Hemodynamics and risk assessment 2 years after the initiation of upfront ambrisentan‒tadalafil in pulmonary arterial hypertension.

BACKGROUND: Upfront combination therapy with ambrisentan and tadalafil has been reported to improve the condition of patients with pulmonary arterial hypertension (PAH) more than with either drug alone. However, little is known about the long-term associated changes in hemodynamics and risk assessment scores. METHODS: This was a multicenter, retrospective analysis of clinical data in 106 patients with newly diagnosed PAH. Clinical evaluations, including demographics, medical history, World Health Organization (WHO) functional class (FC) and 6-minute walk distance (6MWD), right heart catheterization, and Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk score 2.0, were assessed over 48 months of ambrisentan‒tadalafil therapy. RESULTS: At baseline, 9 patients (9%) showed a low (<7), 48 patients (45%) showed an intermediate (7-8), and 49 patients (46%) showed a high (>8) REVEAL risk score. At a median follow-up of 2 years, 45 patients (43%) showed a low, 47 patients (44%) showed an intermediate, and 14 patients (13%) showed a high REVEAL score, along with improvements in WHO FC, 6MWD and a decrease in mean pulmonary artery pressure and N-terminal pro brain natriuretic peptide (all p < 0.001). Pulmonary vascular resistance (PVR) decreased by 37% from 11.5 ± 6.5 to 7.2 ± 4.1 Wood units (p < 0.001). A total of 61 patients (57%) remained in intermediate-risk or high-risk categories. Low-risk patients had either a decrease in PVR of >50% or a stroke volume within the limits of normal. CONCLUSIONS: Initial combination therapy with ambrisentan and tadalafil in PAH improves the REVEAL risk score in proportion to decreased PVR and preserved stroke volume but still insufficiently so in approximately 50% of the patients.

Performance of a new quantitative computed tomography index for interstitial lung disease assessment in systemic sclerosis.

Quantitative high resolution computed tomography (HRCT) may objectively assess systemic sclerosis (SSc)-interstitial lung disease (ILD) extent, using three basic densitometric measures: mean lung attenuation (MLA), skewness, and kurtosis. This prospective study aimed to develop a composite index - computerized integrated index (CII) - that accounted for MLA, skewness, and kurtosis by means of Principal Component Analysis over HRCTs of 83 consecutive SSc subjects, thus eliminating redundancies. Correlations among CII, cardiopulmonary function and immune-inflammatory biomarkers (e.g. sIL-2Rα and CCL18 serum levels) were explored. ILD was detected in 47% of patients at visual HRCT assessment. These patients had worse CII values than patients without ILD. The CII correlated with lung function at both baseline and follow-up, and with sIL-2Rα and CCL18 serum levels. The best discriminating CII value for ILD was 0.1966 (AUC = 0.77; sensitivity = 0.81 [95%CI:0.68-0.92]; specificity = 0.66 [95%CI:0.52-0.80]). Thirty-four percent of patients without visual trace of ILD had a CII lower than 0.1966, and 67% of them had a diffusing lung capacity for CO <80% of predicted. We showed that this new composite CT index for SSc-ILD assessment correlates with both lung function and immune-inflammatory parameters and could be sufficiently sensitive for capturing early lung density changes in visually ILD-free patients.

Echocardiographic assessment of right ventricular contractile reserve in healthy subjects.

BACKGROUND: Exercise-induced increase in pulmonary artery systolic pressure (PASP) as a possible measure of right ventricular (RV) contractile reserve has been shown to predict survival in severe pulmonary hypertension. However, RV contractile reserve can also be measured by changes in stroke volume (SV), tricuspid annular plane systolic excursion (TAPSE), or tricuspid annular systolic velocity (S'). The limits of normal values and the functional significance of these changes in healthy subjects are not well known. METHODS: In this prospective study, 90 healthy subjects (45 male, mean age 39 ± 13 years) underwent exercise stress echocardiography with measurement of TAPSE, S', TAPSE/PASP, SV, and PASP at rest and peak exercise. Maximum and minimum normal values were reported for all indices. RESULTS: Normal values of exercise-induced changes (Δ) were 4 to 10 mm for TAPSE, 6 to 14 cm/s for S', 12 to 57 mm Hg for PASP, 0 to 96 mL for SV, and -1.2 to 0 mm/mm Hg for TAPSE/PASP. At peak exercise, women showed lower ΔTAPSE/PASP, ΔPASP, ΔS', and ΔSV, but higher TAPSE/PASP than men. Aging was associated with decreased ΔTAPSE/PASP, ΔTAPSE, ΔS', ΔPASP, and ΔSV. In addition, ΔS', ΔTAPSE/PASP, ΔPASP, and ΔSV, but not ΔTAPSE, were directly correlated with maximum workload. CONCLUSIONS: Our results provide age- and sex-related limits of normal for RV contractile reserve as assessed by exercise stress echocardiography and demonstrate that RV systolic function indices (PASP, TAPSE, S', and TAPSE/PASP) correlate with maximum exercise capacity.

Accuracy and precision of echocardiography versus right heart catheterization for the assessment of pulmonary hypertension.

BACKGROUND: Echocardiographic studies have contributed to progress in the understanding of the pathophysiology of the pulmonary circulation and have been shown to be useful for screening for and prognostication of pulmonary hypertension, but are considered unreliable for the diagnosis of pulmonary hypertension. We explored this apparent paradox with rigorous Bland and Altman analysis of the accuracy and the precision of measurements collected in a large patient population. METHODS: A total of 161 patients referred for a suspicion of pulmonary hypertension were prospectively evaluated by a Doppler echocardiography performed by dedicated cardiologists within 1 h of an indicated right heart catheterization. RESULTS: Nine of the patients (6%) were excluded due to an insufficient signal quality. Of the remaining 152 patients, 10 (7%) had no pulmonary hypertension and most others had either pulmonary arterial hypertension (36%) or pulmonary venous hypertension (40%) of variable severities. Mean pulmonary artery pressure, left atrial pressure and cardiac output were nearly identical at echocardiography and catheterization, with no bias and tight confidence intervals, respectively ± 3 mm Hg, ± 5 mm Hg and ± 0.3 L/min. However, the ± 2SD limits of agreement were respectively of + 19 and - 18 mm Hg for mean pulmonary artery pressure, + 8 and - 12 mm Hg for left atrial pressure and + 1.8 and - 1.7 L/min for cardiac output. CONCLUSIONS: Doppler echocardiography allows for accurate measurements of the pulmonary circulation, but with moderate precision, which explains why the procedure is valid for population studies but cannot be used for the individual diagnosis of pulmonary hypertension.