Penalized Model-Based Unsupervised Phenomapping Unravels Distinctive HFrEF Phenotypes With Improved Outcomes Discrimination From Sacubitril/Valsartan Treatment Independent of MAGGIC Score.

Background The angiotensin receptor-neprilysin inhibitor (LCZ696) has emerged as a promising pharmacological intervention against renin-angiotensin system inhibitor in reduced ejection fraction heart failure (HFrEF). Whether the therapeutic benefits may vary among heterogeneous HFrEF subgroups remains unknown. Methods and Results This study comprised a pooled 2-center analysis including 1103 patients with symptomatic HFrEF with LCZ696 use and another 1103 independent HFrEF control cohort (with renin-angiotensin system inhibitor use) matched for age, sex, left ventricular ejection fraction, and comorbidity conditions. Three main distinct phenogroup clusterings were identified from unsupervised machine learning using 29 clinical variables: phenogroup 1 (youngest, relatively lower diabetes prevalence, highest glomerular filtration rate with largest left ventricular size and left ventricular wall stress); phenogroup 2 (oldest, lean, highest diabetes and vascular diseases prevalence, lowest highest glomerular filtration rate with smallest left ventricular size and mass), and phenogroup 3 (lowest clinical comorbidity with largest left ventricular mass and highest hypertrophy prevalence). During the median 1.74-year follow-up, phenogroup assignment provided improved prognostic discrimination beyond Meta-Analysis Global Group in Chronic Heart Failure risk score risk score (all net reclassification index P<0.05) with overall good calibrations. While phenogroup 1 showed overall best clinical outcomes, phenogroup 2 demonstrated highest cardiovascular death and worst renal end point, with phenogroup 3 having the highest all-cause death rate and HF hospitalization among groups, respectively. These findings were broadly consistent when compared with the renin-angiotensin system inhibitor control as reference group. Conclusions Phenomapping provided novel insights on unique characteristics and cardiac features among patients with HFrEF with sacubitril/valsartan treatment. These findings further showed potentiality in identifying potential sacubitril/valsartan responders and nonresponders with improved outcome discrimination among patients with HFrEF beyond clinical scoring.

QRS Fragmentation in Preserved Ejection Fraction Heart Failure: Functional Insights, Pathological Correlates, and Prognosis.

Background Fragmented QRS (fQRS) morphology as a surrogate marker of the possible presence of myocardial scarring has been shown to confer a higher risk in patients with reduced ejection fraction heart failure. We aimed to investigate the pathophysiological correlates and prognostic implications of fQRS in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results We consecutively studied 960 patients with HFpEF (76.4±12.7 years, men: 37.2%). fQRS was assessed using a body surface ECG during hospitalization. QRS morphology was available and classified into 3 categories among 960 subjects with HFpEF as non-fQRS, inferior fQRS, and anterior/lateral fQRS groups. Despite comparable clinical features in most baseline demographics among the 3 fQRS categories, anterior/lateral fQRS showed significantly higher B-type natriuretic peptide/troponin levels (both P<0.001), with both the inferior and anterior/lateral fQRS HFpEF groups demonstrating a higher degree of unfavorable cardiac remodeling, greater extent of myocardial perfusion defect, and slower coronary flow phenomenon (all P<0.05). Patients with anterior/lateral fQRS HFpEF exhibited significantly altered cardiac structure/function and more impaired diastolic indices (all P<0.05). During a median of 657 days follow-up, the presence of anterior/lateral fQRS conferred a doubled HF re-admission risk (adjusted hazard ratio 1.90, P<0.001), with both inferior and anterior/lateral fQRS having a higher risk of cardiovascular and all-cause death (all P<0.05) by using Cox regression models. Conclusions The presence of fQRS in HFpEF was associated with more extensive myocardial perfusion defects and worsened mechanics, which possibly denotes a more severe involvement of cardiac damage. Early recognition in such patients with HFpEF likely benefits from targeted therapeutic interventions.

Impact of Perineural Invasion and Preexisting Type 2 Diabetes on Patients with Esophageal Squamous Cell Carcinoma Receiving Neoadjuvant Chemoradiotherapy.

Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the cornerstone treatment strategy in locally advanced esophageal squamous cell carcinoma (ESCC). Despite this high- intensity multimodality therapy, most patients still experience recurrences and metastases, especially those who do not achieve a pathological complete response (pCR) after neoCRT. Here, we focused on identifying poor prognostic factors. In this retrospective cohort study; we enrolled 140 patients who completed neoCRT plus surgery treatment sequence with no interval metastasis. Overall, 45 of 140 patients (32.1%) achieved a pCR. The overall survival, disease-free survival (DFS), and metastasis-free survival was significantly better in patients with a pCR than in patients with a non-pCR. In the non-pCR subgroup, the presence of perineural invasion (PNI) and preexisting type 2 diabetes (T2DM) were two factors adversely affecting DFS. After adjusting for other factors, multivariate analysis showed that the hazard ratio (HR) was 2.354 (95% confidence interval [CI] 1.240-4.467, p = 0.009) for the presence of PNI and 2.368 (95% CI 1.351-4.150, p = 0.003) for preexisting T2DM. Patients with a combination of both factors had the worst survival. In conclusion, PNI and preexisting T2DM may adversely affect the prognosis of patients with ESCC receiving neoadjuvant chemoradiotherapy.

Both epicardial and peri-aortic adipose tissue blunt heart rate recovery beyond body fat mass.

Background: Epicardial adipose tissue (EAT) as a marker of metabolic disorders has been shown to be closely associated with a variety of unfavorable cardiovascular events and cardiac arrhythmias. Data on regional-specific visceral adiposity outside the heart and its modulation on autonomic dysfunction, particularly heart rate recovery after exercise, remain obscure. Methods: We studied 156 consecutive subjects (mean age: 49.3 ± 8.0 years) who underwent annual health surveys and completed treadmill tests. Multi-detector computed tomography-based visceral adiposity, including EAT and peri-aortic fat (PAF) tissue, was quantified using dedicated software (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). We further correlated EAT and PAF with blood pressure and heart rate (HR) recovery information from an exercise treadmill test. Metabolic abnormalities were scored by anthropometrics in combination with biochemical data. Results: Increased EAT and PAF were both associated with a smaller reduction in systolic blood pressure during the hyperventilation stage before exercise compared to supine status (ß-coefficient (coef.): -0.19 and -0.23, respectively, both p < 0.05). Both visceral adipose tissue mediated an inverted relationship with heart rate recovery at 3 (EAT: ß-coef.: -0.3; PAF: ß-coef.: -0.36) and 6 min (EAT: ß-coef.: -0.32; PAF: ß-coef.: -0.34) after peak exercise, even after adjusting for baseline clinical variables and body fat composition (all p < 0.05). Conclusion: Excessive visceral adiposity, whether proximal or distal to the heart, may modulate the autonomic response by lowering the rate of HR recovery from exercise after accounting for clinical metabolic index. Cardiac autonomic dysfunction may partly explain the increase in cardiovascular morbidity and mortality related to both visceral fats.

The association of pericardial fat and peri-aortic fat with severity of nonalcoholic fatty liver disease.

Visceral adipose tissue (VAT) is associated with central obesity, insulin resistance and metabolic syndrome. However, the association of body-site specific adiposity and non-alcoholic fatty liver disease (NAFLD) has not been well characterized. We studies 704 consecutive subjects who underwent annual health survey in Taiwan. All subjects have been divided into three groups including normal (341), mild (227) and moderate and severe (136) NAFLD according to ultrasound finding. Pericardial (PCF) and thoracic peri-aortic adipose tissue (TAT) burden was assessed using a non-contrast 16-slice multi-detector computed tomography (MDCT) dataset with off-line measurement (Aquarius 3DWorkstation, TeraRecon, SanMateo, CA, USA). We explored the relationship between PCF/TAT, NAFLD and cardiometabolic risk profiles. Patients with moderate and mild NAFLD have greater volume of PCF (100.7 ± 26.3vs. 77.1 ± 21.3 vs. 61.7 ± 21.6 ml, P < 0.001) and TAT (11.2 ± 4.1 vs. 7.6 ± 2.6 vs. 5.5 ± 2.6 ml, P < 0.001) when compared to the normal groups. Both PCF and TAT remained independently associated with NAFLD after counting for age, sex, triglyceride, cholesterol and other cardiometabolic risk factors. In addition, both PCF and TAT provided incremental prediction value for NAFLD diagnosis. (AUROC: 0.85 and 0.87, 95%, confidence interval: 0.82-0.89 and 0.84-0.90). Both visceral adipose tissues strongly correlated with the severity of NAFLD. Compared to PCF, TAT is more tightly associated with NAFLD diagnosis in a large Asian population.

Association of Female Menopause With Atrioventricular Mechanics and Outcomes.

Background: Despite known sex differences in cardiac structure and function, little is known about how menopause and estrogen associate with atrioventricular mechanics and outcomes. Objective: To study how, sex differences, loss of estrogen in menopause and duration of menopause, relate to atrioventricular mechanics and outcomes. Methods: Among 4051 asymptomatic adults (49.8 ± 10.8 years, 35%women), left ventricular (LV) and left atrial (LA) mechanics were assessed using speckle-tracking. Results: Post-menopausal (vs. pre-menopausal) women had similar LV ejection fraction but reduced GLS, reduced PALS, increased LA stiffness, higher LV sphericity and LV torsion (all p < 0.001). Multivariable analysis showed menopause to be associated with greater LV sphericity (0.02, 95%CI 0.01, 0.03), higher indexed LV mass (LVMi), lower mitral e', lower LV GLS (0.37, 95%CI 0.04-0.70), higher LV torsion, larger LA volume, worse PALS (∼2.4-fold) and greater LA stiffness (0.028, 95%CI 0.01-0.05). Increasing years of menopause was associated with further reduction in GLS, markedly worse LA mechanics despite greater LV sphericity and higher torsion. Lower estradiol levels correlated with more impaired LV diastolic function, impaired LV GLS, greater LA stiffness, and increased LV sphericity and LV torsion (all p < 0.05). Approximately 5.5% (37/669) of post-menopausal women incident HF over 2.9 years of follow-up. Greater LV sphericity [adjusted hazard ratio (aHR) 1.04, 95%CI 1.00-1.07], impaired GLS (aHR 0.87, 95%CI 0.78-0.97), reduced peak left atrial longitudinal strain (PALS, aHR 0.94, 95%CI 0.90-0.99) and higher LA stiffness (aHR 10.5, 95%CI 1.69-64.6) were independently associated with the primary outcome of HF hospitalizations in post-menopause. Both PALS < 23% (aHR:1.32, 95%CI 1.01-3.49) and GLS < 16% (aHR:5.80, 95%CI 1.79-18.8) remained prognostic for the incidence of HF in post-menopausal women in dichotomous analyses, even after adjusting for confounders. Results were consistent with composite outcomes of HF hospitalizations and 1-year all-cause mortality as well. Conclusion: Menopause was associated with greater LV/LA remodeling and reduced LV longitudinal and LA function in women. The cardiac functional deficit with menopause and lower estradiol levels, along with their independent prognostic value post-menopause, may elucidate sex differences in heart failure further.

Insights on Distinct Left Atrial Remodeling Between Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) commonly coexist with overlapping pathophysiology like left atrial (LA) remodeling, which might differ given different underlying mechanisms. Objectives: We sought to investigate the different patterns of LA wall remodeling in AF vs. HFpEF. Methods: We compared LA wall characteristics including wall volume (LAWV), wall thickness (LAWT), and wall thickness heterogeneity (LAWT[SD]) and LA structure, function among the controls (without AF or HFpEF, n = 115), HFpEF alone (n = 59), AF alone (n = 37), and HFpEF+AF (n = 38) groups using multi-detector computed tomography and echocardiography. Results: LA wall remodeling was most predominant and peak atrial longitudinal strain (PALS) was worst in HFpEF+AF patients as compared to the rest. Despite lower E/e' (9.8 ± 3.8 vs. 13.4 ± 6.4) yet comparable LA volume, LAWT and PALS in AF alone vs. HFpEF alone, LAWV [12.6 (11.6-15.3) vs. 12.0 (10.2-13.7); p = 0.01] and LAWT(SD) [0.68 (0.61-0.71) vs. 0.60 (0.56-0.65); p < 0.001] were significantly greater in AF alone vs. HFpEF alone even after multi-variate adjustment and propensity matching. After excluding the HFpEF+AF group, both LAWV and LAWT [SD] provided incremental values when added to PALS or LAVi (all p for net reclassification improvement <0.05) in discriminating AF alone, with LAWT[SD] yielding the largest C-statistic (0.78, 95% CI: 0.70-0.86) among all LA wall indices. Conclusions: Despite a similar extent of LA enlargement and dysfunction in HFpEF vs. AF alone, larger LAWV and LAWT [SD] can distinguish AF from HFpEF alone, suggesting the distinct underlying pathophysiological mechanism of LA remodeling in AF vs. HFpEF.

Quantitative volumetric computed tomography embolic analysis, the Qanadli score, biomarkers, and clinical prognosis in patients with acute pulmonary embolism.

Detailed descriptions of acute pulmonary emboli (PE) morphology, total embolic volume (TEV), and their effects upon patients' clinical presentation and prognosis remain largely unexplored. We studied 201 subjects with acute PE to the emergency department of a single medical center from April 2009 to December 2014. Patient hemodynamics, Troponin I and D-dimer levels, echocardiography, and the 30-day, 90-day and long-term mortality were obtained. Contrast-enhanced computed tomography (CT) of pulmonary structures and 3-dimensional measures of embolic burden were performed. The results showed a linear association between the greater TEV and each of the following 4 variables (increasing incidence of right ventricular (RV) dysfunction, higher systolic pulmonary artery pressure (sPAP), greater RV diameter, and RV/left ventricular (LV) ratio (all p < 0.001)). Among the measures of CT and echocardiography, TEV and RV/LV ratio were significantly associated with impending shock. In backward stepwise logistic regression, TEV, age and respiratory rate remained independent associated with impending shock (OR: 1.58, 1.03, 1.18, respectively and all p < 0.005).Total embolic burden assessed by CT-based quantification serves as a useful index for stressed cardiopulmonary circulation condition and can provide insights into RV dysfunction and the prediction of impending shock.

Association of Non-Alcoholic Fatty Liver Disease and Hepatic Fibrosis with Epicardial Adipose Tissue Volume and Atrial Deformation Mechanics in a Large Asian Population Free from Clinical Heart Failure.

Non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease share several cardiometabolic risk factors. Excessive visceral fat can manifest as ectopic fat depots over vital organs, such as the heart and liver. This study assessed the associations of NAFLD and liver fibrosis with cardiac structural and functional disturbances. We assessed 2161 participants using ultrasound, and categorized them as per the NAFLD Fibrosis Score into three groups: (1) non-fatty liver; (2) fatty liver with low fibrosis score; and (3) fatty liver with high fibrosis score. Epicardial fat volume (EFV) was measured through multidetector computed tomography. All participants underwent echocardiographic study, including tissue Doppler-based E/e' ratio and speckle tracking-based left ventricular global longitudinal strain, peak atrial longitudinal strain (PALS), and atrial longitudinal strain rates during systolic, early and late-diastolic phases (ALSRsyst, ALSRearly. ALSRlate). Larger EFV, decreased e' velocity, PALS, ALSRsyst, and ALSRearly, along with elevated E/e' ratio, were seen in all groups, especially in those with high fibrosis scores. After multivariate adjustment for traditional risk factors and EFV, fibrosis scores remained significantly associated with elevated E/e' ratio, LA stiffness, and decreased PALS (ß: 0.06, 1.4, −0.01, all p < 0.05). Thus, NAFLD is associated with LV diastolic dysfunction and subclinical changes in LA contractile mechanics.

Radiomics for the Prediction of Response to Antifibrotic Treatment in Patients with Idiopathic Pulmonary Fibrosis: A Pilot Study.

Antifibrotic therapy has changed the treatment paradigm for idiopathic pulmonary fibrosis (IPF); however, a subset of patients still experienced rapid disease progression despite treatment. This study aimed to determine whether CT-based radiomic features can predict therapeutic response to antifibrotic agents. In this retrospective study, 35 patients with IPF on antifibrotic treatment enrolled from two centers were divided into training (n = 26) and external validation (n = 9) sets. Clinical and pulmonary function data were collected. The patients were categorized into stable disease (SD) and progressive disease (PD) groups based on functional or radiologic criteria. From pretreatment non-enhanced high-resolution CT (HRCT) images, twenty-six radiomic features were extracted through whole-lung texture analysis, and six parenchymal patterns were quantified using dedicated imaging platforms. The predictive factors for PD were determined via univariate and multivariate logistic regression analyses. In the training set (SD/PD: 12/14), univariate analysis identified eight radiomic features and ground-glass opacity percentage (GGO%) as potential predicators of PD. However, multivariate analysis found that the single independent predictor was the sum entropy (accuracy, 80.77%; AUC, 0.75). The combined sum entropy-GGO% model improved the predictive performance in the training set (accuracy, 88.46%; AUC, 0.77). The overall accuracy of the combined model in the validation set (SD/PD: 7/2) was 66.67%. Our preliminary results demonstrated that radiomic features based on pretreatment HRCT could predict the response of patients with IPF to antifibrotic treatment.

Pulmonary vascular volume is associated with DLCO and fibrotic score in idiopathic pulmonary fibrosis: an observational study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a disease that primarily occurs in elderly individuals. However, it is difficult to diagnose and has a complex disease course. High-resolution computed tomography (HRCT) and lung function testing are crucial for its diagnosis and follow-up. However, the correlation of HRCT findings with lung function test results has not been extensively investigated. METHODS: This study retrospectively analysed the medical records and images of patients with IPF. Patients with evident emphysema and lung cancer were excluded. The diagnosis of all the included cases was confirmed following a discussion among specialists from multiple disciplines. The correlation of HRCT findings, including fibrotic score, HRCT lung volume, pulmonary artery trunk (PA) diameter and pulmonary vascular volume (PVV), with lung function test parameters, such as forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), was analysed. RESULTS: A total of 32 patients were included. Higher fibrotic and PVV scores were significantly correlated with lower DLCO (r = - 0.59, p = 0.01; r = - 0.43, p = 0.03, respectively) but not with FVC. Higher PVV score significantly correlated with higher fibrotic score (r = 0.59, p < 0.01) and PA diameter (r = 0.47, p = 0.006). CONCLUSION: Our study demonstrated the structural and functional correlation of IPF. The extent of lung fibrosis (fibrotic score) and PVV score were associated with DLCO but not with FVC. The PA diameter, which reflects the pulmonary artery pressure, was found to be associated with the PVV score.

Pericardial fat, thoracic peri-aortic adipose tissue, and systemic inflammatory marker in nonalcoholic fatty liver and abdominal obesity phenotype.

Researchers have conducted many studies about the relationships between peri-cardiovascular fat, nonalcoholic fatty liver disease (NAFLD), waist circumference, and cardiovascular disease (CVD). Nevertheless, the relationship between NAFLD and pericardial fat (PCF)/thoracic peri-aortic adipose tissue (TAT) phenotypes was still unknown. This study aimed to explore whether PCF/TAT was associated with NAFLD/abdominal obesity (AO) phenotypes in different high-sensitivity C-reactive protein (hs-CRP) levels. We consecutively studied 1655 individuals (mean age, 49.44 ± 9.76 years) who underwent a health-screening program. We showed a significant association between PCF/TAT and NAFLD/AO phenotypes in the cross-sectional study. We observed that the highest risk occurred in both abnormalities' groups, and the second highest risk occurred in the AO-only group. Subjects with AO had a significantly increased risk of PCF or TAT compared to those with NAFLD. Notably, the magnitude of the associations between PCF/TAT and NAFLD/AO varied by the level of systemic inflammatory marker (hs-CRP level). We suggested that people with AO and NAFLD must be more careful about changes in PCF and TAT. Regular measurement of waist circumference (or AO) can be a more accessible way to monitor peri-cardiovascular fat (PCF and TAT), which may serve as a novel and rapid way to screen CVD in the future.

Relationship between lung injury extent and phenotype manifested in non-contrast CT and cardiac injury during acute stage of COVID-19.

PURPOSE: This study evaluated the diagnostic values of the extent of lung injury manifested in non-contrast enhanced CT (NCCT) images, the inflammatory and immunological biomarkers C-reactive protein (CRP) and lymphocyte for detecting acute cardiac injury (ACI) in patients with COVID-19. The correlations between the NCCT-derived parameters and arterial blood oxygen level were also investigated. METHODS: NCCT lung images and blood tests were obtained in 143 patients with COVID-19 in approximately two weeks after symptom onset, and arterial blood gas measurement was also acquired in 113 (79%) patients. The diagnostic values of normal, moderately and severely abnormal lung parenchyma volume relative to the whole lungs (RVNP, RVMAP, RVSAP, respectively) measured from NCCT images for detecting the heart injury confirmed with high-sensitivity troponin I assay was determined. RESULTS: RVNP, RVMAP and RVSAP exhibited similar accuracy for detecting ACI in COVID-19 patients. RVNP was significantly lower while both RVMAP and RVSAP were significantly higher in the patients with ACI. All of the NCCT-derived parameters exhibited poor linear and non-linear correlations with PaO2 and SaO2. The patients with ACI had a significantly higher CRP level but a lower lymphocyte level compared to the patients without ACI. Combining one of these two biomarkers with any of the three NCCT-derived parameter further improved the accuracy for predicting ACI in patients with COVID-19. CONCLUSION: The NCCT-delineated normal and abnormal lung parenchmyma tissues were statistically significant predictors of ACI in patients with COVID-19, but both exhibited poor correlations with the arterial blood oxygen level. The incremental diagnostic values of lymphocyte and CRP suggested viral infection and inflammation were closely related to the heart injury during the acute stage of COVID-19.

Association of Region-Specific Cardiac Adiposity With Dysglycemia and New-Onset Diabetes.

Background Visceral adipose tissue is assumed to be an important indicator for insulin resistance and diabetes beyond overweight/obesity. We hypothesized that region-specific visceral adipose tissue may regulate differential biological effects for new-onset diabetes regardless of overall obesity. Methods and Results We quantified various visceral adipose tissue measures, including epicardial adipose tissue, paracardial adipose tissue, interatrial fat, periaortic fat, and thoracic aortic adipose tissue in 1039 consecutive asymptomatic participants who underwent multidetector computed tomography. We explored the associations of visceral adipose tissue with baseline dysglycemic indices and new-onset diabetes. Epicardial adipose tissue, paracardial adipose tissue, interatrial fat, periaortic fat, and thoracic aortic adipose tissue were differentially and independently associated with dysglycemic indices (fasting glucose, postprandial glucose, HbA1c, and homeostasis model assessment of insulin resistance) beyond anthropometric measures. The superimposition of interatrial fat and thoracic aortic adipose tissue on age, sex, body mass index, and baseline homeostasis model assessment of insulin resistance expanded the likelihood of baseline diabetes (from 67.2 to 86.0 and 64.4 to 70.8, P for ∆ ꭕ2: <0.001 and 0.011, respectively). Compared with the first tertile, the highest interatrial fat tertile showed a nearly doubled risk for new-onset diabetes (hazard ratio, 2.09 [95% CI, 1.38-3.15], P<0.001) after adjusting for Chinese Visceral Adiposity Index. Conclusions Region-specific visceral adiposity may not perform equally in discriminating baseline dysglycemia or diabetes, and showed differential predictive performance in new-onset diabetes. Our data suggested that interatrial fat may serve as a potential marker for new-onset diabetes.

Quantification of Cancer-Developing Idiopathic Pulmonary Fibrosis Using Whole-Lung Texture Analysis of HRCT Images.

Idiopathic pulmonary fibrosis (IPF) patients have a significantly higher risk of developing lung cancer (LC). There is only limited evidence of the use of texture-based radiomics features from high-resolution computed tomography (HRCT) images for risk stratification of IPF patients for LC. We retrospectively enrolled subjects who suffered from IPF in this study. Clinical data including age, gender, smoking status, and pulmonary function were recorded. Non-contrast chest CT for fibrotic score calculation and determination of three dimensional measures of whole-lung texture and emphysema were performed using a promising deep learning imaging platform. The results revealed that among 116 subjects with IPF (90 non-cancer and 26 lung cancer cases), the radiomics features showed significant differences between non-cancer and cancer patients. In the training cohort, the diagnostic accuracy using selected radiomics features with AUC of 0.66-0.73 (sensitivity of 80.0-85.0% and specificity of 54.2-59.7%) was not inferior to that obtained using traditional risk factors, such as gender, smoking status, and emphysema (%). In the validation cohort, the combination of radiomics features and traditional risk factors produced a diagnostic accuracy of 0.87 AUC and an accuracy of 75.0%. In this study, we found that whole-lung CT texture analysis is a promising tool for LC risk stratification of IPF patients.

Atrioventricular Longitudinal Mechanics Using Novel Speckle-Tracking Improved Risk Stratification Beyond Baseline Thyroid Hormone in Asymptomatic Subclinical Hypothyroidism.

BACKGROUND: Hypothyroidism is reportedly associated with increased cardiovascular risk and heart failure. We aimed to elucidate the mechanistic influence of atrio-ventricular deformations and their prognostic utilizations in asymptomatic subclinical hypothyroidism (SCH). METHODS: We assessed speckle-tracking of deformations among 4173 population-based asymptomatic individuals classified as euthyroid (0.25< thyroid-stimulating hormone [TSH] ≤4.0 µIU/mL, n=3799) or having mild (4< TSH ≤10.0 µIU/mL, n=349) or marked (TSH >10 µIU/mL, n=25) SCH. We further related deformational indices to outcomes of atrial fibrillation and heart failure. RESULTS: Despite borderline differences in indexed left ventricular mass and left atrial volume (P=0.054 and 0.051), those classified as mild and marked SCH presented with modest but significant reductions of global longitudinal strain, and showed elevated E/tissue Doppler imaging (TDI)-e', markedly diminished peak atrial longitudinal strain and higher left atrial stiffness (all P<0.05) when compared with euthyroid subjects. A higher TSH level was independently associated with reduced TDI-s'/TDI-e', worse global atrio-ventricular strains (global longitudinal strain/peak atrial longitudinal strain), elevated E/TDI-e', and worsened left atrial strain rate components (all P<0.05). Over a median 5.6 years (interquartile range, 4.7-6.5 years) follow-up, myocardial deformations yielded independent risk prediction using Cox regression in models adjusted for baseline covariates, N-terminal pro-brain natriuretic peptide, E/e', and treatment effect. Incorporation of global atrio-ventricular strain (global longitudinal strain/peak atrial longitudinal strain) and strain rates further showed improved risk reclassification when added to the baseline TSH strata (classified as euthyroid and mild and marked SCH; all P<0.05). Cox regression models remained significant with improved risk reclassification beyond TSH-based strata by using slightly different deformational cutoffs after excluding marked SCH group. CONCLUSIONS: Hypothyroidism, even when asymptomatic, may widely influence subclinical atrio-ventricular mechanical functions that may lead to higher heart failure and atrial fibrillation risk. We proposed the potential usefulness and prognostic utilization of myocardial strains in such population.

Correction: Associations of obesity and malnutrition with cardiac remodeling and cardiovascular outcomes in Asian adults: A cohort study.

[This corrects the article DOI: 10.1371/journal.pmed.1003661.].

Visceral adiposity index outperforms conventional anthropometric assessments as predictor of diabetes mellitus in elderly Chinese: a population-based study.

BACKGROUND: This study assessed the performance of visceral adiposity index and body shape index in predicting diabetes mellitus (DM) risk and compared their predictive ability to that of body mass index and waist circumference. METHODS: Among 8249 consecutive subjects who attended the Nationwide Health Check Up System for Senior Citizens (≥ 65 years) between 2008 and 2018, we examined the associations of several adiposity indices with DM risk and explored gender differences. RESULTS: Among all adiposity indicators, Chinese visceral adiposity index (CVAI) demonstrated the highest discriminatory ability for diabetes mellitus with area under receiver operating characteristic curves (AUC) of 0.65, 0.68, and 0.66 for men, women, and all participants, respectively, and optimal cut-offs set as 126.09 in men and 117.77 in women. Compared with body shape index (ABSI), both CVAI and VAI were strongly associated with baseline DM (adjusted OR: 4.85, 95% CI: 4.05-5.82 and 4.22, 95% CI: 3.53-5.05 for 4th vs 1st quartile groups by CVAI and VAI, P < 0.001), which was more pronounced in older adult women (Pinteraction < 0.05). Over a median of 5.25 years (IQR: 3.07-6.44 years) follow-up, Cox regression models showed higher predictive ability of CVAI and VAI compared to ABSI. Further, both CVAI and VAI independently predicted new-onset DM (adjusted HR: 1.29, 95% CI: 1.22-1.37 and 1.16, 95% CI: 1.11-1.21 by CVAI and VAI) and composite endpoint of new DM and death among those without baseline DM. CONCLUSIONS: Our population-based data demonstrated that Chinese visceral adiposity index may serve as a superior clinical indicator of diabetes when compared with conventional anthropometric indices among older adult Chinese, especially in women.

CT Assessment of Myocardial Perfusion and Fractional Flow Reserve in Coronary Artery Disease: A Review of Current Clinical Evidence and Recent Developments.

Coronary computed tomography angiography (CCTA) is routinely used for anatomical assessment of coronary artery disease (CAD). However, invasive measurement of fractional flow reserve (FFR) is the current gold standard for the diagnosis of hemodynamically significant CAD. CT-derived FFRCT and CT perfusion are two emerging techniques that can provide a functional assessment of CAD for risk stratification and clinical decision making. Several clinical studies have shown that the diagnostic performance of concomitant CCTA and functional CT assessment for detecting hemodynamically significant CAD is at least non-inferior to that of other routinely used imaging modalities. This article aims to review the current clinical evidence and recent developments in functional CT techniques.

Thoracic Aortic Calcification and Pre-Clinical Hypertension by New 2017 ACC/AHA Hypertension Guidelines.

The recently revised 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension (HTN) guidelines employ a lower blood pressure threshold to define HTN, aiming for earlier prevention of HTN-related cardiovascular diseases (CVD). Thoracic aortic calcification (TAC), a new surrogate marker of aging and aortic medial layer degeneration, and different stages of HTN, according to the 2017 ACC/AHA HTN guidelines, remain unknown. We classified 3022 consecutive asymptomatic individuals enrolled into four HTN categories using the revised 2017 ACC/AHA guidelines: normal blood pressure (NBP), elevated blood pressure (EBP), and stage 1 (S1) and stage 2 (S2) HTN. The coronary artery calcification score and TAC metrics (total Agaston TAC score, total plaque volume (mm3), and mean density (Hounsfield units, HU)) were measured using multi-detector computed tomography. Compared to NBP, a graded and significant increase in the TAC metrics was observed starting from EBP and S1 and S2 HTN, using the new 2017 ACC/AHA guidelines (NBP as reference; all trends: p < 0.001). These differences remained consistent after being fully adjusted. Older age (>50 years), S1 and S2 HTN, prevalent diabetes, and chronic kidney disease (<60 mL/min/1.73 m2) are all independently contributing factors to higher TAC risk using multivariate stepwise logistic regressions (all p ≤ 0.001). The optimal cutoff values of systolic blood pressure, diastolic blood pressure, and pulse pressure were 121, 74, and 45 mmHg, respectively, for the presence of TAC after excluding subjects with known CVD and ongoing HTN medication treatment. Our data showed that the presence of TAC starts at a stage of elevated blood pressure not categorized as HTN from the updated 2017 ACC/AHA hypertension guidelines.