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Background Pulmonary hypertension is a heterogeneous disease, and a significant portion of patients at risk for it have CT imaging available. Advanced automated processing techniques could be leveraged for early detection, screening, and development of quantitative phenotypes. Pruning and vascular tortuosity have been previously described in pulmonary arterial hypertension (PAH), but the extent of these phenomena in arterial vs venous pulmonary vasculature and in exercise pulmonary hypertension (ePH) have not been described. Research Question What are the arterial and venous manifestations of pruning and vascular tortuosity using CT imaging in PAH, and do they also occur in ePH? Study Design and Methods A cohort of patients with PAH and ePH and control subjects with available CT angiograms were retrospectively identified to examine the differential arterial and venous presence of pruning and tortuosity in patients with precapillary pulmonary hypertension not confounded by lung or thromboembolic disease. The pulmonary vasculature was reconstructed, and an artificial intelligence method was used to separate arteries and veins and to compute arterial and venous vascular volumes and tortuosity. Results A total of 42 patients with PAH, 12 patients with ePH, and 37 control subjects were identified. There was relatively lower (median [interquartile range]) arterial small vessel volume in subjects with PAH (PAH 14.7 [11.7-16.5; P < .0001]) vs control subjects (16.9 [15.6-19.2]) and venous small vessel volume in subjects with PAH and ePH (PAH 8.0 [6.5-9.6; P < .0001]; ePH, 7.8 [7.5-11.4; P = .004]) vs control subjects (11.5 [10.6-12.2]). Higher large arterial volume, however, was only observed in the pulmonary arteries (PAH 17.1 [13.6-23.4; P < .0001] vs control subjects 11.4 [8.1-15.4]). Similarly, tortuosity was higher in the pulmonary arteries in the PAH group (PAH 3.5 [3.3-3.6; P = .0002] vs control 3.2 [3.2-3.3]). Interpretation Lower small distal pulmonary vascular volume, higher proximal arterial volume, and higher arterial tortuosity were observed in PAH. These can be quantified by using automated techniques from clinically acquired CT scans of patients with ePH and resting PAH., Graphical Abstract

Although the diagnosis of pulmonary hypertension requires invasive testing, imaging serves an important role in the screening, classification, and monitoring of patients with pulmonary vascular disease (PVD). The development of advanced imaging techniques has led to improvements in the understanding of disease pathophysiology, noninvasive assessment of hemodynamics, and stratification of patient risk. This article discusses the current role of advanced imaging and the emerging novel techniques for visualizing the lung parenchyma, mediastinum, and heart in PVD.

BACKGROUND: Approximately 30–50% of hemodynamically stable patients presenting with acute pulmonary embolism (PE) have evidence of right ventricular (RV) dysfunction. These patients are classified as submassive PE and the role of reperfusion therapy remains unclear. We sought to identify the circumstances under which catheter-directed thrombolysis (CDT) would represent high-value care for submassive PE. METHODS: We used a computer-based, individual-level, state-transition model with one million simulated patients to perform a cost-effectiveness analysis comparing the treatment of submassive PE with CDT followed by anticoagulation to treatment with anticoagulation alone. Because RV function impacts prognosis and is commonly used in PE outcomes research, our model used RV dysfunction to differentiate health states. One-way, two-way, and probabilistic sensitivity analyses were used to quantify model uncertainty. RESULTS: Our base case analysis generated an incremental cost-effectiveness ratio (ICER) of $119,326 per quality adjusted life year (QALY). Sensitivity analyses resulted in ICERs consistent with high-value care when CDT conferred a reduction in the absolute probability of RV dysfunction of 3.5% or more. CDT yielded low-value ICERs if the absolute reduction was less than 1.56%. INTERPRETATION: Our model suggests that catheter-directed thrombolytics represents high-value care compared to anticoagulation alone when CDT offers an absolute improvement in RV dysfunction of 3.5% or more, but there is substantial uncertainly around these results. We estimated the monetary value of clarifying the costs and consequences surrounding RV dysfunction after submassive PE to be approximately $268 million annually, suggesting further research in this area could be highly valuable.

Background Relative enlargement of the pulmonary artery (PA) on chest CT imaging is associated with respiratory exacerbations in patients with COPD or cystic fibrosis. We sought to determine whether similar findings were present in patients with asthma and whether these findings were explained by differences in ventricular size. Methods We measured the PA and aorta diameters in 233 individuals from the Severe Asthma Research Program III cohort. We also estimated right, left, and total epicardial cardiac ventricular volume indices (eERVVI, eELVVI, and eETVVI, respectively). Associations between the cardiac and PA measures (PA-to-aorta [PA/A] ratio, eERVVI-to-eELVVI [eRV/eLV] ratio, eERVVI, eELVVI, eETVVI) and clinical measures of asthma severity were assessed by Pearson correlation, and associations with asthma severity and exacerbation rate were evaluated by multivariable linear and zero-inflated negative binomial regression. Results Asthma severity was associated with smaller ventricular volumes. For example, those with severe asthma had 36.1 mL/m2 smaller eETVVI than healthy control subjects (P = .003) and 14.1 mL/m2 smaller eETVVI than those with mild/moderate disease (P = .011). Smaller ventricular volumes were also associated with a higher rate of asthma exacerbations, both retrospectively and prospectively. For example, those with an eETVVI less than the median had a 57% higher rate of exacerbations during follow-up than those with eETVVI greater than the median (P = .020). Neither PA/A nor eRV/eLV was associated with asthma severity or exacerbations. Conclusions In patients with asthma, smaller cardiac ventricular size may be associated with more severe disease and a higher rate of asthma exacerbations. Trial Registry ClinicalTrials.gov; No.: NCT01761630; URL: www.clinicaltrials.gov

The risk factors and clinical outcomes of quantitative interstitial abnormality progression over time have not been characterized.What are the associations of quantitative interstitial abnormality progression with lung function, exercise capacity, and mortality? What are the demographic and genetic risk factors for quantitative interstitial abnormality progression?Quantitative interstitial abnormality progression between visits 1 and 2 was assessed from 4,635 participants in the Genetic Epidemiology of COPD (COPDGene) cohort and 1,307 participants in the Pittsburgh Lung Screening Study (PLuSS) cohort. We used multivariable linear regression to determine the risk factors for progression and the longitudinal associations between progression and FVC and 6-min walk distance, and Cox regression models for the association with mortality.Age at enrollment, female sex, current smoking status, and the MUC5B minor allele were associated with quantitative interstitial abnormality progression. Each percent annual increase in quantitative interstitial abnormalities was associated with annual declines in FVC (COPDGene: 8.5 mL/y; 95% CI, 4.7-12.4 mL/y; P .001; PLuSS: 9.5 mL/y; 95% CI, 3.7-15.4 mL/y; P = .001) and 6-min walk distance, and increased mortality (COPDGene: hazard ratio, 1.69; 95% CI, 1.34-2.12; P .001; PLuSS: hazard ratio, 1.28; 95% CI, 1.10-1.49; P = .001).The objective, longitudinal measurement of quantitative interstitial abnormalities may help identify people at greatest risk for adverse events and most likely to benefit from early intervention.

Background Right ventricular (RV) dysfunction is associated with shortened life expectancy in heart failure with preserved ejection fraction (HFpEF). The contribution of pulmonary vascular dysfunction to RV dysfunction in HFpEF is not well understood. Methods We investigated rest and exercise invasive pulmonary hemodynamics, ventilation, and gas exchange in 67 patients with HFpEF (of whom 28 had an abnormal pulmonary vascular response during exercise referred to as HFpEF+PVR group and 39 had a normal pulmonary vascular response during exercise referred to as HFpEF group) and in 21 matched control subjects. Results Both groups of patients with HFpEF had a markedly decreased peak oxygen consumption (Vo2), decreased oxygen delivery, and impaired chronotropic response. Single beat analysis of RV pressure waveforms was used to compute the end-systolic elastance (Ees) and pulmonary arterial elastance (Ea). Right ventricular-pulmonary artery (RV-PA) coupling was measured as the ratio of Ees/Ea. Exercise was associated with a preserved Ees response but a decreased Ees/Ea in patients with HFpEF with a normal PVR response, indicating partially preserved RV contractile reserve. In HFpEF+PVR, exercise-induced increase in Ees was markedly reduced, resulting in decreased Ees/Ea and RV-PA uncoupling. Patients with HFpEF+PVR with an exercise-induced decrease in Ees/Ea had lower pulmonary artery compliance, lower peak Vo2, and lower stroke volume than patients with HFpEF. Conclusions We conclude that RV-PA uncoupling is common in HFpEF and is caused by both intrinsic RV contractile impairment and afterload mismatch. Resting and dynamic RV-PA uncoupling in HFpEF is driven by an increase in RV pulsatile rather than resistive afterload. However, with the additive effects of increased RV resistive afterload, RV-PA uncoupling worsens dynamically during exercise.

Background:In acute pulmonary embolism, chest computed tomography angiography derived metrics, such as the right ventricle (RV): left ventricle ratio are routinely used for risk stratification. Paucity of intraparenchymal blood vessels has previously been described, but their association with clinical biomarkers and outcomes has not been studied. We sought to determine if small vascular volumes measured on computed tomography scans were associated with an abnormal RV on echocardiography and mortality. We hypothesized that decreased small venous volume would be associated with greater RV dysfunction and increased mortality.Methods:A retrospective cohort of patients with intermediate risk pulmonary embolism admitted to Brigham and Women’s Hospital between 2009 and 2017 was assembled, and clinical and radiographic data were obtained. We performed 3-dimensional reconstructions of vasculature to assess intraparenchymal vascular volumes. Statistical analyses were performed using multivariable regression and cox proportional hazards models, adjusting for age, sex, lung volume, and small arterial volume.Results:Seven hundred twenty-two subjects were identified of whom 573 had documented echocardiography. A 50% reduction in small venous volume was associated with an increased risk of RV dilation (relative risk: 1.38 [95% CI, 1.18–1.63],PPPP=0.004 and hazard ratio: 1.84 [95% CI, 1.11–3.04],P=0.019, respectively).Conclusions:Loss of small venous volume quantified from computed tomography angiography is associated with increased risk of abnormal RV on echocardiography, abnormal cardiac biomarkers, and higher risk of 30- and 90-day mortality. Small venous volume may be a useful marker for assessing disease severity in acute pulmonary embolism.

Loss of small pulmonary arteries measured as the ratio of blood vessel volume in arteries5 mm

Pulmonary hypertension is characterized histologically by intimal and medial thickening in the small pulmonary arteries, eventually resulting in vascular “pruning.” Computed tomography (CT)-based quantification of pruning is associated with clinical measures of pulmonary hypertension, but it is not established whether CT-based pruning correlates with histologic arterial remodeling. Our sample consisted of 138 patients who underwent resection for early-stage lung adenocarcinoma. From histologic sections, we identified small pulmonary arteries and measured the relative area comprising the intima and media (VWA%), with higher VWA% representing greater histologic remodeling. From pre-operative CTs, we used image analysis algorithms to calculate the small vessel volume fraction (BV5/TBV) as a CT-based indicator of pruning (lower BV5/TBV represents greater pruning). We investigated relationships of CT pruning and histologic remodeling using Pearson correlation, simple linear regression, and multivariable regression with adjustment for age, sex, height, weight, smoking status, and total pack-years. We also tested for effect modification by sex and smoking status. In primary models, more severe CT pruning was associated with greater histologic remodeling. The Pearson correlation coefficient between BV5/TBV and VWA% was –0.41, and in linear regression models, VWA% was 3.13% higher (95% CI: 1.95–4.31%, p

Rationale: Patients with COVID-19 critical illness are at high risk for multiorgan dysfunction, most commonly acute kidney injury (AKI). We sought to characterize the rates of thrombotic and hemorrhagic complications in patients with COVID-19 ARDS as a function of coexisting AKI. Methods: We performed a single-center retrospective analysis of all patients with severe COVID-19 infection, admitted to ICU level of care between 3/1/2020 and 6/1/2020, and we obtained patient data through the Research Patient Data Registry. We excluded patients who did not develop AKI, those who were admitted with a primary medical problem unrelated to coexisting COVID-19 infection, and those with end stage renal disease. We stratified patients into two cohorts: Those with AKI not requiring renal replacement therapy (RRT) and AKI requiring RRT. All data collection was approved by the IRB at Mass General Brigham (IRB #2020P001674). All data was analyzed using Excel and R version 4.0.1 (2020-06-06) when comparing groups-medians and interquartile ranges are reported. Pearson's Chi-squared test was used during statistical analysis. Results: 272 patients were identified, of which 136 patients were excluded from further study due to reasons as above. Of the remaining 136 patients analyzed, all developed AKI as per AKIN criteria, and we identified those who did not require RRT (100), and those who were initiated on RRT (36). Median age was 66 ± 9.75, and 57 ± 7.12, respectively. 38% (38/100) and 27.7% (10/36) were female, respectively. Complications investigated included non-cerebrovascular hemorrhage (17% vs. 38.88%, p 0.014), cerebrovascular hemorrhage (4% vs. 16.66%, p 0.033), thromboembolic phenomena (24% vs 38.8%, p 0.136) and overall ICU Mortality (48% vs 38.8%, p 0.45). Conclusions: Patients with COVID-19 ARDS and associated AKI had a high number of hemorrhagic and thromboembolic complications. There is a higher incidence of hemorrhagic and thromboembolic complications in the AKI-RRT group, with CVA-and non-CVAhemorrhagic complications being statistically significant. Overall ICU mortality was apparently lower in the AKIRRT group, without reaching statistical significance. Our data highlight a clinically most relevant topic, defining COVID-19 patients with AKI as a high-risk population for thromboembolic and hemorrhagic complications, and underlining the importance of careful decisions regarding prophylactic anticoagulant strategies.

Introduction:Acute kidney injury (AKI) is a common complication in critically ill patients and has been extremely common during the 2020 COVID-19 pandemic in patients admitted to the adult intensive care unit with severe viral pneumonia and acute respiratory distress syndrome. We investigated the incidence and outcomes of AKI in this population comparing the COVID-19 pandemic to the H1N1 pandemic of 2009. Methods: We performed a single-center retrospective analysis of all patients with severe COVID-19 infection, admitted to ICU level of care between 3/1/2020 and 6/1/2020 and we obtained patient data via the research patient data registry. We excluded patients who were admitted with a complaint unrelated to their COVID-19 infection and patients with end-stage renal disease. We stratified patients based on presence of AKI and further stratified the AKI group for the need for Renal Replacement Therapy (RRT). All data collection was approved by the IRB at Mass General Brigham (IRB #2020P001674). All data was analyzed using Excel and R version 4.0.1 (2020-06-06). When comparing groups, medians and interquartile ranges are reported. Wilcoxon Rank Sum test was used for statistical analysis. Results: 272 patients were identified of which 31 patients were excluded from further study due to reasons as above. The remaining 241 patients were analyzed, and the median age was 64 (52-72) with, 40.6% females. 79.6% (192) of patients were Intubated with a median lowest PaO2/FiO2 ratio of 124 (91.4-177.5).105/241 (43.5%) did not develop AKI and 136/241 (56.4%) developed AKI, of which 36 had AKI requiring RRT. Patients with AKI had a higher length of hospitalization (20 ± 10.75 vs 15 ± 8.5, p 0.055), Increased pressor days (11 ± 9 vs 4 ± 6.5, P

Purpose: International clinical practice guidelines call for initial volume resuscitation of at least 30 mL/kg body weight for patients with sepsis-induced hypotension or shock. Although not considered in the guidelines, preexisting cardiac dysfunction may be an important factor clinicians weigh in deciding the quantity of volume resuscitation for patients with septic shock. Methods: We conducted a multicenter survey of clinicians who routinely treat patients with sepsis to evaluate their beliefs, behaviors, knowledge, and perceived structural barriers regarding initial volume resuscitation for patients with sepsis and concomitant heart failure with reduced ejection fraction (HFrEF) Results: A total of 317 clinicians at 9 US hospitals completed the survey (response rate 47.3%). Most respondents were specialists in either internal medicine or emergency medicine. Substantial heterogeneity was found regarding sepsis resuscitation preferences for patients with concomitant HFrEF. The belief that patients with septic shock and HFrEF should be exempt from current sepsis bundle initiatives was shared by 39.4% of respondents. A minimum fluid challenge of ∼30 mL/kg or more was deemed appropriate in septic shock by only 56.4% of respondents for patients with concomitant HFrEF, compared to 89.1% of respondents for patients without HFrEF ( P < .01). Emergency medicine physicians were most likely to feel that Conclusions: Clinical equipoise exists regarding initial volume resuscitation for patients with sepsis-induced hypotension or shock and concomitant HFrEF. Future studies and clinical practice guidelines should explicitly address resuscitation in this subpopulation.

Rationale: Cor pulmonale (right ventricular [RV] dilation) and cor pulmonale parvus (RV shrinkage) are both described in chronic obstructive pulmonary disease (COPD). The identification of emphysema as a shared risk factor suggests that additional disease characterization is needed to understand these widely divergent cardiac processes. Objectives: To explore the relationship between computed tomography measures of emphysema and distal pulmonary arterial morphology with RV volume, and their association with exercise capacity and mortality in ever-smokers with COPD enrolled in the COPDGene Study. Methods: Epicardial (myocardium and chamber) RV volume (RV(EV)), distal pulmonary arterial blood vessel volume (arterial BV5: vessels

Recent studies show that pulmonary vascular diseases may specifically affect arteries or veins through different physiologic mechanisms. To detect changes in the two vascular trees, physicians manually analyze the chest computed tomography (CT) image of the patients in search of abnormalities. This process is time consuming, difficult to standardize, and thus not feasible for large clinical studies or useful in real-world clinical decision making. Therefore, automatic separation of arteries and veins in CT images is becoming of great interest, as it may help physicians to accurately diagnose pathological conditions. In this paper, we present a novel, fully automatic approach to classify vessels from chest CT images into arteries and veins. The algorithm follows three main steps: first, a scale-space particles segmentation to isolate vessels; then a 3-D convolutional neural network (CNN) to obtain a first classification of vessels; finally, graph-cuts' optimization to refine the results. To justify the usage of the proposed CNN architecture, we compared different 2-D and 3-D CNNs that may use local information from bronchus- and vessel-enhanced images provided to the network with different strategies. We also compared the proposed CNN approach with a random forests (RFs) classifier. The methodology was trained and evaluated on the superior and inferior lobes of the right lung of 18 clinical cases with noncontrast chest CT scans, in comparison with manual classification. The proposed algorithm achieves an overall accuracy of 94%, which is higher than the accuracy obtained using other CNN architectures and RF. Our method was also validated with contrast-enhanced CT scans of patients with chronic thromboembolic pulmonary hypertension to demonstrate that our model generalizes well to contrast-enhanced modalities. The proposed method outperforms state-of-the-art methods, paving the way for future use of 3-D CNN for artery/vein classification in CT images.

Introduction: PAH is characterized by a loss of pulmonary vascular complexity. In this study, total, arterial, and venous vasculatures of patients with PAH and with ePAH were analyzed using fractal analysis and compared against controls Methods: Data from 1514 consecutive right heart catheterizations from 4/27/2011 to 10/2/2018 representing subjects referred to our dyspnea center were searched for availability of imaging. 388 CT angiography (CTA) scans were identified (used given retrospective availability of thin slice reconstructions). Three initial cohorts (no overlap) were identified from individuals in this set. Control patients had normal resting and exercise hemodynamics and no history of cardiopulmonary disease. The second group met the current definition of PAH (resting mean pulmonary arterial pressure >20mmHg, pulmonary vascular resistance >3 Wood Units, pulmonary capillary wedge pressure Results: Venous fractal dimensions of controls (2.10±0.07) were higher than those of PAH (2.03±0.08; p=3e-6) and of ePAH (2.04±0.13; p=0.008). Total fractal dimension also yielded higher values for controls (2.30±0.05) compared against PAH (2.28±0.07; p=0.009) and ePAH (2.26±0.10; p=0.04). No significant differences were found between arterial fractal dimensions of controls (2.17±0.04) against those of PAH (2.16±0.07; p=0.15) and of ePAH (2.15±0.10; p=0.14). Conclusions: Fractal dimension allows for non-invasive characterization of pulmonary vascular complexity. Using this method, patients with PAH or ePAH were found to have lower total and venous vascular complexities than controls without PAH or ePAH.

Introduction: Increased vascular tortuosity has been proposed as a marker of pulmonary arterial hypertension (PAH). In this analysis, we compared arterial and venous vascular tortuosity between controls and subjects with resting PAH. Furthermore, we examined if abnormalities could be detected in exercise PAH (EPAH), thought to be an early form of PAH. Methods: From an institutional registry, 388 patients with both right heart catheterization and computed tomography angiography (CTA) data were selected. Within this cohort, three distinct groups were identified: 1) controls, who had no cardiopulmonary disease and normal resting and exercise hemodynamics; 2) EPAH, with normal resting hemodynamics but age-adjusted pre-capillary pulmonary hypertension on exertion, and 3) PAH, defined as resting mPAP >20mmHg, pulmonary vascular resistance >3 Wood Units, and pulmonary capillary wedge pressure 10% was defined as the number of arterial segments with tortuosity >10% divided by the same venous measure. Analysis was performed with Wilcoxon rank sum tests in R 3.5. Results: There were 99 patients in the final cohort, including 47 (47.4%) with PAH, 12 (12.1%) with EPAH, and 40 (40.4%) without disease. Compared to controls, median arterial tortuosity was increased in PAH (3.3 ± 0.1% vs. 3.4 ± 0.1%, p=0.0009; Figure 1) but not in EPAH (3.3 ± 0.1%, p=0.82). Median venous tortuosity did not differ between groups. AV>10% was increased in EPAH (vs. controls, 1.86 ± 0.38 vs. 1.56 ± 0.44, p=0.03) and resting PAH (2.0 ± 1.2 p=2e-6). Conclusions: Increased arterial tortuosity on CTA is a biomarker of resting PAH. When corrected for venous tortuosity, arterial tortuosity also appears to be abnormal in EPAH. Figure 1 . Arterial vessels in PAH, EPAH, and control subjects. Red segments have tortuosity > 10%.

Pulmonary hypertension (PH) is a disease in which there is an elevated pressure in the pulmonary vasculature leading to anatomic changes that can be identified on imaging. While right heart catheterization (RHC) is the gold standard for definitive diagnosis, there are many steps prior to catheterization in evaluating a patient with suspected PH. Computed Tomography (CT) is often used as one of the initial imaging modalities in the workup of suspected PH and is usually obtained in all patients with suspected or confirmed PH. In other cases, CT scans done for other purposes can suggest findings of PH that would alert clinicians to an additional possible diagnosis. Patients diagnosed with PH often have very complex hemodynamics as well as medical comorbidities, and referral to a center that specializes in PH is always recommended. There have been newly proposed classifications for the different groups of PH as well as a new definition for the diagnosis of PH. Various findings may require a specific CT to be completed with or without contrast or an electrocardiogram (ECG)-gated CT. This article reviews the current literature and provides a pictorial reference of CT findings associated with PH that can lead to a proposed diagnosis and, possibly, the underlying etiology of PH.

BackgroundCardiorespiratory fitness is not limited by pulmonary mechanical reasons in the majority of adults. However, the degree to which lung function contributes to exercise response patterns among ostensibly healthy individuals remains unclear.MethodsWe examined 2314 Framingham Heart Study participants who underwent cardiopulmonary exercise testing (CPET) and pulmonary function testing. We investigated the association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and diffusing capacity of the lung for carbon monoxide (DLCO) with the primary outcome of peak oxygen uptake (V′O2) along with other CPET parameters using multivariable linear regression. Finally, we investigated the association of total and peripheral pulmonary blood vessel volume with peak V′O2.ResultsWe found lower FEV1, FVC and DLCO were associated with lower peak V′O2. For example, a 1 L lower FEV1 and FVC was associated with a 7.1% (95% CI 5.1–9.1%) and 6.0% (95% CI 4.3–7.7%) lower peak V′O2, respectively. By contrast, FEV1/FVC was not associated with peak V′O2. Lower lung function was associated with lower oxygen uptake efficiency slope, oxygen pulse slope, V′O2 at anaerobic threshold (AT), minute ventilation (V′E) at AT and breathing reserve. In addition, lower total and peripheral pulmonary blood vessel volume were associated with lower peak V′O2.ConclusionsIn a large, community-based cohort of adults, we found lower FEV1, FVC and DLCO were associated with lower exercise capacity, as well as oxygen uptake efficiency slope and ventilatory efficiency. In addition, lower total and peripheral pulmonary blood vessel volume were associated with lower peak V′O2. These findings underscore the importance of lung function and blood vessel volume as contributors to overall exercise capacity.

Imaging continues to be the modality of choice for the diagnosis of venous thromboembolic disease, particularly when incorporated into diagnostic algorithms. Improvement in imaging techniques as well as new imaging modalities and processing methods have improved diagnostic accuracy and additionally are being leveraged in prognostication and decision making for choice of intervention. In this article, we review the role of imaging in diagnosis and prognostication of venous thromboembolism. We also discuss emerging imaging approaches that may in the near future find clinical usefulness in improving diagnosis and prognostication as well as differentiating disease phenotypes.

Background Right ventricular (RV) dysfunction and heart failure with preserved ejection fraction may contribute to exercise intolerance in obesity. To further define RV exercise responses, we investigated RV–arterial coupling in obesity with and without development of exercise pulmonary venous hypertension (ePVH). Methods RV–arterial coupling defined as RV end-systolic elastance/pulmonary artery elastance (Ees/Ea) was calculated from invasive cardiopulmonary exercise test data in 6 controls, 8 obese patients without ePVH (Obese−ePVH) and 8 obese patients with ePVH (Obese+ePVH) within a larger series. ePVH was defined as a resting pulmonary arterial wedge pressure

Rationale and Objectives Imaging-based assessment of cardiovascular structure and function provides clinically relevant information in smokers. Non-cardiac-gated thoracic computed tomographic (CT) scanning is increasingly leveraged for clinical care and lung cancer screening. We sought to determine if more comprehensive measures of ventricular geometry could be obtained from CT using an atlas-based surface model of the heart. Materials and Methods Subcohorts of 24 subjects with cardiac magnetic resonance imaging (MRI) and 262 subjects with echocardiography were identified from COPDGene, a longitudinal observational study of smokers. A surface model of the heart was manually initialized, and then automatically optimized to fit the epicardium for each CT. Estimates of right and left ventricular (RV and LV) volume and free-wall curvature were then calculated and compared to structural and functional metrics obtained from MRI and echocardiograms. Results CT measures of RV dimension and curvature correlated with similar measures obtained using MRI. RV and LV volume obtained from CT inversely correlated with echocardiogram-based estimates of RV systolic pressure using tricuspid regurgitation jet velocity and LV ejection fraction respectively. Patients with evidence of RV or LV dysfunction on echocardiogram had larger RV and LV dimensions on CT. Logistic regression models based on demographics and ventricular measures from CT had an area under the curve of >0.7 for the prediction of elevated right ventricular systolic pressure and ventricular failure. Conclusions These data suggest that non-cardiac-gated, non-contrast-enhanced thoracic CT scanning may provide insight into cardiac structure and function in smokers.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality worldwide [1]. Pulmonary hypertension (PH) has been associated with reduced survival among individuals with COPD [2] and is an independent risk factor for mortality following acute exacerbations of COPD (AECOPD) [3]. Measurement of the pulmonary artery to aorta (PA:A) ratio by computed tomography (CT) and assessment of PA enlargement (PA:A>1) outperforms echocardiography in identifying PH in severe COPD [4], and PA enlargement has been independently associated with risk for total and severe AECOPD in two large prospective COPD cohorts [5]. Studies of population-based [6] and non-COPD [7] cohorts have indicated an association between PA enlargement on CT and mortality. However, these studies did not include adjustment for other factors associated with COPD severity, known risk factors for COPD mortality, and risk factors for atherosclerotic cardiovascular disease (ASCVD), which is a major cause of mortality in COPD. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. LaFon reports grants from NIH, during the conduct of the study. Conflict of interest: Dr. Bhatt reports grants from NIH, during the conduct of the study; other from ProterixBio, personal fees from Sunovion, personal fees from GlaxoSmithKline, outside the submitted work. Conflict of interest: Dr. Labaki has nothing to disclose. Conflict of interest: Dr. Rahaghi has nothing to disclose. Conflict of interest: None Conflict of interest: Dr. Bowler has nothing to disclose. Conflict of interest: Dr. Regan has nothing to disclose. Conflict of interest: Related to the topic of COPD: Dr. Make reports funding from the NHLBI for the COPDGene study; grants and medical advisory boards from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, and Sunovian; personal fees for DSMB from Spiration and Shire/Baxalta; CME personal fees from WebMD, National Jewish Health, American College of Chest Physicians, Projects in Knowledge, Hybrid Communications, SPIRE Learning, Ultimate Medical Academy, Catamount Medical, Eastern Pulmonary Society, Catamount Medical Communications Medscape, Eastern VA Medical Center, Academy Continued Healthcare Learning, and Mt. Sinai Medical Center; royalites from Up-To-Date; medical advisory boards from Novartis, Phillips, Third Pole, Science 24/7, and Vernoa; grants from Pearl; outside the submitted work. Conflict of interest: Dr. Crapo has nothing to disclose. Conflict of interest: Dr. San Jose Estepar reports grants from NIH, during the conduct of the study; grants from NIH, personal fees from Toshiba, personal fees from Boehringer Ingelheim, personal fees from Eolo Medical, outside the submitted work; and he is also a founder and co-owner of Quantitative Imaging Solutions which is a company that provides image based consulting and develops software to enable data sharing. Conflict of interest: Dr. Diaz reports grants from National Institues of Health, from Brigham and Women's Hospital, during the conduct of the study. Conflict of interest: Dr. Silverman reports grants from NIH, during the conduct of the study; grants and other from GlaxoSmithKline, outside the submitted work. Conflict of interest: Dr. Han reports grants from NIH, during the conduct of the study; personal fees from GSK, personal fees from BI, personal fees from Mylan, personal fees from AstraZeneca, other from Novartis, other from Sunovion, outside the submitted work. Conflict of interest: Dr. Hobbs has nothing to disclose. Conflict of interest: Dr. Cho reports grants from NIH, from null, during the conduct of the study; grants from GSK, personal fees from Genentech, outside the submitted work. Conflict of interest: Dr. Washko has nothing to disclose. Conflict of interest: Dr. Dransfield reports grants from NIH, during the conduct of the study; grants from Department of Defense , personal fees and other from Boehringer Ingelheim, personal fees and other from GlaxoSmithKline, other from Novartis, personal fees and other from AstraZeneca, other from Yungjin, personal fees and other from PneumRx/BTG, other from Pulmonx, personal fees from Genentech, other from Boston Scientific , personal fees from Quark Pharmaceuticals, grants from NIH, personal fees from Mereo, grants from American Lung Association, outside the submitted work. Conflict of interest: Dr. Wells reports grants from NIH/NHLBI, during the conduct of the study; grants from NIH/NCATS, grants from Bayer, grants and other from GSK, other from Boehringer Ingelheim, grants and other from Mereo BioPharma, other from Quintiles, other from PRA, outside the submitted work.

Relative enlargement of the pulmonary artery (PA) on chest CT imaging is associated with respiratory exacerbations in patients with COPD or cystic fibrosis. We sought to determine whether similar findings were present in patients with asthma and whether these findings were explained by differences in ventricular size.We measured the PA and aorta diameters in 233 individuals from the Severe Asthma Research Program III cohort. We also estimated right, left, and total epicardial cardiac ventricular volume indices (eERVVI, eELVVI, and eETVVI, respectively). Associations between the cardiac and PA measures (PA-to-aorta [PA/A] ratio, eERVVI-to-eELVVI [eRV/eLV] ratio, eERVVI, eELVVI, eETVVI) and clinical measures of asthma severity were assessed by Pearson correlation, and associations with asthma severity and exacerbation rate were evaluated by multivariable linear and zero-inflated negative binomial regression.Asthma severity was associated with smaller ventricular volumes. For example, those with severe asthma had 36.1 mL/mIn patients with asthma, smaller cardiac ventricular size may be associated with more severe disease and a higher rate of asthma exacerbations.ClinicalTrials.gov; No.: NCT01761630; URL: www.clinicaltrials.gov.

Background Exercise stress testing of the pulmonary circulation may uncover decreased pulmonary vascular (PV) distensibility as a cause of impaired aerobic exercise capacity and right ventricular (RV)-pulmonary arterial (PA) uncoupling. As such, it may help in the differential diagnosis of unexplained dyspnea, including pulmonary hypertension (PH) and/or heart failure with preserved ejection fraction (HFpEF). We investigated rest and exercise invasive pulmonary hemodynamics, ventilation, and gas exchange in patients with unexplained dyspnea, including 44 patients with HFpEF (of whom 20 had a normal pulmonary vascular resistance [PVR] during exercise [ie, passive HFpEF] and 24 had a higher than normal exercise PVR), 22 patients with exercise PH, 19 patients with pulmonary arterial hypertension (PAH), and 24 age- and sex-matched normal control subjects. Methods A PV distensibility coefficient α (%/mm Hg) was determined from multipoint PV pressure-flow plots. RV-PA coupling was quantified from the analysis of RV pressure curves to determine ratios of end-systolic to arterial elastances (Ees/Ea). Aerobic exercise capacity was estimated by peak oxygen consumption. Results The α coefficient decreased from 1.35 ± 0.58%/mm Hg in control subjects and 1.1 ± 0.48%/mm Hg in patients with passive HFpEF to 0.62 ± 0.32%/mm Hg in exercise PH, 0.54 ± 0.27%/mm Hg in HFpEF with high exercise PVR, and 0.18 ± 0.16%/mm Hg in PAH. On multivariate analysis, PV distensibility was associated with decreased Ees/Ea and maximal volume of oxygen consumed. Conclusions PV distensibility is an early and sensitive hemodynamic marker of PV disease that is associated with RV-PA uncoupling and decreased aerobic exercise capacity.

Right ventricular (RV) dysfunction is associated with shortened life expectancy in heart failure with preserved ejection fraction (HFpEF). The contribution of pulmonary vascular dysfunction to RV dysfunction in HFpEF is not well understood.We investigated rest and exercise invasive pulmonary hemodynamics, ventilation, and gas exchange in 67 patients with HFpEF (of whom 28 had an abnormal pulmonary vascular response during exercise referred to as HFpEF+PVR group and 39 had a normal pulmonary vascular response during exercise referred to as HFpEF group) and in 21 matched control subjects.Both groups of patients with HFpEF had a markedly decreased peak oxygen consumption (VoWe conclude that RV-PA uncoupling is common in HFpEF and is caused by both intrinsic RV contractile impairment and afterload mismatch. Resting and dynamic RV-PA uncoupling in HFpEF is driven by an increase in RV pulsatile rather than resistive afterload. However, with the additive effects of increased RV resistive afterload, RV-PA uncoupling worsens dynamically during exercise.

Online_Supplement for Equipoise in Appropriate Initial Volume Resuscitation for Patients in Septic Shock With Heart Failure: Results of a Multicenter Clinician Survey by Gabriel Wardi, Ian Joel, Julian Villar, Michael Lava, Eric Gross, Vaishal Tolia, Raghu R. Seethala, Robert L. Owens, Rebecca E. Sell, Sydney B. Montesi, Farbod N. Rahaghi, Somnath Bose, Ashish Rai, Elizabeth K. Stevenson, Jakob McSparron, Vaishal Tolia and Jeremy R. Beitler in Journal of Intensive Care Medicine

Supplemental Material for Dynamic right ventricular–pulmonary arterial uncoupling during maximum incremental exercise in exercise pulmonary hypertension and pulmonary arterial hypertension by Inderjit Singh, Farbod N. Rahaghi, Robert Naeije, Rudolf K.F. Oliveira, Rebecca R. Vanderpool, Aaron B. Waxman and David M. Systrom in Pulmonary Circulation

Schistosomiasis is a prevalent cause of pulmonary arterial hypertension (PAH) currently classified as Group 1 pulmonary hypertension (PH) [1]. In comparison to other etiologies of PAH such as idiopathic PAH, Schistosomiasis-associated PAH (Sch-PAH) has not been extensively studied. Potential mechanisms of PAH development in schistosomiasis include systemic and localised lung inflammation, involvement of other organs such as the liver and spleen, and direct blockage of precapillary vessels from parasite egg embolisation. Currently, the diagnosis of Sch-PAH relies on hemodynamics assessment using right heart catheterisation. In several etiologies of PH, loss of visualised distal vascular volume has been quantified from pulmonary angiography [2, 3] and computed tomography (CT) of the lungs [4–6]. Additionally, loss of distal vascular volume has been shown to be associated with loss of vascular cross-sectional area histologically [7]. In this pilot study we hypothesised that relative loss of arterial pulmonary vascular volume differentially correlates with hemodynamics in Sch-PAH patients, compared to a group of control subjects. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Funke-Chambour reports grants from roche, grants and personal fees from Boehringer Ingelheim, outside the submitted work;. Dr. Funke-Chambour reports grants from roche, grants and personal fees from Boehringer Ingelheim, outside the submitted work;. Conflict of interest: Dr. Rahaghi reports grants from NHLBI/NIH, during the conduct of the study. Conflict of interest: Dr. Hilton has nothing to disclose. Conflict of interest: Dr. Correa has nothing to disclose. Conflict of interest: Dr. Loureiro has nothing to disclose. Conflict of interest: Dr. Ota-Arakaki has nothing to disclose. Conflict of interest: Dr. Verrastro has nothing to disclose. Conflict of interest: Dr. Lee reports other from NANO X IMAGING LTD (NNOX), outside the submitted work. Conflict of interest: Dr. Mickael has nothing to disclose. Conflict of interest: Dr. Nardelli has nothing to disclose. Conflict of interest: Dr. Systrom has nothing to disclose. Conflict of interest: Dr. Waxman has nothing to disclose. Conflict of interest: Dr. Washko reports grants from NIH, grants and other from Boehringer Ingelheim, other from Quantitative Imaging Solutions, other from PulmonX, grants and other from Janssen Pharmaceuticals, other from GlaxoSmithKline, other from Novartis, other from Vertex, other from CSL Behring, outside the submitted work; and Dr. Washko's spouse works for Biogen . Conflict of interest: Dr. San Jose Estepar reports grants from NIH-NHLBI, during the conduct of the study; personal fees from LeukoLabs, grants and personal fees from Boehringer Ingelheim, personal fees from Chiesi, from null, outside the submitted work; and he is also a founder and co-owner of Quantitative Imaging Solutions which is a company that provides image based consulting and develops software to enable data sharing. Conflict of interest: Dr. Graham reports grants from NIH, during the conduct of the study. Conflict of interest: Dr. Oliveira has nothing to disclose.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have morphologic changes to the pulmonary vasculature. These include pruning of the distal vessels, dilation of the proximal vessels, and increased vascular tortuosity. Advances in image processing and computer vision enable objective detection and quantification of these processes in clinically acquired computed tomographic (CT) scans. Three-dimensional reconstructions of the pulmonary vasculature were created from the CT angiograms of 18 patients with CTEPH diagnosed using imaging and hemodynamics as well as 15 control patients referred to our Dyspnea Clinic and found to have no evidence of pulmonary vascular disease. Compared to controls, CTEPH patients exhibited greater pruning of the distal vasculature (median density of small-vessel volume: 2.7 [interquartile range (IQR): 2.5–3.0] vs. 3.2 [3.0–3.8]; P = 0.008), greater dilation of proximal arteries (median fraction of blood in large arteries: 0.35 [IQR: 0.30–0.41] vs. 0.23 [0.21–0.31]; P = 0.0005), and increased tortuosity in the pulmonary arterial tree (median: 4.92% [IQR: 4.85%–5.21%] vs. 4.63% [4.39%–4.92%]; P = 0.004). CTEPH was not associated with dilation of proximal veins or increased tortuosity in the venous system. Distal pruning of the vasculature was correlated with the cardiac index (R = 0.51, P = 0.04). Quantitative models derived from CT scans can be used to measure changes in vascular morphology previously described subjectively in CTEPH. These measurements are also correlated with invasive metrics of pulmonary hemodynamics, suggesting that they may be used to assess disease severity. Further work in a larger cohort may enable the use of such measures as a biomarker for diagnostic, phenotyping, and prognostic purposes.

Objective Prior work has described the relationship between pulmonary vascular pruning on computed tomography (CT) scans and metrics of right-sided heart dysfunction in smokers. In this analysis, we sought to look at pruning on a lobar level, as well as examine the effect of the arterial and venous circulation on this association. Methods Automated vessel segmentation applied to noncontrast CT scans from the COPDGene Study in 24 subjects with cardiac magnetic resonance imaging scans was used to create a blood volume distribution profile. These vessels were then manually tracked to their origin and characterized as artery or vein. Results Assessment of pruning on a lobar level revealed associations between pruning and right ventricular function previously not observed on a global level. The right ventricular mass index, the right ventricular end-systolic volume index, and pulmonary arterial-to-aorta ratio were associated with both arterial and venous pruning, whereas right ventricular ejection fraction was associated with only arterial pruning. Conclusions Lobar assessment and segmentation of the parenchymal vasculature into arterial and venous components provide additional information about the relationship between loss of vasculature on CT scans and right ventricular dysfunction.

BackgroundExposure to cigarette smoke has been shown to lead to vascular remodelling. Computed tomography (CT) imaging measures of vascular pruning have been associated with pulmonary vascular disease, an important morbidity associated with smoking. In this study we compare CT-based measures of distal vessel loss to histological vascular and parenchymal changes.MethodsA retrospective review of 80 patients who had undergone lung resection identified patients with imaging appropriate for three-dimensional (3D) vascular reconstruction (n=18) and a second group for two-dimensional (2D) analysis (n=19). Measurements of the volume of the small vessels (3D) and the cross-sectional area of the small vessels (2 cross-section) were computed. Histological measures of cross-sectional area of the vasculature and loss of alveoli septa were obtained for all subjects.ResultsThe 2D cross-sectional area of the vasculature on CT imaging was associated with the histological vascular cross-sectional area (r=0.69; p=0.001). The arterial small vessel volume assessed by CT correlated with the histological vascular cross-sectional area (r=0.50; p=0.04), a relationship that persisted even when adjusted for CT-derived measures of emphysema in a regression model.ConclusionsLoss of small vessel volume in CT imaging of smokers is associated with histological loss of vascular cross-sectional area. Imaging-based quantification of pulmonary vasculature provides a noninvasive method to study the multiscale effects of smoking on the pulmonary circulation.

Purpose To determine if interstitial features at chest CT enhance the effect of emphysema on clinical disease severity in smokers without clinical pulmonary fibrosis. Materials and Methods In this retrospective cohort study, an objective CT analysis tool was used to measure interstitial features (reticular changes, honeycombing, centrilobular nodules, linear scar, nodular changes, subpleural lines, and ground-glass opacities) and emphysema in 8266 participants in a study of chronic obstructive pulmonary disease (COPD) called COPDGene (recruited between October 2006 and January 2011). Additive differences in patients with emphysema with interstitial features and in those without interstitial features were analyzed by using t tests, multivariable linear regression, and Kaplan-Meier analysis. Multivariable linear and Cox regression were used to determine if interstitial features modified the effect of continuously measured emphysema on clinical measures of disease severity and mortality. Results Compared with individuals with emphysema alone, those with emphysema and interstitial features had a higher percentage predicted forced expiratory volume in 1 second (absolute difference, 6.4%; P < .001), a lower percentage predicted diffusing capacity of lung for carbon monoxide (DLCO) (absolute difference, 7.4%; P = .034), a 0.019 higher right ventricular-to-left ventricular (RVLV) volume ratio (P = .029), a 43.2-m shorter 6-minute walk distance (6MWD) (P < .001), a 5.9-point higher St George's Respiratory Questionnaire (SGRQ) score (P < .001), and 82% higher mortality (P < .001). In addition, interstitial features modified the effect of emphysema on percentage predicted DLCO, RVLV volume ratio, 6WMD, SGRQ score, and mortality (P for interaction < .05 for all). Conclusion In smokers, the combined presence of interstitial features and emphysema was associated with worse clinical disease severity and higher mortality than was emphysema alone. In addition, interstitial features enhanced the deleterious effects of emphysema on clinical disease severity and mortality.

Loss of the peripheral pulmonary vasculature, termed vascular pruning, is associated with disease severity in patients with chronic obstructive pulmonary disease.To determine if pulmonary vascular pruning is associated with asthma severity and exacerbations.We measured the total pulmonary blood vessel volume (TBV) and the blood vessel volume of vessels less than 5 mmCompared with healthy control subjects, patients with severe asthma had more pulmonary vascular pruning. Among those with asthma, those with poor asthma control had more pruning than those with well-controlled disease. Pruning of the pulmonary vasculature was also associated with lower percent predicted FEVPruning of the peripheral pulmonary vasculature is associated with asthma severity, control, and exacerbations, and with lung function and eosinophilia.