Abstract
This study evaluated long-term outcome of pulmonary thromboendarterectomy (PTE) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Survival, functional status, quality of life, health care utilization, and relationships between these parameters and postoperative pulmonary hemodynamics were assessed. Questionnaires were mailed to 420 patients who were more than 1 yr post-PTE; 308 responded (mean age, 56 yr [range, 19–89 yr]; mean years since PTE, 3.3 [range, 1– 16]). Survival after PTE was 75% at > 6 yr. After surgery, symptoms were markedly reduced. Median distance walked was 5,280 ft; 56 patients could walk “indefinitely.” Of the working population, 62% of patients unemployed before PTE returned to work. Post-PTE patients scored several quality of life components of the Rand SF-36 slightly lower than reported normals but significantly higher than did pre-PTE patients. Ten percent of patients used oxygen. Ninety-three percent were in NYHA Class I or II. Disease-related hospitalizations/ER visits were minimal. A relationship was shown between 48 h postoperative pulmonary vascular resistance (PVR) and walking and stair-climbing ability, NYHA class, dyspnea scores, and the physical function and general health quality of life components. These data indicate that PTE offers most CTEPH patients substantial improvement in survival, function, and quality of life, with minimal disease-related health care utilization.
Patients with chronic thromboembolic pulmonary hypertension (CTEPH) present with progressive exertional dyspnea and fatigue that respond poorly to medical management (1, 2). Over periods of months to years, symptoms worsen and right ventricular dysfunction intervenes. Survival of nonoperated patients with CTEPH beyond the onset of symptoms has not been firmly established, although Riedel and coworkers (1) reported a median survival of 2–3 yr from initial diagnosis, with longevity adversely affected by the severity of pulmonary hypertension.
Pulmonary thromboendarterectomy (PTE) for select patients offers a potential surgical remedy for this condition. The removal of organized thromboembolic material from the major pulmonary vessels can restore pulmonary hemodynamics to normal or near normal levels in most patients undergoing this operation (3-6). Furthermore, as experience has accumulated, postoperative mortality has progressively declined. A report of 273 consecutive patients undergoing PTE at the University of California, San Diego (UCSD) has shown an in- hospital mortality of 6.6% (7).
Follow-up studies of patients undergoing PTE surgery have demonstrated sustained improvement in pulmonary hemodynamics (4-6, 8, 9). However, limited information is available addressing the long-term effects of this operation on functional status, survival, and quality of life issues. The New York Heart Association (NYHA) functional classification has been reported to be improved at 1 yr or more post-PTE surgery (4, 6, 8, 9). Rich and coworkers (10) measured quality of life after PTE (mean, 14.3 mo post-PTE) in a preliminary study of nine patients, finding that overall quality of life was better when compared with end-stage cardiac patients, with fewer cardiopulmonary symptoms and improved functional status.
Using a cross-sectional survey, this study reports the overall postoperative status of PTE patients in terms of survival, functional status, quality of life, and health care utilization 1 yr or more beyond their surgery. An additional objective was to evaluate the relationship between indices of functional status and postoperative pulmonary hemodynamic measurements.
Between 1970 and 1994 at the University of California, San Diego Medical Center, there were 514 patients who underwent PTE and survived to hospital discharge. A national death index (NDI) search was performed in September 1994 and again in August 1996 in an attempt to identify patients who had died after discharge. Fifty-one individuals died of various causes, reducing the population to 463 surviving patients who were more than 1 yr beyond PTE. One hundred twenty-three patients could not be contacted. Fifteen patients did not return surveys. Seventeen patients were excluded, 14 owing to inability to understand English and 3 because of persistent pulmonary hypertension after PTE requiring lung transplantation. The final cohort, then, consisted of 308 patients, 66.5% (308 of 463) of the target population.
Collected data were derived from three self-administered questionnaires distributed by mail: the PTE Follow-up Questionnaire, the UCSD Shortness of Breath Questionnaire, and the Rand 36-Item Health Survey. The PTE Follow-up Questionnaire focused on functional status, including the patient's estimate of the New York Heart Association (NYHA) class of disability, prevalence of symptoms, walking distance, stair-climbing ability, and work status, and on health care utilization, including disease-related hospitalizations and emergency room visits. It was piloted on 14 patients to establish reliability using the test-retest method, with a 0.87 agreement (range, 0.77–1.00; median, 0.85).
The previously validated UCSD Shortness of Breath (SOB) Questionnaire (11) provided a symptom-specific (dyspnea) estimate of functional status during 23 activities of daily living (ADL). The severity of dyspnea is rated on a scale of 0 to 5, with 0 = none, 1 = sometimes, 2 = half of the time, 3 = most of the time, 4 = all of the time, and 5 = no longer able to perform activity because of dyspnea.
The Rand 36-Item Health Survey (SF-36), adapted from the Medical Outcomes Study (12), provided information related to quality of life. The questionnaire consists of 36 items that address eight health concepts: physical function, role limitations due to physical function, emotional well-being, role limitations due to emotional problems, bodily pain, social function, energy/fatigue, and general health.
Available data on the Rand SF-36 previously obtained from a separate cohort of 39 PTE patients who had been surveyed before surgery was also used (13).
The number of respondents used for analysis of various elements differed because some respondents did not answer all questions. Several patients, who responded to health care utilization questions in terms of symptoms rather than diagnosis, had to be reached by phone to clarify whether the reasons for hospitalization were disease related or nondisease related. Various strategies were employed to locate patients, including contacting the next of kin and referring physicians. Military patients posed a problem because their records were not retained at the referring facility but had traveled with them to subsequent assignments.
Human Subjects Committee approval and informed consent were obtained.
Statistical analyses used included descriptive statistics, Kaplan-Meier actuarial survival curves, the Pearson correlation coefficient, and the unpaired Student t test. To account for multiple comparisons, a p value of 0.01 was used to indicate significance.
The population consisted of 181 men and 127 women, with a mean age at survey of 56.2 yr (SD, 15.6 yr; median, 58.7; range, 19–89 yr). The time since PTE was on average 3.3 yr (SD, 2.7 yr; median, 2.3 yr; range, 1–16 yr).
The Kaplan–Meier survival curve (Figure 1) depicts time elapsed from date of surgery until time of death or last follow-up (either date of survey or date of NDI search), with an initial decline representing in-hospital patient deaths (n = 54), and subsequent changes due to postdischarge deaths (n = 51). In 532 post-PTE patients, 75% of patients survived beyond 6 yr, with up to 19 yr of follow-up. The postdischarge causes of death are depicted in Figure 2. The predominant cause of death was persistent pulmonary hypertension or recurrent pulmonary emboli. The known time period since PTE averaged 2.73 yr for 45 of these patients.
Fig. 1. Kaplan–Meier survival plot depicting time elapsed from date of PTE surgery until time of death or last follow-up, with an initial decline representing in-hospital deaths and subsequent changes due to postdischarge deaths. Survival probability is shown as 75% of patients surviving beyond 6 yr, with up to 19 yr of follow- up (n = 532).
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Fig. 2. Posthospital causes of death in 51 PTE patients (mean years since PTE, 2.73 in 45 patients). *COPD, interstitial fibrosis; **cause unknown. PE = pulmonary emboli; CVA = cardiovascular accident; C/P = cardiopulmonary; GI (G.I.) = gastrointestinal.
[More] [Minimize]Of 306 patients self-reporting NYHA class of disability (Table 1), 170 (56%) identified themselves as NYHA Class I, 112 (37%) as Class II, 20 (6.5%) as Class III, and 4 (1%) as Class IV.
| NYHA | n | Percent | ||
|---|---|---|---|---|
| I | 170 | 56 | ||
| II | 112 | 37 | ||
| III | 20 | 6 | ||
| IV | 4 | 1 |
The mean score of the UCSD SOB Questionnaire was 0.64 ± 0.71 (median, 0.43; range 0–3.95) for all 23 activities. The mean score for rating the degree of dyspnea during level walking was 0.58. Of 303 patients, 191 (63%) had no dyspnea walking on a level, 76 (25%) sometimes experienced dyspnea, 15 (5%) were dyspneic half of the time, 15 (5%) had dyspnea most of the time, and 6 (2%) were dyspneic during level walking all of the time.
In the PTE Follow-up Questionnaire, 306 patients answered the question: “How would you rate your shortness of breath since surgery?” with choices on a Likert scale of much worse, worse, same as before, improved, much improved. Of these patients, 224 (73.2%) said their dyspnea was much improved, 70 (22.9%) were improved, 8 (2.6%) were about the same, and 2 (< 1%) were worse. The presence of dyspnea at rest was reported by 9 patients (2.9%). However, 190 patients (62.1%) had some dyspnea during “significant” exercise.
The prevalence of cardiopulmonary symptoms was reported as follows: 57 (18.6%) patients were aware of “heart palpitations”; 115 (37.5%) had some leg or ankle edema; 95 (30.9%) experienced fatigue; 44 (14.3%) had occasional dizziness; 6 (1.9%) had “passed out” at least once; 32 (10.4%) had chest pain; 50 (16.3%) experienced some coughing; and 7 (2.3%) had hemoptysis.
Fifty-six of 306 patients (18.3%) claimed they could walk “indefinitely” on the level. For analysis purposes, 10 city blocks was defined as 1 mi or 5,280 ft; thereby allocating 1 city block as 528 ft. Of the 250 remaining patients, the median distance walked was 5,280 ft (range, 0–31,680 ft or 6 mi). Eight patients said they were able to walk 60 ft or less (range, 0–60 ft; mean age, 56.9 yr). However, one of these patients was 83 yr old and had suffered an intervening stroke, whereas another had undergone a partial foot amputation. Figure 3 depicts self-reported distance walked.
Fig. 3. Box-and-whisker plot of self-reported distance walked expressed on a log scale, with the box showing 25th, 50th, and 75th percentiles and the whiskers showing 10th and 90th percentiles. The median is 5,280 ft for 250 post-PTE patients; 56 post-PTE patients could walk “indefinitely.”
[More] [Minimize]Two hundred ninety patients answered the question pertaining to how many flights of stairs they could climb. One flight of stairs was defined as 10 steps. Twenty-one patients (7.2%) said they could climb stairs “indefinitely.” Of the remaining patients, the range of flights climbed was 0–40, with a median of 2.0 flights. Only 14 (4.8%) patients could climb less than one flight.
Supplemental oxygen was not being used by 89.6% (n = 275) of patients surveyed. Of the 32 patients still using oxygen, 25% (8 of 32) lived at altitudes above 3,000 ft. Fifteen patients (5%) used oxygen at rest, 22 (7.2%) during exertion, and 29 (9.4%) during sleep. The mean duration of oxygen use after PTE, for patients discharged on oxygen, was 7.1 wk (range, 1–64 wk).
One hundred thirty-three patients (43.3% of the population) returned to work after surgery. Fifty-one of these patients had been working before PTE; 61.7% (82 of 133) of the patient group returned to work after PTE. The average time elapsed before returning to work was 16.6 ± 18.3 wk (median, 10 wk; range 2–104 wk). One hundred eleven patients (36.2% of the population) were retired before surgery and remained retired. Sixty-three patients (20.5% of the population) were disabled before surgery and remained disabled. Thirty-five patients (11.4%) were able to perform volunteer work after surgery. One hundred patients (32.6%) had resumed all or part of their housework, although a large number of male patients did not respond to this question.
The first question in the Rand 36-Item Health Survey, “In general, would you say your health is: excellent, very good, good, fair, poor?” (1-5), was analyzed separately. Of 298 respondents, 53 (18%) reported excellent health, 92 (31%) reported very good health, 2 (0.7%) reported between very good and good health, 102 (34%) reported good health, 2 (0.7%) reported between good and fair health, 39 (13%) reported fair health, 1 (0.3%) reported between fair and poor health, and 7 (2%) reported poor health. The mean score was 2.53 ± 1.01 (very good to good).
The eight concepts in the Rand Health Survey are summarized in Figure 4. Each score is based on a possible 100 as the best score. Normal mean scores for the SF-36, reported by McHorney and coworkers (14) for 1,692 patients (mean age, 46.4 yr) who responded to a random mail survey, are presented for comparison. The post-PTE patients scored significantly lower (p < 0.01) in four of the eight concepts of quality of life, including physical function, role limits due to physical function, general health, and emotional well-being. Conversely, post-PTE patients reported less bodily pain than the normals and scored higher in energy/fatigue (p < 0.01). Role limits due to emotional causes and social function were similar for both groups. However, when the post-PTE patients were compared with a separate cohort of 39 PTE patients who had been surveyed before surgery (13), all health concepts were significantly improved except emotional well-being, which remained unchanged.
Fig. 4. Comparison of Rand SF-36 scores of 306 post-PTE patients (solid squares) with those of reported normals (14) (solid diamonds) and 39 pre-PTE patients (solid triangles). *p < 0.01, **p < 0.001, ***p < 0.0001, compared with post-PTE patients.
[More] [Minimize]In response to the question, “How do you feel about the quality of your life since the surgery?,” with choices on a Likert scale of much worse, worse, same as before, improved, and much improved (1-5), 0 patients said much worse or worse, 9 (3%) said same as before, 61 (20.2%) said improved, and 232 (76.8%) said much improved.
Hospitalizations and emergency room visits since PTE surgery were classified as disease related or nondisease related. Disease-related (DR) was defined as that which could possibly be attributed to residual CTEPH postoperatively, or to the treatment of the patient's CTEPH. The number of hospitalizations classified as DR for the total time since surgery (range, 1–16 yr) averaged 0.13 ± 0.48 per year (median, 0; range, 0–6.17). Two hundred fifty-six patients (83.4%) had no DR admissions. Fifty-one patients (16.6%) had 78 hospitalizations: 38 patients had 1 admission each, 6 patients had 2 admissions each, 5 patients had 3 admissions each, 1 patient had 6 admissions, and 1 patient had 7 admissions. The number of DR hospital days since surgery averaged 0.78 ± 3.27 d/yr (median, 0 d/yr; range, 1–28.84 d/yr), with a total of 451 d spent in the hospital. Twenty patients spent < 5 d in the hospital, 18 spent 5–10 d, 7 spent 11–20 d, and 6 spent 21–49 d. Figure 5 depicts DR reasons for admissions. The number of DR emergency room visits for the total time since surgery averaged 0.07 ± 0.32 visits per year (median, 0; range 0–2.49), with a total of 44 visits made by 17 patients (5.5%).
Fig. 5. Possible disease-related hospitalizations of post-PTE patients. DVT = deep venous thrombus; CHF = congestive heart failure.
[More] [Minimize]Morbidity, which may have occurred as a result of PTE surgery, was reported by 12 patients. These conditions included atrial flutter, a known complication of PTE surgery (three patients); short-term memory loss and attention deficit (two patients); chronic chest wall discomfort (four patients); impaired vision and visual migraines (two patients), and pericardial restriction requiring two surgeries for correction (one patient).
The UCSD Shortness of Breath Questionnaire scores were correlated with NYHA class to test for convergent validity (because both measure dyspnea during activities of daily living), resulting in a correlation coefficient of r = 0.75, p < 0.0001.
Post-PTE (48 h) pulmonary vascular resistance (PVR) and cardiac output (CO) measurements were correlated with various measures of functional status (Table 2). A relationship was shown between both the PVR and CO and the distance post-PTE patients could walk and the flights of stairs they could climb. The NYHA class and the UCSD SOB Questionnaire scores also significantly correlated with PVR. In the Rand 36-Item Health Survey, the physical function component correlated with both PVR and CO. The general health component correlated only with the PVR (Table 3). Quality of life (Likert scale) also significantly correlated with the PVR.
| PVR (r value) | CO (r value) | |||
|---|---|---|---|---|
| NYHA class | 0.20§ | −0.08 | ||
| UCSD SOB score | 0.21§ | −0.12 | ||
| Distance walked, ft | −0.31‖ | 0.17¶ | ||
| Flights climbed | −0.25‖ | 0.19§ | ||
| Quality of Life, Likert | −0.15¶ | 0.05 | ||
| SOB, Likert | 0.14 | −0.12 | ||
| DR hospitalizations | 0.05 | −0.03 | ||
| DR days hospitalized | 0.08 | −0.01 | ||
| DR ER visits | 0.01 | −0.06 |
| PVR (r value) | CO (r value) | |||
|---|---|---|---|---|
| Physical function | −0.25‡ | 0.17§ | ||
| Role limits, physical | −0.11 | 0.04 | ||
| Emotional well-being | −0.08 | 0.13 | ||
| Role limits, emotional | −0.05 | 0.06 | ||
| Social function | −0.07 | 0.12 | ||
| Pain | −0.09 | 0.02 | ||
| Energy/fatigue | −0.12 | 0.09 | ||
| General health | −0.24‡ | 0.12 |
The central conclusion of this retrospective analysis of the long-term status of patients who have undergone pulmonary thromboendarterectomy is that the majority of individuals reported good functional status and quality of life, with minimal disease-related health care utilization after surgery. The described functional status, whereby 93% of patients were NYHA Class I or II, substantiates an earlier report in which 117 patients were in Class I (73%) or Class II (23%) 1 yr after PTE (4). It also supports more recent findings in which 95% of 65 patients were NYHA Class I and II at post-PTE month 13–18 (6). In addition, in the current study, functional status was improved as evidenced by good walking and stair-climbing ability, reduced prevalence of cardiopulmonary symptoms related to pulmonary hypertension, and limited use of supplemental oxygen. Many patients who were unable to work before PTE returned to work, and most could perform activities of daily living.
Quality of life, as measured by the Rand SF-36, was shown to be considerably better for the post-PTE patients than for a separate cohort of pre-PTE patients. Although quality of life of the post-PTE patients was rated slightly below that of reported normals, the post-PTE patients were also somewhat older (a mean of 10 yr) than the unaffected individuals.
NYHA class as reported in this study represents each patient's conception of his or her own level of disability and not that of a physician or other medical professional. It might be useful to determine if a medical professional would rate these patients with the same degree of disability, although convergent validity was demonstrated between patient conceptions of NYHA class and patient scores on the UCSD SOB Questionnaire.
It is noteworthy that approximately 3% of patients reported shortness of breath at rest, whereas almost 62% experienced some shortness of breath with exercise. It may be argued that dyspnea during exercise is a poor indicator of limitation in functional status because exertional dyspnea will occur to some degree in most individuals, depending on the extent of the exercise and their level of conditioning. Because many of the study patients were able to walk long distances and climb numerous flights of stairs, it would seem that dyspnea during exercise was not a limiting factor.
This study was further limited in several areas. First, not all surveys were filled out. Many patients had undergone surgery in the distant past (the first patient ever operated was in 1970). Fifty-one patients had died, and 123 could not be located. Another issue was that not all surveys were fully completed. Questions were left blank or answered incompletely. Because educational backgrounds varied, it may be that not all patients understood all questions.
Although considerable effort was taken in the design of the cover letter to reduce the impact of personal involvement with the investigator, it is possible that some of the patients may have had a strong connection with the investigator and introduced bias into the results through potential exaggeration of responses.
There was also potential for error because information was obtained through a mailing of self-administered questionnaires and the responses were internal/subjective and not corroborated by a health care professional. Symptoms related to clinical pathology may have been more accurately elicited by clinical interview. For example, on the basis of the reasons given by patients for reasons for doctor visits, no accurate determination could be made as to whether the visits were related to pulmonary hypertension or to some other illness.
Survival time after pulmonary thromboendarterectomy was demonstrated to be considerably greater than reported survival time without surgery, suggesting that a longer life expectancy can be achieved for patients with chronic thromboembolic pulmonary hypertension after PTE surgery.
Whereas improved pulmonary hemodynamics have been reported previously after pulmonary thromboendarterectomy, this long-term follow-up study found the majority of post-PTE patients in good functional status and quality of life, with minimal utilization of health care services. Because this study was cross-sectional by design, a longitudinal prospective study is needed to delineate better the functional benefits of this unique operative procedure.
The authors acknowledge Andrew Ries, M.D., M.P.H., for his assistance in analyzing and interpreting results. The authors also gratefully acknowledge Paul Shragg, Computer Systems Manager, for his invaluable assistance with data analysis. In addition, the authors appreciate the diligent administrative support provided for the Pulmonary Vascular Program by Rosemary O'Brien, Gayle Lister, and Julie Neher.
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