Haemodynamic definitions and updated clinical classification of pulmonary hypertension.

Since the 1st World Symposium on Pulmonary Hypertension (WSPH) in 1973, pulmonary hypertension (PH) has been arbitrarily defined as mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest, measured by right heart catheterisation. Recent data from normal subjects has shown that normal mPAP was 14.0±3.3 mmHg. Two standard deviations above this mean value would suggest mPAP >20 mmHg as above the upper limit of normal (above the 97.5th percentile). This definition is no longer arbitrary, but based on a scientific approach. However, this abnormal elevation of mPAP is not sufficient to define pulmonary vascular disease as it can be due to an increase in cardiac output or pulmonary arterial wedge pressure. Thus, this 6th WSPH Task Force proposes to include pulmonary vascular resistance ≥3 Wood Units in the definition of all forms of pre-capillary PH associated with mPAP >20 mmHg. Prospective trials are required to determine whether this PH population might benefit from specific management.Regarding clinical classification, the main Task Force changes were the inclusion in group 1 of a subgroup "pulmonary arterial hypertension (PAH) long-term responders to calcium channel blockers", due to the specific prognostic and management of these patients, and a subgroup "PAH with overt features of venous/capillaries (pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis) involvement", due to evidence suggesting a continuum between arterial, capillary and vein involvement in PAH

Transmission of ultrasonic contrast through the lungs

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Non-invasive assessment of pulmonary vascular resistance in pulmonary hypertension: Current knowledge and future direction

Pulmonary Hypertension (PHT) is relatively common, dangerous and under-recognised. Pulmonary hypertension is not a diagnosis in itself; it is caused by a number of differing diseases each with different treatments and prognoses. Therefore, timely and accurate recognition of the underlying cause for PHT is essential for appropriate management. This is especially true for patients with Pulmonary Arterial Hypertension (PAH) in the current era of disease-specific drug therapy. Measurement of Pulmonary Vascular Resistance (PVR) helps separate pre-capillary from post-capillary PHT, and is measured with right heart catheterisation (RHC). Echocardiography has been used to derive a number of non-invasive surrogates for PVR, with varying accuracy. Ultimately, the goal of non-invasive assessment of PVR is to separate PHT due to left heart disease from PHT due to increased PVR, to help streamline investigation and subsequent treatment. In this review, we summarise the physiology and pathophysiology of pulmonary blood flow, the various causes of pulmonary hypertension, and non-invasive surrogates for PVR

Endothelial dysfunction and lung capillary injury in cardiovascular diseases

Cardiac dysfunction of both systolic and diastolic origins leads to increased left atrial pressure, lung capillary injury and increased resistance to gas transfer. Acutely, pressure-induced trauma disrupts the endothelial and alveolar anatomical configuration and definitively causes an impairment of cellular pathways involved in fluid-flux regulation and gas exchange efficiency, a process well identified as stress failure of the alveolar-capillary membrane. In chronic heart failure (HF), additional stimuli other than pressure may trigger the true remodeling process of capillaries and small arteries characterized by endothelial dysfunction, proliferation of myofibroblasts, fibrosis and extracellular matrix deposition. In parallel there is a loss of alveolar gas diffusion properties due to the increased path from air to blood (thickening of extracellular matrix) and loss of fine molecular mechanism involved in fluid reabsorption and clearance. Deleterious changes in gas transfer not only reflect the underlying lung tissue damage but also portend independent prognostic information and may play a role in the pathogenesis of exercise limitation and ventilatory abnormalities observed in these patients. Few currently approved treatments for chronic HF have the potential to positively affect structural remodeling of the lung capillary network; angiotensin-converting enzyme inhibitors are one of the few currently established options. Recently, more attention has been paid to novel therapies specifically targeting the nitric oxide pathway as a suitable target to improve endothelial function and permeability as well as alveolar gas exchange properties

Insights into the pulmonary vascular complications of heart failure with preserved ejection fraction

Pulmonary hypertension in the setting of heart failure with preserved ejection fraction (PH-HFpEF) is a growing public health problem that is increasing in prevalence. While PH-HFpEF is defined by a high mean pulmonary artery pressure, high left ventricular end-diastolic pressure and a normal ejection fraction, some HFpEF patients develop PH in the presence of pulmonary vascular remodelling with a high transpulmonary pressure gradient or pulmonary vascular resistance. Ageing, increased left atrial pressure and stiffness, mitral regurgitation, as well as features of metabolic syndrome, which include obesity, diabetes and hypertension, are recognized as risk factors for PH-HFpEF. Qualitative studies have documented that patients with PH-HFpEF develop more severe symptoms than those with HFpEF and are associated with more significant exercise intolerance, frequent hospitalizations, right heart failure and reduced survival. Currently, there are no effective therapies for PH-HFpEF, although a number of candidate drugs are being evaluated, including soluble guanylate cyclase stimulators, phosphodiesterase type 5 inhibitors, sodium nitrite and endothelin receptor antagonists. In this review we attempt to provide an updated overview of recent findings pertaining to the pulmonary vascular complications in HFpEF in terms of clinical definitions, epidemiology and pathophysiology. Mechanisms leading to pulmonary vascular remodelling in HFpEF, a summary of pre-clinical models of HFpEF and PH-HFpEF, and new candidate therapeutic strategies for the treatment of PH-HFpEF are summarized

Peripheral Microangiopathy Changes in Pulmonary Arterial Hypertension Related to Systemic Sclerosis: Data From a Multicenter Observational Study

Systemic sclerosis (SSc) is a connective tissue disease characterized by immune-system alterations, fibrosis involving the skin and internal organs and diffuse microangiopathy. Pulmonary arterial hypertension (PAH) is a severe complication of SSc affecting about 10-15% of the patients and it is a leading cause of mortality. Due to the devastating nature of SSc-PAH, there is a clear need to systematically adopt appropriate screening programs. Nail fold videocapillaroscopy (NVC) studies have shown a more severe peripheral microvascular dysfunction in SSc patients with PAH suggesting that abnormalities in peripheral microcirculation may correlate with pulmonary microangiopathy. This is a cross-sectional study involving four tertiary University Rheumatology Units in the Center-North of Italy. Seventy patients, 35 adults with SSc and PAH confirmed by RHC (F/M 34/1; median age 65.2 ± 8.9 SD yrs), and 35 SSc patients without PAH were enrolled (F/M 3471; median age 63.3 ± 10.3 SD yrs). Clinical, laboratoristic and instrumental data were collected and NVC was performed in all patient. Specific NVC parameters were evaluated and a semi-quantitative rating scale was adopted to score these changes. Finally, patients were distributed into the suitable NVC pattern belonging to the scleroderma pattern. Our aim was to compare the peripheral microangiopathy changes in SSc patients with and without PAH, and to investigate the relationship between NVC findings and the main hemodynamic parameters of pulmonary vasculopathy. Patients with SSc-PAH+ showed a significant higher frequency of interstitial lung disease (ILD). No significant differences regarding clinical and laboratoristic parameters were observed. NVC abnormalities, avascular areas were more frequent in SSc patients with PAH, respect to those without (p = 0.03), and capillary density was significantly lower when considering grade 3 (p = 0.02). A higher NVC semiquantitative mean was found in SSc-PAH+ patients and a greater rate of the "late" pattern was detected in SSc-PAH+ subjects in respect to PAH- (57.1% vs. 25.7%) (p = 0.03). A significant correlations between pulmonary pressure values (sPAP by TTE and mPAP by RHC) and the capillary density (Spearman's rho 0.35, p = 0.04 for both). Our findings provide additional evidence to the literature data, confirming that a higher degree of peripheral nailfold microangiopathy is more common in SSc-PAH patients, and further strengthening the concept that NVC changes may run parallel with similar abnormalities inside pulmonary microcirculation

On the Reaction of the Mammalian Lung to Trauma

1. Mouse and rat lungs punctured by cold sterile needles show local atelectasis with a transient and reversible swelling of the alveolar lining cells. No evidence of the injury can be seen, by naked-eye or microscopically, a week later. 2. Burns of lung produced by heated needles are organised from a boundary or demarcation zone of lung tissue and converted to functioning lung by the ingrowth of bronchial branches from pre-existing bronchi. 3. Excision of wedges of lung tissue in cats is followed by local scarring and the ultimate reformation of lung tissue in the scar. This process occurs through bronchial proliferation together with alveolar formation in the margins of the scar, processes which depend primarily on the active motility of the lung