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Table 1.  
Clinical Characteristics of Study Population
Clinical Characteristics of Study Population
Table 2.  
Primary and Secondary Outcomes in Patients With a Negative CTPA Result, With and Without Limitations
Primary and Secondary Outcomes in Patients With a Negative CTPA Result, With and Without Limitations
1.
Anderson  DR, Kahn  SR, Rodger  MA,  et al.  Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007;298(23):2743-2753.
PubMedArticle
2.
Carrier  M, Righini  M, Wells  PS,  et al.  Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications: a systematic review and meta-analysis of the management outcome studies. J Thromb Haemost. 2010;8(8):1716-1722.
PubMedArticle
3.
Stein  PD, Goodman  LR, Hull  RD, Dalen  JE, Matta  F.  Diagnosis and management of isolated subsegmental pulmonary embolism: review and assessment of the options. Clin Appl Thromb Hemost. 2012;18(1):20-26.
PubMedArticle
4.
Burge  AJ, Freeman  KD, Klapper  PJ, Haramati  LB.  Increased diagnosis of pulmonary embolism without a corresponding decline in mortality during the CT era. Clin Radiol. 2008;63(4):381-386.
PubMedArticle
5.
Wiener  RS, Schwartz  LM, Woloshin  S.  Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171(9):831-837.
PubMedArticle
6.
Sheh  SH, Bellin  E, Freeman  KD, Haramati  LB.  Pulmonary embolism diagnosis and mortality with pulmonary CT angiography versus ventilation-perfusion scintigraphy: evidence of overdiagnosis with CT? AJR Am J Roentgenol. 2012;198(6):1340-1345.
PubMedArticle
Research Letter
Less Is More
March 2015

Computed Tomographic Pulmonary AngiographyClinical Implications of a Limited Negative Result

Author Affiliations
  • 1Departments of Radiology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York
  • 2Department Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York
JAMA Intern Med. 2015;175(3):447-449. doi:10.1001/jamainternmed.2014.7202

A substantial proportion of computed tomographic pulmonary angiography (CTPA) results are degraded by patient-related and technical factors, yielding a limited negative interpretation, which qualifies the definitive exclusion of pulmonary embolism. This leads to diagnostic uncertainty and may affect patient management. A multicenter randomized clinical trial of CTPA vs ventilation-perfusion scintigraphy considered CTPA results negative if no pulmonary embolism was demonstrated to the lobar level.1 Investigators have explicitly questioned the clinical relevance of small pulmonary emboli,2,3 and there is growing concern that pulmonary embolism is overdiagnosed on CTPA.4,5

We hypothesized that a limited negative CTPA result portends similar clinical outcomes to a definitively negative result; thus, emphasis on examination limitations may, in fact, be detrimental.

Methods

This retrospective cohort study was approved by the institutional review board of the Montefiore Medical Center, which waived written informed consent. Included were all adults with suspected pulmonary embolism who underwent CTPA from July 1, 2011, through June 30, 2012, at the 3 emergency departments or inpatient sites of Montefiore Medical Center, Bronx, New York. We defined a limited negative CTPA result as one that reported no pulmonary embolism but also explicitly stated a limitation or qualification in the report impression. The primary outcome was 90-day venous thromboembolism incidence, a measure of the false-negative rate. Secondary outcomes were additional imaging, initiation of anticoagulation treatment, and bleeding complications.

Results

The study population comprised 2553 patients with mean (SD) age 55 (18) years, 66% women and 85% ethnic minorities. A total of 264 CTPA results (10%) were positive; 1663 (65%) were definitively negative; 569 (22%) were limited negative; and 57 (2%) were nondiagnostic for pulmonary embolism. In all, 25% of negative CTPA results (569 of 2232) were limited negative. Patients with limited negative CTPA results were more similar to patients with definitely negative results than they were to patients with positive results in their baseline characteristics and outcomes (Table 1).

The false-negative rate (90-day venous thromboembolism incidence) for patients with a limited negative CTPA result was 1.4% vs 1.8% for patients with a definitively negative CTPA result (odds ratio [OR], 0.78; 95% CI, 0.35-1.70). This persisted after adjustment for several confounders (Table 2).

Patients with limited negative vs definitively negative CTPA results had more additional imaging with ventilation-perfusion scintigraphy (OR, 4.30; 95% CI, 1.83-10.11) and initiation of anticoagulation treatment (OR, 1.47; 95% CI, 1.17-1.87). There was a trend toward increased bleeding events (OR, 1.62; 95% CI, 0.98-2.69) in patients with limited vs definitively negative CTPA results.

Discussion

At the population level, pulmonary embolism diagnosis has essentially doubled since CTPA replaced ventilation-perfusion scanning as the dominant imaging modality for suspected pulmonary embolism in the United States without accompanying changes in risk factors or mortality, but with an increase in bleeding complications.4,5 Patients diagnosed with pulmonary embolism by CTPA have a less severe disease spectrum than those diagnosed with scintigraphy and only half the odds of death.6

The present study demonstrates that patients with limited negative CTPA results in which small emboli cannot be excluded have similar outcomes to those with definitively negative studies. Further diagnostic testing or initiation of anticoagulation therapy is likely unnecessary in a substantial proportion of these patients, and careful consideration of the pretest probability is warranted.

Limitations of this study include its retrospective cohort and its single health system design with the inherent potential for unmeasured confounders, underreporting, and uncaptured events. However, these limitations are unlikely to create a systematic bias.

In conclusion, patients with limited negative CTPA results are indistinguishable from those with definitively negative results in false-negative rate (90-day venous thromboembolism incidence). These patients are more likely to be reimaged with ventilation-perfusion scanning and anti-coagulated. Physicians have grown accustomed to advanced CT technology with submillimeter resolution such that a “limited” study often reflects only a minor deficiency in the usual superb image quality. A limited negative CTPA result should not be automatically interpreted as an indication of clinical uncertainty because the question of “clinically relevant” pulmonary embolism has most likely already been answered.

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Article Information

Corresponding Author: Linda B. Haramati, MD, MS, Department of Radiology, Montefiore Medical Center and Albert Einstein College of Medicine, 111 E 210th St, Bronx, NY 10467 (lharamati@gmail.com).

Published Online: January 12, 2015. doi:10.1001/jamainternmed.2014.7202.

Author Contributions: Dr Yu had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Yu, Haramati.

Acquisition, analysis, or interpretation of data: Yu, Nayak, Levsky, Haramati.

Drafting of the manuscript: Yu, Nayak, Levsky, Haramati.

Critical revision of the manuscript for important intellectual content: Yu, Levsky, Haramati.

Statistical analysis: Yu.

Administrative, technical, or material support: Yu, Nayak, Haramati.

Study supervision: Levsky, Haramati.

Conflict of Interest Disclosures: Dr Haramati’s spouse is a board member of Kryon, Bioprotect, and Orthospace. No other conflicts are reported.

Previous Presentation: Preliminary analysis of these results was presented as an electronic exhibit and informal oral presentation at the Radiological Society of North America Annual Meeting; December 3, 2013; Chicago, Illinois.

Additional Information: Dr Yu is now with the Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia.

References
1.
Anderson  DR, Kahn  SR, Rodger  MA,  et al.  Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007;298(23):2743-2753.
PubMedArticle
2.
Carrier  M, Righini  M, Wells  PS,  et al.  Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications: a systematic review and meta-analysis of the management outcome studies. J Thromb Haemost. 2010;8(8):1716-1722.
PubMedArticle
3.
Stein  PD, Goodman  LR, Hull  RD, Dalen  JE, Matta  F.  Diagnosis and management of isolated subsegmental pulmonary embolism: review and assessment of the options. Clin Appl Thromb Hemost. 2012;18(1):20-26.
PubMedArticle
4.
Burge  AJ, Freeman  KD, Klapper  PJ, Haramati  LB.  Increased diagnosis of pulmonary embolism without a corresponding decline in mortality during the CT era. Clin Radiol. 2008;63(4):381-386.
PubMedArticle
5.
Wiener  RS, Schwartz  LM, Woloshin  S.  Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171(9):831-837.
PubMedArticle
6.
Sheh  SH, Bellin  E, Freeman  KD, Haramati  LB.  Pulmonary embolism diagnosis and mortality with pulmonary CT angiography versus ventilation-perfusion scintigraphy: evidence of overdiagnosis with CT? AJR Am J Roentgenol. 2012;198(6):1340-1345.
PubMedArticle
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