Physical examination revealed no obesity (70 kg/172 cm, BMI 23.7 kg/m2) and no clinical signs of heart failure. Fixed splitting of the second heart sound, was notable on auscultation with systolic murmur at the base of the heart, and BP was 140/100 mmHg. Electrocardiogram demonstrated sinus rhythm, HR 73/min, QRS axis was +118°, with the changes in accordance to the previously known right bundle branch block (Figure 1). Chest X-ray was merely non-specific with enlarged heart shadow and prominent hilar vasculature. Echocardiography examination revealed normal left heart structures, left-ventricular end-diastolic diameter (LVEDD) 4.8 cm, left-ventricular end-systolic diameter (LVESD) 3.5 cm and a borderline left-ventricular ejection fraction (LVEF) 55%. Right ventricle (RV) was significantly enlarged (4.6 cm) with RV hypertrophy, and estimated systolic pressure (RVSP) of 78 mmHg. Diameter of the pulmonary artery was 3.3 cm, pulmonary regurgitation PR 2+, tricuspid regurgitation TR 2-3+, spontaneous contrast was present in the inferior caval vein (VCI) VCI - 15 mm in inspirum). Small circular pericardial effusion (6 mm) was present in the diastole.
At the initial six-minute walk test the patient was able to reach 370 m only. Lung function tests revealed normal findings and perfusion/ventilation scan detected no defects. Furthermore, chest CT scan confirmed enlargement of the main pulmonary artery to 4.2 cm, right 3.2 cm, left 3 cm. Marked enlargement of lobar and segmental branches with no signs of thromboembolic events was also notable. Moderate pericardial effusion of 20 HU density was still present as well. Vascular ultrasound examination of leg veins (Colour-Duplex scan) also revealed no signs of deep vein thrombosis. Doppler indexes of peripheral leg arteries were lower in the right than in the left leg: right anterior tibial artery (ATA) 0.80 right posterior tibial artery (ATP) 0.80, and for the left leg ATA was 0.93, and ATP 0.93.
Cardiac catheterization revealed the following pressures (systolic/diastolic/mean): right atrium (RA) 13/8/11 mmHg, right ventricle (RV) 107/0-10 mmHg, pulmonary artery (PA) 119/29/63 mmHg, pulmonary capillary wedge pressure (PCWP) 15/6/13 mmHg. Cardiac index (CI) was depressed to 1.6 l/min/m2 and pulmonary vascular resistance (PVR) was markedly increased 1381.2 (dyne*sec)/cm5.
Nitric oxide (NO) vasoreactivity test was negative.
Figure 1. Electrocardiogram at presentation revealed sinus rhythm, P pulmonale, and a right bundle branch configuration.
During the same cardiac catheterization procedure coronary angiography was performed which revealed: 80% proximal stenosis of the right coronary artery (RCA), and medial stenosis of the circumflex artery 30-40%. Significant stenosis of the RCA was successfully treated with stent implantation (Tsunami Gold 3.5x18 mm). On discharge, unfortunately no specific therapy for primary pulmonary hypertension (PAH) could be reimbursed in Serbia and the patient received: Aspirin 100 mg qd, Clopidogrel 75 mg qd for 3 months after bare-metal stent implantation (oral anticoagulation therapy with acenocoumarol to the target INR 2-3 afterwards), gliclazide 80 mg tid, simvastatin 40 mg qd, nifedipine R 20 mg bid, Lasix 40 mg every other day, and spironolactone 12.5 mg qd.
In May 2007 patient was admitted again due to the worsening of effort tolerance, dyspnoea and vertigo. Echocardiography revealed no significant deterioration apart from much larger PE (16 mm in diastole). In cardiac catheterization, mild worsening of haemodynamics was noted (Table 1). Coronary angiography revealed no progression of coronary artery disease, with no in-stent restenosis.
Table 1. Worsening of pulmonary artery hypertension after two years without PAH-specific treatment.
At the time of this hospitalization, reimbursement of sildenafil treatment became possible for patients with PAH. However, its application could have potentially dangerous hypotensive effect in the presence of moderate/large pericardial effusion (16 mm in diastole).
How would you proceed?
Would you slowly introduce PAH-specific treatment first hoping to be helpful in reduction of the pericardial effusion as well, or first drain the pericardial effusion and than be more aggressive with the up-titration of the PAH-specific treatment?
Since pericardial effusion was much larger then it would be expected in a patient with right heart failure only, we decided to initially drain the pericardial effusion and to introduce the PAH-specific treatment afterwards (Figure 2).
During the hospitalization, no recurrence of pericardial effusion was noted and Sildenafil 25 mg tid was introduced since June 2007 (slowly up-titrated to 50 mg tid). Nifedipine was stopped, and Digoxin 0.25 mg qd 5/2 days/week was added to the treatment. Clinical follow-up in the next three years revealed no worsening of symptoms or haemodynamics, as well as no recurrence of pericardial effusion in echocardiography (Table 2). The results of the 6MWT could be maintained to 650-700 m with no need to increase the doses of diuretics.
Table 2. Haemodynamics after drainage of pericardial effusion and introduction of high doses of sildenafil in the management of pulmonary artery hypertension
Figure 2. Subxiphoid pericardiocentesis (A), insertion of a 7F pericardial catheter and intrapericardial application of 40 ml of Ultravist contrast media (B) and subsequent drainage of 300 ml of pericardial effusion (C) and finally after complete drainage of total of 600 ml of serous pericardial effusion (D). Catheter was kept for prolonged, intermittent drainage for the following 4 days.
The presence of pericardial effusion in PAH usually represents advanced right heart failure and is associated with a poor prognosis. Small or moderate pericardial effusion is present in up to 54% of patients . However, pericardial effusion could be a part of clinical presentation of systemic lupus erythematodes, scleroderma or other systemic autoimmune diseases, but also a sign of the previously unknown co-morbidity (neoplastic disease, viral infection, thyroid disease, renal failure, etc.).
Patients with cor pulmonale and circumferential pericardial effusion develop an atypical form of cardiac tamponade with isolated left heart compression. Pre-existing pulmonary arterial hypertension can modify the classic presentation. Symptoms and signs of right heart failure could already be present, so a high index of suspicion for tamponade is required in the presence of symptoms indicating worsening of right heart failure. When the pericardial pressure starts to increase in a patent with cor pulmonale, elevated pressure in right heart chambers prevent right atrial and ventricular compression, but while the pericardial pressure rises to the point to exceed left chambers pressure, this results first in diastolic collapse of left atrium and later on in left ventricle collapse due to a transient reversal of the transmural pressure [2,3]. Signs of impaired filling of left ventricle ensue leading to a drop in cardiac output. The most probable mechanism of accumulation of pericardial fluid in patients with PAH is transudation and impaired re-absorption of pericardial fluid due to elevated venous hydrostatic pressure in the setting of cor pulmonale.
In the setting of PAH, large haemodynamically significant pericardial effusions might be treated surgically and/or conservative and it is known that prognosis of patients with this complication is poor [4,5]. However, our patient has been stable for 3 years after pericardiocentesis on low doses of furosemide, after up-titration of sildenafil to 50 mg tid (NT-proBNP before 600 ng/L, at the time of detection 1029 ng/L and one year after detection of circumferential pericardial effusion 601 ng/L).
Additional regular repeated echocardiographic examinations were performed. The right ventricle-to-right atrial pressure gradient may be difficult to estimate in the setting of severe tricuspid regurgitation, when there is a large colour flow regurgitant jet. In this case, the peak velocity may not reflect the true pressure gradient.
In conclusion, patients with advanced PAH have often a chronic pericardial effusion. It is the result of increased transudation and impaired re-absorption due to elevated venous pressure. These patients have pre-existent symptoms and signs of chronic right heart failure. High degree of suspicion is required to detect of development of an atypical form of tamponade with isolated compression of left heart chambers. Transthoracic echocardiography provides a rapid access to the correct diagnosis, a prompt relief of symptoms following the ultrasound guided pericardiocentesis and important diagnostic tool for regular follow up of patients thereafter.
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