During the first 2 trimesters, there is an increase in blood volume up to 50 % that, together with a decrease in both pulmonary and systemic vascular resistance, results in an increased cardiac output [25, 26]. In the pregnant patient with PAH, the elevated pulmonary vascular resistance compounded with the increase in cardiac output results in substantially increased in pulmonary arterial pressure that may progressively overwhelm the right ventricle. The peri- and postpartum stages, in particular, are associated with right ventricular weakening due to increased cardiac preload from rapid increases in cardiac venous return mediated by uterine contractions during labor, shift of uteroplacental blood flow back to the systemic circulation, and withdrawal of vena cava compression by the gravid uterus [27, 28]. By contrast, blood loss associated with either vaginal (~500 ml) or cesarean (~1000 ml) delivery resulting in acutely decreased preload occurring in the setting of right ventricular failure may promote systemic hypotension and tissue hypoxia. Ultimately, the physician must be observant of these rapid and unpredictable shifts in cardiopulmonary hemodynamics and be prepared to rapidly intervene in order to prevent a catastrophic clinical outcome.

Pregnancy remains one of the major triggers for the manifestation of PAH in previously asymptomatic patients with an estimated overall incidence of 1.1 in 100,000 women [27, 29–31]. Despite the availability of current PAH-specific therapies, PAH remains a major cause of mortality in pregnancy accounting for 30–56 % of all peripartum fatalities [32, 33]. In addition, there is also a high risk for perinatal mortality of offspring born to PAH mothers given the stress on fetal growth and normal development due to reduced placental blood flow and oxygen delivery [34, 35]. Studies done prior to the availability of advanced PAH therapies have shown that elevated systemic pulmonary pressure (sPAP > 40 mmHg) and a higher NYHA functional class correlate positively with clinical deterioration and the need for an earlier delivery [36]. Premature delivery or termination of pregnancy may be necessary in some patients in the setting of clinical deterioration threatening their health and/or that of the unborn child. With the introduction of PAH-specific therapies to routine clinical practice, a reduction in PAH-related mortality during pregnancy has been observed, with one study reporting a mortality of rate of ~25 % vs. 50–70 % in the time period prior to availability of PAH-specific agents. In this study, use of advanced PAH therapies (e.g. prostanoids, ERAs) as well as calcium channel blockers in vasoreactive patients were associated with a better outcome [37]. Despite these encouraging observations, it is important to stress that PAH in pregnancy remains associated with an unacceptable rate of life-threatening complications and PAH patients should be counseled on use of available contraception methods to prevent pregnancy altogether or, if pregnant, strong consideration to early termination is often necessary.

For the patients in whom pregnancy is pursued despite knowledge of the associated risks, it is imperative to establish an aggressive plan for frequent clinical monitoring by a multidisciplinary group that should include a PH expert, maternal-fetal medicine specialist, and cardiac anesthesiologist [38, 39]. The most frequent complications during pregnancy tend to occur during the second and early third trimester when the hemodynamic changes peak [33, 37]. In anticipation of this, visits during the first trimester should focus on assessing the need for either initiating or adjusting PAH-specific drugs as well as conventional therapies such as diuretics or anticoagulants. The latter is especially important given that pregnancy is a prothrombotic state with a fivefold risk of clotting events that could result in catastrophic outcomes in these clinically vulnerable patients [40, 41]. The choice of anticoagulant should be the result of a carefully-thought process and, when possible, in line with current consensus recommendations to minimize risks to the fetus, as some agents, such as warfarin, are associated with teratogenicity and should be avoided during early pregnancy. The most commonly used anticoagulants in pregnancy are either low or high molecular weight heparins since neither of these compound classes can cross the placental barrier [42, 43]. Despite lack of clear evidence, the general consensus is that anticoagulation should be initiated early in pregnancy, continued until the beginning to labor when it should be held to minimize blood loss during delivery period and restarted postpartum to prevent clot formation.

Consensus guideline recommendations for determining optimal PAH-specific therapy for pregnant patients are lacking; however, currently available drugs offer a range of options of that can help the clinician optimize management of PAH during pregnancy. There are four FDA-approved available drug classes for the treatment of PAH: (1) phosphodiesterase 5 inhibitors (PDE5-I), (2) soluble guanylate cyclases (sGCs), (3) endothelin receptor antagonist (ERAs) and (4) prostanoids [44–46]. There are two currently available PDE5-I: sildenafil and tadalafil. Both agents are orally active and induce vasodilatation by increasing the availability of nitric oxide (NO) in the pulmonary circulation [47]. Use of these agents during pregnancy appears to be safe based on several published clinical reports. Riociguat, the only available sGC in the market, is a vasodilator that synergizes with NO to increase vasodilation and reduce pulmonary vascular resistance [48, 49]. Studies in animals have shown that Riociguat is teratogenic and, therefore, its use is contraindicated in pregnancy. Similarly, all available ERAs (bosentan, ambrisentan and macitentan) are contraindicated in pregnancy since use of bosentan in mice is associated with birth defects such as craniofacial malformations, patent ductus arteriosus and other vascular malformations [46, 50–52]. The most potent of the available PAH specific drugs are the prostanoids, prostacyclin analogues that induce potent pulmonary and systemic vasodilatation. The available prostanoids can be found in various formulations: treprostinil is available as an oral (Orenitram) [53], inhaled, subcutaneous and intravenous agent whereas iloprost and epoprostenol are only available in inhaled and intravenous formulations, respectively [54–56]. While not all formulations have been tested in pregnancy, there have been multiple reports of prostanoids being safely used in pregnancy to treat PAH. At present, there are no well-controlled studies to evaluate teratogenic effects of prostanoids on pregnant women, a fact that has led the FDA to assign them a pregnancy risk category B (no documented evidence of harm in humans, teratogenic effects not seen in animals). Nevertheless, manufacturers of these drugs still advise caution when using any of these compounds in pregnant patients.

The most challenging stages of pregnancy for the clinical team managing PAH in pregnancy are labor and delivery, in which the goals of care should be to ensure the health of both mother and child by supporting cardiopulmonary hemodynamics [36, 38]. It is imperative that fetal monitoring is instituted throughout the course of labor for early detection of signs of fetal stress requiring immediate intervention. Pain control should also be instituted early as the sympathetic surge associated with pain can result in severe cardiac stress and ischemia. The choice of anesthesia to assist with pain control must also be weighted carefully as some agents can induce both profound systemic vasodilatation and myocardial suppression resulting in a substantial fall in cardiac output and tissue hypoxia [57]. When possible, regional anesthesia should be chosen over general anesthesia as the former can provide excellent pain control without the need for intubation that the latter entails [58–60]. However, one must be aware that common forms of regional anesthesia such as epidural spinal block carry the risk of inducing hypotension due to sympathetic blockade and may adversely impact cardiopulmonary function. To avoid this complication, it is advised that the epidural anesthesia is administered slowly with while simultaneously monitoring the vitals signs of both the mother and fetus. Despite the ongoing debate concerning the optimal method of delivery, some physicians favor vaginal delivery as it presents the advantage of minimizing blood loss and preventing sudden changes in cardiac preload [61, 62]. On the other hand, cesarean delivery can be used to rapidly intervene in cases of severe fetal stress and to avoid severe hemodynamic swings induced by Valsalva maneuvers required to conduct vaginal delivery but it must be stressed that blood loss is higher with cesarean vs. vaginal delivery and this could result in hemodynamic complications ranging from hypotension to sudden cardiopulmonary collapse [39]. Finally, induction with oxytocin should be avoided as this can produce increases in pulmonary vascular resistance and tachycardia that could result in cardiopulmonary collapse and death [63, 64].

Whether the patient is either considering or has already undergone successful pregnancy and delivery, it is imperative for the PH clinician to inform the patient of the risks associated with PAH in pregnancy and the rationale for contraception [65]. The current PAH guidelines recommend the simultaneous implementation of two different methods of contraception in female patients of reproductive age [44, 66]. Barrier methods such as condoms and spermicidal gels should not be used alone given their relatively high failure rate and should always be combined with other contraceptive methods such as the progesterone only pill, the etonogestrel-releasing subdermal implant or an intrauterine device (IUD).

A proposed algorithm for the management of the pregnant PH patient is shown in Fig. 22.2 [67]. It must be stressed that PAH is a strong predictor for mortality in pregnancy and should be avoided when at all possible by ensuring patient education and institution of dual contraceptive methods. In patients that choose to carry their pregnancy to term, it is imperative to assemble a multidisciplinary team that will closely monitor the patient’s clinical course. Furthermore, timely institution of PAH specific therapies to achieve optimal control of cardiopulmonary hemodynamics should help mitigate the impact of volume gain and respiratory changes associated with pregnancy. Ultimately, the most important goal of care is to ensure that both mother and fetus remain clinically stable throughout the pregnancy and delivery and that plans are in place to prevent future pregnancies.

It is well known that the presence of moderate PH increases the risk of morbidity and mortality in both cardiac and non-cardiac surgery. One study showed that, among 2,149 patients undergoing coronary artery bypass grafting (CABG), PH was a major predictor for perioperative mortality [68]. The EuroSCORE study has also shown that PH was an independent risk factor for perioperative mortality in patients undergoing cardiac surgery [69]. Perioperative mortality and complication rates for non-cardiac surgery have been estimated to range between 7 and 42 % in one study [70], and 14 and 18 % in another [71]. While the specific risk factors that influence the incidence of life-threatening complications for PH patient in the perioperative setting are not well established, it is critical for the PH specialist to initiate a thorough management protocol that will help prepare the anesthesia and surgical team for managing acute complications related to pulmonary vascular and/or right ventricular disease.

A PH specialist should evaluate patients who require non-emergent surgery within a week of the planned surgery. This way, both patient and surgical characteristics can be thoroughly assessed and a multi-disciplinary team approach can be instituted.