Three-dimensional echocardiography and 2D-3D speckle tracking imaging in chronic pulmonary hypertension. diagnostic accuracy in detecting hemodynamic signs of RV failure

Background and objective. Our aim was to compare three-dimensional (3D) and 2D and 3D speckle tracking (2D-STE, 3D-STE) echocardiographic parameters with conventional right ventricular (RV) indexes in patients with chronic pulmonary hypertension (PH), and investigate whether these techniques could result in better correlation with hemodynamic variables indicative of heart failure. Methods. Seventy-three adult patients (mean age, 53±13 years; 44% male) with chronic PH of different etiologies were studied by echocardiography and cardiac catheterization (25 precapillary PH from pulmonary arterial hypertension, 23 obstructive pulmonary heart disease, and 23 postcapillary PH from mitral regurgitation). Thirty healthy subjects (mean age, 54±15 years; 43% male) served as controls. Standard 2D measurements (RV-FAC -fractional area change-, TAPSE -tricuspid annular plane systolic excursion-) and mitral and tricuspid tissue Doppler annular velocities were obtained. RV 3D volumes, and global and regional ejection fraction (3D-RVEF) were determined. RV strains were calculated by 2D-STE and 3D-STE. Results. RV 3D global-free-wall longitudinal strain (3DGFW-RVLS), 2D global-free-wall longitudinal strain (GFW-RVLS), apical-free-wall longitudinal strain (AFW-RVLS), basal-free-wall longitudinal strain (BFW-RVLS), and 3D-RVEF were lower in patients with pre-capillary PH (p<0.0001) and post-capillary PH (p<0.01) compared to controls. 3DGFW-RVLS (HR 4.6, 95% CI 2.79-8.38, p=0.004) and 3D-RVEF (HR 5.3, 95% CI 2.85-9.89, p=0.002) were independent predictors of mortality. ROC curves showed that the thresholds offering an adequate compromise between sensitivity and specificity for detecting hemodynamic signs of RV failure were 39% for 3D-RVEF (AUC 0.89), -17% for 3DGFW-RVLS (AUC 0.88), -18% for GFW-RVLS (AUC 0.88), -16% for AFW-RVLS (AUC 0.85), 16mm for TAPSE (AUC 0.67), and 38% for RV-FAC (AUC 0.62). Conclusions. In chronic PH, 3D, 2D-STE and 3D-STE parameters indicate global and regional RV dysfunction that is associated with RV failure hemodynamics better than conventional echo indices

The Association Between Rate and Severity of Exacerbations in Chronic Obstructive Pulmonary Disease: An Application of a Joint Frailty-Logistic Model.

Exacerbations are a hallmark of chronic obstructive pulmonary disease (COPD). Evidence suggests the presence of substantial between-individual variability (heterogeneity) in exacerbation rates. The question of whether individuals vary in their tendency towards experiencing severe (versus mild) exacerbations, or whether there is an association between exacerbation rate and severity, has not yet been studied. We used data from the MACRO Study, a 1-year randomized trial of the use of azithromycin for prevention of COPD exacerbations (United States and Canada, 2006-2010; n = 1,107, mean age = 65.2 years, 59.1% male). A parametric frailty model was combined with a logistic regression model, with bivariate random effects capturing heterogeneity in rate and severity. The average rate of exacerbation was 1.53 episodes/year, with 95% of subjects having a model-estimated rate of 0.47-4.22 episodes/year. The overall ratio of severe exacerbations to total exacerbations was 0.22, with 95% of subjects having a model-estimated ratio of 0.04-0.60. We did not confirm an association between exacerbation rate and severity (P = 0.099). A unified model, implemented in standard software, could estimate joint heterogeneity in COPD exacerbation rate and severity and can have applications in similar contexts where inference on event time and intensity is considered. We provide SAS code (SAS Institute, Inc., Cary, North Carolina) and a simulated data set to facilitate further uses of this method

Joint modeling of survival and longitudinal data: Carrico index data example

Aim: When the respiratory system is unable to adequately absorb oxygen or excrete carbon dioxide, acute respiratory failure (ARF) develops. A current area of study is the survival analysis of patients with acute hypercapnic respiratory failure (AHRF) in the field of pulmonary diseases. In the follow-up period, several biochemical markers are repeatedly measured, such as respiration rate and Carrico Index; however, baseline or averaged values are mostly related to treatment failure. Although this approach is not inaccurate, it causes information loss, which leads to biased estimates. This prospective cohort study primarily looked at the relationship between changes in Carrico Index&nbsp;and failure of treatment&nbsp;in AHRF&nbsp;patients. Methods: We included 86 patients from Ankara University School of Medicine Pulmonary Diseases Department. The association between the trajectory of the Carrico Index and failure in AHRF patients was examined using a joint modeling approach for longitudinal and survival data. Results: Results showed that averaged Carrico Index change was inversely and significantly associated with failure (HR: 0.97, 95% CI: -0.05 to 1.97). With hazard ratios of 1.43 and 1.4, chronic health evaluation II (Apache II), and COPD Assesment test (CAT) were positively correlated with failure risk. Conclusions: The present study demonstrate that applying the risk predictors' trajectory through an appropriate statistical method improved accuracy and avoid biased results

Prognostic variables and scores identifying the end of life in COPD: a systematic review.

INTRODUCTION: COPD is a major cause of mortality, and the unpredictable trajectory of the disease can bring challenges to end-of-life care. We aimed to investigate known prognostic variables and scores that predict prognosis in COPD in a systematic literature review, specifically including variables that contribute to risk assessment of patients for death within 12 months. METHODS: We conducted a systematic review on prognostic variables, multivariate score or models for COPD. Ovid MEDLINE, EMBASE, the Cochrane database, Cochrane CENTRAL, DARE and CINAHL were searched up to May 1, 2016. RESULTS: A total of 5,276 abstracts were screened, leading to 516 full-text reviews, and 10 met the inclusion criteria. No multivariable indices were developed with the specific aim of predicting all-cause mortality in stable COPD within 12 months. Only nine indices were identified from four studies, which had been validated for this time period. Tools developed using expert knowledge were also identified, including the Gold Standards Framework Prognostic Indicator Guidance, the RADboud Indicators of Palliative Care Needs, the Supportive and Palliative Care Indicators Tool and the Necesidades Paliativas program tool. CONCLUSION: A number of variables contributing to the prediction of all-cause mortality in COPD were identified. However, there are very few studies that are designed to assess, or report, the prediction of mortality at or less than 12 months. The quality of evidence remains low, such that no single variable or multivariable score can currently be recommended

Evaluation of the Kinetics of Pancreatic Stone Protein as a Predictor of Ventilator-Associated Pneumonia

Funding Information: This study was partially supported by Abionic, CIBERES, and Research and Innovation Institute Parc Tauli (I3PT). A.C. acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII; Sara Borrell 2021: CD21/00087). The funding sources had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or in the decision to submit the manuscript for publication. Publisher Copyright: © 2023 by the authors.BACKGROUND: Ventilator-associated pneumonia (VAP) is a severe condition. Early and adequate antibiotic treatment is the most important strategy for improving prognosis. Pancreatic Stone Protein (PSP) has been described as a biomarker that increases values 3–4 days before the clinical diagnosis of nosocomial sepsis in different clinical settings. We hypothesized that serial measures of PSP and its kinetics allow for an early diagnosis of VAP. METHODS: The BioVAP study was a prospective observational study designed to evaluate the role of biomarker dynamics in the diagnosis of VAP. To determine the association between repeatedly measured PSP and the risk of VAP, we used joint models for longitudinal and time-to-event data. RESULTS: Of 209 patients, 43 (20.6%) patients developed VAP, with a median time of 4 days. Multivariate joint models with PSP, CRP, and PCT did not show an association between biomarkers and VAP for the daily absolute value, with a hazard ratio (HR) for PSP of 1.01 (95% credible interval: 0.97 to 1.05), for CRP of 1.00 (0.83 to 1.22), and for PCT of 0.95 (0.82 to 1.08). The daily change of biomarkers provided similar results, with an HR for PSP of 1.15 (0.94 to 1.41), for CRP of 0.76 (0.35 to 1.58), and for PCT of 0.77 (0.40 to 1.45). CONCLUSION: Neither absolute PSP values nor PSP kinetics alone nor in combination with other biomarkers were useful in improving the prediction diagnosis accuracy in patients with VAP. Clinical Trial Registration: Registered retrospectively on August 3rd, 2012. NCT02078999.publishersversionpublishe

Evaluation of the Kinetics of Pancreatic Stone Protein as a Predictor of Ventilator-Associated Pneumonia

Ventilator-associated pneumonia (VAP) is a severe condition. Early and adequate antibiotic treatment is the most important strategy for improving prognosis. Pancreatic Stone Protein (PSP) has been described as a biomarker that increases values 3-4 days before the clinical diagnosis of nosocomial sepsis in different clinical settings. We hypothesized that serial measures of PSP and its kinetics allow for an early diagnosis of VAP. METHODS: The BioVAP study was a prospective observational study designed to evaluate the role of biomarker dynamics in the diagnosis of VAP. To determine the association between repeatedly measured PSP and the risk of VAP, we used joint models for longitudinal and time-to-event data. RESULTS: Of 209 patients, 43 (20.6%) patients developed VAP, with a median time of 4 days. Multivariate joint models with PSP, CRP, and PCT did not show an association between biomarkers and VAP for the daily absolute value, with a hazard ratio (HR) for PSP of 1.01 (95% credible interval: 0.97 to 1.05), for CRP of 1.00 (0.83 to 1.22), and for PCT of 0.95 (0.82 to 1.08). The daily change of biomarkers provided similar results, with an HR for PSP of 1.15 (0.94 to 1.41), for CRP of 0.76 (0.35 to 1.58), and for PCT of 0.77 (0.40 to 1.45). CONCLUSION: Neither absolute PSP values nor PSP kinetics alone nor in combination with other biomarkers were useful in improving the prediction diagnosis accuracy in patients with VAP. Clinical Trial Registration: Registered retrospectively on August 3rd, 2012. NCT02078999

Modeling Heart Failure Predictive Mortality in Skilled Nursing Facilities

Problem: Approximately 25% of skilled nursing facility (SNF) patients are diagnosed with heart failure (HF). The heart failure mortality trajectory is non-linear and there are no useable mortality models from clinical records for use by healthcare providers in the SNF setting. A mortality risk model for patients with HF is important so that palliative care interventions may be offered to improve patients’ quality of life during the end stages of dying. Assessment items captured routinely by the SNF Resident Assessment Instrument –Minimum Data Set 3.0 (RAI-MDS) instrument may be useful in identifying those patients whose declining condition warrants discussion of palliative care.Methodology: Data from 1827 eligible HF patient’s RAI-MDS assessments, who resided in Midwest SNFs during 2013-14, were investigated in a retrospective cross-sectional exploratory method. Discrete survival analysis and logistic regression were used to determine which factors predict mortality so as to allow future creation of a model to prompt palliative care discussions. Results: Nine variables embedded in the RAI-MDS were selected based upon a literature review of HF mortality prediction models. Five of the nine variables demonstrated predictive hazard ratios (HR) in the SNF setting. These included re-admission after hospitalization (HR 1.323), reduced renal function (HR 1.187), presence of dyspnea (HR 1.285), age 85 and older (HR 1.828), and having three or more diagnoses (HR 1.345). Not predictive were having diagnoses of diabetes or hypertension, being sixty-five to eighty-four years of age, and gender. Conclusions: The mortality predictors identified in this study may facilitate development of a HF mortality risk model specific to patients in SNFs. Such a model may be useful in making decisions regarding when to institute palliative care discussions with SNF patients and their families

Association of abnormal lung function and its subtypes with arterial stiffness: A longitudinal cohort study

BACKGROUND: Prior studies have reported the cross-sectional relationship between lung function and arterial stiffness, while the longitudinal association remains unclear to date. This study aimed to investigate whether abnormal lung function and its subtypes at baseline are associated with increased arterial stiffness using a cohort. METHODS AND RESULTS: This was a secondary analysis extracting 2461 participants from Beijing Health Management Cohort as baseline and annually followed for development of arterial stiffness. Abnormal lung function was defined by forced expiratory volume in 1s \u3c 80% of the predicted value, forced vital capacity of the predicted value, or forced expiratory volume in 1s/ forced vital capacity ratio \u3c 70%. Increased arterial stiffness was determined by brachial-ankle pulse wave velocity ≥ 1400 cm/s. Cox proportional hazards model was used to calculate the hazard ratio and population attributable fraction. The mean age was 42.8±8.1 years, and 444 (18.0%) cases developed increased arterial stiffness during a median follow-up of 3.0 years. The adjusted hazard ratio (95% CI) of arterial stiffness was 1.47 (95% CI, 1.10–1.96) for abnormal lung function, with a population attributable fraction of 3.9% (95% CI, 0.8–7.1). Of subtypes, only obstructive ventilatory dysfunction was significantly associated with arterial stiffness (adjusted hazard ratio, 2.06 [95% CI, 1.27–3.36]), not restricted ventilatory dysfunction (adjusted hazard ratio, 0.95 [95% CI, 0.54–1.65]). Consistent results were observed on multiple sensitivity analyses. CONCLUSIONS: Our study indicated a longitudinal association of abnormal lung function with increased arterial stiffness using a large cohort, especially for the obstructive ventilatory dysfunction

COPDGene® 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease

Background:Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. Methods:Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. Results:Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics. Conclusions:A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop