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Valvular Heart Disease
Chapter 18
Valvular Heart Disease J.C. Plana
Chapter Outline Preexisting Lesions Valve Disease as a Result of the Malignancy Valve Disease due to Radiation Therapy Valve Disease Related to Infectious Complications of Chemotherapy
127 127 128
Valve Disease Related to Cardiotoxic Effects of Chemotherapy 128 Evaluation of Valvular Disease in Patients With Potential Cardiotoxicity From Cancer Chemotherapeutic Agents 129 References 130
128
Cancer therapeutics do not affect the cardiac valves directly. However, valvular heart disease may manifest in the oncologic patient for a number of other reasons: (1) preexisting valvular heart disease; (2) as a result of the malignancy itself; (3) due to concomitant or previous radiation therapy; (4) due to endocarditis in the setting of immune suppression as a complication of chemotherapy; or (5) as a result of left ventricular (LV) remodeling in the setting of cancer therapeutics-related cardiac dysfunction (CTRCD).
PREEXISTING LESIONS Valve disease is highly prevalent in the general population with both mitral valve prolapse (MVP) and bicuspid aortic valve (BAV) each occurring in up to 2% of the population [1,2]. Additionally, degenerative disease, particularly of the aortic valve, is highly prevalent in older individuals.
VALVE DISEASE AS A RESULT OF THE MALIGNANCY Valve disease is an uncommon complication of primary neoplastic disease. Primary or secondary cardiac tumors may impact valve function by their local extension.
Anticancer Treatments and Cardiotoxicity. DOI: http://dx.doi.org/10.1016/B978-0-12-802509-3.00018-2 © 2017 Elsevier Inc. All rights reserved.
127
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SECTION | III Cardiovascular Complications of Cancer Treatments
However, what is more common is the development of nonthrombotic or marantic endocarditis. This condition is particularly prevalent in patients with lung, prostate, pancreas, or colon cancer. They most commonly occur in the left-sided valves and may result in thromboembolism. The valve lesions may vary in size from microscopic to large bulky lesions easily identifiable on transthoracic echocardiography. The lesions consist of a network of fibrin and platelets and may be associated with disseminated intravascular coagulopathy. The lesions may lead to impaired valve coaptation and regurgitation, which may evolve to be severe in nature. Rarely, the lesions are sufficiently bulky to give rise to significant stenosis. However, it is thromboembolism from these lesions that are most consequential to the patient, rather than their hemodynamic impact. Anticoagulation may lead to their resolution or at least a reduction in their size.
VALVE DISEASE DUE TO RADIATION THERAPY Valve disease may occur secondary to previous or concomitant radiation therapy [3 5]. The pathological effects of radiation on valve tissue usually are not manifest acutely but rather develop over decades. Both valvular stenosis and regurgitation may occur, with regurgitation being somewhat more frequent. Left-sided valves are more commonly affected and radiation often leads to calcification of the valve and the subvalvular apparatus. The mitroaortic intervalvular fibrosa is particularly prone. As radiation may cause or exacerbate already existing coronary artery disease, ischemic valve lesions may also occur.
VALVE DISEASE RELATED TO INFECTIOUS COMPLICATIONS OF CHEMOTHERAPY Cancer therapeutics may lead to pancytopenia which can be complicated by the development of bacteremia and endocarditis [6,7]. This is more likely to occur in those with predisposing valve lesions (i.e., MVP and BAV) but may occur even with normal valves in the setting of overwhelming bacteremia. Patients may develop endocarditis associated with the presence of bacteremia in the setting of a central venous catheter placed for vascular access during chemotherapeutic regimens.
VALVE DISEASE RELATED TO CARDIOTOXIC EFFECTS OF CHEMOTHERAPY Valve disease may occur as a consequence of CTRCD. This usually manifests as mitral regurgitation from annular dilation or apical tethering in the setting of LV dysfunction and compensatory LV remodeling. Secondary tricuspid regurgitation may also occur due to right ventricular dysfunction or increased pulmonary arterial pressure in the setting of LV dysfunction. Both
Valvular Heart Disease Chapter | 18
129
secondary mitral and tricuspid regurgitation occur later in the course of CTRCD, usually once significant dysfunction and geometric ventricular remodeling have occurred.
EVALUATION OF VALVULAR DISEASE IN PATIENTS WITH POTENTIAL CARDIOTOXICITY FROM CANCER CHEMOTHERAPEUTIC AGENTS Echocardiography is the technique of choice in the evaluation of valvular disease in patients being screened for suspected cardiotoxicity from cancer chetherapeutics. Given the high prevalence of preexisting valve lesions and their impact on potential chemotherapeutic regimens, a careful echocardiographic examination of valve structure and function should be carried out before the initiation of cancer therapeutics, even in the absence of significant physical examination findings. Although physical examination may yield evidence of significant valve disease, milder lesions may not be audible and lesions associated with increased risk of endocarditis, for instance BAV, may not be apparent. Careful evaluation of the structure of each of the valves should be performed, paying careful attention to the presence of mobile echodensities suggestive of endocarditis or of calcification of the valve. Assessment of the severity of valvular stenosis or regurgitation should be performed based on the current ASE and EAE recommendations [8 11]. Although a complete transthoracic Doppler echocardiographic evaluation is often sufficient to evaluate the valve pathology and the hemodynamic consequences of valve dysfunction, transesophageal echocardiography may be of incremental value in the setting of suspected endocarditis, when transthoracic echo images are suboptimal or when there is concern for tumor involvement of valve tissue. Both CT scanning and MRI are not usually required in the routine evaluation of valve disease in oncologic patients but may have a role in assessing tumor infiltration of valvular structures or when radiation induced constriction or restrictive cardiomyopathy. Cardiac MRI may also be valuable in following ventricular volumes and function in patients with significant valve regurgitation. Patients receiving chemotherapy with potential cardiotoxicity should have a careful reevaluation of valve structure and function on subsequent echocardiograms throughout the course of their treatment and subsequently. Patients with significant or changing valvular findings need to be evaluated more frequently and the relationship of the various therapeutic treatments to these structural and hemodynamic derangements assessed at each visit. The indications for follow-up and interventions on specific valve lesions should be based on the guidelines published by the American Heart Association/ American College of Cardiology and the European Society of Cardiology [12,13], though these need to be adjusted to the individual prognosis and clinical situation of the patient.
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SECTION | III Cardiovascular Complications of Cancer Treatments
REFERENCES [1] Freed LA, Levy D, Levine RA, Larson MG, Evans JC, Fuller DL, et al. New prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med 1999;341:1 347. [2] Roberts WC. The congenitally bicuspid aortic valve. A study of 85 autopsy cases. Am J Cardiol 1970;26:72 83. [3] Hamza A, Tunick PA, Kronzon I. Echocardiographic manifestations of complications of radiation therapy. Echocardiography 2009;26:724 8. [4] Heidenreich PA, Kapoor JR. Radiation induced heart disease: systemic disorders in heart disease. Heart 2009;95:252 8. [5] Heidenreich PA, Hancock SL, Lee BK, Mariscal CS, Schnittger I. Asymptomatic cardiac disease following mediastinal irradiation. J Am Coll Cardiol 2003;42:743 9. [6] Edoute Y, Haim N, Rinkevich D, Brenner B, Reisner SA. Cardiac valvular vegetations in cancer patients: a prospective echocardiographic study of 200 patients. Am J Med 1997; 102:252 8. [7] Eiken P, Edwards W, Tazelaar H, McBane R, Zehr K. Surgical pathology of nonbacterial thrombotic endocarditis in 30 patients, 1985 2000. Mayo Clinic Proc 2001;76:1204 12. [8] Baumgartner H, Hung J, Bermejo J, Chambers JB, Evangelista A, Griffin BP, et al. EAE/ ASE. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. Eur J Echocardiogr 2009;10:1 25. [9] Lancellotti P, Tribouilloy C, Hagendorff A, Moura L, Popescu BA, Agricola E, et al. European Association of Echocardiography. European Association of Echocardiography recommendations for the assessment of valvular regurgitation. Part 1: aortic and pulmonary regurgitation (native valve disease). Eur J Echocardiogr 2010;11:223 44. [10] Lancellotti P, Moura L, Pierard LA, Agricola E, Popescu BA, Tribouilloy C, et al. European Association of Echocardiography. European Association of Echocardiography recommendations for the assessment of valvular regurgitation. Part 2: mitral and tricuspid regurgitation (native valve disease). Eur J Echocardiogr 2010;11:307 32. [11] Zoghbi WA, Enriquez-Sarano M, Foster E, Grayburn PA, Kraft CD, Levine RA, et al. American Society of Echocardiography. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 2003;16:777 802. [12] Bonow RO, Carabello BA, Chatterjee K, de Leon Jr AC, Faxon DP, Freed MD, et al. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2008;52:e1 142. [13] Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baro´n-Esquivias G, Baumgartner H, et al. Guidelines on the management of valvular heart disease (version 2012): The Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2012;33:2451 96. [14] Hering D, Faber L, Horstkotte D. Echocardiographic features of radiation-associated valvular disease. Am J Cardiol 2003;92:226 30.
Valvular Heart Disease J.C. Plana
Chapter Outline Preexisting Lesions Valve Disease as a Result of the Malignancy Valve Disease due to Radiation Therapy Valve Disease Related to Infectious Complications of Chemotherapy
127 127 128
Valve Disease Related to Cardiotoxic Effects of Chemotherapy 128 Evaluation of Valvular Disease in Patients With Potential Cardiotoxicity From Cancer Chemotherapeutic Agents 129 References 130
128
Cancer therapeutics do not affect the cardiac valves directly. However, valvular heart disease may manifest in the oncologic patient for a number of other reasons: (1) preexisting valvular heart disease; (2) as a result of the malignancy itself; (3) due to concomitant or previous radiation therapy; (4) due to endocarditis in the setting of immune suppression as a complication of chemotherapy; or (5) as a result of left ventricular (LV) remodeling in the setting of cancer therapeutics-related cardiac dysfunction (CTRCD).
PREEXISTING LESIONS Valve disease is highly prevalent in the general population with both mitral valve prolapse (MVP) and bicuspid aortic valve (BAV) each occurring in up to 2% of the population [1,2]. Additionally, degenerative disease, particularly of the aortic valve, is highly prevalent in older individuals.
VALVE DISEASE AS A RESULT OF THE MALIGNANCY Valve disease is an uncommon complication of primary neoplastic disease. Primary or secondary cardiac tumors may impact valve function by their local extension.
Anticancer Treatments and Cardiotoxicity. DOI: http://dx.doi.org/10.1016/B978-0-12-802509-3.00018-2 © 2017 Elsevier Inc. All rights reserved.
127
128
SECTION | III Cardiovascular Complications of Cancer Treatments
However, what is more common is the development of nonthrombotic or marantic endocarditis. This condition is particularly prevalent in patients with lung, prostate, pancreas, or colon cancer. They most commonly occur in the left-sided valves and may result in thromboembolism. The valve lesions may vary in size from microscopic to large bulky lesions easily identifiable on transthoracic echocardiography. The lesions consist of a network of fibrin and platelets and may be associated with disseminated intravascular coagulopathy. The lesions may lead to impaired valve coaptation and regurgitation, which may evolve to be severe in nature. Rarely, the lesions are sufficiently bulky to give rise to significant stenosis. However, it is thromboembolism from these lesions that are most consequential to the patient, rather than their hemodynamic impact. Anticoagulation may lead to their resolution or at least a reduction in their size.
VALVE DISEASE DUE TO RADIATION THERAPY Valve disease may occur secondary to previous or concomitant radiation therapy [3 5]. The pathological effects of radiation on valve tissue usually are not manifest acutely but rather develop over decades. Both valvular stenosis and regurgitation may occur, with regurgitation being somewhat more frequent. Left-sided valves are more commonly affected and radiation often leads to calcification of the valve and the subvalvular apparatus. The mitroaortic intervalvular fibrosa is particularly prone. As radiation may cause or exacerbate already existing coronary artery disease, ischemic valve lesions may also occur.
VALVE DISEASE RELATED TO INFECTIOUS COMPLICATIONS OF CHEMOTHERAPY Cancer therapeutics may lead to pancytopenia which can be complicated by the development of bacteremia and endocarditis [6,7]. This is more likely to occur in those with predisposing valve lesions (i.e., MVP and BAV) but may occur even with normal valves in the setting of overwhelming bacteremia. Patients may develop endocarditis associated with the presence of bacteremia in the setting of a central venous catheter placed for vascular access during chemotherapeutic regimens.
VALVE DISEASE RELATED TO CARDIOTOXIC EFFECTS OF CHEMOTHERAPY Valve disease may occur as a consequence of CTRCD. This usually manifests as mitral regurgitation from annular dilation or apical tethering in the setting of LV dysfunction and compensatory LV remodeling. Secondary tricuspid regurgitation may also occur due to right ventricular dysfunction or increased pulmonary arterial pressure in the setting of LV dysfunction. Both
Valvular Heart Disease Chapter | 18
129
secondary mitral and tricuspid regurgitation occur later in the course of CTRCD, usually once significant dysfunction and geometric ventricular remodeling have occurred.
EVALUATION OF VALVULAR DISEASE IN PATIENTS WITH POTENTIAL CARDIOTOXICITY FROM CANCER CHEMOTHERAPEUTIC AGENTS Echocardiography is the technique of choice in the evaluation of valvular disease in patients being screened for suspected cardiotoxicity from cancer chetherapeutics. Given the high prevalence of preexisting valve lesions and their impact on potential chemotherapeutic regimens, a careful echocardiographic examination of valve structure and function should be carried out before the initiation of cancer therapeutics, even in the absence of significant physical examination findings. Although physical examination may yield evidence of significant valve disease, milder lesions may not be audible and lesions associated with increased risk of endocarditis, for instance BAV, may not be apparent. Careful evaluation of the structure of each of the valves should be performed, paying careful attention to the presence of mobile echodensities suggestive of endocarditis or of calcification of the valve. Assessment of the severity of valvular stenosis or regurgitation should be performed based on the current ASE and EAE recommendations [8 11]. Although a complete transthoracic Doppler echocardiographic evaluation is often sufficient to evaluate the valve pathology and the hemodynamic consequences of valve dysfunction, transesophageal echocardiography may be of incremental value in the setting of suspected endocarditis, when transthoracic echo images are suboptimal or when there is concern for tumor involvement of valve tissue. Both CT scanning and MRI are not usually required in the routine evaluation of valve disease in oncologic patients but may have a role in assessing tumor infiltration of valvular structures or when radiation induced constriction or restrictive cardiomyopathy. Cardiac MRI may also be valuable in following ventricular volumes and function in patients with significant valve regurgitation. Patients receiving chemotherapy with potential cardiotoxicity should have a careful reevaluation of valve structure and function on subsequent echocardiograms throughout the course of their treatment and subsequently. Patients with significant or changing valvular findings need to be evaluated more frequently and the relationship of the various therapeutic treatments to these structural and hemodynamic derangements assessed at each visit. The indications for follow-up and interventions on specific valve lesions should be based on the guidelines published by the American Heart Association/ American College of Cardiology and the European Society of Cardiology [12,13], though these need to be adjusted to the individual prognosis and clinical situation of the patient.
130
SECTION | III Cardiovascular Complications of Cancer Treatments
REFERENCES [1] Freed LA, Levy D, Levine RA, Larson MG, Evans JC, Fuller DL, et al. New prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med 1999;341:1 347. [2] Roberts WC. The congenitally bicuspid aortic valve. A study of 85 autopsy cases. Am J Cardiol 1970;26:72 83. [3] Hamza A, Tunick PA, Kronzon I. Echocardiographic manifestations of complications of radiation therapy. Echocardiography 2009;26:724 8. [4] Heidenreich PA, Kapoor JR. Radiation induced heart disease: systemic disorders in heart disease. Heart 2009;95:252 8. [5] Heidenreich PA, Hancock SL, Lee BK, Mariscal CS, Schnittger I. Asymptomatic cardiac disease following mediastinal irradiation. J Am Coll Cardiol 2003;42:743 9. [6] Edoute Y, Haim N, Rinkevich D, Brenner B, Reisner SA. Cardiac valvular vegetations in cancer patients: a prospective echocardiographic study of 200 patients. Am J Med 1997; 102:252 8. [7] Eiken P, Edwards W, Tazelaar H, McBane R, Zehr K. Surgical pathology of nonbacterial thrombotic endocarditis in 30 patients, 1985 2000. Mayo Clinic Proc 2001;76:1204 12. [8] Baumgartner H, Hung J, Bermejo J, Chambers JB, Evangelista A, Griffin BP, et al. EAE/ ASE. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. Eur J Echocardiogr 2009;10:1 25. [9] Lancellotti P, Tribouilloy C, Hagendorff A, Moura L, Popescu BA, Agricola E, et al. European Association of Echocardiography. European Association of Echocardiography recommendations for the assessment of valvular regurgitation. Part 1: aortic and pulmonary regurgitation (native valve disease). Eur J Echocardiogr 2010;11:223 44. [10] Lancellotti P, Moura L, Pierard LA, Agricola E, Popescu BA, Tribouilloy C, et al. European Association of Echocardiography. European Association of Echocardiography recommendations for the assessment of valvular regurgitation. Part 2: mitral and tricuspid regurgitation (native valve disease). Eur J Echocardiogr 2010;11:307 32. [11] Zoghbi WA, Enriquez-Sarano M, Foster E, Grayburn PA, Kraft CD, Levine RA, et al. American Society of Echocardiography. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 2003;16:777 802. [12] Bonow RO, Carabello BA, Chatterjee K, de Leon Jr AC, Faxon DP, Freed MD, et al. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2008;52:e1 142. [13] Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baro´n-Esquivias G, Baumgartner H, et al. Guidelines on the management of valvular heart disease (version 2012): The Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2012;33:2451 96. [14] Hering D, Faber L, Horstkotte D. Echocardiographic features of radiation-associated valvular disease. Am J Cardiol 2003;92:226 30.