulmonary hypertension often have other associated cardiac diseases and comorbid conditions. Cardiac surgery can be successfully performed with an acceptable mortality, and risk factors for poor perioperative outcome can be identified by preoperative clinical characteristics. Younger patients have the best long-term survival, and most survivors experienced long-term improvement in functional status.
Key Words: mitral valve • stenosis • hypertension, pulmonary • surgery
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Pulmonary hypertension increases the perioperative risk in patients undergoing mitral valve surgery,1 2 3 4 5 6 7 with a reported mortality as high as 31%.4 Some investigators8 9 10 11 12 13 have failed to demonstrate this association, but comparison of these studies is difficult because of differences in patient demographics, definitions of pulmonary hypertension, surgical techniques, associated cardiac diseases, and postoperative care. Several studies1 2 3 4 6 7 11 14 were conducted before the routine use of cardioplegic techniques and advanced postoperative care, and other studies1 3 4 8 9 11 included heterogeneous populations of patients with mixed mitral valve disease and other valvular or coronary arterial lesions. Few studies have addressed the long-term outcome of such patients. In addition, new interest in the problem of mitral stenosis with severe pulmonary hypertension has resulted from the development of a nonsurgical therapeutic alternative, percutaneous balloon mitral valvuloplasty.15 16 17 18 19 Thus, in the present study, we retrospectively examined patients with rheumatic mitral stenosis and severe pulmonary hypertension treated surgically at our institution over an 11-year period to determine predictors of acute outcome and long-term survival.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Study Population
The study population consisted of 43 patients with mitral stenosis and severe PA hypertension who underwent mitral valve surgery at the Hospital of the University of Pennsylvania between 1981 and 1992. Patients were identified by review of operative reports and medical records. A total of 524 patients underwent mitral valve surgery during the study period. Patients were included if they had severe pulmonary hypertension (PA systolic pressure
60 mm Hg or mean PA pressure 50 mm Hg) and did not have
significant mitral regurgitation (mitral
regurgitation 
1+ by left ventriculography or mild by
echocardiographic determination).
Data Collection and Definitions
Chart review was conducted by
two physicians. The following
demographic, historical, and physical examination data were collected:
patients' age, sex, NYHA functional classification, clinical signs of
right heart failure (jugular vein distension >10 cm, ascites, or edema
extending above the knees), history of hypertension, coronary
artery disease and angina, prior cardiac surgery, diabetes mellitus,
lung disease, renal insufficiency, liver disease, morbid obesity, and
other serious illness. Patients requiring hospitalization for worsening
symptoms over a period of 4 weeks and undergoing surgery on the
initial hospitalization were defined as having acute
presentations and the need for urgent surgery. Laboratory
data included ECG analysis of rhythm and the presence of right
ventricular hypertrophy (right axis deviation
and R/S ratio >1 in V1) or left ventricular
hypertrophy (left axis deviation and voltage of S wave in
V2 + R wave in V5 35 mV or R wave in aVL 13
mV). Preoperative right heart catheterization was
performed in all patients, and most underwent coronary
angiography (98%), left ventriculography (86%), and aortography
(67%). Echocardiography also was performed in
72%. Left ventricular EF was determined by ventriculogram
when available or by echocardiography. The EF was
considered normal if 50%, mildly decreased if between 35% and 50%,
and moderate to severely decreased if 35%.
Operative data recorded included type of mitral valve surgery, other surgical procedures, and cross-clamp and cardiopulmonary bypass time. All operations used cold antegrade crystalloid or blood cardioplegia and standard cardiopulmonary bypass. Patients were hemodynamically monitored during and after operation with arterial and Swan-Ganz PA catheters.
Data Analysis
The early results of surgery were examined in
regard to two end
points: (1) death within 30 days of surgery and (2) major
complications. Major complications included death, reoperation, stroke,
renal or respiratory failure, myocardial infarction, or need for
continued hospitalization at 30 days. Long-term follow-up was
conducted by phone interview. Patients were questioned regarding their
level of activity, subsequent hospitalizations, and specifically about
the occurrence of stroke, myocardial infarction, bleeding
complications, and the need for repeat cardiac
catheterization or cardiac surgery. If the patient had
died, family members or local physicians were questioned as to the date
and cause of death.
Data were entered into a spreadsheet (Microsoft
Excel) and
analyzed with SPSS statistical software for
MacIntosh (SPSS, Inc). Continuous variables are reported as
mean±SD. Univariate analysis of predictors of
early outcome was performed with Student's t test
(continuous variables) and 
2 analysis
or Fisher's test (categorical variables).
Multivariate analysis was performed by stepwise
logistic regression. Survival analysis was performed with
Kaplan-Meier analysis and Cox regression. Results were
considered significant if P.05.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Baseline Characteristics of the Study Population
The study population consisted of 43 patients, 81% women, with a mean age of 62±13 years (range, 34 to 82 years) (Table 1
). Twenty-one (49%) had a history of systemic
hypertension, and 4 (9%) had a prior myocardial infarction. Serious
noncardiac comorbid conditions were present in almost half of the
patients, and 5 (12%) had two or more comorbid diseases (Table
2). Atrial fibrillation was present in 79%. One
third had undergone prior cardiac surgery for valvular disease.
All patients were symptomatic, and the majority (88%) were
in NYHA functional class III or IV; 42% also had clinical evidence of
right heart failure. Patient demographics are summarized in Table
1.
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Preoperative Catheterization and
Echocardiographic Parameters
Cardiac catheterization demonstrated a
mean PA
systolic pressure of 81±18 mm Hg (range, 58 to 135 mm Hg),
an average PA mean pressure of 50±9 mm Hg (range, 35 to 70 mm Hg),
and a mean pulmonary vascular resistance of 6.1±3.0 Wood units
(range, 1.4 to 12.6). Mean mitral valve area was 0.7±0.3
cm2. Cardiac output and cardiac index were 3.6±1.1 L/min
and 2.1±0.6
L · min-1 · m-2,
respectively. Sixteen patients (37%) also had aortic stenosis,
with a mean gradient of 35±17 mm Hg and a mean valve area of
0.7±0.2
cm2, and severe aortic insufficiency was present
in 6 patients (14%). Significant coronary artery disease
(50% narrowing) involving at least one artery was present in
more than one third of patients. Tricuspid valve
regurgitation by Doppler
echocardiography was present in 19 patients
(44%) and was graded as severe in 10 (23%).
Hemodynamic data are summarized in Table 3.
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Results of Surgery
Eleven patients (26%) had acute
presentations as
defined in the "Methods," although none were in cardiogenic
shock. Operations included open mitral commissurotomy (3), mitral valve
replacement (40), aortic valve replacement (18), tricuspid
valvuloplasty with Devega repair or Carpentier ring placement (7), CABG
(11), closure of an atrial septal defect (1), and repair of a sinus of
Valsalva aneurysm (1). Eighteen patients underwent mitral valve
surgery without concomitant aortic valve or coronary artery
surgery. All valve replacements were with St Jude prostheses. Three
patients (7%) required the placement of an intra-aortic balloon
pump to assist weaning from cardiopulmonary bypass.
Postoperative hemodynamics showed statistically
significant decreases in PA pressures and increases in cardiac output
and cardiac index (Table 3
).
There were five
perioperative deaths (11.6%). All five
patients had persistently low cardiac output states after surgery, two
requiring placement of an intra-aortic balloon pump to be weaned
from cardiopulmonary bypass. Contributing causes of death
included bleeding complications requiring emergent reoperation in two
of the five patients and perioperative myocardial
infarction in two patients. Coronary artery disease and history
of prior myocardial infarction were not predictive of
perioperative mortality; however, the occurrence of
postoperative myocardial infarction was a statistically significant
predictor of death (P.05).
Preoperative characteristics
that were predictors of
perioperative death (P.05) were need for
urgent surgery, right heart failure, impaired left
ventricular EF, and increased left ventricular
diastolic pressure. Poor NYHA functional status, elevated
right ventricular systolic pressure, and elevated
aortic diastolic pressure also showed trends toward
increased mortality (.05P.1). There was no difference in
perioperative mortality between patients undergoing or
not undergoing concomitant cardiac procedures of aortic valve
replacement or bypass surgery (11% versus 12%, P=NS).
Twelve patients (28%) died or had another major complication as
defined in the "Methods." Preoperative predictors of major
complications (P.05) included need for urgent surgery,
right ventricular hypertrophy, and elevated
right ventricular diastolic pressure. Trends
toward complications (.05P.1) were associated with
concomitant CABG, right heart failure, and increased PA
systolic pressure. Multivariate
analysis by stepwise logistic regression revealed only acute
presentation and right ventricular
hypertrophy as significant predictors of death and major
complications, respectively. After surgery, there was a significant
decline in mean PA pressure, from 50 to 33 mm Hg, and 79% of patients
experienced a decrease of 10 mm Hg (Table 3). Neither the
pulmonary vascular resistance nor the absolute or change in PA
pressure was predictive of perioperative mortality or
major complications.
Survival Analysis
Kaplan-Meier actuarial analysis
demonstrated an 80%
5-year and a 64% 10-year survival (Fig 1). The mean
follow-up period in patients surviving surgery was 6.4±3.7 years.
Four patients were lost to follow-up. There were five interval
deaths due to pneumonia, stroke, and transfusion-related HIV, and
two unexplained sudden deaths, one of which occurred several days after
total hip arthroplasty. Advanced age was the only significant predictor
of decreased long-term survival (P<.05). Patients older
than the median age of 61 years (mean age, 71.5±6.1 years) had a 63%
survival, while those younger than 60 years (mean age, 52.4±7.7 years)
had a 94% survival at 5 years (Fig 2). At 10 years,
survival was 21% among the older patients, while only one interval
death occurred in the younger group (Fig 2). There was no
difference in
follow-up mortality in patients with or without concomitant aortic
valve or coronary artery surgery.
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Functional NYHA status was improved
by one class or more in 25
patients, which represents 76% of the survivors for whom
follow-up was available (Fig 3). Overall, 61% of
patients were alive and improved by surgery, with a mean follow-up
of 77±44 months (range, 15 to 140 months). At the time of
follow-up, 23 patients (82%) were in NYHA class I or II, five
(18%) were in class III, and no patients were in class IV. The mean
NYHA class improved from 3.2±0.6 before surgery to 1.7±0.8 in
the
surviving patients (P<.05). Nine patients (27%) required
hospital admission for cardiovascular diagnoses during
the follow-up period. There were two admissions for congestive
heart failure, one of which occurred within 2 weeks of surgery. One
patient sustained a myocardial infarction, and a second required bypass
surgery for progression of coronary artery disease 96 months
after surgery. Two patients were admitted for arrhythmias; one
required placement of a permanent pacemaker. The remainder of the
diagnoses included chest pain of unclear cause, stroke, and severe
epistaxis. One patient who was initially classified as having a major
complication in the perioperative period secondary to
renal failure requiring dialysis at the time of discharge had
subsequent improvement in his renal function and no longer requires
dialysis.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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This retrospective analysis of patients with severe pulmonary hypertension and mitral stenosis treated surgically demonstrates a perioperative mortality of 12% and a survival of 80% at 5 years, with >90% follow-up. Survivors demonstrated marked symptomatic improvement, with 82% in NYHA classes I and II. The study population reflects patients currently referred to a tertiary care facility in the United States with this problem. These patients tend to be older and have more associated cardiac lesions and comorbidity than patients with recent rheumatic fever presented in earlier studies.
Previous Studies
Pulmonary hypertension has been considered a
risk factor
for poor outcome in patients undergoing mitral valve replacement, with
operative mortality rates ranging from 15% to
31%.1 2 3 4 5 6 7
Najafi et al7 found the degree of pulmonary
hypertension to be strongly correlated with
perioperative mortality, ranging from 16% in patients
with mild pulmonary hypertension to 61% in patients with
systemic pulmonary pressures.
Other factors that increase operative risk in patients undergoing mitral valve surgery include age,1 4 5 8 12 20 left ventricular EF,1 8 20 functional class,1 5 7 8 12 14 type of surgery (valvuloplasty versus valve replacement),4 10 presence of coronary artery disease,1 5 8 12 14 concomitant surgery,4 8 12 14 mitral regurgitation,1 2 5 10 12 13 and mitral valve calcification.2 4 The heterogeneity of study populations in regard to these factors has limited the generalizability of these results.
Recently, several reports have demonstrated improved outcome, 6% to 8% perioperative mortality, in patients with pulmonary hypertension undergoing mitral valve replacement.9 13 These authors attributed the improved survival of their patients to the routine use of cardioplegia and improved postoperative care in an intensive care unit.
Present Study
In light of the conflicting data on the risk of
pulmonary
hypertension in patients undergoing mitral valve replacement, we
conducted this study with the goals of determining operative and
long-term morbidity and mortality, as well as to identify
preoperative predictors of outcome. We excluded patients with greater
than mild mitral regurgitation to make the study
population more homogeneous. To the best of our knowledge,
this is the largest case series of patients with pure mitral
stenosis and severe pulmonary hypertension undergoing
mitral valve surgery that provides long-term follow-up.
Our study demonstrates that mitral valve replacement can be done in patients with an acceptable albeit increased operative mortality of 11.6%. Camara et al9 reported more favorable results, with an operative mortality of 5.6%; however, the patients in our study were older (62 versus 48 years) and had a greater incidence of comorbid cardiac disease, including coronary artery disease requiring concomitant CABG (37% versus 5.6%) and aortic valve disease requiring valve replacement (42% versus 0%). Similarly, McIlduff et al13 reported an operative mortality of 7.7% in a population (average age, 57 years) with lower rates of concomitant aortic valve replacement (27%) and CABG (15%).
Predictors of operative mortality included acute presentation, decreased left ventricular EF, right heart failure, and increased left ventricular end-diastolic pressure. The association of the need for urgent surgery and mortality has been noted in previous studies5 8 20 and probably reflects more severe or decompensated disease. In our study, 11 patients (26%) had acute presentations with rapid clinical deterioration requiring urgent surgery. This factor was predictive of both operative mortality and major complications. Preoperative NYHA functional status has been previously identified as a predictor of operative mortality,1 5 7 8 12 14 and this was confirmed in our study. Similarly, decreased EF1 8 14 and increased left ventricular end-diastolic pressure1 5 8 have been identified in several studies as risk factors for operative mortality in patients undergoing mitral valve surgery. Our study also identified clinical right heart failure as a predictor of operative mortality and both elevated right ventricular systolic pressure and right ventricular hypertrophy as predictors of poor outcome. These findings probably reflect more severe or long-standing pulmonary hypertension and may increase the risk of right ventricular failure after surgery. In this regard, other investigators have also identified severe tricuspid regurgitation and the need for concomitant tricuspid valve surgery as risk factors for operative mortality in this population.5 12 21 22
Longitudinal follow-up demonstrated a survival of 80% at 5 years
and 64% at 10 years. Age was the only perioperative
variable predictive of survival. When patients were stratified into
two groups by the median age, patients 60 years old (mean, 52.4±7.7
years) had a 94% 5-year survival, which is similar to the 86% 5-year
survival reported by Camara et al,9 despite the higher
incidence of other comorbid cardiac conditions in our patients. NYHA
functional status improved by one class or more in 73% of the
survivors for whom follow-up was available.
Implications for Alternative Therapy
In recent years, there
has been increasing interest in using
percutaneous balloon valvuloplasty as an alternative to
surgery in patients with mitral stenosis. This procedure has a
very low mortality and excellent early efficacy and appears to result
in good midterm improvement at 5 years.23 The acute
results and safety of the procedure in patients with long-standing
mitral stenosis and severe pulmonary hypertension have
been reported, but no long-term follow-up is available.
Five recent case series have reported the use of balloon mitral valvuloplasty in patients with mitral stenosis and pulmonary hypertension.15 16 17 18 19 Procedural success rates ranged from 88% to 100%. Major complications occurred in 0% to 6% of patients. Mitral regurgitation increased by more than one grade in 7% to 40% of patients. Clinical improvement in NYHA functional classification occurred in 80% to 91% of patients.15 16 19 Fourteen percent of patients had clinical deterioration with significant restenosis (>50% reduction in postvalvuloplasty mitral valve area) during a mean follow-up of 7 to 14 months,15 18 19 and up to 64% had a decrease in valve area.15
Improvement of PA pressure was demonstrated in several of these studies. Mean PA pressures declined from 51 to 40 mm Hg in the Alfonso et al19 study and from 60 to 41 mm Hg in the Wisenbaugh et al17 study. These results are similar to our surgical series, in which the mean PA pressures declined from 50 to 33 mm Hg. The Georgeson et al18 study, however, demonstrated smaller declines in right ventricular systolic pressure, from 53±4 to 48±4 mm Hg (P<.001), and 17-month follow-up demonstrated an increase to 53 mm Hg, which was not significantly different from prevalvuloplasty.
These studies demonstrate that balloon valvuloplasty can be technically performed in patients with severe pulmonary hypertension, but with variable success and risk. This procedure appears to be most efficacious in younger patients without comorbid cardiac disease. Long-term symptomatic improvement has yet to be demonstrated for balloon valvuloplasty in this patient population. In studies of older patients with associated coronary artery and aortic valve disease, the results were less favorable.15 16 18 Direct comparison with our study group is difficult, but our procedural mortality (12%) is comparable to the 9% found by Lefevre et al.16 In addition, the patients referred for surgery had a high frequency of other associated cardiac conditions.
Limitations of the Study
The limitations of our study are its
small size and retrospective
design. The small number of patients limits the statistical power of
the study. Our study population includes a number of patients who
required other cardiac surgical procedures in addition to mitral valve
surgery. This could limit the generalizability of our findings.
However, we found no difference in either 30-day or long-term
mortality between patients requiring or not requiring additional
cardiac surgery. Despite these limitations, this study is the largest
reported series of patients with severe pulmonary hypertension
and mitral stenosis undergoing mitral valve surgery in the
modern surgical era.
Summary
This study demonstrates that mitral valve surgery can
be performed
in older patients with mitral stenosis, severe
pulmonary hypertension, and comorbid cardiac and noncardiac
disease with an acceptable but increased perioperative
risk. Younger patients with mitral stenosis and severe
pulmonary hypertension have an excellent long-term survival
after surgery, and the majority of survivors experience
symptomatic improvement. Predictors of operative mortality
and long-term survival may identify subgroups of patients who could
be treated by alternative therapies such as balloon valvuloplasty.
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Selected Abbreviations and Acronyms |
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References |
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TopAbstractIntroductionMethods Results Discussion References |
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