Thromboembolic Pulmonary Hypertension Research Articles

Management of heart failure with pulmonary hypertension

Heart failure (HF) and pulmonary hypertension (PH) coexist frequently and contribute to each other. Because PH often is an insidious disease, the cornerstone of management is the early identification and treatment of its underlying causes, such as left-sided heart disease, left to right shunts, and pulmonary disorders. A practical clinical classification has been proposed by the Third World Symposium on Pulmonary Arterial Hypertension for the purpose of diagnosis and treatment of PH. Thromboembolic pulmonary hypertension should always be considered. Recent studies using vasodilators such as prostacyclins and endothelin antagonists give new hope in the otherwise poor prognosis of idiopathic pulmonary arterial hypertension and its related conditions. Despite optimum medical management, transplantation (lung/heart-lung) remains the choice in severely symptomatic patients.

Multislice Computed Tomography for Pulmonary Embolism — A Technological Marvel

Rapid and accurate diagnosis of pulmonary embolism will improve survival and quality of life because treatment decreases mortality and the likelihood that thromboembolic pulmonary hypertension or t...

Normal Pulmonary Capillary Blood Volume in Patients With Chronic Infiltrative Lung Disease and High Pulmonary Artery Pressure

Pulmonary capillary blood volume (Qc), a component of diffusing capacity of the lung for carbon monoxide (Dlco), is increased in postcapillary pulmonary hypertension due to valve disease, but is decreased in primitive and thromboembolic pulmonary hypertension. This study was performed to evaluate which way pulmonary Qc is affected in patients with chronic infiltrative lung disease according to the value of systolic pulmonary artery pressure (SPAP). Twenty-four patients who were nonsmokers and had chronic infiltrative lung disease secondary to connective tissue disease (12 patients), asbestosis (1 patient), sarcoidosis (5 patients), or of unknown origin (6 patients), and 8 control subjects underwent pulmonary function tests and Doppler echocardiography. Total lung capacity, alveolar-arterial oxygen pressure difference, Dlco, and conductance of the alveolar-capillary membrane (Dm) did not differ between patients with low SPAP (LPAP) [ie, < 30 mm Hg] or high SPAP (HPAP). Patients with LPAP, but not HPAP, experienced significant decreases in pulmonary Qc, whatever the cause of the disease. There was a strong positive correlation between SPAP and Qc scaled by Dm to account for infiltrative disease severity (r = 0.68; p < 0.001). We thus conclude that pulmonary Qc is not decreased as expected in patients with chronic infiltrative lung disease and high pulmonary artery pressure. A high Qc/Dm ratio should encourage the physician to look for HPAP compatible with pulmonary hypertension, whatever the etiology of lung infiltrative disease.

Blue rubber bleb nevus syndrome and pulmonary hypertension: an unusual association

Introduction Blue rubber bleb nevus syndrome (BRBNS) is a rare congenital systemic angiodysplasia with multiple vascular malformations in the skin, gastrointestinal tract and, less often, in other internal organs and the brain. Case report A 36-year-old man with past history of BRBNS was admitted to our hospital for progressive dyspnea and fatigue. Primary pulmonary hypertension (PPH) was diagnosed. He then developed acute abdominal pain and dyspnea, dying in a few hours due to sudden cardiac arrest. Postmortem examination demonstrated angiomatous lesions located in the skin, small bowel, heart, lungs, liver and thyroid. The lesions were slightly raised, soft and compressible and microscopically consisted of dilated vascular channels lined by a flattened endothelium. The vascular wall was formed by several layers of smooth muscle cells, intermixed with abundant aggregates of elastic lamellae and thin collagen fibers. Luminal thrombi were a frequent finding. In the small bowel, we identified the presence of an abnormally large artery directly opening into a thin-walled venous channel. The most striking finding in the lungs was the presence of thrombi of varying age in the lumen of segmental and elastic arteries, as well as muscular arteries and arterioles. Severe medial hypertrophy of muscular arteries and muscolarization of arterioles were also present. Intimal proliferative lesions and plexiform lesions were never observed. Conclusion The pulmonary findings are consistent with recurrent thromboembolic events from shunts in the visceral lesions. To our knowledge, this is the first report of BRBNS with visceral arterovenous (AV) fistulae complicated by thromboembolic pulmonary hypertension (PH).

Pulmonary hypertension

Pulmonary hypertension, in its simplest sense, is elevation of the pulmonary artery pressure above normal. A multitude of diseases may increase the pulmonary artery pressure and result in right ventricular dysfunction. The treatments of pulmonary hypertension are as varied as its causes. The past decade has realized remarkable growth in knowledge of the mechanisms of pulmonary arterial hypertension and, concurrently, therapies for this once uniformly fatal disease. In addition to continuous intravenous epoprostenol, subcutaneous treprostinil and oral bosentan are now FDA approved for the treatment of pulmonary arterial hypertension. Other forms of pulmonary hypertension, such as pulmonary venous hypertension, pulmonary hypertension related to diseases of the respiratory system, and thromboembolic pulmonary hypertension will be discussed.

Acute and short-term haemodynamic effect of Sildenafil in pulmonary hypertension: Egyptian pilot study of seven patients

Pulmonary hypertension (PH) patients usually present with heart failure, limited exercise tolerance and limited life expectancy. Vasodilators might cause a deterioration in gas exchange. There have been isolated case reports where oral Sildenafil, a selective phosphodiestrase inhibitor (PDEI), has been used as an alternative to prostacyclin in primary PH with early success. Our aim was to assess acute and short-term effect of Sildenafil in patients with PH with different etiologies. Seven patients have been studied (four female, three male; mean age 49 ± 12 years). They included two patients with primary PH, two patients with Eisinmenger syndrome, two patients with thromboembolic PH and one patient with Bilharzial PH. Following clinical evaluation, all patients were subjected to Swan–Ganz catheterization and the mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and mixed venous oxygen saturation (mVO2) were invasively measured. Patients were also subjected to echocardiographic evaluation of the right ventricular diameter (RVD) in the short axis, of the left ventricular stroke volume (SV) and of the cardiac output (COP). Readings were recorded before, 3 days and 3 months after the start of Sildenafil. We used oral Sildenafil (25 mg) every 6 hours for all patients.

Prognoses of primary pulmonary hypertension and chronic majorvessel thromboembolic pulmonary hypertension determined from cumulative survival curves.

Primary pulmonary hypertension (PPH) has a grave prognosis, and chronic majorvessel thromboembolic pulmonary hypertension (TPH) also has a poor prognosis. The purpose of the study is to elucidate the inherent prognoses of two serious diseases. Thirty-two patients with PPH (aged 33+/-15 years, 1SD) and 48 patients with TPH (aged 50+/-14 years, 1SD) were used to determine survival curves using Kaplan and Meier's method from the baseline diagnostic catheterization. Definitive diagnosis was made by cardiac catheterization, ultrasonic echocardiography, ventilation-perfusion lung scanning, and pulmonary angiography. Mean pulmonary artery pressure (PAm) at the initial examination was 56+/-16 (mean+/-1SD) mmHg for patients with PPH and 50+/-13 mmHg for those with TPH, and did not differ significantly between the two groups. Although these two diseases exhibited equally elevated pulmonary arterial pressures, possibly indicative of a poor prognosis, the survival curves obtained from the prospective study for the two diseases were quite different (p<0.001 by generalized Wilcoxon test, p<0.01 by Log-rank test). Mean survival was calculated to be 3.6 years for PPH and 6.8 years for TPH. Patients with TPH had a longer survival than those with PPH, despite the fact that the age at diagnosis of PPH was younger by 17 years on average than that of TPH. The inherent prognoses of the two chronic pulmonary hypertensive diseases prior to the introduction of the recently developed new treatment options are shown and likely indicate that the pulmonary vascular lesions in PPH are consistently progressive, while those of TPH are not as progressive.

Treatment of pulmonary hypertension with the continuous infusion of a prostacyclin analogue, iloprost

ObjectiveTo compare prostacyclin with an analogue, iloprost, in treatment of severe pulmonary hypertension.PatientsEight patients with severe pulmonary hypertension: primary in five, thromboembolic pulmonary hypertension in three.MethodsAll patients underwent right heart...

Plasma Brain Natriuretic Peptide Levels Increase in Proportion to the Extent of Right Ventricular Dysfunction in Pulmonary Hypertension

Objectives. This study sought to investigate the influence of right ventricular (RV) hemodynamic variables and function on the secretion of brain natriuretic peptide (BNP) in patients with isolated RV overload.Background. Plasma BNP is known to increase in proportion to the degree of left ventricular (LV) overload. However, whether BNP secretion is also regulated in the presence of RV overload remains unknown.Methods. Plasma BNP and atrial natriuretic peptide (ANP) levels in the pulmonary artery were measured in 44 patients with RV overload: 18 with RV volume overload (RVVO) due to atrial septal defect and 26 with RV pressure overload (RVPO) due to primary or thromboembolic pulmonary hypertension. Right heart catheterization was performed in all patients. RV and LV ejection fraction, myocardial mass and volume of the four chambers were determined by using electron beam computed tomography.Results. Although both plasma BNP and ANP levels were significantly elevated in patients with RV overload compared with values in control subjects, plasma BNP and the BNP/ANP ratio were significantly higher in patients with RVPO than with RVVO (BNP 294 ± 72 vs. 48 ± 14 pg/ml; BNP/ANP 1.6 ± 0.2 vs. 0.8 ± 0.2, both p < 0.05). Plasma BNP correlated positively with mean pulmonary artery pressure (r = 0.73), total pulmonary resistance (r = 0.79), mean right atrial pressure (r = 0.79), RV end-diastolic pressure (r = 0.76) and RV myocardial mass (r = 0.71); it correlated negatively with cardiac output (r = −0.33) and RV ejection fraction (r = −0.71). Plasma BNP significantly decreased from 315 ± 120 to 144 ± 54 pg/ml with long-term vasodilator therapy (total pulmonary resistance decreased from 23 ± 4 to 15 ± 3 Wood U).Conclusions. Plasma BNP increases in proportion to the extent of RV dysfunction in pulmonary hypertension.

Nitric oxide inhalation inhibits platelet aggregation and platelet-mediated pulmonary thrombosis in rats.

Endothelium-derived nitric oxide (NO) inhibits in vitro platelet aggregation via a cGMP-dependent mechanism. The effect of inhaled NO on platelet-mediated pulmonary thrombosis following intravenous thrombotic challenge with collagen was examined in rats and compared with the effect of G4120, a cyclic Arg-Gly-Asp-containing synthetic pentapeptide that binds to the platelet glycoprotein IIb/IIIa receptor. Intraplatelet cGMP dose-dependently increased from 39 +/- 6 fmol/10(8) platelets in control to 46 +/- 6, 68 +/- 13, and 81 +/- 13 fmol/10(8) platelets after inhalation with 20, 40, and 80 ppm NO, respectively (P < .05 for 40 and 80 ppm). Ex vivo platelet aggregation of platelet-rich plasma induced by 1 microgram/mL collagen was reduced from 75 +/- 4% in control rats to 22 +/- 10% and 20 +/- 7% in rats ventilated with 40 and 80 ppm NO, respectively, and to 30 +/- 9% in G4120-treated rats (each P < .05 versus control). Circulating platelet counts 3 minutes after collagen injection were significantly higher in the inhaled NO and G4120 groups compared with control rats (250,000 +/- 18,000 and 223,000 +/- 10,000/microL versus 160,000 +/- 18,000/microL, each P < .05). The rise in pulmonary arterial pressure after collagen injection was significantly reduced in NO- and G4120-treated rats (26 +/- 1 and 27 +/- 1 versus 32 +/- 1 mm Hg in control rats, each P < .05). The number of pulmonary resistance vessels containing platelet thrombi was significantly smaller after inhaled NO and G4120 treatment compared with control (56 +/- 3% and 50 +/- 3% versus 68 +/- 3%, respectively; P < .05). Thus, NO inhalation reduces in vivo activation of circulating platelets and platelet-rich thrombosis in thromboembolic pulmonary hypertension. Inhalation of NO may be useful in cardiovascular diseases associated with platelet activation.

Thromboembolic and Primary Pulmonary Hypertension

Thromboembolic and Primary Pulmonary Hypertension

The management of pulmonary hypertension secondary to chronic thromboembolic disease

I N THE UNITED States it is estimated that 600,000 people experience pulmonary embolus each year. 1-3 Approximately 50,000 of these patients die, but in the vast majority, the pulmonary emboli resolve rapidly and substantially, resulting in no residual symptoms or hemodynamic sequelae. However, in a small minority of patients with extensive embolization, the emboli fail to resolve and undergo fibrovascular organization, causing chronic obstruction to pulmonary arterial blood flow. This can subsequently result in a condition known as chronic pulmonary thromboembolic hypertension (CPTH). The diagnosis, pathophysiology, and treatment of acute pulmonary embolism (PE) are discussed elsewhere in this symposium. The concept of chronic pulmonary thromboembolism (CPT) has been known to exist for many years, having been first suspected by Hart (1916) and Moller (1920). 4 An association of CPT with progressive respiratory insufficiency was made in 1928 by Ljungdahl. 5 However, for many years, the condition was regarded as an autopsy curiosity, and antemortem diagnosis was unusual. The small number of patients who were diagnosed with this condition received only medical management for the secondary pulmonary hypertension, including oxygen, vasodilator, fibrinolytic, and anticoagulant therapy. Long-term prognosis was very poor. This changed as advances in cardiac surgical techniques led to the ability to perform thromboendarterectomy which offered a surgical cure. With a potential cure available, there was an increased impetus toward making an early diagnosis. This was facilitated by advances in diagnostic techniques and an increased awareness of the characteristic clinical presentation. The diagnosis of CPT involving the major pulmonary vessels is now made more often during a patient's lifetime, and it has become apparent that CPTH is more common than was once previously thought. Although the exact incidence of pulmonary hypertension secondary to unresolved emboli is not known, Jamieson et al 6 have estimated that this sequel may develop in 0.1% to 0.2% of survivors of an acute embolic event, or in 540 to 1080 patients per year. The disorder is often amenable to surgical therapy, with successful thromboendarterectomy offering the best chance of long-term survival. 6-8 To date, there have been over 400 cases of pulmonary thromboendarterectomy reported, with the vast majority coming from the University of California at San Diego (UCSD) Medical Center (San Diego, California).

Primary pulmonary hypertension and thromboembolicpulmonary hypertension—similarities and differences

In a retrospective study of 36 patients with primary pulmonary hypertension (PPH) and 16 patients with chronic large vessel thromboembolic pulmonary hypertension (TPH) the diagnostic value of clinical features, chest radiographs, electrocardiographs, radionuclide lung scanning and cardiac catheterization was assessed. PPH patients were younger, had higher prevalence of Raynaud's phenomenon, right axis deviation, right ventricular hypertrophy on electrocardiograph and higher pulmonary artery pressures than TPH patients, but these features were not diagnostic. Although pulmonary angiography is considered by some to be necessary in distinguishing these two conditions, radionuclide lung scanning proved a safe and effective noninvasive method for this purpose.

Tension pneumopericardium as a complication of single-lung transplantation

Tension pneumopericardium is distinctly uncommon in the adult population. We present a case of tension pneumopericardium as a complication of lung transplantation in a 54-year-old woman with thromboembolic pulmonary hypertension who underwent single-lung transplantation.

The “Primary” Antiphospholipid Syndrome

The antiphospholipid syndrome--the association of venous and/or arterial thromboses, often accompanied by thrombocytopenia in the presence of the antiphospholipid antibodies ("lupus anticoagulant" antibodies to cardiolipin)--is seen mainly in patients with systemic lupus erythematosus (SLE) and the closely related "lupus-like" disease, i.e., lupus patients not conforming to the 1982 revised American Rheumatism Association classification for SLE. It is also seen in a group of patients who do not manifest any of the major clinical or serologic features of SLE, the majority of whom do not appear to progress to classical lupus. A multicenter study of 70 of these patients is documented and their major clinical and serologic characteristics examined: They have been characterized as suffering from a "primary" antiphospholipid syndrome and present typically with a history of deep vein thromboses, often accompanied by pulmonary thromboembolism, which in a few is complicated by thromboembolic pulmonary hypertension, arterial occlusions (most commonly strokes), or fetal loss. The events are often recurrent and may be accompanied by hemocytopenias (thrombocytopenia and less frequently Coombs positivity and/or hemolytic anemia). They are often antinuclear antibody-negative and are always negative for antibodies to dsDNA and to ENA, typical serologic features of SLE. There may be a family history of SLE or a familial clotting tendency in a minority. The group of patients presented appears to be closely related, but distinctly separate from SLE.

The treatment of venous thromboembolism

Venous thromboembolism is usually treated with heparin followed by oral anticoagulants for approximately 3 months. The optimal length of heparin therapy is uncertain. There is now good evidence that treatment failures are associated with inadequate heparin effects. Heparin can be administered with similar safety and effectiveness by either intravenous infusion or 2 hourly subcutaneous injection. Oral anticoagulant therapy is effective and safe if given in a dose which prolongs the prothrombin time to an international normalized ratio of 2.0 to 2.5. Thrombolytic therapy is indicated in patients with major pulmonary embolism and in selected patients with recent acute venous thrombosis. Vena caval interruption is usually confined to patients who have contraindications to anticoagulant therapy. Surgical removal of thromboembolic obstruction should be considered in selected patients with thromboembolic pulmonary hypertension.

Treatment of venous thromboembolism

Venous thromboembolism is usually treated with heparin followed by oral anticoagulants for approximately 3 months. The optimal length of heparin therapy is uncertain. There is now good evidence that treatment failures are associated with inadequate heparin effects. Heparin can be administered with similar safety and effectiveness by either intravenous infusion or 2 hourly subcutaneous injection. Oral anticoagulant therapy is effective and safe if given in a dose which prolongs the prothrombin time to an international normalized ratio of 2.0 to 2.5. Thrombolytic therapy is indicated in patients with major pulmonary embolism and in selected patients with recent acute venous thrombosis. Vena caval interruption is usually confined to patients who have contraindications to anticoagulant therapy. Surgical removal of thromboembolic obstruction should be considered in selected patients with thromboembolic pulmonary hypertension.

Perfusion lung scanning: differentiation of primary from thromboembolic pulmonary hypertension.

Of eight patients with pulmonary arterial hypertension, final diagnosis established by autopsy or angiography, four had primary hypertension and four hypertension from thromboembolism. The perfusion lung scan was distinctly different in the two groups. The lung scan in primary pulmonary hypertension was associated with nonsegmental, patchy defects of perfusion, while in thromboembolic hypertensives it was characterized by segmental and/or lobar defects of perfusion with or without subsegmental defects. The perfusion lung scan is a valuable, noninvasive study in the evaluation of the patient with pulmonary hypertension of undetermined cause and in the exclusion of occult large-vessel pulmonary thromboembolism.

Primary pulmonary hypertension: natural history and the importance of thrombosis.

A long-term retrospective follow-up study was made of 120 patients (33 male, 87 female patients) with primary pulmonary hypertension--diagnosed by strict clinical and hemodynamic criteria--to obtain a better understanding of the natural history and possible pathogenetic mechanisms of the disease. The mean age at diagnosis was 34 (3 to 64) years, but only 24 patients (21%) remained alive 5 years later. Lung tissue obtained at autopsy from 56 patients revealed two major pathologic types: thromboembolic pulmonary hypertension in 32 patients (57%) and plexogenic pulmonary arteriopathy in 18 (32%). Thus, in more than half the patients undergoing autopsy the major histologic feature was thrombi without any evidence of plexiform lesions. The two groups were similar with respect to their clinical and hemodynamic features and short survival. Of the variables tested for prognostic importance by stepwise multivariate analysis, only two were significant: pulmonary arterial oxygen saturation (p less than .00001) and anticoagulant therapy (p = .01). Anticoagulant therapy is recommended for patients with primary pulmonary hypertension.

Clinical investigations: Differentiation of Patients with Primary and Thromboembolic Pulmonary Hypertension

Twenty-five consecutive patients with obliterative pulmonary hypertension were studied. Primary pulmonary hypertension (17 patients) or chronic thromboembolic pulmonary hypertension (eight patients) was diagnosed by pulmonary angiography or autopsy. Clinical symptoms, physical findings, chest roentgenograms, electrocardiograms, and pulmonary function studies did not differentiate the patients with primary pulmonary hypertension (PPH) from those with chronic thromboembolic pulmonary hypertension (TPH). All eight patients with TPH had a lung scan interpreted as high probability for pulmonary emboli while all 17 patients with PPH had a lung scan interpreted as normal or low probability for emboli. While there was close clinical similarity between patients with PPH and TPH, the presence of a normal or low probability lung scan excluded the diagnosis of TPH.