Brynn E. Stenehjem, Timothy G. Dirks, Andrew W. Shafer, Shawna Reed, Peter J. Stokman, and Eric R. Fenstad (2017) Surgically Curable Pulmonary Hypertension. Journal of the Minneapolis Heart Institute Foundation: January 2017, Vol. 1, No. 1, pp. 79-83.
Brynn E. Stenehjem, BA, Timothy G. Dirks, MD, Andrew W. Shafer, MD, Shawna Reed, RN, Peter J. Stokman, MD, and Eric R. Fenstad, MD, MsC, FACC
Minneapolis Heart Institute, Minneapolis, MN
Disclosures: Unrelated to this project, Dr. Fenstad receives speaking honoraria from Actelion, Gilead, and Bayer.
Address for correspondence:
Eric Fenstad, MD, MsC, FACC
Minneapolis Heart Institute
920 E 28th Street #300
Minneapolis, Minnesota 55407
Chronic thromboembolic pulmonary hypertension is 1 of 5 classifications of pulmonary hypertension. A patient with progressive dyspnea on exertion for the past 2 years underwent diagnostic testing and was found to be a surgical candidate for pulmonary thromboendarterectomy. Diagnostic criteria for chronic thromboembolic pulmonary hypertension include mean pulmonary artery pressure ≥25 mm Hg and pulmonary artery wedge pressure ≤15 mm Hg with a positive ventilation–perfusion scan or chest computed tomography angiogram consistent with pulmonary embolism after 3 months of optimal anticoagulation.
Keywords: chronic thromboembolic pulmonary hypertension, pulmonary hypertension, pulmonary thromboendarterectomy, ventilation-perfusion scan
Pulmonary hypertension (PH) describes elevated blood pressure in the pulmonary arteries due to either pre- or postcapillary changes. Currently, PH has 5 broad classifications due to either pulmonary arterial hypertension (PAH or group 1); left-sided heart disease (group 2); chronic lung disease or hypoxia (group 3); chronic thromboembolic PH (CTEPH, group 4); and unclear/miscellaneous mechanism (group 5). Right heart catheterization remains the gold standard for diagnosis and helps determine classification and treatment options. Ventilation-perfusion (VQ) imaging is the screening test to rule in or rule out CTEPH. In chronic thromboembolic PH, options may include surgical or medical treatments. Patients should be managed in expert PH centers.
A 51-year-old female presented with progressive dyspnea on exertion for the past 2 years. The patient denied chest pain but noted constant persistent chest pressure and tightness at rest over the past year without exacerbation from exertion. She denied syncope, presyncope, orthopnea, or paroxysmal nocturnal dyspnea. Past history was significant for obstructive sleep apnea, obesity, and an unprovoked pulmonary embolism (PE) 2 years prior. Thrombophilia workup at that time was negative. She was treated with warfarin and international normalized ratio (INR) remained therapeutic in the interim. On physical exam, the patient had normal carotid upstrokes, jugular venous pressure <10 cm H2O, regular rate and rhythm, with normal S1 and accentuated P2 component of the second heart sound, a soft grade I/VI systolic murmur at the left lower sternal border that increased with inspiration, clear lung sounds, no pulsatile liver, and +2 pitting edema to the knee joints bilaterally with venous stasis skin changes. The electrocardiogram (ECG) demonstrated sinus rhythm with a ventricular rate of 83 beats per minute and right axis deviation with right ventricular (RV) hypertrophy (Figure 1). Labs were significant for a normal creatinine of 1.02 mg/dL, normal hemoglobin 13.4 g/dL, elevated BNP at 296 pg/dL, normal aspartate and alanine aminotransferase, and negative antinuclear antibody. Workup for thrombophilia was negative.
Baseline ECG demonstrating normal sinus rhythm, right axis deviation, and RV hypertrophy with strain pattern.
The echocardiogram demonstrated severe RV enlargement with borderline RV systolic dysfunction (tricuspid annular plane systolic excursion, 18 mm), and an estimated right ventricular systolic pressure (RVSP) of 105 mm Hg with septal flattening during systole and diastole (Figure 2A–D), consistent RV pressure, and volume overload. The left ventricle was small with left ventricular ejection fraction of 70%, normal valve function, and normal diastolic filling pressure (E/e’ 5). Ventilation-perfusion imaging was consistent with high probability for PE (Figure 3). Chest computed tomography (CT) angiography demonstrated acute and chronic PE in the proximal right and left main pulmonary arteries (PAs) as well as the bilateral smaller segmental and subsegmental pulmonary arteries (Figure 4). The patient achieved 182 m on a 6-minute walk test with mild desaturation to 88% on room air during exercise. Right heart catheterization and demonstrated hemodynamics consistent with PH with negative vasodilator challenge (Table 1). Given the positive VQ scan and right heart catheterization hemodynamics, along with appropriate duration of therapeutic anticoagulation, a diagnosis of CTEPH was made.
Transthoracic echocardiogram demonstrating. A. Right ventricular enlargement. B. Severe RV enlargement with septal flattening in diastole. C. Elevated tricuspid regurgitant velocity of 4.6 m/second. D. Inferior vena cava plethora with <50% inspiratory collapse.
Ventilation-perfusion scan demonstrating multiple segmental and subsegmental perfusion defects with normal ventilation consistent with high probability for PE.
Chest CT angiogram demonstrating intravascular webs and proximal thrombi in the right segmental and subsegmental PAs consistent with proximal CTEPH.
Right heart catheterization hemodynamics at rest and with vasodilator challenge.
The patient was started on riociguat and slowly uptitrated to 2.5 mg 3 times daily over the next month. Anticoagulation was transitioned to rivaroxaban 20 mg daily. The patient was evaluated at 3-month intervals at a PH center and at 6 months’ post-initiation of riociguat and rivaroxaban, chest CT angiography was repeated. The gated ECG chest CT demonstrated resolution of acute pulmonary thromboemboli but persistent intravascular thread-like webs and pruning of the proximal segmental pulmonary arteries. Given her proximal disease, diminished quality of life with ongoing severe dyspnea with minimal exertion and chest pressure, she was referred to a cardiovascular surgeon for a pulmonary thromboendarterectomy (PTE). The procedure was performed without complication (Figure 5) and on 3-month follow-up, the patient had near normalization of estimated RVSP (40 mm Hg) and normal RV size/function with a profound improvement in quality of life and resolution of her dyspnea and chest pressure. The patient’s 6-minute walk distance was 347 m. At 6 months’ post-PEA, riociguat was discontinued and the patient has remained symptom-free.
Surgical specimen from PEA demonstrating proximal and distal obstruction.
Chronic thromboembolic PH is classified as group 4 pulmonary hypertension in most updated classification schema (Table 2).1 Symptoms are often nonspecific resulting in a median time from symptom onset to diagnosis of 14 months.2 Diagnostic criteria for CTEPH include mean pulmonary artery pressure (mPAP) ≥25 mm Hg and pulmonary artery wedge pressure (PAWP) ≤15 mm Hg with a positive VQ scan or chest CT angiogram consistent with pulmonary embolism after 3 months of optimal anticoagulation. Approximately 2% to 5% of patients with acute PE will go on to develop CTEPH, occurring within the first 2 years post-PE.3,4 However, upwards of 25% to 40% of patients with diagnosed CTEPH have no history of venous thromboembolism.2,5 Unlike PAH, no genetic link has been identified in CTEPH. However, risk factors include previous splenectomy, venous thromboembolism history, history of infected ventriculoatrial shunts or device leads, thyroid replacement therapy, cancer, lupus anticoagulant/antiphospholipid antibodies, and chronic inflammation.6Pathologic specimens demonstrate organized fibrotic and microthrombotic obstructions within the pulmonary arterial medial layer with corresponding intimal hypertrophy and inflammation. Plexiform and thrombotic lesions are commonly visualized comprising complex intravascular webs in the subsegmental pulmonary arteries and smaller arterioles.7
Pulmonary hypertension classification.
Chest CT angiography determines whether CTEPH is present in the proximal or distal circulation. Pulmonary TE is indicated in proximal disease while medical therapy is utilized for distal disease not amenable to surgical thromboendarterectomy (approximately 37% of patients).8 Table 3 illustrates the treatment approach to CTEPH and other types of PH. Pulmonary TE is performed in experienced centers with a mortality rate approaching 0% (5-year survival: 82%) while achieving surgical cure in the majority of patients (65%–89%).9
Pulmonary hypertension treatment algorithm.
Pulmonary TE is performed through median sternotomy incision. Systemic heparin is administered. Cardiopulmonary bypass is performed via central aortic infusion and bicaval venous drainage cannulae. Bypass is initiated in the patient and deep hypothermic arrest is achieved with cooling to 20°C. Left ventricular and PA vents are placed. When the heart fibrillates, an aortic cross-clamp is applied and the heart is arrested using antegrade cardioplegia. The right PA is exposed and an arteriotomy is made from under the aorta to under the superior vena cava. The pulmonary thrombus is separated from the PA wall using forceps and an endarterectomy dissector. Thrombus is separated starting in the main PA and extended into the subsegmental PA branches. Circulatory arrest is initiated once the venous regurgitation from the PA vasculature obscures visualization. One circulatory arrest cycle of 20 to 25 minutes is generally long enough to complete one side of the dissection. After completion of the right pulmonary endarterectomy, cardiopulmonary bypass is reinitiated and the right PA arteriotomy is closed with 5-0 prolene suture. The left pulmonary endarterectomy is performed in a similar fashion using circulatory arrest. After completion of the endarterectomy on both sides, the patient is rewarmed, weaned from bypass, heparin is reversed, and the sternotomy incision is closed. Patients are managed in the intensive care unit postoperatively with inotropic support, diuresis, and mechanical ventilation; typically extubated within 1 to 2 days; and discharged home within 15 days.10,11 Surgical complications include reperfusion lung injury that can be managed with venovenous extracorporeal membrane oxygenation. Residual PH may be present in up to 35% of patients requiring ongoing medical therapy. In-hospital mortality has improved dramatically: from 16.8% between 1970 and 1988, to 2.2% between 1999 and 2010, when performed in a high-volume center.11 Hemodynamic benefits include a reduction in pulmonary vascular resistance (PVR; 8.99 ± 4.79 Wood units [WU] preop versus 3.17 ± 1.86 Wood units postop) and reduction in mPAP (45.5 ± 11.6 mm Hg preop versus 26.0 ± 8.4 mm Hg postop). Ten-year survival rate was 75%.
Medical therapy consists predominantly of a soluble guanylate cyclase stimulator, riociguat resulting in an increase in 6-minute walk distance, improved hemodynamics on right heart catheterization, improved functional class, and improved quality of life.12Recently, balloon PA angioplasty has also been used to treat nonoperative disease or for patients with high surgical risk. Guidelines recommend referral to expert centers for management.
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