Prognostic value of follow-up vasoreactivity test in pulmonary arterial hypertension.

Acute vasoreactivity test with inhaled nitric oxide (NO) is performed during diagnostic right heart catheterization (RHC) to identify patients with pulmonary arterial hypertension (PAH) who respond to calcium channel blockers. Our purpose was to investigate the prognostic importance of follow-up vasoreactivity test after treatment. We retrospectively analyzed 36 PAH patients (mean age, 47 years; 61 % treatment-naïve), who underwent diagnostic and follow-up RHC and vasoreactivity tests at our center. The primary outcome was all-cause mortality. The median time between baseline and follow-up RHC was 9.7 months. Absolute change in mean pulmonary arterial pressure (ΔmPAP) during NO challenge was less pronounced after treatment, but there was great variability among patients. Overall cohort was dichotomized into two groups: preserved vasoreactivity (ΔmPAP ≤ -1 mmHg) and less vasoreactivity (ΔmPAP ≥0 mmHg) at follow-up RHC. Less vasoreactivity group had higher usage rate of endothelin receptor antagonists and parenteral prostacyclin analogues. During a median observation period of 6.3 years after follow-up RHC, 7 patients died, of which 6 showed less vasoreactivity at follow-up. Absolute ΔmPAP ≥0 at follow-up RHC was associated with all-cause mortality in univariable Cox regression analysis (hazard ratio, 8.728; 95 % confidence interval, 1.045-72.887; p = 0.045), whereas other hemodynamic parameters were not. Absolute ΔmPAP ≥0 at follow-up RHC was associated with all-cause mortality in multivariable Cox analysis adjusted for age and known PAH prognostic factors (HR, 12.814; 95 % CI, 1.088-150.891; p = 0.043). Kaplan-Meier survival analysis revealed a significantly worse survival of less vasoreactivity group compared to preserved vasoreactivity group (log-rank test, p = 0.016). Follow-up vasoreactivity test after treatment could contribute to the detection of high-risk subgroups who might need careful monitoring and referral for lung transplantation.

Ishii S ，Hatano M ，Maki H ，Minatsuki S ，Saito A ，Yagi H ，Shimbo M ，Soma K ，Numata G ，Fujiwara T ，Takeda N ，Komuro I ... -  《-》

Is There Value in Repeating Inhaled Nitric Oxide Vasoreactivity Tests in Patients with Pulmonary Arterial Hypertension?

Tooba R ，Almoushref A ，Tonelli AR 《-》

Prognostic Value of Follow-Up Hemodynamic Variables After Initial Management in Pulmonary Arterial Hypertension.

Hemodynamic variables such as cardiac index and right atrial pressure have consistently been associated with survival in pulmonary arterial hypertension (PAH) at the time of diagnosis. Recent studies have suggested that pulmonary arterial compliance may also predict prognosis in PAH. The prognostic importance of hemodynamic values achieved after treatment initiation is less well established. Our objective was to evaluate the prognostic importance of clinical and hemodynamic variables during follow-up, including pulmonary arterial compliance, after initial management in PAH. We evaluated incident patients with idiopathic, drug- and toxin-induced, or heritable PAH enrolled in the French pulmonary hypertension registry between 2006 and 2016 who had a follow-up right-sided heart catheterization (RHC). The primary outcome was death or lung transplantation. We used stepwise Cox regression and the Kaplan-Meier method to assess variables obtained at baseline and at first follow-up RHC. Of 981 patients, a primary outcome occurred in 331 patients (33.7%) over a median follow-up duration of 2.8 years (interquartile range, 1.1-4.6 years). In a multivariable model considering only baseline variables, no hemodynamic variables independently predicted prognosis. Median time to first follow-up RHC was 4.6 months (interquartile range, 3.7-7.8 months). At first follow-up RHC (n=763), New York Heart Association functional class, 6-minute walk distance, stroke volume index (SVI), and right atrial pressure were independently associated with death or lung transplantation, adjusted for age, sex, and type of PAH. Pulmonary arterial compliance did not independently predict outcomes at baseline or during follow-up. The adjusted hazard ratio for SVI was 1.28 (95% confidence interval, 1.11-1.49; P<0.01) per 10-mL/m2 decrease and for right atrial pressure was 1.05 (95% confidence interval, 1.02-1.09; P<0.01) per 1-mm Hg increase. Among patients who had 2 (n=355) or 3 (n=193) low-risk prognostic features at follow-up, including a cardiac index ≥2.5 L·min-1·m-2, 6-minute walk distance >440 m, and New York Heart Association class I or II functional class, lower SVI was still associated with higher rates of death or lung transplantation (P<0.01). SVI and right atrial pressure were the hemodynamic variables that were independently associated with death or lung transplantation at first follow-up RHC after initial PAH treatment. These findings suggest that the SVI could be a more appropriate treatment target than cardiac index in PAH.

Weatherald J ，Boucly A ，Chemla D ，Savale L ，Peng M ，Jevnikar M ，Jaïs X ，Taniguchi Y ，O'Connell C ，Parent F ，Sattler C ，Hervé P ，Simonneau G ，Montani D ，Humbert M ，Adir Y ，Sitbon O ... -  《-》

Positive Vasoreactivity Testing in Pulmonary Arterial Hypertension: Therapeutic Consequences, Treatment Patterns, and Outcomes in the Modern Management Era.

Gerhardt F ，Fiessler E ，Olsson KM ，Kayser MZ ，Kovacs G ，Gall H ，Ghofrani HA ，Badr Eslam R ，Lang IM ，Benjamin N ，Grünig E ，Halank M ，Lange TJ ，Ulrich S ，Leuchte H ，Held M ，Klose H ，Ewert R ，Wilkens H ，Pizarro C ，Skowasch D ，Wissmüller M ，Hellmich M ，Olschewski H ，Hoeper MM ，Rosenkranz S ... -  《-》

Calcium channel blockers in patients with pulmonary arterial hypertension receiving PAH-specific treatment.

Calcium channel blockers (CCB) are the first effective therapy for vasoreactive patients with idiopathic pulmonary arterial hypertension (IPAH). However, the advent of modern PAH-specific drugs may undermine the role of vasoreactivity tests and CCB treatment. We aimed to clarify the effect of acute vasoreactivity testing and CCB on patients with IPAH receiving PAH-specific treatment. We retrospectively investigated consecutive patients with IPAH (n = 136) diagnosed between 2000 and 2020 and collected data from patients who underwent acute vasoreactivity testing using inhaled nitric oxide (NO). The effects of vasoreactivity testing and CCB therapy were reviewed. Long-term survival was analysed using the Kaplan-Meier method. Acute vasoreactivity testing was performed in 49% of patients with IPAH (n = 67), including 23 patients (34%) receiving PAH-specific therapy without vasoreactivity testing. Eight patients (12%), including three patients (4.4%) receiving PAH-specific therapy, presented acute responses at vasoreactivity testing. They received high-dose CCB therapy (CCB monotherapy for five patients [7.5%] and CCB therapy and PAH-specific therapy for three patients [4.4%]). They presented a significant improvement in clinical parameters and near-normalisation of haemodynamics (mean pulmonary arterial pressure decreased from 46 [interquartile range: 40-49] to 19.5 [interquartile range: 18-23] mmHg [P < .001] at 1-year follow-up). All eight vasoreactive responders receiving CCB therapy showed better long-term survival than non-responders treated with PAH-specific therapy (P < .001). CCB therapy benefited patients with IPAH who showed acute response to vasoreactivity testing using inhaled NO, even when receiving modern PAH-specific therapy. Acute vasoreactive responders may benefit more from CCB than from PAH-specific therapy.

Hirakawa K ，Asano R ，Ueda J ，Aoki T ，Tsuji A ，Ogo T ... -  《-》