Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Role of Arterial Hypertension and Hypertension-Mediated Organ Damage in Cardiotoxicity of Anticancer Therapies

Role of Arterial Hypertension and Hypertension-Mediated Organ Damage in Cardiotoxicity of... Purpose of the Review Arterial hypertension (AH) is the most common cardiovascular (CV) risk factor in the community and in oncologic patients. It also represents the most important CV condition predisposing to anticancer treatment-related cardiotoxicity. This risk is heightened in the presence of cardiac AH-mediated organ damage (HMOD). Influence of AH and HMOD on the development of cardiotoxicity will be reviewed, with a focus on specific scenarios and implications for management of oncologic patients. Recent Findings Not adequately controlled AH before or during anticancer treatments and/or development of AH during or after completion of such therapies have detrimental effects on the clinical course of oncologic patients, particularly if HMOD is present. Summary As overlooking CV health can jeopardize the success of anticancer treatments, the goal for clinicians caring for the oncologic patient should include the treatment of AH and HMOD. Keywords Arterial hypertension · Arterial hypertension-mediated organ damage · Anthracycline · Anti-VEGF · Cardiotoxicity · Cardio-oncology Introduction Beside cardiotoxicity, cancer patients are also at increased risk of developing CV disease (CVD) in the long term after Cardiovascular (CV) adverse events related to anticancer completion of anticancer treatments [9], and such risk is therapies are defined as cardiotoxicity. This term represents a heightened in the presence of a worse CV risk profile [10, •• heterogeneous group of conditions including but not limited 11 ]. The burden and need for treatment of CV comor- to left ventricular dysfunction (LVD) and overt heart failure bidities in cancer patients, once overlooked, have thus been (HF), myocarditis, venous thromboembolism, arterial occlu- recognized as essential for an integrated strategy of CV pre- sive events, arrhythmias, and arterial hypertension (AH) [1, vention in the field of cardio-oncology [1 , 12, 13]. • • 2 , 3 , 4, 5]. Occurrence of cardiotoxicity mainly depends on two factors: the type of anticancer treatment with its inherent toxicity and the individual CV risk profile [6 , 7, 8]. The Importance of Arterial Hypertension in Cancer Patients AH is the most common comorbidity in cancer patients, * Giacomo Tini found in about 35–38% of the general oncologic population giacomo.tinimelato@uniroma1.it [14–16]. It is typically considered the most important CV Division of Cardiology, Department of Clinical factor favoring cardiotoxicity, in particular LVD [17]. AH and Molecular Medicine, University of Rome Sapienza, is known to have per se a detrimental CV effect and often Sant’Andrea Hospital, Rome, Italy clusters with other CV risk factors, thus worsening the over- IRCCS San Raffaele Pisana, Rome, Italy all individual risk profile [18]. This is true also in oncologic Cardiovascular Disease Unit, IRCCS Ospedale Policlinico patients. For example, in an administrative database study San Martino–IRCCS Italian Cardiology Network, Genoa, on oncologic patients eligible for anti-vascular endothelial Italy Vol.:(0123456789) 1 3 Current Heart Failure Reports growth factor (anti-VEGF) therapies, those with AH had to be checked, as it represents a proxy of even greater risk also more commonly other CV risk factors and comorbidi- for cardiotoxicities [34]. ties [19]. Moreover, patients affected by AH prior to starting The influence of AH and HMOD on the development anticancer therapy are at higher odds of developing an eleva- of cardiotoxicity is not limited to the time when anticancer tion of blood pressure (BP) values as cardiotoxicity [17]. therapies are delivered. In cancer survivors who had received For these reasons, an aggressive and careful treatment cardiotoxic drugs such as anthracyclines, cardiotoxicity may of AH in oncologic patients has been advocated, yet it is occur even years after end of treatment, and its development •• • still often overlooked [17, 20 , 21]. Furthermore, in the may be triggered by various stressors including AH [2 ]. oncologic setting, CV risk factors are usually defined based Therefore, in oncologic patients, both pre-existing and on the clinical history (i.e., present vs. absent) regardless of post hoc AH (considering “index time” the administration whether they are controlled or not, thus hindering the pos- of anticancer therapies) exert severe and detrimental effects. sibility of assessing their true influence on the risk of cardio- •• toxicity [12, 22 ]. Therefore, a close collaboration between oncologists and cardiologists is highly recommended before When Arterial Hypertension Represents initiation of anticancer treatments. Cardiotoxicity: the Case of Anti‑VEGF Agents It is important to point out that such considerations refer to the whole spectrum of anticancer treatments and not only Anti-VEGF agents comprise three groups of drugs: human- to classic chemotherapy. Contemporary anticancer treat- ized monoclonal antibodies that directly bind to VEGF, ments include, for example, hormone therapy for a variety tyrosine kinase inhibitors (TKIs), and soluble decoy recep- of cancers. AH plays an important role also in these settings. tors acting as “VEGF traps” [35]. Virtually, all patients Indeed, hormone treatments may cause elevation of BP val- treated with anti-VEGF agents develop an increase in BP ues, as in the case of abiraterone for prostate cancer [23], or values, and adverse events related to AH may occur in up worsen the overall CV profile, above which AH may be a to 60% of cases depending on the specific agent (Table  1) superimposed stressor, as in the case of hormone therapy for [17, 36]. AH is mainly an “on-target” effect of anti-VEGF breast cancer [24, 25]. drugs, meaning that the rise in BP values is due to the same The adverse pathological effects of AH are enhanced in mechanisms by which these agents exert their anticancer the presence of the so-called AH-mediated organ damage effect. In particular, by inhibiting VEGF receptor 2, these (HMOD). The development of HMOD in the vessels, heart anticancer agents determine a reduction in nitric oxide (NO) •• [26, 27 , 28], and kidney [29, 30] is related to adverse out- production in vessels, which in turn causes vasoconstriction, comes in the general AH population and contributes fur- augmentation of peripheral resistances, and overproduction ther to worsen the overall CV profile [31] both in men and of reactive oxygen species [37, 38]. Moreover, inhibition of women [32]. Moreover, despite the prevalence of HMOD VEGF also induces kidney glomerular lesion, proteinuria associated with increasing BP values, it can be found across and worsening renal function, and even a direct myocardial the whole “spectrum” of AH (i.e., not only in long-standing damage [17, 39, 40]. These latter events are instead due to AH or severely uncontrolled AH) and in each BP category “o- ff target” ee ff cts. Anti-VEGF agents also increase levels of •• its presence increases CV risk significantly [33 ]. Thus, endothelin 1, a molecule with vasoconstrictive effect, which also in oncologic individuals, the presence of HMOD needs elicits endothelial cell apoptosis, resulting in microcapillary Table 1 Anti-VEGF agents and Anti-VEGF agent Therapeutic target Incidence of arterial related incidence of arterial hypertension hypertension Bevacizumab VEGF ligand 22–24% Sunitinib VEGFR, PDGFR, KIT, FLT3, CSR, RET 15–34% Sorafenib VEGFR, PDGFR, KIT, FLT3, RET 17–29% Axitinib VEGFR 40% Pazopanib VEGFR, PDGFR, FGFR, KIT, Itk, Lck, c-FMS 36–46% Ponatinib VEGFR, PDGFR, FGFR, EPH, BCR-ABL, KIT, FLT3, 67% RET, Src, TIE2 Regorafenib VEGFR, PDGFR, FGFR, KIT, RET, BRAF 28–48% Cabozantinib VEGFR, KIT, FLT3, RET, MET, TRKB, AXL, TIE2 32–37% Vandetanib VEGFR, EGFR, RET 24% 1 3 Current Heart Failure Reports rarefactions, and induces renal thrombotic microangiopathy a ponatinib dose reduction, with maintained efficacy and [17]. higher safety [50–52]. At the clinical level, thus, anti-VEGF agents are well- This evidence highlights the importance of a baseline known to cause AH and AH-related disorders. Trials and evaluation of cancer patients scheduled to receive potentially real-world data have indeed shown that these anticancer cardiotoxic treatments in order to assess and, if necessary, •• drugs are associated with renal adverse events and HF [17, mitigate the individual CV risk profile [17, 53 ]. 35, 41]. AH due to anti-VEGF, and consequent HMOD, have a significant clinical impact, as these CV events may be severe and cause discontinuation of the anticancer treat- When Arterial Hypertension Triggers ment [42]. Since most anti-VEGF therapies are delivered in Cardiotoxicity: the Case of Anthracycline advanced cancer settings, interruption of treatment may have important prognostic implications. Cardiotoxicity due to anthracyclines occurs mainly due to The most important risk factor for BP increase due to three mechanisms. Traditionally, it has been related to an anti-VEGF agents is preexisting AH [43]. Accordingly, iron-mediated overproduction of reactive oxygen species the risk of AH-related adverse events due to anti-VEGF is [54]. Moreover, anthracyclines target the DNA topoisomer- heightened in the presence of preexisting AH and HMOD, ase II isoenzymes α and β. The latter is responsible for car- both renal and cardiac [1, 35, 44]. Thus, caution is required diotoxicity, since its inhibition in cardiomyocytes causes if a patient scheduled to receive anti-VEGF agents has a double-stranded breaks in DNA, transcriptome changes, history of chronic kidney disease, proteinuria, myocardial reactive oxygen species formation, and apoptosis [55, 56]. infarction or HF. The quick and uncontrolled increase in BP Finally, metabolites of anthracyclines accumulate within that frequently occurs with these drugs may rapidly decom- cardiomyocytes and contribute to persisting cardiotoxic pensate the preexisting clinical status [17]. damage [57]. According to the “multiple-hit” hypothesis, Nevertheless, AH due to anti-VEGF agents appears easily cardiotoxicity due to anthracyclines occur when the direct manageable [17, 45]. Despite some degree of damage due to damage of the drug, combined with other stressors (aging the intrinsic toxicity of these drugs being hardly avoidable, it and comorbidities), reaches a “point-of-no-return” threshold has been shown that if the increase in BP is well controlled, [2 , 58]. At the clinical level, this has two main implica- the added value of preexisting HMOD onto the risk of renal tions. First, anthracycline cardiotoxicity is amplified by CV •• and CV adverse events may be attenuated [22 , 46]. We risk factors and amplifies CV risk factor-induced cardiac have previously shown that a baseline cardio-oncologic thor- damage [59] (Fig. 1). Secondly, anthracycline cardiotoxicity ough CV assessment of cancer patients scheduled to receive may occur even years after end of treatment (i.e., long-term anti-VEGF agents was instrumental to optimize their CV cardiotoxicity) [2 ]. profile (given the high prevalence of risk factors, frequently Monitoring and management of CV risk profile are of not adequately controlled) and to set up AH management. primary importance in anthracycline recipients [12]. AH is This approach consists of advising the patient and the refer- recognized as the most important CV risk factor associated ring oncologist regarding the possibility of BP increase and with anthracycline cardiotoxicity [17, 60]. Moreover, can- •• of the importance of BP control [17, 22 ]. If the patient has cer patients treated with anthracycline with known AH have preexisting and uncontrolled AH, therapy is optimized. In been reported to be more likely to undergo therapy discon- case of newly diagnosed AH, an anti-hypertensive therapy tinuation or delay or a reduction in anthracycline doses, with is suggested (usually with low-dose combination of angio- significant prognostic implications [61]. tensin-converting enzyme inhibitors and calcium channel AH may trigger anthracycline cardiotoxicity both if it blockers). Consequently, we found that preexisting AH, even is pre-existing and when it develops after anticancer treat- if not adequately controlled at baseline, and chronic kidney ment (Fig. 1). In the first case, AH is the substrate on which disease were no longer associated with the occurrence of CV anthracyclines exert their direct damage; in the second sce- •• and renal events during anti-VEGF treatment [22 ]. Fur- nario, AH is the “second hit”, exacerbating the prior anthra- thermore, it has been shown that ponatinib causes both AH cycline effect [ 17]. However, while preexisting LVD and and direct vascular damage, and patients with prior history previous myocardial infarction are conditions easy to “spot,” of AH or of HMOD (especially peripheral arterial occlusive AH may cause subtle damage to the heart. Cardiac HMOD disease) have an up to twofold increased risk of CV adverse may manifest as left ventricular hypertrophy (LVH) or as HF events, in particular arterial occlusive events [47–49]. Nev- with preserved ejection fraction, which may be difficult to ertheless, it has been shown that if patients with AH sched- identify in inter-critical, well-compensated phases [62, 63]. uled to receive ponatinib are strictly controlled and their BP In patients scheduled to receive anthracyclines, AH should is well treated, the risk of CV adverse events is reduced. be recognized as an important risk factor for cardiotoxicity Moreover, patients burdened by HMOD may be eligible for [17], with such risk being further increased in the presence 1 3 Current Heart Failure Reports Fig. 1 Cardiotoxicity due to anthracycline: the multiple-hit hypothesis •• of HMOD. In a recent study, it has been shown that patients evaluate CV health before initiation of cancer treatment [7, 22 ] with AH affected by lymphoma and receiving anthracycline for patients in whom it would otherwise be overlooked or con- had a greater risk of cardiotoxicity if presenting LVH [64]. sidered too late (i.e., when cardiotoxicity has already occurred). However, beside an adequate and meticulous treatment of AH, The proposal by the Heart Failure Association and the Interna- few strategies have proven beneficial for the prevention of tional Cardio-Oncology Society provides charts to estimate the anthracycline-induced cardiotoxicity [2 , 65]. This is a very risk of cardiotoxicity for the main classes of anticancer therapies •• important concept when one considers implications for long- [53 ]. The importance of CV prevention strategies, targeted at term follow-up of cancer patients who received anthracycline adequate control of classic CV risk factors in oncologic patients, therapy, and the possibility of incident new-onset AH (and has then furthermore stressed in the recent European Society of even HMOD). Indeed, cancer patients with both pre-existing Cardiology guidelines on cardio-oncology published in 2022 •• and post hoc CV conditions (compared to those without) have [69 ]. The guidelines recommend an aggressive treatment of worse short-term [66] and long-term outcomes [10] after anti- CV risk factors, both during and after anticancer treatment com- cancer treatment completion. Similarly, CV risk factors, AH pletion, with a particular mention for AH. Indeed, guidelines in particular, play an important role in CV event occurrence remark the importance of adequate BP control, especially in in childhood cancer survivors [67]. oncologic patients with known AH and in those scheduled to Thus, anthracycline recipients should be advised to con- receive anti-VEGF agents. tinue life-long CV monitoring [1, 17]. Once cardiotoxicity Yet, how to perform a baseline cardio-oncology evalua- has developed, cardioactive drugs as beta-blockers, angio- tion varies taking into account several factors, including the tensin-converting enzyme inhibitors, or angiotensin receptor patient status, the specific scheduled anticancer treatment, blockers surely may play a role in attenuating the detrimental and the organization of each cardio-oncology center [17, effects of anthracyclines; however, primary prevention still 70]. While in the majority of cases a well-performed medi- represents the best way to avoid cardiotoxicity. Consistently, cal history collection, a cardiologic visit, and an ECG are AH must be treated promptly, as cardiac HMOD is irrevers- largely enough for a baseline cardio-oncology evaluation, ible. In this context, cardio-oncology practice may serve as some specific cases are worthy of further attention. First, it an important tool promoting CV health and prevention in the should be kept in mind a paramount concept that holds true •• oncologic setting [7, 22 , 68]. for each CV risk factor, and here it is reported for AH: not all patients have known AH or, if known, adequately controlled AH. The importance of a baseline evaluation stands in the Practical Implications fact that not only the presence versus absence of a CV risk factor is checked, but the adequate versus inadequate con- •• In 2020, the Heart Failure Association of the European Society trol of such risk factor is performed [12, 17, 22 ], which of Cardiology, together with the International Cardio-Oncology is somehow more important than only knowing if a CV risk Society, published a proposal for routine assessment of CV risk factor is present. Since HMOD may be concealed, all patients in oncologic patients scheduled to receive anticancer treatments with AH (not only those symptomatic or with a prior his- •• associated with cardiotoxicities [53 ]. This was a welcome tory of CV events) should be advised to perform a compre- acknowledgement of the fact that a baseline cardio-oncology hensive HMOD screening [17, 18, 52] if not scheduled as visit may provide a unique opportunity to comprehensively a routine procedure. Echocardiography may be performed 1 3 Current Heart Failure Reports in the same occasion of the visit, with a significant added References value to the baseline consultation. Even though this approach may be perceived as time consuming or not cost-effective, Papers of particular interest, published recently, have it is reasonable to assume that a one-time-only thorough been highlighted as: CV check-up in the oncologic setting holds great potential • Of importance and may represent an investment to avoid unplanned car- •• Of major importance diologic evaluations during anticancer treatment, with the 1. Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, risk of holding a therapy [7, 68]. Hence, patients with AH Asteggiano R, Galderisi M, et al. 2016 ESC position paper on scheduled to receive specific anticancer treatments such as cancer treatments and cardiovascular toxicity developed under •• ponatinib [53 ] should be checked for HMOD and, in par- the auspices of the ESC committee for practice guidelines ticular, peripheral arterial occlusive disease. This would not the task force for cancer treatments and cardiovascular toxic- ity of the European Society of Cardiology (ESC). Eur Heart J. only significantly reduce the risk of arterial occlusive events 2016;37(36):2768–801. (the most frequent CV toxicity with ponatinib) but also allow 2.• Spallarossa P, Maurea N, Cadeddu C, Madonna R, Mele D, to modulate the dose of the anticancer treatment based on the Monte I, et al. A recommended practical approach to the man- CV risk profile of each patient [50–52]. agement of anthracycline-based chemotherapy cardiotoxicity: an opinion paper of the working group on drug cardiotoxicity Thus, the baseline cardio-oncology evaluation helps to cus- and cardioprotection, Italian Society of Cardiology. J Cardiovasc tomize management of CV profile for each patient and con- Med. 2016;17:e84. (Physiopathological mechanisms revision currently to lower the risk for cardiotoxicities [17]. In the case and practical recommendations for prevention and manage- of AH, its presence and, most importantly, control should be ment of anthracycline-related cardiotoxicity.) 3.• Maurea N, Spallarossa P, Cadeddu C, Madonna R, Mele D, assessed; when AH is present, HMOD must be checked. Monte I, et al. A recommended practical approach to the man- agement of target therapy and angiogenesis inhibitors cardio- toxicity: an opinion paper of the working group on drug car- diotoxicity and cardioprotection, Italian Society of Cardiology. Conclusions J Cardiovasc Med. 2016;17:e93-104. (Physiopathological mechanisms revision and practical recommendations for AH is the most important CV condition predisposing to anti- prevention and management of anti-VEGF agents-related cancer treatment-related cardiotoxicity. This risk is height- cardiotoxicity.) 4. Spallarossa P, Sarocchi M, Tini G, Arboscello E, Toma M, ened in the presence of cardiac HMOD. Moreover, AH may Ameri P, et al. How to monitor cardiac complications of immune itself be an adverse effect of anticancer treatment, leading to checkpoint inhibitor therapy. Front Pharmacol. 2020;11:972. therapy discontinuation and poor outcomes. Therefore, the 5. Mohammed T, Singh M, Tiu JG, Kim AS. Etiology and management of good assessment and control of CV risk profile, including hypertension in patients with cancer. Cardiooncology. 2021;7(1):14. 6.• Cameron AC, Touyz RM, Lang NN. Vascular complications of the optimization of AH therapy, are of primary importance cancer chemotherapy. Can J Cardiol. 2016;32(7):852–62. First in the management of cancer patients. As overlooking CV review recognizing the multifactorial mechanisms causing health can jeopardize the success of anticancer treatments, cardiotoxicity (inherent drug toxicity, patient's cardiovas- the goal for clinicians caring for the oncologic patient should cular risk profile and genetic predisposition). 7. Tini G, Ameri P, Buzzatti G, Sarocchi M, Murialdo R, Guglielmi G, et al. include the treatment of AH and HMOD. Diversity of cardiologic issues in a contemporary cohort of women with breast cancer. Front Cardiovasc Med. 2021;8:654728. 8. Sharalaya Z, Collier P. Prevention of cardiotoxicities with tradi- Funding Open access funding provided by Università degli Studi di tional and novel chemotherapeutic agents. Curr Heart Fail Rep. Roma La Sapienza within the CRUI-CARE Agreement. 2018;15(4):260–9. 9. Sturgeon KM, Deng L, Bluethmann SM, Zhou S, Trifiletti Declarations DM, Jiang C, et al. A population-based study of cardiovascu- lar disease mortality risk in US cancer patients. Eur Heart J. Conflict of Interest The authors declare no competing interests. 2019;40(48):3889–97. 10. Armenian SH, Xu L, Ky B, Sun C, Farol LT, Pal SK, et  al. Open Access This article is licensed under a Creative Commons Attri- Cardiovascular disease among survivors of adult-onset can- bution 4.0 International License, which permits use, sharing, adapta- cer: a community-based retrospective cohort study. JCO. tion, distribution and reproduction in any medium or format, as long 2016;34(10):1122–30. as you give appropriate credit to the original author(s) and the source, 11.•• Hershman DL, Till C, Shen S, Wright JD, Ramsey SD, Barlow provide a link to the Creative Commons licence, and indicate if changes WE, et al. Association of cardiovascular risk factors with cardiac were made. The images or other third party material in this article are events and survival outcomes among patients with breast can- included in the article's Creative Commons licence, unless indicated cer enrolled in SWOG clinical trials. JCO. 2018;36(26):2710– otherwise in a credit line to the material. If material is not included in 7. (Large scale study ultimately recognizing the impact the article's Creative Commons licence and your intended use is not of baseline cardiovascular risk factors on development of permitted by statutory regulation or exceeds the permitted use, you will cardiotoxicity.) need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://cr eativ ecommons. or g/licen ses/ b y/4.0/ . 1 3 Current Heart Failure Reports 12. Tini G, Sarocchi M, Ameri P, Arboscello E, Spallarossa P. The 27.•• Volpe M, Battistoni A, Tocci G, Rosei EA, Catapano AL, Coppo need for cardiovascular risk factor prevention in cardio-oncol- R, et al. Cardiovascular risk assessment beyond systemic coro- ogy. JACC Heart Fail. 2019;7(4):367–8. nary risk estimation: a role for organ damage markers. J Hyper- 13. Yin AB, Brewster AM, Barac A, Thoman W, Oeffinger KC, Gil- tens. 2012;30(6):1056–64. (Description of the importance of christ SC. Cardiovascular prevention strategies in breast cancer. arterial hypertension mediated organ damage recognition to JACC CardioOncology. 2019;1(2):322–5. adequately assess individual cardiovascular risk profile.) 14. Piccirillo JF, Tierney RM, Costas I, Grove L, Spitznagel EL. 28. Piskorz D. Hypertensive mediated organ damage and hyper- Prognostic importance of comorbidity in a hospital-based cancer tension management. How to assess beneficial effects of anti- registry. JAMA. 2004;291(20):2441–7. hypertensive treatments? High Blood Press Cardiovasc Prev. 15. Unger JM, Hershman DL, Fleury ME, Vaidya R. Association of 2020;27(1):9–17. patient comorbid conditions with cancer clinical trial participa- 29. Viazzi F, Leoncini G, Conti N, Tomolillo C, Giachero G, tion. JAMA Oncol. 2019;5(3):326–33. Vercelli M, et al. Combined effect of albuminuria and esti- 16. Battistoni A, Tocci G, Coluccia R, Burnier M, Ruilope LM, mated glomerular filtration rate on cardiovascular events and Volpe M. Antihypertensive drugs and the risk of cancer: a criti- all-cause mortality in uncomplicated hypertensive patients. J cal review of available evidence and perspective. J Hypertens. Hypertens. 2010;28(4):848–55. 2020;38(6):1005–15. 30. Sciarretta S, Valenti V, Tocci G, Pontremoli R, Rosei EA, 17. Tini G, Sarocchi M, Tocci G, Arboscello E, Ghigliotti G, Novo Ambrosioni E, et al. Association of renal damage with cardio- G, et al. Arterial hypertension in cancer: the elephant in the vascular diseases is independent of individual cardiovascular room. Int J Cardiol. 2019;15(281):133–9. risk profile in hypertension: data from the Italy-developing 18. Williams B, Mancia G, Spiering W, AgabitiRosei E, Azizi M, education and awareness on microalbuminuria in patients with Burnier M, et al. 2018 ESC/ESH guidelines for the manage- hypertensive disease study. J Hypertens. 2010;28(2):251–8. ment of arterial hypertension the task force for the management 31. Tocci G, Figliuzzi I, Presta V, Attalla El Halabieh N, Citoni of arterial hypertension of the European Society of Cardiology B, Coluccia R, et al. Adding markers of organ damage to risk (ESC) and the European Society of Hypertension (ESH). Eur score models improves cardiovascular risk assessment: pro- Heart J. 2018;39(33):3021–104. spective analysis of a large cohort of adult outpatients. Int J 19. Liu F, Hidru TH, Gao R, Lin Y, Liu Y, Fang F, et al. Cancer Cardiol. 2017;248:342–8. patients with potential eligibility for vascular endothelial growth 32. Muiesan ML, Paini A, Aggiusti C, Bertacchini F, Rosei CA, factor antagonists use have an increased risk for cardiovascular Salvetti M. Hypertension and organ damage in women. High diseases comorbidities. J Hypertens. 2020;38(3):426–33. Blood Press Cardiovasc Prev. 2018;25(3):245–52. 20.•• Hershman DL, Accordino MK, Shen S, Buono D, Crew KD, 33.•• Vasan RS, Song RJ, Xanthakis V, Beiser A, DeCarli C, Mitch- Kalinsky K, et al. Association between nonadherence to cardio- ell GF, et al. Hypertension-mediated organ damage: preva- vascular risk factor medications after breast cancer diagnosis lence, correlates, and prognosis in the community. Hyperten- and incidence of cardiac events. Cancer. 2020;126(7):1541–9. sion. 2022;79(3):505–15. (Contemporary description of (Large scale study recognizing the importance of adequate prevalence and significance of arterial hypertension medi- control of cardiovascular risk factors before and during can- ated organ damage: for each blood pressure category, the cer treatment, as nonadherence to cardiovascular medica- presence of organ damage significantly increase cardiovas - tions is associated with development of cardiotoxicity.) cular risk.) 21. Izzedine H, Ederhy S, Goldwasser F, Soria JC, Milano G, Cohen 34. Bruno G, Bringhen S, Maffei I, Iannaccone A, Crea T, Ravera A, et al. Management of hypertension in angiogenesis inhibitor- A, et al. Cardiovascular organ damage and blood pressure levels treated patients. Ann Oncol. 2009;20(5):807–15. predict adverse events in multiple myeloma patients undergoing 22.•• Tini G, Sarocchi M, Sirello D, Murialdo R, Fornarini G, Buz- carfilzomib therapy. Cancers. 2019;11(5):622. zatti G, et  al. Cardiovascular risk profile and events before 35. Touyz RM, Herrmann J. Cardiotoxicity with vascular endothe- and after treatment with anti-VEGF drugs in the setting of a lial growth factor inhibitor therapy. npj Precision Onc. structured cardio-oncologic program. Eur J PrevCardiolog. 2018;2(1):1–11. 2020;6:204748732092305. (Small real-world study showing 36. Small HY, Montezano AC, Rios FJ, Savoia C, Touyz RM. that reaching an adequate blood pressure control before ini- Hypertension due to antiangiogenic cancer therapy with vas- tiation of anti-VEGF agents therapy makes arterial hyper- cular endothelial growth factor inhibitors: understanding and tension no longer associated with cardiotoxicity.) managing a new syndrome. Can J Cardiol. 2014;30(5):534–43. 23. Cavo A, Rubagotti A, Zanardi E, Fabbroni C, Zinoli L, Di Meg- 37. Pandey AK, Singhi EK, Arroyo JP, Ikizler TA, Gould ER, Brown lio A, et al. Abiraterone acetate and prednisone in the pre- and J, et al. Mechanisms of VEGF (vascular endothelial growth fac- post-docetaxel setting for metastatic castration-resistant prostate tor) inhibitor-associated hypertension and vascular disease. cancer: a mono-institutional experience focused on cardiovascu- Hypertension. 2018;71(2):e1-8. lar events and their impact on clinical outcomes. Ther Adv Med 38. Neves KB, Rios FJ, van der Mey L, Alves-Lopes R, Cameron Oncol. 2018;10:1758834017745819. AC, Volpe M, et al. VEGFR (vascular endothelial growth factor 24. Mehta LS, Watson KE, Barac A, Beckie TM, Bittner V, Cruz- receptor) inhibition induces cardiovascular damage via redox- Flores S, et al. Cardiovascular disease and breast cancer: where sensitive processes. Hypertension. 2018;71(4):638–47. these entities intersect: a scientific statement from the American 39. Bohdan M, Kowalczys A, Mickiewicz A, Gruchała M, Lewicka Heart Association. Circulation [Internet]. 2018 Feb 20 [cited E. Cancer therapy-related cardiovascular complications in clini- 2020 Jul 12];137(8). Available from: https:// www. ahajo urnals. cal practice: current perspectives. JCM. 2021;10(8):1647. org/ doi/ 10. 1161/ CIR. 00000 00000 000556. 40. Maurea N, Coppola C, Piscopo G, Galletta F, Riccio G, Esposito 25. Lanza O, Ferrera A, Reale S, Solfanelli G, Petrungaro M, Tini- E, et al. Pathophysiology of cardiotoxicity from target therapy Melato G, et al. New insights on the toxicity on heart and vessels and angiogenesis inhibitors. J Cardiovasc Med (Hagerstown). of breast cancer therapies. Med Sci (Basel). 2022;10(2):27. 2016;17(Suppl 1):S19-26. 26. Drazner MH. The progression of hypertensive heart disease. 41. Witteles RM, Telli M. Underestimating cardiac toxicity in cancer Circulation. 2011;123(3):327–34. trials: lessons learned? JCO. 2012;30(16):1916–8. 1 3 Current Heart Failure Reports 42. Schmidinger M. Understanding and managing toxicities of vas- 56. Mercurio V, Pirozzi F, Lazzarini E, Marone G, Rizzo P, Agnetti cular endothelial growth factor (VEGF) inhibitors. Eur J Cancer G, et al. Models of heart failure based on the cardiotoxicity of Suppl. 2013;11(2):172–91. anticancer drugs. J Card Fail. 2016;22(6):449–58. 43. Hamnvik OPR, Choueiri TK, Turchin A, McKay RR, Goyal 57. Menna P, Paz OG, Chello M, Covino E, Salvatorelli E, Minotti L, Davis M, et al. Clinical risk factors for the development of G. Anthracycline cardiotoxicity. Expert Opin Drug Saf. hypertension in patients treated with inhibitors of the VEGF 2012;11(sup1):S21-36. signaling pathway: hypertension with anti-VEGF therapies. Can- 58. Mele D, Tocchetti CG, Pagliaro P, Madonna R, Novo G, Pepe cer. 2015;121(2):311–9. A, et al. Pathophysiology of anthracycline cardiotoxicity. J Car- 44. Touyz RM, Herrmann SMS, Herrmann J. Vascular toxicities diovasc Med. 2016;17:e3. with VEGF inhibitor therapies–focus on hypertension and arte- 59. Salvatorelli E, Menna P, Minotti G. Managing anthracycline- rial thrombotic events. J Am Soc Hypertens. 2018;12(6):409–25. induced cardiotoxicity: beginning with the end in mind. Future 45. Rizzoni D, De Ciuceis C, Porteri E, Agabiti-Rosei C, Agabiti- Cardiol. 2015;11(4):363–6. Rosei E. Use of antihypertensive drugs in neoplastic patients. 60. Pinder MC, Duan Z, Goodwin JS, Hortobagyi GN, Giordano High Blood Press Cardiovasc Prev. 2017;24(2):127–32. SH. Congestive heart failure in older women treated with 46. Boursiquot BC, Zabor EC, Glezerman IG, Jaimes EA. Hyper- adjuvant anthracycline chemotherapy for breast cancer. JCO. tension and VEGF (vascular endothelial growth factor) receptor 2007;25(25):3808–15. tyrosine kinase inhibition: effects on renal function. Hyperten- 61. Szmit S, Jurczak W, Zaucha JM, Drozd-Sokołowska J, sion. 2017;70(3):552–8. Spychałowicz W, Joks M, et al. Pre-existing arterial hyperten- 47. Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre PD, Paquette R, sion as a risk factor for early left ventricular systolic dysfunction Chuah C, et al. Ponatinib efficacy and safety in Philadelphia following (R)-CHOP chemotherapy in patients with lymphoma. chromosome-positive leukemia: final 5-year results of the phase J Am Soc Hypertens. 2014;8(11):791–9. 2 PACE trial. Blood. 2018;132(4):393–404. 62. Nadruz W. Myocardial remodeling in hypertension. J Hum 48. Haguet H, Douxfils J, Mullier F, Chatelain C, Graux C, Dogné Hypertens. 2015;29(1):1–6. JM. Risk of arterial and venous occlusive events in chronic 63. Lewis GA, Schelbert EB, Williams SG, Cunnington C, Ahmed myeloid leukemia patients treated with new generation BCR- F, McDonagh TA, et al. Biological phenotypes of heart fail- ABL tyrosine kinase inhibitors: a systematic review and meta- ure with preserved ejection fraction. J Am Coll Cardiol. analysis. Expert Opin Drug Saf. 2017;16(1):5–12. 2017;70(17):2186–200. 49. Januzzi JL, Garasic JM, Kasner SE, McDonald V, Petrie MC, 64. Tanaka Y, Tanaka H, Hatazawa K, Yamashita K, Sumimoto K, Seltzer J, et al. Retrospective analysis of arterial occlusive events Shono A, et al. Impact of hypertension on left ventricular func- in the PACE trial by an independent adjudication committee. J tion in patients after anthracycline chemotherapy for malignant Hematol Oncol. 2022;15(1):1. lymphoma. Int J Cardiol. 2021;15(323):126–32. 50. Iurlo A, Cattaneo D, Orofino N, Bucelli C, Molica M, Brec- 65. Minotti G. The International Cardioncology Society-ONE trial: cia M. Low-dose ponatinib in intolerant chronic myeloid leu- not all that glitters is for cardioncologists only. Eur J Cancer. kemia patients: a safe and effective option. Clin Drug Investig. 2018;97:27–9. 2018;38(5):475–6. 66. Hussain M, Hou Y, Watson C, Moudgil R, Shah C, Abra- 51. Cortes JE, Lomaia E, Turkina A, Moiraghi B, Undurraga Sutton ham J, et  al. Temporal trends of cardiac outcomes and M, Pavlovsky C, et al. Interim analysis (IA) of OPTIC: a dose- impact on survival in patients with cancer. Am J Cardiol. ranging study of three ponatinib (PON) starting doses. JCO. 2020;15(137):118–24. 2020;38(15_suppl):7502–7502. 67. Chen Y, Chow EJ, Oeffinger KC, Border WL, Leisenring WM, 52. Breccia M, Pregno P, Spallarossa P, Arboscello E, Ciceri F, Meacham LR, et al. Traditional cardiovascular risk factors and Giorgi M, et  al. Identification, prevention and management individual prediction of cardiovascular events in childhood can- of cardiovascular risk in chronic myeloid leukaemiapatients cer survivors. J Natl Cancer Inst. 2020;112(3):256–65. candidate to ponatinib: an expert opinion. Ann Hematol. 68. Tini G, Cuomo A, Battistoni A, Sarocchi M, Mercurio V, 2017;96(4):549–58. Ameri P, et al. Baseline cardio-oncologic risk assessment in 53.•• Lyon AR, Dent S, Stanway S, Earl H, Brezden-Masley C, Cohen- breast cancer women and occurrence of cardiovascular events: Solal A, et al. Baseline cardiovascular risk assessment in can- the HFA/ICOS risk tool in real-world practice. Int J Cardiol. cer patients scheduled to receive cardiotoxic cancer therapies: 2021;S0167–5273(21):01876–83. a position statement and new risk assessment tools from the 69.•• Lyon AR, López-Fernández T, Couch LS, Asteggiano R, Aznar cardio-oncology study group of the Heart Failure Association MC, Bergler-Klein J, et  al. 2022 ESC guidelines on cardio- of the European Society of Cardiology in collaboration with oncology developed in collaboration with the European Hema- the International Cardio-Oncology Society. Eur J Heart Fail. tology Association (EHA), the European Society for Therapeutic 2020;22(11):1945–60. (European Society of Cardiology Heart Radiology and Oncology (ESTRO) and the International Cardio- Failure Association and International Cardio-Oncology Soci- Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229–361. ety joint position statement highlighting the importance of a (Recently published European Society of Cardiology guide- baseline Cardio-Oncology evaluation before specific antican- lines on Cardio-Oncology. The paper highlights the impor- cer treatments are initiated to effectively assess cardiovascu - tance of CV risk stratification in all oncologic patients before lar risk and initiate strategies to prevent cardiotoxicity.) initiation of anticancer treatments and recommend adequate 54. Menna P, Salvatorelli E, Minotti G. Anthracycline degradation and aggressive control of CV risk factors in primary preven- in cardiomyocytes: a journey to oxidative survival. Chem Res tion in the oncologic population.) Toxicol. 2010;23(1):6–10. 70. Tini G, Spallarossa P. How cardio-oncology is called to prove 55. Lazzarini E, Balbi C, Altieri P, Pfeffer U, Gambini E, Canepa its maturity. Int J Cardiol. 2019;01(288):130–1. M, et al. The human amniotic fluid stem cell secretome effec - tively counteracts doxorubicin-induced cardiotoxicity. Sci Rep. Publisher's Note Springer Nature remains neutral with regard to 2016;21(6):29994. jurisdictional claims in published maps and institutional affiliations. 1 3 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Current Heart Failure Reports Springer Journals

Role of Arterial Hypertension and Hypertension-Mediated Organ Damage in Cardiotoxicity of Anticancer Therapies

Loading next page...
 
/lp/springer-journals/role-of-arterial-hypertension-and-hypertension-mediated-organ-damage-YZqM7bH4YD

References (76)

Publisher
Springer Journals
Copyright
Copyright © The Author(s) 2023
ISSN
1546-9530
eISSN
1546-9549
DOI
10.1007/s11897-023-00590-5
Publisher site
See Article on Publisher Site

Abstract

Purpose of the Review Arterial hypertension (AH) is the most common cardiovascular (CV) risk factor in the community and in oncologic patients. It also represents the most important CV condition predisposing to anticancer treatment-related cardiotoxicity. This risk is heightened in the presence of cardiac AH-mediated organ damage (HMOD). Influence of AH and HMOD on the development of cardiotoxicity will be reviewed, with a focus on specific scenarios and implications for management of oncologic patients. Recent Findings Not adequately controlled AH before or during anticancer treatments and/or development of AH during or after completion of such therapies have detrimental effects on the clinical course of oncologic patients, particularly if HMOD is present. Summary As overlooking CV health can jeopardize the success of anticancer treatments, the goal for clinicians caring for the oncologic patient should include the treatment of AH and HMOD. Keywords Arterial hypertension · Arterial hypertension-mediated organ damage · Anthracycline · Anti-VEGF · Cardiotoxicity · Cardio-oncology Introduction Beside cardiotoxicity, cancer patients are also at increased risk of developing CV disease (CVD) in the long term after Cardiovascular (CV) adverse events related to anticancer completion of anticancer treatments [9], and such risk is therapies are defined as cardiotoxicity. This term represents a heightened in the presence of a worse CV risk profile [10, •• heterogeneous group of conditions including but not limited 11 ]. The burden and need for treatment of CV comor- to left ventricular dysfunction (LVD) and overt heart failure bidities in cancer patients, once overlooked, have thus been (HF), myocarditis, venous thromboembolism, arterial occlu- recognized as essential for an integrated strategy of CV pre- sive events, arrhythmias, and arterial hypertension (AH) [1, vention in the field of cardio-oncology [1 , 12, 13]. • • 2 , 3 , 4, 5]. Occurrence of cardiotoxicity mainly depends on two factors: the type of anticancer treatment with its inherent toxicity and the individual CV risk profile [6 , 7, 8]. The Importance of Arterial Hypertension in Cancer Patients AH is the most common comorbidity in cancer patients, * Giacomo Tini found in about 35–38% of the general oncologic population giacomo.tinimelato@uniroma1.it [14–16]. It is typically considered the most important CV Division of Cardiology, Department of Clinical factor favoring cardiotoxicity, in particular LVD [17]. AH and Molecular Medicine, University of Rome Sapienza, is known to have per se a detrimental CV effect and often Sant’Andrea Hospital, Rome, Italy clusters with other CV risk factors, thus worsening the over- IRCCS San Raffaele Pisana, Rome, Italy all individual risk profile [18]. This is true also in oncologic Cardiovascular Disease Unit, IRCCS Ospedale Policlinico patients. For example, in an administrative database study San Martino–IRCCS Italian Cardiology Network, Genoa, on oncologic patients eligible for anti-vascular endothelial Italy Vol.:(0123456789) 1 3 Current Heart Failure Reports growth factor (anti-VEGF) therapies, those with AH had to be checked, as it represents a proxy of even greater risk also more commonly other CV risk factors and comorbidi- for cardiotoxicities [34]. ties [19]. Moreover, patients affected by AH prior to starting The influence of AH and HMOD on the development anticancer therapy are at higher odds of developing an eleva- of cardiotoxicity is not limited to the time when anticancer tion of blood pressure (BP) values as cardiotoxicity [17]. therapies are delivered. In cancer survivors who had received For these reasons, an aggressive and careful treatment cardiotoxic drugs such as anthracyclines, cardiotoxicity may of AH in oncologic patients has been advocated, yet it is occur even years after end of treatment, and its development •• • still often overlooked [17, 20 , 21]. Furthermore, in the may be triggered by various stressors including AH [2 ]. oncologic setting, CV risk factors are usually defined based Therefore, in oncologic patients, both pre-existing and on the clinical history (i.e., present vs. absent) regardless of post hoc AH (considering “index time” the administration whether they are controlled or not, thus hindering the pos- of anticancer therapies) exert severe and detrimental effects. sibility of assessing their true influence on the risk of cardio- •• toxicity [12, 22 ]. Therefore, a close collaboration between oncologists and cardiologists is highly recommended before When Arterial Hypertension Represents initiation of anticancer treatments. Cardiotoxicity: the Case of Anti‑VEGF Agents It is important to point out that such considerations refer to the whole spectrum of anticancer treatments and not only Anti-VEGF agents comprise three groups of drugs: human- to classic chemotherapy. Contemporary anticancer treat- ized monoclonal antibodies that directly bind to VEGF, ments include, for example, hormone therapy for a variety tyrosine kinase inhibitors (TKIs), and soluble decoy recep- of cancers. AH plays an important role also in these settings. tors acting as “VEGF traps” [35]. Virtually, all patients Indeed, hormone treatments may cause elevation of BP val- treated with anti-VEGF agents develop an increase in BP ues, as in the case of abiraterone for prostate cancer [23], or values, and adverse events related to AH may occur in up worsen the overall CV profile, above which AH may be a to 60% of cases depending on the specific agent (Table  1) superimposed stressor, as in the case of hormone therapy for [17, 36]. AH is mainly an “on-target” effect of anti-VEGF breast cancer [24, 25]. drugs, meaning that the rise in BP values is due to the same The adverse pathological effects of AH are enhanced in mechanisms by which these agents exert their anticancer the presence of the so-called AH-mediated organ damage effect. In particular, by inhibiting VEGF receptor 2, these (HMOD). The development of HMOD in the vessels, heart anticancer agents determine a reduction in nitric oxide (NO) •• [26, 27 , 28], and kidney [29, 30] is related to adverse out- production in vessels, which in turn causes vasoconstriction, comes in the general AH population and contributes fur- augmentation of peripheral resistances, and overproduction ther to worsen the overall CV profile [31] both in men and of reactive oxygen species [37, 38]. Moreover, inhibition of women [32]. Moreover, despite the prevalence of HMOD VEGF also induces kidney glomerular lesion, proteinuria associated with increasing BP values, it can be found across and worsening renal function, and even a direct myocardial the whole “spectrum” of AH (i.e., not only in long-standing damage [17, 39, 40]. These latter events are instead due to AH or severely uncontrolled AH) and in each BP category “o- ff target” ee ff cts. Anti-VEGF agents also increase levels of •• its presence increases CV risk significantly [33 ]. Thus, endothelin 1, a molecule with vasoconstrictive effect, which also in oncologic individuals, the presence of HMOD needs elicits endothelial cell apoptosis, resulting in microcapillary Table 1 Anti-VEGF agents and Anti-VEGF agent Therapeutic target Incidence of arterial related incidence of arterial hypertension hypertension Bevacizumab VEGF ligand 22–24% Sunitinib VEGFR, PDGFR, KIT, FLT3, CSR, RET 15–34% Sorafenib VEGFR, PDGFR, KIT, FLT3, RET 17–29% Axitinib VEGFR 40% Pazopanib VEGFR, PDGFR, FGFR, KIT, Itk, Lck, c-FMS 36–46% Ponatinib VEGFR, PDGFR, FGFR, EPH, BCR-ABL, KIT, FLT3, 67% RET, Src, TIE2 Regorafenib VEGFR, PDGFR, FGFR, KIT, RET, BRAF 28–48% Cabozantinib VEGFR, KIT, FLT3, RET, MET, TRKB, AXL, TIE2 32–37% Vandetanib VEGFR, EGFR, RET 24% 1 3 Current Heart Failure Reports rarefactions, and induces renal thrombotic microangiopathy a ponatinib dose reduction, with maintained efficacy and [17]. higher safety [50–52]. At the clinical level, thus, anti-VEGF agents are well- This evidence highlights the importance of a baseline known to cause AH and AH-related disorders. Trials and evaluation of cancer patients scheduled to receive potentially real-world data have indeed shown that these anticancer cardiotoxic treatments in order to assess and, if necessary, •• drugs are associated with renal adverse events and HF [17, mitigate the individual CV risk profile [17, 53 ]. 35, 41]. AH due to anti-VEGF, and consequent HMOD, have a significant clinical impact, as these CV events may be severe and cause discontinuation of the anticancer treat- When Arterial Hypertension Triggers ment [42]. Since most anti-VEGF therapies are delivered in Cardiotoxicity: the Case of Anthracycline advanced cancer settings, interruption of treatment may have important prognostic implications. Cardiotoxicity due to anthracyclines occurs mainly due to The most important risk factor for BP increase due to three mechanisms. Traditionally, it has been related to an anti-VEGF agents is preexisting AH [43]. Accordingly, iron-mediated overproduction of reactive oxygen species the risk of AH-related adverse events due to anti-VEGF is [54]. Moreover, anthracyclines target the DNA topoisomer- heightened in the presence of preexisting AH and HMOD, ase II isoenzymes α and β. The latter is responsible for car- both renal and cardiac [1, 35, 44]. Thus, caution is required diotoxicity, since its inhibition in cardiomyocytes causes if a patient scheduled to receive anti-VEGF agents has a double-stranded breaks in DNA, transcriptome changes, history of chronic kidney disease, proteinuria, myocardial reactive oxygen species formation, and apoptosis [55, 56]. infarction or HF. The quick and uncontrolled increase in BP Finally, metabolites of anthracyclines accumulate within that frequently occurs with these drugs may rapidly decom- cardiomyocytes and contribute to persisting cardiotoxic pensate the preexisting clinical status [17]. damage [57]. According to the “multiple-hit” hypothesis, Nevertheless, AH due to anti-VEGF agents appears easily cardiotoxicity due to anthracyclines occur when the direct manageable [17, 45]. Despite some degree of damage due to damage of the drug, combined with other stressors (aging the intrinsic toxicity of these drugs being hardly avoidable, it and comorbidities), reaches a “point-of-no-return” threshold has been shown that if the increase in BP is well controlled, [2 , 58]. At the clinical level, this has two main implica- the added value of preexisting HMOD onto the risk of renal tions. First, anthracycline cardiotoxicity is amplified by CV •• and CV adverse events may be attenuated [22 , 46]. We risk factors and amplifies CV risk factor-induced cardiac have previously shown that a baseline cardio-oncologic thor- damage [59] (Fig. 1). Secondly, anthracycline cardiotoxicity ough CV assessment of cancer patients scheduled to receive may occur even years after end of treatment (i.e., long-term anti-VEGF agents was instrumental to optimize their CV cardiotoxicity) [2 ]. profile (given the high prevalence of risk factors, frequently Monitoring and management of CV risk profile are of not adequately controlled) and to set up AH management. primary importance in anthracycline recipients [12]. AH is This approach consists of advising the patient and the refer- recognized as the most important CV risk factor associated ring oncologist regarding the possibility of BP increase and with anthracycline cardiotoxicity [17, 60]. Moreover, can- •• of the importance of BP control [17, 22 ]. If the patient has cer patients treated with anthracycline with known AH have preexisting and uncontrolled AH, therapy is optimized. In been reported to be more likely to undergo therapy discon- case of newly diagnosed AH, an anti-hypertensive therapy tinuation or delay or a reduction in anthracycline doses, with is suggested (usually with low-dose combination of angio- significant prognostic implications [61]. tensin-converting enzyme inhibitors and calcium channel AH may trigger anthracycline cardiotoxicity both if it blockers). Consequently, we found that preexisting AH, even is pre-existing and when it develops after anticancer treat- if not adequately controlled at baseline, and chronic kidney ment (Fig. 1). In the first case, AH is the substrate on which disease were no longer associated with the occurrence of CV anthracyclines exert their direct damage; in the second sce- •• and renal events during anti-VEGF treatment [22 ]. Fur- nario, AH is the “second hit”, exacerbating the prior anthra- thermore, it has been shown that ponatinib causes both AH cycline effect [ 17]. However, while preexisting LVD and and direct vascular damage, and patients with prior history previous myocardial infarction are conditions easy to “spot,” of AH or of HMOD (especially peripheral arterial occlusive AH may cause subtle damage to the heart. Cardiac HMOD disease) have an up to twofold increased risk of CV adverse may manifest as left ventricular hypertrophy (LVH) or as HF events, in particular arterial occlusive events [47–49]. Nev- with preserved ejection fraction, which may be difficult to ertheless, it has been shown that if patients with AH sched- identify in inter-critical, well-compensated phases [62, 63]. uled to receive ponatinib are strictly controlled and their BP In patients scheduled to receive anthracyclines, AH should is well treated, the risk of CV adverse events is reduced. be recognized as an important risk factor for cardiotoxicity Moreover, patients burdened by HMOD may be eligible for [17], with such risk being further increased in the presence 1 3 Current Heart Failure Reports Fig. 1 Cardiotoxicity due to anthracycline: the multiple-hit hypothesis •• of HMOD. In a recent study, it has been shown that patients evaluate CV health before initiation of cancer treatment [7, 22 ] with AH affected by lymphoma and receiving anthracycline for patients in whom it would otherwise be overlooked or con- had a greater risk of cardiotoxicity if presenting LVH [64]. sidered too late (i.e., when cardiotoxicity has already occurred). However, beside an adequate and meticulous treatment of AH, The proposal by the Heart Failure Association and the Interna- few strategies have proven beneficial for the prevention of tional Cardio-Oncology Society provides charts to estimate the anthracycline-induced cardiotoxicity [2 , 65]. This is a very risk of cardiotoxicity for the main classes of anticancer therapies •• important concept when one considers implications for long- [53 ]. The importance of CV prevention strategies, targeted at term follow-up of cancer patients who received anthracycline adequate control of classic CV risk factors in oncologic patients, therapy, and the possibility of incident new-onset AH (and has then furthermore stressed in the recent European Society of even HMOD). Indeed, cancer patients with both pre-existing Cardiology guidelines on cardio-oncology published in 2022 •• and post hoc CV conditions (compared to those without) have [69 ]. The guidelines recommend an aggressive treatment of worse short-term [66] and long-term outcomes [10] after anti- CV risk factors, both during and after anticancer treatment com- cancer treatment completion. Similarly, CV risk factors, AH pletion, with a particular mention for AH. Indeed, guidelines in particular, play an important role in CV event occurrence remark the importance of adequate BP control, especially in in childhood cancer survivors [67]. oncologic patients with known AH and in those scheduled to Thus, anthracycline recipients should be advised to con- receive anti-VEGF agents. tinue life-long CV monitoring [1, 17]. Once cardiotoxicity Yet, how to perform a baseline cardio-oncology evalua- has developed, cardioactive drugs as beta-blockers, angio- tion varies taking into account several factors, including the tensin-converting enzyme inhibitors, or angiotensin receptor patient status, the specific scheduled anticancer treatment, blockers surely may play a role in attenuating the detrimental and the organization of each cardio-oncology center [17, effects of anthracyclines; however, primary prevention still 70]. While in the majority of cases a well-performed medi- represents the best way to avoid cardiotoxicity. Consistently, cal history collection, a cardiologic visit, and an ECG are AH must be treated promptly, as cardiac HMOD is irrevers- largely enough for a baseline cardio-oncology evaluation, ible. In this context, cardio-oncology practice may serve as some specific cases are worthy of further attention. First, it an important tool promoting CV health and prevention in the should be kept in mind a paramount concept that holds true •• oncologic setting [7, 22 , 68]. for each CV risk factor, and here it is reported for AH: not all patients have known AH or, if known, adequately controlled AH. The importance of a baseline evaluation stands in the Practical Implications fact that not only the presence versus absence of a CV risk factor is checked, but the adequate versus inadequate con- •• In 2020, the Heart Failure Association of the European Society trol of such risk factor is performed [12, 17, 22 ], which of Cardiology, together with the International Cardio-Oncology is somehow more important than only knowing if a CV risk Society, published a proposal for routine assessment of CV risk factor is present. Since HMOD may be concealed, all patients in oncologic patients scheduled to receive anticancer treatments with AH (not only those symptomatic or with a prior his- •• associated with cardiotoxicities [53 ]. This was a welcome tory of CV events) should be advised to perform a compre- acknowledgement of the fact that a baseline cardio-oncology hensive HMOD screening [17, 18, 52] if not scheduled as visit may provide a unique opportunity to comprehensively a routine procedure. Echocardiography may be performed 1 3 Current Heart Failure Reports in the same occasion of the visit, with a significant added References value to the baseline consultation. Even though this approach may be perceived as time consuming or not cost-effective, Papers of particular interest, published recently, have it is reasonable to assume that a one-time-only thorough been highlighted as: CV check-up in the oncologic setting holds great potential • Of importance and may represent an investment to avoid unplanned car- •• Of major importance diologic evaluations during anticancer treatment, with the 1. Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, risk of holding a therapy [7, 68]. Hence, patients with AH Asteggiano R, Galderisi M, et al. 2016 ESC position paper on scheduled to receive specific anticancer treatments such as cancer treatments and cardiovascular toxicity developed under •• ponatinib [53 ] should be checked for HMOD and, in par- the auspices of the ESC committee for practice guidelines ticular, peripheral arterial occlusive disease. This would not the task force for cancer treatments and cardiovascular toxic- ity of the European Society of Cardiology (ESC). Eur Heart J. only significantly reduce the risk of arterial occlusive events 2016;37(36):2768–801. (the most frequent CV toxicity with ponatinib) but also allow 2.• Spallarossa P, Maurea N, Cadeddu C, Madonna R, Mele D, to modulate the dose of the anticancer treatment based on the Monte I, et al. A recommended practical approach to the man- CV risk profile of each patient [50–52]. agement of anthracycline-based chemotherapy cardiotoxicity: an opinion paper of the working group on drug cardiotoxicity Thus, the baseline cardio-oncology evaluation helps to cus- and cardioprotection, Italian Society of Cardiology. J Cardiovasc tomize management of CV profile for each patient and con- Med. 2016;17:e84. (Physiopathological mechanisms revision currently to lower the risk for cardiotoxicities [17]. In the case and practical recommendations for prevention and manage- of AH, its presence and, most importantly, control should be ment of anthracycline-related cardiotoxicity.) 3.• Maurea N, Spallarossa P, Cadeddu C, Madonna R, Mele D, assessed; when AH is present, HMOD must be checked. Monte I, et al. A recommended practical approach to the man- agement of target therapy and angiogenesis inhibitors cardio- toxicity: an opinion paper of the working group on drug car- diotoxicity and cardioprotection, Italian Society of Cardiology. Conclusions J Cardiovasc Med. 2016;17:e93-104. (Physiopathological mechanisms revision and practical recommendations for AH is the most important CV condition predisposing to anti- prevention and management of anti-VEGF agents-related cancer treatment-related cardiotoxicity. This risk is height- cardiotoxicity.) 4. Spallarossa P, Sarocchi M, Tini G, Arboscello E, Toma M, ened in the presence of cardiac HMOD. Moreover, AH may Ameri P, et al. How to monitor cardiac complications of immune itself be an adverse effect of anticancer treatment, leading to checkpoint inhibitor therapy. Front Pharmacol. 2020;11:972. therapy discontinuation and poor outcomes. Therefore, the 5. Mohammed T, Singh M, Tiu JG, Kim AS. Etiology and management of good assessment and control of CV risk profile, including hypertension in patients with cancer. Cardiooncology. 2021;7(1):14. 6.• Cameron AC, Touyz RM, Lang NN. Vascular complications of the optimization of AH therapy, are of primary importance cancer chemotherapy. Can J Cardiol. 2016;32(7):852–62. First in the management of cancer patients. As overlooking CV review recognizing the multifactorial mechanisms causing health can jeopardize the success of anticancer treatments, cardiotoxicity (inherent drug toxicity, patient's cardiovas- the goal for clinicians caring for the oncologic patient should cular risk profile and genetic predisposition). 7. Tini G, Ameri P, Buzzatti G, Sarocchi M, Murialdo R, Guglielmi G, et al. include the treatment of AH and HMOD. Diversity of cardiologic issues in a contemporary cohort of women with breast cancer. Front Cardiovasc Med. 2021;8:654728. 8. Sharalaya Z, Collier P. Prevention of cardiotoxicities with tradi- Funding Open access funding provided by Università degli Studi di tional and novel chemotherapeutic agents. Curr Heart Fail Rep. Roma La Sapienza within the CRUI-CARE Agreement. 2018;15(4):260–9. 9. Sturgeon KM, Deng L, Bluethmann SM, Zhou S, Trifiletti Declarations DM, Jiang C, et al. A population-based study of cardiovascu- lar disease mortality risk in US cancer patients. Eur Heart J. Conflict of Interest The authors declare no competing interests. 2019;40(48):3889–97. 10. Armenian SH, Xu L, Ky B, Sun C, Farol LT, Pal SK, et  al. Open Access This article is licensed under a Creative Commons Attri- Cardiovascular disease among survivors of adult-onset can- bution 4.0 International License, which permits use, sharing, adapta- cer: a community-based retrospective cohort study. JCO. tion, distribution and reproduction in any medium or format, as long 2016;34(10):1122–30. as you give appropriate credit to the original author(s) and the source, 11.•• Hershman DL, Till C, Shen S, Wright JD, Ramsey SD, Barlow provide a link to the Creative Commons licence, and indicate if changes WE, et al. Association of cardiovascular risk factors with cardiac were made. The images or other third party material in this article are events and survival outcomes among patients with breast can- included in the article's Creative Commons licence, unless indicated cer enrolled in SWOG clinical trials. JCO. 2018;36(26):2710– otherwise in a credit line to the material. If material is not included in 7. (Large scale study ultimately recognizing the impact the article's Creative Commons licence and your intended use is not of baseline cardiovascular risk factors on development of permitted by statutory regulation or exceeds the permitted use, you will cardiotoxicity.) need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://cr eativ ecommons. or g/licen ses/ b y/4.0/ . 1 3 Current Heart Failure Reports 12. Tini G, Sarocchi M, Ameri P, Arboscello E, Spallarossa P. The 27.•• Volpe M, Battistoni A, Tocci G, Rosei EA, Catapano AL, Coppo need for cardiovascular risk factor prevention in cardio-oncol- R, et al. Cardiovascular risk assessment beyond systemic coro- ogy. JACC Heart Fail. 2019;7(4):367–8. nary risk estimation: a role for organ damage markers. J Hyper- 13. Yin AB, Brewster AM, Barac A, Thoman W, Oeffinger KC, Gil- tens. 2012;30(6):1056–64. (Description of the importance of christ SC. Cardiovascular prevention strategies in breast cancer. arterial hypertension mediated organ damage recognition to JACC CardioOncology. 2019;1(2):322–5. adequately assess individual cardiovascular risk profile.) 14. Piccirillo JF, Tierney RM, Costas I, Grove L, Spitznagel EL. 28. Piskorz D. Hypertensive mediated organ damage and hyper- Prognostic importance of comorbidity in a hospital-based cancer tension management. How to assess beneficial effects of anti- registry. JAMA. 2004;291(20):2441–7. hypertensive treatments? High Blood Press Cardiovasc Prev. 15. Unger JM, Hershman DL, Fleury ME, Vaidya R. Association of 2020;27(1):9–17. patient comorbid conditions with cancer clinical trial participa- 29. Viazzi F, Leoncini G, Conti N, Tomolillo C, Giachero G, tion. JAMA Oncol. 2019;5(3):326–33. Vercelli M, et al. Combined effect of albuminuria and esti- 16. Battistoni A, Tocci G, Coluccia R, Burnier M, Ruilope LM, mated glomerular filtration rate on cardiovascular events and Volpe M. Antihypertensive drugs and the risk of cancer: a criti- all-cause mortality in uncomplicated hypertensive patients. J cal review of available evidence and perspective. J Hypertens. Hypertens. 2010;28(4):848–55. 2020;38(6):1005–15. 30. Sciarretta S, Valenti V, Tocci G, Pontremoli R, Rosei EA, 17. Tini G, Sarocchi M, Tocci G, Arboscello E, Ghigliotti G, Novo Ambrosioni E, et al. Association of renal damage with cardio- G, et al. Arterial hypertension in cancer: the elephant in the vascular diseases is independent of individual cardiovascular room. Int J Cardiol. 2019;15(281):133–9. risk profile in hypertension: data from the Italy-developing 18. Williams B, Mancia G, Spiering W, AgabitiRosei E, Azizi M, education and awareness on microalbuminuria in patients with Burnier M, et al. 2018 ESC/ESH guidelines for the manage- hypertensive disease study. J Hypertens. 2010;28(2):251–8. ment of arterial hypertension the task force for the management 31. Tocci G, Figliuzzi I, Presta V, Attalla El Halabieh N, Citoni of arterial hypertension of the European Society of Cardiology B, Coluccia R, et al. Adding markers of organ damage to risk (ESC) and the European Society of Hypertension (ESH). Eur score models improves cardiovascular risk assessment: pro- Heart J. 2018;39(33):3021–104. spective analysis of a large cohort of adult outpatients. Int J 19. Liu F, Hidru TH, Gao R, Lin Y, Liu Y, Fang F, et al. Cancer Cardiol. 2017;248:342–8. patients with potential eligibility for vascular endothelial growth 32. Muiesan ML, Paini A, Aggiusti C, Bertacchini F, Rosei CA, factor antagonists use have an increased risk for cardiovascular Salvetti M. Hypertension and organ damage in women. High diseases comorbidities. J Hypertens. 2020;38(3):426–33. Blood Press Cardiovasc Prev. 2018;25(3):245–52. 20.•• Hershman DL, Accordino MK, Shen S, Buono D, Crew KD, 33.•• Vasan RS, Song RJ, Xanthakis V, Beiser A, DeCarli C, Mitch- Kalinsky K, et al. Association between nonadherence to cardio- ell GF, et al. Hypertension-mediated organ damage: preva- vascular risk factor medications after breast cancer diagnosis lence, correlates, and prognosis in the community. Hyperten- and incidence of cardiac events. Cancer. 2020;126(7):1541–9. sion. 2022;79(3):505–15. (Contemporary description of (Large scale study recognizing the importance of adequate prevalence and significance of arterial hypertension medi- control of cardiovascular risk factors before and during can- ated organ damage: for each blood pressure category, the cer treatment, as nonadherence to cardiovascular medica- presence of organ damage significantly increase cardiovas - tions is associated with development of cardiotoxicity.) cular risk.) 21. Izzedine H, Ederhy S, Goldwasser F, Soria JC, Milano G, Cohen 34. Bruno G, Bringhen S, Maffei I, Iannaccone A, Crea T, Ravera A, et al. Management of hypertension in angiogenesis inhibitor- A, et al. Cardiovascular organ damage and blood pressure levels treated patients. Ann Oncol. 2009;20(5):807–15. predict adverse events in multiple myeloma patients undergoing 22.•• Tini G, Sarocchi M, Sirello D, Murialdo R, Fornarini G, Buz- carfilzomib therapy. Cancers. 2019;11(5):622. zatti G, et  al. Cardiovascular risk profile and events before 35. Touyz RM, Herrmann J. Cardiotoxicity with vascular endothe- and after treatment with anti-VEGF drugs in the setting of a lial growth factor inhibitor therapy. npj Precision Onc. structured cardio-oncologic program. Eur J PrevCardiolog. 2018;2(1):1–11. 2020;6:204748732092305. (Small real-world study showing 36. Small HY, Montezano AC, Rios FJ, Savoia C, Touyz RM. that reaching an adequate blood pressure control before ini- Hypertension due to antiangiogenic cancer therapy with vas- tiation of anti-VEGF agents therapy makes arterial hyper- cular endothelial growth factor inhibitors: understanding and tension no longer associated with cardiotoxicity.) managing a new syndrome. Can J Cardiol. 2014;30(5):534–43. 23. Cavo A, Rubagotti A, Zanardi E, Fabbroni C, Zinoli L, Di Meg- 37. Pandey AK, Singhi EK, Arroyo JP, Ikizler TA, Gould ER, Brown lio A, et al. Abiraterone acetate and prednisone in the pre- and J, et al. Mechanisms of VEGF (vascular endothelial growth fac- post-docetaxel setting for metastatic castration-resistant prostate tor) inhibitor-associated hypertension and vascular disease. cancer: a mono-institutional experience focused on cardiovascu- Hypertension. 2018;71(2):e1-8. lar events and their impact on clinical outcomes. Ther Adv Med 38. Neves KB, Rios FJ, van der Mey L, Alves-Lopes R, Cameron Oncol. 2018;10:1758834017745819. AC, Volpe M, et al. VEGFR (vascular endothelial growth factor 24. Mehta LS, Watson KE, Barac A, Beckie TM, Bittner V, Cruz- receptor) inhibition induces cardiovascular damage via redox- Flores S, et al. Cardiovascular disease and breast cancer: where sensitive processes. Hypertension. 2018;71(4):638–47. these entities intersect: a scientific statement from the American 39. Bohdan M, Kowalczys A, Mickiewicz A, Gruchała M, Lewicka Heart Association. Circulation [Internet]. 2018 Feb 20 [cited E. Cancer therapy-related cardiovascular complications in clini- 2020 Jul 12];137(8). Available from: https:// www. ahajo urnals. cal practice: current perspectives. JCM. 2021;10(8):1647. org/ doi/ 10. 1161/ CIR. 00000 00000 000556. 40. Maurea N, Coppola C, Piscopo G, Galletta F, Riccio G, Esposito 25. Lanza O, Ferrera A, Reale S, Solfanelli G, Petrungaro M, Tini- E, et al. Pathophysiology of cardiotoxicity from target therapy Melato G, et al. New insights on the toxicity on heart and vessels and angiogenesis inhibitors. J Cardiovasc Med (Hagerstown). of breast cancer therapies. Med Sci (Basel). 2022;10(2):27. 2016;17(Suppl 1):S19-26. 26. Drazner MH. The progression of hypertensive heart disease. 41. Witteles RM, Telli M. Underestimating cardiac toxicity in cancer Circulation. 2011;123(3):327–34. trials: lessons learned? JCO. 2012;30(16):1916–8. 1 3 Current Heart Failure Reports 42. Schmidinger M. Understanding and managing toxicities of vas- 56. Mercurio V, Pirozzi F, Lazzarini E, Marone G, Rizzo P, Agnetti cular endothelial growth factor (VEGF) inhibitors. Eur J Cancer G, et al. Models of heart failure based on the cardiotoxicity of Suppl. 2013;11(2):172–91. anticancer drugs. J Card Fail. 2016;22(6):449–58. 43. Hamnvik OPR, Choueiri TK, Turchin A, McKay RR, Goyal 57. Menna P, Paz OG, Chello M, Covino E, Salvatorelli E, Minotti L, Davis M, et al. Clinical risk factors for the development of G. Anthracycline cardiotoxicity. Expert Opin Drug Saf. hypertension in patients treated with inhibitors of the VEGF 2012;11(sup1):S21-36. signaling pathway: hypertension with anti-VEGF therapies. Can- 58. Mele D, Tocchetti CG, Pagliaro P, Madonna R, Novo G, Pepe cer. 2015;121(2):311–9. A, et al. Pathophysiology of anthracycline cardiotoxicity. J Car- 44. Touyz RM, Herrmann SMS, Herrmann J. Vascular toxicities diovasc Med. 2016;17:e3. with VEGF inhibitor therapies–focus on hypertension and arte- 59. Salvatorelli E, Menna P, Minotti G. Managing anthracycline- rial thrombotic events. J Am Soc Hypertens. 2018;12(6):409–25. induced cardiotoxicity: beginning with the end in mind. Future 45. Rizzoni D, De Ciuceis C, Porteri E, Agabiti-Rosei C, Agabiti- Cardiol. 2015;11(4):363–6. Rosei E. Use of antihypertensive drugs in neoplastic patients. 60. Pinder MC, Duan Z, Goodwin JS, Hortobagyi GN, Giordano High Blood Press Cardiovasc Prev. 2017;24(2):127–32. SH. Congestive heart failure in older women treated with 46. Boursiquot BC, Zabor EC, Glezerman IG, Jaimes EA. Hyper- adjuvant anthracycline chemotherapy for breast cancer. JCO. tension and VEGF (vascular endothelial growth factor) receptor 2007;25(25):3808–15. tyrosine kinase inhibition: effects on renal function. Hyperten- 61. Szmit S, Jurczak W, Zaucha JM, Drozd-Sokołowska J, sion. 2017;70(3):552–8. Spychałowicz W, Joks M, et al. Pre-existing arterial hyperten- 47. Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre PD, Paquette R, sion as a risk factor for early left ventricular systolic dysfunction Chuah C, et al. Ponatinib efficacy and safety in Philadelphia following (R)-CHOP chemotherapy in patients with lymphoma. chromosome-positive leukemia: final 5-year results of the phase J Am Soc Hypertens. 2014;8(11):791–9. 2 PACE trial. Blood. 2018;132(4):393–404. 62. Nadruz W. Myocardial remodeling in hypertension. J Hum 48. Haguet H, Douxfils J, Mullier F, Chatelain C, Graux C, Dogné Hypertens. 2015;29(1):1–6. JM. Risk of arterial and venous occlusive events in chronic 63. Lewis GA, Schelbert EB, Williams SG, Cunnington C, Ahmed myeloid leukemia patients treated with new generation BCR- F, McDonagh TA, et al. Biological phenotypes of heart fail- ABL tyrosine kinase inhibitors: a systematic review and meta- ure with preserved ejection fraction. J Am Coll Cardiol. analysis. Expert Opin Drug Saf. 2017;16(1):5–12. 2017;70(17):2186–200. 49. Januzzi JL, Garasic JM, Kasner SE, McDonald V, Petrie MC, 64. Tanaka Y, Tanaka H, Hatazawa K, Yamashita K, Sumimoto K, Seltzer J, et al. Retrospective analysis of arterial occlusive events Shono A, et al. Impact of hypertension on left ventricular func- in the PACE trial by an independent adjudication committee. J tion in patients after anthracycline chemotherapy for malignant Hematol Oncol. 2022;15(1):1. lymphoma. Int J Cardiol. 2021;15(323):126–32. 50. Iurlo A, Cattaneo D, Orofino N, Bucelli C, Molica M, Brec- 65. Minotti G. The International Cardioncology Society-ONE trial: cia M. Low-dose ponatinib in intolerant chronic myeloid leu- not all that glitters is for cardioncologists only. Eur J Cancer. kemia patients: a safe and effective option. Clin Drug Investig. 2018;97:27–9. 2018;38(5):475–6. 66. Hussain M, Hou Y, Watson C, Moudgil R, Shah C, Abra- 51. Cortes JE, Lomaia E, Turkina A, Moiraghi B, Undurraga Sutton ham J, et  al. Temporal trends of cardiac outcomes and M, Pavlovsky C, et al. Interim analysis (IA) of OPTIC: a dose- impact on survival in patients with cancer. Am J Cardiol. ranging study of three ponatinib (PON) starting doses. JCO. 2020;15(137):118–24. 2020;38(15_suppl):7502–7502. 67. Chen Y, Chow EJ, Oeffinger KC, Border WL, Leisenring WM, 52. Breccia M, Pregno P, Spallarossa P, Arboscello E, Ciceri F, Meacham LR, et al. Traditional cardiovascular risk factors and Giorgi M, et  al. Identification, prevention and management individual prediction of cardiovascular events in childhood can- of cardiovascular risk in chronic myeloid leukaemiapatients cer survivors. J Natl Cancer Inst. 2020;112(3):256–65. candidate to ponatinib: an expert opinion. Ann Hematol. 68. Tini G, Cuomo A, Battistoni A, Sarocchi M, Mercurio V, 2017;96(4):549–58. Ameri P, et al. Baseline cardio-oncologic risk assessment in 53.•• Lyon AR, Dent S, Stanway S, Earl H, Brezden-Masley C, Cohen- breast cancer women and occurrence of cardiovascular events: Solal A, et al. Baseline cardiovascular risk assessment in can- the HFA/ICOS risk tool in real-world practice. Int J Cardiol. cer patients scheduled to receive cardiotoxic cancer therapies: 2021;S0167–5273(21):01876–83. a position statement and new risk assessment tools from the 69.•• Lyon AR, López-Fernández T, Couch LS, Asteggiano R, Aznar cardio-oncology study group of the Heart Failure Association MC, Bergler-Klein J, et  al. 2022 ESC guidelines on cardio- of the European Society of Cardiology in collaboration with oncology developed in collaboration with the European Hema- the International Cardio-Oncology Society. Eur J Heart Fail. tology Association (EHA), the European Society for Therapeutic 2020;22(11):1945–60. (European Society of Cardiology Heart Radiology and Oncology (ESTRO) and the International Cardio- Failure Association and International Cardio-Oncology Soci- Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229–361. ety joint position statement highlighting the importance of a (Recently published European Society of Cardiology guide- baseline Cardio-Oncology evaluation before specific antican- lines on Cardio-Oncology. The paper highlights the impor- cer treatments are initiated to effectively assess cardiovascu - tance of CV risk stratification in all oncologic patients before lar risk and initiate strategies to prevent cardiotoxicity.) initiation of anticancer treatments and recommend adequate 54. Menna P, Salvatorelli E, Minotti G. Anthracycline degradation and aggressive control of CV risk factors in primary preven- in cardiomyocytes: a journey to oxidative survival. Chem Res tion in the oncologic population.) Toxicol. 2010;23(1):6–10. 70. Tini G, Spallarossa P. How cardio-oncology is called to prove 55. Lazzarini E, Balbi C, Altieri P, Pfeffer U, Gambini E, Canepa its maturity. Int J Cardiol. 2019;01(288):130–1. M, et al. The human amniotic fluid stem cell secretome effec - tively counteracts doxorubicin-induced cardiotoxicity. Sci Rep. Publisher's Note Springer Nature remains neutral with regard to 2016;21(6):29994. jurisdictional claims in published maps and institutional affiliations. 1 3

Journal

Current Heart Failure ReportsSpringer Journals

Published: Feb 1, 2023

Keywords: Arterial hypertension; Arterial hypertension-mediated organ damage; Anthracycline; Anti-VEGF; Cardiotoxicity; Cardio-oncology

There are no references for this article.