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Frontiers in Physiology 2023The primary impact of ventilation and ventilatory efforts on left ventricular (LV) function in left ventricular dysfunction relate to how changes in intrathoracic... (Review)
Review
The primary impact of ventilation and ventilatory efforts on left ventricular (LV) function in left ventricular dysfunction relate to how changes in intrathoracic pressure (ITP) alter the pressure gradients for venous return into the chest and LV ejection out of the chest. Spontaneous inspiratory efforts by decreasing ITP increase both of these pressure gradients increasing venous blood flow and impeding LV ejection resulting in increased intrathoracic blood volume. In severe heart failure states when lung compliance is reduced, or airway resistance is increased these negative swings in ITP can be exacerbated leading to LV failure and acute cardiogenic pulmonary edema. By merely reversing these negative swings in ITP by the use of non-invasive continuous positive airway pressure (CPAP), these profoundly detrimental forces can be immediately reversed, and cardiovascular stability can be restored in moments. This forms the clinical rationale for the immediate use of CPAP for the treatment of acute cardiogenic pulmonary edema. Increasing ITP during positive pressure ventilation decreases the pressure gradients for venous return and LV ejection decreasing intrathoracic blood volume. In a hypovolemic patient even with LV dysfunction this can result in hypotension due to inadequate LV preload. Minor increases in ITP as occur using pressure-limited positive-pressure ventilation primarily reverse the increased LV afterload of negative swings in ITP and if fluid overload was already present, minimally alter cardiac output. The effect of changes in lung volume on LV function are related primarily to its effects on right ventricular (RV) function through changes in pulmonary vascular resistance and overdistention (hyperinflation). In acute lung injury with alveolar collapse, positive pressure ventilation may reduce pulmonary vascular resistance if alveolar recruitment predominates. Hyperinflation, however, impedes diastolic filling while simultaneously increasing pulmonary vascular resistance. Thus, increasing lung volume can reduce RV afterload by reversing hypoxic pulmonary vasoconstriction or increase afterload by overdistention. Hyperinflation can also impede RV filling. All of these processes can be readily identified at the bedside using echocardiography.
PubMed: 37614756
DOI: 10.3389/fphys.2023.1237741 -
Qatar Medical Journal 2024
PubMed: 38680407
DOI: 10.5339/qmj.2024.qitc.30 -
Respiratory Investigation Jan 2024Recent advances in imaging analysis have enabled evaluation of ventilation and perfusion in specific regions by chest computed tomography (CT) and magnetic resonance... (Review)
Review
Recent advances in imaging analysis have enabled evaluation of ventilation and perfusion in specific regions by chest computed tomography (CT) and magnetic resonance imaging (MRI), in addition to modalities including dynamic chest radiography, scintigraphy, positron emission tomography (PET), ultrasound, and electrical impedance tomography (EIT). In this review, an overview of current functional imaging techniques is provided for each modality. Advances in chest CT have allowed for the analysis of local volume changes and small airway disease in addition to emphysema, using the Jacobian determinant and parametric response mapping with inspiratory and expiratory images. Airway analysis can reveal characteristics of airway lesions in chronic obstructive pulmonary disease (COPD) and bronchial asthma, and the contribution of dysanapsis to obstructive diseases. Chest CT is also employed to measure pulmonary blood vessels, interstitial lung abnormalities, and mediastinal and chest wall components including skeletal muscle and bone. Dynamic CT can visualize lung deformation in respective portions. Pulmonary MRI has been developed for the estimation of lung ventilation and perfusion, mainly using hyperpolarized Xe. Oxygen-enhanced and proton-based MRI, without a polarizer, has potential clinical applications. Dynamic chest radiography is gaining traction in Japan for ventilation and perfusion analysis. Single photon emission CT can be used to assess ventilation-perfusion (V˙/Q˙) mismatch in pulmonary vascular diseases and COPD. PET/CT V˙/Q˙ imaging has also been demonstrated using "Galligas". Both ultrasound and EIT can detect pulmonary edema caused by acute respiratory distress syndrome. Familiarity with these functional imaging techniques will enable clinicians to utilize these systems in clinical practice.
Topics: Humans; Positron Emission Tomography Computed Tomography; Lung; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Tomography, X-Ray Computed; Magnetic Resonance Imaging
PubMed: 37948969
DOI: 10.1016/j.resinv.2023.09.004 -
JACC. Cardiovascular Imaging Nov 2023Quantification of pulmonary edema and congestion is important to guide diagnosis and risk stratification, and to objectively evaluate new therapies in heart failure.... (Review)
Review
Quantification of pulmonary edema and congestion is important to guide diagnosis and risk stratification, and to objectively evaluate new therapies in heart failure. Herein, we review the validation, diagnostic performance, and clinical utility of noninvasive imaging modalities in this setting, including chest x-ray, lung ultrasound (LUS), computed tomography (CT), nuclear medicine imaging methods (positron emission tomography [PET], single photon emission CT), and magnetic resonance imaging (MRI). LUS is a clinically useful bedside modality, and fully quantitative methods (CT, MRI, PET) are likely to be important contributors to a more accurate and precise evaluation of new heart failure therapies and for clinical use in conjunction with cardiac imaging. There are only a limited number of studies evaluating pulmonary congestion during stress. Taken together, noninvasive imaging of pulmonary congestion provides utility for both clinical and research assessment, and continued refinement of methodologic accuracy, validation, and workflow has the potential to increase broader clinical adoption.
Topics: Humans; Pulmonary Edema; Predictive Value of Tests; Lung; Ultrasonography; Heart Failure
PubMed: 37632500
DOI: 10.1016/j.jcmg.2023.06.023 -
Journal of the American College of... Jan 2024Endothelin receptor antagonist (ERA) and phosphodiesterase 5 inhibitor (PDE5i) combination therapy is recommended for low-/intermediate-risk pulmonary arterial... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Endothelin receptor antagonist (ERA) and phosphodiesterase 5 inhibitor (PDE5i) combination therapy is recommended for low-/intermediate-risk pulmonary arterial hypertension (PAH) patients. A fixed-dose combination of the ERA macitentan and PDE5i tadalafil (M/T FDC) in a once-daily, single tablet would simplify treatment.
OBJECTIVES
The multicenter, double-blind, adaptive phase 3 A DUE study investigated the efficacy and safety of M/T FDC vs macitentan 10 mg and vs tadalafil 40 mg monotherapies in PAH patients, including treatment-naïve and prior ERA or PDE5i monotherapy-treated patients.
METHODS
World Health Organization functional class II-III patients were randomized to M/T FDC, macitentan, or tadalafil depending on their PAH treatment (treatment-naïve, ERA, or PDE5i monotherapy) at baseline. The primary endpoint was change in pulmonary vascular resistance (PVR) at week 16.
RESULTS
In total, 187 patients were randomized to single-tablet M/T FDC (n = 108), macitentan (n = 35), or tadalafil (n = 44). PVR reduction with M/T FDC was significantly greater vs macitentan (29%; geometric mean ratio 0.71; 95% CL: 0.61-0.82; P < 0.0001) and vs tadalafil (28%; geometric mean ratio 0.72; 95% CL: 0.64-0.80; P < 0.0001). Three patients died in the M/T FDC arm (judged unrelated to treatment). Adverse events (AEs) leading to discontinuation, serious AEs, and those of special interest (anemia, hypotension, and edema) were more frequent with M/T FDC.
CONCLUSIONS
Macitentan and tadalafil FDC significantly improved PVR vs monotherapies in PAH patients, with a safety and tolerability profile consistent with the individual components. The A DUE study supports M/T FDC as a once-daily, single-tablet combination for initial therapy and escalation to double combination therapy in patients with PAH. (Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension [PAH]) [A DUE]; NCT03904693).
Topics: Humans; Pulmonary Arterial Hypertension; Tadalafil; Combined Modality Therapy; Phosphodiesterase 5 Inhibitors; Endothelin Receptor Antagonists; Tablets; Pyrimidines; Sulfonamides
PubMed: 38267108
DOI: 10.1016/j.jacc.2023.10.045