Number of attempts and interventions to obtain a valid pulmonary artery wedge pressure.

Background: A valid pulmonary artery wedge pressure (PAWP) is essential for the hemodynamic characterization of pulmonary hypertension (PH). We prospectively investigated the methodology for obtaining a valid PAWP measurement, while assessing the impact of prespecified factors on its determination.

Methods: In this prospective observational cohort study, we included consecutive patients who underwent right heart catheterization (RHC) using fluoroscopy at the Pulmonary Vascular Disease program at Cleveland Clinic, between February and May 2023.

Efficacy and determinants of response to inhaled treprostinil in pulmonary hypertension - interstitial lung disease.

Inhaled treprostinil has shown to improve exercise capacity in patients with pulmonary hypertension-interstitial lung disease (PH-ILD). We evaluated the efficacy and determinants of favorable response to inhaled treprostinil at six months. METHODS: Of the 106 patients screened, 42 were eligible for this retrospective single-center study.

Plasma catecholamines in patients undergoing invasive cardiopulmonary exercise test for exercise intolerance.

Background: Invasive cardiopulmonary exercise testing (iCPET) combines traditional cardiopulmonary exercise testing with invasive hemodynamic measurements to assess exercise intolerance, which can be caused by preload insufficiency (PI), characterized by low ventricular filling pressures and reduced cardiac output during exertion. We hypothesize that plasma catecholamine levels at rest and during exercise correlate with hemodynamic parameters in PI.

Methods: We included adult patients who underwent iCPET for exercise intolerance and had plasma catecholamines measured at rest and peak exercise.

Impact of body position on hemodynamic measurements during exercise: A tale of two bikes.

The addition of exercise testing during right heart catheterization (RHC) is often required to accurately diagnose causes of exercise intolerance like early pulmonary vascular disease, occult left heart disease, and preload insufficiency. We tested the influence of body position (supine vs. seated) on hemodynamic classification both at rest and during exercise.

Fluid loading during the hemodynamic evaluation of pulmonary hypertension: a cross-sectional study.

Background: Compensated pulmonary hypertension due to left heart disease (PH-LHD) may be difficult to identify based on resting hemodynamics. Fluid challenge is commonly used to unmask occult PH-LHD. We sought to determine the hemodynamic effect of fluid loading and its association with the clinical pretest probability of PH-LHD.

Can Inhaled Nitric Oxide Response Predict Tolerance to Therapies and Survival in Patients With Combined Precapillary and Postcapillary Pulmonary Hypertension?

Inhaled nitric oxide (iNO) relaxes the pulmonary circulation and variably increases the left ventricular preload and pulmonary artery wedge pressure (PAWP)-hemodynamic information that may help guide treatment decisions and assess prognosis in patients with combined precapillary and postcapillary pulmonary hypertension (PH). We included consecutive patients with combined precapillary and postcapillary PH (mean pulmonary artery pressure >20 mm Hg, PAWP >15 mm Hg, and pulmonary vascular resistance [PVR] >2 Woods unit [WU]) who underwent right-sided cardiac catheterization with iNO at the Cleveland Clinic Pulmonary Vascular Disease program between 2017 and 2022. We included 104 patients with baseline PAWP and PVR of 22.

Impact on Pulmonary Hypertension Hemodynamic Classification Based on the Methodology Used to Measure Pulmonary Artery Wedge Pressure and Cardiac Output.

Guidelines recommend using end-expiration pulmonary pressure measurements to determine the hemodynamic subgroups in pulmonary hypertension. Pulmonary artery wedge pressure (PAWP) determinations averaged across the respiratory cycle (PAWPav) instead of PAWP at end-expiration (PAWPee) and cardiac output (CO) measured by Fick (CO) instead of thermodilution (CO) may affect the hemodynamic classification of pulmonary hypertension. To assess the impact on the pulmonary hypertension hemodynamic classification of the use of PAWPee versus PAWPav as well as CO versus CO.

Does veno-arterial carbon dioxide gradient provide an adequate estimation of cardiac index in pulmonary hypertension?

Aims: Pulmonary hypertension (PH) management is dependent on cardiac output (CO) assessment. The gold standard Fick method for CO and cardiac index (CI) measurement is not widely available. An accessible and reliable method for CO/CI estimation is needed not only in catheterization labs but also in other environments such as the intensive care unit, where pulmonary artery catheters are less likely to be used.

Simultaneous Measurement of Endothelial Cell Proliferation and Cell Cycle Stage Using Flow Cytometry.

Endothelial cell proliferation rate is an important indicator of vascular health. Being able to detect the rate of endothelial cell proliferation, or cell cycle disturbances after intervention is a valuable tool for analysing any beneficial or detrimental effects of treatments in vitro. Here, we describe a straightforward flow cytometric-based method of proliferation and cell cycle tracking that can be performed on human endothelial cells in culture over several days.

Use of a Thin Layer Assay for Assessing the Angiogenic Potential of Endothelial Cells In Vitro.

Angiogenesis is essential for wound healing and regeneration and plays a significant role in several pathologies including cancer and atherosclerosis. In vitro assays offer simple and powerful tools for investigating the regulation of the angiogenic functions of primary endothelial cells (ECs) before moving to in vivo studies. The classic in vitro two-dimensional angiogenesis assay utilizes Basement Membrane Extract (BME) to study the differentiation and sprouting of ECs over a 24-h period.

Impact of Esophageal Pressure Measurement on Pulmonary Hypertension Diagnosis in Patients With Obesity.

Background: Elevated intrathoracic pressure could affect pulmonary vascular pressure measurements and influence pulmonary hypertension (PH) diagnosis and classification. Esophageal pressure (P) measurement adjusts for the increase in intrathoracic pressure, better reflecting the pulmonary hemodynamics in patients with obesity.

Research Question: In individuals with obesity, what is the impact of adjusting pulmonary hemodynamic determinations for P on PH diagnosis and classification? Can P be estimated by positional or respiratory hemodynamic changes?

Study Design And Methods: In this prospective cohort study, we included patients with obesity who underwent right heart catheterization and demonstrated elevated pulmonary artery wedge pressure (PAWP; ≥ 12 mm Hg).

Challenges with tunneled dialysis catheter placement with subcutaneous emphysema.

Central vein catheter is a convenient and preferred vascular access for blood purification therapy in intensive care unit. Utilizing ultrasound to access the central vein is considered standard of care. However, critically ill patients can pose challenges while acquiring an optimal ultrasound image.

Effect of pulmonary artery catheter balloon inflation on pulmonary hemodynamics.

Background: Right heart catheterization (RHC), including a pulmonary artery wedge pressure (PAWP) determination, is necessary to categorize the hemodynamic type of pulmonary hypertension (PH). The potential hemodynamic implications of a pulmonary artery catheter (PAC) balloon inflation in PH have not been formally tested.

Methods: We assessed the hemodynamic impact of the PAC balloon inflation during RHC by measuring systolic, diastolic, and mean pulmonary artery pressure (mPAP) in all patients, and cardiac output (CO) by thermodilution in a subgroup of patients.

Safety of Bedside Placement of Tunneled Hemodialysis Catheters in the Intensive Care Unit: Translating from the COVID-19 Experience.

Background: Critically ill patients with coronavirus disease 2019 (COVID-19) and kidney dysfunction often require tunneled hemodialysis catheter (TDC) placement for kidney replacement therapy, typically under fluoroscopic guidance to minimize catheter-related complications. This entails transportation of patients outside the intensive care unit to a fluoroscopy suite, which may potentially expose many healthcare providers to COVID-19. One potential strategy to mitigate the risk of viral transmission is to insert TDCs at the bedside, using ultrasound and anatomic landmarks only, without fluoroscopic guidance.

Right heart catheterization for pulmonary hypertension during the coronavirus disease 2019 pandemic.

Right heart catheterization is an essential diagnostic modality in the evaluation of pulmonary hypertension. The coronavirus disease 2019 pandemic has resulted in deferral of elective procedures including right heart catheterization. The benefits of proceeding with right heart catheterization, such as further characterization of hemodynamic subtype and severity of pulmonary hypertension, initiation of targeted pulmonary arterial hypertension therapy, as well as further hemodynamic testing, need to be carefully balanced with the risk of potentially exposing both patients and health care personnel to coronavirus disease 2019 infection.

Pharmacokinetic and Pharmacodynamic Analyses To Determine the Optimal Fixed Dosing Regimen of Iclaprim for Treatment of Patients with Serious Infections Caused by Gram-Positive Pathogens.

Iclaprim is a bacterial dihydrofolate reductase inhibitor that is currently being evaluated in two phase 3 trials for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). Prior animal infection model studies suggest that the pharmacokinetic/pharmacodynamic (PK/PD) drivers for efficacy are area under the concentration-time curve from 0 to 24 h at steady state (AUC), AUC/MIC, and time above the MIC during the dosing interval ( > MIC), while QTc prolongation was associated with the maximal concentration at steady state () in a thorough QTc phase 1 study. Using PK data collected from 470 patients from the previously conducted phase 3 complicated skin and skin structure infection (cSSSI) trials, population PK modeling and Monte Carlo simulation (MCS) were used to identify a fixed iclaprim dosage regimen for the ongoing phase 3 ABSSSI studies that maximizes AUC, AUC/MIC, and > MIC while minimizing the probability of a of ≥800 ng/ml relative to the values for the previously employed cSSSI regimen of 0.

Replicatively senescent human fibroblasts reveal a distinct intracellular metabolic profile with alterations in NAD+ and nicotinamide metabolism.

Cellular senescence occurs by proliferative exhaustion (PEsen) or following multiple cellular stresses but had not previously been subject to detailed metabolomic analysis. Therefore, we compared PEsen fibroblasts with proliferating and transiently growth arrested controls using a combination of different mass spectroscopy techniques. PEsen cells showed many specific alterations in both the NAD+ de novo and salvage pathways including striking accumulations of nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) in the amidated salvage pathway despite no increase in nicotinamide phosphoribosyl transferase or in the NR transport protein, CD73.