Integrating Right Ventricular Pressure Waveform Analysis With Two-Point Volume Measurement for Quantification of Systolic and Diastolic Function: Experimental Validation and Clinical Application.

OBJECTIVE: To define in an experimental model the variance, accuracy, precision, and concordance of single-beat measures of right ventricular (RV) contractility and diastolic capacitance relative to conventional reference standards, and apply the methods to a clinical data set. DESIGN: A retrospective, observational analysis of recorded pressure waveforms and RV volume measurements. SETTING: At a university laboratory. PARTICIPANTS: Archived data from previous studies of anesthetized swine and awake patients undergoing clinically-indicated right-heart catheterization. INTERVENTIONS: Recording of RV pressure with simultaneous measurement of RV volume by conductance (swine) or 3-dimensional (3D) echocardiography (humans) during changes in contractility and/or loading conditions. MEASUREMENTS AND MAIN RESULTS: Using experimental data, single-beat measures of RV contractility quantified as end-systolic elastance, and diastolic capacitance quantified as the predicted volume at an end-diastolic pressure of 15 mmHg (V15), were compared to multi-beat, preload- variant, reference standards using correlation, Bland-Altman analysis, and 4-quadrant concordance testing. This analysis indicated that the methods were not directly interchangeable with reference standards, but were sufficiently robust to suggest potential clinical utility. Clinical application supported this potential by demonstrating enhanced assessment of the response to inhaled nitric oxide in patients undergoing diagnostic right-heart catheterization. CONCLUSIONS: Study results supported the possibility of integrating automated RV pressure analysis with RV volume measured by 3D echocardiography to create a comprehensive assessment of RV systolic and diastolic function at the bedside.

Noninvasive determinants of pulmonary hypertension in interstitial lung disease.

Pulmonary hypertension (PH) in interstitial lung disease (ILD) is associated with increased mortality and impaired exertional capacity. Right heart catheterization is the diagnostic standard for PH but is invasive and not readily available. Noninvasive physiologic evaluation may predict PH in ILD. Forty-four patients with PH and ILD (PH-ILD) were compared with 22 with ILD alone (non-PH ILD). Six-min walk distance (6MWD, 223 ± 131 vs. 331 ± 125 m, p = 0.02) and diffusing capacity for carbon monoxide (DLCO, 33 ± 14% vs. 55 ± 21%, p < 0.001) were lower in patients with PH-ILD. PH-ILD patients exhibited a lower gas-exchange derived pulmonary vascular capacitance (GXCAP, 251 ± 132 vs. 465 ± 282 mL × mmHg, p < 0.0001) and extrapolated maximum oxygen uptake (VO2max) (56 ± 32% vs. 84 ± 37%, p = 0.003). Multivariate analysis was performed to determine predictors of VO2 max. GXCAP was the only variable that predicted extrapolated VO2 max among PH-ILD and non-PH ILD patients. Receiver operating characteristic curve analysis assessed the ability of individual noninvasive variables to distinguish between PH-ILD and non-PH ILD patients. GXCAP (area under the curve [AUC] 0.85 ± 0.04, p < 0.0001) and delta ETCO2 (AUC 0.84 ± 0.04, p < 0.0001) were the strongest predictors of PH-ILD. A CART analysis selected GXCAP, estimated right ventricular systolic pressure (eRVSP) by echocardiogram, and FVC/DLCO ratio as predictive variables for PH-ILD. With this analysis, the AUC improved to 0.94 (sensitivity of 0.86 and sensitivity of 0.93). Patients with a GXCAP ≤ 416 mL × mmHg had an 82% probability of PH-ILD. Patients with GXCAP ≤ 416 mL × mmHg and high FVC/DLCO ratio >1.7 had an 80% probability of PH-ILD. Patients with GXCAP ≤ 416 mL × mmHg and an elevated eRVSP by echocardiogram >43 mmHg had 100% probability of PH-ILD. The incorporation of GXCAP with either eRVSP or FVC/DLCO ratio distinguishes between PH-ILD and non-PH-ILD with high probability and may therefore assist in determining the need to proceed with a diagnostic right heart catheterization and potential initiation of pulmonary arterial hypertension-directed therapy in PH-ILD patients.

Defining end-systolic pressure for single-beat estimation of right ventricle-pulmonary artery coupling: simple but not really.

Surrogates of right ventricle (RV) end-systolic pressure (ESP) used to determine RV-pulmonary artery coupling vary across studies. ESP using point of maximal time varying elastance provides most accurate estimate of actual ESP. https://bit.ly/3xuqX3B.

Sex Differences and the Role of Sex Hormones in Pulmonary Hypertension.

Pulmonary arterial hypertension is characterized by progressive pulmonary vascular remodeling and the eventual development of right heart failure. Multiple mechanisms are responsible, including vasoconstriction, metabolic flux, and inflammation. Since the early descriptions of pulmonary hypertension, female sex has been associated with increased prevalence of the disease, with research showing both detrimental and beneficial effects of estrogen and its metabolites. This article aims to describe how the female paradox arises from sex differences in pulmonary hypertension and how this has an impact on pathophysiology and future treatment.

Arterial load and right ventricular-vascular coupling in pulmonary hypertension.

Right ventricular (RV) functional adaptation to afterload determines outcome in pulmonary hypertension (PH). RV afterload is determined by the dynamic interaction between pulmonary vascular resistance (PVR), characteristic impedance (Zc), and wave reflection. Pulmonary vascular impedance (PVZ) represents the most comprehensive measure of RV afterload; however, there is an unmet need for an easier bedside measurement of this complex variable. Although a recent study showed that Zc and wave reflection can be estimated from RV pressure waveform analysis and cardiac output, this has not been validated. Estimations of Zc and wave reflection coefficient (λ) were validated relative to conventional spectral analysis in an animal model. Zc, λ, and the single-beat ratio of end-systolic to arterial elastance (Ees/Ea) to estimate RV-pulmonary arterial (PA) coupling were determined from right heart catheterization (RHC) data. The study included 30 pulmonary artery hypertension (PAH) and 40 heart failure with preserved ejection fraction (HFpEF) patients [20 combined pre- and postcapillary PH (Cpc-PH) and 20 isolated postcapillary PH, (Ipc-PH)]. Also included were 10 age- and sex-matched controls. There was good agreement with minimal bias between estimated and spectral analysis-derived Zc and λ. Zc in PAH and Cpc-PH groups exceeded that in the Ipc-PH group and controls. λ was increased in Ipc-PH (0.84 ± 0.02), Cpc-PH (0.87 ± 0.05), and PAH groups (0.85 ± 0.04) compared with controls (0.79 ± 0.03); all P values were <0.05. λ was the only afterload parameter associated with RV-PA coupling in PAH. In the PH-HFpEF group, RV-PA uncoupling was independent of RV afterload. Our findings indicate that Zc and λ derived from an RV pressure curve can be used to improve estimation of RV afterload. λ is the only afterload measure associated with RV-PA uncoupling in PAH, whereas RV-PA uncoupling in PH-HFpEF appears to be independent of afterload consistent with an inherent abnormality of the RV myocardium.NEW & NOTEWORTHY Pulmonary vascular impedance (PVZ) represents the most comprehensive measure of right ventricle (RV) afterload; however, measurement of this variable is complex. We demonstrate that characteristic impedance (Zc) and a wave reflection coefficient, λ, can be derived from RV pressure waveform analysis. In addition, RV dysfunction in left heart disease is independent of its afterload. The current study provides a platform for future studies to examine the pharmacotherapeutic effects and prognosis of different measures of RV afterload.

Evaluation of a Multidisciplinary Disease Management Program to Achieve Asthma Control in Seven Safety Net Hospitals in Louisiana.

The objective was to evaluate a multidisciplinary guideline-driven disease management program focused on achievement of asthma control among sustained patients with confirmed asthma in Louisiana and to assess factors affecting achievement of asthma control. Data were extracted from the electronic health records of 1596 adults with confirmed asthma, sustained care for >1 year in the outpatient setting, and ≥2 recorded Asthma Control Test (ACT) scores. Multivariable logistic regression modeling was used to assess the association of demographic variables, comorbidities, and process measures with the best achieved asthma control as represented by the highest ACT score. Most subjects were female (81.1%) and African American (63.9%). Approximately half of them (48.9%) were able to achieve asthma control (ACT ≥20). The most prevalent comorbidities were hypertension (79.8%), rhinitis (55.3%), and obesity (50.5%). Most patients received pulmonary function testing (PFT) (88.6%), controller medication therapy (85.5%), or written asthma action plans (92.7%). Asthma control was positively associated with presence of PFT (OR = 1.63, 95% CI: 1.13, 2.37) and being a "never" smoker (OR = 1.49, 95% CI: 1.08, 2.04). Asthma control was less likely to be achieved by patients who were African American (OR = 0.68, 95% CI: 0.52, 0.87), had more comorbidities (OR = 0.89, 95% CI: 0.83, 0.96), or were on more medications (OR = 0.79, 95% CI: 0.72, 0.88). Asthma control was achieved in 48.9% of an adult, primarily African American population with the implementation of comprehensive guideline-driven care. Furthermore, this is the first study to observe that the presence of PFT may be associated with asthma control.

Diagnostic utility of sub-maximum cardiopulmonary exercise testing in the ambulatory setting for heart failure with preserved ejection fraction.

Pulmonary hypertension is commonly associated with heart failure with preserved ejection fraction. In heart failure with preserved ejection fraction, the elevated left-sided filling pressures result in isolated post-capillary pulmonary hypertension or combined pre- and post-capillary pulmonary hypertension. Although right heart catheterization is the gold standard for diagnosis, it is an invasive test with associated risks. The ability of sub-maximum cardiopulmonary exercise test as an adjunct diagnostic tool in pulmonary hypertension-associated heart failure with preserved ejection fraction is not known. Forty-six patients with heart failure with preserved ejection fraction and pulmonary hypertension (27 patients with combined pre- and post-capillary pulmonary hypertension and 19 patients with isolated post-capillary pulmonary hypertension) underwent sub-maximum cardiopulmonary exercise test followed by right heart catheterization. The study also included 18 age- and gender-matched control subjects. Several sub-maximum gas exchange parameters were examined to determine the ability of sub-maximum cardiopulmonary exercise test to distinguish between isolated post-capillary pulmonary hypertension and combined pre- and post-capillary pulmonary hypertension. Conventional echocardiogram measures did not distinguish between isolated post-capillary pulmonary hypertension and combined pre- and post-capillary pulmonary hypertension. Compared to isolated post-capillary pulmonary hypertension, combined pre- and post-capillary pulmonary hypertension had greater ventilatory equivalent for carbon dioxide (VE/VCO2) slope, reduced delta end-tidal CO2 change during exercise, reduced oxygen uptake efficiency slope, and reduced gas exchange determined pulmonary vascular capacitance. The latter was significantly associated with right heart catheterization determined pulmonary artery compliance (r = 0.5; p = 0.0004). On univariate analysis, sub-maximum VE/VCO2, delta end-tidal carbon dioxide, and gas exchange determined pulmonary vascular capacitance emerged as independent predictors of the extrapolated maximum oxygen uptake (%predicted) (ß-coefficient values of -7.32, 95% CI: -13.3 - (-1.32), p = 0.01; 8.01, 95% CI: 1.96-14.05, p = 0.01; 8.78, 95% CI: 2.26-15.29, p = 0.01, respectively). Sub-maximum gas exchange parameters obtained during cardiopulmonary exercise test in an ambulatory setting allows for discrimination between isolated post-capillary pulmonary hypertension and combined pre- and post-capillary pulmonary hypertension. Additionally, sub-maximum cardiopulmonary exercise test derived VE/VCO2, delta end-tidal carbon dioxide, and gas exchange determined pulmonary vascular capacitance influences aerobic capacity in heart failure with preserved ejection fraction.

Assessing Response to Therapy for Nontuberculous Mycobacterial Lung Disease: Quo Vadis?

Assessing progression of disease or response to treatment remains a major challenge in the clinical management of nontuberculous mycobacterial (NTM) infections of the lungs. Serial assessments of validated measures of treatment response address whether the current therapeutic approach is on track toward clinical cure, which remains a fundamental question for clinicians and patients during the course of NTM disease treatment. The 2015 NTM Research Consortium Workshop, which included a patient advisory panel, identified treatment response biomarkers as a priority area for investigation. Limited progress in addressing this challenge also hampers drug development efforts. The Biomarker Qualification Program at the FDA supports the use of a validated treatment response biomarker across multiple drug development programs. Current approaches in clinical practice include microbiologic and radiographic monitoring, along with symptomatic and quality-of-life assessments. Blood-based monitoring, including assessments of humoral and cell-mediated NTM-driven immune responses, remain under investigation. Alignment of data collection schemes in prospective multicenter studies, including the support of biosample repositories, will support identification of treatment response biomarkers under standard-of-care and investigational therapeutic strategies. In this review, we outline the role of treatment monitoring biomarkers in both clinical practice and drug development frameworks.