i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) 5 4 3 e5 4 5
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/ihj
Case Report
An unusual cause of acute cor pulmonale e Significance of the ‘continuous diaphragm sign’ Sandeep Mohanan a,*, C.G. Sajeev b, Kader Muneer c, G. Rajesh d, M.N. Krishnan e, Vivek Pillai a a
Senior Resident, Department of Cardiology, Calicut Government Medical College, Kerala, India Professor, Department of Cardiology, Calicut Government Medical College, Kerala, India c Associate Professor, Department of Cardiology, Calicut Government Medical College, Kerala, India d Additional Professor, Department of Cardiology, Calicut Government Medical College, Kerala, India e Professor and Head, Department of Cardiology, Calicut Government Medical College, Kerala, India b
article info
abstract
Article history:
A patient presented with chest pain and clinical features of acute right heart failure. Initial
Received 3 September 2013
work up revealed the presence of severe PAH. Acute pulmonary embolism is the com-
Accepted 11 August 2014
monest and most life-threatening cause for acute cor pulmonale. Even though the clinical
Available online 16 September 2014
picture suggested pulmonary embolism, a subtle sign was missed from the first chest X-ray taken in the emergency department. However on reanalysis the ‘continuous diaphragm
Keywords:
sign’ later guided us towards the diagnosis. Our case represents one of the first reports of a
Pneumomediastinum
rare etiology for acute cor pulmonale e hypersensitivity pneumonitis. Right ventricular
Cor pulmonale
dysfunction was caused by an acute rise in pulmonary artery pressures as well as by the
Hypersensitivity pneumonitis
compressive effects of pneumomediastinum. We emphasize the role played by a good quality chest X-ray early in the management of acute chest pain syndromes. However pulmonary embolism should be ruled out conclusively before redirecting attention to less malignant conditions. Copyright © 2014, Cardiological Society of India. All rights reserved.
A 27 year old male presented with sudden onset severe retrosternal chest pain and dyspnea lasting for 5e6 h. He had no significant past medical history or addictions. The symptoms developed while working at a stone-quarry where he was employed as a manual laborer.
1.
Clinical examination
On examination he was conscious, tachypnoeic and had ongoing pain. The pulse rate was 116/min, with a low volume and thready
character. All peripheral pulses were equally palpable. The respiratory rate was 38/min and supine blood pressure was 94/ 68 mmHg. JVP was elevated 10 cm above the sternal angle with prominent ‘a’ and ‘v’ waves. Oxygen saturation by pulse oximetry was 84% on room air. Cardiovascular system examination revealed a loud S2, a loud pan systolic murmur with a scratchy rub-like character over the left lower parasternal area and an RVS3. Respiratory system examination revealed fine basal inspiratory creps. Provisional clinical diagnoses of acute myocardial infarction (MI), myopericarditis, pulmonary embolism, pericardial tamponade and pneumothorax were considered.
* Corresponding author. “Deepthi”, Kavu Stop, Chevayoor P.O, Calicut, Kerala 673017, India. Fax: þ91 495 2355331. E-mail address: [email protected] (S. Mohanan). http://dx.doi.org/10.1016/j.ihj.2014.08.005 0019-4832/Copyright © 2014, Cardiological Society of India. All rights reserved.
544
2.
i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) 5 4 3 e5 4 5
Investigations
ECG showed sinus tachycardia, first degree AV block and T inversions in lead II, III and V1 to V4. An emergency chest Xray was of a poor quality. However there was no cardiomegaly, pleural effusion or significant pneumothorax. Arterial blood gases revealed significant hypoxemia (pO2 of 55 mmHg). Blood investigations showed leukocytosis with normal renal and hepatic function. The D-dimer level was 3450 ng/ml, and cardiac biomarkers (creatine kinase-MB fraction and quantitative troponin-I) were negative. Transthoracic echocardiography showed right atrial (RA) and ventricular (RV) enlargement, poor RV free wall movements (Mc Connell's sign) and moderate tricuspid regurgitation (TR) with a TR gradient of 60 mmHg. The left ventricular (LV) function was good (Ejection fraction 64%) and there was no evidence of LV regional wall motion abnormalities, structural heart disease or pericardial effusion. The findings suggested evidence of acute severe pulmonary artery hypertension (PAH) with RV dysfunction. However the parasternal echo window was poor and hence it was not possible to further characterize the pulmonary vessels and the presence of thrombi. A Doppler study of the lower limb vessels did not reveal any evidence of deep vein thrombosis. Considering his hemodynamic instability, clinical picture and investigation findings we kept a high index of suspicion for pulmonary embolism. It was hence decided not to risk the delays of a contrast CT scan. The cath-lab was activated for an emergency pulmonary angiography with adhoc intervention if needed. Meanwhile he was managed with high flow oxygen, opioid analgesics, inotropes and supportive therapy. Angiography, however, revealed no evidence of thrombi in the lower limb/pelvic veins, main pulmonary artery or its main branches. Pulmonary artery pressures were 65/28 with a mean of 41 mmHg and RV dysfunction was evidenced by pulmonary artery pulsus alternans. Since a pulmonary parenchymal cause for acute RV dysfunction was now highly likely, an erect chest X-ray (PA view) was repeated once the patient had stabilized. The ‘continuous diaphragm sign’ was now demonstrated and the radiolucency outlined the lower half of the cardiac border (Fig. 1), which suggested the presence of pneumomediastinum. There were also bilateral haziness and nodular shadows in both lung fields. The main pulmonary artery segment and the descending pulmonary artery appeared dilated. A high resolution CT of the chest subsequently revealed diffuse ground glassing with centrilobular nodules distributed symmetrically on bilateral lung fields, dilated MPA and a pneumomediastinum anterior to the heart which minimally compressed the RV (Fig. 2). The radiological features were suggestive of acute hypersensitivity pneumonitis. Subsequently pulmonary function test (PFT) showed features of combined obstructive and restrictive lung disease. On directed history-taking he revealed that he had been caretaking his employer's pigeons since previous 2 months. He was managed conservatively with oral steroids and improved gradually. A repeat echocardiogram after 1 week showed only trivial TR and an otherwise normal study with good biventricular function. He was advised against pigeon-
Fig. 1 e Erect chest X-ray PA view demonstrating the ‘continuous diaphragm sign’ (black arrows) e a thin radiolucent line between the lower cardiac border and upper border of the mid diaphragm, suggestive of pneumomediastinum. Fine reticulonodular shadows (red arrow) are noted diffusely in both lung fields.
breeding and discharged. The diagnosis was established by radiological resolution as well as symptomatic improvement after 6 months. Presently he is doing well with minimal symptoms and has normal PFT parameters.
3.
Discussion
To our knowledge, hypersensitivity pneumonitis (HP) as a cause for acute cor pulmonale has not been previously
Fig. 2 e Contrast enhanced CT of chest (lung window, just below tracheal bifurcation) showing diffuse bilateral reticular shadows and centrilobular nodules. A pneumomediastinum is seen anterior to the cardiac shadow, compressing the right ventricle. The findings were suggestive of hypersensitivity pneumonitis.
i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) 5 4 3 e5 4 5
reported. The etiology is likely pigeon-breeding (Bird fancier's lung) considering the typical temporal history and clinical improvement after contact with pigeons was stopped. Acute respiratory insults such as acute respiratory distress syndrome and the ‘chest-syndrome’ of sickle cell disease are known to cause acute cor pulmonale.1,2 However in this patient, the occurrence of pneumomediastinum significantly contributed to his acute presentation and also probably to the severe though transient RV dysfunction. Pneumomediastinum as the presenting feature of HP is a very rare entity.3 Overdistention and emphysema which occurs with obliteration of respiratory bronchioles is considered to be the pathophysiological basis.4 This primary event is followed by the Macklin effect which is the sequence of alveolar rupture, air-tracking along bronchovascular tissue planes and final spreading into the mediastinum. The Macklin effect has previously been demonstrated in several cases of spontaneous pneumomediastinum.5 Our patient being a manual laborer weight bearing induced Valsalva's maneuver may have precipitated the alveolar rupture. The primary differentials to be considered in an acute chest pain syndrome with hemodynamic compromise are acute MI, pulmonary embolism, pneumothorax, myopericarditis, acute Type-A aortic dissection and rarely pneumomediastinum. Pneumomediastinum when present is often associated with subcutaneous emphysema, pneumothorax or pleural effusion. However these associated findings are helpful only in around 30e70% patients.6,7 When present in isolation, a careful screening of the cardiac borders on a frontal chest X-ray offers the diagnosis. The ‘continuous diaphragm sign’ is a subtle sign of pneumomediastinum, first described by Levin in 1973, seen on a PA chest X-ray view as a radiolucent line between the upper border of the central diaphragm and lower cardiac border.8 It may also rarely be seen in pneumopericardium.9 Still, a CT chest is required for the diagnosis in around 30e50% of cases of spontaneous mediastinum.6,10 Acute cor pulmonale occurs due to rapid elevations of the pulmonary artery pressures, especially beyond a mean of 40 mmHg, causing RV failure and decreased cardiac output.11 Other contributors in the present case may be 1) hypoxia due to the acute pneumonitis which additionally worsened myocardial supply/demand mismatch in the RV, and 2) pneumomediastinum which compressed the RV free wall and impaired its diastolic properties. Tension pneumomediastinum by itself has been reported to lead to RV failure.12 Pulmonary embolism being the most common and lifethreatening etiology for acute cor pulmonale should always be ruled out in similar scenarios. Even though patient may initially appear stable, the evolution to RV failure and shock is
545
rapid in massive PE, with a mortality of 25e40%.13 Our case nonetheless stresses on the importance of analyzing a good quality chest X-ray in the initial work up of an acute chest pain syndrome for early exclusion of pulmonary parenchymalpleural causes.
Conflicts of interest All authors have none to declare.
references
1. Vieillard-Baron A, Schmitt JM, Augarde R, et al. Acute cor pulmonale in acute respiratory distress syndrome submitted to protective ventilation: incidence, clinical implications, and prognosis. Crit Care Med. 2001 Aug;29:1551e1555. 2. Mekontso Dessap A, Leon R, Habibi A, et al. Pulmonary hypertension and cor pulmonale during severe acute chest syndrome in sickle cell disease. Am J Respir Crit Care Med. 2008 Mar 15;177:646e653. 3. Koschel D, Handzhiev S, Cardoso C, et al. Pneumomediastinum as a primary manifestation of chronic hypersensitivity pneumonitis. Med Sci Monit. 2011;17:CS152eCS155. 4. Ichikawa Y, Tokunaga N, Kinoshita M, Rikimaru T, Kaji M. Subcutaneous and mediastinal emphysema associated with hypersensitivity pneumonitis. Chest. 1991 Mar;99:759e761. 5. Sakai M, Murayama S, Gibo M, Akamine T, Nagata O. Frequent cause of the Macklin effect in spontaneous pneumomediastinum: demonstration by multidetector-row computed tomography. J Comput Assist Tomogr. 2006 JaneFeb;30:92e94. 6. Caceres M, Braud RL, Maekawa R, Weiman DS, Garrett Jr HE. Secondary pneumomediastinum: a retrospective comparative analysis. Lung. 2009 SepeOct;187:341e346. 7. Macia I, Moya J, Ramos R, et al. Spontaneous pneumomediastinum: 41 cases. Eur J Cardiothorac Surg. 2007 Jun;31:1110e1114. 8. Levin B. The continuous diaphragm sign. A newly-recognized sign of pneumomediastinum. Clin Radiol. 1973 Jul;24:337e338. 9. Brander L, Ramsay D, Dreier D, et al. Continuous left hemidiaphragm sign revisited: a case of spontaneous pneumopericardium and literature review. Heart. 2002;88:e5. 10. Caceres M, Ali SZ, Braud R, Weiman D, Garrett Jr HE. Spontaneous pneumomediastinum: a comparative study and review of the literature. Ann Thorac Surg. 2008 Sep;86:962e966. 11. McIntyre KM, Sasahara AA. The hemodynamic response to pulmonary embolism in patients without prior cardiopulmonary disease. Am J Cardiol. 1971;28:288e294. 12. Van Stiegmann G, Brantigan CO, Hopeman AR. Tension pneumomediastinum. Arch Surg. 1977 Oct;112:1212e1215. 13. Douketis JD. Prognosis in pulmonary embolism. Curr Opin Pulm Med. 2001;7:354e359.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/ihj
Case Report
An unusual cause of acute cor pulmonale e Significance of the ‘continuous diaphragm sign’ Sandeep Mohanan a,*, C.G. Sajeev b, Kader Muneer c, G. Rajesh d, M.N. Krishnan e, Vivek Pillai a a
Senior Resident, Department of Cardiology, Calicut Government Medical College, Kerala, India Professor, Department of Cardiology, Calicut Government Medical College, Kerala, India c Associate Professor, Department of Cardiology, Calicut Government Medical College, Kerala, India d Additional Professor, Department of Cardiology, Calicut Government Medical College, Kerala, India e Professor and Head, Department of Cardiology, Calicut Government Medical College, Kerala, India b
article info
abstract
Article history:
A patient presented with chest pain and clinical features of acute right heart failure. Initial
Received 3 September 2013
work up revealed the presence of severe PAH. Acute pulmonary embolism is the com-
Accepted 11 August 2014
monest and most life-threatening cause for acute cor pulmonale. Even though the clinical
Available online 16 September 2014
picture suggested pulmonary embolism, a subtle sign was missed from the first chest X-ray taken in the emergency department. However on reanalysis the ‘continuous diaphragm
Keywords:
sign’ later guided us towards the diagnosis. Our case represents one of the first reports of a
Pneumomediastinum
rare etiology for acute cor pulmonale e hypersensitivity pneumonitis. Right ventricular
Cor pulmonale
dysfunction was caused by an acute rise in pulmonary artery pressures as well as by the
Hypersensitivity pneumonitis
compressive effects of pneumomediastinum. We emphasize the role played by a good quality chest X-ray early in the management of acute chest pain syndromes. However pulmonary embolism should be ruled out conclusively before redirecting attention to less malignant conditions. Copyright © 2014, Cardiological Society of India. All rights reserved.
A 27 year old male presented with sudden onset severe retrosternal chest pain and dyspnea lasting for 5e6 h. He had no significant past medical history or addictions. The symptoms developed while working at a stone-quarry where he was employed as a manual laborer.
1.
Clinical examination
On examination he was conscious, tachypnoeic and had ongoing pain. The pulse rate was 116/min, with a low volume and thready
character. All peripheral pulses were equally palpable. The respiratory rate was 38/min and supine blood pressure was 94/ 68 mmHg. JVP was elevated 10 cm above the sternal angle with prominent ‘a’ and ‘v’ waves. Oxygen saturation by pulse oximetry was 84% on room air. Cardiovascular system examination revealed a loud S2, a loud pan systolic murmur with a scratchy rub-like character over the left lower parasternal area and an RVS3. Respiratory system examination revealed fine basal inspiratory creps. Provisional clinical diagnoses of acute myocardial infarction (MI), myopericarditis, pulmonary embolism, pericardial tamponade and pneumothorax were considered.
* Corresponding author. “Deepthi”, Kavu Stop, Chevayoor P.O, Calicut, Kerala 673017, India. Fax: þ91 495 2355331. E-mail address: [email protected] (S. Mohanan). http://dx.doi.org/10.1016/j.ihj.2014.08.005 0019-4832/Copyright © 2014, Cardiological Society of India. All rights reserved.
544
2.
i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) 5 4 3 e5 4 5
Investigations
ECG showed sinus tachycardia, first degree AV block and T inversions in lead II, III and V1 to V4. An emergency chest Xray was of a poor quality. However there was no cardiomegaly, pleural effusion or significant pneumothorax. Arterial blood gases revealed significant hypoxemia (pO2 of 55 mmHg). Blood investigations showed leukocytosis with normal renal and hepatic function. The D-dimer level was 3450 ng/ml, and cardiac biomarkers (creatine kinase-MB fraction and quantitative troponin-I) were negative. Transthoracic echocardiography showed right atrial (RA) and ventricular (RV) enlargement, poor RV free wall movements (Mc Connell's sign) and moderate tricuspid regurgitation (TR) with a TR gradient of 60 mmHg. The left ventricular (LV) function was good (Ejection fraction 64%) and there was no evidence of LV regional wall motion abnormalities, structural heart disease or pericardial effusion. The findings suggested evidence of acute severe pulmonary artery hypertension (PAH) with RV dysfunction. However the parasternal echo window was poor and hence it was not possible to further characterize the pulmonary vessels and the presence of thrombi. A Doppler study of the lower limb vessels did not reveal any evidence of deep vein thrombosis. Considering his hemodynamic instability, clinical picture and investigation findings we kept a high index of suspicion for pulmonary embolism. It was hence decided not to risk the delays of a contrast CT scan. The cath-lab was activated for an emergency pulmonary angiography with adhoc intervention if needed. Meanwhile he was managed with high flow oxygen, opioid analgesics, inotropes and supportive therapy. Angiography, however, revealed no evidence of thrombi in the lower limb/pelvic veins, main pulmonary artery or its main branches. Pulmonary artery pressures were 65/28 with a mean of 41 mmHg and RV dysfunction was evidenced by pulmonary artery pulsus alternans. Since a pulmonary parenchymal cause for acute RV dysfunction was now highly likely, an erect chest X-ray (PA view) was repeated once the patient had stabilized. The ‘continuous diaphragm sign’ was now demonstrated and the radiolucency outlined the lower half of the cardiac border (Fig. 1), which suggested the presence of pneumomediastinum. There were also bilateral haziness and nodular shadows in both lung fields. The main pulmonary artery segment and the descending pulmonary artery appeared dilated. A high resolution CT of the chest subsequently revealed diffuse ground glassing with centrilobular nodules distributed symmetrically on bilateral lung fields, dilated MPA and a pneumomediastinum anterior to the heart which minimally compressed the RV (Fig. 2). The radiological features were suggestive of acute hypersensitivity pneumonitis. Subsequently pulmonary function test (PFT) showed features of combined obstructive and restrictive lung disease. On directed history-taking he revealed that he had been caretaking his employer's pigeons since previous 2 months. He was managed conservatively with oral steroids and improved gradually. A repeat echocardiogram after 1 week showed only trivial TR and an otherwise normal study with good biventricular function. He was advised against pigeon-
Fig. 1 e Erect chest X-ray PA view demonstrating the ‘continuous diaphragm sign’ (black arrows) e a thin radiolucent line between the lower cardiac border and upper border of the mid diaphragm, suggestive of pneumomediastinum. Fine reticulonodular shadows (red arrow) are noted diffusely in both lung fields.
breeding and discharged. The diagnosis was established by radiological resolution as well as symptomatic improvement after 6 months. Presently he is doing well with minimal symptoms and has normal PFT parameters.
3.
Discussion
To our knowledge, hypersensitivity pneumonitis (HP) as a cause for acute cor pulmonale has not been previously
Fig. 2 e Contrast enhanced CT of chest (lung window, just below tracheal bifurcation) showing diffuse bilateral reticular shadows and centrilobular nodules. A pneumomediastinum is seen anterior to the cardiac shadow, compressing the right ventricle. The findings were suggestive of hypersensitivity pneumonitis.
i n d i a n h e a r t j o u r n a l 6 6 ( 2 0 1 4 ) 5 4 3 e5 4 5
reported. The etiology is likely pigeon-breeding (Bird fancier's lung) considering the typical temporal history and clinical improvement after contact with pigeons was stopped. Acute respiratory insults such as acute respiratory distress syndrome and the ‘chest-syndrome’ of sickle cell disease are known to cause acute cor pulmonale.1,2 However in this patient, the occurrence of pneumomediastinum significantly contributed to his acute presentation and also probably to the severe though transient RV dysfunction. Pneumomediastinum as the presenting feature of HP is a very rare entity.3 Overdistention and emphysema which occurs with obliteration of respiratory bronchioles is considered to be the pathophysiological basis.4 This primary event is followed by the Macklin effect which is the sequence of alveolar rupture, air-tracking along bronchovascular tissue planes and final spreading into the mediastinum. The Macklin effect has previously been demonstrated in several cases of spontaneous pneumomediastinum.5 Our patient being a manual laborer weight bearing induced Valsalva's maneuver may have precipitated the alveolar rupture. The primary differentials to be considered in an acute chest pain syndrome with hemodynamic compromise are acute MI, pulmonary embolism, pneumothorax, myopericarditis, acute Type-A aortic dissection and rarely pneumomediastinum. Pneumomediastinum when present is often associated with subcutaneous emphysema, pneumothorax or pleural effusion. However these associated findings are helpful only in around 30e70% patients.6,7 When present in isolation, a careful screening of the cardiac borders on a frontal chest X-ray offers the diagnosis. The ‘continuous diaphragm sign’ is a subtle sign of pneumomediastinum, first described by Levin in 1973, seen on a PA chest X-ray view as a radiolucent line between the upper border of the central diaphragm and lower cardiac border.8 It may also rarely be seen in pneumopericardium.9 Still, a CT chest is required for the diagnosis in around 30e50% of cases of spontaneous mediastinum.6,10 Acute cor pulmonale occurs due to rapid elevations of the pulmonary artery pressures, especially beyond a mean of 40 mmHg, causing RV failure and decreased cardiac output.11 Other contributors in the present case may be 1) hypoxia due to the acute pneumonitis which additionally worsened myocardial supply/demand mismatch in the RV, and 2) pneumomediastinum which compressed the RV free wall and impaired its diastolic properties. Tension pneumomediastinum by itself has been reported to lead to RV failure.12 Pulmonary embolism being the most common and lifethreatening etiology for acute cor pulmonale should always be ruled out in similar scenarios. Even though patient may initially appear stable, the evolution to RV failure and shock is
545
rapid in massive PE, with a mortality of 25e40%.13 Our case nonetheless stresses on the importance of analyzing a good quality chest X-ray in the initial work up of an acute chest pain syndrome for early exclusion of pulmonary parenchymalpleural causes.
Conflicts of interest All authors have none to declare.
references
1. Vieillard-Baron A, Schmitt JM, Augarde R, et al. Acute cor pulmonale in acute respiratory distress syndrome submitted to protective ventilation: incidence, clinical implications, and prognosis. Crit Care Med. 2001 Aug;29:1551e1555. 2. Mekontso Dessap A, Leon R, Habibi A, et al. Pulmonary hypertension and cor pulmonale during severe acute chest syndrome in sickle cell disease. Am J Respir Crit Care Med. 2008 Mar 15;177:646e653. 3. Koschel D, Handzhiev S, Cardoso C, et al. Pneumomediastinum as a primary manifestation of chronic hypersensitivity pneumonitis. Med Sci Monit. 2011;17:CS152eCS155. 4. Ichikawa Y, Tokunaga N, Kinoshita M, Rikimaru T, Kaji M. Subcutaneous and mediastinal emphysema associated with hypersensitivity pneumonitis. Chest. 1991 Mar;99:759e761. 5. Sakai M, Murayama S, Gibo M, Akamine T, Nagata O. Frequent cause of the Macklin effect in spontaneous pneumomediastinum: demonstration by multidetector-row computed tomography. J Comput Assist Tomogr. 2006 JaneFeb;30:92e94. 6. Caceres M, Braud RL, Maekawa R, Weiman DS, Garrett Jr HE. Secondary pneumomediastinum: a retrospective comparative analysis. Lung. 2009 SepeOct;187:341e346. 7. Macia I, Moya J, Ramos R, et al. Spontaneous pneumomediastinum: 41 cases. Eur J Cardiothorac Surg. 2007 Jun;31:1110e1114. 8. Levin B. The continuous diaphragm sign. A newly-recognized sign of pneumomediastinum. Clin Radiol. 1973 Jul;24:337e338. 9. Brander L, Ramsay D, Dreier D, et al. Continuous left hemidiaphragm sign revisited: a case of spontaneous pneumopericardium and literature review. Heart. 2002;88:e5. 10. Caceres M, Ali SZ, Braud R, Weiman D, Garrett Jr HE. Spontaneous pneumomediastinum: a comparative study and review of the literature. Ann Thorac Surg. 2008 Sep;86:962e966. 11. McIntyre KM, Sasahara AA. The hemodynamic response to pulmonary embolism in patients without prior cardiopulmonary disease. Am J Cardiol. 1971;28:288e294. 12. Van Stiegmann G, Brantigan CO, Hopeman AR. Tension pneumomediastinum. Arch Surg. 1977 Oct;112:1212e1215. 13. Douketis JD. Prognosis in pulmonary embolism. Curr Opin Pulm Med. 2001;7:354e359.
