Atorvastatin and left atrial function during anthracycline-based chemotherapy

Journal of Cardiovascular Magnetic Resonance, vol. 27, pp. 101946

Abstract

BACKGROUND: Structural and functional abnormalities of the left atrium (LA) predict adverse outcomes such as heart failure and mortality in many patients with heart disease. However, the effect of anthracyclines on LA structural and functional abnormalities remains incompletely characterized. Further, atorvastatin prevented the anthracycline-associated decline in the left ventricular ejection fraction; however, whether atorvastatin protects against anthracycline-associated impairment of LA structure and function is currently unknown. METHODS: In the STOP-CA randomized clinical trial, participants with lymphoma treated with anthracyclines were randomized to placebo (n=150) or atorvastatin (n=150) for 12 months. In post hoc analyses, CMR-derived LA volumetric and functional measurements (reservoir [GLS], conduit, and booster strain) were measured at baseline and 12 months using feature tracking (FT). The primary endpoint was the difference in the proportion of participants with a ≥1 SD decrease in LA GLS between the atorvastatin and placebo groups. The secondary endpoint was a ≥20% relative decrease in LA GLS. Other exploratory endpoints included volume indices and emptying fractions. RESULTS: Of 300 participants, 158 (mean age 51±16years, 48% female, 83 with atorvastatin) had paired CMR-derived LA strain and volumetric data at baseline and follow-up. Both groups had similar baseline characteristics and cancer treatment. All LA strain and volumetric measures were similar between the two groups at baseline. Among the placebo group, LA GLS decreased from baseline to follow-up (35.5±8.8 vs 32.4±8.2%, p=0.007). A ≥1 SD absolute decrease in LA GLS (8.8% units) was observed among 24% with atorvastatin and 28% with placebo (p=0.59). Similarly, a ≥20% relative decrease in GLS was observed in 25% vs 31% (p=0.48). Participants over 50 had an almost 10% (9.9%, 95% confidence interval: -18.75, -1.12) greater relative decrease in LA GLS with anthracyclines. There were no differences between cardiac hospitalization rates with a ≥1 SD absolute decrease (5% vs 8%, p=0.72) in LA GLS at 24 months. Among other indices of LA structure and function, the LA total emptying fraction also decreased from baseline to follow-up, with no differences between groups at follow-up. CONCLUSION: Atorvastatin did not attenuate the decline in CMR-derived LA GLS among lymphoma patients undergoing anthracycline-based chemotherapy. CLINICAL TRIAL REGISTRATION: NCT02943590; https://clinicaltrials.gov/study/NCT02943590.

Authors 18

1. Vencel Juhász corresponding

   Semmelweis University · Harvard University · Massachusetts General Hospital

   Affiliation as printed

   Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Heart and Vascular Center, Semmelweis University, Budapest, Hungary. Electronic address: vjuhasz@mgh.harvard.edu

   Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Heart and Vascular Center, Semmelweis University, Budapest, Hungary. Electronic address: vjuhasz@mgh.harvard.edu

2. Zsófia D. Drobni

   Semmelweis University

   Affiliation as printed

   Heart and Vascular Center, Semmelweis University, Budapest, Hungary

3. Thiago Quinaglia

   Harvard University · Massachusetts General Hospital

   Affiliation as printed

   Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

   Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

4. Hannah K. Gilman

   Harvard University · Massachusetts General Hospital

   Affiliation as printed

   Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

   Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

5. Giselle Alexandra Suero Abreu

   Harvard University · Massachusetts General Hospital

   Affiliation as printed

   Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

   Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

6. Azin Ghamari

   Harvard University · Massachusetts General Hospital

   Affiliation as printed

   Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

   Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

7. Julius Cornelis Heemelaar Aachen

   Leiden University · Harvard University · Leiden University Medical Center · Massachusetts General Hospital

   Affiliation as printed

   Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Leiden University Medical Center, Cardiology Department, Leiden, the Netherlands

   Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Leiden University Medical Center, Cardiology Department, Leiden, the Netherlands

8. Donna S Neuberg

   Dana-Farber Cancer Institute

   Affiliation as printed

   Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

   Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts

9. Yuchi Han

   Hospital of the University of Pennsylvania · University of Pennsylvania

   Affiliation as printed

   Division of Cardiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA

   Division of Cardiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania

10. Bonnie Ky

    Hospital of the University of Pennsylvania · University of Pennsylvania

    Affiliation as printed

    Division of Cardiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Division of Cardiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania

11. Raymond Y.K. Kwong

    Brigham and Women's Hospital

    Affiliation as printed

    Cardiology Division, Brigham and Women's Hospital, Boston, Massachusetts, USA

    Cardiology Division, Brigham and Women's Hospital, Boston, Massachusetts

12. James Louis Januzzi

    Harvard University · Massachusetts General Hospital · Baim Institute for Clinical Research

    Affiliation as printed

    Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Baim Institute for Clinical Research, Boston, Massachusetts, USA

    Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Baim Institute for Clinical Research, Boston, Massachusetts

13. Aarti H. Asnani

    Beth Israel Deaconess Medical Center · Harvard University

    Affiliation as printed

    Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

    Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

14. Negareh Mousavi

    McGill University Health Centre · McGill University

    Affiliation as printed

    Division of Cardiology, McGill University Hospital, Montreal, Quebec, Canada

15. Robert Allyn Redd Aachen Cardiology Department

    Leiden University Medical Center

    Affiliation as printed

    Leiden University Medical Center, Cardiology Department, Leiden, the Netherlands

16. Michael Jerosch‐Herold

    Brigham and Women's Hospital

    Affiliation as printed

    Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA

    Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts

17. Marielle Scherrer‐Crosbie

    Hospital of the University of Pennsylvania · University of Pennsylvania

    Affiliation as printed

    Division of Cardiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Division of Cardiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania

18. Tomas G. Neilan

    Brigham and Women's Hospital · Harvard University · Massachusetts General Hospital

    Affiliation as printed

    Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Cardiology Division, Brigham and Women's Hospital, Boston, Massachusetts, USA

    Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Cardiology Division, Brigham and Women's Hospital, Boston, Massachusetts