Long-term Outcome of Cardiac Surgery in Patients With Mitral Stenosis and Severe Pulmonary Hypertension
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.
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.
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.
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 χ2 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.
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⇓.
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⇓.
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 (.05≤P≤.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 (.05≤P≤.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.
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.
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.
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.
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.
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.
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.
Selected Abbreviations and Acronyms
|CABG||=||coronary artery bypass graft surgery|
|NYHA||=||New York Heart Association|
Presented in part at the 67th Scientific Sessions of the American Heart Association, Dallas, Tex, November 17, 1994.
- Copyright © 1995 by American Heart Association
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