Impact of hypertension on left ventricular function in patients after anthracycline chemotherapy for malignant lymphoma
Introduction
Anthracyclines are widely used in the treatment of solid tumors and hematologic malignancies, including malignant lymphomas, and have resulted in important survival gains. However, anthracyclines can also lead to cardiovascular toxicity, including left ventricular (LV) dysfunction, heart failure (HF) and increased cardiovascular mortality [1,2]. Anthracycline-induced decline in LV ejection fraction (LVEF) can occur in 15–17% of patients, and 2–3% may suffer from severe HF [3]. LV dysfunction caused by cancer chemotherapy is known as cancer therapeutics-related cardiac dysfunction (CTRCD) which has become a leading cause of morbidity and mortality for cancer survivors [2,4], with the mortality rate for patients with CTRCD reportedly being as high as 60% by 2 years after treatment [5]. Patients without HF symptoms or LV structural abnormalities, but with a history of using cardiotoxins, are currently included in Stage A HF [6] because of the irreversible LV myocardial changes due to anticancer drugs, changes such as myocyte loss, interstitial fibrosis leading to diminished LV contractility, reduced LV wall thickness, and progressive LV dilation. Although early detection of subclinical LV dysfunction is thus essential for delaying progression to HF in patients with a history of using cardiotoxins, the assessment of such dysfunction can be challenging. A recent position paper on cancer treatments and cardiovascular toxicity from the European Society of Cardiology (ESC) lists several factors associated with risk of cardiotoxicity following treatment with anthracyclines [7]. Hypertension, one of these factors, is considered an important risk factor for the development of CTRCD as a pre-existing condition before anthracycline chemotherapy. Hypertension is also a major risk factor for the development of both HF with preserved LVEF (HFpEF) and reduced LVEF (HFrEF), a risk that extends across all age ranges [8]. However, the impact of hypertension and LV hypertrophy (LVH), which is associated with a high incidence of hypertension, on LV function in patients with malignant lymphoma and preserved LVEF has not been fully investigated. The aim of this study was thus to investigate the impact of hypertension and LVH on LV function in patients with malignant lymphoma and with preserved LVEF who have been treated with anthracycline chemotherapy.
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Study population
For this study, 92 patients with malignant lymphoma who underwent anthracycline chemotherapy at Kobe University Hospital between June 2008 and May 2019 were retrospectively enrolled. Excluded were patients with: (1) no echocardiographic examination before or after anthracycline chemotherapy; (2) previous history of anthracycline chemotherapy at baseline echocardiography; (3) LV systolic dysfunction, defined as a LVEF <50%.; (4) history of bone marrow transplantation; (5) more than moderate
Baseline characteristics
The baseline clinical and echocardiographic characteristics of the 92 patients with malignant lymphoma are summarized in Table 1A. Their mean age was 55.0 ± 17.2 years old, 49% were female, LVEF was 65 ± 5%, and the average cumulative anthracycline dose was 262.4 mg/m2 (149.7, 382.6). Table 1B shows a comparison of echocardiographic parameters between baseline and after the termination of anthracycline chemotherapy. LV size was significantly larger and LVEF significantly decreased after the
Discussion
The findings of our study demonstrate that complicating hypertension was associated with a decrease in LVEF and the development of CTRCD after anthracycline chemotherapy in patients with malignant lymphoma and preserved LVEF. Furthermore, the presence of LVH was a significant parameter, in addition to the complication of hypertension, for predicting CTRCD.
Conclusion
Hypertension, especially when complicated by LVH, was found to be associated with LV dysfunction after anthracycline chemotherapy in patients with malignant lymphoma and preserved LVEF. Watchful observation or early therapeutic intervention may thus be needed for such patients.
Author statement
Yusuke Tanaka: Collection of data, writing and final approval of the manuscript.
Hidekazu Tanaka: Collection of data, writing and final approval of the manuscript, and responsible for ensuring that the descriptions are accurate and agreed by all authors.
Keiko Hatazawa: Revising the manuscript critically and final approval of the manuscript.
Kentaro Yamashita: Revising the manuscript critically and final approval of the manuscript.
Keiko Sumimoto: Revising the manuscript critically and final
Declaration of Competing Interest
The authors declare that there is no conflict of interest.
Acknowledgments
The authors are grateful for the support of the entire staff of the Echocardiographic Laboratory of the Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine Kobe Japan.
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2022, International Journal of Cardiology: Cardiovascular Risk and PreventionCitation Excerpt :GLS is a highly-sensitive methodology facilitated by speckle-tracking echocardiography, which can indicate structural cardiac changes before LVEF decline and thus is predictive of future cardiovascular events including heart failure and of all-cause mortality [30,43–45]. Tanaka et al. showed GLS decline was significantly higher in hypertensive patients, relative to normotensive patients, following receipt of anthracyclines [9]. Despite promising, it remains difficult to attribute these changes to anthracyclines alone as hypertension itself can cause GLS decline [44].
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