- Email: [email protected]
Con: Dynamic Left Ventricular Outflow Tract Obstruction Should Be Considered an “Unexpected” Finding in Patients With End-Stage Liver Disease Undergoing Dobutamine Stress Echocardiography in Preparation for Liver Transplantation
Author’s Accepted Manuscript Con: Dynamic LVOT Obstruction Should Be Considered an “Unexpected” Finding in Patients with End Stage Liver Disease Undergoing Dobutamine Stress Echocardiography in Preparation for Liver Transplantation Sandeep Khanna, Ronak Raval, Ihab Dorotta www.elsevier.com/locate/buildenv
PII: DOI: Reference:
S1053-0770(17)30417-2 http://dx.doi.org/10.1053/j.jvca.2017.04.025 YJCAN4107
To appear in: Journal of Cardiothoracic and Vascular Anesthesia Cite this article as: Sandeep Khanna, Ronak Raval and Ihab Dorotta, Con: Dynamic LVOT Obstruction Should Be Considered an “Unexpected” Finding in Patients with End Stage Liver Disease Undergoing Dobutamine Stress Echocardiography in Preparation for Liver Transplantation, Journal of Cardiothoracic and Vascular Anesthesia, http://dx.doi.org/10.1053/j.jvca.2017.04.025 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Con: Dynamic LVOT Obstruction Should Be Considered an “Unexpected” Finding in Patients with End Stage Liver Disease Undergoing Dobutamine Stress Echocardiography in Preparation for Liver Transplantation.
Sandeep Khanna, MD*, Ronak Raval, MD†, Ihab Dorotta, MD†
From the * Department of General Anesthesiology, Cleveland Clinic Foundation, Cleveland, OH; and †Department of Anesthesiology, Loma Linda University Medical Center, Loma Linda, CA.
Corresponding Author. Also address reprint requests to
Sandeep Khanna, MD, Cleveland Clinic Foundation Department of General Anesthesiology 9500 Euclid Avenue, NA 3 Cleveland, Ohio 44195. E-mail: [email protected]
1
Physiologic homeostasis requires a delicate balance between multiple organ systems. The cardiopulmonary and hepatic systems are intricately linked such that end stage disease affecting one system typically leads to profound dysfunction in the other. The presence of cardiac cirrhosis in heart failure and cirrhotic cardiomyopathy in end stage liver disease are manifest examples of this relationship.1,2 Fatigue and shortness of breath are common symptoms in cirrhotic patients.3,4 Dyspnea is often attributed to respiratory muscle abnormalities, restriction from ascites, hepatopulmonary syndrome, portopulmonary hypertension or hepatic hydrothorax.5,6 Alternately, dyspnea can be a manifestation of cirrhotic cardiomyopathy or coronary artery disease. 2,7-9 Traditionally, the cirrhotic physiology was thought to be protective against coronary artery disease (CAD) given the presence of hypolipemia, thrombocytopenia, hypocoagulability and hypotension.7 However, prevalence of CAD in patients with cirrhosis is either equal to or greater than the incidence in the normal population, and ranges from 2.5 to 27%.8 Consequently, guidelines from the American Heart Association and the Association for Study of Liver Diseases support the use of Dobutamine Stress Echocardiography (DSE) as an initial screening modality, emphasizing that positive tests may require confirmation with left heart catheterization.8,9 Dobutamine is a synthetic catecholamine with a strong affinity for β receptors. Its inotropic effect exceeds its chronotropic ability.10 Pharmacologically, the basis of DSE is to induce a myocardial oxygen supply-demand mismatch and evaluate chronotropic competence. Typically patients who develop regional wall motion abnormalities or cannot achieve a 85% or greater maximum predicted heart rate are subjected to further cardiac work up to evaluate extent of coronary artery disease.11
2
In susceptible patients, the inotropic effect of dobutamine can lead to vigorous myocardial contraction and result in midcavitary or left ventricular outflow tract obstruction (LVOTO). Such patients who do not have resting LVOTO but develop intracavitary obstruction during DSE with gradients of more than 30 mmHg are said to have latent LVOTO.12,13 This is in contrast to dynamic LVOTO which has a resting gradient of > 30 mmHg. Dynamic LVOTO is seen in patients with hypertrophic cardiomyopathy (HCM) and its mechanism is well established.14-16 Latent LVOTO has been reported in patients with and without left ventricular hypertrophy, postmitral valve repair and aortic valve surgery, and with acute coronary syndromes, apical ballooning syndrome, amyloidosis and Anderson-Fabry disease.17-22 Interestingly, HCM patients without dynamic LVOTO have been shown to have latent LVOTO.12 Mechanistically, latent LVOTO can arise from a narrow LVOT or basal septal hypertrophy with septal bulging.13,23,24 The latter is typically seen in the elderly and hypertensive population. Patients with either form of LVOTO can present with dyspnea, chest pain, fatigue or heart failure with preserved ejection fraction, and have worse survival.12,13,16,23-28
Pellikka et al were among the first to describe the development of an intracavitary gradient during DSE in 1992.29 In their study, 12 of 57 (21%) patients developed LVOTO during DSE. Interestingly, 83% of their patients who developed LVOTO during DSE had a history of chest pain or dyspnea but only 33% of patients had demonstrable ischemic changes on DSE. They pointed out that the clinical symptoms of chest pain and dyspnea in the absence of significant CAD may be related to intracavitary obstruction. Luria et al, in their bid to investigate the clinical significance of this finding, studied 394 patients who underwent DSE.30 Sixty-nine patients developed an intraventricular gradient > 36 mmHg at the peak of dobutamine infusion to
3
yield a latent LVOTO prevalence of 17.5%. Additionally, the number of patients who underwent DSE for evaluation of unexplained chest pain or dyspnea was significantly greater in the group with LVOTO (75.3% vs 54.9%; p < 0.002). Surprisingly, only 6 of the 69 patients who developed LVOTO had known CAD, and only 2 of the 69 patients had a positive DSE. The mechanism leading to chest pain and dyspnea in the other 67 patients could not be attributed to CAD. Interestingly, the group demonstrating latent LVOTO did have a higher prevalence of basal septal hypertrophy (33% vs 16.9%; p < 0.002). It is now known that basal septal hypertrophy in itself can contribute to the genesis of heart failure with preserved ejection fraction.25 Similarly, Dawn et al studied 362 consecutive patients without aortic stenosis, mitral valve prolapse, and/or LVOT or midcavitary obstruction at rest, undergoing clinically indicated DSE.27 Twelve percent of their patients developed dynamic LVOTO during DSE. At a mean follow up period of 31 ± 13 months, these patients were more likely to develop or complain of chest pain, syncope or near-syncope as compared to patients who did not develop any LVOTO. Henein et al have demonstrated that LVOTO rather than diastolic dysfunction or myocardial ischemia is responsible for dyspnea in non-HCM patients with septal hypertrophy.28 Negative inotropic therapy has been shown to ameliorate symptoms in such patients.26,31,32 Data from these studies strongly suggest that latent LVOTO is a significant cause of dyspnea and future cardiac events. The cardiology literature examining the clinical significance of LVOTO during DSE in both HCM and non-HCM patients is robust, but surprisingly there is a paucity of studies specifically looking at this phenomenon in patients with end-stage liver disease. In their retrospective study, Maraj et al did not find any difference in short term outcomes in cirrhotic patients with and without inducible LVOT gradients during DSE.33 The prevalence of latent LVOTO was 43%, significantly higher than the 12 to 21% prevalence previously reported in 4
non-cirrhotic populations.26-30 They postulated that vasoplegia and hyperdynamic circulation in cirrhosis potentiate LVOTO. Follow-up of patients was only for 5 days postoperatively, and long-term outcomes were not examined. Post-liver transplant cardiovascular events are a leading cause of non-graft related morbidity and mortality.34,35 While short-term mortality results from heart failure, long-term mortality is driven primarily by CAD. Although we know with certainty that patients with latent LVOTO in the normal population are prone to developing heart failure, it is currently unknown if the same holds true for liver graft recipients.
In the absence of contradictory evidence, it may be prudent to consider the development of LVOTO during DSE in pre-transplant end-stage liver disease patients an unexpected finding as it may be a marker for outflow tract abnormalities, and may lead to increased future cardiac morbidity.
5
References 1. Møller S, Bernardi M: Interactions of the heart and the liver. Eur Heart J 34:2804-11, 2013 2. Milani A, Zaccaria R, Bombardieri G, et al: Cirrhotic cardiomyopathy. Dig Liver Dis 39:507-15, 2007 3. Singh C, Sager JS: Pulmonary complications of cirrhosis. Med Clin North Am 93:87183, 2009 4. Ramalingam VS, Ansari S, Fisher M: Respiratory complication in liver disease. Crit Care Clin 32:357-69, 2016 5. Kaltsakas G, Antoniou E, Palamidas AF, et al: Dyspnea and respiratory muscle strength in end-stage liver disease. World J Hepatol 5:56-63, 2013 6. Sameh AA, Maha Y, Hany AH: Respiratory muscle strength, hypoxemia and dyspnea in liver cirrhosis patients. Egyptian Journal of Chest Diseases and Tuberculosis. 63:105964, 2014 7. An J, Shim JH, Kim SO, et al: Prevalence and prediction of coronary artery disease in patients with liver cirrhosis: A registry-based matched case-control study. Circulation 130:1353-62, 2014 8. Lentine KL, Costa SP, Weir MR, et al: Cardiac disease evaluation and management among kidney and liver transplantation candidates: A scientific statement from the American Heart Association and the American College of Cardiology Foundation: Endorsed by the American Society of Transplant Surgeons, American Society of Transplantation, and National Kidney Foundation. Circulation 126:617-63, 2012
6
9. Murray KF, Carithers RL Jr, et al: AASLD Practice Guidelines: Evaluation of the patient for liver transplantation. Hepatology 41:1407-32 10. Overgaard CB, Dzavik V: Inotropes and vasopressors: A review of physiology and clinical use in cardiovascular disease. Circulation 118:1047-56, 2008 11. Gottdiener JS, Bednarz J, Devereux R, et al: American Society of Echocardiography recommendations for using echocardiography in clinical trials. J Am Soc Echocardiogr 20:1021-34, 2004 12. Vaglio JC Jr., Ommen SR, Nishimura RA, et al: Clinical characteristics and outcomes of patients with hypertrophic cardiomyopathy with latent obstruction. Am Heart J 156:3427, 2008 13. Hiroaki S, Hitoshi S, Tokuhisa U, et al: Basic echocardiographic features of patients with latent left ventricular outflow tract obstruction without left ventricular hypertrophy. Int Heart J 53:230-3, 2012 14. Jiang L, Levine RA, King ME, et al: An integrated mechanism for systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy based on echocardiographic observations. Am Heart J 113:633-44, 1987 15. Sherrid M, Chu CK, Delia E, et al: An echocardiographic study of the fluid mechanics of obstruction in hypertrophic cardiomyopathy. J Am Coll Cardiol 22:816-25, 1993 16. Maron MS, Olivotto I, Zenovich AG, et al: Hypertrophic cardiomyopathy is predominantly a disease of the left ventricular outflow tract. Circulation114: 2232-9, 2006 17. Melero JM, Rodríguez I, Such M, et al: Left ventricular outflow with mitral mechanical prosthesis. Ann Thorac Surg 68:55-7, 1999
7
18. Bartunek J, Sys SU, Rodrigues AC, et al: Abnormal systolic intraventricular flow velocities after valve replacement for aortic stenosis. Mechanisms, predictive factors, and prognostic significance. Circulation 93:712-9, 1996 19. Haley JH, Sinak LJ, Tajik AJ, et al: Dynamic left ventricular outflow tract obstruction in acute coronary syndromes: An important cause of new systolic murmur and cardiogenic shock. Mayo Clin Proc 74:901-6, 1999 20. Merli E, Sutcliffe S, Gori M, et al: Tako-tsubo cardiomyopathy: New insights into the possible underlying pathophysiology Eur J Echocardiogr 7:53-61, 2006 21. Dinwoodey DL, Skinner M, Maron MS, et al: Light-chain amyloidosis with echocardiographic features of hypertrophic cardiomyopathy Am J Cardiol 101:674-6, 2008 22. Calcagnino M, O'Mahony C, Coats C, et al: Exercise-induced left ventricular outflow tract obstruction in symptomatic patients with Anderson-Fabry disease. J Am Coll Cardiol 58:88-9, 2011 23. Masaaki S, Tokuhisa U, Shunsuke M, et al: Dynamic narrowing of left ventricular outflow tract--Possible mechanism of latent left ventricular outflow obstruction. Journal of Cardiology Cases 2:74-7, 2010 24. Kelshiker MA, Mayet J, Unsworth B, et al. Basal septal hypertrophy. Curr Cardiol Rev 9:325-30, 2013 25. Park SM, Kim MN, Kim SA, et al: Clinical significance of dynamic left ventricular outflow tract obstruction during dobutamine stress echocardiography in women with suspected coronary artery disease. Circ J 79:2255-62, 2015
8
26. Barletta G, Del Bene MR, Gallini C, et al: The clinical impact of dynamic intraventricular obstruction during dobutamine stress echocardiography. Int J Cardiol 70:179-89, 1999 27. Dawn B, Paliwal VS, Raza ST, et al: Left ventricular outflow tract obstruction provoked during dobutamine stress echocardiography predicts future chest pain, syncope, and near syncope. Am Heart J 149:908-16, 2005 28. Henein MY, O’Sullivan C, Sutton GC, et al: Stress-induced left ventricular outflow tract obstruction: A potential cause of dyspnea in the elderly. J Am Coll Cardiol 30:1301-7, 1997 29. Pellikka PA, Oh JK, Bailey KR, et al: Dynamic intraventricular obstruction during dobutamine stress echocardiography: A new observation. Circulation 86:1429-32, 1992 30. Luria D, Klutstein MW, Rosenmann D, et al: Prevalence and significance of left ventricular outflow gradient during dobutamine echocardiography. Eur Heart J 20:38692, 1999 31. Al-Nasser F, Duncan A, Sharma R, et al: Beta-blocker therapy for dynamic leftventricular outflow tract obstruction. Int J Cardiol 86:199-205, 2002 32. Ranasinghe I, Yeoh T, Yiannikas J: Negative ionotropic agents for the treatment of left ventricular outflow tract obstruction due to sigmoid septum and concentric left ventricular hypertrophy. Heart Lung Circ 20:579-86, 2011 33. Maraj S, Jacobs LE, Maraj R, et al. Inducible left ventricular outflow tract gradient during dobutamine stress echocardiography: An association with intraoperative hypotension but not a contraindication to liver transplantation. Echocardiography 21:6815, 2004
9
34. Zaky A, Bendjelid K: Appraising cardiac dysfunction in liver transplantation: an ongoing challenge. Liver Int 35:12-29, 2015 35. Therapondos G, Flapan AD, Plevris JN, et al: Cardiac morbidity and mortality related to orthotopic liver transplantation. Liver Transpl 10:1441-53, 2004
10
PII: DOI: Reference:
S1053-0770(17)30417-2 http://dx.doi.org/10.1053/j.jvca.2017.04.025 YJCAN4107
To appear in: Journal of Cardiothoracic and Vascular Anesthesia Cite this article as: Sandeep Khanna, Ronak Raval and Ihab Dorotta, Con: Dynamic LVOT Obstruction Should Be Considered an “Unexpected” Finding in Patients with End Stage Liver Disease Undergoing Dobutamine Stress Echocardiography in Preparation for Liver Transplantation, Journal of Cardiothoracic and Vascular Anesthesia, http://dx.doi.org/10.1053/j.jvca.2017.04.025 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Con: Dynamic LVOT Obstruction Should Be Considered an “Unexpected” Finding in Patients with End Stage Liver Disease Undergoing Dobutamine Stress Echocardiography in Preparation for Liver Transplantation.
Sandeep Khanna, MD*, Ronak Raval, MD†, Ihab Dorotta, MD†
From the * Department of General Anesthesiology, Cleveland Clinic Foundation, Cleveland, OH; and †Department of Anesthesiology, Loma Linda University Medical Center, Loma Linda, CA.
Corresponding Author. Also address reprint requests to
Sandeep Khanna, MD, Cleveland Clinic Foundation Department of General Anesthesiology 9500 Euclid Avenue, NA 3 Cleveland, Ohio 44195. E-mail: [email protected]
1
Physiologic homeostasis requires a delicate balance between multiple organ systems. The cardiopulmonary and hepatic systems are intricately linked such that end stage disease affecting one system typically leads to profound dysfunction in the other. The presence of cardiac cirrhosis in heart failure and cirrhotic cardiomyopathy in end stage liver disease are manifest examples of this relationship.1,2 Fatigue and shortness of breath are common symptoms in cirrhotic patients.3,4 Dyspnea is often attributed to respiratory muscle abnormalities, restriction from ascites, hepatopulmonary syndrome, portopulmonary hypertension or hepatic hydrothorax.5,6 Alternately, dyspnea can be a manifestation of cirrhotic cardiomyopathy or coronary artery disease. 2,7-9 Traditionally, the cirrhotic physiology was thought to be protective against coronary artery disease (CAD) given the presence of hypolipemia, thrombocytopenia, hypocoagulability and hypotension.7 However, prevalence of CAD in patients with cirrhosis is either equal to or greater than the incidence in the normal population, and ranges from 2.5 to 27%.8 Consequently, guidelines from the American Heart Association and the Association for Study of Liver Diseases support the use of Dobutamine Stress Echocardiography (DSE) as an initial screening modality, emphasizing that positive tests may require confirmation with left heart catheterization.8,9 Dobutamine is a synthetic catecholamine with a strong affinity for β receptors. Its inotropic effect exceeds its chronotropic ability.10 Pharmacologically, the basis of DSE is to induce a myocardial oxygen supply-demand mismatch and evaluate chronotropic competence. Typically patients who develop regional wall motion abnormalities or cannot achieve a 85% or greater maximum predicted heart rate are subjected to further cardiac work up to evaluate extent of coronary artery disease.11
2
In susceptible patients, the inotropic effect of dobutamine can lead to vigorous myocardial contraction and result in midcavitary or left ventricular outflow tract obstruction (LVOTO). Such patients who do not have resting LVOTO but develop intracavitary obstruction during DSE with gradients of more than 30 mmHg are said to have latent LVOTO.12,13 This is in contrast to dynamic LVOTO which has a resting gradient of > 30 mmHg. Dynamic LVOTO is seen in patients with hypertrophic cardiomyopathy (HCM) and its mechanism is well established.14-16 Latent LVOTO has been reported in patients with and without left ventricular hypertrophy, postmitral valve repair and aortic valve surgery, and with acute coronary syndromes, apical ballooning syndrome, amyloidosis and Anderson-Fabry disease.17-22 Interestingly, HCM patients without dynamic LVOTO have been shown to have latent LVOTO.12 Mechanistically, latent LVOTO can arise from a narrow LVOT or basal septal hypertrophy with septal bulging.13,23,24 The latter is typically seen in the elderly and hypertensive population. Patients with either form of LVOTO can present with dyspnea, chest pain, fatigue or heart failure with preserved ejection fraction, and have worse survival.12,13,16,23-28
Pellikka et al were among the first to describe the development of an intracavitary gradient during DSE in 1992.29 In their study, 12 of 57 (21%) patients developed LVOTO during DSE. Interestingly, 83% of their patients who developed LVOTO during DSE had a history of chest pain or dyspnea but only 33% of patients had demonstrable ischemic changes on DSE. They pointed out that the clinical symptoms of chest pain and dyspnea in the absence of significant CAD may be related to intracavitary obstruction. Luria et al, in their bid to investigate the clinical significance of this finding, studied 394 patients who underwent DSE.30 Sixty-nine patients developed an intraventricular gradient > 36 mmHg at the peak of dobutamine infusion to
3
yield a latent LVOTO prevalence of 17.5%. Additionally, the number of patients who underwent DSE for evaluation of unexplained chest pain or dyspnea was significantly greater in the group with LVOTO (75.3% vs 54.9%; p < 0.002). Surprisingly, only 6 of the 69 patients who developed LVOTO had known CAD, and only 2 of the 69 patients had a positive DSE. The mechanism leading to chest pain and dyspnea in the other 67 patients could not be attributed to CAD. Interestingly, the group demonstrating latent LVOTO did have a higher prevalence of basal septal hypertrophy (33% vs 16.9%; p < 0.002). It is now known that basal septal hypertrophy in itself can contribute to the genesis of heart failure with preserved ejection fraction.25 Similarly, Dawn et al studied 362 consecutive patients without aortic stenosis, mitral valve prolapse, and/or LVOT or midcavitary obstruction at rest, undergoing clinically indicated DSE.27 Twelve percent of their patients developed dynamic LVOTO during DSE. At a mean follow up period of 31 ± 13 months, these patients were more likely to develop or complain of chest pain, syncope or near-syncope as compared to patients who did not develop any LVOTO. Henein et al have demonstrated that LVOTO rather than diastolic dysfunction or myocardial ischemia is responsible for dyspnea in non-HCM patients with septal hypertrophy.28 Negative inotropic therapy has been shown to ameliorate symptoms in such patients.26,31,32 Data from these studies strongly suggest that latent LVOTO is a significant cause of dyspnea and future cardiac events. The cardiology literature examining the clinical significance of LVOTO during DSE in both HCM and non-HCM patients is robust, but surprisingly there is a paucity of studies specifically looking at this phenomenon in patients with end-stage liver disease. In their retrospective study, Maraj et al did not find any difference in short term outcomes in cirrhotic patients with and without inducible LVOT gradients during DSE.33 The prevalence of latent LVOTO was 43%, significantly higher than the 12 to 21% prevalence previously reported in 4
non-cirrhotic populations.26-30 They postulated that vasoplegia and hyperdynamic circulation in cirrhosis potentiate LVOTO. Follow-up of patients was only for 5 days postoperatively, and long-term outcomes were not examined. Post-liver transplant cardiovascular events are a leading cause of non-graft related morbidity and mortality.34,35 While short-term mortality results from heart failure, long-term mortality is driven primarily by CAD. Although we know with certainty that patients with latent LVOTO in the normal population are prone to developing heart failure, it is currently unknown if the same holds true for liver graft recipients.
In the absence of contradictory evidence, it may be prudent to consider the development of LVOTO during DSE in pre-transplant end-stage liver disease patients an unexpected finding as it may be a marker for outflow tract abnormalities, and may lead to increased future cardiac morbidity.
5
References 1. Møller S, Bernardi M: Interactions of the heart and the liver. Eur Heart J 34:2804-11, 2013 2. Milani A, Zaccaria R, Bombardieri G, et al: Cirrhotic cardiomyopathy. Dig Liver Dis 39:507-15, 2007 3. Singh C, Sager JS: Pulmonary complications of cirrhosis. Med Clin North Am 93:87183, 2009 4. Ramalingam VS, Ansari S, Fisher M: Respiratory complication in liver disease. Crit Care Clin 32:357-69, 2016 5. Kaltsakas G, Antoniou E, Palamidas AF, et al: Dyspnea and respiratory muscle strength in end-stage liver disease. World J Hepatol 5:56-63, 2013 6. Sameh AA, Maha Y, Hany AH: Respiratory muscle strength, hypoxemia and dyspnea in liver cirrhosis patients. Egyptian Journal of Chest Diseases and Tuberculosis. 63:105964, 2014 7. An J, Shim JH, Kim SO, et al: Prevalence and prediction of coronary artery disease in patients with liver cirrhosis: A registry-based matched case-control study. Circulation 130:1353-62, 2014 8. Lentine KL, Costa SP, Weir MR, et al: Cardiac disease evaluation and management among kidney and liver transplantation candidates: A scientific statement from the American Heart Association and the American College of Cardiology Foundation: Endorsed by the American Society of Transplant Surgeons, American Society of Transplantation, and National Kidney Foundation. Circulation 126:617-63, 2012
6
9. Murray KF, Carithers RL Jr, et al: AASLD Practice Guidelines: Evaluation of the patient for liver transplantation. Hepatology 41:1407-32 10. Overgaard CB, Dzavik V: Inotropes and vasopressors: A review of physiology and clinical use in cardiovascular disease. Circulation 118:1047-56, 2008 11. Gottdiener JS, Bednarz J, Devereux R, et al: American Society of Echocardiography recommendations for using echocardiography in clinical trials. J Am Soc Echocardiogr 20:1021-34, 2004 12. Vaglio JC Jr., Ommen SR, Nishimura RA, et al: Clinical characteristics and outcomes of patients with hypertrophic cardiomyopathy with latent obstruction. Am Heart J 156:3427, 2008 13. Hiroaki S, Hitoshi S, Tokuhisa U, et al: Basic echocardiographic features of patients with latent left ventricular outflow tract obstruction without left ventricular hypertrophy. Int Heart J 53:230-3, 2012 14. Jiang L, Levine RA, King ME, et al: An integrated mechanism for systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy based on echocardiographic observations. Am Heart J 113:633-44, 1987 15. Sherrid M, Chu CK, Delia E, et al: An echocardiographic study of the fluid mechanics of obstruction in hypertrophic cardiomyopathy. J Am Coll Cardiol 22:816-25, 1993 16. Maron MS, Olivotto I, Zenovich AG, et al: Hypertrophic cardiomyopathy is predominantly a disease of the left ventricular outflow tract. Circulation114: 2232-9, 2006 17. Melero JM, Rodríguez I, Such M, et al: Left ventricular outflow with mitral mechanical prosthesis. Ann Thorac Surg 68:55-7, 1999
7
18. Bartunek J, Sys SU, Rodrigues AC, et al: Abnormal systolic intraventricular flow velocities after valve replacement for aortic stenosis. Mechanisms, predictive factors, and prognostic significance. Circulation 93:712-9, 1996 19. Haley JH, Sinak LJ, Tajik AJ, et al: Dynamic left ventricular outflow tract obstruction in acute coronary syndromes: An important cause of new systolic murmur and cardiogenic shock. Mayo Clin Proc 74:901-6, 1999 20. Merli E, Sutcliffe S, Gori M, et al: Tako-tsubo cardiomyopathy: New insights into the possible underlying pathophysiology Eur J Echocardiogr 7:53-61, 2006 21. Dinwoodey DL, Skinner M, Maron MS, et al: Light-chain amyloidosis with echocardiographic features of hypertrophic cardiomyopathy Am J Cardiol 101:674-6, 2008 22. Calcagnino M, O'Mahony C, Coats C, et al: Exercise-induced left ventricular outflow tract obstruction in symptomatic patients with Anderson-Fabry disease. J Am Coll Cardiol 58:88-9, 2011 23. Masaaki S, Tokuhisa U, Shunsuke M, et al: Dynamic narrowing of left ventricular outflow tract--Possible mechanism of latent left ventricular outflow obstruction. Journal of Cardiology Cases 2:74-7, 2010 24. Kelshiker MA, Mayet J, Unsworth B, et al. Basal septal hypertrophy. Curr Cardiol Rev 9:325-30, 2013 25. Park SM, Kim MN, Kim SA, et al: Clinical significance of dynamic left ventricular outflow tract obstruction during dobutamine stress echocardiography in women with suspected coronary artery disease. Circ J 79:2255-62, 2015
8
26. Barletta G, Del Bene MR, Gallini C, et al: The clinical impact of dynamic intraventricular obstruction during dobutamine stress echocardiography. Int J Cardiol 70:179-89, 1999 27. Dawn B, Paliwal VS, Raza ST, et al: Left ventricular outflow tract obstruction provoked during dobutamine stress echocardiography predicts future chest pain, syncope, and near syncope. Am Heart J 149:908-16, 2005 28. Henein MY, O’Sullivan C, Sutton GC, et al: Stress-induced left ventricular outflow tract obstruction: A potential cause of dyspnea in the elderly. J Am Coll Cardiol 30:1301-7, 1997 29. Pellikka PA, Oh JK, Bailey KR, et al: Dynamic intraventricular obstruction during dobutamine stress echocardiography: A new observation. Circulation 86:1429-32, 1992 30. Luria D, Klutstein MW, Rosenmann D, et al: Prevalence and significance of left ventricular outflow gradient during dobutamine echocardiography. Eur Heart J 20:38692, 1999 31. Al-Nasser F, Duncan A, Sharma R, et al: Beta-blocker therapy for dynamic leftventricular outflow tract obstruction. Int J Cardiol 86:199-205, 2002 32. Ranasinghe I, Yeoh T, Yiannikas J: Negative ionotropic agents for the treatment of left ventricular outflow tract obstruction due to sigmoid septum and concentric left ventricular hypertrophy. Heart Lung Circ 20:579-86, 2011 33. Maraj S, Jacobs LE, Maraj R, et al. Inducible left ventricular outflow tract gradient during dobutamine stress echocardiography: An association with intraoperative hypotension but not a contraindication to liver transplantation. Echocardiography 21:6815, 2004
9
34. Zaky A, Bendjelid K: Appraising cardiac dysfunction in liver transplantation: an ongoing challenge. Liver Int 35:12-29, 2015 35. Therapondos G, Flapan AD, Plevris JN, et al: Cardiac morbidity and mortality related to orthotopic liver transplantation. Liver Transpl 10:1441-53, 2004
10