Skip to main content

Advertisement

SpringerLink
Log in

Incidence, predictive factors, management, and survival impact of atrial fibrillation in non-Hodgkin lymphoma

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Atrial fibrillation (AF) and cancer are common disorders in the general population but there are few studies in patients with both diseases. More specifically, there are scarce data on AF in patients with non-Hodgkin lymphoma (NHL). We assessed the incidence, predictive factors, management, and survival impact of AF in a cohort of patients with NHL from a single institution between 2002 and 2016 (n = 747). Twenty-three patients were diagnosed with AF before and 40 after the diagnosis of NHL (of the later, 16 were secondary to an extracardiac comorbidity and 24 unrelated to any triggering event [primary AF]). The 5-year cumulative incidence of new-onset AF was 4% (95% confidence interval [CI] 3–6%). Age and hypertension were the only predictive factors for the development of AF. Management of AF was heterogeneous, primarily with anti-vitamin K agents but also antiplatelet therapy in a significant proportion of patients. Among the 63 patients, there were six episodes of ischemic stroke/transient ischemic attack and four venous thromboembolic events, with four major bleeding episodes. Overall survival (OS) was inferior in patients with AF (HR 0.1, 95% CI 0.01–0.7, p = 0.02), largely due to secondary AF. We conclude that the incidence of new-onset AF in NHL patients seemed somewhat higher than in the general population, although with similar predictive factors. The management was heterogeneous, and the risk of ischemic and hemorrhagic events did not seem higher than in cancer-free patients. Survival was particularly poor for patients with secondary AF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE (2001) Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and risk factors in atrial fibrillation (ATRIA) study. JAMA 285:2370–2375

    Article  PubMed  CAS  Google Scholar 

  2. Farmakis D, Parissis J, Filippatos G (2014) Insights into onco-cardiology: atrial fibrillation in cancer. J Am Coll Cardiol 63:945–953. https://doi.org/10.1016/j.jacc.2013.11.026

    Article  PubMed  Google Scholar 

  3. Fitzpatrick T, Carrier M, Le Gal G (2017) Cancer, atrial fibrillation, and stroke. Thromb Res 155:101–105. https://doi.org/10.1016/j.thromres.2017.05.006

    Article  PubMed  CAS  Google Scholar 

  4. Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B, Marchiori A, Sabbion P, Prins MH, Noventa F, Girolami A (2002) Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 100:3484–3488. https://doi.org/10.1182/blood-2002-01-0108

    Article  PubMed  CAS  Google Scholar 

  5. Trujillo-Santos J, Nieto JA, Tiberio G, Piccioli A, Di Micco P, Prandoni P, Monreal M, Registry RIETE (2008) Predicting recurrences or major bleeding in cancer patients with venous thromboembolism. Findings from the RIETE registry. Thromb Haemost 100:435–439

    Article  PubMed  CAS  Google Scholar 

  6. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW (2008) Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 111:4902–4907. https://doi.org/10.1182/blood-2007-10-116327

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Shanafelt TD, Parikh SA, Noseworthy PA, Goede V, Chaffee KG, Bahlo J, Call TG, Schwager SM, Ding W, Eichhorst B, Fischer K, Leis JF, Chanan-Khan AA, Hallek M, Slager SL, Kay NE (2017) Atrial fibrillation in patients with chronic lymphocytic leukemia (CLL). Leuk Lymphoma 58:1630–1639. https://doi.org/10.1080/10428194.2016.1257795

    Article  PubMed  CAS  Google Scholar 

  8. Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383

    Article  PubMed  CAS  Google Scholar 

  9. Crandall MA, Bradley DJ, Packer DL, Asirvatham SJ (2009) Contemporary management of atrial fibrillation: update on anticoagulation and invasive management strategies. Mayo Clin Proc 84:643–662. https://doi.org/10.1016/S0025-6196(11)60754-4

    Article  PubMed  PubMed Central  Google Scholar 

  10. Schulman S, Kearon C (2005) Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 3:692–694. https://doi.org/10.1111/j.1538-7836.2005.01204.x

    Article  PubMed  CAS  Google Scholar 

  11. Cea-Calvo L, Redón J, Lozano JV, Fernández-Pérez C, Martí-Canales JC, Llisterri JL, González-Esteban J, Aznar J, Investigators of the PREV-ICTUS Study (2007) Prevalence of atrial fibrillation in the Spanish population aged 60 years or more. The PREV-ICTUS study. Rev Esp Cardiol 60:616–624

    Article  PubMed  Google Scholar 

  12. Gómez-Doblas JJ, Muñiz J, Martin JJ, Rodríguez-Roca G, Lobos JM, Awamleh P, Permanyer-Miralda G, Chorro FJ, Anguita M, Roig E, OFRECE study collaborators (2014) Prevalence of atrial fibrillation in Spain. OFRECE study results. Rev Esp Cardiol (Engl Ed) 67:259–269. https://doi.org/10.1016/j.rec.2013.07.014

    Article  Google Scholar 

  13. Lau DH, Nattel S, Kalman JM, Sanders P (2017) Modifiable risk factors and atrial fibrillation. Circulation 136:583–596. https://doi.org/10.1161/CIRCULATIONAHA.116.023163

    Article  PubMed  Google Scholar 

  14. Hu YF, Liu CJ, Chang PM, Tsao HM, Lin YJ, Chang SL, Lo LW, Tuan TC, Li CH, Chao TF, Chung FP, Liao JN, Chen TJ, Chen SA (2013) Incident thromboembolism and heart failure associated with new-onset atrial fibrillation in cancer patients. Int J Cardiol 165:355–357. https://doi.org/10.1016/j.ijcard.2012.08.036

    Article  PubMed  Google Scholar 

  15. Hart RG, Pearce LA, Aguilar MI (2007) Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 146:857–867

    Article  PubMed  Google Scholar 

  16. Ogilvie IM, Newton N, Welner SA, Cowell W, Lip GY (2010) Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med 123:638–645.e4. https://doi.org/10.1016/j.amjmed.2009.11.025

    Article  PubMed  CAS  Google Scholar 

  17. Arts DL, Visscher S, Opstelten W, Korevaar JC, Abu-Hanna A, van Weert HC (2013) Frequency and risk factors for under- and over-treatment in stroke prevention for patients with non-valvular atrial fibrillation in general practice. PLoS One 8:e67806. https://doi.org/10.1371/journal.pone.0067806

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Kakkar AK, Mueller I, Bassand JP, Fitzmaurice DA, Goldhaber SZ, Goto S, Haas S, Hacke W, Lip GY, Mantovani LG, Turpie AG, van Eickels M, Misselwitz F, Rushton-Smith S, Kayani G, Wilkinson P, Verheugt FW, Registry Investigators GARFIELD (2013) Risk profiles and antithrombotic treatment of patients newly diagnosed with atrial fibrillation at risk of stroke: perspectives from the international, observational, prospective GARFIELD registry. PLoS One 8:e63479. https://doi.org/10.1371/journal.pone.0063479

    Article  PubMed  PubMed Central  Google Scholar 

  19. Mochalina N, Jöud A, Carlsson M, Sandberg MEC, Själander A, Juhlin T, Svensson PJ (2016) Antithrombotic therapy in patients with non-valvular atrial fibrillation in Southern Sweden: a population-based cohort study. Thromb Res 140:94–99. https://doi.org/10.1016/j.thromres.2016.02.023

    Article  PubMed  CAS  Google Scholar 

  20. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R, Deftereos S, Dobrev D, Ferro JM, Filippatos G, Fitzsimons D, Gorenek B, Guenoun M, Hohnloser SH, Kolh P, Lip GY, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo JL, Taylor CJ, Van Gelder IC, Voors AA, Windecker S, Zamorano JL, Zeppenfeld K (2016) 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace 18:1609–1678. https://doi.org/10.1093/europace/euw295

    Article  PubMed  Google Scholar 

  21. Lip GY, Laroche C, Dan GA, Santini M, Kalarus Z, Rasmussen LH, Ioachim PM, Tica O, Boriani G, Cimaglia P, Diemberger I, Hellum CF, Mortensen B, Maggioni AP (2014) ‘Real-world’ antithrombotic treatment in atrial fibrillation: the EORP-AF pilot survey. Am J Med 127:519–29.e1. https://doi.org/10.1016/j.amjmed.2013.12.022

    Article  PubMed  Google Scholar 

  22. Gorst-Rasmussen A, Skjøth F, Larsen TB, Rasmussen LH, Lip GY, Lane DA (2015) Dabigatran adherence in atrial fibrillation patients during the first year after diagnosis: a nationwide cohort study. J Thromb Haemost 13:495–504. https://doi.org/10.1111/jth.12845

    Article  PubMed  CAS  Google Scholar 

  23. Martinez C, Katholing A, Wallenhorst C, Freedman SB (2016) Therapy persistence in newly diagnosed non-valvular atrial fibrillation treated with warfarin or NOAC. A cohort study. Thromb Haemost 115:31–39. https://doi.org/10.1160/TH15-04-0350

    Article  PubMed  Google Scholar 

  24. Lee YJ, Park JK, Uhm JS, Kim JY, Pak HN, Lee MH, Sung JH, Joung B (2016) Bleeding risk and major adverse events in patients with cancer on oral anticoagulation therapy. Int J Cardiol 203:372–378. https://doi.org/10.1016/j.ijcard.2015.10.166

    Article  PubMed  Google Scholar 

  25. Ambrus DB, Reisman JI, Rose AJ (2016) The impact of new-onset cancer among veterans who are receiving warfarin for atrial fibrillation and venous thromboembolism. Thromb Res 144:21–26. https://doi.org/10.1016/j.thromres.2016.05.028

    Article  PubMed  CAS  Google Scholar 

  26. Denas G, Pengo V, Joppi R, Prandoni P (2015) Cancer as a risk factor for stroke in atrial fibrillation patients receiving long-term oral anticoagulant therapy. Thromb Res 136:488. https://doi.org/10.1016/j.thromres.2015.06.011

    Article  PubMed  CAS  Google Scholar 

  27. Short NJ, Connors JM (2014) New oral anticoagulants and the cancer patient. Oncologist 19:82–93. https://doi.org/10.1634/theoncologist.2013-0239

    Article  PubMed  CAS  Google Scholar 

  28. Vedovati MC, Germini F, Agnelli G, Becattini C (2015) Direct oral anticoagulants in patients with VTE and cancer: a systematic review and meta-analysis. Chest 147:475–483. https://doi.org/10.1378/chest.14-0402

    Article  PubMed  Google Scholar 

  29. Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR, Hokusai VTE Cancer Investigators (2018) Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 378:615–624. https://doi.org/10.1056/NEJMoa1711948.

    Article  PubMed  CAS  Google Scholar 

  30. Melloni C, Dunning A, Granger CB, Thomas L, Khouri MG, Garcia DA, Hylek EM, Hanna M, Wallentin L, Gersh BJ, Douglas PS, Alexander JH, Lopes RD (2017) Efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation and a history of cancer: insights from the ARISTOTLE trial. Am J Med 130:1440–1448. https://doi.org/10.1016/j.amjmed.2017.06.026

    Article  PubMed  CAS  Google Scholar 

  31. Ording AG, Horváth-Puhó E, Adelborg K, Pedersen L, Prandoni P, Sørensen HT (2017) Thromboembolic and bleeding complications during oral anticoagulation therapy in cancer patients with atrial fibrillation: a Danish nationwide population-based cohort study. Cancer Med 6:1165–1172. https://doi.org/10.1002/cam4.1054

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Shah S, Norby FL, Datta YH, Lutsey PL, MacLehose RF, Chen LY, Alonso A (2018) Comparative effectiveness of direct oral anticoagulants and warfarin in patients with cancer and atrial fibrillation. Blood Adv 2:200–209. https://doi.org/10.1182/bloodadvances.2017010694

    Article  PubMed  PubMed Central  Google Scholar 

  33. de Weerdt I, Koopmans SM, Kater AP, van Gelder M (2017) Incidence and management of toxicity associated with ibrutinib and idelalisib: a practical approach. Haematologica 102:1629–1639. https://doi.org/10.3324/haematol.2017.164103

    Article  PubMed  PubMed Central  Google Scholar 

  34. Thorp BC, Badoux X (2018) Atrial fibrillation as a complication of ibrutinib therapy: clinical features and challenges of management. Leuk Lymphoma 59:311–320. https://doi.org/10.1080/10428194.2017.1339874

    Article  PubMed  CAS  Google Scholar 

  35. Wiczer TE, Levine LB, Brumbaugh J, Coggins J, Zhao Q, Ruppert AS, Rogers K, McCoy A, Mousa L, Guha A, Heerema NA, Maddocks K, Christian B, Andritsos LA, Jaglowski S, Devine S, Baiocchi R, Woyach J, Jones J, Grever M, Blum KA, Byrd JC, Awan FT (2017) Cumulative incidence, risk factors, and management of atrial fibrillation in patients receiving ibrutinib. Blood Adv 1:1739–1748

    PubMed  PubMed Central  CAS  Google Scholar 

  36. Navi BB, Reiner AS, Kamel H, Iadecola C, Okin PM, Elkind MSV, Panageas KS, DeAngelis LM (2017) Risk of arterial thromboembolism in patients with Cancer. J Am Coll Cardiol 70:926–938. https://doi.org/10.1016/j.jacc.2017.06.047

    Article  PubMed  PubMed Central  Google Scholar 

  37. Schwarzbach CJ, Schaefer A, Ebert A, Held V, Bolognese M, Kablau M, Hennerici MG, Fatar M (2012) Stroke and cancer: the importance of cancer-associated hypercoagulation as a possible stroke etiology. Stroke 43:3029–3034. https://doi.org/10.1161/STROKEAHA.112.658625

    Article  PubMed  Google Scholar 

  38. Navi BB, Reiner AS, Kamel H, Iadecola C, Elkind MS, Panageas KS, DeAngelis LM (2015) Association between incident cancer and subsequent stroke. Ann Neurol 77:291–300. https://doi.org/10.1002/ana.24325

    Article  PubMed  PubMed Central  Google Scholar 

  39. Patell R, Gutierrez A, Rybicki L, Khorana AA (2017) Usefulness of CHADS2 and CHA2DS2-VASc scores for stroke prediction in patients with cancer and atrial fibrillation. Am J Cardiol 120:2182–2186. https://doi.org/10.1016/j.amjcard.2017.08.038

    Article  PubMed  Google Scholar 

  40. Elbadawi A, Elgendy IY, Ha LD, Baig B, Saad M, Adly H, Ogunbayo GO, Olorunfemi O, Mckillop MS, Maffett SA (2018) In-hospital cerebrovascular outcomes of patients with atrial fibrillation and cancer (from the National Inpatient Sample Database). Am J Cardiol 121:590–595. https://doi.org/10.1016/j.amjcard.2017.11.027

    Article  PubMed  Google Scholar 

  41. D'Souza M, Carlson N, Fosbøl E, Lamberts M, Smedegaard L, Nielsen D, Torp-Pedersen C, Gislason G, Schou M (2018) CHA2DS2-VASc score and risk of thromboembolism and bleeding in patients with atrial fibrillation and recent cancer. Eur J Prev Cardiol 25:651–658. https://doi.org/10.1177/2047487318759858

    Article  PubMed  Google Scholar 

  42. Santi RM, Ceccarelli M, Bernocco E, Monagheddu C, Evangelista A, Valeri F, Monaco F, Vitolo U, Cortelazzo S, Cabras MG, Spina M, Baldini L, Boccomini C, Chiappella A, Bari A, Luminari S, Visco C, Calabrese M, Limberti G, Levis A, Contino L, Ciccone G, Ladetto M (2017) Khorana score and histotype predicts incidence of early venous thromboembolism in non-Hodgkin lymphomas. A pooled-data analysis of 12 clinical trials of Fondazione Italiana Linfomi (FIL). Thromb Haemost (in press) 117:1615–1621. https://doi.org/10.1160/TH16-11-0895.

    Article  Google Scholar 

  43. Caruso V, Di Castelnuovo A, Meschengieser S, Lazzari MA, de Gaetano G, Storti S, Iacoviello L, Donati MB (2010) Thrombotic complications in adult patients with lymphoma: a meta-analysis of 29 independent cohorts including 18 018 patients and 1149 events. Blood 115:5322–5328. https://doi.org/10.1182/blood-2010-01-258624

    Article  PubMed  CAS  Google Scholar 

  44. Navi BB, Reiner AS, Kamel H, Iadecola C, Okin PM, Elkind MSV, Panageas KS, DeAngelis LM (2018) Reply: arterial thromboembolism in non-hodgkin lymphoma, as the presentation of occult cancer, and with cancer therapies. J Am Coll Cardiol 71:260–262. https://doi.org/10.1016/j.jacc.2017.10.088

    Article  PubMed  Google Scholar 

  45. Amioka M, Sairaku A, Ochi T, Okada T, Asaoku H, Kyo T, Kihara Y (2016) Prognostic significance of new-onset atrial fibrillation in patients with non-Hodgkin's lymphoma treated with anthracyclines. Am J Cardiol 118:1386–1389. https://doi.org/10.1016/j.amjcard.2016.07.049

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology. ICO-Hospital Germans Trias i Pujol. Institut de Recerca Josep Carreras, Universitat Autònoma de Barcelona, Ctra. Canyet s/n, 08916, Badalona, Spain

    Marc Sorigue, Olga Garcia, Edurne Sarrate, Mireia Franch-Sarto, Gladys Ibarra, Javier Grau, Elisa Orna, Josep-Maria Ribera & Juan-Manuel Sancho

  2. Department of Cardiology, Hospital Germans Trias i Pujol, Badalona, Spain

    Francisco Gual-Capllonch

Authors
  1. Marc Sorigue
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francisco Gual-Capllonch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olga Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Edurne Sarrate
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mireia Franch-Sarto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gladys Ibarra
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Javier Grau
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Elisa Orna
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Josep-Maria Ribera
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Juan-Manuel Sancho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marc Sorigue.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

ESM 1

(DOC 97 kb)

ESM 2

(DOC 52 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sorigue, M., Gual-Capllonch, F., Garcia, O. et al. Incidence, predictive factors, management, and survival impact of atrial fibrillation in non-Hodgkin lymphoma. Ann Hematol 97, 1633–1640 (2018). https://doi.org/10.1007/s00277-018-3346-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-018-3346-1

Keywords

Search

Navigation