Does Systemic Sclerosis-associated Interstitial Lung Disease Burn Out? Specific Phenotypes of Disease Progression.

RATIONALE Previous studies have suggested that interstitial lung disease (ILD) progresses most rapidly early in the course of systemic sclerosis-associated (SSc)-ILD, and that SSc-ILD is often more stable or even "burned out" after the first 4 years following diagnosis. OBJECTIVES Our objectives were to determine whether an apparent plateau in pulmonary function decline is due to survival bias and to identify distinct prognostic phenotypes of ILD progression. METHODS Consecutive patients with SSc-ILD from a single center were included. Pulmonary function measurements were typically performed every 6 months. Study participants were categorized into long-term survivors (>8 yr survival from diagnosis), and those with medium-term and short-term mortality (4-8 and <4 yr survival, respectively). We excluded those censored with less than 8 years of follow-up. Subject-specific slopes for change in forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (Dl) were calculated using generalized linear models with mixed effects. The rate of decline in FVC was compared across prognostic groups. RESULTS The cohort included 171 study participants with SSc-ILD. A plateau in the progression of FVC was apparent in the full cohort analysis but disappeared with stratification into prognostic subgroups to account for survival bias. Those with short-term mortality had a higher annual rate of decline in FVC (-4.10 [95% confidence interval (CI), -7.92 to -0.28] vs. -2.14 [95% CI, -3.31 to -0.97] and -0.94 [-1.46 to -0.42]; P = 0.003) and Dl (-5.28 [95% CI, -9.58 to -0.99] vs. -3.13 [95% CI, -4.35 to -1.92] and -1.32 [95% CI, -2.01 to -0.63]; P < 0.001) than those with medium-term mortality and long-term survival with adjustment for age, sex, and pack-years. Change in FVC in the previous year did not predict FVC change in the subsequent year. CONCLUSIONS Adults with SSc-ILD have distinct patterns of physiological progression that remain relatively consistent during long-term follow-up; however, recent change in FVC cannot be used to predict future change in FVC within shorter follow-up intervals. The findings of this study provide important information on the course of disease in SSc-ILD and identify specific phenotypes of progression that may improve clinical decision-making and design of future therapeutic trials

Impact of sublingual nitroglycerin dosage on FFRCT assessment and coronary luminal volume-to-myocardial mass ratio.

OBJECTIVES: Fractional flow reserve computed tomography (FFRCT) depends upon nitroglycerin (NTG) inducing maximal hyperemia. However, the impact of NTG dosages on FFRCT analysis including coronary volume-to-mass ratio (V/M) is unknown. METHODS: Eighty patients with repeat coronary CT angiograms (CCTAs) with different sublingual spray NTG doses (0.4 mg and 0.8 mg) were retrospectively analyzed with 45 patients excluded. Patient and scan demographics, post-stenosis and nadir FFRCT values, coronary volume, and coronary volume-to-mass ratio (V/M) were compared at initial CCTA (0.4 mg NTG) and follow-up CCTA (0.8 mg NTG). Differences were compared by Wilcoxon signed-rank test. RESULTS: Thirty-five patients were included (time between CCTAs, 3.9 ± 1.6 years). Segment involvement score was 2.4 ± 3.3 and 2.8 ± 3.4 at initial and repeat CCTA (0.4 and 0.8 mg NTG), respectively (p = 0.004). There was similar image quality (4.1 ± 0.7 vs 4.1 ± 0.8; p = 0.51). Nadir FFRCT values did not differ in the left (0.4 mg, 0.80 ± 0.08 vs 0.8 mg, 0.80 ± 0.03; p = 0.66), right (0.4 mg, 0.90 ± 0.04 vs 0.8 mg, 0.90 ± 0.06; p = 0.25), or circumflex coronaries (0.4 mg, 0.87 ± 0.06 vs 0.8 mg, 0.88 ± 0.06; p = 0.34). Post-stenosis FFRCT values did not differ (p = 0.65). Coronary volume increased with 0.8 mg of NTG (2639 ± 753 mm3 vs 2844.8 ± 827 mm3; p = 0.009) but V/M ratio did not (p = 0.20). CONCLUSIONS: Use of 0.8 mg versus 0.4 mg of NTG in routine clinical CCTAs significantly increased coronary volume determined from FFRCT analysis but did not alter FFRCT or V/M. Further evaluation of repeat CCTAs in a more contemporaneous fashion using varied nitrate doses and disease severity is needed. KEY POINTS: • Fractional flow reserve from computed tomography (FFRCT) is a noninvasive method for evaluating the coronary arteries and relies on nitroglycerin (NTG) to induce coronary vasodilation, but the impact of different NTG dosages is unknown. • Retrospective analysis evaluated use of different NTG doses on FFRCT. • Increased NTG dose increased coronary luminal volume on FFRCTanalysis, but did not change FFRCTvalues

Effect of a calcium deblooming algorithm on accuracy of coronary computed tomography angiography.

BACKGROUND: Coronary artery calcification is a significant contributor to reduced accuracy of coronary computed tomographic angiography (CTA) in the assessment of coronary artery disease severity. The aim of the current study is to assess the impact of a prototype calcium deblooming algorithm on the diagnostic accuracy of CTA. METHODS: 40 patients referred for invasive catheter angiography underwent CTA and invasive catheter angiography. The CTA were reconstructed using a standard soft tissue kernel (CTASTAND) and a deblooming algorithm (CTADEBLOOM). CTA studies were read with and without the deblooming algorithm blinded to the invasive coronary angiogram findings. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value for the detection of stenosis ≥50% or ≥70% were evaluated using quantitative coronary angiography as the reference standard. Image quality was assessed using a 5-point scale, and the presence of image artifact recorded. RESULTS: All studies were diagnostic with 548 segments available for evaluation. Image score was 3.64 ± 0.72 with CTADEBLOOM, versus 3.56 ± 0.72 with CTASTAND (p = 0.38). CTADEBLOOM had significantly less calcium blooming artifact than CTASTAND (12.5% vs. 47.5%, p = 0.001). Based on a 50% stenosis threshold for defining significant disease, the Sensitivity/Specificity/PPV/NPV/Accuracy were 65.9/84.9/27.6/96.6/83.4 for CTADEBLOOM and 75.0/81.9/26.6/97.4/81.4 for CTASTAND using a ≥50% threshold. CTADEBLOOM specificity was significantly higher than CTASTAND (84.9% vs. 81.5%, p = 0.03), with no difference between the algorithms in sensitivity (p = 0.22), or accuracy (p = 0.15). These results remained unchanged when a stenosis threshold of ≥70% was used. Interobserver agreement was fair with both techniques (CTADEBLOOM k = 0.38, CTASTAND k = 0.37). CONCLUSION: In this proof of concept study, coronary calcification deblooming using a prototype post-processing algorithm is feasible and reduces calcium blooming with an improvement of the specificity of the CTA exam

Hypertrophic Cardiomyopathy (HCM): New insights into Coronary artery remodelling and ischemia from FFRCT.

INTRODUCTION: Angina, myocardial ischemia, and coronary artery physiology in hypertrophic cardiomyopathy (HCM) are poorly understood. However, coronary computed tomography angiography (CCTA) with fractional flow reserve from CT (FFRCT) analysis offers a non-invasive method for evaluation of coronary artery volume to myocardial mass ratio (V/M) that may provide insight into such mechanisms. Thus, we sought to investigate changes in V/M in HCM. METHODS: A retrospective analysis was performed on 37 HCM patients and 37 controls matched for age, sex, and cardiovascular risk factors; CCTA-derived coronary artery lumen volume (V) and myocardial mass (M) were used to determine V/M. FFRCT values were calculated for the left anterior descending (LAD), left circumflex (LCx) and right coronary (RCA) arteries as well as the 3-vessel cumulative FFRCT values. RESULTS: HCM patients had significantly increased myocardial mass (176 ± 84 vs. 119 ± 27 g, p < 0.0001) and total coronary artery luminal volume (4112 ± 1139 vs. 3290 ± 924 mm3, p < 0.0001) that resulted from increases in segmented luminal volumes of both the left and right coronary artery systems. However, HCM patients had significantly decreased V/M (23.8 ± 5.9 vs. 26.5 ± 5.3 mm3/g; p = 0.026) which was further decreased when restricting V/M analysis to those HCM patients with septal hypertrophy (22.4 mm3/g, p = 0.01) that was mild-moderately predictive of HCM (AUC = 0.68). HCM patients also showed significantly lower nadir FFRCT values in the LCx (0.87 ± 0.06 vs. 0.91 ± 0.06, p = 0.02), and cumulative 3-vessel FFRCT values (2.58 ± 0.18 vs. 2.63 ± 0.14, p = 0.006). CONCLUSIONS: HCM patients demonstrate significantly greater coronary volume. Despite this, HCM patients suffer from decreased V/M. Further prospective studies evaluating the relationship between V/M, angina, and heart failure in HCM are needed

Pathological Comparisons of Paraseptal and Centrilobular Emphysema in Chronic Obstructive Pulmonary Disease

Rationale: Although centrilobular emphysema (CLE) and paraseptal emphysema (PSE) are commonly identified on multidetector computed tomography (MDCT), little is known about the pathology associated with PSE compared with that of CLE.Objectives: To assess the pathological differences between PSE and CLE in chronic obstructive pulmonary disease (COPD).Methods: Air-inflated frozen lung specimens (n = 6) obtained from patients with severe COPD treated by lung transplantation were scanned with MDCT. Frozen tissue cores were taken from central (n = 8) and peripheral (n = 8) regions of each lung, scanned with micro-computed tomography (microCT), and processed for histology. The core locations were registered to the MDCT, and a percentage of PSE or CLE was assigned by radiologists to each of the regions. MicroCT scans were used to measure number and structural change of terminal bronchioles. Furthermore, microCT-based volume fractions of CLE and PSE allowed classifying cores into mild emphysema, CLE-dominant, and PSE-dominant.Measurements and Main Results: The percentages of PSE measured on MDCT and microCT were positively associated (P = 0.015). The number of terminal bronchioles per milliliter of lung and cross-sectional lumen area were significantly lower and wall area percentage was significantly higher in CLE-dominant regions compared with mild emphysema and PSE-dominant regions (all P  0.5). Immunohistochemistry showed significantly higher infiltration of neutrophils (P = 0.002), but not of macrophages, CD4, CD8, or B cells, in PSE compared with CLE regions.Conclusions: The terminal bronchioles are relatively preserved, whereas neutrophilic inflammation is increased in PSE-dominant regions compared with CLE-dominant regions in patients with COPD.status: publishe