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 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 28  |  Issue : 4  |  Page : 233-235

Transcatheter aortic valve replacement and cardiac resynchronization therapy in cancer-related cardiotoxicity


Department of Cardiology, Monaldi Hospital, AORN dei Colli, Naples, Italy

Date of Web Publication24-Dec-2018

Correspondence Address:
Enrico Melillo
Aorn dei Colli, Monaldi Hospital, Via Leonardo Bianchi, Naples 80131
Italy
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcecho.jcecho_46_18

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  Abstract 


Cardiotoxicity related to antineoplastic agents is a rising and growing issue, therefore early recognition and prompt management can impact on the overall prognosis of cancer patients. We report the case of a 70-year-old woman without cardiovascular risk factors, with a medical history of non-Hodgkin lymphoma and chronic myeloid leukemia treated with chemotherapy and radiotherapy, who underwent transcatheter aortic valve replacement for severe aortic stenosis and cardiac resynchronization therapy for further development of complete left bundle branch block, with a significant improvement of her functional status and left ventricle systolic function in a long-term follow-up.

Keywords: Aortic valve replacement, cardiac resynchronization therapy, cardiac toxicity, left ventricular function


How to cite this article:
Melillo E, Ascione L, Palmiero G, Caso VM, Caso P. Transcatheter aortic valve replacement and cardiac resynchronization therapy in cancer-related cardiotoxicity. J Cardiovasc Echography 2018;28:233-5

How to cite this URL:
Melillo E, Ascione L, Palmiero G, Caso VM, Caso P. Transcatheter aortic valve replacement and cardiac resynchronization therapy in cancer-related cardiotoxicity. J Cardiovasc Echography [serial online] 2018 [cited 2019 May 21];28:233-5. Available from: http://www.jcecho.org/text.asp?2018/28/4/233/248412




  Introduction Top


Cardiotoxicity related to antineoplastic agents is a rising and growing issue, therefore early recognition and prompt management can impact on the overall prognosis of cancer patients. We report the case of a 70-year-old woman without cardiovascular risk factors, with a medical history of non-Hodgkin lymphoma and chronic myeloid leukemia treated with chemotherapy and radiotherapy, who underwent transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) and cardiac resynchronization therapy (CRT) for further development of complete left bundle branch block (LBBB), with a significant improvement of her functional status and left ventricle systolic function in a long-term follow-up.


  Case Report Top


A 70-year-old woman was admitted to our cardiology department for acute pulmonary edema. Her medical history was unremarkable for cardiovascular risk factors and previous cardiac disease. Ten-year ago, she was diagnosed a non-Hodgkin lymphoma, treated with CHOP (Cyclofosfamide 750 mg/m2 for 6 days, doxorubicin cumulative dose of 500 mg/m2, vincristine 1,5 mg/m2 for 6 days, and prednisone 100 mg orally for 5 days) chemotherapy regimen plus mediastinal radiotherapy (XRT) of 40 Gy completed 9 years ago. One year before, she was diagnosed chronic myeloid leukemia, treated with imatinib mesylate (600 mg orally once a day). Transthoracic echocardiography revealed a dilated and globally hypokinetic left ventricle with severe impairment of systolic function (ejection fraction [EF] 25%) [Figure 1]a, thickening and hypomobility of aortic cusps with mean/peak pressure gradient of 21/30 mmHg and a continuity equation derived aortic valve area (AVA) of 0.5 cm2 (indexed stroke volume 16 mL/mq). There was also a moderate-severe functional mitral regurgitation with elevated systolic pulmonary artery pressure (PAPs). Transesophageal echocardiography confirmed the severity of mitral regurgitation and showed a planimetric AVA of 0.7 cm2 [Figure 1]b. Low-dose (up to 20 ug/kg/min) dobutamine-stress echocardiography (DSE) confirmed the severe degree of AS, with only a slight increase of mean/peak pressure gradient (26/42 mmHg), an AVA of 0.5 cm2 and no flow reserve (indexed stroke volume 18.5 mL/mq) [Figure 2]. There were no significant lesions at coronary angiography [Figure 3]a and [Figure 3]b, while right heart catheterization showed moderate increase in PAPs. After Heart team discussion, the patient underwent TAVR with a balloon-expandable prosthesis (Sapien 3, Edwards Lifesciences) with good final result [Figure 3]c. The patient was discharged with aspirin, clopidogrel, beta blocker, and ACE inhibitor therapy. At 6 months' follow-up, the patient referred an improvement of dyspnea (NYHA II), with no residual transprothesic gradient and a moderate mitral regurgitation, but developed LBBB with QRS width of 150 ms. In accordance with the current guidelines, she underwent CRT-defibrillator (CRT-D) therapy. At 12 months' follow-up after CRT-D, the patient referred no more episodes of congestive heart failure, an impressing recovery of the left ventricle systolic function (EF 51%, Global Longitudinal Strain −15% [Figure 4]a and [Figure 4]b and a significant reduction of mitral regurgitation to a mild degree.
Figure 1: (a) Transthoracic echocardiography showing severe impairment of left ventricle systolic function; (b) Mid esophageal aortic valve short axis view with planimetric aortic valve area measure

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Figure 2: Aortic valve area and pressure gradients measured during dobutamine stress echocardiography confirming the severe degree of aortic stenosis

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Figure 3: Coronary angiography showing the absence of significant lesions: (a) Left coronary artery (b) Right coronary artery; (c) Transcatheter aortic valve replacement with a balloon-expandable prosthesis (Sapien 3, Edwards Lifesciences)

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Figure 4: Follow-up after cardiac resynchronization therapy-defibrillator showing significant improvement of the left ventricle systolic function. (a) Ejection fraction measured with Simpson's method; (b) Bull's eye of left ventricle speckle tracking global longitudinal strain

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  Discussion Top


The progressive improvement of oncological therapies has increased life expectancy of cancer patients; therefore, both chemotherapy and radiation-induced heart disease are expected to increase as well in the future. Anthracyclines are well known to cause chemotherapy-induced cardiomyopathy (CCMP).[1] XRT with mediastinal involvement is associated with a broad spectrum of cardiac damage, that may not manifest until many years after treatment, including cardiomyopathy and valvular disease.[2] Valvular heart disease is reported in as many as 81% of patients with previous mediastinal XRT, with a higher involvement of aortic and mitral valve, characterized by leaflet fibrotic thickening, retractions and calcification and a latent interval of 10–20 years between XRT exposure and development of clinical disease.[3] This setting of patients with severe aortic valve stenosis and previous chest XRT undergoing surgical aortic valve replacement (SAVR) have shown a worse survival compared to patients non exposed to XRT principally due to impaired pulmonary reserve, a mean higher surgical risk score and previous XRT exposure.[4] The higher surgical risk is principally related to radiation-induced fibrosis of thoracic and mediastinal tissues, such as chest wall and pericardial fibrosis and extracardiac vascular injury.[2] The current valvular heart disease guidelines consider previous chest wall XRT as a condition favoring TAVR over SAVR since this condition is not considered in surgical risk scores.[5] Previous studies have demonstrated that TAVR is a feasible, effective and low mortality procedure in patients with severe AS and XRT exposure making it a valid therapeutic option for high surgical risk patients.[6],[7] Our patient showed an AVA of 0.5 cm2, no flow reserve and a mean gradient <40 mmHg during DSE, probably related to a more advanced LV impairment related both to afterload mismatch and to chemotherapy-related cardiotoxic effect. Although in the current American guidelines, patients are considered to have true severe low flow low gradient AS when the mean gradient is >40 mmHg with an AVA <1 cm2 during DSE,[8] these criteria have not been completely validated. Annabi et al. showed that DSE criteria of mean gradient >40 mmHg have low sensitivity for identifying true severe AS, while peak AVA ≤1 cm2 better classified a higher number of patients with severe AS than mean gradient criteria.[9] Hence, a lower DSE mean gradient does not necessarily indicate the presence of nonsevere AS but may be observed in patients where the lack of contractile reserve, due to extended myocardial impairment, is associated with a poor increase in mean gradient. In our case, the simultaneous presence of severe mitral regurgitation may have led to an underestimation in the assessment of AS severity by decreasing forward stroke volume, as well as an overestimation of the degree of mitral regurgitation in the presence of high postload conditions. The coexistence of aortic valve stenosis and functional mitral regurgitation in a patient with left ventricular dysfunction represents a challenging clinical condition where the right therapeutic choice is not a simple task. The current recommended management of combined aortic and mitral valve disease is to postpone mitral valve surgery, since the resolution of aortic valve stenosis may be associated with an improvement in the severity of mitral regurgitation.[5] Moreover, combined percutaneous aortic valve replacement and mitral valve repair in high-risk patients are feasible, although there is not enough experience to be recommended.[5] For further development of LBBB after TAVR, the patient underwent CRT-D therapy. The impressive recovery of left ventricle systolic function after CRT raises a question about the role and efficacy of CRT in a particular subset like CCMP. In the largest series to date, Rickard et al. retrospectively demonstrated a significant improvement in the left ventricle ejection fraction, end diastolic and end systolic diameters, degree of mitral regurgitation, and NYHA functional class after CRT in 18 patients with adriamycin-induced cardiomyopathy, with comparable results to that seen in other forms of nonischemic cardiomyopathy.[10] However, the potential benefit of CRT in this population needs to be more accurately determined. The current ongoing MADICT-CHIC trial (Multicenter Automatic Defibrillator Implantation Trial–Chemotherapy-Induced Cardiomyopathy; NCT02164721) will be the first prospective trial investigating the effect of CRT on the left ventricle systolic function and diameters and on all-cause mortality in anthracycline-induced cardiomyopathy, giving an additional step toward the comprehension and treatment of CCMP.


  Conclusions Top


Cardiovascular toxicity of cancer treatments has become a widespread issue in clinical practice. We have to keep in mind that cancer patients are exposed to a “cocktail” of cardiotoxic drugs and treatments, so it is sometimes difficult to determine the specific underlying responsible mechanism of cardiac damage. However, the current advanced heart failure therapies and new mininvasive valvular heart disease treatments have to be considered feasible and effective also in the setting of cancer-related cardiotoxicity.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Spallarossa P, Maurea N, Cadeddu C, Madonna R, Mele D, Monte I, et al. A recommended practical approach to the management of anthracycline-based chemotherapy cardiotoxicity: An opinion paper of the working group on drug cardiotoxicity and cardioprotection, Italian Society of Cardiology. J Cardiovasc Med (Hagerstown) 2016;17 Suppl 1:S84-92.  Back to cited text no. 1
    
2.
Jaworski C, Mariani JA, Wheeler G, Kaye DM. Cardiac complications of thoracic irradiation. J Am Coll Cardiol 2013;61:2319-28.  Back to cited text no. 2
    
3.
Tamura A, Takahara Y, Mogi K, Katsumata M. Radiation-induced valvular disease is the logical consequence of irradiation. Gen Thorac Cardiovasc Surg 2007;55:53-6.  Back to cited text no. 3
    
4.
Donnellan E, Masri A, Johnston DR, Pettersson GB, Rodriguez LL, Popovic ZB, et al. Long-term outcomes of patients with mediastinal radiation-associated severe aortic stenosis and subsequent surgical aortic valve replacement: A matched cohort study. J Am Heart Assoc 2017;6. pii: e005396.  Back to cited text no. 4
    
5.
Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J 2017;38:2739-91.  Back to cited text no. 5
    
6.
Dijos M, Reynaud A, Leroux L, Réant P, Cornolle C, Roudaut R, et al. Efficacy and follow-up of transcatheter aortic valve implantation in patients with radiation-induced aortic stenosis. Open Heart 2015;2:e000252.  Back to cited text no. 6
    
7.
Bouleti C, Amsallem M, Touati A, Himbert D, Iung B, Alos B, et al. Early and late outcomes after trans-catheter aortic valve implantation in patients with previous chest radiation. Heart 2016;102:1044-51.  Back to cited text no. 7
    
8.
Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol 2014;63:2438-88.  Back to cited text no. 8
    
9.
Annabi MS, Touboul E, Dahou A, Burwash IG, Bergler-Klein J, Enriquez-Sarano M, et al. Dobutamine stress echocardiography for Management of low-flow, low-gradient aortic Stenosis. J Am Coll Cardiol 2018;71:475-85.  Back to cited text no. 9
    
10.
Rickard J, Kumbhani DJ, Baranowski B, Martin DO, Tang WH, Wilkoff BL. Usefulness of cardiac resynchronization therapy in patients with adriamycin-induced cardiomyopathy. Am J Cardiol 2010;105:522-6.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


This article has been cited by
1 Antineoplastics
Reactions Weekly. 2019; 1738(1): 30
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