Poor Cardiac Output Reserve in Pulmonary Arterial Hypertension is Associated With Right Ventricular Stiffness and Impaired Interventricular Dependence.

BACKGROUND: Pulmonary arterial hypertension is characterized by poor exercise tolerance. The contribution of right ventricular (RV) diastolic function to the augmentation of cardiac output during exercise is not known. This study leverages pressure-volume (p-V) loop analysis to characterize the impact of RV diastology on poor flow augmentation during exercise in PAH. METHODS: RV p-V loops were measured in 41 PAH patients at rest and during supine bike exercise. Patients were stratified by median change in cardiac index during exercise into two groups: high and low CI reserve. Indices of diastolic function (end-diastolic elastance, Eed) and ventricular interdependence (left ventricular transmural pressure, LVTMP) were compared at matched exercise stages. RESULTS: Compared to patients with high CI reserve, those with low reserve exhibited lower exercise stroke volume (36 versus 49 ml·m-2, p=0.0001), with higher associated exercise afterload (Ea 1.76 versus 0.90 mmHg·mL-1, p<0.0001), RV stiffness (Eed 0.68 versus 0.26 mmHg·mL-1, p=0.003), and right-sided pressures (RA 14 versus 8 mmHg, p=0.002). Higher right-sided pressures led to significantly lower LV filling among the low CI reserve subjects (LVTMP -4.6 versus 3.2 mmHg, p=0.0001). Interestingly, low exercise flow reserve correlated significantly with high afterload and RV stiffness, but not with RV contractility nor RV-PA coupling. CONCLUSIONS: Patients with poor exercise CI reserve exhibit poor exercise RV afterload, stiffness, and right-sided filling pressures that depress LV filling and stroke work. High afterload and RV stiffness were the best correlates to low flow reserve in PAH. Exercise unmasked significant pathophysiologic PAH differences unapparent at rest.

Utilizing Deep Learning and Computed Tomography to Determine Pulmonary Nodule Activity in Patients With Nontuberculous Mycobacterial-Lung Disease.

PURPOSE: To develop and evaluate a deep convolutional neural network (DCNN) model for the classification of acute and chronic lung nodules from nontuberculous mycobacterial-lung disease (NTM-LD) on computed tomography (CT). MATERIALS AND METHODS: We collected a data set of 650 nodules (316 acute and 334 chronic) from the CT scans of 110 patients with NTM-LD. The data set was divided into training, validation, and test sets in a ratio of 4:1:1. Bounding boxes were used to crop the 2D CT images down to the area of interest. A DCNN model was built using 11 convolutional layers and trained on these images. The performance of the model was evaluated on the hold-out test set and compared with that of 3 radiologists who independently reviewed the images. RESULTS: The DCNN model achieved an area under the receiver operating characteristic curve of 0.806 for differentiating acute and chronic NTM-LD nodules, corresponding to sensitivity, specificity, and accuracy of 76%, 68%, and 72%, respectively. The performance of the model was comparable to that of the 3 radiologists, who had area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy of 0.693 to 0.771, 61% to 82%, 59% to 73%, and 60% to 73%, respectively. CONCLUSIONS: This study demonstrated the feasibility of using a DCNN model for the classification of the activity of NTM-LD nodules on chest CT. The model performance was comparable to that of radiologists. This approach can potentially and efficiently improve the diagnosis and management of NTM-LD.

Association of clinical and imaging characteristics with pulmonary function testing in patients with Long-COVID.

Purpose: The purpose of this study is to identify clinical and imaging characteristics associated with post-COVID pulmonary function decline. Methods: This study included 22 patients recovering from COVID-19 who underwent serial spirometry pulmonary function testing (PFT) before and after diagnosis. Patients were divided into two cohorts by difference between baseline and post-COVID follow-up PFT: Decline group (>10 % decrease in FEV1), and Stable group (≤10 % decrease or improvement in FEV1). Demographic, clinical, and laboratory data were collected, as well as PFT and chest computed tomography (CT) at the time of COVID diagnosis and follow-up. CTs were semi-quantitatively scored on a five-point severity scale for disease extent in each lobe by two radiologists. Mann-Whitney U-tests, T-tests, and Chi-Squared tests were used for comparison. P-values <0.05 were considered statistically significant. Results: The Decline group had a higher proportion of neutrophils (79.47 ± 4.83 % vs. 65.45 ± 10.22 %; p = 0.003), a higher absolute neutrophil count (5.73 ± 2.68 × 109/L vs. 3.43 ± 1.74 × 109/L; p = 0.031), and a lower proportion of lymphocytes (9.90 ± 4.20 % vs. 21.21 ± 10.97 %; p = 0.018) compared to the Stable group. The Decline group also had significantly higher involvement of ground-glass opacities (GGO) on follow-up chest CT [8.50 (4.50, 14.50) vs. 3.0 (1.50, 9.50); p = 0.032] and significantly higher extent of reticulations on chest CT at time of COVID diagnosis [6.50 (4.00, 9.00) vs. 2.00 (0.00, 6.00); p = 0.039] and follow-up [5.00 (3.00, 13.00) vs. 2.00 (0.00, 5.00); p = 0.041]. ICU admission was higher in the Decline group than in the Stable group (71.4 % vs. 13.3 %; p = 0.014). Conclusions: This study provides novel insight into factors influencing post-COVID lung function, irrespective of pre-existing pulmonary conditions. Our findings underscore the significance of neutrophil counts, reduced lymphocyte counts, pulmonary reticulation on chest CT at diagnosis, and extent of GGOs on follow-up chest CT as potential indicators of decreased post-COVID lung function. This knowledge may guide prediction and further understanding of long-term sequelae of COVID-19 infection.

Low-affinity insulin-like growth factor binding protein 7 and its association with pulmonary arterial hypertension severity and survival.

Insulin-like growth factor (IGF) binding proteins (IGFBPs) are a family of growth factor modifiers, some of which are known to be independently associated with pulmonary arterial hypertension (PAH) survival. IGF factor binding protein 7 (IGFBP7) is a unique low-affinity IGFBP that, independent of IGF, stimulates prostacyclin production. This study proposed to establish associations between IGFBP7 and PAH severity and survival, using enrollment and longitudinal samples. Serum IGFBP7 levels were significantly elevated in patients with PAH compared to controls. After adjusting for age and sex, logarithmic increases in IGFBP7 were associated with a 20 m shorter six-minute walk distance (6MWD; p < 0.001), a 2-3 mmHg higher mean right atrial pressure (p < 0.001 and 0.02), and a higher likelihood of a greater REVEAL 2.0 risk category placement (p < 0.001). Kaplan-Meier analysis demonstrated significantly decreased survival with IGFBP7 above the median and Cox multivariable analysis adjusted for age and sex, demonstrated higher serum IGFBP7 was an independent predictor of survival. Though the exact mechanism is still unknown, given IGFBP7's role as a prostacyclin stimulant, it has potential use as a therapeutic target for disease modulation.