HIPERTENSAO PULMONAR PDF

Diagnostic evaluation and classification of pulmonary hypertension. Knowledge regarding the pathophysiology of pulmonary hypertension has grown in recent years, allowing the identification of well-defined risk factors and specific clinical conditions that may lead to development of the disease. In addition, better systems of classifying pulmonary hypertension, based on systematic investigation, have also been developed, thereby facilitating the design of more efficacious therapeutic approaches. Currently, there is an ongoing search to identify clinical situations in which pulmonary hypertension can be diagnosed early, which would allow therapeutic measures to be initiated in the early stages, thereby avoiding its progression.

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Back to Summary. J Bras Pneumol. Therefore, an update of certain aspects of PH diagnosis and treatment is necessary. In this article, we review what has changed in thediagnosis and treatment of PH in recent years. Various tests, which present a broad spectrum of sensitivity and specificity, can be used for the initial evaluation of patients suspected of having PH. Nevertheless, due to their broad availability and low cost, they can be employed in PH screening programs.

Chest X-rays also play an important role in the diagnosis of other diseases, such as those that impair the lung parenchyma and can cause dyspnea Figure 2a. Chest CT Computed angiotomography of the chest plays a significant role in the diagnostic evaluation of PH.

The diameter of the PA trunk is significantly larger in patients with PH than in normal individuals and correlates well with PA pressure measurements. However, echocardiography is a test that has significant limitations, such as the fact that it is highly examiner-dependent and that a significant proportion of patients present with a poor acoustic window. Although some studies have shown a significant correlation between echocardiography findings and RHC values, one group of authors recently reported that the RAP and PASP values estimated by echocardiography differ significantly from those measured by RHC.

It was also shown that cardiac output Qt as measured by echocardiography is not useful and that echocardiography typically overestimates pressures. In addition to PASP estimates, dilation and right ventricular dysfunction should be considered to constitute indirect signs of PH. Despite its limitations, echocardiography continues to be the principal screening tool for PH because it is a noninvasive and readily available test, as well as being useful in identifying left heart malformations and diseases.

Because right ventricular function plays a significant role in the prognosis of patients with PH, it is necessary to measure right ventricular function appropriately.

The characteristics of the right ventricle RV are quite different from those of the left ventricle LV. Unlike the LV, which has thick, cone-shaped walls, the RV has thin, semilunar or crescent-shaped walls, and the myocardial mass of the RV is significantly lower and more trabecular than is that of the LV.

The contraction pattern is also different; in the RV, longitudinal contraction of the myocardial fibers predominates, whereas, in the LV, spiral movement predominates. Therefore, it does not seem sufficient or appropriate to evaluate right ventricular function with the same tools used to evaluate left ventricular function. New techniques for a better estimation of right ventricular function have been studied. The determination of tricuspid annular plane systolic excursion TAPSE has been shown to be a useful tool.

This technique calculates the degree to which the pulmonary valve ring is shifted, in relation to the right ventricular apex during systole. The authors found that a TAPSE Other techniques for the evaluation of right ventricular function, such as the comparison between the right ventricular area at systole and that at diastole-designated right ventricular fractional area change-and the comparison between the right ventricular end-diastolic area and the left ventricular end-diastolic area, have been studied and might prove useful in patients with PH.

Magnetic resonance imaging Advances in the techniques for acquiring and processing magnetic resonance imaging of the heart have allowed three-dimensional evaluation of the RV and detailed tomographic visualization of its morphology. Cardiac magnetic resonance imaging CMRI creates a clear distinction between the myocardium and intracavitary blood, presenting well-defined myocardial and endocardial borders. Other studies have shown ventricular septal bowing, together with a reduction in the LV volume in early diastole, revealing impaired left ventricular function associated with right ventricular dysfunction.

In patients with PH, PA compliance values are significantly lower. Two studies used CMRI before treatment initiation and months after treatment initiation. In one of the studies, the patients received epoprostenol, and in the other, they received bosentan. In another study, CMRI was used before and after pulmonary thromboendarterectomy. Diagnosis If a patient suspected of having PH has been screened and signs consistent with increased pressure levels in the pulmonary circulation have been detected in the initial tests, the need to perform RHC to confirm the diagnosis of PH should be evaluated, because a definitive diagnosis of PH can only be established by invasive pressure measurements Figure 3.

Since the last Brazilian consensus, there have been changes in the definition of PH. The group of specialists who reviewed the data that had been published up until the time of the meeting concluded that the data collected during exercise were extremely heterogeneous regarding the load used, the duration of the exercise, and the position of the patient during exercise, factors that might influence PA pressure measurements.

Due to this lack of standardization, a decision was made to remove exercise-induced PH from the definition of PH. This does not mean that exercise-induced PH does not exist; it only means that the data collected to date are not sufficiently robust to provide a definition of exercise-induced PH values. This underscores the importance of conducting new studies in this field in order to provide an appropriate definition of exercise-induced PH. When individuals from different age brackets were compared, there was only a slight, less than significant, variation in the MPAP at rest.

The acute test with a vasodilator should be performed during the initial hemodynamic evaluation in patients with precapillary PH. The test can be performed with NO, prostacyclin, or adenosine. A positive acute test result predicts the clinical and hemodynamic response to calcium channel blockers.

It should be highlighted that idiopathic PH is a differential diagnosis, and it is fundamental to follow an appropriate flowchart to facilitate the diagnostic investigation Figure 4.

Classification There have been various changes in the clinical classification of PH. Although the basic structure of the Venice classification-five principal groups and their respective subgroups-was maintained, pathologies have been moved from one group or subgroup to another. In addition, some new groups or subgroups have been created, whereas others have been eliminated. These changes are described below. The former and current classifications are compared in Chart 2.

There have been no changes in subgroup 1. Subgroup 1. This change resulted from recent studies demonstrating the role of certain drugs in inducing PAH without changing its clinical course, as demonstrated for fenfluramine. The subgroup formerly known as "collagen vascular disease" is now designated "connective tissue diseases". The subgroup formerly known as "congenital systemic-pulmonary shunts" is now designated "congenital heart diseases".

The subgroup designated "other" was eliminated from the current classification, and two new subgroups were created: subgroup 1. Patients with schistosomiasis used to be allocated to the group of embolic diseases-group 4, in the previous classification-because it was believed that the mechanism that led to PH in this pathology was associated with the mechanic obstruction of pulmonary vessels by eggs of the parasite.

Anatomic pathology studies have demonstrated that the pulmonary involvement in schistosomiasis is similar to that found in IPAH, being accompanied by the development of plexiform lesions and hypertrophy of the tunica intima and tunica media, regardless of the obstruction by the parasite.

Studies conducted in Brazil have also contributed to this change in the classification. One of these studies demonstrated that the clinical characteristics of patients with schistosomiasis and PH are similar to those of patients with IPAH.

Therefore, this change in the classification has a significant impact on Brazil and on all countries in which schistosomiasis is endemic. Concluding the changes in group 1, subgroup 1' read "one prime" was created.

This subgroup comprises pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis, because the histopathological features of these two entities have been shown to overlap. It is currently believed that they can represent different phases of the evolution of the same pathology. A decision was made to maintain the two entities in the group related to primarily arterial involvement, due to their degree of clinical response to the treatment with PAH-specific drugs, among other reasons.

Group 2 is designated "[PH] owing to left heart disease", in order to highlight the causal relationship between cardiac involvement and the development of PH, because this is potentially the most common cause of PH. This group was subdivided into three subgroups: 2. In group 3, the term "associated with" was changed to "owing to", reinforcing the causal importance of pulmonary involvement.

The last subgroup comprises chronic bronchiectasis, cystic fibrosis, and a recently recognized syndrome in which fibrosis predominates in the lung bases and emphysema predominates in the lung apices. Group 4, formerly known as "[PH] due to embolic disease, chronic thrombotic disease, or both", is now designated "chronic thromboembolic pulmonary hypertension" CTEPH.

The subdivision of obstruction into distal obstruction and proximal obstruction was removed from the classification, because the definitions of "proximal" and "distal" are difficult to standardize and vary among centers, making a definitive classification imprecise. This change should result in patients diagnosed with PH due to CTEPH being immediately referred to tertiary-care centers at which there are professionals with experience in performing thromboendarterectomy, so that operability can be determined by a multidisciplinary team.

Group 5 was changed from "miscellaneous" to "[PH] with unclear multifactorial mechanisms" and is now divided into four subgroups: "hematologic disorders"; "systemic disorders"; "metabolic disorders"; and a subgroup designated "others", which comprises a variety of conditions associated with PH. Treatment After the diagnosis of PH has been established by RHC and the disease has been clinically classified, PH treatment can be discussed, because the definition of the clinical group determines the treatment to be given.

The general measures and the supportive therapy should be evaluated for any patient with PH; however, the largest amount of evidence, even regarding the general measures, is based on studies of patients with PAH, that is, group 1 patients. General measures and supportive therapy All patients diagnosed with PH should receive some general instructions. The patients should be instructed not to do heavy physical exercise and to limit physical activity when experiencing mild dyspnea.

They should receive influenza vaccination and pneumococcal vaccination because infection is a major cause of morbidity and mortality in these patients. Female patients of childbearing age should be instructed to use contraceptive methods, because pregnancy significantly increases mortality in patients with PH. Although there is no consensus regarding the ideal type of contraception for patients with PH, it should be borne in mind that concomitant use of bosentan and oral contraceptives can reduce the effect of the latter.

Patients in functional class III or IV, as well as those with hypoxemia PaO2 Supplemental oxygen therapy is indicated for patients with hypoxemia PaO2 The use of anticoagulants in patients with PH is controversial, because there have been no randomized controlled studies evaluating the effects of anticoagulation in these patients. The rationale for the indication of anticoagulation for these patients originates from the histopathological findings of microvascular thrombosis, activation of the coagulation system, and platelet dysfunction in patients with IPAH, which have led to the assumption that these patients present with a prothrombotic state.

In a meta-analysis of the theme, conducted in , the authors concluded that anticoagulation should be indicated, given that 5 of the 7 studies analyzed demonstrated that anticoagulation was beneficial. In the absence of any contraindications, the use of oral anticoagulants is indicated for patients with PH, with the objective of maintaining an international normalized ratio of 1.

Attention should be given to patients with liver disease and scleroderma, because these patients might be at a higher risk for bleeding; likewise, attention should be given to the interaction between anticoagulants and the PAH-specific treatment. Some studies, for instance, have suggested that concomitant use of anticoagulants and sitaxsentan can increase the risk of bleeding.

However, there has been no confirmation that all subgroups of patients with PAH respond to the specific drugs that are currently available. There is also some evidence for patients with HIV infection. However, for patients with portopulmonary hypertension, schistosomiasis, or hemolytic anemia, it is still impossible to indicate the use of the same drugs, and clinical studies specifically designed to investigate those indications are needed.

If the patient presents pulmonary vasoreactivity, as assessed by the acute test, treatment with a calcium channel blocker should be initiated, and, if there is a sustained clinical response, the drug should be maintained, together with supportive treatment. The survival rates in patients who respond to the use of a calcium channel blocker are significantly higher than in those who do not respond well to the drug.

Therefore, the use of a calcium channel blocker is contraindicated for patients who do not present pulmonary vasoreactivity or those who have not undergone the acute test, due to the risk of clinical deterioration. The calcium channel blocker to be used can be nifedipine, diltiazem, or amlodipine.

However, in patients with high heart rates, diltiazem is the drug of choice. The treatment should be initiated with low doses, which should be progressively increased in accordance with the tolerance limit of the patient. The classes of specific drugs that are approved for use in PAH patients, that is, in group 1 patients, are as follows: prostacyclin analogues; phosphodiesterase-5 inhibitors; and endothelin receptor antagonists. Prostacyclin analogues Prostacyclin analogues constitute the first class of drugs to be approved for PH-specific treatment.

Prostacyclin analogues can be administered intravenously, subcutaneously, orally, or by inhalation. Epoprostenol In an open randomized study conducted in , clinical and hemodynamic improvements, as well as increased survival, were described in PAH patients who used epoprostenol in combination with conventional therapy anticoagulation, diuretics, and oxygen therapy , when compared with those who used the conventional therapy in isolation.

Epoprostenol should be administered intravenously, through a tunneled catheter, and continuously, through a portable infusion pump, due to its short half-life. The most common side effects are jaw pain, flushing, diarrhea, nausea, and vomiting. Catheter-related complications, such as infection and thrombosis, as well as those related to the functioning of the equipment, have often been reported.

Although epoprostenol is unavailable for use in Brazil, it is the only drug for functional class IV patients that has a grade of recommendation of A.

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