Intermediate-term results of heart-lung transplantation for cystic fibrosis

doi:10.1016/0140-6736(92)91842-V

The Lancet

Volume 339, Issue 8809, 27 June 1992, Pages 1583-1587

https://doi.org/10.1016/0140-6736(92)91842-V Get rights and content

Abstract

Between September, 1984, and March, 1991, 79 patients underwent heart-lung transplantation for end-stage cystic fibrosis at the Harefield Hospital. Short-term outcome has already been reported, and we now present intermediate-term results. The overall actuarial patient survival was 69% at 1 year, 52% at 2 years, and 49% at 3 years. 17 patients had diabetes mellitus with a survival of 62% to 1 year and 51% to 2 years. 23 patients had one or more other possible high-risk factors, and survival of these patients was 64% at 1 year and 57% at 2 years, compared with 71% and 49%, respectively, in the low-risk group (n=56). Pseudomonas aeruginosainfection was the most common respiratory infection encountered postoperatively. 92% of patients had at least one episode of acute rejection during the first 3 postoperative months. Lung function was greatly improved after transplantation, the mean forced expiratory volume in 1 s and forced vital capacity increasing from 22% and 35% predicted, respectively, preoperatively to 68% and 70% predicted, respectively, by the sixth postoperative month. This improvement was maintained at 1, 2, and 3 years after transplantation. Lymphoproliferative disorders (4 patients) were successfully treated. Obliterative bronchiolitis developed in 17 patients and the cumulative probability of getting this complication at 1, 2, and 3 years postoperatively was 17%, 23%, and 48%, respectively. Overall, 7 patients were retransplanted. There was no coronary artery disease in the 37 patients who underwent coronary angiography at 1 year, 14 at 2 years, and 9 at 3 years after surgery. 58 patients donated their hearts for subsequent "domino" heart transplantation. Our 51/2-year experience with heart-lung transplantation is encouraging but the shortage of donor organs and the complication of obliterative bronchiolitis are the two main obstacles to be overcome.

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Cited by (72)

Cystic fibrosis related diabetes (CFRD) prognosis
2021, Journal of Clinical and Translational Endocrinology
Citation Excerpt :
Diabetes associated with transplantation can be categorized as either pre-existing before surgery, or diabetes that develops post-transplant. Prior to transplant, 29–65% of CF patients have been described as having diabetes [29,30]. Diabetes has been associated as a risk factor for death while waiting for a lung transplant, likely related to the underlying severity of illness in these patients [31].
Cystic fibrosis related diabetes (CFRD) occurs in at least 40–50% of adults with CF. With other forms of diabetes, microvascular and macrovascular disease are the major causes of morbidity and mortality. Macrovascular disease is rare in CF. While microvascular disease does occur in this population, there are CF-specific diabetes complications that have a more important impact on prognosis. The additional diagnosis of diabetes in CF is associated with decreased lung function, poor nutritional status, and an overall increase in mortality from lung disease. These negative findings start even before the clinical diagnosis of CFRD, during the period when patients experience abnormal glucose tolerance related to insulin insufficiency. The main mechanisms by which CFRD negatively affects prognosis are thought to be a combination of 1) protein catabolism, decreased lean body mass and undernutrition resulting from insulin insufficiency, and 2) an increased pro-inflammatory and pro-infectious state related to intermittent hyperglycemia. With the introduction of CFTR modulators, the care of CF patients has been revolutionized and many aspects of CF health such as BMI and lung function are improving. The impact of these drugs on the adverse prognosis related to the diagnosis of diabetes in CF, as well as the potential to delay or prevent onset of CFRD remain to be determined.
Does Sildenafil produce a sustained benefit in patients with pulmonary hypertension associated with parenchymal lung and cardiac disease?
2007, Vascular Pharmacology
Sildenafil may be of benefit for selected patients with pulmonary hypertension associated with parenchymal lung and cardiac diseases. However the medium term benefits of this treatment for such patients is unclear.
16 consecutive patients with secondary pulmonary hypertension who had been on maximal appropriate therapy received Sildenafil 50 mg tds following assessment which included right heart catheter, 2D echocardiography and six minute walk test. Right heart catheterisation, 2D echocardiography and six minute walk test were performed after eight weeks treatment, at 12 months and at six monthly intervals thereafter. Baseline medications were continued.
16 patients with pulmonary hypertension associated with inoperable chronic pulmonary thromboembolism (6 patients), valvular heart disease (4), chronic obstructive pulmonary disease (3), idiopathic pulmonary fibrosis (2), and obstructive sleep apnoea (1) were studied. The age range was 42 to 81 (median 68) years and the period of follow up was 12 to 51 (median 22) months. Six minute walk increased significantly, p = 0.002, from baseline to long term follow up. The improvement in 14 patients ranged from 14 m to 300 m with a percentage increase of 5% to 567% increase. In one patient there was no change and in one patient the six minute walk test fell as a consequence of progression of known arthritis. The mean pulmonary artery pressure was significantly reduced at long term follow up (p = 0008). The pulmonary vascular resistance (PVR) fell in eleven patients, this reduction ranged from 0.2 woods units to 8.7 woods units (mean reduction 3.3 woods units). The percentage reduction in PVR ranged from 7% to 71% with a mean reduction of 43%. In five patients the pulmonary vascular resistance increased. 2D echocardiography showed a sustained improvement in right ventricular function in 11 patients. There were no deaths during follow up.
Sildenafil may have a role for selected patients with pulmonary hypertension associated with cardiac and pulmonary diseases. The medication seems well tolerated and for some patients is effective within 8 weeks and results in a sustained long term improvement in haemodynamics and exercise capacity.
A potential role for sildenafil in the management of pulmonary hypertension in patients with parenchymal lung disease
2006, Vascular Pharmacology
Sildenafil offers potential to treat patients with pulmonary hypertension by selectively inhibiting phosphodiesterase type five pathways in the lung. It is recommended for selected patients with pulmonary arterial hypertension, but its role in the management of pulmonary hypertension associated with parenchymal lung disease is unclear.
Seven patients (68–86 years) with end stage chronic obstructive pulmonary disease (COPD, 4) and idiopathic pulmonary fibrosis (IPF, 3) were referred to our unit. All patients had a long-term history of chronic lung disease and were on maximal appropriate therapy prescribed by their referring pulmonologist. Thromboembolic disease was excluded by pulmonary angiography and all patients had had high resolution thoracic CT scan. At assessment right heart catheterisation, 2D echocardiography and 6-min walk test were performed prior to commencement of sildenafil 50 mg tds. Their medication was otherwise unchanged. After 8 weeks treatment, right heart catheterisation, 2D echocardiography and 6-min walk test were repeated.
The pulmonary vascular resistance was reduced in six patients (from 13, 3, 3, 6.5, 3.5 and 10.5 wood units to 9.7, 2.5, 2.8, 4.4, 2.5 and 5.4 wood units, respectively). Six-minute walk test increased in six patients (from 110 m, 210 m, 80 m, 30 m, 210 m and 80 m to 130 m, 312 m, 120 m, 82 m, 244 m and 100 m, respectively). One patient with COPD did not demonstrate a favourable response although their cardiac output increased on sildenafil therapy. 2D echocardiography showed a reduction in estimated PA pressure in six patients with an improvement in right ventricular systolic function in two COPD patients.
Our results suggest that sildenafil may have a role for selected patients with COPD and IPF who have pulmonary hypertension.
Lung transplantation for non-cystic fibrosis bronchiectasis: Analysis of a 13-year experience
2005, Journal of Heart and Lung Transplantation
Lung transplantation is a well-established treatment for end-stage cystic fibrosis, and there are considerable data on medium- and long-term results. However, less information exists about transplantation for non-cystic fibrosis bronchiectasis.
Between December 1988 and June 2001, 22 patients (12 men, 10 women) underwent transplantation for bronchiectasis not due to cystic fibrosis. Procedures were bilateral sequential single-lung transplants (BSSLTX) in 4 patients, en bloc double lung transplants (DLTX) in 5, heart-lung transplants (HLTX) in 6, and single-lung transplants (SLTX) in 7. Lifelong outpatient follow-up was continued at a minimum of every 6 months.
One-year Kaplan-Meier survival for all patients was 68% (95% confidence interval [CI], 54%–91%), and 5-year survival was 62% (95% CI, 41–83%). One-year survival after SLTX was 57% (95% CI, 20%–94%) vs 73% (95% CI, 51–96%) for those receiving 2 lungs. At 6 months, mean forced expiratory volume in 1 second was 73% predicted (range, 58%–97%), and mean forced vital capacity was 68% predicted (range, 53%–94%) after receiving 2 lungs (n = 10); in the SLTX group at 6 months, mean forced expiratory volume in 1 second was 50% predicted (range, 34%–61%), and mean forced vital capacity was 53% predicted (range 46–63%) (n = 4).
Survival and lung function after transplantation for non-cystic fibrosis bronchiectasis was similar to that after transplantation for cystic fibrosis. A good outcome is possible after single lung transplantation in selected patients.
'Double or quits': Perceptions and management of organ transplantation by adults with cystic fibrosis
2003, Social Science and Medicine
Medical sociologists have often considered lay perceptions of the risks of medical interventions, yet in many empirical studies respondents are people who are not likely to be exposed to a particular intervention. Furthermore, it has been well documented that risk perceptions may change over time and with diminishing health state. This paper explores perceptions and management of the risks of organ transplantation amongst adults with cystic fibrosis (CF), the most common autosomal recessive genetic disease in the UK. Although the focus of medical research is now on providing gene replacement therapy to this group, transplantation is currently the last treatment that an adult with CF can be offered when all other treatment has failed to maintain their health. Thirty-one respondents with varying degrees of health state from a specialist CF centre were interviewed as part of a larger study concerning perceptions of health and risks of treatment. Interviews were audiotaped, transcribed and analysed using ATLAS-ti. During analysis respondents’ transcripts were divided into two groups: firstly those who did not anticipate needing a transplant in the near future (if at all) and secondly those who were currently being considered for transplantation, on the transplant list, or who had already received donor organs. The paper focuses on themes arising from interview transcripts and finds that although the focus of risk differs between the two groups, the influence of luck is perceived as strong for both groups and emotion work features heavily in those undergoing the transplant process. Contrary to previous research, fears of inheriting donor characteristics are not found amongst adults with CF, but rather body components are commodified when talking of both giving and receiving organs.
Lung and heart-lung transplantation in patients with end-stage cystic fibrosis: The Stanford experience
2002, Annals of Thoracic Surgery
Citation Excerpt :
In our experience, the average differential ischemic time between the first lung and the second lung was 136 minutes for an off-pump procedure and 69 minutes for an on-pump procedure (both lungs) (p < 0.0001). Lower incidences of cerebrovascular accidents and comparable hemorrhagic complications have been observed compared with other reports [14, 17]. In recent years, we have introduced several modifications to our intraoperative strategy to help minimize the chance of postoperative hemorrhage and the need of reexploration.
Background. Bilateral lung (BLTx) and heart-lung transplantation have gained wide acceptance as treatment of end-stage lung disease from cystic fibrosis. We reviewed our 13-year experience with thoracic transplantation for cystic fibrosis with an operative approach that favors use of cardiopulmonary bypass for BLTx.
Methods. Sixty-four patients with cystic fibrosis underwent heart-lung transplantation (n = 22, 34.4%) or BLTx (n = 42, 65.6%) between 1988 and 2000. Mean age and weight at transplantation were 29 ± 8 years and 51 ± 11 kg, respectively. Mean follow-up for survivors was 4.4 ± 3.6 years. Immunosuppression regimen included cyclosporine, tapered corticosteroids, azathioprine, and induction therapy with OKT3 (murine monoclonal antibodies) or rabbit antithymocyte globulin. Cardiopulmonary bypass was used in all but 5 patients (7.8%). However, in 8 (19%) of the 42 patients having BLTx, only the grafting of the second lung was performed with cardiopulmonary bypass.
Results. The operative mortality rate was 1.6%. The actuarial survival rates at 1 year, 3 years, 5 years and 10 years were 93.2%, 77.7%, 61.8%, and 48.1%, respectively, with no significant difference between BLTx and heart-lung transplantation. The major hospital complications were pneumonia (n = 11, 17.2%) and bleeding (n = 8, 12.5%). Clinically significant reperfusion injury was observed in 6 patients, 3 of whom required reintubation. Freedom from acute lung rejection beyond 1 year was 47.7%. One patient underwent late retransplantation, and 4 required bronchial stenting. Obliterative bronchiolitis accounted for eight (50.0%) of 16 late deaths.
Conclusions. Though postoperative bleeding and pneumonia are still of concern, satisfactory early and intermediate-term results can be expected in patients undergoing BLTx or heart-lung transplantation for cystic fibrosis. Cardiopulmonary bypass can be used for BLTx with no adverse impact on intermediate and long-term outcomes.

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CLINICAL PRACTICEIntermediate-term results of heart-lung transplantation for cystic fibrosis

Abstract

J Clin Epidermiol

Lancet

Ann Thorac Surg

Cystic fibrosis in adolescents and adults

Thorax

Managing adults with cystic fibrosis

Br Med J

Report of the Royal College of Physicians. Recommendations for care of CF patients in the UK

Cystic fibrosis in the United Kingdom 1977-1985: an improving picture

Br Med J

CLINICAL PRACTICE
Intermediate-term results of heart-lung transplantation for cystic fibrosis