Eduardo B. Saad, MD
|
Carlos Eduardo Reis, MD
| Ricardo Amorin, MD |
A 45 year old woman was admitted to the Federal University of Rio de Janeiro Hospital with acute onset dyspnea, started three days before while at rest, exacerbated with minimal efforts and left posterior chest pain worsened by deep breath.
An insidious onset of dyspnea at moderate activity, fatigue, simetrical leg edema, ascites and dry cough, sometimes with bloody sputum started two years before. She had also orthopnea, multiple migrating small painful vessels throughout the thorax and abdomen and unmeasured weight loss. Thereafter, symptoms progressively worsened up to the point of dyspnea at minimal efforts and the patient became confined to bed most of the time.
One year before admission, thrombosis of the Inferior Vena Cava and multiple deep venous thrombosis of both legs was diagnosed. She was started on Warfarin. Three months before admission, she had thrombosis of the right Subclavian, Axillary and Braquial veins and partial thrombosis of the right Internal Jugular vein . An hematological investigation for a procoagulant abnormality, which included levels of Protein C, S, Antithrombin III, Lupus Anticoagulant, Anticardiolipin antibodies, Resistance to Activated Protein C ( Factor V Leiden ) and a complete blood count, could not reveal any abnormalities. Screening for occult malignancies with fecal occult blood, thoracic and abdominal CT scans and GI series were negative.
Two weeks before admission there was an exacerbation of the edema in the right leg, associated with local heat and redness. She denied fever, chills, night sweats, palpitations, sleep disturbances, urinary or fecal abnormalities, joint complaints and neurological deficits.
She had a history of epilepsy in childhood, controlled with Cabamazepine . Her past medical history also included a subtotal hysterectomy 7 years before admission, cholecystectomy 6 years before, surgery for renal stones 2 years before, a single bout of bacterial pneumonia 2 years before, and a cured left carpal tunnel syndrome in the past year.
There was no history of miscarriage. She denied use of oral contraceptives, smoking, alcohol abuse, illicit drugs or risk factors for HIV infection. She used to be very active before, working as a housewife. Family history was negative.
On admission, the patient was afebrile and in no acute distress. Heart rate was 110, Respirations of 23 / min and blood pressure 130 x 90 mmHg. There was no
lymphadenopathy and the thyroid was normal.
The jugular venous pressure was around 14 mmHg with a large V wave and hepatojugular reflux. Carotids pulses were normal and no bruits were heard. She was using accessory muscles of respiration.
A right ventricular heave was palpated at the left sternal border and the pulmonary component of the second heart sound was felt. There was a third heart sound at the lower left sternal border, and the pulmonary component of the second was increased. A tricuspid holosystolic crescendo regurgitating murmur of 3+ / 6+ intensity was heard at the lower left sternal border that increased during inspiration.
The lungs were clear. Abdominal examination revealed moderate ascites, extensive collateral circulation of the Inferior Vena Cava type and a painful liver at 6 cm from the costal margin.
There was also bilateral leg edema, with signs of chronic venous insufficiency as hyperpigmentation, supficial varicosities and a bright thin skin ( figure 1 ). Tenderness was elicited upon compression of the calf muscles.
Laboratory findings revealed a hematocrit of 36 %, hemoglobin 11 g/dl, normal platelet and white cell counts, electrolytes and renal function. Arterial blood gases : pH - 7.39, pCO2 - 30, pO2 - 73, O2 Sat. - 94 %, HCO3 - 18. Clearly, the symptoms of fatigue and dyspnea could not be explained by a severe anemia or by decreased oxygen blood content, as would be the case if she had a severe pulmonary parenchymal disorder or a hematological abnormality.
Chest X-ray showed right heart enlargement and signs of Pulmonary Arterial Hypertension, with increased hilar shadows and decreased peripheral pulmonary vasculature, so excluding pulmonary parenchymal disorders. An Echocardiographic examination showed severe Pulmonary Arterial Hypertension ( estimated pulmonary systolic pressure of 70 mmHg, with a left bulging of the interventricular septum ), moderate tricuspid regurgitation and right atrial and ventricular enlargement, with normal left ventricular function. There was no left to right shunts, ruling out cardiac disorders and suggesting a pulmonary vascular disease to explain the Pulmonary Hypertension. ( figure 2 ) .
Ventilation - Perfusion scan revealed perfusion deficit areas in the right lower lobe and in left upper lobe, with normal ventilation ( ventilation - perfusion mismatch ), characterizing pulmonary thromboembolism and ruling out Primary Pulmonary Hypertension.
A duplex scan showed venous thrombosis in both the iliacs, femorals and popliteals vessels, some with signs of organization, characterizing an old thrombotic process mixed with ongoing deep venous thrombosis.
Venous dissection for right heart catheterization revealed multiple thrombi in the arm veins, right heart catheterization revealed pulmonary artery and right ventricular systolic pressures of 75 mmHg, with a mean of 35 mmHg. Pulmonary angiography showed occlusive thrombus at the right inferior lobar artery and multiple proximal thrombotic stenosis of the pulmonary vessels ( figure 3 and 3a). These results confirmed the diagnosis of severe Pulmonary Arterial Hypertension due to Chronic Pulmonary thromboembolism, with an anatomy suitable for surgical therapy with a Pulmonary Thromboendarterectomy, due to the proximal location of the thrombi and the relative sparing of the distal pulmonary tree. Occlusion of the Inferior Vena Cava, as showed by Cavography, precluded the insertion of a Caval filter.
A Pulmonary Thromboendartectomy was performed by means of a median sternotomy, which revealed a severely hyperthrophic right ventricle and multiple pulmonary thrombi in both proximal vessels, most covered by an intimal proliferation, characterizing a chronic organizing process ( figures 4 and 4a ). There was no complications in the postoperative period except for moderate hypoxemia, and she was discharged after three weeks of hospitalization using Warfarin. A repeated Pulmonary Angiography 3 days after surgery revealed no significant changes in the peripheral pulmonary circulation and the pulmonary artery systolic pressure was 60 mmHg. The right lower lobe circulation appeared somewhat improved ( figure 5 ). These results were interpreted as a partial failure of recanalization, which could be due to unsuspected distal pulmonary vessel disease18 or to rethrombosis of the pulmonary circulation. A repeated angiogram is planned 3 months after surgery.
Chronic Pulmonary Thromboembolism is a rare sequel of acute pulmonary embolism, occurring in 0.013 - 0.2 % of the estimated 600.000 yearly cases in the U.S1. It is one of the few treatable causes of pulmonary hypertension, as surgical pulmonary thromboendarterectomy is now performed in specialized centers worldwide15,16,17.
When untreated, pulmonary hypertension carries a bad prognosis, with a 5 year mortality of 70 % when the mean pulmonary artery pressure is over 30 mmHg and 90 % when over 50 mmHg1. Clearly, more effective treatments are needed to improve the natural history of this serious disease. Until recently, the only options available for treating these patients were anticoagulant therapy and Inferior Cava filter, which are not actually curative, as they only decrease the incidence of new embolic episodes. As surgical and myocardial protection techniques developed, a surgical treatment became an option in selected cases.
In patients with Chronic Thromboembolic Pulmonary Hypertension ( CTPH ), a history of deep venous thrombosis or pulmonary embolism is rarely detected. Usually, the onset is insidious, with dyspnea being the most frequent symptom1. So, in the majority of patients, no clues to the thromboembolic etiology of the Pulmonary hypertension is elicited by history and physical examination, necessitating a high level of suspicion and specialized imaging procedures, in order to make the diagnosis. This is of great importance, as the main differential diagnosis, namely Primary Pulmonary Hypertension, Left to Right shunts and Reactive Pulmonary Hypertension due to left ventricular dysfunction or valvular heart disease, have different prognosis and treatments. The patient under discussion had a typical hypercoagulable syndrome, leading rapidly to a search for the diagnosis, although this kind of presentation is atypical. In less than 10 % of cases1, a hypercoagulable state can be diagnosed, as in our patient, but some recent series report up to 30 %5 of diagnosed hypercoagulability. These differences are probably due to the limited number of patients studied7,8, as well as to differences in the methods of investigation for a hypercoagulable state.
CTPH rarely leads to pulmonary infarction, as collaterals from hyperthrophic and dilated bronquial arteries supply the vascularization from the pulmonary arteries. So, total chronic occlusions do not preclude attempts to opening the pulmonary arteries as the lung tissues are viable.
Diagnosis needs a high degree of clinical suspicion and is based on scintigraphic and pulmonary arteriographic findings. On Ventilation - Perfusion Scans, CTPH can be differentiated from Primary Pulmonary Hypertension ( PPH ) by its segmental or larger perfusion defects with a normal ventilation scan ( Ventilation - Perfusion mismatch ), while on PPH the perfusion defects are diffuse or less than segmental.
Pulmonary angiography2 is the gold standard for the diagnosis and also is needed for assessment of the feasibility of Pulmonary Thromboendarterectomy, the treatment of choice. It shows webs, bands, stenosis and total occlusions of the proximal pulmonary tree, with intimal irregularities and rounded terminations of pulmonary branches. It must be emphasized that its interpretation is quite different from that in Acute Pulmonary Embolism, where thrombi can be readily detected as a sharp filling defect in a branch of the pulmonary tree. In CTPH, however, “ oddly shaped pulmonary arteries “ are frequently seen, as thrombi are rarely detected as such2,16. So, an experienced angiographer is needed for accurate analysis of the angiogram, as it can show atypical morphology. This invasive evaluation carries an acceptable mortality of 0.2 % and a complication rate of 4.5 %1.
Recently, spiral CT scans has allowed excellent vascular opacification of the pulmonary arteries, and thrombi in the pulmonary arteries can be directly visualized11. This non invasive method is being evaluated as an alternative to Pulmonary Angiography. The sensitivity of spiral CT scans in confirming the diagnosis of CTPH is reported to be more than 90 %, and the decision concerning the operability is possible on its basis in more than 80 % of cases10. CT depiction of bronquial arteries, dilatation and tortuosity provides indicators for CTPH, even though its degree cannot be estimated9. This imaging method holds promise in the diagnosis, evaluation of operative feasibility and postoperative follow up of CTPH patients, but current experience and limitations still do not permit it to substitute Pulmonary Angiography, the gold standard.
Pulmonary Thromboendarterectomy is now the treatment of choice for CPTE, being a perspective of cure for an otherwise fatal disease. It is a complex procedure, done at limited number of centers, through a median sternotomy in cardiopulmonary bypass and deep hypothermia, necessitating long periods of total cardiac arrest3. Current criteria for surgery5 include patients in NYHA class III and IV, with a Pulmonary Vascular Resistance ( PVR ) > 300 dynes . s . cm5 , thrombus location in the main, lobar or segmental arteries, the absence of severe associated diseases, and patients willingness to accept a surgical mortality between 10 - 20 %. CTPH is being defined in trials as a mean resting pulmonary artery pressure > 25 mmHg with a mean pulmonary wedge pressure < 12 mmHg, associated with at least one segmental or larger perfusion lung scan defect and an angiographic pattern of CTPH5, as above.
Given the relatively high mortality of the procedure and potential serious complications, namely persistent pulmonary hypertension ( by means of rethrombosis or incomplete thromboendarterectomy ) and pulmonary reperfusion edema16,20, careful selection of patients and operative variables are crucial in achieving good results. Recent trials are trying to define predictors of operative mortality1,12, of which the most important are severe hemodynamic disease ( PVR > 1.100 dynes . s . cm5, pulmonary artery systolic pressure > 50 mmHg ), reduction in PVR of less than 50 % after surgery and a prolonged bypass time.
The reported results of Pulmonary Thromboendarterectomy are very encouraging1,14,15,16,17. Although reported mortality in large experienced centers are between 8.7 %3 and 25 %12, most patients go back to heart failure NYHA class I or II, with significant reductions in PVR and right ventricular dimensions, and improves cardiac index and right ventricular function; most importantly, these patients tend to return to a normal productive life. It has to be remembered that the only alternative to these severely ill patients would be lung or heart - lung transplantation, with its attendant problems of organ donation, imunossupression, rejection and a 1 year survival rate of 70 % and 4 year survival rate of 40 %6. Long term results of Pulmonary Thromboendarterectomy are also reported to be very good4,13,14, with 95 % of patients being in NYHA class I or II at 12 months4, and with sustained and progressive improvement when patients are followed for about 2 years13,14. The most important aspect of long term postoperative care is that patients need to be maintained on lifelong anticoagulation, in addition to the insertion of caval filter, which is usually inserted preoperatively if there are no contraindications, as in the patient under discussion ( complete chronic occlusion of the Inferior Vena Cava ).
Our patient did not have an encouraging early angiographic result, and by the time of this report it is too early to make conclusions about clinical improvement. The most important lesson from this case is that Pulmonary Thromboendarterectomy is a relatively safe, feasible and potentially curative treatment for CTPH, as shown by a surgery done in a country where organ transplantation is still starting to be done and resources are scarce. For this particular patient, we are planning to repeat non invasive and angiographic evaluation regularly, to document possible progressive improvements. Meanwhile, she is receiving intensive anticoagulant therapy and is starting on a rehabilitation protocol.
We are indebted to Prof. Edson A. Saad for kindly reviewing this manuscript.
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