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Circulation. 1995;92:2252-2258

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(Circulation. 1995;92:2252-2258.)
© 1995 American Heart Association, Inc.


Articles

Single Lung Transplantation for Pulmonary Hypertension

Single Institution Experience in 34 Patients

Michael K. Pasque, MD; Elbert P. Trulock, MD; Joel D. Cooper, MD; Anastasios N. Triantafillou, MD; Charles B. Huddleston, MD; Michael Rosenbloom, MD; Sudhir Sundaresan, MD; James L. Cox, MD; G. Alexander Patterson, MD

From the Division of Cardiothoracic Surgery, Division of Pulmonary Medicine, and Division of Cardiothoracic Anesthesiology, Washington University Medical Center at Barnes Hospital, St Louis, Mo.

Correspondence to Michael K. Pasque, MD, Division of Cardiothoracic Surgery, Washington University Medical School, One Barnes Hospital Plaza, Queeny Tower, Ste 3103, St Louis, MO 63110.


*    Abstract
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*Abstract
down arrowIntroduction
down arrowMethods
down arrowResults
down arrowDiscussion
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Background The present study considered the uniformity and durability of the cardiopulmonary response to single lung transplantation in patients with severe pulmonary hypertension, as well as its effect on length and quality of survival.

Methods and Results Thirty-four patients with pulmonary hypertension underwent evaluation, single lung transplantation, and follow-up assessment between November 1, 1989, and June 1, 1994. Operative survival for the entire group of patients was reasonable, with 91% (31 of 34 patients) surviving and being discharged from the hospital following transplantation. The actuarial survival for these 34 patients at 1-, 2-, and 3-year follow-up was 78%, 66%, and 61%, respectively. In the subgroup of 24 patients with primary pulmonary hypertension (PPH), 96% (23 of 24) were successfully discharged from the hospital after transplantation. The actuarial survival for this isolated PPH subgroup at 1-, 2-, and 3-year follow-up was 87%, 76%, and 68%, respectively. The uniform, early posttransplant normalization of pulmonary vascular resistance and right ventricular ejection fraction appears to persist throughout the 4-year follow-up period. Despite a high prevalence of bronchiolitis obliterans, the majority of survivors remain in New York Heart Association functional class I or II and are employed.

Conclusions Single lung transplantation can be performed in patients with end-stage pulmonary vascular disease with reasonable expectations for a relatively low operative mortality; immediate, complete, and durable amelioration of pulmonary hypertension and right ventricular failure; and optimal use of limited donor organ supply.


Key Words: lung • transplantation • hypertension • pulmonary


*    Introduction
up arrowTop
up arrowAbstract
*Introduction
down arrowMethods
down arrowResults
down arrowDiscussion
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Single lung transplantation has been successfully accomplished in a wide spectrum of patients with end-stage pulmonary disease.1 Frustration with the limited success and applicability of other treatment options for patients with end-stage pulmonary hypertension led to the use of single lung transplantation in this high-risk patient subset. Single lung transplantation has the advantage of increased donor organ availability but preserves the dilated, hypertrophied, and functionally impaired right ventricle that characterizes this patient population. Previous reports from a similar patient population—pulmonary hypertensive patients undergoing thromboendarterectomy for chronic pulmonary embolism—have described a favorable hemodynamic response despite compromised preoperative right ventricular function.2 Nonetheless, the full hemodynamic response to single lung transplantation in patients with end-stage pulmonary hypertension was not readily predictable.

Answers to the following questions were considered critical in the evaluation of single lung transplantation as a therapeutic option in this patient group: (1) Would single lung transplantation normalize pulmonary vascular resistance, and, if so, over what time frame could these ameliorative changes be expected to occur? (2) Would the anticipated drop in pulmonary vascular resistance normalize right ventricular function, and, if so, over what time frame would this improvement occur? (3) Would the anticipated improvement in right-side hemodynamics occur quickly enough to allow reasonable perioperative morbidity and mortality and therefore a reasonable hospital discharge rate compared with other treatment options? (4) If improvement in pulmonary vascular resistance and right ventricular function were documented in the early postoperative period, would this improvement persist at interval follow-up, and how would this durability affect interval survival? (5) Would functional status improve, and would these improvements be durable despite the ventilation-perfusion mismatch that results from the anticipated overperfusion of the transplanted lung? (6) How would bronchiolitis obliterans impact the long-term results in this patient population?

Several of these questions regarding early hemodynamic response and operative mortality have been sequentially answered as data have become available. Specifically, immediate posttransplant hemodynamics were characterized by an analysis of the hourly systemic arterial, pulmonary arterial, pulmonary capillary wedge, and central venous pressures measured in our first seven patients over the first 48 hours after transplantation.3 This analysis demonstrated almost immediate amelioration of markedly elevated pulmonary vascular resistance, with stabilization of hemodynamics and an immediate, gratifying improvement in right ventricular function.

In an attempt to further define the early response to single lung replacement in this critically ill patient subset, this same group of seven patients was more completely characterized at 3-month follow-up by right heart catheterization and radionuclide ventilation-perfusion scanning and ventriculography.4 This follow-up study confirmed the early stability of the hemodynamic improvement documented during the first 2 days after transplant, further characterized the ventilation-perfusion mismatch, and documented the marked improvement in right ventricular function.

In light of these early favorable results, single lung transplantation continued to be offered as a transplant option for patients with end-stage pulmonary vascular disease referred to the Barnes Hospital lung transplant program. The complete experience with single lung transplantation in 34 patients is reviewed, with specific attention to the therapeutic effectiveness of this treatment option as assessed at interval follow-up.


*    Methods
up arrowTop
up arrowAbstract
up arrowIntroduction
*Methods
down arrowResults
down arrowDiscussion
down arrowReferences
 
Patient Population
The study population consisted of all of the patients referred to the lung transplant program at Barnes Hospital with symptoms referable to end-stage pulmonary vascular disease who were evaluated, placed on a transplant waiting list, and subsequently underwent single lung transplantation during the 4.5 years between November 1, 1989, and June 1, 1994.

Thoracic Donor Organ Utilization
Efficiency of thoracic organ donor utilization was assessed by documenting the total number of patients who were transplanted with the opposite single lungs and the hearts of the donors used for the single lung transplant procedures in our patient population. These data are relevant in comparisons with other transplant options, such as heart-lung and bilateral lung transplantation.

Operative Technique
The technical aspects of single lung transplantation in patients with pulmonary hypertension have been described previously in detail3 4 and have changed minimally. Previous reports described the routine use of femoral arterial cannulation for cardiopulmonary bypass. Over the last several years, the technique has evolved into the almost exclusive use of complete intrathoracic cannulation. Right single lung transplantation has been used exclusively if simultaneous repair of an associated intracardiac defect is planned. Ascending aortic as well as right atrial or bicaval cannulation is easily performed through a standard right posterolateral thoracotomy. Likewise, cannulation of the descending thoracic aorta, with pulmonary arterial cannulation for venous return, is readily performed through a left thoracotomy. We continue to stress the importance of careful donor lung selection, as well as the routine use of intraoperative transesophageal echocardiography, postimplantation positive end-expiratory pressure, and 24 to 48 hours of postoperative sedation and mechanical ventilation.

Posttransplant Survival
Operative mortality was defined as any death occurring within 30 days of transplantation or any death (even beyond 30 days) occurring before discharge from the hospital. Actuarial survival was determined as described below in "Statistical Analysis." Operative mortality and actuarial survival were calculated for the entire group of 34 patients with pulmonary vascular disease, as well as for the subset of 24 patients with PPH.

PPH Survival Comparison
Actuarial survival data from the isolated subset of PPH patients was compared with the nontransplanted natural history predicted for the same group of patients by the formula published by the Patient Registry for the Characterization of Primary Pulmonary Hypertension.5 This formula uses hemodynamic data obtained at catheterization to predict expected survival and was generated and validated by the registry survival data. The formula incorporates mean pulmonary artery pressure (x), mean right atrial pressure (y), and cardiac index (z) and predicts a patient's chances of survival [where P(t) indicates the patient's chances of survival and t=1, 2, 3, 4, or 5 years] after diagnosis:




To make this comparison more clinically relevant, survival data for the entire group of 42 patients with PPH who were evaluated and listed for single lung transplantation by the Washington University lung transplant program during the study period were examined. Of this group, 1 patient was excluded because of incomplete hemodynamic data for entry into the registry formula. In addition, 3 patients were excluded because they were selected during the later stages of the study period for bilateral lung replacement (all 3 were successfully transplanted and are still alive). The final study group therefore included 14 patients with PPH who were evaluated and listed but not transplanted in addition to the 24 PPH patients (out of the total transplant group of 34) who were transplanted. For the purposes of this comparison only, actuarial survival was calculated with the date of listing for transplantation being used as the entry point for all patients.

Therefore, we calculated both an actuarial and predicted (PPH registry formula) survival for all patients with PPH who were listed for lung transplantation during the study period. Comparison of these two survival curves, therefore, should reasonably compare single lung transplantation as a therapeutic modality with the natural history of the disease as predicted by the registry formula. This comparison was made from the time of listing for transplantation (not from the time of transplantation) and included all evaluated patients (not just those who were ultimately transplanted) in hopes of supplying efficacy information to the clinician who is faced with the clinical decision to refer for lung transplantation or continue with nontransplantation therapeutic options. This comparison more appropriately incorporates the influence of long waiting lists, donor organ shortages, and the very significant mortality accrued while waiting for a suitable donor organ.

Hemodynamics
Hemodynamic follow-up of our first 7 patients for the immediate 48 hours following transplantation3 as well as the initial 3-month follow-up4 has been reported previously. The present study included a summary of pretransplant and follow-up cardiac catheterization data for the entire group of 34 patients. In addition, pretransplant data were compared with the latest available follow-up information for all patients who had at least one posttransplant cardiac catheterization.

Ventricular Function
The pretransplant and 3-month posttransplantation right and left ventricular ejection fraction data (by radionuclide ventriculography) for our first 7 patients has been reported previously and the methodology described.4 The current report includes a summary of right and left ventricular ejection fraction data (pretransplant and at 3-month, 6-month, and yearly intervals after transplantation) for the entire group of 34 patients. Also reviewed is a comparison of the pretransplant and latest follow-up ejection fraction data for all transplant survivors who had at least one posttransplant scan.

Ventilation-Perfusion Imaging
The pretransplant and 3-month posttransplant ventilation-perfusion scan data for our first 7 patients has been reported previously and the methodology described.4 The current report includes a summary of ventilation-perfusion scan data before and after transplantation for the entire group of 34 patients. Also reviewed is a comparison of the pretransplant and latest follow-up ventilation-perfusion scan data for all transplant survivors who had at least one complete posttransplant scan.

Functional Capacity
General functional capacity was assessed for patients surviving as of June 1, 1994, by characterization of pretransplant and latest NYHA functional classification (I to IV) as well as their return to partial or full employment (including housewife) or school.

Bronchiolitis Obliterans
Close surveillance for functional (by pulmonary function testing) or pathological (by transbronchial biopsy) evidence of bronchiolitis obliterans is carried out at routine intervals in all lung transplant patients. More than 4 months after transplantation, all patients are considered to be at risk for development of bronchiolitis obliterans. Classification is by the formula described by an ad hoc working group established under the auspices of the International Society for Heart and Lung Transplantation.6 This classification system adopted the term "obliterative bronchiolitis syndrome," which uses FEV1 as a clinical indicator of the severity of the obstructive airway disease that is most commonly associated with chronic lung allograft dysfunction. The severity of OBS is categorized by four stages based on the percentage decrease in FEV1 from the best posttransplant level: Stage 0 indicates no significant abnormality, FEV1 80% or more of baseline value; Stage 1, mild OBS, FEV1 66% to 80% of baseline value; Stage 2, moderate OBS, FEV1 51% to 65% of baseline value; and Stage 3, severe OBS, FEV1 50% or less of baseline value. Each stage is further categorized as being with or without pathological evidence of obliterative bronchiolitis.

Statistical Analysis
Statistical comparisons between data groups were made by use of Student's t test. Pretransplant and latest posttransplant NYHA functional class data were compared by use of the Wilcoxon signed rank test. Actuarial survival data were calculated by use of the Kaplan-Meier estimator. The Mantel-Haenszel log rank test was used for comparisons of actuarial survival between groups. All calculations were done with SYSTAT: The System for Statistics7 on a personal computer. All results are expressed as mean±SD; a value of P<.05 was considered statistically significant.


*    Results
up arrowTop
up arrowAbstract
up arrowIntroduction
up arrowMethods
*Results
down arrowDiscussion
down arrowReferences
 
Patient Population
The study population consisted of 34 consecutive patients with pulmonary hypertension who underwent evaluation and subsequent single lung transplantation during the 4.5 years between November 1, 1989, and June 1, 1994, with follow-up completed in all patients until June 1, 1994. All of these patients were referred for lung replacement with symptoms referable to pulmonary hypertension. Age range was from 23 to 56 years, with a mean of 37±9 years. Twenty-six of the 34 patients were female. In this group of 34 patients with end-stage pulmonary hypertension, there were 24 patients with the presumed diagnosis of PPH and 10 patients with secondary pulmonary hypertension.

In the group of patients with secondary pulmonary hypertension, there were 7 with associated cardiac abnormalities and the presumed diagnosis of Eisenmenger's syndrome. The Eisenmenger group included 3 patients with large ostium secundum ASDs, 1 with a sinus venosus ASD with associated partial anomalous pulmonary venous return, and 1 with a VSD, all of which were repaired at the time of transplantation. Two other patients had previously undergone total correction of a VSD and a combination of patent ductus arteriosus, coarctation of the aorta, and VSD, respectively. The surgical correction of these abnormalities was performed early in childhood, with pulmonary hypertension becoming a problem later in life. Although it is not absolutely clear that their pulmonary hypertension resulted from the associated cardiac defects, they are categorized with the Eisenmenger group. Three other patients had severe secondary pulmonary hypertension associated with sarcoidosis, pulmonary fibrosis, andL-tryptophan poisoning, respectively.

Donor Thoracic Organ Utilization
Efficiency of donor thoracic organ utilization was assessed by documentation of the use of the opposite lung and heart in each of the donors for the 34 transplant procedures. There were three instances in which a single donor was utilized for simultaneous single lung transplant procedures in 2 patients with pulmonary hypertension at our institution. In addition, the heart and opposite lung were utilized either at our institution or another transplant center for an additional 28 and 20 transplant procedures, respectively. The total was therefore 82 transplant procedures in 82 separate patients from 31 donors. Since the lack of sufficient donor lungs is the single most important factor limiting effectiveness of lung transplantation in pulmonary hypertension, efficiency of donor utilization is especially important in evaluating overall effectiveness of single lung, bilateral lung, or heart-lung transplant procedures.

Posttransplant Survival
Thirty-one (91%) of the 34 patients with pulmonary hypertension survived the transplant procedure and were discharged from the hospital. Actuarial survival for this group of patients at 1-, 2-, and 3-year follow-up was 78%, 66%, and 61%, respectively (Fig 1Down). The originally reported4 first 7 consecutive patients are all still alive after more than 4 years of follow-up.



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Figure 1. Graphic demonstration of actuarial survival (from the time of transplantation) curves for the entire group of 34 patients with pulmonary hypertension (PH) and for the isolated group of 24 patients with PPH.

In the isolated group of 24 patients with PPH, 23 (96%) survived and were discharged after transplantation. The actuarial survival for this isolated PPH subgroup at 1-, 2-, and 3-year follow-up was 87%, 76%, and 68%, respectively (Fig 1Up). A comparison of these results with the actuarial survival of the isolated group of 10 patients with secondary pulmonary hypertension revealed no significant difference between the two groups (P=.117), although the study groups were small.

PPH Survival Comparison
As described in "Methods," 42 patients with PPH were evaluated and listed for transplantation during the study period. Four patients were excluded from this total group (3 patients underwent bilateral lung transplantation and 1 lacked complete data for entry into the registry formula), leaving a total study population of 38 patients (24 of whom received transplants). The actuarial survival of these 38 patients from the time of listing for transplantation was compared with the survival rate predicted by the NIH Registry on Primary Pulmonary Hypertension formula for that same group of 38 patients. The resulting survival curves are graphically represented in Fig 2Down.



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Figure 2. Graphic demonstration of the actuarial survival (from the time of listing for transplantation) curve for 38 patients with PPH who were evaluated and listed in the Barnes Hospital lung transplantation program between November 1, 1989, and June 1, 1994. Also demonstrated is the 5-year predicted survival curve (natural history without transplantation) for that same group of 38 patients as determined by the survival formula generated from the Patient Registry for the Characterization of Primary Pulmonary Hypertension.5

Hemodynamics
A summary of pretransplant and posttransplant (at 3 to 12 months and at subsequent yearly intervals) cardiac catheterization data for the entire group of 34 patients is presented in Table 1Down. Pretransplant data are also compared with the latest available follow-up information for all patients who had at least one posttransplant cardiac catheterization (n=28) in Table 1Down.


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Table 1. Hemodynamics

Ventricular Function
A summary of pretransplant and posttransplant (at 3-month, 6-month, and yearly intervals) right and left ventricular ejection fraction data from the entire transplant group is presented in Table 2Down, with a comparison of pretransplant and latest posttransplant right and left ventricular ejection fraction data for all patients who had at least one posttransplant scan (n=28).


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Table 2. Biventricular Ejection Fraction Data Obtained by Radionuclide Scan

Ventilation-Perfusion Imaging
A summary of pretransplant and posttransplant (at 3 to 12 months and at subsequent yearly intervals) ventilation-perfusion scan data from the entire transplant group is presented in Table 3Down, with a comparison of pretransplantation and latest posttransplantation ventilation-perfusion scan data for all patients who had at least one complete posttransplant scan (n=30).


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Table 3. Pulmonary Ventilation-Perfusion Data Obtained by Radionuclide Scan

Functional Capacity
All patients were NYHA functional class III or IV before transplantation. Among currently surviving transplant recipients (n=23), 20 were in functional class III and 3 were in functional class IV before transplantation. At a mean of 2.42±1.50 years after transplantation, the great majority of surviving patients (21 of 23, 91%) remain in NYHA functional class I or II, despite varying degrees of bronchiolitis obliterans: NYHA I, 16 patients; NYHA II, 5; NYHA III, 2; and NYHA IV, 0. Currently, full- or part-time employment or student status is enjoyed by 19 of 23 survivors (83%).

Bronchiolitis Obliterans
Latest bronchiolitis obliterans status, as of June 1, 1994, is classified according to the working formula established by an ad hoc committee under the auspices of the International Society for Heart and Lung Transplantation.6 This formula incorporates both functional and pathological evidence for bronchiolitis obliterans in determining status. All patients are now more than 4 months posttransplant and are considered at risk for the development of bronchiolitis obliterans.

Either functional or pathological evidence for bronchiolitis obliterans has been documented (to variable degrees) in 6 of 23 current survivors (26%). The bronchiolitis obliterans staging of these 6 current survivors includes 2 patients each with stage 0(b) and stage 2(a) and 1 each with stage 2(b) and 3(b). In addition, bronchiolitis obliterans was documented to some degree in 35% (11 of 31) of all operative survivors. In the first 7 transplanted patients, all of whom have survived more than 4 years since transplantation, 4 (57%) have some degree of bronchiolitis obliterans: 0(b)=1, 2(a)=2, and 2(b)=1. Five (45%) of the 11 deaths that have occurred in the 34 transplanted patients were due to bronchiolitis obliterans.

The latest available mean pulmonary artery pressure, pulmonary vascular resistance, right ventricular ejection fraction, transplanted lung perfusion, and transplanted lung ventilation data for all operative survivors with bronchiolitis obliterans were compared with similar data gathered from the operative survivors without bronchiolitis obliterans. There were no significant differences between these two groups of patients in any of these areas of testing.


*    Discussion
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up arrowAbstract
up arrowIntroduction
up arrowMethods
up arrowResults
*Discussion
down arrowReferences
 
Effective treatment options for patients with end-stage pulmonary hypertension remain limited. Although pulmonary hemodynamics can be favorably altered in some fortunate patients by treatment with vasodilator therapy,8 9 10 the majority will die of causes secondary to the cardiac or systemic effects of their pulmonary hypertension. Lung replacement by lung transplantation is a logical alternative therapy as long as it can be carried out with reasonable operative mortality, freedom from recurrence of the primary disease process, and reasonable expectations for freedom from the complications of transplantation that would limit quality and quantity of life. Heart-lung transplantation in patients with pulmonary hypertension11 12 13 14 has demonstrated therapeutic effectiveness but has been limited by a restricted supply of suitable donor heart-lung blocks, the complexity of the operation, the replacement of a heart that has been secondarily (and presumably reversibly) injured, and the occurrence of bronchiolitis obliterans.

Despite several obvious advantages in this high-risk patient population, the potential application of single lung transplantation was approached with legitimate concern with regard to the previously outlined questions concerning the immediacy, completeness, quality, and durability of the therapeutic response. Questions regarding the immediacy of reversal of pulmonary hypertension, immediacy of right ventricular recovery, and associated operative morbidity and mortality were addressed early in the course of our experience.3 4 The present review of our complete experience in 34 patients supplies further information regarding these questions but also supplies a 4-year interval response to questions concerning (1) the long-term durability of pulmonary hemodynamic and right ventricular recovery and the associated interval survival results; (2) functional status, including the significance of the obligate ventilation-perfusion mismatch; and (3) the impact of bronchiolitis obliterans.

The operative survival of 91% in our entire experience of 34 single lung transplants and the 96% operative survival in the isolated subset of PPH patients further support our previously published conclusions regarding the safety of this transplant procedure.3 4 Single lung transplantation is a relatively straightforward surgical procedure that can be carried out in this compromised group of patients with reasonable expectations of operative survival and discharge from the hospital.

Hemodynamic follow-up for up to 4 years after transplantation (Table 1Up) demonstrated satisfying durability of the complete pulmonary hemodynamic normalization that we previously documented in the early posttransplant period.3 4 Likewise, right ventricular ejection fraction, which normalized early after transplantation,4 has remained normal throughout 4 years of follow-up (Table 2Up). The durability of these responses is responsible, at least in part, for the very reasonable moderate-term survival in these patients (Figs 1Up and 2Up).

Significantly, in the transplanted group, there have been no late deaths secondary to cardiovascular events such as sudden death, heart failure, or arrhythmia. Such events are almost uniformly responsible for the dismal survival in nontransplanted patients with pulmonary hypertension. Clearly, single lung transplantation, at the follow-up intervals reported here, eliminates the primary cause of death in patients with end-stage pulmonary hypertension. Short-term survival after transplantation appears to be dependent on the absence of complications related to the operative procedure itself, while long-term survival is dependent on the absence of complications specific to lung transplantation and immunosuppression, such as infection, acute rejection, and bronchiolitis obliterans.

When survival after single lung transplantation in our isolated subgroup of patients with PPH is compared with nontransplant survival (PPH registry survival formula applied to the same group of patients), there is a clear divergence of the survival curves at 1 year after listing for transplantation (Fig 2Up). Our comparison included the entire group of PPH patients who were listed for transplantation during the study intervals (rather than just the 24 transplanted PPH patients) in hopes of supplying clinically relevant information regarding the effectiveness of referral for transplantation in improving the otherwise dismal, nontransplant natural history of this disease process. By evaluating these patients from the time of their listing for transplantation rather than from the time of actual transplantation, we incorporated into the comparison the possibility that patients might die while awaiting transplantation. Comparison of transplant outcome with the expected natural history of PPH (with current medical therapy) must incorporate those patients who are evaluated and listed but die before transplantation, because the often long waiting list times are an indisputable obstacle to success with this therapeutic option.

Pretransplant survival data of the 38 patients described in this report further support the PPH registry formula. The actuarial survival curve (Fig 2Up) essentially follows the registry formula–predicted curve to a point that is nearly coincident with the average time on the waiting list for the 24 patients who ultimately received transplants (208±169 days). The actuarial survival curve diverges at this point and remains widely divergent beyond the 4-year interval.

When functional status is considered, use of the single lung transplant option appears well justified. The fear of dyspnea on exertion secondary to the obligate ventilation-perfusion mismatch was a reasonable concern before attempting single lung transplantation in this group of patients. Indeed, the relative overperfusion of the transplanted lung persisted to the 4-year follow-up and appears to be uniform in our entire group of 34 patients (Table 3Up). Nonetheless, our fear that significant dyspnea on exertion would be a uniform and disabling problem in transplant survivors has not been substantiated by our clinical experience with the uncomplicated posttransplant survivor. Almost all patients with uncomplicated posttransplant courses have described excellent exercise tolerance during vigorous outdoor activities and exercise. Functional status after single lung transplantation is not inherently compromised or limited by the obligate ventilation-perfusion mismatch.

On the other hand, if surveillance is regimented and complete, functional and/or pathological changes consistent with bronchiolitis obliterans will be found in a large segment of any lung transplant population, especially as long-term follow-up is completed. The pulmonary hypertension lung transplantation group is no exception, as the early heart-lung transplantation experience demonstrated.12 13 14 It is intuitive that the functional debilitation associated with bronchiolitis obliterans would be compounded by the ventilation-perfusion mismatch that exists in single lung transplant patients. With the occurrence of bronchiolitis obliterans, the transplanted lung, which receives an average of 87±7% of the pulmonary blood flow at 1 year of follow-up, is subjected to a process that destroys its ventilatory capacity.

Despite the occurrence of some degree of bronchiolitis obliterans in a large portion of our patients, functional status, as assessed by NYHA functional class and employment status, appears quite reasonable in the entire group of current survivors at the reported average interval. This is especially notable in light of the very compromised functional status of the majority of pulmonary hypertensive patients before transplantation, which has almost uniformly prevented even monitored physical rehabilitation during the pretransplant waiting period.

In areas with limited donor supply, single lung transplantation may be specifically attractive with regard to optimizing efficiency of donor utilization. The 31 donors who supplied single lungs to the 34 patients reported in this series supplied thoracic organs to a total of 82 recipients. Because it is well recognized that the availability of suitable donor organs is the limiting factor in the therapeutic application of thoracic organ transplantation, efficient donor organ utilization is of paramount importance.

In summary, single lung transplantation appears to be a reasonable transplant option for patients with end-stage pulmonary hypertension. The relative simplicity of this surgical procedure makes it especially attractive in this critically ill group of patients because it can be done quickly with a short period of cardiopulmonary bypass, can be combined easily with simultaneous repair of intracardiac defects, can be performed with a very reasonable operative morbidity and mortality, and can serve the greatest number of patients in the shortest period of time by optimal donor organ utilization. Our experience has demonstrated an early and complete normalization of hemodynamics that persists for at least 4 years after transplantation. Single lung transplantation clearly represents a satisfactory therapeutic modality for completely preventing the predominant occurrence of cardiovascular death in this critically ill subset of patients. Functional status in the absence of bronchiolitis obliterans appears quite reasonable despite the obligate ventilation-perfusion mismatch. As is the case in all subgroups of lung transplant recipients, bronchiolitis obliterans limits long-term survival. These results support the further cautious application of single lung transplantation in patients with end-stage pulmonary vascular disease.


*    Selected Abbreviations and Acronyms
 
ASD(s) = atrial septal defect(s)
FEV1 = forced expiratory volume in one second
NYHA = New York Heart Association
OBS = obliterative bronchiolitis syndrome
PPH = primary pulmonary hypertension
VSD = ventricular septal defect


*    Acknowledgments
 
We would like to acknowledge the following individuals for their assistance in the preparation of this manuscript: secretarial services and data management assistance were provided by Sheryl Goessling and Cindy Camillo, RN; assistance in organizing and obtaining patient follow-up data was provided by the coordinators, nurses, and secretaries affiliated with the lung transplant program at Barnes Hospital: Laura Ochoa, RN, Kate Sander, RN, Greg Richardson, RN, Jenny Manley, RN, Mary Pohl, RN, Susanna Hobdy, and Christal Hayes; statistical analysis was performed by Richard B. Schuessler, PhD; and assistance in preparing the description of radionuclide methodology was provided by Henry Royal, MD.

Received January 10, 1995; revision received March 23, 1995; accepted May 10, 1995.


*    References
up arrowTop
up arrowAbstract
up arrowIntroduction
up arrowMethods
up arrowResults
up arrowDiscussion
*References
 

  1. Trulock EP, Cooper JD, Kaiser LR, Pasque MK, Ettinger NA, Dresler CM. Lung transplantation: the Washington University/Barnes Hospital experience. JAMA. 1991;266:1943-1946. [Abstract]
  2. Moser KM, Daily PO, Peterson K, Dembitsky W, Vapnek JM, Shure D, Utley J, Archibald C. Thromboendarterectomy for chronic, major vessel thromboembolic pulmonary hypertension: immediate and long-term results in 42 patients. Ann Intern Med. 1987;107:560-565.
  3. Pasque MK, Kaiser LR, Dresler CM, Trulock EP, Triantafillou AN, Cooper JD. Single lung transplantation for pulmonary hypertension: technical aspects and immediate hemodynamic results. J Thorac Cardiovasc Surg. 1992;103:475-482. [Abstract]
  4. Pasque MK, Trulock EP, Kaiser LR, Cooper JD. Single lung transplantation for pulmonary hypertension: three-month hemodynamic follow-up. Circulation. 1991;84:2275-2279. [Abstract/Free Full Text]
  5. D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, Levy PS, Pietra GG, Reid LM, Reeves JT, Rich S, Vreim CE, Williams GW, Wu M. Survival in patients with primary pulmonary hypertension: results from a national prospective registry. Ann Intern Med. 1991;115:343-349.
  6. Cooper JD, Billingham M, Egan T, Hertz MI, Higenbottam T, Lynch J, Mauer J, Paradis I, Patterson GA, Smith C, Trulock EP, Vreim C, Yousem S, for the International Society for Heart and Lung Transplantation. A working formulation for the standardization of nomenclature and for clinical staging of chronic dysfunction in lung allografts. J Heart Lung Transplant. 1993;12:713-716. [Medline] [Order article via Infotrieve]
  7. Wilkinson L. SYSTAT: The System for Statistics. Evanston, Ill: SYSTAT, Inc; 1989.
  8. Rich S, Kaufmann E, Levy PS. The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. N Engl J Med. 1992;327:76-81. [Abstract]
  9. Weir EK, Rubin LJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Elliott CG, Fishman AP, Goldring RM, Groves BM, Kernis JT, Koerner SK, Levy PS, Pietra GG, Reid LM, Rich S, Vreim CE, Williams GW, Wu M. The acute administration of vasodilators in primary pulmonary hypertension: experience from the National Institutes of Health Registry on Primary Pulmonary Hypertension. Am Rev Respir Dis. 1989;140:1623-1630. [Medline] [Order article via Infotrieve]
  10. Rubin LJ. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Ann Intern Med. 1990;112:485-491.
  11. Reitz BA, Wallwork J, Hunt SA, Billingham M, Oyer P, Stinson EB, Shumway NE. Heart-lung transplantation: successful therapy for patients with pulmonary vascular disease. N Engl J Med. 1982;306:557-564. [Abstract]
  12. Yacoub MH, Khaghani A, Miyamura H, Sono J. Heart-lung transplantation: Harefield experience. Jpn J Surg. 1990;20:247-251. [Medline] [Order article via Infotrieve]
  13. McCarthy PM, Starnes VA, Theodore J, Stinson EB, Oyer PE, Shumway NE. Improved survival after heart-lung transplantation. J Thorac Cardiovasc Surg. 1990;99:54-60. [Abstract]
  14. Hutter JA, Scott JP, Deespins P, Stewart S, Higenbottam T, Wallwork J. Heart-lung transplantation at Papworth Hospital. Eur J Cardiothorac Surg. 1989;3:300-304.[Abstract]



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