Updated clinical classification of pulmonary hypertension.

A national registry was begun in 1981 to collect data from 32 centers on patients diagnosed by uniform criteria as having primary pulmonary hypertension. Entered into the registry were 187 patients with a mean age (+/- SD) of 36 +/- 15 years (range, 1 to 81), and a female-to-male ratio of 1.7:1 overall. The mean interval from onset of symptoms to diagnosis was 2 years. The most frequent presenting symptoms included dyspnea (60%), fatigue (19%), and syncope (or near syncope) (13%). Raynaud phenomenon was present in 10% (95% of whom were female) and a positive antinuclear antibody test, in 29% (69% female). Pulmonary function studies showed mild restriction (forced vital capacity [FVC], 82% of predicted) with a reduced diffusing capacity for carbon monoxide (DLCO), and hypoxemia with hypocapnia. The mean (+/- SD) right atrial pressure was 9.7 +/- 6 mm Hg; mean pulmonary artery pressure, 60 +/- 18 mm Hg; cardiac index, 2.3 +/- 0.9 L/min X m2; and pulmonary vascular resistance index, 26 +/- 14 mm Hg/L/min X m2 for the group. Although no deaths or sustained morbid events occurred during the diagnostic evaluation of the patients, the typically long interval from initial symptoms to diagnosis emphasizes the need to develop strategies to make the diagnosis earlier.

Primary pulmonary hypertension: a national prospective study

Background. Constriction of small pulmonary arteries and arterioles and focal vascular injury are features of pulmonary hypertension. Because thromboxane A2 is both a vasoconstrictor and a potent stimulus for platelet aggregation, it may be an important mediator of pulmonary hypertension. Its effects are antagonized by prostacyclin, which is released by vascular endothelial cells. We tested the hypothesis that there may be an imbalance between the release of thromboxane A2 and prostacyclin in pulmonary hypertension, reflecting platelet activation and an abnormal response of the pulmonary vascular endothelium. Methods. We used radioimmunoassays to measure the 24-hour urinary excretion of two stable metabolites of thromboxane A2 and a metabolite of prostacyclin in 20 patients with primary pulmonary hypertension, 14 with secondary pulmonary hypertension, 9 with severe chronic obstructive pulmonary disease (COPD) but no clinical evidence of pulmonary hypertension, and 23 normal controls. Results. The...

https://www.nejm.org/doi/pdf/10.1056/NEJM199207093270202

An Imbalance between the Excretion of Thromboxane and Prostacyclin Metabolites in Pulmonary Hypertension

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role, essentially in the screening proposing criteria for estimating the presence of PH mainly based on tricuspid regurgitation peak velocity and systolic artery pressure (sPAP). The therapy of PAH consists of non-specific drugs including oral anticoagulation and diuretics as well as PAH specific therapy. Diuretics are one of the most important treatment in the setting of PH because right heart failure leads to fluid retention, hepatic congestion, ascites and peripheral edema. Current recommendations propose oral anticoagulation aiming for targeting an International Normalized Ratio (INR) between 1.5-2.5. Target INR for patients displaying chronic thromboembolic PH is between 2–3. Better understanding in pathophysiological mechanisms of PH over the past quarter of a century has led to the development of medical therapeutics, even though no cure for PAH exists. Several specific therapeutic agents were developed for the medical management of PAH including prostanoids (epoprostenol, trepoprostenil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan) and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). This review discusses the current state of art regarding to epidemiologic aspects of PH, diagnostic approaches and the current classification of PH. In addition, currently available specific PAH therapy is discussed as well as future treatments.

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Pulmonary arterial hypertension

https://journal.chestnet.org/article/S0012-3692(15)37531-0/pdf

Medical Therapy For Pulmonary Arterial Hypertension: ACCP Evidence-Based Clinical Practice Guidelines

Morphologic and morphometric studies were carried out on pulmonary vessels in lung tissue from 156 patients, for whom a diagnosis of primary pulmonary hypertension had been made. This material was collected from 51 medical centers. Chronic pulmonary thromboembolism can be recognized by organizing thrombi, patchy intimal fibrosis, and intra-arterial septa. The media is only slightly thicker than normal; in 31 of the 156 cases the vascular lesions corresponded to this pattern. Other conditions such as chronic pulmonary venous hypertension, pulmonary veno-occlusive disease, sarcoidosis, chronic bronchitis, and pulmonary schistosomiasis could also be classified from the morphologic criteria. The largest group comprised 110 cases showing medial hypertrophy, laminar intimal fibrosis, and often fibrinoid necrosis, arteritis, and plexiform lesions. These alterations suggest that they were initiated by vasoconstriction. In children the sex ratio is equal; in adults there are almost four females to one male. In the...

Primary Pulmonary Hypertension

Reversibility of plexogenic pulmonary arteriopathy following banding of the pulmonary artery

The histopathology of the lungs is described in 13 patients with pulmonary veno-occlusive disease. The patients were mostly children or young adults and there was no sex preference as is seen in primary pulmonary hypertension.

The pathology of pulmonary veno-occlusive disease

Specimens of the lung taken for biopsy at operation on 80 patients with complete transposition of the great vessels were histologically studied in correlation with the clinical and hemodynamic data in these cases. In a group of 31 cases of intact ventricular septum and patent foramen ovale, the media of the pulmonary arteries was generally thinner than normal, and to a lesser extent that of the pulmonary veins was also, while the lumina of the vessels were wide. This was especially observed in cases in which the hematocrit was high. Possibly, this phenomenon is based on dilatation of the arteries and is related to the increased total blood volume. Intimal fibrosis, when observed, was suggestive of organized thrombi. In a group of 28 patients with ventricular septal defect and equal pressures in the left and right ventricles, there was generally marked medial hypertrophy and concentric intimal proliferation in the pulmonary arteries. In cases of pulmonic stenosis, on the other hand, the media of the pulmon...

The Pulmonary Vasculature in Complete Transposition of the Great Vessels, Judged from Lung Biopsies

Of a total of over 1,000 lung biopsies, carried out over a 3½-year period on patients, the great majority of whom were operated on for various acquired or congenital cardiac diseases, 86 were on patients operated upon for atrial septal defect, 99 on patients with a ventricular septal defect, and 82 on patients with patent ductus arteriosus. The morphological data, particularly with regard to the lung vessels, were correlated with hemodynamic findings in these patients. In atrial septal defect the pulmonary vessels did not differ significantly from those in normal controls of the same ages. Notably there were no differences between patients with relatively low pulmonary arterial flow and those with high flow. In patent ductus arteriosus the only difference was an increase in intimal fibrosis of the pulmonary arteries as compared to normals. In ventricular septal defect, on the other hand, there was an increase in thickness of both media and intima and also in incidence of hemosiderosis. These changes did s...

Noeke Wagenvoort

Papers

Primary Pulmonary Hypertension

Reversibility of plexogenic pulmonary arteriopathy following banding of the pulmonary artery

The pathology of pulmonary veno-occlusive disease

The Pulmonary Vasculature in Complete Transposition of the Great Vessels, Judged from Lung Biopsies

Effect of flow and pressure on pulmonary vessels. A semiquantitative study based on lung biopsies.