Comprehensive assessment of device-based therapy for heart failure with reduced ejection fraction

Background: Despite a recommendation by the European guidelines, the use of implantable cardioverter defibrillators (ICD) for the primary prevention of sudden cardiac death (SCD) in patients with heart failure with reduced ejection fraction (HFrEF) is scarce. This might be explained by a lower risk of SCD in contemporary patients with HFrEF, so that the need for primary prevention ICD use in these patients has been questioned.

Aims: The overall aim of this thesis was to further evaluate the controversies regarding the use of device-based therapy and particularly regarding the primary prevention use of ICDs in contemporary treated patients with HFrEF. The specific aims were to:・Evaluate the association between primary prevention ICD use and mortality in contemporary treated patients with HFrEF (Study I);・Investigate the association between primary prevention ICD use and mortality in contemporary treated patients with HFrEF eligible for cardiac resynchronization therapy (CRT, Study II);・Explore the association between socioeconomic status and use of device-based therapies and outcomes in patients with heart failure (Study III);・Describe the impact of the predicted risk of SCD and all-cause mortality on primary prevention ICD use, as well as on its association with mortality in patients with HFrEF (Study IV).

Methods and Results: For all studies, the Swedish Heart Failure Registry (SwedeHF) was used, and patients eligible for primary prevention ICD use (Study I and IV), patients also treated with CRT (Study II) and patients with available information on socioeconomic status (Study III) were further selected. Study I. Only 10% of the patients eligible for ICD use were actually treated with the device. In a propensity score matched cohort, ICD use was associated with a 27% lower 1-year and a 12% lower 5-year risk of all-cause mortality. The findings were consistent across several prespecified sub-groups, including older vs. younger patients and those with vs. without ischemic heart disease. Study II. Among patients with CRT, ICD use was less likely in older patients, females and those not referred to heart failure nurse-led outpatient clinics. In a propensity score matched cohort, combined use of CRT and ICD was associated with a 24% lower 1-year and a 18% lower 3-year risk of all-cause mortality. Study III. Lower socioeconomic status, defined as the prevalence of lower income and/or lower education and/or living alone, was associated with a lower likelihood of referral to specialized follow-up care and a lower likelihood of ICD use; and also with a higher risk of heart failure hospitalization and all-cause mortality, even after adjustments for heart failure severity and treatments. Study IV. Patients elgible for primary prevention ICD use were categorized by two readily available clinical scores (Seattle Heart Failure Model and Seattle Proportional Risk Model) into four groups based on their predicted SCD/mortality risk being high/low. Even in patients with a high SCD and a low mortality risk, ICDs were only used in 18.2%. Relevant predictors of ICD non-use were follow-up in primary care (vs. specialized care) and lower socioeconomic status. Primary prevention ICD use was only associated with a lower all-cause/cardiovascular mortality risk in patients with a high predicted SCD but a low predicted mortality risk.

Conclusions: In contemporary HFrEF patients, even in those treated with CRT, primary prevention ICD use was associated with a lower mortality risk (Study I and II). Nevertheless, ICDs were still underused for the primary prevention of SCD in patients with HFrEF, even if they had a high predicted SCD risk (Study I and IV). Lower quality of HF care and lower socioeconomic status were relevant barriers to the implementation of primary prevention ICD use (Study III and IV), which highlights the need to improve both HF care and the access to it (Study III). Furthermore, the relatively low magnitude of the mortality risk reduction with primary prevention ICD use in contemporary patients with HFrEF calls for better patient selection, which can be achieved by applying easily applicable clinical scores (Study IV).

List of scientific papers

I. Benedikt Schrage, Alicia Uijl, Lina Benson, Dirk Westermann, Marcus Ståhlberg, Davide Stolfo, Ulf Dahlström, Cecilia Linde, Frieder Braunschweig, Gianluigi Savarese. Association between use of primary prevention implantable cardioverter-defibrillators and mortality in patients with heart failure. A prospective propensity-score matched analysis from the Swedish heart failure registry. Circulation. 2019, 140, 1530-1539.
https://doi.org/10.1161/CIRCULATIONAHA.119.043012

II. Benedikt Schrage, Lars H Lund, Michael Melin, Lina Benson, Alicia Uijl, Ulf Dahlström, Frieder Braunschweig, Cecilia Linde, Gianluigi Savarese. Cardiac resynchronisation therapy with or without defibrillator in patients with heart failure. Europace. 2022, 24, 48-57.
https://doi.org/10.1093/europace/euab233

III. Benedikt Schrage, Lars H. Lund, Lina Benson, Davide Stolfo, Anna Ohlsson, Ragnar Westerling, Dirk Westermann, Anna Strömberg, Ulf Dahlström, Frieder Braunschweig, João Pedro Ferreira, Gianluigi Savarese. Lower socioeconomic status predicts higher mortality and morbidity in patients with heart failure. Heart. 2021, 107, 229-236.
https://doi.org/10.1136/heartjnl-2020-317216

IV. Benedikt Schrage, Lars H. Lund, Lina Benson, Ulf Dahlström, Ramin Shadman, Cecilia Linde, Frieder Braunschweig, Wayne C. Levy, Gianluigi Savarese. Predictors of primary prevention implantable cardioverter defibrillator use in heart failure with reduced ejection fraction: Impact of the predicted risk of sudden cardiac death and all-cause mortality. [Submitted]