Background
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease with poor prognosis if left untreated. Although a number of risk factors have been reported, the exact prevalence is controversial and varies between published cohorts. Therefore, the aim of the present study was to investigate the prevalence of risk factors in patients with CTEPH with a special emphasis on thyroid disease.
Methods
Between 01/2014 and 12/2015 patients with confirmed CTEPH scheduled for pulmonary endarterectomy (PEA) at a German expert referral center were included in the present study. Information on risk factors including history of thyroid disease were assessed and patients were reclassified regarding their thyroid function based on laboratory measurements (TSH, fT3, fT4). Additionally, a systematic literature research on studies investigating risk factors of CTEPH was performed to allow a comparison with the present study findings.
Results
Overall, 228 patients (median age, 63 [IQR, 52-72] years; 47.7% female; NYHA class III/IV, 77.5%; mean PA pressure, 43 [34-51] mmHg) were included in the analysis. Interestingly, almost all patients reported a history of venous thromboembolism (VTE, 91.7%); of those 93.8% with pulmonary embolism (PE). The median time from diagnosis of PE to diagnosis of CTEPH was 667 (184-2072, n=193) days. The most common prothrombotic disorder was a diagnosis of antiphospholipid syndrome (n=15, 6.6%).
Overall, 55 patients (24.2%) had a history of thyroid disease. The majority had a history of hypothyroidism (n=43, 18.9%); of those, 93.0% received thyroid hormone replacement (THR) therapy. Reclassification of patients into groups with normal, elevated or decreased TSH revealed a hypothyroid function in 6.1% and a hyperthyroid function in 4.4% of patients; of those, 4.8% of patients had no history of thyroid disease. Overall, more than every 10th patient scheduled for PEA had a thyroid dysfunction (Figure 1).
Patients with a hypothyroid function had higher NT-proBNP plasma concentrations (1878 [1524-3378] vs. 744 [183-2121] pg/ml; p=0.020) and a lower cardiac index (CI; 1.7 [1.7-2.1] vs. 2.3 [1.9-3.0] l/min/m²; p=0.019) compared to patients with a euthyroid function.
Thirteen patients (5.7%) died during a median follow-up time of 486 (338-688) days. Elevated fT4 plasma concentrations above the assay specific cut-off were more frequently observed in patients who died compared to survivors (3 [42.9%] vs. 13 [5.6%]; p=0.010) and were associated with a 9.7-fold increased risk of all-cause mortality (95% CI, 2.1-44.1; p=0.003). In Kaplan-Meier analyses, elevation of fT4 was – in contrast to THR therapy – associated with a reduced probability of survival.
Conclusion
In 228 CTEPH patients undergoing PEA, a history of VTE (91.7%) was the most prevalent risk factor; 86.0% of all patients reported a history of PE. As many as 28.9% of all patients had a thyroid disease or dysfunction. Compared to euthyroid patients, patients with hypothyroid function had more often hemodynamic and functional impairment. fT4 elevation was associated with an increased risk of all-cause mortality after PEA; however, thyroid disease, dysfunction or therapy were not associated with outcomes.