| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
Duke University Medical Center Durham, NC
Dr. Tapson is Professor of Medicine, Pulmonary Allergy and Critical Care, Department of Medicine, Duke University Medical Center.
Correspondence to: Victor Tapson, MD, FCCP, Pulmonary Allergy and Critical Care, Department of Medicine, Duke University Medical Center, Durham, NC 27710; e-mail: tapso001{at}mc.duke.edu
Untreated idiopathic pulmonary arterial hypertension (PAH) is characterized by a progressive elevation of pulmonary artery pressure, followed by worsening right ventricular failure and ultimately death.1 With the most aggressive medical approaches (continuous IV prostacyclin therapy), survival is only approximately 63% at 3 years.23 Patients with idiopathic PAH and a patent foramen ovale (PFO) appear to live longer than those without a PFO.4 Individuals with Eisenmenger syndrome (anatomic right-to-left shunt) have a better prognosis than those with PAH without a shunt, based on a slowly progressive increase in pressure and gradual evolution of right ventricular hypertrophy that enable the ventricle to cope with very high pressures.5 Creation of an interatrial communication has been shown to preserve systemic output by decompressing the dysfunctional right ventricle, offering temporary clinical benefit to very ill patients with idiopathic PAH in whom therapy is failing.6789
In this issue of CHEST (see page 977), Kurzyna and colleagues10 from Warsaw, Poland present their experience with 14 balloon atrial septostomy (BAS) procedures in 11 patients, 9 of whom had idiopathic PAH. Based on the initial cardiac index (1.54 + 0.34 L/min m2), mixed venous O2 saturation values, and pulmonary vascular resistance values, this was a cohort of patients with very advanced disease. The procedure led to significant improvement in immediate cardiac index (CI) [increase in CI in all but one patient], although other postprocedure hemodynamic parameters did not improve. Functional class improvement, albeit somewhat subjective, was encouraging, with five patients improving from New York Heart Association class III to II, and one patient improving from class IV to III. Considering the severity of disease, any benefit might be considered encouraging. As expected, the price to pay was compromised oxygenation. One critically ill patient died at day 24, and three others died during the 12-month follow-up; there were no procedure-related deaths. In this study, the baseline CI was lower than in several other previous series,89 although there were fewer class IV patients than in the other studies. While overall survival did not differ from that predicted in historical control subjects, clearly, some patients benefited.
Over a decade ago, continuous IV epoprostenol became the first Federal Drug Administration-approved drug for PAH after demonstrating improved mortality in a prospective, randomized trial.11 Four other drugs have since been approved, and lung transplantation has come to the clinical forefront. With these advances, why the interest in BAS? First, patients still worsen in spite of aggressive medical therapy23; and second, the story is a bit different many places outside of the United States. The authors have considerable experience with the management of PAH, but as in many countries have limited pharmacologic options. Their expertise with BAS has arisen from the need to provide therapy to very sick individuals. Most centers in the United States offer the procedure only rarely, and many experienced pulmonary hypertension clinicians have never performed one. While the drugs registered by the European Agency for the Evaluation of Medicinal Products (sildenafil, bosentan, and iloprost) are formally available in all European Union countries including Poland, availability does not equate with reimbursement by national health insurance, and cost is usually prohibitive. Certain drugs not registered in the European Union, such as treprostinil, can sometimes be applied for and obtained. Enrollment of patients in clinical trials in Poland enables a few patients to continue on drugs in the extension phase of the trial. Therapy for PAH is even less accessible in certain other Eastern European countries.
Unfortunately, BAS is contraindicated in those patients who are in the most dire need of intervention; those with markedly elevated pulmonary vascular resistance, arterial oxygen saturations < 80% at rest, and severe right-heart failure (low CI and high right atrial pressure) appear more likely to worsen or die after BAS.678912 Massive right-to-left shunting may result in inadequate pulmonary blood flow and severe hypoxemia. Thus, there appears to be a window of opportunity for this procedure, and the authors of this study from Warsaw caution that the preferred approach for BAS is elective rather than "rescue," although this distinction may sometimes be blurred in clinical practice. While this investigation is small and uncontrolled, it reminds us that despite advances in the approach to treating PAH, septostomy is alive and relied on. While the study design is not ideal, it is the best that can be done; we will likely never see a prospective, randomized trial, and the procedure will remain best performed in the hands of a small number of experienced clinicians. At present, it is indicated for advanced New York Heart Association class III and class IV patients with recurrent syncope and/or right-heart failure despite all available medical treatments, unless the disease is simply too advanced.712 It is used either as a palliative bridge to lung transplantation or as the sole treatment modality when other options are not available.
Medical therapy for PAH continues to evolve. In addition to the currently Food and Drug Administration-approved drugs (epoprostenol, treprostinil, iloprost, bosentan, and sildenafil), other related and unrelated drugs are being explored. Completely new directions include the use of imatinib, a drug that selectively suppresses the tyrosine kinase pathway conveying potent antiproliferative effects. This drug has proven effective in case reports of very ill PAH patients in whom aggressive therapy fails.13 Therapy for PAH is expensive, ranging from $10,000 to $35,000/yr for single-agent oral therapy, to well over $100,000/yr for parenteral therapy. Both cost and availability limit therapeutic options, particularly outside of the United States. Thus, BAS maintains a place in the therapeutic armamentarium for PAH; and in certain countries, it may be of critical importance, whether as a bridge to possible additional therapy, or the potential opportunity for a few more months of life. Still, we need better treatment and better access to it, particularly in patients with very advanced PAH. This disease is a worldwide problem, without worldwide access to therapy.
Footnotes
The author has received research grants from and served on consulting/advisory boards for Actelion, Encysive Lungs Rx, Pfizer, and United Therapeutics.
References
Related Article
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
