Asian Cardiovasc Thorac Ann 2008;16:37-42
© 2008 Asia Publishing EXchange Ltd
Mitral Valve Replacement in Severe Pulmonary Arterial Hypertension
Mohammad Mubeen, MCh,
Amrendra K Singh, MD,
Surendra K Agarwal, MCh,
Jeewan Pillai, MS,
Shalini Kapoor, MD1,
Ashok K Srivastava, MCh
Department of Cardiovascular and Thoracic Surgery
1 Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
For reprint information contact: Surendra K Agarwal, MCh, Tel: 91 522266 8700 Ext. 2208, Fax: 91 522 266 8017, Email: surendra{at}sgpgi.ac.in, Department of Cardiovascular and Thoracic Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014 (UP), India.
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ABSTRACT
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The immediate postoperative hemodynamics in 43 patients with severe pulmonary arterial hypertension who underwent mitral valve replacement between January 2000 and September 2001 were studied prospectively. The mean age was 30.6 years. There was mitral stenosis in 19 (44.1%), mitral regurgitation in 9 (20.9%), and mixed lesions in 15 (34.9%). In 36 patients (83.7%, group 1) pulmonary arterial pressure was sub-systemic, with a mean of 58.1 mm Hg and pulmonary vascular resistance of 743.4 dyne·s·cm–5. Seven patients (16.3%, group 2) had supra-systemic pulmonary arterial pressure of 83.2 mm Hg and pulmonary vascular resistance of 1,529 dyne·s·cm–5. Lung biopsies were taken from the right lower lobe in 24 patients. Operative mortality was 5.5% in group 1 and 28.5% in group 2. After mitral valve replacement, the pulmonary arterial pressure and vascular resistance decreased significantly in group 1. In group 2, pulmonary arterial pressure decreased significantly but pulmonary vascular resistance remained elevated. Pulmonary vascular changes did not progress beyond grade III (Heath-Edwards’ classification). Mitral valve replacement is safe even in the presence of severe pulmonary arterial hypertension as long as pulmonary arterial pressures are below systemic pressures. Lung biopsy did not help in identifying patients with irreversible pulmonary arterial changes.
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INTRODUCTION
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The development of pulmonary arterial hypertension (PAH) has long been considered a risk factor for poor outcome in patients undergoing mitral valve replacement (MVR), with operative mortality ranging from 15% to 31%.1,2 Therefore, many surgeons deny operations to this high-risk group. At least 3 mechanisms contribute to PAH in mitral valve disease: passive transmission of elevated left atrial pressure, reactive pulmonary arteriolar vasoconstriction, and morphologic changes in the pulmonary vasculature. The reactive component is known to decrease immediately after mitral valve surgery. Medial hypertrophy or intimal fibrosis in the pulmonary arterioles may or may not slowly regress after MVR.3 This prospective study was conducted to assess the immediate postoperative hemodynamics in patients who underwent MVR in the presence of severe PAH, and to identify patients with irreversible pulmonary arterial changes because of structural changes in the pulmonary capillary bed.
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PATIENTS AND METHODS
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This prospective study was conducted between January 2000 and September 2001. There were 205 MVR operations performed during this period, of which 43 (21%) were in patients with rheumatic mitral valve disease and severe PAH, defined as mean pulmonary arterial pressure (PAP) > 50 mm Hg. The mean age was 30.6 years. Patients with significant aortic valve disease or coronary artery disease were excluded from the study. The 43 patients were divided into 36 with severe PAH in whom the systolic PAP did not exceed systemic pressure (group 1), and 7 with supra-systemic PAP (group 2). The baseline characteristics of these patients are shown in Table 1
. In group 1, the dominant valvular lesion was mitral stenosis (MS) in 14 (39%) patients, mitral regurgitation (MR) in 9 (25%), and mixed lesions in 13 (36%); in group 2, MS was present in 5 (71%) and mixed lesions in 2 (29%). Dominant MS was defined as a mitral valve orifice area < 1.0 cm2, dominant MR was defined as a ratio of jet area to left atrial area > 40%, and a mixed lesion met the criteria for both MS and MR. Right ventricular hypertrophy was defined on the basis of electrocardiographic and 2-dimensional transthoracic echocardiographic criteria. All preoperative assessments were carried out by 2-dimensional transthoracic echocardiography. Cardiac catheterization was not undertaken in any of these patients. All hemodynamic measurements were made in the operating room, with continuous electrocardiographic monitoring and invasive arterial blood pressure recording. A thermodilution catheter was placed in the pulmonary artery to measure PAP, pulmonary capillary wedge pressure, pulmonary vascular resistance, and cardiac index. Cardiac output was assessed by a thermodilution technique using 5% dextrose as an indicator. In the later part of the study, the thermodilution catheter was replaced with a continuous cardiac output catheter. These measurements were obtained preoperatively before the induction of general anesthesia, postoperatively immediately after MVR when the patient had been weaned from cardiopulmonary bypass (CPB), once again when the hemodynamics had been stabilized, and 24 hours after the operation. Preoperative hemodynamic values of both groups are shown in Table 2.
All patients were operated on through a median sternotomy on CPB with moderate general hypothermia (28°C–30°C). The mitral valve was approached through the left atrium in 31 (72%) patients, via the superior septum in 7 (16%), and transseptally in 5 (12%). Preservation of the posterior mitral leaflet was possible in 27 (63%) patients. All patients underwent MVR with a mechanical prosthesis: a Starr-Edwards ball and cage valve (Baxter Healthcare, Santa Ana, CA, USA) in 23, a Sorin bileaflet mechanical prosthesis (Sorin Biomedica, Saluggia, VC, Italy) in 18, and a St. Jude Medical (St. Jude Medical, Inc., St. Paul, MN, USA) bileaflet mechanical prosthesis in 2. De Vega tricuspid annuloplasty was performed in 14 (33%) patients with severe tricuspid regurgitation. The mean CPB time was 67.6 min (range, 32–137 min) and the mean aortic cross clamping time was 32.8 min (range, 17–85 min). Immediately after coming off CPB, a lung biopsy was taken from the right lower lobe in 24 (56%) patients to determine pulmonary vasculature changes. The changes were graded according to the classification of Heath and Edwards.4
All patients were given narcotic analgesics and vasodilator therapy in the form of nitroglycerine infusion until the hemodynamics stabilized and they could be extubated. Four patients in group 2 also needed milrinone infusion in the initial 24 hours. The use of inotropic agents (dopamine, adrenaline, and dobutamine) was determined by the patient’s hemodynamic status, and they were discontinued when the hemodynamics became stable and the patient was extubated. An intraaortic balloon pump was not utilized as the basic problem was right ventricular dysfunction due to PAH. We could not use nitric oxide and sildenafil for treatment of PAH due to non-availability of these agents at the time of this study. All patients received acenocoumarin when they were extubated. For those on long-term ventilation, acenocoumarin was given through a nasogastric tube. The therapeutic goal was to maintain a prothrombin ratio of 2.5–3.0. All patients also received a daily dose of 75 mg acetylsalicylic acid. All survivors were discharged on the above treatment protocol.
The values are given as mean ± standard deviation and range. A paired Student’s t test was used for comparison of two groups of data, where applicable. A p value < 0.05 was considered significant.
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RESULTS
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Four patients died in the immediate postoperative period, constituting an overall mortality rate of 9.3%. Two of these (5.6%) were in group 1, and 2 (28.6%) belonged to group 2. All deaths were caused by persistent low cardiac output due to right ventricular failure. The operative mortality for routine MVR without significant PAH at our institute was 2.4% during this period.
In group 1, the mean PAP fell by 38% from a mean preoperative level of 59.8 to 37.1 mm Hg immediately following MVR ( p < 0.01). Although it continued to decrease over the next 24 hours, this further decrease was not statistically significant (Figure 1). Similarly, the pulmonary vascular resistance (PVR) decreased by 48% from a mean preoperative value of 757.4 to 396.4 dyne·s·cm–5 immediately after MVR ( p < 0.01; Figure 2). Mean cardiac index increased from 1.98 to 2.76 L·min–1·m–2 (p < 0.01; Figure 3). In group 2, the mean PAP fell by 22% from a mean preoperative level of 83.2 to 64.5 mm Hg immediately following MVR ( p < 0.01); it decreased over the next 24 hours but this was not statistically significant (Figure 1). The PVR decreased by 24% from a mean preoperative value of 1,433 to 1,083 dyne·s·cm–5 immediately after MVR ( p > 0.05). Pulmonary vascular resistance continued to decrease significantly 24 hours after the operation (Figure 2). This group of patients showed persistent low cardiac output even after MVR. Mean cardiac index increased marginally from 1.1 to 1.25 L·min–1·m–2 (p > 0.05; Figure 3).
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Figure 1. Changes in mean pulmonary arterial pressures (PAP) in patients with severe pulmonary arterial hypertension below (group 1) and above systemic arterial pressure (group 2).
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Figure 2. Changes in pulmonary vascular resistance (PVR) of patients with severe pulmonary arterial hypertension below (group 1) and above systemic arterial pressure (group 2).
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Figure 3. Changes in cardiac index of patients with severe pulmonary arterial hypertension below (group 1) and above systemic arterial pressure (group 2).
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Seventeen (40%) patients needed prolonged ventilation, defined as > 48 hours. Five (12%) patients had persistent right ventricular dysfunction requiring prolonged inotropic support; 4 of these 5 belonged to group 2. Seven (16%) patients developed pleural effusion requiring tube thoracostomy. Three patients (7%) had a thromboembolic complication: one developed right hemiparesis, computed tomography of the brain revealed a left middle cerebral artery infarct that was managed conservatively with partial recovery; another had a transient ischemic attack involving the right upper limb, he recovered completely within 24 hours; the third patient had an embolism in the left lower limb on the first postoperative day and underwent successful embolectomy. Pulmonary vascular changes did not progress beyond grade III of the Heath-Edwards’ classification in 24 patients from whom a lung biopsy was taken (Table 3, Figures 4 and 5).
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Figure 4. Small muscular artery with evidence of medial hypertrophy from a patient in group 1 (Heath-Edwards grade II; hematoxylin and eosin stain, original magnification x400).
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Figure 5. Plexogenic pulmonary arteriopathy showing concentric laminar intimal fibrosis with narrowing of the lumen from a patient in group 2 (Heath-Edwards grade III; hematoxylin and eosin stain, original magnification x400).
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The mean follow-up was 14 ± 8 months (range, 4–22 months) and was complete in 37/39 (95%) survivors. There were no known late deaths. New York Heart Association functional class improved by at least one class in the majority of patients: 13 (35%) were in class I, 19 (51%) in class II, and 5 (14%) in class III. Pulmonary arterial pressure calculated by tricuspid regurgitation velocity was possible in only 19 (51%) patients. The mean PAP was 39 mm Hg (range, 36–47 mm Hg) in 15 patients in group 1, and 51 mm Hg (range, 48–55 mm Hg) in 4 patients in group 2. The most common complications during follow-up were related to anticoagulation. Three (8%) patients presented with thromboembolic complications, all had cerebrovascular infarcts involving the left middle cerebral artery and right hemiparesis. They all had a prothrombin ratio < 2.0 and were managed conservatively. The acenocoumarin dose was increased, and intravenous heparin was also given until the prothrombin ratio stabilized to > 2.5–3.0. Six (16%) patients presented with hemorrhagic complications, of whom 2 had bleeding from the gums and 4 had gastrointestinal bleeding. All had a prothrombin ratio > 3.5–4.0. They were managed conservatively by reducing the dose of acenocoumarin and transfusing fresh frozen plasma.
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DISCUSSION
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Pulmonary arterial hypertension has long been considered a risk factor for poor outcome in patients undergoing MVR, with operative mortality ranging from 15%–31%.1,2 Najafi and colleagues5 found the degree of PAH correlated strongly with perioperative mortality, ranging from 16% in patients with mild PAH to 23% in severe PAH and 61% when PAP was at systemic levels. Recently, several reports have demonstrated improved outcome in patients with PAH undergoing MVR, with perioperative mortality ranging from 2.3%–10%.6–9 The improved outcome was attributed to better myocardial preservation, preservation of the subvalvular apparatus, and improved postoperative care. In our study, the overall operative mortality rate was 9.3%, which is consistent with recent reports. However, the mortality rate in patients with severe PAH (group 1) was 5.5%, while that in patients with supra-systemic PAP was 28.5%, indicating the advanced nature of their disease.
Numerous studies have examined hemodynamic changes in this subset of patients at different intervals after mitral valve procedures. Most have demonstrated an immediate reduction in PAP and PVR, signifying a sudden drop in left atrial pressure and reversal of the severe spastic pulmonary vasoconstriction that accompanies left atrial hypertension in some patients.10–12 Others have shown slow regression of elevated PAP and PVR several months postoperatively.6,7,13,14 These reports point toward the involvement of multiple factors in the development of PAH in mitral valve disease. There have been studies of closed mitral commissurotomy and balloon mitral valvotomy in this subgroup of patients from India, which have shown good results in terms of survival, postoperative functional class, and hemodynamics.15,16 In our study the mean PAP and PVR fell significantly immediately following MVR, and this decline continued over the next 24 hours in patients with severe PAH (group 1). Our group 2 patients showed the unique characteristics of advanced disease, which is seen only in developing countries. This prompted us to operate on these patients on the basis that relief of obstruction at the valvular level might reduce the reactive component of pulmonary vascular disease, and this might alleviate some of the debilitating symptoms. Intravenous milrinone was also used in the perioperative period in 4 of these patients with supra-systemic PA pressures. Although the mean PAP fell significantly from 83.2 to 65.4 mm Hg, it remained within the definition of severe PAH. The PVR showed no significant reduction immediately after MVR, but a gradual regression was seen over a 24-hour period and the fall was significant at 24 hours when compared with the preoperative values. This indicates the reactive component of pulmonary arterial vasoconstriction, which may be responsible for part of the disproportionate elevation of PVR seen in as many as 20% of patients undergoing mitral valve procedures.
The persistence of residual elevated PAP and PVR well beyond the normal limit in both groups of patients suggests an irreversible component of the increased PVR. Lung biopsies showed that the pulmonary vascular changes did not progress beyond Heath-Edwards’ grade III, suggesting potential reversibility in all patients, including those with supra-systemic PAP. This finding does not correlate with the clinical course of these patients. However, we took the biopsies from a single site, which might not have been representative of the pulmonary vasculature changes. Other variables that determine the immediate and long-term results of surgery in this subset of patients include advanced age, acute presentation, decreased left ventricular ejection fraction, functional class, right heart failure and increased left ventricular end-diastolic pressure.5–8 Vincens and colleagues7 identified clinical right heart failure as a predictor of operative mortality, and both right ventricular systolic pressure and right ventricular hypertrophy as predictors of poor outcome. Others have identified severe tricuspid regurgitation and the need for concomitant tricuspid surgery as risk factors for operative mortality in this population.13,14 In our study, 47% of patients had right ventricular hypertrophy and/or dilatation, and 33% had severe tricuspid regurgitation.
Despite the high operative mortality in most series of MVR in patients with severe PAH, a striking improvement in survival was noted.5–8 In our series, functional class improved by one class or more in the majority of survivors. Long-term morbidity was related mainly to anticoagulation and was attributed to poor patient compliance due to illiteracy in this part of the world. Repair of the mitral valve in patients with predominant MR could have avoided these complications but it was not undertaken because of the high rate of repair failure in patients with rheumatic etiology of mitral regurgitation as well as severe subvalvular pathology with calcification of leaflets in most of them.17
We acknowledge that the lack of follow-up of pulmonary vascular dynamics by catheterization constitutes a limitation of this study and was related primarily to economic factors. The small number of patients limits the statistical significance of the study. Despite these limitations, to the best of our knowledge, this study is the only series of patients with supra-systemic PAP undergoing MVR in the modern era. A postoperative lung biopsy might have added to the information, but this was not undertaken as most of the patients refused consent for it.
We concluded that MVR is safe and effective even in the presence of severe PAH as long as the pulmonary arterial pressures are below systemic pressures. With supra-systemic PAP, MVR carries a high risk of mortality, and the patient continues to have persistent PAH in the postoperative period. A lung biopsy did not help in identifying patients with irreversible pulmonary arterial changes in whom surgery could be avoided, although the presence of a higher percentage of patients with grade III changes in group 2 might indicate some usefulness of a preoperative lung biopsy.
Presented at the 48th Annual Conference of the Indian Association of Cardiovascular-Thoracic Surgeons, Chennai, India, February 14–17, 2002.
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REFERENCES
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ABSTRACT
INTRODUCTION
