Capillary pCO2 helps distinguishing idiopathic pulmonary arterial hypertension from pulmonary hypertension due to heart failure with preserved ejection fraction

Rationale: The demographics of patients with idiopathic pulmonary arterial hypertension (IPAH) are changing and this diagnosis is increasingly being made in older patients. However, diagnostic misclassifications are common as it may be difficult to differentiate between IPAH and pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF). We investigated the hypothesis that the capillary pCO(2) (p(c)CO(2)) may help distinguishing between idiopathic pulmonary arterial hypertension (IPAH) and pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF). Methods: In a cross-sectional study, we retrospectively assessed p(c)CO(2) levels (obtained from arterialized capillary blood at the time of diagnosis) from patients with IPAH or PH-HFpEF, respectively. Receiver operated characteristics (ROC) were used to determine the p(c)CO(2) level providing the best discrimination between these two conditions. PcCO2 values were considered helpful if they were associated with a negative predictive value >0.9 to excluded either IPAH or PH-HFpEF. Results: The study enrolled 185 patients, 99 with IPAH (74% female; age 47 +/- 17 years; body mass index 26 +/- 5 kg/m(2), PAPm 53 +/- 12 mmHg, PAWP 8 +/- 3 mmHg), and 86 with PH-HFpEF (64% female; age 69 +/- 10 years; body mass index 30 +/- 6 kg/m(2), PAPm 47 +/- 10 mmHg, PAWP 21 +/- 5 mmHg). PcCO2 at time of diagnosis was 33 +/- 4 mmHg in the IPAH group and 40 +/- 5 mmHg in the PH-HFpEF group (p < 0.001), respectively. According to ROC analysis, a p(c)CO(2) of 36 mmHg was the best discriminator between both entities with an area under curve of 0.87 (p < 0.001). The likelihood of PH-HFpEF was <10% in patients with a PcCO2 < 34 mmHg, whereas the likelihood of IPAH was <10% in patients with a PcCO2 > 41 mmHg. Conclusions: PcCO2 levels were significantly lower in IPAH compared to PH-HFpEF and may provide useful information in differentiating between both conditions.