MADRID – The use of a two-step algorithm significantly increased the rate at which pulmonary arterial hypertension was diagnosed in patients with systemic sclerosis in a prospective, observational, cross-sectional study.
The results of the DETECT study, presented at the annual European Congress of Rheumatology, showed that the two-step algorithm had a sensitivity of 96% for correctly identifying the condition, which was higher than the 71% sensitivity obtained using methods recommended currently by the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. The ESC/ERS recommendations are mainly based on consensus rather than robust evidence, and focus on the use of transthoracic echocardiography.
"DETECT is unique because it shows that if you just do an echocardiogram that you miss 29% of people who subsequently have pulmonary arterial hypertension [PAH], whereas if you apply the DETECT algorithm you miss only 4% of the people," Dr. Dinesh Khanna, director of the scleroderma program at the University of Michigan, Ann Arbor, said in an interview.
Dr. Khanna, who was a coinvestigator in the study, added: "PAH is a leading cause of mortality; it has high prevalence [and] it has a median survival of 2 to 3 years. ... You don’t want to miss these patients." Dr. Khanna presented recommendations for annual screening of PAH in systemic sclerosis patients at another session at the meeting.
Although 4% of patients are still being missed, this is a dramatic improvement over current clinical practice, said DETECT investigator Dr. Christopher Denton, who presented the findings of the international, multicenter trial. The study was also recently published online (Ann. Rheum. Dis. 2013 May 18 [doi: 10.1136/annrheumdis-2013-203301]).
Dr. Christopher P. Denton
"There is a general feeling that patients need to be screened so that diagnoses can be made and licensed therapies can be initiated," said Dr. Denton of the Royal Free Hospital in London. "The goal of the study was to rationalize a large number of potential variables into a small number that could be developed into a risk score," he added, and "ultimately to ensure that the most appropriate patients are referred for diagnostic right heart catheter studies." Right heart catheterization (RHC) remains the only method for confirming a diagnosis of PAH.
A total of 646 adult patients with established scleroderma (greater than 3 years) and reduced diffusing capacity of the lung for carbon monoxide (DLCO less than 60% of predicted) were screened and 466 enrolled in the study. All of them underwent RHC, and 145 (31%) were found to have PAH. This was defined as a mean pulmonary arterial pressure of 25 mm Hg or higher.
Of the 145 patients with PAH, 87 met World Health Organization (WHO) group 1 criteria for mild PAH, and this was the group of interest, as a diagnosis of PAH "had been robustly excluded" by normal methods, Dr. Denton said. This group of patients was compared with the group that did not have PAH (n = 321).
Patients with WHO group 1 PAH were slightly older than patients who did not have PAH (mean ages, 61 and 56 years). The PAH patients also tended to have a longer disease duration (163 vs. 130 months) and had slightly lower DLCO (43% vs. 48% of predicted).
The DETECT investigators examined 112 variables, including demographic and clinical parameters, serum tests, and electro- and echocardiogram results, that they thought might be able to help differentiate patients with PAH from those without it. After expert analysis and various types of statistical modeling, they ended up with eight items that were used to develop the two-step algorithm.
Step 1 of the algorithm involves testing for lung function, expressed as a ratio of the percentage predicted forced vital capacity and DLCO; the presence of current or past telangiectasia; serum anticentromere antibody positivity; serum levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP); serum urate levels; and right axis deviation on an electrocardiogram. Step 2 involves measurement of two echocardiographic parameters: right atrium area and tricuspid regurgitation velocity.
"The aim is to make this a computer-based system," Dr. Denton explained. A trial electronic version of the tool is being tested, which involves the aforementioned clinical variables being entered first to determine if an echocardiogram is warranted, and then determining if the results of the echocardiogram warrant further referral for RHC.
The rates of referral for RHC were higher if the two-step algorithm was used, compared with the use of ESC/ERS guideline-recommended methods (62% and 40%). The specificity of the algorithm was 48%, with positive and negative predictive values of 35% and 98%, respectively. The values for guideline-recommended methods were 69%, 40%, and 89%.