February 2015 Tucson Pulmonary Journal Club: Fibrinolysis for PE

Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-11. [CrossRef] [PubMed]

The role of fibrinolytic therapy among patients with intermediate-risk pulmonary embolism (PE) is controversial (1). When right ventricular dysfunction and myocardial injury are associated with PE, there is an increased risk of adverse events (2). However, the risk of bleeding with fibrinolytic therapy has previously been thought to outweigh the benefits among patients without overt hemodynamic collapse.

The Pulmonary Embolism Thrombolysis (PEITHO) trial was a multi-center, double-blind, placebo-controlled randomized trial designed to investigate the efficacy and safety of single-bolus injection with tenecteplase plus heparin anticoagulation versus heparin anticoagulation alone among normotensive patients with intermediate risk PE (3). The study included 1005 adult patients who were randomized within fifteen days of symptom onset; randomization occurred when both right ventricular dysfunction (echocardiography or spiral computed tomography) and myocardial injury (troponin I or T) were present. All patients were followed for 30 days. The primary outcome was death or hemodynamic collapse within 7 days of randomization. Safety outcomes included major extra cranial and intracranial hemorrhage within 7 days.

Fibrinolytic therapy was associated with less frequent hemodynamic collapse or death within 7 days of treatment (2.6% vs 5.6%, p=0.02). The result was primarily driven by fewer instances of hemodynamic collapse in tenecteplase group (1.6% vs 5.0%, p=0.002). At 30 days, there was no difference in mortality from any cause between the tenecteplase and usual care groups, 2.5% versus 3.2%, respectively (p=0.42). However, tenecteplase therapy was associated with higher risk of major bleeding and stroke than usual care, 11.5% versus 2.4% (p<0.001) and 2.4% versus 0.2% (p=0.003), respectively. Subgroup analysis showed a trend towards increased bleeding in patients older than 75 years though this was not significant (p=0.09).

PEITHO is a relatively large, expensive, randomized controlled trial that provides little guidance on the optimal care of patients with intermediate risk PE. While improvement in the composite outcome of death or hemodynamic decompensation was significant (Odds Ratio 0.44, CI_95% 0.23-0.87), the benefit was primarily driven by less frequent hemodynamic compromise. Furthermore, any treatment benefit must be weighed against a substantially increased risk of major bleeding (Odds Ratio 5.55, CI_95% 2.3-13.39) or stroke (Odds Ratio 12.10, CI_95% 1.57-93.39). Given that follow-up is limited to 30 days and no patient-reported/patient-centered outcomes are available, it is difficult to provide patients or clinicians with the evidence they need to weigh the risks and benefits. Until better data are available, thrombolytic therapy for intermediate risk PE still remains weakly supported due to unclear efficacy and high risks of major bleeding or stroke, particularly among older patients.

Aarthi Ganesh MD, Christian Bime MD, and Joe Gerald PhD

University of Arizona

Tucson, AZ

References

1. Konstantinides S, Goldhaber SZ. Pulmonary embolism: risk assessment and management. Eur Heart J. 2012;33:3014-22. [CrossRef] [PubMed]
2. Konstantinides S. Acute pulmonary embolism. N Engl J Med. 2008;359:2804-13. [CrossRef] [PubMed]
3. Meyer G, Vicaut E, Danays T, et al; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-11. [CrossRef] [PubMed] 

Reference as: Ganesh A, Bime C, Gerald J. February 2015 Tucson pulmonary journal club: fibrinolysis for PE. Southwest J Pulm Crit Care. 2015;10(2):97-8. doi: http://dx.doi.org/10.13175/swjpcc028-15 PDF

January 2013 Pulmonary Journal Club

Kartalija M, Ovrutsky AR, Bryan CL, Pott GB, Fantuzzi G, Thomas J, Strand MJ, Bai X, Ramamoorthy P, Rothman MS, Nagabhushanam V, McDermott M, Levin AR, Frazer-Abel A, Giclas PC, Korner J, Iseman MD, Shapiro L, Chan ED. Patients with nontuberculous mycobacterial lung disease exhibit unique body and immune phenotypes. Am J Respir Crit Care Med. 2013;187(2):197-205. Abstract

Among patients with nontuberculous mycobacterial (NTM) lung disease is a subset of previously healthy women with a slender body morphotype, often with scoliosis and/or pectus excavatum. The authors enrolled 103 patients with NTM and 101 uninfected control subjects of similar demographics. Patients with

NTM had significantly lower body mass index and body fat and were significantly taller than control subjects. Scoliosis, pectus excavatum and gastroesophageal reflux were significantly more prevalent in patients with NTM. The normal relationships between the adipokines and body fat were lost and IFN-g and IL-10 levels were significantly suppressed in stimulated whole blood of patients with NTM.

The description in this article extends the description of the “Lady Windermere syndrome” first described in the early 1990’s by Reich and Johnson (1). They described 6 elderly women who were immunocompetent, had no significant smoking history or underlying pulmonary disease, and developed Mycobacterium avium complex (MAC). They hypothesized that these women could have had the habit of voluntary suppression of cough, responsible for the inability to clear secretions from the lung. However, it is now known that the adiopectins have immunomodulatory functions and the findings suggest that the underlying pathophysiology may be an immune deficit.

Søyseth V, Bhatnagar R, Holmedahl NH, Neukamm A, Høiseth AD, Hagve TA, Einvik G, Omland T. Acute exacerbation of COPD is associated with fourfold elevation of cardiac troponin T. Heart. 2013;99(2):122-6. Abstract

The authors investigated if acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with myocardial injury, expressed as elevated cardiac troponin T (Trop). In a cross-sectional study, Trops in patients hospitalized for AECOPD were compared with COPD patients in their stable state. Mean Trops were elevated in the AECOPD group (25.8 ng/l) compared to the reference group (4.55 ng/l).  Higher Trops were associated with the presence of pathological q-waves (p=0.012) and electrocardiographic left ventricular hypertrophy (p=0.039), long-term oxygen treatment (p=0.002) and decreasing forced expiratory volume in 1 s (p=0.014).

Slight elevations of Trops in patients admitted to the hospital are common, including AECOPD patients. This study suggests that elevated Trops do no necessarily indicate underlying cardiac disease and that cardiac consultation and/or workup is not necessarily indicated in every AECOPD patient with a slight elevation in Trops. Clinical judgment as to whether a cardiac condition coexists with the AECOPD must be used.

Richard A. Robbins, MD

References

1. Reich JM, Johnson RE. Mycobacterium avium complex pulmonary infection presenting as isolated lingular or middle lobe pattern: the lady Windermere Syndrome. Chest 1992;101:1605-9.

Referece as: Robbins RA. January 2013 pulmonary journal club. Southwest J Pulm Crit Care 2013:6(1):41-42. PDF