Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 30  |  Issue : 5  |  Page : 11-16

Vascular damage – Coronary artery disease


1 Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
2 Department of Cardiology, University Hospital Città della Scienza e Salute, Molinette Hospital, Turin, Italy
3 Department of Cardiology, Hospital Policlinico of Bari, Bari, Italy

Date of Submission11-Apr-2020
Date of Acceptance03-Oct-2019
Date of Web Publication10-Apr-2020

Correspondence Address:
Dr. Christian Cadeddu Dessalvi
Department of Medical Sciences and Public Health, University of Cagliari, Cagliari
Italy
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcecho.jcecho_3_19

Rights and Permissions
  Abstract 


Cardiovascular complications during chemotherapy and radiotherapy are becoming an increasing problem because many patients with cancer are treated with agents that exert significant vascular toxicity. Coronary heart disease in patients with cancer presents particular challenges, which directly impact the management of both the coronary disease and malignancy. Several chemotherapeutic agents have been shown to trigger ischemic heart disease, and as it has happened for myocardial cardiotoxicity, more attention should be dedicated to improving early recognition and prevention of cardiac vascular toxicity. Cardiac imaging could facilitate early detection of vascular toxicity, but a thorough risk stratification should always be performed to identify patients at higher risk of vascular impairment.

Keywords: Cardiotoxicity, coronary artery disease, echocardiography, vascular toxicity


How to cite this article:
Cadeddu Dessalvi C, Deidda M, Giorgi M, Colonna P. Vascular damage – Coronary artery disease. J Cardiovasc Echography 2020;30, Suppl S1:11-6

How to cite this URL:
Cadeddu Dessalvi C, Deidda M, Giorgi M, Colonna P. Vascular damage – Coronary artery disease. J Cardiovasc Echography [serial online] 2020 [cited 2021 Mar 8];30, Suppl S1:11-6. Available from: https://www.jcecho.org/text.asp?2020/30/5/11/282279




  Introduction Top


Cardiovascular diseases (CVDs) and cancer represent the two leading causes of death[1] in populations, often exposed to the same risk factors.

Advancements in the treatment of cancer have improved the prognosis of patients with a wide range of malignancies,[2] and in parallel, there has been increasing attention to cardiovascular effects of chemotherapeutic agents. In this context, the acute negative vascular effect of chemotherapeutic agents has become more relevant because of the latent effects of direct and indirect cardiovascular toxicity.

Chemotherapy vascular complications (CVCs) might occur as a result of an “off-target” drug effect or, importantly, as a result of the interplay between signaling pathways required for normal vascular function and those required for tumor growth.

CVCs often are due to endothelial dysfunction, with impaired vasorelaxant effects and anti-inflammatory and vascular reparative functions. The propensity to develop cardiovascular complications reflects the complex interplay between the patient's baseline risk profile and preexisting CVD, such as coronary artery disease (CAD). In this regard, chest radiotherapy is able to accelerate the atherosclerosis process, resulting in early-onset CAD.


  Coronary Damage Induced by Chemotherapy and Radiotherapy Top


Pathophysiology of coronary damage varies depending on the specific chemotherapy used.

For most agents, vascular toxicity often reflects endothelial dysfunction, with loss of vasorelaxant effects and impairment of anti-inflammatory and vascular reparative functions. Moreover, in addition to the procoagulant effect of cancer per se, most agents further enhance platelet activity by decreasing endothelial nitric oxide (NO) bioavailability.[3]

Alkylating agents were among the first drugs shown to induce these cardiac complications. Platinum-based compounds (e.g. cisplatin) resulted associated with acute and late cardiovascular side effects like hypertension, myocardial ischemia and vascular acute complications.[3],[4] In this setting, thrombus formation could be potentially due to endothelial cell damage and dysfunction, leading to a hypercoagulable state with platelet activation, adhesion, and aggregation; increased von Willebrand factor level; and reduced NO bioavailability.[3] Long-lasting cardiotoxicity has been associated with previous therapy with cisplatin, whose plasma levels remain measurable for up to 20 years after the conclusion of the treatment leading to cumulative dysfunction of endothelial cells.[5] Therefore, in this case, long-lasting presence of circulating cisplatin in patients' blood correlates with both pathophysiologic mechanisms and clinical events.

Fluoropyrimidines are the second most common cause of chemotherapy-induced cardiotoxicity;[6] they, particularly 5-fluorouracil, cause angina-like chest pain, in rare cases myocardial infarction, arrhythmias, ventricular tachycardia, heart failure and cardiogenic shock, and QT prolongation with torsades de pointes.[7],[8]

5-FU and capecitabine could determine CTX by coronary thrombosis, with arteritis and vasospasm proposed as possible mechanisms. Definite 5-FU metabolites showed to be associated with cardiotoxicity. The conversion of capecitabine into 5-FU and of the latter into its active metabolites needs the action of the enzyme thymidine phosphorylase, which is an angiogenic factor[9],[10] upregulated in stable and unstable atherosclerotic plaque.[11] On the other hand, the unfavorable effects on endothelium could also be mediated by increased levels of endothelin-1, which could cause vasospasm and ischemia [Figure 1].
Figure 1: The main mechanism of chemotherapy-induced vascular toxicity

Click here to view


Furthermore, 5-FU can directly cause vascular damage, reducing endothelial NO synthase activity and endothelium-independent vasoconstriction via protein kinase C, leading to a Prinzmetal-type angina phenomenon.[12]

Beyond the acute effects on the coronary arteries in terms of vasospasm and possibly thrombus formation, 5-FU seems to be not associated with the accelerated coronary atherosclerosis. However, endothelial and myocardial cell apoptoses have been evidenced in experimental studies[12] and 5-FU is able to determine a dose-dependent increase in red blood cell viscosity, thus causing a reduction in blood flow velocity, which could predispose to thrombus formation. Previous CAD constitutes a risk factor for 5-FU-related vasospastic angina, because vasospasm tends to occur at sites of thrombus and plaque formation.[13]

Taxanes and vinca alkaloids exert their antineoplastic effect by altering the cellular microtubule mass, which represents one of the most successful targets for chemotherapy agents. Taxanes have significant antiangiogenic properties and cause disruption of the cytoskeleton and endothelial cell dysfunction.[12] At low doses, they prevent cell motility and cell–cell interactions,[12],[14] whereas at higher doses, they cause microtubule deficiency, endothelial cell detachment, and apoptosis. Paclitaxel impairs vascular smooth muscle cell migration and endothelial cell proliferation;[12] moreover, it might also enhance endothelial tissue factor expression determining prothrombotic effects.[12],[15]

Taxanes vascular side effects are amplified by the combination with angiogenesis inhibitors. The use of bevacizumab with paclitaxel in patients with advanced breast cancer increases the rate of severe thrombotic events from 1.5% to 2.1%.[16]

Vincristine and vinblastine are vinca alkaloids that bind tubulin and induce cell death. Their main cardiovascular side effects are myocardial ischemia and infarction, which seem to occur during or shortly after therapy and to be related to coronary artery vasospasm.[13]

Vascular endothelial growth factor inhibitors (VEGF-I), recently implemented for the treatment of solid and hematological malignancies, showed to induce hypertention as the most common cardiovascular complication.[17] Moreover, the interruption of VEGF signaling is associated with vascular toxicity and clinical sequelae such as acute coronary syndromes, stroke, venous thrombosis, and thromboembolism.[12],[13],[18] Although the absolute increase in risk is relatively small (0.8% and 1.8% for myocardial infarction and arterial thrombosis, respectively), it is clinically important, particularly for patients with preexisting risk factors or previous vascular disease, in particular CAD.[19]

On the other hand, tyrosine kinase inhibitors, including ponatinib, nilotinib, and dasatinib, are associated with acute arterial thrombosis. This is especially evident for ponatinib,[19] which was associated with a nearly 12% incidence of arterial thrombotic events at 2 years.[19]

The absolute increase in risk is, respectively, 0.8% and 1.8% for myocardial infarction and arterial thrombosis; although it is relatively small, it remains clinically important, particularly in patients with preexisting risk factors or vascular disease. Previous CADs are a particularly important risk factor for developing vascular complications,[19] and the pretreatment screening for preexisting CAD of patients candidates to antiangiogenic therapy should be reasonable.

In addition, a particularly high incidence of acute arterial thrombosis has been found following treatment with tyrosine kinase inhibitors, such as ponatinib, nilotinib, and dasatinib, developed for use in the setting of hematologic malignancy. This negative effect is especially evident for ponatinib,[19] whose use has been associated with a incidence of arterial thrombotic events at 2 years nearly 12%, most events occurring as acute thrombotic process.[19]

Finally, chest radiotherapy, which is commonly used to treat malignancies such as breast cancer and Hodgkin's disease, is associated with cardiovascular complications, especially CAD; in fact, mediastinal radiation is able to accelerate the atherosclerosis process, resulting in early-onset CAD.[20]


  Coronary Artery Disease as a Risk Factor Before Cancer Therapy Top


It is obvious that the presence of CAD is a potential life-threatening factor for cancer patients. The activation of cytokines and chemokines such as growth factors in several cancers induces thrombus formation known as paraneoplastic syndrome, which can cause acute myocardial infarction via hemostatic activation.[21] Thus, cancer patients with undetected CAD, especially in the presence of thrombocytosis and hyperfibrinogenemia, are predisposed to major cardiac events during chemotherapy.[22]

A history of myocardial infarction demonstrates the presence of CAD in patients with cancer. Depending on the extent of infarction, left ventricular dysfunction may be observed. The severity of left ventricular dysfunction is crucial for an individual patient with cancer because left ventricular ejection fraction (LVEF) remains the most important parameter for the decision whether to perform a cardiotoxic chemotherapy.[23]

As a consequence of the paraneoplastic syndrome, this cohort of patients is at high risk of myocardial reinfarction. For a cancer patient with severe CAD, the pivotal decision of whether to initiate chemotherapy, which could represent the only curative treatment, is dependent on the results of risk stratification by the oncologist. Typically, there is no optimized interdisciplinary approach to monitor the residual myocardial function in short-term echocardiographic investigations with modern modalities, which would allow detecting potential cardiotoxicity at an early stage, enabling proper treatment, and guiding chemotherapy by monitoring signs of cardiotoxicity.

Chronic heart failure due to end-stage CAD at the time of cancer diagnosis can also be a substantial limitation for chemotherapy. Worsening of heart failure is often compounded by the necessity of induced hypervolemia to increase the renal clearance of destroyed tissue products due to the biological degradation of tumor cells. On the other hand, cardiological treatment of chronic heart failure with volume restriction and diuretics administration often induces renal failure, which further limits chemotherapy.


  Management of Chemotherapy in Patients With Chronic Coronary Disease – Role of Imaging Techniques Top


The clinical diagnosis of CAD is normally based on symptoms such as cardiac dyspnea, angina, or palpitations during rest or stress-induced ischemia. The first cardiac alteration of the ischemic cascade is the diastolic dysfunction, followed by wall motion abnormalities, which are the first sign of stress-induced ischemia in conventional stress echocardiography (ECG); with the increasing myocardial ischemia, also, electrocardiographic alterations and angina can be observed.

Acute chest pain can be caused by acute myocardial infarction and can present as ST- or non-ST-segment elevation infarction, which needs interventional therapy when possible.[24] The imaging criteria of acute myocardial infarction are constituted by the evidence of new loss of viable myocardium tissue and/or new regional wall motion abnormalities.[25] In a new patient, detected wall motion abnormalities must be classified as acute, whereas, in the absence of nonischemic causes, loss of viable myocardium, with thinned tissue that fails to contract, can indicate a prior myocardial infarction.

Angina can be classified as unstable or stable. In unstable angina, cardiac imaging normally documents regional wall motion abnormalities, which corresponds pathophysiologically to hibernating myocardium.

Stable angina includes stress-induced angina and wall motion abnormalities in patients with known and previously treated CAD or with known cardiovascular risk factors.

The modalities for the diagnosis of CAD and myocardial damage in cancer patients are similar than general population. ECG, cardiac magnetic resonance (CMR) tomography, myocardial scintigraphy, and nuclear imaging modalities[26],[27] are the main imaging techniques we can apply in this setting.

Radionuclide angiography (MUGA) has been indicated to evaluate LV systolic function in patients undergoing chemotherapy for many years.[28] Serial imaging using MUGA effectively monitors chemotherapy-related damage because of its high accuracy and reproducibility of LVEF measurements. However, radiation exposure remains the main disadvantage of MUGA, which reduces its use given the increasing availability of other imaging techniques.[29]

ECG and CMR remain the two most commonly used imaging techniques for noninvasive cardiotoxicity evaluation.

CMR is a distinctive noninvasive validated technique to identify myocardial necrosis/fibrosis by acquiring T1 inversion recovery sequences after about 10 min following gadolinium-based contrast injection. With this approach called late gadolinium enhancement, the necrotic/fibrotic areas retaining the contrast appear hyperintense and their presence is strongly correlated with the prognosis in all cardiomyopathies.[30] However, especially for repetitive follow-up investigations, transthoracic ECG, including tissue velocity imaging and speckle tracking, is the most often used imaging modality in this clinical setting.[26],[31]

Early alterations due to chemotherapy-induced myocardial damage can be reflected by impairment of diastolic left ventricular function.[32] The echocardiographic assessment of diastolic dysfunction includes the determination of left atrial size and emptying function as well as A-wave velocity and A-wave duration of the retrograde flow in the pulmonary vein. An increase of the retrograde A-wave velocity of more than 35 cm/s and a larger duration of the retrograde flow during A-wave in the pulmonary vein than of the orthograde transmitral flow are indications for impairment of diastolic filling capacity of the left ventricle.

Cardiotoxicity affecting left ventricular myocardium is still detected on reduction of LVEF, which remains influenced by high interobserver variability in conventional bidimensional ECG. To increase accuracy, three-dimensional (3D) transthoracic ECG was shown to yield more reproducible values of left ventricular volumes and LVEF.[33] However, actual echocardiographic techniques such as deformation imaging with tissue Doppler and speckle tracking provide better insights into myocardial alterations due to cardiotoxicity, especially during early stages of the disease.[34]

Global longitudinal strain peak seems to be a more robust parameter than LVEF in detecting myocardial cardiotoxicity. Other parameters such as radial and circumferential strain are promising options. Analysis of the dynamics of cardiac rotation was shown to be able to detect cardiotoxicity earlier than analysis of LVEF and global longitudinal peak systolic strain.[35] Recent studies showed promising data on the role of cardiac mechanics evaluated by means of both bidimentional and tridimentional speckle tracking imaging.[36]

Some studies performed with ECG reported an additional role of stress imaging, revealing that patients treated with chemotherapy have reduced contractile reserve in comparison to healthy individuals;[37],[38] however, none of these studies reported a prognostic value. Other studies did not report an incremental value of the stress imaging in patients without suspicion of myocardial ischemia.[39],[40] Hence, when myocardial ischemia secondary to chemotherapy is clinically suspected, stress imaging can be used as indicated by the actual guidelines of the European Society of Cardiology on stable CAD (SCAD).[41] In patients with intermediate pretest probability of SCAD an imaging stress test should be preferred to an exercise ECG test.[41]

Dobutamine stress ECG combined with tissue Doppler velocity imaging during diastole as well as CMR tomography was proposed as an alternative approach to evaluate not only an increased ischemic risk but also an early myocardial dysfunction during chemotherapy.[37]

The monitoring of coronary damage and detection of microcirculatory dysfunction can be performed via the assessment of coronary flow reserve during adenosine or dipyridamole stress.[42],[43] Whereas the flow pattern of the epicardial coronary arteries, maximum velocities >4 m/s, and reduced coronary flow reserve (<2) are markers of severe epicardial stenosis, reduced coronary flow reserve in the presence of normal flow patterns can be interpreted as coronary microcirculatory dysfunction.[44] In patients undergoing chemotherapy, nonspecific signs of myocardial alterations can often be identified and related on the phenomenon of global or regional postsystolic radial shortening. This contraction pattern can be induced by edema or inflammation, which could also induce microvascular dysfunction. Monitoring of the microvascular properties during treatment with chemotherapeutic agents can be performed by measuring coronary flow reserve during vasodilator stress to document therapeutical effects. In addition, myocardial contrast ECG may be able to measure myocardial perfusion, but this approach is not yet established in routine clinical practice.[26]

Strategies to prevent myocardial damage induced by chemotherapy imply accurate risk stratification and early detection of cardiotoxicity.[45],[46] It is obvious that all available diagnostic tools, including electrocardiography, ECG, nuclear imaging, CMR tomography, and analysis of biomarkers,[47] should be used. New cardioprotective strategies should be implemented in the future after convincing data will be provided.[48],[49]


  Conclusions Top


CAD is a major risk factor and obstacle in the treatment of cancer. Baseline cardiovascular assessment is vital for the selection of appropriate chemotherapy, and preexisting cardiac disease must be treated aggressively.[50]

Several chemotherapeutic agents are known to trigger ischemic heart disease, and as it has happened for myocardial cardiotoxicity, more attention should be directed to early recognition and prevention of cardiac vascular toxicity.

An interdisciplinary approach based on the principles of oncology and cardiology should extend chemotherapeutic options for patients with CAD and reduced left ventricular function, provided that comprehensive, accurate, and frequent follow-up, mainly by ECG, is performed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Heron M, Hoyert DL, Murphy SL, Xu J, Kochanek KD, Tejada-Vera B. Deaths: Final data for 2006. Natl Vital Stat Rep 2009;57:1-34.  Back to cited text no. 1
    
2.
Suter TM, Ewer MS. Cancer drugs and the heart: Importance and management. Eur Heart J 2013;34:1102-11.  Back to cited text no. 2
    
3.
Daher IN, Yeh ET. Vascular complications of selected cancer therapies. Nat Clin Pract Cardiovasc Med 2008;5:797-805.  Back to cited text no. 3
    
4.
Madeddu C, Deidda M, Piras A, Cadeddu C, Demurtas L, Puzzoni M. Pathophysiology of cardiotoxicity induced by nonanthracycline chemotherapy. J Cardiovasc Med (Hagerstown) 2016;17 Suppl 1:S12-8.  Back to cited text no. 4
    
5.
Vaughn DJ, Palmer SC, Carver JR, Jacobs LA, Mohler ER. Cardiovascular risk in long-term survivors of testicular cancer. Cancer 2008;112:1949-53.  Back to cited text no. 5
    
6.
Sorrentino MF, Kim J, Foderaro AE, Truesdell AG 5-fluorouracil induced cardiotoxicity: Review of the literature. Cardiol J 2012;19:453-8.  Back to cited text no. 6
    
7.
Saif MW, Shah MM, Shah AR. Fluoropyrimidine-associated cardiotoxicity: Revisited. Expert Opin Drug Saf 2009;8:191-202.  Back to cited text no. 7
    
8.
Focaccetti C, Bruno A, Magnani E, Bartolini D, Principi E, Dallaglio K, et al. Effects of 5-fluorouracil on morphology, cell cycle, proliferation, apoptosis, autophagy and ROS production in endothelial cells and cardiomyocytes. PLoS One 2015;10:e0115686.  Back to cited text no. 8
    
9.
Bronckaers A, Gago F, Balzarini J, Liekens S. The dual role of thymidine phosphorylase in cancer development and chemotherapy. Med Res Rev 2009;29:903-53.  Back to cited text no. 9
    
10.
Ishikawa F, Miyazono K, Hellman U, Drexler H, Wernstedt C, Hagiwara K, et al. Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature 1989;338:557-62.  Back to cited text no. 10
    
11.
Ignatescu MC, Gharehbaghi-Schnell E, Hassan A, Rezaie-Majd S, Korschineck I, Schleef RR, et al. Expression of the angiogenic protein, platelet-derived endothelial cell growth factor, in coronary atherosclerotic plaques:In vivo correlation of lesional microvessel density and constrictive vascular remodeling. Arterioscler Thromb Vasc Biol 1999;19:2340-7.  Back to cited text no. 11
    
12.
Soultati A, Mountzios G, Avgerinou C, Papaxoinis G, Pectasides D, Dimopoulos MA, et al. Endothelial vascular toxicity from chemotherapeutic agents: Preclinical evidence and clinical implications. Cancer Treat Rev 2012;38:473-83.  Back to cited text no. 12
    
13.
Meinardi MT, Gietema JA, van Veldhuisen DJ, van der Graaf WT, de Vries EG, Sleijfer DT. Long-term chemotherapy-related cardiovascular morbidity. Cancer Treat Rev 2000;26:429-47.  Back to cited text no. 13
    
14.
Tocchetti CG, Cadeddu C, Di Lisi D, Femminò S, Madonna R, Mele D, et al. From molecular mechanisms to clinical management of antineoplastic drug-induced cardiovascular toxicity: A translational overview. Antioxid Redox Signal 2019;30:2110-53.  Back to cited text no. 14
    
15.
Wood SC, Tang X, Tesfamariam B. Paclitaxel potentiates inflammatory cytokine-induced prothrombotic molecules in endothelial cells. J Cardiovasc Pharmacol 2010;55:276-85.  Back to cited text no. 15
    
16.
Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007;357:2666-76.  Back to cited text no. 16
    
17.
Small HY, Montezano AC, Rios FJ, Savoia C, Touyz RM. Hypertension due to antiangiogenic cancer therapy with vascular endothelial growth factor inhibitors: Understanding and managing a new syndrome. Can J Cardiol 2014;30:534-43.  Back to cited text no. 17
    
18.
Ranpura V, Hapani S, Chuang J, Wu S. Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis inhibitor bevacizumab in cancer patients: A meta-analysis of randomized controlled trials. Acta Oncol 2010;49:287-97.  Back to cited text no. 18
    
19.
Herrmann J, Lerman A. An update on cardio-oncology. Trends Cardiovasc Med 2014;24:285-95.  Back to cited text no. 19
    
20.
Raghunathan D, Khilji MI, Hassan SA, Yusuf SW. Radiation-induced cardiovascular disease. Curr Atheroscler Rep 2017;19:22.  Back to cited text no. 20
    
21.
Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017;377:1119-31.  Back to cited text no. 21
    
22.
Franchini M, Montagnana M, Favaloro EJ, Lippi G. The bidirectional relationship of cancer and hemostasis and the potential role of anticoagulant therapy in moderating thrombosis and cancer spread. Semin Thromb Hemost 2009;35:644-53.  Back to cited text no. 22
    
23.
Mele D, Nardozza M, Spallarossa P, Frassoldati A, Tocchetti CG, Cadeddu C, et al. Current views on anthracycline cardiotoxicity. Heart Fail Rev 2016;21:621-34.  Back to cited text no. 23
    
24.
Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2016;37:267-315.  Back to cited text no. 24
    
25.
Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD. Third universal definition of myocardial infarction. Eur Heart J 2012;33:2551-67.  Back to cited text no. 25
    
26.
Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: A report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2014;15:1063-93.  Back to cited text no. 26
    
27.
Jiji RS, Kramer CM, Salerno M. Non-invasive imaging and monitoring cardiotoxicity of cancer therapeutic drugs. J Nucl Cardiol 2012;19:377-88.  Back to cited text no. 27
    
28.
Gottdiener JS, Mathisen DJ, Borer JS, Bonow RO, Myers CE, Barr LH, et al. Doxorubicin cardiotoxicity: Assessment of late left ventricular dysfunction by radionuclide cineangiography. Ann Intern Med 1981;94:430-5.  Back to cited text no. 28
    
29.
Pepe A, Pizzino F, Gargiulo P, Perrone-Filardi P, Cadeddu C, Mele D, et al. Cardiovascular imaging in the diagnosis and monitoring of cardiotoxicity: Cardiovascular magnetic resonance and nuclear cardiology. J Cardiovasc Med (Hagerstown) 2016;17 Suppl 1:S45-54.  Back to cited text no. 29
    
30.
Mahrholdt H, Wagner A, Judd RM, Sechtem U, Kim RJ. Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies. Eur Heart J 2005;26:1461-74.  Back to cited text no. 30
    
31.
Zito C, Longobardo L, Cadeddu C, Monte I, Novo G, Dell'Oglio S, et al. Cardiovascular imaging in the diagnosis and monitoring of cardiotoxicity: Role of echocardiography. J Cardiovasc Med (Hagerstown) 2016;17 Suppl 1:S35-44.  Back to cited text no. 31
    
32.
Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2016;29:277-314.  Back to cited text no. 32
    
33.
Lorenzini C, Lamberti C, Aquilina M, Rocca A, Cortesi P, Corsi C, et al. Reliability of left ventricular ejection fraction from three-dimensional echocardiography for cardiotoxicity onset detection in patients with breast cancer. J Am Soc Echocardiogr 2017;30:1103-10.  Back to cited text no. 33
    
34.
Thavendiranathan P, Poulin F, Lim KD, Plana JC, Woo A, Marwick TH. Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: A systematic review. J Am Coll Cardiol 2014;63:2751-68.  Back to cited text no. 34
    
35.
Cadeddu C, Piras A, Dessì M, Madeddu C, Mantovani G, Scartozzi M, et al. Timing of the negative effects of trastuzumab on cardiac mechanics after anthracycline chemotherapy. Int J Cardiovasc Imaging 2017;33:197-207.  Back to cited text no. 35
    
36.
Zhang KW, Finkelman BS, Gulati G, Narayan HK, Upshaw J, Narayan V, et al. Abnormalities in 3-dimensional left ventricular mechanics with anthracycline chemotherapy are associated with systolic and diastolic dysfunction. JACC Cardiovasc Imaging 2018;11:1059-68.  Back to cited text no. 36
    
37.
Yildirim A, Sedef Tunaoglu F, Pinarli FG, Ilhan M, Oguz A, Karadeniz C, et al. Early diagnosis of anthracycline toxicity in asymptomatic long-term survivors: Dobutamine stress echocardiography and tissue Doppler velocities in normal and abnormal myocardial wall motion. Eur J Echocardiogr 2010;11:814-22.  Back to cited text no. 37
    
38.
Jarfelt M, Kujacic V, Holmgren D, Bjarnason R, Lannering B. Exercise echocardiography reveals subclinical cardiac dysfunction in young adult survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer 2007;49:835-40.  Back to cited text no. 38
    
39.
Bountioukos M, Doorduijn JK, Roelandt JR, Vourvouri EC, Bax JJ, Schinkel AF, et al. Repetitive dobutamine stress echocardiography for the prediction of anthracycline cardiotoxicity. Eur J Echocardiogr 2003;4:300-5.  Back to cited text no. 39
    
40.
Lanzarini L, Bossi G, Laudisa ML, Klersy C, Aricò M. Lack of clinically significant cardiac dysfunction during intermediate dobutamine doses in long-term childhood cancer survivors exposed to anthracyclines. Am Heart J 2000;140:315-23.  Back to cited text no. 40
    
41.
Task Force Members, Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, et al. 2013 ESC guidelines on the management of stable coronary artery disease: The task force on the management of stable coronary artery disease of the European society of cardiology. Eur Heart J 2013;34:2949-3003.  Back to cited text no. 41
    
42.
Lethen H, Tries HP, Kersting S, Lambertz H. Validation of noninvasive assessment of coronary flow velocity reserve in the right coronary artery. A comparison of transthoracic echocardiographic results with intracoronary Doppler flow wire measurements. Eur Heart J 2003;24:1567-75.  Back to cited text no. 42
    
43.
Wada T, Hirata K, Shiono Y, Orii M, Shimamura K, Ishibashi K, et al. Coronary flow velocity reserve in three major coronary arteries by transthoracic echocardiography for the functional assessment of coronary artery disease: A comparison with fractional flow reserve. Eur Heart J Cardiovasc Imaging 2014;15:399-408.  Back to cited text no. 43
    
44.
Holte E, Vegsundvåg J, Hegbom K, Hole T, Wiseth R. Transthoracic Doppler echocardiography for detection of stenoses in the left coronary artery by use of poststenotic coronary flow profiles: A comparison with quantitative coronary angiography and coronary flow reserve. J Am Soc Echocardiogr 2013;26:77-85.  Back to cited text no. 44
    
45.
Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, Asteggiano R, Galderisi M, et al. 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC committee for practice guidelines: The task force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J 2016;37:2768-801.  Back to cited text no. 45
    
46.
Spallarossa P, Maurea N, Cadeddu C, Madonna R, Mele D, Monte I, et al. Arecommended 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. 46
    
47.
Novo G, Cadeddu C, Sucato V, Pagliaro P, Romano S, Tocchetti CG, et al. Role of biomarkers in monitoring antiblastic cardiotoxicity. J Cardiovasc Med (Hagerstown) 2016;17 Suppl 1:S27-34.  Back to cited text no. 47
    
48.
Madonna R, Cadeddu C, Deidda M, Giricz Z, Madeddu C, Mele D, et al. Cardioprotection by gene therapy: A review paper on behalf of the working group on drug cardiotoxicity and cardioprotection of the Italian Society of Cardiology. Int J Cardiol 2015;191:203-10.  Back to cited text no. 48
    
49.
Cadeddu C, Mercurio V, Spallarossa P, Nodari S, Triggiani M, Monte I, et al. Preventing antiblastic drug-related cardiomyopathy: Old and new therapeutic strategies. J Cardiovasc Med (Hagerstown) 2016;17 Suppl 1:S64-75.  Back to cited text no. 49
    
50.
Maurea N, Spallarossa P, Cadeddu C, Madonna R, Mele D, Monte I, et al. Arecommended practical approach to the management of target therapy and angiogenesis inhibitors 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:S93-104.  Back to cited text no. 50
    


    Figures

  [Figure 1]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Coronary Damage ...
Coronary Artery ...
Management of Ch...
Conclusions
References
Article Figures

 Article Access Statistics
    Viewed585    
    Printed37    
    Emailed0    
    PDF Downloaded43    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]