Analysis of causes of death in patients with implanted defibrillators

Abstract

Aims

Implantable cardioverter defibrillators (ICDs) are used for primary or secondary prevention of sudden cardiac death. We sought to clarify prognosis and causes of death after ICD implantation.

Methods and results

A total of 2743 patients with ICDs implanted during 1990–2020 were analyzed. Median age was 68.5 (59.6–74.6) years; 21% women, median left ventricular ejection fraction (LVEF) was 30 (23–35), 52% had an ischemic etiology and 77% had a primary preventive indication. Mortality rate after 10 years was 22, 44, 55, and 72% in the 1st, 2nd, 3rd, and 4th age quartile, respectively. The calculated median sex and age adjusted loss of life years compared to the average German population was 9.7 (6.1–14.0) years. Prognosis was independently related to sex, age, LVEF, and glomerular filtration rate. 713 out of 852 deaths could be classified to a specific cause. Congestive heart failure (CHF) accounted for death in 214 (30%) and sudden death (SD) for 144 patients (20%). Postmortem interrogation of devices in 74 patients revealed VT/VF in 39 and no episodes in 35 patients. Cancer was identified as the cause of death in 121 patients (17% of cases), of which 36 were bronchial carcinomas. 73 (10%) of patients died due to infection. 67 patients (9%) died within 24 h of procedures. Compared to other causes, significantly more life years were lost associated with procedures and SD: 9.3 (5.7–12.9) versus 12.1 (7.4–15.2) and 11.9 (7.6–17.8) years.

Conclusion

Life expectancy of ICD patients is lower than for the general population. Mortality is predominantly due to CHF, but there is still a considerable rate of SD. The occurrence of cancers, most importantly bronchial carcinomas, and infections, warrants protective measures. Some deaths during procedures are possibly preventable. Patients with ICDs comprise a vulnerable cohort, and treatment has to be optimized in many directions to improve prognosis.

Graphic abstract

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References

  1. 1.

    Køber L, Thune JJ, Nielsen JC, Haarbo J, Videbæk L, Korup E, Jensen G, Hildebrandt P, Steffensen FH, Bruun NE, Eiskjær H, Brandes A, Thøgersen AM, Gustafsson F, Egstrup K, Videbæk R, Hassager C, Svendsen JH, Høfsten DE, Torp-Pedersen C, Pehrson S, for the DANISH Investigator (2016) Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med 375:1221–1230

    Article  Google Scholar 

  2. 2.

    Packer M (2020) What causes sudden death in patients with chronic heart failure and a reduced ejection fraction? Eur Heart J 41:1757–1763

    Article  Google Scholar 

  3. 3.

    Taylor CJ, Ordóñez-Mena JM, Roalfe AK, Lay-Flurrie S, Jones NR, Marshall T, Hobbs FR (2019) Trends in survival after a diagnosis of heart failure in the United Kingdom 2000–2017: population based cohort study. BMJ 364(l223):1–10

    Google Scholar 

  4. 4.

    Packer M (1985) Sudden unexpected death in patients with congestive heart failure: a second frontier. Circulation 72:681–685

    CAS  Article  Google Scholar 

  5. 5.

    German Statistical Federal Agency Online 2020: https://www-enesis.destatis.de/genesis

  6. 6.

    Scrucca L, Santucci A, Aversa F (2007) Competing risk analysis using R: an easy guide for clinicians. Bone Marrow Transplant 40(4):381–387

    CAS  Article  Google Scholar 

  7. 7.

    Guandalini GS, Liang JJ, Marchlinski FE (2019) Ventricular tachycardia ablation: past, present, and future perspectives. JACC Clin Electrophysiol 5(12):1363–1383

    Article  Google Scholar 

  8. 8.

    Tseng ZH, Hayward RM, Clark NM, Mulvanny CG, Colburn BJ, Ursell PC, Olgin JE, Hart AP, Moffatt E (2015) Sudden death in patients with cardiac implantable electronic devices. JAMA Intern Med 175(8):1342–1350

    Article  Google Scholar 

  9. 9.

    Tini G, Bertero E, Alessio A, Sormani MP, Maack C, De Boer RA, Canepa M, Ameri P (2020) Cancer mortality in trials of heart failure with reduced ejection fraction: a systematic review and meta-analysis. J Am Heart Assoc 9(e016309):1–29

    Google Scholar 

  10. 10.

    de Berrington GA, Mahesh M, Kim KP, Bhargavan M, Lewis R, Mettler F, Land C (2009) Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 169(22):2071–2077

    Article  Google Scholar 

  11. 11.

    Hill KD, Einstein AJ (2016) New approaches to reduce radiation exposure. Trends Cardiovasc Med 26(1):55–65

    Article  Google Scholar 

  12. 12.

    Patz EF Jr, Goodman PC, Bepler G (2000) Screening for lung cancer. N Engl J Med 343(22):1627–1633

    Article  Google Scholar 

  13. 13.

    de Koning HJ, van der Aalst CM, de Jong PA, Scholten ET, Nackaerts K, Heuvelmans MA, Lammers JJ, Weenink C, Yousaf-Khan U, Horeweg N, van’t Westeinde S, Prokop M, Mali WP, Mohamed Hoesein FAA, van Ooijen PMA, Aerts JGJV, den Bakker MA, Thunnissen E, Verschakelen J, Vliegenthart R, Walter JE, Ten Haaf K, Groen HJM, Oudkerk M (2020) Reduced lung-cancer mortality with volume CT screening in a randomized trial. N Engl J Med 382(6):503–513

    Article  Google Scholar 

  14. 14.

    Drozd M, Garland E, Walker AMN, Slater TA, Koshy A, Straw S, Gierula J, Paton M, Lowry J, Sapsford R, Witte KK, Kearney MT, Cubbon RMK (2020) Infection-related hospitalization in heart failure with reduced ejection fraction. A prospective observational cohort study. Circ Heart Failure 13:e006746

    Article  Google Scholar 

  15. 15.

    Barbagelata E, Cillóniz C, Dominedò C, Torres A, Nicolini A, Solidoro P (2020) Gender differences in community-acquired pneumonia. Minerva Med 111(2):153–165

    Article  Google Scholar 

  16. 16.

    Strassle PD, Sickbert-Bennett EE, Klompas M, Lund JL, Stewart PW, Marx AH, DiBiase LM, Weber DJ (2020) Incidence and risk factors of non-device-associated pneumonia in an acute-care hospital. Infect Control Hosp Epidemiol 41(1):73–79

    Article  Google Scholar 

  17. 17.

    Kifle Y, Wikner JJ, Zotterman J, Ryden L, Farnebo SNFC (2019) Powered implantable temperature sensor. Conf Proc IEEE Eng Med Biol Soc 2019:4359–4362

    CAS  Google Scholar 

  18. 18.

    Poole JE, Olshansky B, Mark DB, Anderson J, Johnson G, Hellkamp AS, Davidson-Ray L, Fishbein DP, Boineau RE, Anstrom KJ, Reinhall PG, Packer DL, Lee KL, Bardy GH, SCD-HeFT Investigators (2020) Long-term outcomes of implantable cardioverter-defibrillator therapy in the SCD-HeFT. J Am Coll Cardiol 76(4):405–415

    Article  Google Scholar 

  19. 19.

    Cleland JGF, Hindricks G, Petrie M (2019) The shocking lack of evidence for implantable cardioverter defibrillators for heart failure; with or without cardiac resynchronization. Eur Heart J 40(26):2128–2130

    Article  Google Scholar 

  20. 20.

    McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O’Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, on behalf of the DAPA-HF Trial committees and investigators (2019) Langkilde AM Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 381:1995–2008

    CAS  Article  Google Scholar 

  21. 21.

    Zeymer U, Clark AL, Barrios V, Damy T, Drożdż J, Fonseca C, Lund LH, Di Comite G, Hupfer S, Maggioni AP (2020) Management of heart failure with reduced ejection fraction in Europe: design of the ARIADNE registry. ESC Heart Fail 7(2):727–736

    Article  Google Scholar 

  22. 22.

    Vaduganathan M, Claggett BL, Jhund PS, Cunningham JW, Ferreira JP, Zannad F, Packer M, Fonarow GC, McMurray JJ, Solomon SD (2020) Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials. Lancet 396(10244):121–128

    CAS  Article  Google Scholar 

  23. 23.

    McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR, on behalf of the PARADIGM-HF Investigators and Committees (2014) Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 371:993–1004

    Article  Google Scholar 

  24. 24.

    Nägele H, Hashagen S, Azizi M, Behrens S, Castel MA (2007) Analysis of terminal arrhythmias stored in the memory of pacemakers from patients dying suddenly. Europace 9(6):380–384

    Article  Google Scholar 

  25. 25.

    Riesinger L, Fichtner S, Schuhmann CG, Estner HL, Czermak T, Graw M, Fischer F, Lackermair K (2019) Postmortem interrogation of cardiac implantable electrical devices may clarify time and cause of death. Int J Legal Med 133(3):883–888

    Article  Google Scholar 

  26. 26.

    Thijssen J, van Rees JB, Venlet J, Borleffs CJ, Höke U, Putter H, van der Velde ET, van Erven L, Schalij MJ (2012) The mode of death in implantable cardioverter-defibrillator and cardiac resynchronization therapy with defibrillator patients: results from routine clinical practice. Heart Rhythm 9(10):1605–1612

    Article  Google Scholar 

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Acknowledgements

We thank all patients, families, general practitioners and clinicians who provided information’s in regard to the study.

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Correspondence to Herbert Nägele.

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Nägele, H., Gröene, E., Stierle, D. et al. Analysis of causes of death in patients with implanted defibrillators. Clin Res Cardiol 110, 895–904 (2021). https://doi.org/10.1007/s00392-021-01825-y

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Keywords

  • Implantable cardioverter defibrillator
  • Heart failure
  • Prognosis
  • Sudden death
  • Infection
  • Cancer
  • Procedures