Pregnancy in women with pulmonary hypertension (PH) is known to be associated with significantly high morbidity and mortality rates, with an estimated mortality between 30% and 56%.1,2,3 The physiological changes that occur during pregnancy and the peripartum period are poorly tolerated. During pregnancy, an index of suspicion should exist for common conditions associated with pregnancy that can be complicated by PH, as these need to be evaluated thoroughly during this critical period. These include pulmonary and amniotic fluid embolisms, which are very common and mostly fatal. Most of the maternal PH-associated deaths occur during labor or within 1 month post-delivery.3 The clinical features of PH are nonspecific during pregnancy, and as a result these patients are often missed. Generally Imaging workups are the gold standard when managing these patients; however they may cause undesirable radiation exposure to the fetus. Pulmonary artery catheterization remains a well-regarded method for diagnosing pulmonary hypertension, although its use in pregnancy and in the intensive care unit has slowly fallen out of favor. Goal-directed bedside echocardiogram and lung ultrasonography are the strongly recommended modalities, and these do provide attractive alternative evaluator approaches in these patients.1
Physiological changes during pregnancy and peripartum period
During pregnancy, multiple physiological changes take place which may further impact on the hemodynamic ramifications in PH. Virtually every organ in the body is affected during pregnancy. The most important and significant change in the cardiovascular system is increased blood volume, which may increase almost 50% above the non-pregnant level at its peaks, during the second to the third trimester of pregnancy.4 Additionally, there are cardiovascular parameters which have added effects during pregnancy. These include heart rate and stroke volume, which lead to a subsequent increase in cardiac output. During normal pregnancy both the systemic and pulmonary vascular dilate, leading to a decrease in systemic (SVR) and pulmonary vascular resistance (PVR). In the presence of PH during pregnancy, pulmonary vascular disease prevents the fall in PVR, leading to a further rise in pulmonary arterial pressure (PAP) with increased cardiac output.5 All these have significant bearing on the overall cardiovascular system during pregnancy.
During the peripartum or post-delivery period, there is subsequent decrease in preload from blood loss and of anesthetic. The converse is also true in that there is increased preload from relief of the inferior caval obstruction (by the uterus), or additional blood return from the contracting uterus and increased fluid intake during labor (iatrogenic). This results in an increase of SVR and PVR and leads to decreased ventricular contractility and function.3 All these changes may be poorly tolerated during this critical period of pregnancy.
Diagnosis approach pulmonary hypertension during pregnancy
The standard approach during the evaluation of pulmonary hypertension in pregnancy simply starts with a basic symptomatology evaluation. The symptoms of PH in pregnancy can be very non-specific, and similar to those of normal physiological changes. Generally the symptoms of PH will include chest pain, cough, and shortness of breath or dyspnea, and all these are common in normal pregnancy. Additionally, patients with right heart failure may present with lower extremity swelling, dizziness, fatigue or syncope: all of which may indicate PH, or normal pregnancy. As a result, this will pose a serious challenge to the attending clinician. The physical examination of these patients (including precordial examination) with PH and right ventricular failure would reveal an elevated jugular venous pulse, a palpable and loud pulmonic component of the second heart sound and a palpable right ventricular heave and systolic murmur of tricuspid regurgitation. It is important to evaluate the pulmonary or the lungs as these will rule out any underlying parenchymal disease. In addition, it is very important to determine any underlying left sided valvular heart disease, left ventricular dysfunction or pulmonary venous hypertension.
II. Relevant Blood or Biochemical Tests
It is mandatory to risk stratify any patient with a suspicion or diagnosis of PH during pregnancy as the prognosis might be dismal, especially in those with advanced disease. The most important blood investigations include full screening for rheumatologic or common connective tissues disease, for example systemic lupus erythromatosis. In addition to these, there are very important biomarkers used for screening, prognostication and for follow-up of these patients. These biomarkers are also very useful in guiding patients’ management, and may include brain natriuretic peptide (BNP), which is additionally useful for monitoring chronic pulmonary arterial hypertension (PAH). In pulmonary embolism, BNP can stratify patients regarding risk for development of right ventricular failure.4 Troponin I leak is very useful for predicting mortality.5 D-Dimers are also very important to rule out pulmonary embolisms in these patients.6,7 These biomarkers should be used in conjunction with the attending clinician’s best judgment and as additives to other modalities.
III. Chest Radiography
Chest radiography (CXR) might be helpful PVRI Chronicle: Volume 1 Issue 2, July - December 2014 with the evaluation of PH patients; however its utility in the high care setting might be limited. The typical findings on CXR in pulmonary hypertension will depend on the chronicity and severity of pulmonary hypertension and these would include right ventricular hypertrophy or enlargement, right atrial enlargement and enlarged pulmonary arteries. The CXR is recommended for identifying parenchymal abnormalities and could be helpful if there is suspicion of a potential pulmonary embolism. However, some of these features may not be obvious on CXR. Other imaging modalities recommended in pregnancy when suspecting pulmonary hypertension/pulmonary embolism would include lung scintigraphy and computed-tomographic pulmonary angiography (CTPA). It is very important to take precautionary measures to prevent radiotherapy exposure to the fetus.
IV. Right Heart Catheterization
Generally the right heart or pulmonary artery (PA) catheterization is the gold standard for the diagnosis of PH.8 However, its use has fallen out of favor in the critically ill patients. Most studies recommend the placement of PA catheters for patients admitted to the intensive care unit with severe PH and RV failure.9-12 Yet its use has not been associated with improved survival13 and there is an increased risk of pulmonary artery rupture and thrombosis.14 Right heart catheterization hasn’t been used routinely in pregnancy as it is associated with risks both in the mother and fetus.
V. Ultrasound modalities recommended for pulmonary hypertension in pregnancy
Compression ultrasound (CUS) has a proven sensitivity of 97% and a specificity of 94% for the diagnosis of proximal deep venous thrombosis (DVT) and this should be recommended as a standard assessment in pregnancy15-18. Ultrasound is a useful tool and is important to implement in the critical care setting, and should be used in pregnancy when there is a suspicion of DVT. Echocardiography should also be performed in these patients, as it provides direct visualization of the right ventricle and other additional abnormalities. Lung ultrasonography may help differentiate the causes of PH in critical care and minimizes radiation exposure in pregnant patients, and as a result should be integrated as an adjunct to the standard chest radiograph and CT scan.19, 20
Common Causes of pulmonary hypertension in pregnancy
The common causes of PH in pregnancy are reported in Table 1. Pregnancy is a physiological condition which is characterized by an increased risk of thromboembolic complications. Pulmonary embolism is regarded a common cause for further thromboembolic issues, and one of the most crucial risk factors to rule out in pregnancy. It is also essential to rule out amniotic fluid embolism in a patient with PAH, as it is commonly associated with acute right ventricle failure and can lead to death. However, it is important to consider other common causes as highlighted in Table 1 and these include collagen vascular diseases and congenital heart diseases.
Improved survival in pregnancy and PH is attributable to the new treatment modalities, including incorporation of a multidisciplinary approach.3,21-23 There is no standardized approach to the management of PH in pregnancy in the current era; successful outcomes are heavily dependent on a methodical approach individualized to each patient in a dedicated clinical care setting. The basic overall approach for the management of PH with right ventricular failure are maintaining right ventricular function and reducing pulmonary vascular resistance, and these principles apply to PH in pregnancy as well. Fluid resuscitation and various vasopressors are used with caution. PH-targeted therapies have been utilized cautiously in pregnant women and require full understanding with regards to their safety in pregnancy. Mainstay therapy for pulmonary embolism is anticoagulation, and the treatment for amniotic fluid embolism predominantly supportive care. Multidisciplinary team approach is therefore crucial to achieving successful outcomes in these difficult cases.
Special management of pulmonary hypertension during pregnancy and labor
Pulmonary embolism (PE) is the most common cause of acute decompensation during the peripartum period. In patients with risk factors for PE should be managed cautiously during pregnancy and it is mandatory to exclude thromboembolic diseases. Heparin remains the mainstay of therapy in thromboembolic diseases during pregnancy, mainly as it does not cross the placenta and does not have teratogenic effects or carry any potential risk for fetal hemorrhage. Low molecular weight heparin (LMWH) is a recommended alternative as its safety during pregnancy has been demonstrated. The main pitfall however is that the two require anti-Xa levels monitoring with dose adjustments. These issues make them unfavorable in real clinical practice, negating their choice over unfractionated heparin. The next line of therapy is coumadin derivatives; however, these cross the placenta and are associated with embryopathy. Warfarin in particular is associated with embryopathy during the first trimester of pregnancy and can cause fetal hemorrhage; nonetheless, the current evidence suggests that if given at a dose of less than 5mg per day, the risk of embryopathy is quite low. Pregnancy is commonly one of the exclusions in clinical trials, and as a result there is not enough evidence on use of thrombolytic therapy in pregnant patients and data on thrombolytic therapy is generally limited to case reports. In other conditions, e.g. acute myocardial infarction, thrombolytic therapy is considered, as with pulmonary embolisms or venous thromboembolisms. The risk of major bleeding should be anticipated with the use of thrombolytic therapy.
II. Amniotic fluid embolisms
Supportive measures are the mainstay of treatments in amniotic fluid embolisms (AFE) patients and the treatment modalities should be to maintain adequate cardiorespiratory in the form of oxygenation, fluid resuscitation, vasopressors, and/or inotropes, and correct coagulopathy. It is very important to consider cardiopulmonary bypass, extracorporeal membrane oxygenation, and intra-aortic balloon counterpulsation as these have been used successfully in previous reports. Newer alternatives include the ventricular assist device (RVAD), which should be considered in severe PH, in particular those with right ventricle failure. In such a case, urgent delivery of the fetus should be should be performed. This will require a multidisciplinary approach including a pediatrician, cardiologist, surgeon and neonatologist.
Special considerations and precautions in patients who present with pulmonary hypertension in the peripartum period
Peripartum period is the most crucial time to closely monitor the PH patients, as that is the time when most maternal deaths occur. It is especially important to pay special attention to pulmonary hypertensive crisis and systemic hypotension. In addition, these patients are prone to develop hypoxemia, bradycardia, pulmonary thromboembolism, and cerebrovascular attack (including convulsions and bleeding tendencies with or without anticoagulant therapy). It is also important to pay special attention to the development of peripartum cardiomyopathy, which may have some influence on post-partum recovery.
Mortality Risk for Mother and Fetus in a Patient with PAH
In the past, the mortality risk in pregnant patients with PH was considered to be significantly high. With retrospective reviews, in a series of 125 pregnancies the mortality risk was reported at 30% in PAH patients, and 36% in pulmonary hypertension associated with Eisenmenger syndrome. However, this was found to be lower than the reported mortality of 56% in patients with PAH associated with other conditions, including those with chronic anorexigen use, collagen vascular diseases, pulmonary thromboembolic disease and chronic liver diseases. These led to more research and subsequently progress in the form of new therapies, which are now available and give hope for further reduction of maternal mortality. However, even though the mortality decreased significantly, maternal mortality rates still remain high. The rate of fetal mortality, heavily associated with maternal death, was also high and reached 7% to 13% in various reports.
Pulmonary hypertension in pregnancy is associated with high morbidity and mortality as pregnancy related changes are poorly tolerated in these patients. Most of the deaths occur during the last month of pregnancy or within the first month post delivery. Most fetal deaths are related to maternal deaths. The symptoms of PH can be very similar to those of normal pregnancy, and as a result these patients can be very easily missed during the evaluation. Though right ventricular catheterization is the gold standard for diagnosing PH, its use in pregnancy is associated with both maternal and fetal risks. Pulmonary embolism and amniotic fluid embolisms (AFE) are regarded as the most common and crucial causes of PH in pregnancy. There are currently no standardized measures to treat pulmonary hypertension in pregnancy. However, anticoagulation and supportive measures are the mainstay of treatment for pulmonary embolism and AFE respectively, as these are quite common in these patients.
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