Download Beyond the Blue: What Fellows Are Reading in Other Journals

Beyond the Blue:
What Fellows Are Reading in Other Journals
Airway Bypass Stents for Emphysema, Algorithm to
Exclude Precapillary Pulmonary Hypertension, and
Sildenafil for Pulmonary Hypertension in Heart Failure
with Preserved Ejection Fraction
Matthew R. Lammi1, Nicholas Panetta1, and Maria Elena Vega1
1Division
of Pulmonary and Critical Care Medicine, Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania
Recommended Reading from the Temple University School of Medicine Fellows; Kathleen Brennan, Program Director
Shah PL, et al. Bronchoscopic Lung-Volume Reduction with
Exhale Airway Stents for Emphysema (EASE Trial):
Randomized, Sham-controlled, Multicentre Trial.
Lancet (1)
Reviewed by Matthew R. Lammi
In selected patients with emphysema, lung volume reduction surgery has been shown to improve exercise capacity, quality of life,
and survival (2). Because of restrictive inclusion criteria and risk
of surgery, there has been interest in bronchoscopic lung volume
reduction as an alternative to lung volume reduction surgery. Creating airway bypass tracts (ABTs) attempts to bypass collapsed
small airways, allowing air to escape on expiration. The Exhale
Airway Stents for Emphysema (EASE) trial was the first randomized, double-blind, sham-controlled study of ABTs (1).
Patients were included if they had homogeneous emphysema
with an FEV1 less than 50% predicted and an RV/TLC greater
than 0.65. Of the 1,522 patients assessed for eligibility, 208 were
randomized to ABT and 107 to sham bronchoscopy. All patients had bronchoscopy under general anesthesia; the intervention group had passages created in the airway and paclitaxel
stents placed to maintain patency. Bayesian analysis did not
show any superiority of ABT for the coprimary efficacy end
point, which was met if the FVC increased by at least 12% and
modified Medical Research Council (mMRC) score fell by 1
point from baseline at 6 months of follow-up. Mean FVC increased on Day 1 in the ABT group, but this returned to baseline
by 3 months. Mean mMRC scores were significantly lower only at
the 6-month time point in the intervention group.
This trial used a robust randomized, sham-controlled study
design that included patients most likely to benefit from the
treatment. There was no benefit in the coprimary end point,
likely due to stent expectoration and low rates of stent patency
(66% on Day 1 and 21% at 6 mo). Although there were no differences in composite safety end points or 6-month mortality between the groups, the risk of chronic obstructive pulmonary
disease exacerbation or infection was almost twofold higher in
(Received in original form February 10, 2012; accepted in final form April 3, 2012)
Correspondence and requests for reprints should be addressed to Matthew R.
Lammi, M.D., Division of Pulmonary and Critical Care Medicine, Department of
Medicine, Temple University School of Medicine, 3401 N. Broad Street, Philadelphia, PA 19140. E-mail: [email protected]
Am J Respir Crit Care Med Vol 185, Iss. 12, pp 1323–1324, Jun 15, 2012
Copyright ª 2012 by the American Thoracic Society
DOI: 10.1164/rccm.201202-0235RR
Internet address: www.atsjournals.org
the treatment group. This highlights the importance of noting individual safety end points that may be masked by reporting
a composite end point alone. The EASE trial demonstrates that
airway bypass tract formation with paclitaxel stents does not improve outcomes in patients with severe homogeneous emphysema. This is an interesting example of how theoretical benefit
was attained through an intervention but was not sustained because of technical aspects of the procedure.
References
1. Shah PL, Slebos D-J, Cardoso PFG, Cetti E, Voelker K, Levine B, Russell
ME, Goldin J, Brown M, Cooper JD, Sybrecht GW; EASE Study Group.
Bronchoscopic lung-volume reduction with Exhale Airway Stents for
Emphysema (EASE trial): randomised, sham-controlled, multicentre
trial. Lancet 2011;378:997–1005.
2. Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A,
Weinmann G, Wood DE; National Emphysema Treatment Trial Research Group. A randomized trial comparing lung-volume-reduction
surgery with medical therapy for severe emphysema. N Engl J Med
2003;348:2059–2073.
Bonderman D, et al. A Noninvasive Algorithm to Exclude
Pre-capillary Pulmonary Hypertension. Eur Respir J (3)
Reviewed by Nicholas Panetta
Current international guidelines recommend right-heart catheterization (RHC) in symptomatic patients at risk for pulmonary hypertension (PH) with systolic pulmonary artery pressures greater
than 36 mm Hg by transthoracic echocardiography (TTE) (4). TTE
is frequently inaccurate in estimating pulmonary artery pressures
and cannot distinguish precapillary PH from postcapillary PH (5).
This study, through retrospective analysis, sought to identify a
noninvasive diagnostic algorithm to identify or exclude precapillary PH, which was then validated prospectively.
Data, including TTE, 12-lead electrocardiography, serum
N-terminal pro–brain natriuretic peptide (NT-proBNP), lung
function tests, and RHC from 251 patients referred for suspicion
of precapillary PH, were used to develop a noninvasive diagnostic decision tree algorithm. A prospective study of 121 patients
then served as temporal validation of this diagnostic algorithm,
which dichotomized patients as “precapillary PH excluded” and
“precapillary PH likely.” A bootstrap approach was also used to
provide internal validation. All patients subsequently underwent
RHC. Precapillary PH was defined as a mean pulmonary artery
pressure greater than 25 mm Hg at rest with a pulmonary capillary wedge pressure less than 15 mm Hg.
1324
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
The noninvasive diagnostic algorithm initially stratified patients by the presence or absence of a right ventricular strain pattern on electrocardiography, and then by a serum NT-proBNP
level below or above 80 pg/ml. Combining TTE with this diagnostic algorithm yielded a sensitivity of 100% and a specificity of
19.3% in the 121 prospectively studied patients.
The results of this study are tempered by the fact that it is based
on data from a single center. Also, it is unclear how the cutoff point
of 80 pg/ml for serum NT-proBNP was established as both groups
in the retrospective analysis had significantly greater values.
This interesting, well-designed study should help clinicians
with the decision of when to further proceed with RHC in the
workup of their patients and when it can be safely withheld, with
the knowledge that a case of true precapillary PH will not be
missed. Further validation at other centers and among a wider
range of patients would be needed before this could be adopted
into regular practice, however.
References
3. Bonderman D, Wexberg P, Martischnig AM, Heinzl H, Lang M-B, Sadushi
R, Skoro-Sajer N, Lang IM. A noninvasive algorithm to exclude precapillary pulmonary hypertension. Eur Respir J 2011;37:1096–1103.
4. Galiè N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA,
Beghetti M, Corris P, Gaine S, Gibbs JS, et al.; ESC Committee for
Practice Guidelines (CPG). Guidelines for the diagnosis and treatment of
pulmonary hypertension. The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology
(ERS) and the European Respiratory Society (ERS), endorsed by the
International Society of Heart and Lung Transplantation (ISHLT). Eur
Heart J 2009;30:2493–2537.
5. Fisher MR, Forfia PR, Chamera E, Housten-Harris T, Champion HC,
Girgis RE, Corretti MC, Hassoun PM. Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension. Am J Respir Crit Care Med 2009;179:615–621.
VOL 185
2012
Guazzi and colleagues (6) conducted a 1-year, double-blind,
placebo-controlled trial with the phosphodiesterase-5 inhibitor
sildenafil in patients with PH and HFpEF. Forty-four patients
were randomly assigned to placebo or sildenafil. At 6 and 12
months, sildenafil was associated with significant improvement in
quality of life and sustained improvement in cardiopulmonary
hemodynamics and lung function.
This was a small but comprehensive study and its results enhance our knowledge of the pathophysiological mechanisms associated with HFpEF and PH. Treatment with sildenafil induced
reduction of pulmonary artery pressures, pulmonary arterial resistance, and pulmonary capillary wedge pressure (PCWP). In
the placebo group, pulmonary arterial resistance increased over
the course of 12 months with unchanged PCWP, suggesting
remodeling rather than simply vasoconstriction. There was also
an improvement in right-heart hemodynamics in the treatment
group suggested by leftward shift of the right ventricular FrankStarling relationship, increased tricuspid annular systolic excursion, right atrial and right ventricular end-diastolic pressures, and
ejection rate. In addition, reduction in right atrial pressure and
PCWP significantly correlated with improvement in the alveolar–
capillary membrane conductance, suggesting that reduction in
these pressures leads to an improvement in pulmonary lymphatic
drainage.
Patients in both arms showed evidence of elevated systemic
blood pressure and PCWP throughout the study. One may wonder whether the improvement in cardiopulmonary hemodynamics and quality of life could have also been achieved with more
aggressive heart failure treatment. Although the results of this
trial are promising and the primary end points of improvement
in pulmonary hemodynamics and right ventricular performance
are important, it will be crucial to verify these findings in a larger
trial and to determine whether the use of sildenafil in patients
with PH and HFpEF will translate into clinical benefit with acceptable safety profile and improved survival.
Guazzi M, et al. Pulmonary Hypertension in Heart Failure with
Preserved Ejection Fraction: A Target of Phosphodiesterase-5
Inhibition in a 1-Year Study. Circulation (6)
Author disclosures are available with the text of this article at www.atsjournals.org.
Reviewed by Maria Elena Vega
References
The presence of pulmonary hypertension (PH) in patients with
heart failure with preserved ejection fraction (HFpEF) is associated with increased morbidity and mortality (7). There is no
specific therapy for PH due to left heart disease and most
advances have focused on the treatment of patients with pulmonary arterial hypertension.
6. Guazzi M, Vicenzi M, Arena R, Guazzi M. Pulmonary hypertension in heart
failure with preserved ejection fraction: a target of phosphodiesterase-5
inhibition in a 1-year study. Circulation 2001;124:164–174.
7. Lam CSP, Roger VL, Rodeheffer RJ, Borlaug BA, Enders FT, Redfield
MM. Pulmonary hypertension in heart failure with preserved ejection
fraction: a community-based study. J Am Coll Cardiol 2009;53:119–
126.