CTA with bilateral pulmonary emboli.

The introduction of CT pulmonary angiography as the first-line test for pulmonary embolism (PE) has brought about a spike in PE diagnoses, but a May 9 article published in the Archives of Internal Medicine has found that more sensitive diagnosis of the disease has not improved mortality for patients, suggesting overdiagnosis from unimportant abnormalities.

First implemented in 1998, CT pulmonary angiography (CTPA) has grown swiftly over the last 13 years, as has the modality’s identification of smaller and incidental emboli. “However, the increased sensitivity of CTPA may have a downside: the detection of emboli that are so small as to be clinically insignificant,” wrote Renda Soylemez Wiener, MD, MPH, from the Pulmonary Center, located at Boston University School of Medicine, and co-authors.

Wiener and colleagues noted that if CTPA were improving the detection and treatment of clinically significant PE, patient data would indicate a growth in PE incidence coupled with falling mortality rates. The drop in mortality would serve as an indicator that more specific diagnoses proved beneficial to patients.

With debate brewing over how radiologists and other physicians should manage incidental findings, the authors sought to examine the effect of growing CTPA usage on PE incidence and mortality. Using the Nationwide Inpatient Sample and Multiple Cause-of-Death databases, Wiener and colleagues compared PE trends between 1993 and 1998 (prior to CTPA usage) and from 1998 to 2003 to determine the relationship between CTPA, diagnosis and outcomes.

The authors found that prior to CTPA, PE incidence grew by a nonsignificant amount (from 59 to 62 cases per 100,000 patients). Following the introduction of CTPA in 1998, however, PE incidence grew from 62 to 112 cases per 100,000 patients.

At the same time, although PE mortality rates fell both before and after the introduction of CTPA, incidence grew under CTPA. Consequently, the accompanying decrease in mortality was markedly smaller than that seen prior to CTPA, a 3 percent drop vs. 8 percent before CTPA.

As mortality from PE remained relatively constant, the percentage of patients with PE who died from any cause decreased substantially after the introduction of CTPA; whereas case fatality decreased by 8 percent prior to CTPA, fatality fell by 36 percent after CTPA.

“Overdiagnosis explains the increased incidence, decreased case fatality and minimal change in mortality we observed,” wrote Wiener and colleagues. The authors argued that an important condition for the increase in PE diagnoses to demonstrate clinical value would be reduced mortality. Otherwise, the data indicate more diagnoses and more treatments for ostensibly unimportant findings.

The authors pointed to the underlying concern of overdiagnosis: increased complications from unnecessary treatments. In fact, Wiener and co-authors observed a 71 percent increase in the rate of complications.

“The concomitant improvement in case fatality is also explained by overdiagnosis. Case fatality (ie, number of deaths/people diagnosed) decreases because the denominator has been inflated with clinically insignificant cases that are only identifiable by highly sensitive tests (corresponding mortality statistic is not distorted, since the denominator includes all people at risk, not just those diagnosed),” Wiener and co-authors wrote.

“Rather than an epidemic of disease, we think the increased incidence of PE reflects an epidemic of diagnostic testing that has created overdiagnosis,” Wiener and colleagues continued.

The authors acknowledged that their reliance on death certificates to estimate PE mortality was flawed, because the records are believed to underestimate deaths from the condition.

Applauding the authors’ findings as well as their admitted limitations, an editorial in AIM cautioned that smaller PE findings might not carry less significance. “There is good evidence that overdiagnosis is a real phenomenon, but it is very likely that a subset of patients with ‘incidental’ PE benefits from therapy,” wrote Victor F. Tapson, MD, from the Center for Pulmonary Vascular Disease at Duke University Medical Center in Durham, N.C.

Tapson added that an important role can be found in the stratification of patients with incidental PE prior to treatment. “It would appear logical that the number of, importance of, and persistence of risk factors present, the amount of residual thrombus, and a patient’s cardiopulmonary reserve might impact on outcome."

“[M]uch of the increased incidence in PE consists of cases that are clinically unimportant, cases that would not have been fatal even if left undiagnosed and untreated,” Wiener and colleagues maintained. “Overdiagnosis of these extra patients matters because treatment of PE can cause real harm.”