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Breathtaking: Platypnea-orthodeoxia Syndrome
DIAGNOSTIC DILEMMA Aimee K. Zaas, MD, Section Editor
Breathtaking: Platypnea-orthodeoxia Syndrome Katarzyna Holcman, MD, Scott J. Cameron, MD, PhD, Elixabeth Laskurain, MD, H. Todd Massey, MD, David R. Trawick, MD, PhD, Hanna Mieszczanska, MD Division of Cardiology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY.
PRESENTATION A patient who was already coping with some respiratory compromise developed more extraordinary impairment. The 34-year-old woman presented with severe dyspnea and hypoxia, which improved while she was lying down. She was being treated for a recurrence of nodular sclerosing Hodgkin’s lymphoma, initially diagnosed as stage IIA. In addition, she had known bleomycin lung toxicity marked by a moderate decrease in lung-diffusing capacity as noted on pulmonary function testing. She had been taking enoxaparin for a pulmonary embolus diagnosed 3 weeks prior to her current presentation. A pulmonary arteriovenous malformation or an intracardiac shunt was suspected. Computerized tomography (CT) revealed a persistent pulmonary thromboembolism without any evidence for arteriovenous malformation.
Intermittent tricuspid valve stenosis resulted from the obstruction. Cardiac magnetic resonance imaging with delayed gadolinium perfusion enhancement showed a homogeneous mass that did not appear to have a local vascular supply (Figure 2). Pertinent laboratory studies revealed anemia (hemoglobin 10 g/dL) and leukopenia (white blood cell count, 3.6 103 cells/mL) with neutropenia (neutrophil count, 0.5 103 cells/mL). An activated partial thromboplastin time was 32.9 sec (normal range, 25.8-37.9 sec), prothrombin time was 14 sec (normal range, 9.2-12.3 sec), and the international normalized ratio was 1.4 (normal range, 1.0-1.2). A random factor Xa assay was therapeutic at 1 units/mL (normal range, 0.4-0.8 units/mL in our laboratory), suggesting that the enoxaparin dosage was in the effective range.
DIAGNOSIS ASSESSMENT On presentation, the patient had a heart rate of 110 beats per minute, a blood pressure of 131/79 mm Hg in the supine position, a respiratory rate of 20 breaths per minute, and a temperature of 98.2 F (36.7 C). In the supine position, her oxygen saturation on room air was 90%; it increased to 93% on 3 L of oxygen. Upon standing, the patient’s oxygen saturation dropped to 80%. The remainder of the physical exam was unremarkable. A standard 12-lead electrocardiogram (ECG) showed sinus tachycardia. A transthoracic echocardiogram with saline contrast revealed normal biventricular performance, a longitudinal right atrial mass oscillating through the tricuspid valve, and a pronounced atrial septal aneurysm with right-to-left cardiac shunting through an interatrial communication (Figure 1). Funding: None. Conflict of Interest: None. Authorship: All authors participated in writing of the manuscript and have reviewed and approved the submitted version. Requests for reprints should be addressed to Hanna Mieszczanska, MD, University of Rochester Medical Center, School of Medicine and Dentistry, 601 Elmwood Avenue, Box 679, Rochester, New York, 14642. E-mail address: [email protected] 0002-9343/$ -see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjmed.2014.02.029
The patient had platypnea-orthodeoxia syndrome resulting from blockage of the tricuspid valve by the right atrial mass. Platypnea-orthodeoxia, which might arise from a pulmonary ventilation-perfusion mismatch, is characterized by paradoxical dyspnea and deoxygenation when the patient is in the sitting or standing position; improvement occurs when the patient is supine. This phenomenon requires an anatomic communication between atria, such as an atrial septal defect or a patent foramen ovale, and a shunt with reverse directional flow upon positional change. Intracardiac shunting can occur with restrictive or constrictive pericarditis, intrinsic pulmonary disorders (emphysema, arteriovenous malformation, interstitial pulmonary fibrosis), severe liver cirrhosis, and compressive aortic aneurysms.1,2 Our patient had an oscillating atrial mass that caused positional tricuspid valve obstruction and functional stenosis. This, in combination with elevated right-sided pressure and right-to-left shunting of blood through the identified intracardiac communication, likely spurred platypneaorthodeoxia. The anatomic and physiologic phenomena in this patient resembled those seen in the rare reverse Lutembacher syndrome, which is characterized by the triad of (functional) tricuspid valve stenosis, elevated atrial
492
The American Journal of Medicine, Vol 127, No 6, June 2014
Figure 1 A right atrial mass could be seen protruding through the tricuspid valve. (A) This is what was seen on a transthoracic echocardiogram, apical 4 chamber view. (B) The mass also was visualized with a transesophageal echocardiogram. An atrial aneurysm is indicated with an arrowhead. RA ¼ right atrium; LA ¼ left atrium; LV ¼ left ventricle; RV ¼ right ventricle; TV ¼ tricuspid valve.
pressure, and shunt reversal causing hypoxemia.3 While right ventricular inflow obstruction from remodeling of the atrial septum can cause reverse Lutembacher physiology and platypnea-orthodeoxia, most reported cases occur in patients with a rheumatic tricuspid valve.4 Common cardiac masses include thrombi, fibroelastomas, and valvular vegetations. More unusual are septal hypertrophy, coronary aneurysms, and malignancies.5 The prevalence of primary cardiac malignancies is small at 0.001%-0.03%. Secondary malignancies occur with around a 30-fold greater frequency, usually as metastatic breast or renal carcinoma, lymphoma, or melanoma.6-8 Cardiac myxomas comprise around two-thirds of primary cardiac masses and tend to be left-sided. Right atrial masses tend to be indolent in nature and often manifest as right-sided heart
Figure 2 Four-chamber cardiac magnetic resonance imaging with delayed perfusion showed no enhancement. The arrowhead indicates a right atrial mass.
failure, tricuspid stenosis, superior vena cava syndrome, or pulmonary embolus—years can pass between the first symptom and the final diagnosis.5 Lymphomatous cardiac infiltration is usually seen in immune-compromised individuals, with around 50% of tumors appearing in the right atrium.9-11 Large right atrial masses have the propensity to embolize, causing a submassive or massive pulmonary embolism or with right-to-left shunting, a paradoxical embolic stroke.
MANAGEMENT Our patient underwent open cardiac surgery, and on pathological examination, the extracted mass proved to be an organized thrombus (Figure 3). Clinically, the mass manifested as platypnea-orthodeoxia syndrome. Ascertaining the etiology of this patient’s progressive dyspnea was challenging. While her restrictive lung disease and
Figure 3 Gross imaging of the right atrial mass showed it to be an organized thrombus.
Holcman et al
Orthodeoxia and Platypnea from a Right Atrial Mass
pulmonary embolus might theoretically elevate right heart pressure to precipitate a functional shunt, we have no data on the patient’s pulmonary artery pressure before or after thrombus extraction. She had affirmed adherence to her enoxaparin therapy, and the factor Xa assay was consistent with therapeutic levels. Tunneled catheter placement preceded the initial diagnosis of pulmonary embolus and likely contributed to the right atrial thrombus burden. CT excluded worsening pulmonary embolic burden or the presence of an arterialvenous malformation. Based on the profound positional hypoxia, a variable intracardiac shunt seemed plausible. Minimally-invasive right-atrial thrombus retrieval can be accomplished via percutaneous endovascular intervention with suction thrombectomy or catheter-directed thrombolysis. A more conservative tactic is the use of anticoagulants and watchful waiting. For our patient, thoracotomy and open cardiac surgery were deemed best by a team of cardiologists and cardiothoracic surgeons at our institution. Ultimately, a 4.5cm x 3.5cm right atrial thrombus, heavily adherent to the right atrium endocardium in the triangle of Koch, was removed after median sternotomy and midline pericardiotomy. The patient was placed on cardiopulmonary bypass with antithrombin III infusion. The right atrium was incised in a ‘hockey-stick’ configuration to allow visualization and removal of the thrombus, and a secundum atrial septal defect was closed. Immediately following the surgical procedure, subcutaneous enoxaparin was restarted, and after 2 days of enoxaparin, the patient’s treatment was changed to warfarin. One month later, the patient presented with chest discomfort from a large pericardial effusion, possibly secondary to postoperative seroma. She underwent pericardiocentesis without further sequelae, and her platypnea-orthodeoxia never returned. Atrial thrombus classification is assigned based on thrombus origin. Type A atrial thrombi, mobile and lobulated, originate in the deep peripheral veins and present a higher risk for pulmonary embolism, whereas type B atrial thrombi are immobile and often associated with a better prognosis.12 Our patient had a type B thrombus that was attached by a stalk to the right atrium, where it had originated. Nonetheless, it posed a greater mortality risk than is usually seen with type B thrombi, since it likely preceded the pulmonary embolus; retrospective analysis of the CT scan at the time of diagnosis did show a clear right atrial opacity suggesting occult thrombus formation. In summary, treatment options for the patient with a large right atrial thrombus range from conservative to minimally-
493
invasive to open surgical extraction. The AngioVac Cannula and Circuit (Angiodynamics, Latham, NY), a percutaneous system for suction thrombectomy, was recently approved by the Food and Drug Administration, and may become an alternative to surgical extraction.13 In a small cohort of patients, little difference in reported outcomes was noted when various techniques were compared.14 The most appropriate mechanism for atrial thrombus removal should be based on the patient’s comorbidities. A team-based approach, comprised of cardiologists, interventional cardiologists, and surgeons, is optimal.
References 1. Cheng TO. Mechanisms of platypnea-orthodeoxia: what causes water to flow uphill? Circulation. 2002;105:e47. 2. Cheng TO. Platypnea-orthodeoxia syndrome: etiology, differential diagnosis, and management. Catheter Cardiovasc Interv. 1999;47: 64-66. 3. Burke MA, Mikati IA. Platypnea-orthodeoxia syndrome associated with bioprosthetic tricuspid valve stenosis and reverse Lutembacher syndrome. Circulation. 2011;123:e222-e224. 4. Bokhari SS, Willens HJ, Lowery MH, Wanner A, Demarchena A. Orthodeoxia platypnea syndrome in a patient with lipomatous hypertrophy of the interatrial septum due to long-term steroid use. Chest. 2011;139:443-445. 5. Kuon E, Kreplin M, Weiss W, Dahm JB. The challenge presented by right atrial myxoma. Herz. 2004;29:702-709. 6. Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia, PA: Elsevier Saunders; 2012. 7. Wilson SR, Leonard JP, Geyer JT, Osborne JR, Weinsaft JW. A worrisome interventricular septum: more than meets the eye. J Am Coll Cardiol. 2011;58:e43. 8. Vahedian J, Sadeghpour A. Arterial homograft and medical therapy in pseudoaneurysm of infrarenal aorta concomitant with recurrent right ventricular thrombus in Behcet’s disease. Saudi Med J. 2006;27: 1401-1403. 9. Anghel G, Zoli V, Petti N, et al. Primary cardiac lymphoma: report of two cases occurring in immunocompetent subjects. Leuk Lymphoma. 2004;45:781-788. 10. Gouldesbrough DR, Carder PJ. Rapidly progressive cardiac failure due to lymphomatous infiltration of the myocardium. Postgrad Med J. 1989;65:668-670. 11. Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC, eds. Pathology and Genetics: Tumours of the Lung, Pleura, Thymus and Heart. Lyon, France: IARC Press; 2004. 12. Cordeiro Piçarra B, Santos AR, Dionisio P, et al. Right atrial thrombus: a rare presentation of plasminogen activator inhibitor deficiency. Rev Port Cardiol. 2012;31:171-174. 13. Todoran TM, Sobieszczyk PS, Levy MS, et al. Percutaneous extraction of right atrial mass using the Angiovac aspiration system. J Vasc Interv Radiol. 2011;22:1345-1347. 14. Chartier L, Béra J, Delomez M, et al. Free-floating thrombi in the right heart: diagnosis, management, and prognostic indexes in 38 consecutive patients. Circulation. 1999;99:2779-2783.
Breathtaking: Platypnea-orthodeoxia Syndrome Katarzyna Holcman, MD, Scott J. Cameron, MD, PhD, Elixabeth Laskurain, MD, H. Todd Massey, MD, David R. Trawick, MD, PhD, Hanna Mieszczanska, MD Division of Cardiology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY.
PRESENTATION A patient who was already coping with some respiratory compromise developed more extraordinary impairment. The 34-year-old woman presented with severe dyspnea and hypoxia, which improved while she was lying down. She was being treated for a recurrence of nodular sclerosing Hodgkin’s lymphoma, initially diagnosed as stage IIA. In addition, she had known bleomycin lung toxicity marked by a moderate decrease in lung-diffusing capacity as noted on pulmonary function testing. She had been taking enoxaparin for a pulmonary embolus diagnosed 3 weeks prior to her current presentation. A pulmonary arteriovenous malformation or an intracardiac shunt was suspected. Computerized tomography (CT) revealed a persistent pulmonary thromboembolism without any evidence for arteriovenous malformation.
Intermittent tricuspid valve stenosis resulted from the obstruction. Cardiac magnetic resonance imaging with delayed gadolinium perfusion enhancement showed a homogeneous mass that did not appear to have a local vascular supply (Figure 2). Pertinent laboratory studies revealed anemia (hemoglobin 10 g/dL) and leukopenia (white blood cell count, 3.6 103 cells/mL) with neutropenia (neutrophil count, 0.5 103 cells/mL). An activated partial thromboplastin time was 32.9 sec (normal range, 25.8-37.9 sec), prothrombin time was 14 sec (normal range, 9.2-12.3 sec), and the international normalized ratio was 1.4 (normal range, 1.0-1.2). A random factor Xa assay was therapeutic at 1 units/mL (normal range, 0.4-0.8 units/mL in our laboratory), suggesting that the enoxaparin dosage was in the effective range.
DIAGNOSIS ASSESSMENT On presentation, the patient had a heart rate of 110 beats per minute, a blood pressure of 131/79 mm Hg in the supine position, a respiratory rate of 20 breaths per minute, and a temperature of 98.2 F (36.7 C). In the supine position, her oxygen saturation on room air was 90%; it increased to 93% on 3 L of oxygen. Upon standing, the patient’s oxygen saturation dropped to 80%. The remainder of the physical exam was unremarkable. A standard 12-lead electrocardiogram (ECG) showed sinus tachycardia. A transthoracic echocardiogram with saline contrast revealed normal biventricular performance, a longitudinal right atrial mass oscillating through the tricuspid valve, and a pronounced atrial septal aneurysm with right-to-left cardiac shunting through an interatrial communication (Figure 1). Funding: None. Conflict of Interest: None. Authorship: All authors participated in writing of the manuscript and have reviewed and approved the submitted version. Requests for reprints should be addressed to Hanna Mieszczanska, MD, University of Rochester Medical Center, School of Medicine and Dentistry, 601 Elmwood Avenue, Box 679, Rochester, New York, 14642. E-mail address: [email protected] 0002-9343/$ -see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjmed.2014.02.029
The patient had platypnea-orthodeoxia syndrome resulting from blockage of the tricuspid valve by the right atrial mass. Platypnea-orthodeoxia, which might arise from a pulmonary ventilation-perfusion mismatch, is characterized by paradoxical dyspnea and deoxygenation when the patient is in the sitting or standing position; improvement occurs when the patient is supine. This phenomenon requires an anatomic communication between atria, such as an atrial septal defect or a patent foramen ovale, and a shunt with reverse directional flow upon positional change. Intracardiac shunting can occur with restrictive or constrictive pericarditis, intrinsic pulmonary disorders (emphysema, arteriovenous malformation, interstitial pulmonary fibrosis), severe liver cirrhosis, and compressive aortic aneurysms.1,2 Our patient had an oscillating atrial mass that caused positional tricuspid valve obstruction and functional stenosis. This, in combination with elevated right-sided pressure and right-to-left shunting of blood through the identified intracardiac communication, likely spurred platypneaorthodeoxia. The anatomic and physiologic phenomena in this patient resembled those seen in the rare reverse Lutembacher syndrome, which is characterized by the triad of (functional) tricuspid valve stenosis, elevated atrial
492
The American Journal of Medicine, Vol 127, No 6, June 2014
Figure 1 A right atrial mass could be seen protruding through the tricuspid valve. (A) This is what was seen on a transthoracic echocardiogram, apical 4 chamber view. (B) The mass also was visualized with a transesophageal echocardiogram. An atrial aneurysm is indicated with an arrowhead. RA ¼ right atrium; LA ¼ left atrium; LV ¼ left ventricle; RV ¼ right ventricle; TV ¼ tricuspid valve.
pressure, and shunt reversal causing hypoxemia.3 While right ventricular inflow obstruction from remodeling of the atrial septum can cause reverse Lutembacher physiology and platypnea-orthodeoxia, most reported cases occur in patients with a rheumatic tricuspid valve.4 Common cardiac masses include thrombi, fibroelastomas, and valvular vegetations. More unusual are septal hypertrophy, coronary aneurysms, and malignancies.5 The prevalence of primary cardiac malignancies is small at 0.001%-0.03%. Secondary malignancies occur with around a 30-fold greater frequency, usually as metastatic breast or renal carcinoma, lymphoma, or melanoma.6-8 Cardiac myxomas comprise around two-thirds of primary cardiac masses and tend to be left-sided. Right atrial masses tend to be indolent in nature and often manifest as right-sided heart
Figure 2 Four-chamber cardiac magnetic resonance imaging with delayed perfusion showed no enhancement. The arrowhead indicates a right atrial mass.
failure, tricuspid stenosis, superior vena cava syndrome, or pulmonary embolus—years can pass between the first symptom and the final diagnosis.5 Lymphomatous cardiac infiltration is usually seen in immune-compromised individuals, with around 50% of tumors appearing in the right atrium.9-11 Large right atrial masses have the propensity to embolize, causing a submassive or massive pulmonary embolism or with right-to-left shunting, a paradoxical embolic stroke.
MANAGEMENT Our patient underwent open cardiac surgery, and on pathological examination, the extracted mass proved to be an organized thrombus (Figure 3). Clinically, the mass manifested as platypnea-orthodeoxia syndrome. Ascertaining the etiology of this patient’s progressive dyspnea was challenging. While her restrictive lung disease and
Figure 3 Gross imaging of the right atrial mass showed it to be an organized thrombus.
Holcman et al
Orthodeoxia and Platypnea from a Right Atrial Mass
pulmonary embolus might theoretically elevate right heart pressure to precipitate a functional shunt, we have no data on the patient’s pulmonary artery pressure before or after thrombus extraction. She had affirmed adherence to her enoxaparin therapy, and the factor Xa assay was consistent with therapeutic levels. Tunneled catheter placement preceded the initial diagnosis of pulmonary embolus and likely contributed to the right atrial thrombus burden. CT excluded worsening pulmonary embolic burden or the presence of an arterialvenous malformation. Based on the profound positional hypoxia, a variable intracardiac shunt seemed plausible. Minimally-invasive right-atrial thrombus retrieval can be accomplished via percutaneous endovascular intervention with suction thrombectomy or catheter-directed thrombolysis. A more conservative tactic is the use of anticoagulants and watchful waiting. For our patient, thoracotomy and open cardiac surgery were deemed best by a team of cardiologists and cardiothoracic surgeons at our institution. Ultimately, a 4.5cm x 3.5cm right atrial thrombus, heavily adherent to the right atrium endocardium in the triangle of Koch, was removed after median sternotomy and midline pericardiotomy. The patient was placed on cardiopulmonary bypass with antithrombin III infusion. The right atrium was incised in a ‘hockey-stick’ configuration to allow visualization and removal of the thrombus, and a secundum atrial septal defect was closed. Immediately following the surgical procedure, subcutaneous enoxaparin was restarted, and after 2 days of enoxaparin, the patient’s treatment was changed to warfarin. One month later, the patient presented with chest discomfort from a large pericardial effusion, possibly secondary to postoperative seroma. She underwent pericardiocentesis without further sequelae, and her platypnea-orthodeoxia never returned. Atrial thrombus classification is assigned based on thrombus origin. Type A atrial thrombi, mobile and lobulated, originate in the deep peripheral veins and present a higher risk for pulmonary embolism, whereas type B atrial thrombi are immobile and often associated with a better prognosis.12 Our patient had a type B thrombus that was attached by a stalk to the right atrium, where it had originated. Nonetheless, it posed a greater mortality risk than is usually seen with type B thrombi, since it likely preceded the pulmonary embolus; retrospective analysis of the CT scan at the time of diagnosis did show a clear right atrial opacity suggesting occult thrombus formation. In summary, treatment options for the patient with a large right atrial thrombus range from conservative to minimally-
493
invasive to open surgical extraction. The AngioVac Cannula and Circuit (Angiodynamics, Latham, NY), a percutaneous system for suction thrombectomy, was recently approved by the Food and Drug Administration, and may become an alternative to surgical extraction.13 In a small cohort of patients, little difference in reported outcomes was noted when various techniques were compared.14 The most appropriate mechanism for atrial thrombus removal should be based on the patient’s comorbidities. A team-based approach, comprised of cardiologists, interventional cardiologists, and surgeons, is optimal.
References 1. Cheng TO. Mechanisms of platypnea-orthodeoxia: what causes water to flow uphill? Circulation. 2002;105:e47. 2. Cheng TO. Platypnea-orthodeoxia syndrome: etiology, differential diagnosis, and management. Catheter Cardiovasc Interv. 1999;47: 64-66. 3. Burke MA, Mikati IA. Platypnea-orthodeoxia syndrome associated with bioprosthetic tricuspid valve stenosis and reverse Lutembacher syndrome. Circulation. 2011;123:e222-e224. 4. Bokhari SS, Willens HJ, Lowery MH, Wanner A, Demarchena A. Orthodeoxia platypnea syndrome in a patient with lipomatous hypertrophy of the interatrial septum due to long-term steroid use. Chest. 2011;139:443-445. 5. Kuon E, Kreplin M, Weiss W, Dahm JB. The challenge presented by right atrial myxoma. Herz. 2004;29:702-709. 6. Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia, PA: Elsevier Saunders; 2012. 7. Wilson SR, Leonard JP, Geyer JT, Osborne JR, Weinsaft JW. A worrisome interventricular septum: more than meets the eye. J Am Coll Cardiol. 2011;58:e43. 8. Vahedian J, Sadeghpour A. Arterial homograft and medical therapy in pseudoaneurysm of infrarenal aorta concomitant with recurrent right ventricular thrombus in Behcet’s disease. Saudi Med J. 2006;27: 1401-1403. 9. Anghel G, Zoli V, Petti N, et al. Primary cardiac lymphoma: report of two cases occurring in immunocompetent subjects. Leuk Lymphoma. 2004;45:781-788. 10. Gouldesbrough DR, Carder PJ. Rapidly progressive cardiac failure due to lymphomatous infiltration of the myocardium. Postgrad Med J. 1989;65:668-670. 11. Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC, eds. Pathology and Genetics: Tumours of the Lung, Pleura, Thymus and Heart. Lyon, France: IARC Press; 2004. 12. Cordeiro Piçarra B, Santos AR, Dionisio P, et al. Right atrial thrombus: a rare presentation of plasminogen activator inhibitor deficiency. Rev Port Cardiol. 2012;31:171-174. 13. Todoran TM, Sobieszczyk PS, Levy MS, et al. Percutaneous extraction of right atrial mass using the Angiovac aspiration system. J Vasc Interv Radiol. 2011;22:1345-1347. 14. Chartier L, Béra J, Delomez M, et al. Free-floating thrombi in the right heart: diagnosis, management, and prognostic indexes in 38 consecutive patients. Circulation. 1999;99:2779-2783.