**19. Late consequences of pulmonary embolism**

Unresolved pulmonary thromboembolic disease can result in significant morbidity and mortality after acute PE and may lead to chronic thromboembolic pulmonary hypertension (CTEPH). The incidence of this condition is not well-documented. In 2012 Korkmaz et al (Korkmaz 2012) evaluated 325 consecutive patients after acute PE for residual thrombus and CTEPH. Residual chronic thrombus was detected in 48%, 27% and 18% of patients at 3, 6 and 12 months respectively. CTEPH (defined echocardiographically as estimated PAP ≥ 50 mmHg) was detected in 4.6% of follow-up echocardiograms. It is unclear if specific interventions at the time of PE could improve the rapidity or extent of thrombus resolution or decrease the likelihood of CTEPH development.

Recently, Kline et al (Kline 2009) reported baseline and 6 month follow-up echocardiography at a single center after acute PE. Elevated pulmonary pressures were defined as an RV systolic pressure (RVSP) ≥ 40 mmHg on echocardiogram. 200 normotensive patients with CTPA proven PE were enrolled. 21 received thrombolytic therapy with alteplase because of subse‐ quent hemodynamic destabilization or respiratory failure. 180 (90%) survived to 6 months. 162 returned for a 6 month reevaluation after PE. In the heparin treated group, 35% had elevated pulmonary pressures initially and 7% were elevated at 6 months. 27% had increased estimated RVSP on subsequent echocardiograms. In the alteplase plus heparin group, 61% had elevated pulmonary pressures initially and 11% on follow-up echocardiogram without any increase in RVSP at follow-up (Kline 2009). These data suggest that thrombolytic therapy is associated with better reduction of RVSP than heparin alone; however, more detailed evaluation is necessary.

### **20. Summary**

**18. Embolectomy**

132 Pulmonary Hypertension

2012).

necessary.

Several interventional techniques including mechanical fragmentation, thrombus aspiration, and direct thrombolytic therapy are currently available for the treatment of acute PE. No clear guidelines can be provided regarding the use of interventional techniques for PE as there are no randomized controlled trials to assess these treatments. ACCP guidelines advise consider‐ ation of these interventions in the setting of massive PE with contraindications to systemic thrombolysis, failed thrombolysis, or likelihood of death before thrombolysis (Kearon 2012). Surgical embolectomy is infrequently required for management of acute PE. There are limited data guiding surgical interventions in this setting. Leacche et al (Leacche 2005) reported surgical outcomes in 47 consecutive patients with acute massive PE treated surgically. Indications for surgery included contraindications to thrombolysis (45%), failed medical treatment (10%) and right ventricular dysfunction (32%). Operative mortality and late mortality were 6% and 12% with the majority (83%) of the late mortality related to metastatic cancer. 86% and 83% of patients were alive 1 and 3 years after surgery, respectively (Leacche 2005). Specific instances when surgical intervention may be indicated are the presence of right atrial thrombus, paradoxical arterial embolism, or closure of a patent foramen ovale (Kearon

Unresolved pulmonary thromboembolic disease can result in significant morbidity and mortality after acute PE and may lead to chronic thromboembolic pulmonary hypertension (CTEPH). The incidence of this condition is not well-documented. In 2012 Korkmaz et al (Korkmaz 2012) evaluated 325 consecutive patients after acute PE for residual thrombus and CTEPH. Residual chronic thrombus was detected in 48%, 27% and 18% of patients at 3, 6 and 12 months respectively. CTEPH (defined echocardiographically as estimated PAP ≥ 50 mmHg) was detected in 4.6% of follow-up echocardiograms. It is unclear if specific interventions at the time of PE could improve the rapidity or extent of thrombus resolution or decrease the

Recently, Kline et al (Kline 2009) reported baseline and 6 month follow-up echocardiography at a single center after acute PE. Elevated pulmonary pressures were defined as an RV systolic pressure (RVSP) ≥ 40 mmHg on echocardiogram. 200 normotensive patients with CTPA proven PE were enrolled. 21 received thrombolytic therapy with alteplase because of subse‐ quent hemodynamic destabilization or respiratory failure. 180 (90%) survived to 6 months. 162 returned for a 6 month reevaluation after PE. In the heparin treated group, 35% had elevated pulmonary pressures initially and 7% were elevated at 6 months. 27% had increased estimated RVSP on subsequent echocardiograms. In the alteplase plus heparin group, 61% had elevated pulmonary pressures initially and 11% on follow-up echocardiogram without any increase in RVSP at follow-up (Kline 2009). These data suggest that thrombolytic therapy is associated with better reduction of RVSP than heparin alone; however, more detailed evaluation is

**19. Late consequences of pulmonary embolism**

likelihood of CTEPH development.

Acute pulmonary thromboembolism is the third most common acute cardiovascular disease (Giuntini 1995) and is associated with significant morbidity and mortality. Thromboembolic obstruction of the pulmonary vasculature frequently causes dyspnea, hypoxia, and chest pain. In severe cases, PE can cause an acute rise in pulmonary pressures precipitating RV dysfunc‐ tion and hemodynamic instability. The increase in hemodynamic pressures is due to both mechanical obstruction of the pulmonary vascular bed as well as the release of vasoconstricting mediators and derangement of neural regulation of vasomotor tone. Hypotension, RV dysfunction, elevated biomarkers (BNP, troponin I, troponin T) and ECG abnormalities with T-wave inversions are markers of poor prognosis. Rapid evaluation and risk stratification are necessary for effective treatment. Hemodynamically stable PE, i.e. low risk PE, is routinely managed with heparin therapy and clinical monitoring. Hemodynamically unstable PE, i.e. massive PE, is frequently managed with thrombolysis. Optimal management of hemodynam‐ ically stable PE with high risk features, i.e. submassive PE, is unclear at this time. Further study to determine best practice in this group is ongoing. Unfortunately, acute PE has both shortterm and long-term consequences. Additional evaluation and characterization of patients at risk to develop long term complications of pulmonary emboli are needed.

## **Author details**

Jean M. Elwing1,2\* and Ralph J. Panos1,2

\*Address all correspondence to: jean.elwing@uc.edu

1 Pulmonary, Critical Care, and Sleep Medicine Division, Cincinnati Veterans Affairs Medi‐ cal Center, Cincinnati, USA

2 Pulmonary, Critical Care, and Sleep Medicine Division, University of Cincinnati College of Medicine, Cincinnati, USA
