Pre-existing arterial hypertension as a risk factor for early left ventricular systolic dysfunction following (R)-CHOP chemotherapy in patients with lymphoma

Szmit, Sebastian; Jurczak, Wojciech; Zaucha, Jan Maciej; Drozd‐Sokołowska, Joanna; Spychałowicz, Wojciech; Joks, Monika; Długosz-Danecka, Monika; Torbicki, Adam

doi:10.1016/j.jash.2014.08.009

Cited by 61 publications

(60 citation statements)

References 39 publications

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“…In turn, this caused the hypertension subgroup to have more delays in subsequent treatment (26.8% versus 14.6% in normotensive group), more reductions of doxorubicin doses (18.3% versus 8.8% in normotensive group), and early discontinuation of chemotherapy (16.9% versus 7.3% in normotensive group). This study substantiated previous evidence and further confirmed arterial hypertension as a significant risk factor predisposing to AIC [17]. Therefore it is evident that preexisting hypertension may reduce the overall effectiveness and prognosis of patients undergoing anthracycline chemotherapy.…”

Section: Hypertension and Exacerbation Of Aicsupporting

confidence: 90%

Potential Therapeutic Strategies for Hypertension‐Exacerbated Cardiotoxicity of Anticancer Drugs

Kuriakose

Kukreja

2016

Oxidative Medicine and Cellular Longevity

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Despite their recognized cardiotoxic effects, anthracyclines remain an essential component in many anticancer regimens due to their superior antitumor efficacy. Epidemiologic data revealed that about one-third of cancer patients have hypertension, which is the most common comorbidity in cancer registries. The purpose of this review is to assess whether anthracycline chemotherapy exacerbates cardiotoxicity in patients with hypertension. A link between hypertension comorbidity and anthracycline-induced cardiotoxicity (AIC) was first suggested in 1979. Subsequent preclinical and clinical studies have supported the notion that hypertension is a major risk factor for AIC, along with the cumulative anthracycline dosage. There are several common or overlapping pathological mechanisms in AIC and hypertension, such as oxidative stress. Current evidence supports the utility of cardioprotective modalities as adjunct treatment prior to and during anthracycline chemotherapy. Several promising cardioprotective approaches against AIC pathologies include dexrazoxane, early hypertension management, and dietary supplementation of nitrate with beetroot juice or other medicinal botanical derivatives (e.g., visnagin and Danshen), which have both antihypertensive and anti-AIC properties. Future research is warranted to further elucidate the mechanisms of hypertension and AIC comorbidity and to conduct well-controlled clinical trials for identifying effective clinical strategies to improve long-term prognoses in this subgroup of cancer patients.

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Section: Hypertension and Exacerbation Of Aicsupporting

confidence: 90%

Potential Therapeutic Strategies for Hypertension‐Exacerbated Cardiotoxicity of Anticancer Drugs

Kuriakose

Kukreja

2016

Oxidative Medicine and Cellular Longevity

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“…However, there have been conflicting reports [22, 29] and it is only in the past decade that studies using large datasets from the Surveillance, Epidemiology and End Results (SEERS)-Medicare database have established hypertension as an independent risk factor, hazard ratios of 1.8 and 1.5 being reported in treatment of lymphoma [10] and early breast cancer [30] respectively. Despite this, interpretation of the literature remains complicated because few data, if any, fully discriminate the contribution of hypertension per se to cardiotoxicity, from the influence of associated comorbidities (including coronary disease, atrial fibrillation, diabetes, renal dysfunction, obesity [10, 29, 31, 32]) and cardiovascular medications (such as ACE inhibitors, mineralocorticoid receptor antagonists and beta-blockers) which may be cardioprotective [33, 34]. Our selected cohort allowed prospective study of the influence of blood pressure, largely unhindered by these considerations.…”

Section: Discussionmentioning

confidence: 99%

Body Surface Area and Baseline Blood Pressure Predict Subclinical Anthracycline Cardiotoxicity in Women Treated for Early Breast Cancer

et al. 2016

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Background and AimsAnthracyclines are highly effective chemotherapeutic agents which may cause long-term cardiac damage (chronic anthracycline cardiotoxicity) and heart failure. The pathogenesis of anthracycline cardiotoxicity remains incompletely understood and individual susceptibility difficult to predict. We sought clinical features which might contribute to improved risk assessment.MethodsSubjects were women with early breast cancer, free of pre-existing cardiac disease. Left ventricular ejection fraction was measured using cardiovascular magnetic resonance before and >12 months after anthracycline-based chemotherapy (>3 months post-Trastuzumab). Variables associated with subclinical cardiotoxicity (defined as a fall in left ventricular ejection fraction of ≥5%) were identified by logistic regression.ResultsOne hundred and sixty-five women (mean age 48.3 years at enrollment) completed the study 21.7 months [IQR 18.0–26.8] after starting chemotherapy. All received anthracyclines (98.8% epirubicin, cumulative dose 400 [300–450] mg/m2); 18% Trastuzumab. Baseline blood pressure was elevated (≥140/90mmHg, mean 147.3/86.1mmHg) in 18 subjects. Thirty-four subjects (20.7%) were identified with subclinical cardiotoxicity, independent predictors of which were the number of anthracycline cycles (odds ratio, OR 1.64 [1.17–2.30] per cycle), blood pressure ≥140/90mmHg (OR 5.36 [1.73–17.61]), body surface area (OR 2.08 [1.36–3.20] per standard deviation (0.16m2) increase), and Trastuzumab therapy (OR 3.35 [1.18–9.51]). The resultant predictive-model had an area under the receiver operating characteristics curve of 0.78 [0.70–0.86].ConclusionsWe found subclinical cardiotoxicity to be common even within this low risk cohort. Risk of cardiotoxicity was associated with modestly elevated baseline blood pressure–indicating that close attention should be paid to blood pressure in patients considered for anthracycline based chemotherapy. The association with higher body surface area suggests that indexing of anthracycline doses to surface area may not be appropriate for all, and points to the need for additional research in this area.

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“…Patients with a medical history of heart diseases, especially those with arterial hypertension, are at particular risk [10]. Selection of high-risk patients based on the results of the physical examination and past medical history proved to be very effective; in the RP cohort the cardiovascular mortality ( n = 9, 14.5%) was nearly 3 times higher compared to 5% in the PLRG observational study.…”

Section: Discussionmentioning

confidence: 99%

Primary Cardioprotection Reduces Mortality in Lymphoma Patients with Increased Risk of Anthracycline Cardiotoxicity, Treated by R-CHOP Regimen

Długosz-Danecka

Gruszka-Westwood

Szmit³

et al. 2018

Chemotherapy

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Background: Advances in anti-lymphoma therapy prolong overall survival, making late adverse effects, like doxorubicin-related cardiotoxicity, an even more important clinical issue. The effectiveness of cardioprotective strategies with close monitoring, angiotensin-converting enzyme inhibitors and/or β-blockers as well as liposomal doxorubicin are still unconfirmed in clinical practice. Methods: This study evaluated the role of a primary cardioprotection strategy in preventing cardiovascular mortality and heart failure occurrence in non-Hodgkin lymphoma (NHL) patients with a high risk of anthracycline cardiotoxicity. Thirty-five NHL patients were subjected prospectively to ramipril and/or bisoprolol at NHL diagnosis, before implementing doxorubicin-containing regimens. Additionally, patients with a diagnosis of asymptomatic/mild heart failure received the liposomal form of doxorubicin. The clinical outcome and frequency of all serious cardiac events were compared with the results in a historical cohort of 62 high-risk cases treated without primary cardioprotection. Results: NHL patients with a primary cardioprotection strategy did not experience cardiovascular deaths in contrast to the retrospective control group where cardiovascular mortality was 14.5% at 3 years (p < 0.05). Primary cardioprotection also decreased the frequency of new cardiotoxicity-related clinical symptoms (2.8 vs. 24.1%; p < 0.05) and prevented the occurrence of cardiac systolic dysfunction (0 vs. 8.5%, respectively; p < 0.05). Although the study was not planned to detect any survival benefit, it demonstrated a trend towards increased response rates (complete response 82 vs. 67%; p not significant) and prolonged survival (projected 5-year overall survival 74 vs. 60%; p < 0.05) for patients treated with primary cardioprotection. Conclusions: A primary personalized cardioprotection strategy decreases the number of cardiac deaths and may potentially prolong overall survival in NHL patients with increased risk of anthracycline cardiotoxicity.

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Pre-existing arterial hypertension as a risk factor for early left ventricular systolic dysfunction following (R)-CHOP chemotherapy in patients with lymphoma

Cited by 61 publications

References 39 publications

Potential Therapeutic Strategies for Hypertension‐Exacerbated Cardiotoxicity of Anticancer Drugs

Potential Therapeutic Strategies for Hypertension‐Exacerbated Cardiotoxicity of Anticancer Drugs

Body Surface Area and Baseline Blood Pressure Predict Subclinical Anthracycline Cardiotoxicity in Women Treated for Early Breast Cancer

Primary Cardioprotection Reduces Mortality in Lymphoma Patients with Increased Risk of Anthracycline Cardiotoxicity, Treated by R-CHOP Regimen

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