Elsevier

International Journal of Cardiology

Volume 323, 15 January 2021, Pages 126-132
International Journal of Cardiology

Impact of hypertension on left ventricular function in patients after anthracycline chemotherapy for malignant lymphoma

https://doi.org/10.1016/j.ijcard.2020.08.019Get rights and content

Highlights

  • Hypertension is considered an important risk factor for CTRCD as well as HF.

  • Hypertension with LVH was strongly associated with CTRCD.

  • Watchful observation may be needed for patients with hypertension and LVH.

Abstract

Background

Hypertension is considered an important risk factors for cancer therapeutics-related cardiac dysfunction (CTRCD) as well as heart failure. However, the impact of hypertension and left ventricular (LV) hypertrophy (LVH), which is associated with hypertension, on LV function in patients treated with anthracycline chemotherapy for malignant lymphoma remains uncertain.

Method

We studied 92 patients with malignant lymphoma and with preserved LV ejection fraction (LVEF). Echocardiography was performed before and two-month after anthracycline chemotherapy. CTRCD was defined as the presence of an absolute decrease in LVEF ≥10% to a final value <53%. LVH was defined as concentric hypertrophy, which was determined as relative wall thickness ≥ 0.42 and LV mass index >95 g/m2 for females and > 115 g/m2 for males.

Results

Relative decrease in LVEF after anthracycline chemotherapy in patients with hypertension (n = 23) was significantly higher than that in patients without hypertension (n = 69) (−5.8% [−9.4, −1.3]) vs. (−1.1% [−4.1, 2.5]); P = .005). Moreover, the prevalence of CTRCD in patients with hypertension tended to be higher than in those without hypertension (17% vs. 5%, p = .09). A sequential logistic model for predicting CTRCD, based on baseline clinical variables including major clinical risk factors, was improved by the addition of the complication of hypertension (P = .049), and further improved by the addition of the presence of LVH (P = .023).

Conclusions

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 by the addition of the presence of LVH.

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.

Section snippets

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.

References (45)

  • G. Curigliano et al.

    Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations

    Ann. Oncol.

    (2020)
  • M. Guglin et al.

    Randomized trial of lisinopril versus carvedilol to prevent trastuzumab cardiotoxicity in patients with breast cancer

    J. Am. Coll. Cardiol.

    (2019)
  • S. Sciomer et al.

    Age at menopause: a fundamental data of interest to acquire in female patients’ anamnesis

    Int. J. Cardiol.

    (2016)
  • G.T. Armstrong et al.

    Modifiable risk factors and major cardiac events among adult survivors of childhood cancer

    J. Clin. Oncol.

    (2013)
  • J.J. Doyle et al.

    Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study

    J. Clin. Oncol.

    (2005)
  • M.J. Hooning et al.

    Long-term risk of cardiovascular disease in 10-year survivors of breast cancer

    J. Natl. Cancer Inst.

    (2007)
  • G.M. Felker et al.

    Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy

    N. Engl. J. Med.

    (2000)
  • C.W. Yancy et al.

    2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the Management of Heart Failure: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the Heart Failure Society of America

    Circulation.

    (2017)
  • J.L. Zamorano et al.

    2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for practice guidelines: the task force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC)

    Eur. Heart J.

    (2016)
  • R.M. Lang et al.

    Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging

    J. Am. Soc. Echocardiogr.

    (2015)
  • K.C. Oeffinger et al.

    Chronic health conditions in adult survivors of childhood cancer

    N. Engl. J. Med.

    (2006)
  • H. Abdel-Qadir et al.

    A population-based study of cardiovascular mortality following early-stage breast Cancer

    JAMA Cardiol.

    (2017)
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      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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