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A 55-Year-Old Woman With Pulmonary Hypertension, Worsening Dyspnea, and Chest Pain
CHEST
Postgraduate Education Corner PULMONARY, CRITICAL CARE, AND SLEEP PEARLS
A 55-Year-Old Woman With Pulmonary Hypertension, Worsening Dyspnea, and Chest Pain Amanda Godfrey, MD; and Hector R. Cajigas, MD, FCCP
CHEST 2014; 145(3):642–645
woman, nonsmoker, with group 1 pulA55-year-old monary arterial hypertension (PAH) secondary to
systemic lupus erythematous, New York Heart Association class II, was hospitalized for 1 day of worsening exertional dyspnea. She had associated intermittent substernal chest pain with radiation to the left arm that was aggravated by coughing and movement. The patient also had one syncopal episode while at rest. Current treatment of PAH included sildenafil, warfarin, and participation in the double-blind placebo-controlled Prostacyclin (PGI2) Receptor Agonist in Pulmonary Arterial Hypertension (GRIPHON) trial investigating selexipag, an oral prostacyclin receptor analog. Prior therapies included inhaled treprostinil, inhaled iloprost, and subcutaneous treprostinil, all discontinued because of intolerance of side effects. Physical Examination Findings and Diagnostic Studies The patient was normotensive, without tachycardia or hypoxemia. Examination of the neck, chest, heart,
and extremities revealed the following: no jugular venous pressure elevation, vesicular breath sounds without wheezing or crackles, accentuated P2 component of S2, and lack of pitting edema, clubbing, or cyanosis. Troponin I level was indeterminate at a peak of 0.07 ng/mL (, 0.05 ng/mL), and brain natriuretic peptide level was elevated at 67 pg/mL (, 50 pg/mL) from a value of 9 pg/mL 1 year earlier. ECG revealed normal sinus rhythm with right axis deviation and ST depression with T wave inversion in the anterior and anterolateral leads. Posteroanterior and lateral chest radiographs are seen in Figures 1A and 1B, respectively. Ventilationperfusion lung scan showed very low probability for pulmonary embolism. Transthoracic echocardiogram demonstrated preserved left ventricular ejection fraction (60%-65%), with pulmonary trunk and aortic root diameter of 52 mm and 22 mm, respectively. Given concern for worsening pulmonary hypertension (PH) and decompensated right ventricular function along with risk for atherosclerotic coronary artery disease with systemic lupus erythematous, the patient was scheduled for both right- and left-sided heart catheterization.
Figure 1. Chest radiograph. A, Posteroanterior. B, Lateral. 642
Postgraduate Education Corner
Figure 2. A, Coronary angiography showing the ostia of the left main coronary artery (arrow) and distal left main coronary artery (arrowhead). B and C, Intravascular ultrasound at the ostia and distal left main coronary artery, respectively. LCMA 5 left main coronary artery.
Right-sided heart catheterization revealed right atrial pressure 6 mm Hg, mean pulmonary artery pressure 59 mm Hg, left ventricular end-diastolic pressure 12 mm Hg, cardiac index 1.2 L/min/m2, and pulmonary vascular resistance of 19 Wood units. Coronary angiography (CA) and corresponding intravascular ultrasound (IVUS) images are seen in Figure 2. What is the diagnosis?
Manuscript received July 25, 2013; revision accepted August 8, 2013. Affiliations: From the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Henry Ford Hospital, Detroit, MI. Correspondence to: Hector R. Cajigas, MD, FCCP, Division of Pulmonary and Critical Care Medicine K-17, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202; e-mail: [email protected] © 2014 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-1735 journal.publications.chestnet.org
CHEST / 145 / 3 / MARCH 2014
643
Diagnosis: Extrinsic compression of the left main coronary artery by the pulmonary artery Discussion Chest pain is a common symptom experienced by patients with PH. Demand ischemia from right ventricular strain and a decrease in coronary perfusion gradient from an elevated right atrial pressure are commonly accepted mechanisms for the cause of anginal symptoms in this patient population. However, the coronary arteries cannot be ignored. Left main coronary artery (LMCA) narrowing is typically the result of atherosclerosis and is found in 3% to 5% of patients undergoing CA. Extrinsic compression of the LMCA by a dilated pulmonary artery (PA) is an increasingly recognized potential cause of angina, left ventricular dysfunction, arrhythmias, and/or sudden death in patients with PH. The exact incidence of this phenomenon in PH is unknown but varies from 5% to 44% in case series of patients with atrial septal defect. In a case series of patients with both idiopathic PAH and congenital heart disease, the incidence was 19%. The mechanism of LMCA compression by the PA is controversial but likely requires several structural changes to occur. Vascular remodeling (intimal thickening, medial hypertrophy, and luminal dilation) that occurs over time is necessary, as acute increases in the intraluminal pressure of a normal PA are not adequate to produce extrinsic compression. Dilation of the PA is critical for LMCA compression to occur. In a series of 12 patients with confirmed extrinsic compression of the LMCA, the ratio of the PA trunk to aortic root diameter ranged from 1.7 to 2.6, with a normal ratio being approximately 1.0. In a larger series of 36 patients with PH, seven patients (19%) had ⱖ 50% obstruction and inferior displacement of the LMCA. Extrinsic compression of the LMCA was associated with increased pulmonary trunk diameter and the ratio of the PA trunk to aortic root diameter. Compression did not occur with a PA trunk diameter , 40 mm and PA trunk to aortic root diameter ratio of , 1.21. The degree of obstruction may also be influenced by the anatomic relationship between the PA trunk and the origin of the LMCA. An origin of the LMCA from the right side of the left sinus of Valsalva increases the risk of compression compared with a more leftward origin. The clinical features of patients presenting with extrinsic compression of the LMCA by the PA in the setting of PH is variable. In one series, 72% of patients with PH had angina, but only 27% of the patients with angina had extrinsic compression of the LMCA. Patients variably demonstrate evidence of ischemia on nuclear imaging and left ventricular dysfunction on echocardiogram. Additionally, syncope and cardiogenic shock 644
are less common presenting manifestations of extrinsic compression of the LMCA. Advances in both invasive and noninvasive imaging have facilitated the recognition of extrinsic compression of the LMCA by the PA. The gold standard for diagnosis is CA with IVUS. On CA, the LMCA appears eccentrically narrowed at the ostium and smoothly tapers open distally (“pencil-point” finding). Additionally, the LMCA is displaced inferiorly relative to the left coronary cusp. IVUS demonstrates slit-like narrowing at the ostia from compression by the PA, without evidence of underlying atherosclerosis. Multidetector CT scan CA allows for simultaneous assessment of the PA trunk diameter, luminal diameter of the LMCA, angle of LMCA take off from the aortic root, and ventricular function. Treatment recommendations for extrinsic compression of the LMCA by the PA are variable and depend on the underlying cause of PH but include coronary artery bypass grafting, percutaneous coronary intervention (PCI), congenital heart disease correction, thromboendarterectomy, and lung or heart-lung transplant. To our knowledge, successful stenting of the LMCA in two patients with PH was first reported in 2001. Additional case reports suggest LMCA PCI in PH is safe and is associated with excellent clinical and angiographic success. Given the technical feasibility, ability to use one stent, and expected low restenosis rates, PCI should be considered the preferred revascularization strategy in patients with extrinsic compression of the LMCA by the PA. Most importantly, vigilance in detecting this potentially lethal complication of PH is necessary. Clinical Course In this case, the constellation of severe PH with marked dilatation of the PAs seen on chest radiograph, as well as anginal symptoms, raised concern for extrinsic compression of the coronary arteries. Cardiology consultation resulted in recommendation for CA to simultaneously delineate anatomy and potentially intervene. CA demonstrated 80% narrowing of the LMCA at the ostia (Fig 2, see arrow). IVUS confirmed the narrowing was secondary to extrinsic compression from the PA opposed to atherosclerosis. Given case series demonstrating that PCI can be performed safely with good technical success regarding opening and stabilizing the compressed LMCA, the decision was made to proceed with placement of a bare metal stent in the LMCA. CA and IVUS confirmed 0% residual stenosis of the LMCA, as seen in Figure 3. The importance of PA dilation in causing extrinsic compression of the LMCA is also highlighted in this case. The PA trunk and aortic root diameters were 52 mm and 22 mm, respectively, with a resultant ratio Postgraduate Education Corner
Figure 3. A, Coronary angiography at the level of the PA with no residual narrowing after placement of the bare metal stent. B, Intravascular ultrasound demonstrating resolution of the LMCA compression by the pulmonary artery after placement of bare metal stent. PA 5 pulmonary artery. See Figure 2 legend for expansion of other abbreviation.
of 2.36. The patient was initiated on clopidogrel 75 mg daily and aspirin 81 mg daily. Additionally, given the severely reduced cardiac index, treatment with IV treprostinil was subsequently initiated; however, this had to be discontinued secondary to intolerance of side effects and lack of social support. At 9-month follow-up she remains free of anginal symptoms. Clinical Pearls 1. Extrinsic compression of the LMCA by the PA is a rarely reported but potentially lethal complication of PAH that can cause angina, left ventricular dysfunction, arrhythmias, or sudden death. 2. Given the technical feasibility, ability to use one stent, and expected low restenosis rates, PCI should be considered the preferred revascularization strategy in selected patients with extrinsic compression of the LMCA. 3. Treatment of extrinsic compression of the LMCA can be life-saving, and, therefore, a high index of suspicion in detecting this complication, through CT scan CA, invasive CA, or both, is necessary. Acknowledgments Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Other contributions: We thank Eric Yang, MD, for preparing the coronary angiography and intravascular ultrasound images. This work was performed at Henry Ford Hospital, Detroit, Michigan. CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
journal.publications.chestnet.org
Suggested Readings Kothari SS, Chatterjee SS, Sharma S, Rajani M, Wasir HS. Left main coronary artery compression by dilated main pulmonary artery in atrial septal defect. Indian Heart J. 1994;46(4): 165-167. Kajita LJ, Martinez EE, Ambrose JA, et al. Extrinsic compression of the left main coronary artery by a dilated pulmonary artery: clinical, angiographic, and hemodynamic determinants. Catheter Cardiovasc Interv. 2001;52(1):49-54. Rich S, McLaughlin VV, O’Neill W. Stenting to reverse left ventricular ischemia due to left main coronary artery compression in primary pulmonary hypertension. Chest. 2001;120(4): 1412-1415. Mesquita SM, Castro CR, Ikari NM, Oliveira SA, Lopes AA. Likelihood of left main coronary artery compression based on pulmonary trunk diameter in patients with pulmonary hypertension. Am J Med. 2004;116(6):369-374. Ginghina C, Popescu BA, Enache R, Ungureanu C, Deleanu D, Platon P. Pulmonary artery dilatation: an overlooked mechanism for angina pectoris. J Cardiovasc Med (Hagerstown). 2008;9(7): 747-750. Caldera AE, Cruz-Gonzalez I, Bezerra HG, et al. Endovascular therapy for left main compression syndrome. Case report and literature review. Chest. 2009;135(6):1648-1650. de Jesus Perez VA, Haddad F, Vagelos RH, Fearon W, Feinstein J, Zamanian RT. Angina associated with left main coronary artery compression in pulmonary hypertension. J Heart Lung Transplant. 2009;28(5):527-530. Safi M, Eslami V, Shabestari AA, et al. Extrinsic compression of left main coronary artery by the pulmonary trunk secondary to pulmonary hypertension documented using 64-slice multidetector computed tomography coronary angiography. Clin Cardiol. 2009;32(8):426-428. Lee MS, Oyama J, Bhatia R, Kim YH, Park SJ. Left main coronary artery compression from pulmonary artery enlargement due to pulmonary hypertension: a contemporary review and argument for percutaneous revascularization. Catheter Cardiovasc Interv. 2010;76(4):543-550.
CHEST / 145 / 3 / MARCH 2014
645
Postgraduate Education Corner PULMONARY, CRITICAL CARE, AND SLEEP PEARLS
A 55-Year-Old Woman With Pulmonary Hypertension, Worsening Dyspnea, and Chest Pain Amanda Godfrey, MD; and Hector R. Cajigas, MD, FCCP
CHEST 2014; 145(3):642–645
woman, nonsmoker, with group 1 pulA55-year-old monary arterial hypertension (PAH) secondary to
systemic lupus erythematous, New York Heart Association class II, was hospitalized for 1 day of worsening exertional dyspnea. She had associated intermittent substernal chest pain with radiation to the left arm that was aggravated by coughing and movement. The patient also had one syncopal episode while at rest. Current treatment of PAH included sildenafil, warfarin, and participation in the double-blind placebo-controlled Prostacyclin (PGI2) Receptor Agonist in Pulmonary Arterial Hypertension (GRIPHON) trial investigating selexipag, an oral prostacyclin receptor analog. Prior therapies included inhaled treprostinil, inhaled iloprost, and subcutaneous treprostinil, all discontinued because of intolerance of side effects. Physical Examination Findings and Diagnostic Studies The patient was normotensive, without tachycardia or hypoxemia. Examination of the neck, chest, heart,
and extremities revealed the following: no jugular venous pressure elevation, vesicular breath sounds without wheezing or crackles, accentuated P2 component of S2, and lack of pitting edema, clubbing, or cyanosis. Troponin I level was indeterminate at a peak of 0.07 ng/mL (, 0.05 ng/mL), and brain natriuretic peptide level was elevated at 67 pg/mL (, 50 pg/mL) from a value of 9 pg/mL 1 year earlier. ECG revealed normal sinus rhythm with right axis deviation and ST depression with T wave inversion in the anterior and anterolateral leads. Posteroanterior and lateral chest radiographs are seen in Figures 1A and 1B, respectively. Ventilationperfusion lung scan showed very low probability for pulmonary embolism. Transthoracic echocardiogram demonstrated preserved left ventricular ejection fraction (60%-65%), with pulmonary trunk and aortic root diameter of 52 mm and 22 mm, respectively. Given concern for worsening pulmonary hypertension (PH) and decompensated right ventricular function along with risk for atherosclerotic coronary artery disease with systemic lupus erythematous, the patient was scheduled for both right- and left-sided heart catheterization.
Figure 1. Chest radiograph. A, Posteroanterior. B, Lateral. 642
Postgraduate Education Corner
Figure 2. A, Coronary angiography showing the ostia of the left main coronary artery (arrow) and distal left main coronary artery (arrowhead). B and C, Intravascular ultrasound at the ostia and distal left main coronary artery, respectively. LCMA 5 left main coronary artery.
Right-sided heart catheterization revealed right atrial pressure 6 mm Hg, mean pulmonary artery pressure 59 mm Hg, left ventricular end-diastolic pressure 12 mm Hg, cardiac index 1.2 L/min/m2, and pulmonary vascular resistance of 19 Wood units. Coronary angiography (CA) and corresponding intravascular ultrasound (IVUS) images are seen in Figure 2. What is the diagnosis?
Manuscript received July 25, 2013; revision accepted August 8, 2013. Affiliations: From the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Henry Ford Hospital, Detroit, MI. Correspondence to: Hector R. Cajigas, MD, FCCP, Division of Pulmonary and Critical Care Medicine K-17, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202; e-mail: [email protected] © 2014 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-1735 journal.publications.chestnet.org
CHEST / 145 / 3 / MARCH 2014
643
Diagnosis: Extrinsic compression of the left main coronary artery by the pulmonary artery Discussion Chest pain is a common symptom experienced by patients with PH. Demand ischemia from right ventricular strain and a decrease in coronary perfusion gradient from an elevated right atrial pressure are commonly accepted mechanisms for the cause of anginal symptoms in this patient population. However, the coronary arteries cannot be ignored. Left main coronary artery (LMCA) narrowing is typically the result of atherosclerosis and is found in 3% to 5% of patients undergoing CA. Extrinsic compression of the LMCA by a dilated pulmonary artery (PA) is an increasingly recognized potential cause of angina, left ventricular dysfunction, arrhythmias, and/or sudden death in patients with PH. The exact incidence of this phenomenon in PH is unknown but varies from 5% to 44% in case series of patients with atrial septal defect. In a case series of patients with both idiopathic PAH and congenital heart disease, the incidence was 19%. The mechanism of LMCA compression by the PA is controversial but likely requires several structural changes to occur. Vascular remodeling (intimal thickening, medial hypertrophy, and luminal dilation) that occurs over time is necessary, as acute increases in the intraluminal pressure of a normal PA are not adequate to produce extrinsic compression. Dilation of the PA is critical for LMCA compression to occur. In a series of 12 patients with confirmed extrinsic compression of the LMCA, the ratio of the PA trunk to aortic root diameter ranged from 1.7 to 2.6, with a normal ratio being approximately 1.0. In a larger series of 36 patients with PH, seven patients (19%) had ⱖ 50% obstruction and inferior displacement of the LMCA. Extrinsic compression of the LMCA was associated with increased pulmonary trunk diameter and the ratio of the PA trunk to aortic root diameter. Compression did not occur with a PA trunk diameter , 40 mm and PA trunk to aortic root diameter ratio of , 1.21. The degree of obstruction may also be influenced by the anatomic relationship between the PA trunk and the origin of the LMCA. An origin of the LMCA from the right side of the left sinus of Valsalva increases the risk of compression compared with a more leftward origin. The clinical features of patients presenting with extrinsic compression of the LMCA by the PA in the setting of PH is variable. In one series, 72% of patients with PH had angina, but only 27% of the patients with angina had extrinsic compression of the LMCA. Patients variably demonstrate evidence of ischemia on nuclear imaging and left ventricular dysfunction on echocardiogram. Additionally, syncope and cardiogenic shock 644
are less common presenting manifestations of extrinsic compression of the LMCA. Advances in both invasive and noninvasive imaging have facilitated the recognition of extrinsic compression of the LMCA by the PA. The gold standard for diagnosis is CA with IVUS. On CA, the LMCA appears eccentrically narrowed at the ostium and smoothly tapers open distally (“pencil-point” finding). Additionally, the LMCA is displaced inferiorly relative to the left coronary cusp. IVUS demonstrates slit-like narrowing at the ostia from compression by the PA, without evidence of underlying atherosclerosis. Multidetector CT scan CA allows for simultaneous assessment of the PA trunk diameter, luminal diameter of the LMCA, angle of LMCA take off from the aortic root, and ventricular function. Treatment recommendations for extrinsic compression of the LMCA by the PA are variable and depend on the underlying cause of PH but include coronary artery bypass grafting, percutaneous coronary intervention (PCI), congenital heart disease correction, thromboendarterectomy, and lung or heart-lung transplant. To our knowledge, successful stenting of the LMCA in two patients with PH was first reported in 2001. Additional case reports suggest LMCA PCI in PH is safe and is associated with excellent clinical and angiographic success. Given the technical feasibility, ability to use one stent, and expected low restenosis rates, PCI should be considered the preferred revascularization strategy in patients with extrinsic compression of the LMCA by the PA. Most importantly, vigilance in detecting this potentially lethal complication of PH is necessary. Clinical Course In this case, the constellation of severe PH with marked dilatation of the PAs seen on chest radiograph, as well as anginal symptoms, raised concern for extrinsic compression of the coronary arteries. Cardiology consultation resulted in recommendation for CA to simultaneously delineate anatomy and potentially intervene. CA demonstrated 80% narrowing of the LMCA at the ostia (Fig 2, see arrow). IVUS confirmed the narrowing was secondary to extrinsic compression from the PA opposed to atherosclerosis. Given case series demonstrating that PCI can be performed safely with good technical success regarding opening and stabilizing the compressed LMCA, the decision was made to proceed with placement of a bare metal stent in the LMCA. CA and IVUS confirmed 0% residual stenosis of the LMCA, as seen in Figure 3. The importance of PA dilation in causing extrinsic compression of the LMCA is also highlighted in this case. The PA trunk and aortic root diameters were 52 mm and 22 mm, respectively, with a resultant ratio Postgraduate Education Corner
Figure 3. A, Coronary angiography at the level of the PA with no residual narrowing after placement of the bare metal stent. B, Intravascular ultrasound demonstrating resolution of the LMCA compression by the pulmonary artery after placement of bare metal stent. PA 5 pulmonary artery. See Figure 2 legend for expansion of other abbreviation.
of 2.36. The patient was initiated on clopidogrel 75 mg daily and aspirin 81 mg daily. Additionally, given the severely reduced cardiac index, treatment with IV treprostinil was subsequently initiated; however, this had to be discontinued secondary to intolerance of side effects and lack of social support. At 9-month follow-up she remains free of anginal symptoms. Clinical Pearls 1. Extrinsic compression of the LMCA by the PA is a rarely reported but potentially lethal complication of PAH that can cause angina, left ventricular dysfunction, arrhythmias, or sudden death. 2. Given the technical feasibility, ability to use one stent, and expected low restenosis rates, PCI should be considered the preferred revascularization strategy in selected patients with extrinsic compression of the LMCA. 3. Treatment of extrinsic compression of the LMCA can be life-saving, and, therefore, a high index of suspicion in detecting this complication, through CT scan CA, invasive CA, or both, is necessary. Acknowledgments Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Other contributions: We thank Eric Yang, MD, for preparing the coronary angiography and intravascular ultrasound images. This work was performed at Henry Ford Hospital, Detroit, Michigan. CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
journal.publications.chestnet.org
Suggested Readings Kothari SS, Chatterjee SS, Sharma S, Rajani M, Wasir HS. Left main coronary artery compression by dilated main pulmonary artery in atrial septal defect. Indian Heart J. 1994;46(4): 165-167. Kajita LJ, Martinez EE, Ambrose JA, et al. Extrinsic compression of the left main coronary artery by a dilated pulmonary artery: clinical, angiographic, and hemodynamic determinants. Catheter Cardiovasc Interv. 2001;52(1):49-54. Rich S, McLaughlin VV, O’Neill W. Stenting to reverse left ventricular ischemia due to left main coronary artery compression in primary pulmonary hypertension. Chest. 2001;120(4): 1412-1415. Mesquita SM, Castro CR, Ikari NM, Oliveira SA, Lopes AA. Likelihood of left main coronary artery compression based on pulmonary trunk diameter in patients with pulmonary hypertension. Am J Med. 2004;116(6):369-374. Ginghina C, Popescu BA, Enache R, Ungureanu C, Deleanu D, Platon P. Pulmonary artery dilatation: an overlooked mechanism for angina pectoris. J Cardiovasc Med (Hagerstown). 2008;9(7): 747-750. Caldera AE, Cruz-Gonzalez I, Bezerra HG, et al. Endovascular therapy for left main compression syndrome. Case report and literature review. Chest. 2009;135(6):1648-1650. de Jesus Perez VA, Haddad F, Vagelos RH, Fearon W, Feinstein J, Zamanian RT. Angina associated with left main coronary artery compression in pulmonary hypertension. J Heart Lung Transplant. 2009;28(5):527-530. Safi M, Eslami V, Shabestari AA, et al. Extrinsic compression of left main coronary artery by the pulmonary trunk secondary to pulmonary hypertension documented using 64-slice multidetector computed tomography coronary angiography. Clin Cardiol. 2009;32(8):426-428. Lee MS, Oyama J, Bhatia R, Kim YH, Park SJ. Left main coronary artery compression from pulmonary artery enlargement due to pulmonary hypertension: a contemporary review and argument for percutaneous revascularization. Catheter Cardiovasc Interv. 2010;76(4):543-550.
CHEST / 145 / 3 / MARCH 2014
645