RV pressure overload and RV dysfunction were found to be the most powerful predictor of in-hospital death among patients with SPE.[7
] However, the best therapeutic intervention for SPE is still controversial. Recent studies were directed toward colt lysis by using TT in order to rapidly minimize the obstructive load and improve RV function. In a randomized study of 101 patients who received r-TPA or heparin,[8
] greater improvement on echocardiography was observed in patients receiving r-TPA at 3 and 24 hours, confirming the efficacy of TT in rapid clot lysis. However, there were no clear clinical advantages. Further studies that looked at different clinical endpoints showed conflicting results.[3
Animal models and clinical investigations demonstrate that the impact of embolic material in the pulmonary vascular outflow tract precipitates an increase in RV impedance, which is predominantly related to the interaction of the mechanical obstruction with the underlying cardiopulmonary status.[10
] Although the embolic material size is certainly the main cause for pulmonary hemodynamic compromise following massive PE, such obstructive load cannot explain the whole picture in SPE, and other factors are also important for abnormal pulmonary physiology seen in this condition.
Substantial evidence indicates that a clot-driven neurohormonal inflammatory mediators’ release[12
] and systemic hypoxia[14
] are essential for the development of bilateral pulmonary vasoconstriction and worsen the V/Q mismatch leading to acute rise in PVR. In an animal study, PE was associated with an early influx of inflammatory cells, and monocyte chemo-attractant protein-1 elevation within the pulmonary artery wall.[15
] Another animal study of hypertensive PE was also associated with a 50- to 100-fold increase in the CXC- chemokines cytokine-induced neutrophil chemo-attractant and macrophage-inflammatory protein in bronchoalveolar fluid.[16
] These results indicate that SPE may induce expression of proinflammatory mediators and establish a proinflammatory environment in the affected patients leading to bilateral vasoconstriction and subsequent acute rise in PVR and RV failure.
Based on this, we hypothesized that treatment of SPE should be directed toward decreasing PVR and probably not rapid clot lysis. Such effect on PVR should lead to rapid improvement of RV function and hopefully the patients’ outcome.
shows our recommend treatment algorithm for patients who presented with SPE.
Algorithm for management of sub-massive PE
We realize that this report has some limitations. First, it is a small case series and lacks a control group. However, to our knowledge, this is the first attempt directed at modifying other underlying pathophysiological derangements in SPE and we believe is worth presenting. Second, the absence of invasive hemodynamic measurements is another weakness in this study, as echocardiography is not the ideal test for accurate measurement of pulmonary hemodynamics. Nevertheless, the improvement in echocardiographic parameters early after treatment with Iloprost in combination with the improvement in clinical and physiological measures may support and enhance the accuracy of echocardiography.
In this small series, we were able to demonstrate for the first time that targeting pulmonary vasculature with a selective pulmonary vasodilator in SPE is safe and potentially beneficial.
We are in the process of starting a randomized controlled study to further study this interesting hypothesis.