0
Correspondence |

Recurrence of Severe Pulmonary Hypertension Following the Removal of a Lung AllograftResponse FREE TO VIEW

Daniel C. Grinnan, MD; Paul Fairman, MD; Janet Pinson, NP
Author and Funding Information

Affiliations: VCU Health System, Richmond, VA,  Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, VA

Correspondence to: Daniel C. Grinnan, MD, VCU Health System, PO Box 980050, Richmond, VA 23298; e-mail: dcgrinnan@vcu.edu



Chest. 2007;132(6):2057-2058. doi:10.1378/chest.07-1724
Text Size: A A A
Published online

Deb et al (June 2006)1 previously reported a patient with pulmonary arterial hypertension (PAH) in whom lung transplantation appeared to have acted as a “bridge to recovery.” Idiopathic PAH was diagnosed in 1992 in the patient, who eventually received a single-lung transplant in 1994. The posttransplant course was complicated by the development of chronic renal failure and chronic rejection. Due to ongoing infection in the allograft, and after determining that the allograft was essentially nonfunctional, the allograft was removed in August 2004. The mean pulmonary arterial pressure was 33 mm Hg prior to explant, and 6 months later a repeat right heart catheterization documented a mean pulmonary arterial pressure of 35 mm Hg. This was the first case showing significant improvement of PAH following lung transplant and subsequent removal of the transplanted lung.

Following a change in the patient’s geographic location, our center assumed care of the patient in August 2006. At that time, the patient was on multiple therapies for recurrent PAH. These included sildenafil (20 mg tid), bosentan (125 mg bid), and IV treprostinil (60 ng/kg/min). Despite this aggressive treatment, the patient’s functional status was class IV, and echocardiograms continued to show signs of right ventricular dilatation and impaired function with elevated pulmonary arterial systolic pressure (70 to 80 mm Hg). Unfortunately, recurrent line infections and difficult central vein access (due to her history of recurrent central access for hemodialysis) precluded the ongoing use of IV treprostinil. The patient was unable to tolerate therapy with subcutaneous remodulin or inhaled iloprost. Compassionate use of imatinib was started at a dosage of 200 mg daily. She was successfully tapered off treprostinil, and the central line was discontinued. The patient has continued to respond well to imatinib therapy with regression to functional class III, improvement in 6-min walk distance from < 100 to 340 m, and stability of estimated pulmonary arterial systolic pressure and right ventricular function seen on echocardiograms. While imatinib has several molecular targets, its ability to block the receptor for platelet-derived growth factor, a powerful mitogen of the pulmonic circulation, could be beneficial in patients with PAH.2Following promising case reports,34 ongoing clinical trials are investigating the use of imatinib in patients with PAH.

The eventual recurrence of PAH in this patient is important to note. The “multiple-hit hypothesis” of PAH assumes that a genetic predisposition, combined with environmental factors, leads to the development of idiopathic PAH. Severe pulmonary hypertension developed in our patient, followed by significant improvement in PAH symptoms and hemodynamics following transplant, followed by recurrence of severe PAH following removal of the transplanted lung. While the use of immunosuppressive medication to prevent allograft rejection may have played a role in the patient’s improved PAH, we believe it unlikely, as these medications have not been effective in the treatment of PAH. Rather, with insertion of the allograft in 1994, an enormous shift in the pulmonary circulation (97% of perfusion to the allograft by ventilation-perfusion scan) permitted a great reduction in the endothelial stress to the vascular bed of the native lung. Following years of reduced endothelial stress after receiving the transplant, the patient’s PAH improved significantly. However, as her allograft eventually failed and was then removed, her native load took on a progressively greater proportion of the pulmonary blood flow. This increase in volume and endothelial stress likely permitted recurrent injury to the vascular endothelium, which, combined with a genetic predisposition, led to the return of severe PAH.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

The author has no conflict of interest to disclose.

Deb, S, Yun, J, Burton, N, et al (2006) Reversal of idiopathic pulmonary arterial hypertension and allograft pneumonectomy after single lung transplantation.Chest130,214-217. [PubMed] [CrossRef]
 
Barst,, Robyn, J PDGF signaling in pulmonary arterial hypertension.J Clin Invest2005;115,2691-2694. [PubMed]
 
Ghofrani, HA, Seeger, W, Grimminger, F Imatinib for the treatment of pulmonary arterial hypertension.N Engl J Med2005;353,1412-1413. [PubMed]
 
Souza, R, Sitbon, O, Parent, F, et al Long term imatinib treatment in pulmonary arterial hypertension.Thorax2006;61,736
 
To the Editor:

On behalf of my co-authors, I would like to thank our colleagues for assuming the care of this complicated patient and providing important follow-up information.1 Their report adds to the growing body of literature attesting to the potential utility of imatinib and possibly other forms of antiproliferative therapy as we move beyond the era of vasodilator therapy in our quest for a cure for this devastating condition.

References
Deb, S, Yun, J, Burton, N, et al Reversal of idiopathic pulmonary arterial hypertension and allograft pneumonectomy after single lung transplantation.Chest2006;130,214-217. [PubMed] [CrossRef]
 

Figures

Tables

References

Deb, S, Yun, J, Burton, N, et al (2006) Reversal of idiopathic pulmonary arterial hypertension and allograft pneumonectomy after single lung transplantation.Chest130,214-217. [PubMed] [CrossRef]
 
Barst,, Robyn, J PDGF signaling in pulmonary arterial hypertension.J Clin Invest2005;115,2691-2694. [PubMed]
 
Ghofrani, HA, Seeger, W, Grimminger, F Imatinib for the treatment of pulmonary arterial hypertension.N Engl J Med2005;353,1412-1413. [PubMed]
 
Souza, R, Sitbon, O, Parent, F, et al Long term imatinib treatment in pulmonary arterial hypertension.Thorax2006;61,736
 
Deb, S, Yun, J, Burton, N, et al Reversal of idiopathic pulmonary arterial hypertension and allograft pneumonectomy after single lung transplantation.Chest2006;130,214-217. [PubMed] [CrossRef]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543