Clinical outcomes after valve surgery for infective endocarditis

<p dir="ltr">Background: Infective endocarditis (IE) is a serious and often fatal disease with an increasing incidence rate. Mortality is 20-30% at one year and up to 50% of patients require cardiac surgery. Previous research on surgically treated IE patients has been limited by small cohorts, lack of granularity, and short or incomplete follow-up. The thesis aims to investigate mortality and morbidity after valve surgery for IE in important patient subgroups.</p><p dir="ltr">Methods and results: The thesis comprises five population-based, observational cohort studies. Studies I-II were single center studies with the study population identified using the local Cardiac Surgery Register, part of SWEDEHEART, while most baseline data was sourced from medical records. Studies III-V were nationwide register-based studies; for which a comprehensive database was created by crosslinking SWEDEHEART with several other Swedish national health registers.</p><p dir="ltr">Study I investigated all-cause mortality and reoperation rates in patients who underwent valve surgery for IE. It compared intravenous drug users (IVDU; n = 55; 11%) with non-IVDUs (n = 455; 89%). Among IVDUs only, reinfection and relapse to drug use were also investigated. There was no difference in 30-day mortality, whereas long-term mortality was more than four times higher among IVDUs as compared with non-IVDUs (adjusted hazard ratio (HR) 4.1, 95% confidence interval (CI): 2.5 to 6.7; P < 0.001). At six years, only 12% of IVDUs remained free from reinfection and relapse to drug use was high.</p><p dir="ltr">Study II investigated all-cause mortality in patients who underwent surgery for aortic valve IE, comparing those patients with a bicuspid aortic valve (BAV; n = 122; 36%) with those with a tricuspid aortic valve (TAV; n = 216; 64%). BAV patients were younger and healthier but had more abscesses than TAV patients. Overall, the mortality rate was similar for BAV and TAV patients (adjusted HR 0.6, 95% CI: 0.4 to 1.1). Among patients with native valve endocarditis patients, the mortality rate was lower for BAV patients (adjusted HR 0.4, 95% CI: 0.2 to 0.9). Among patients with prosthetic valve endocarditis patients, mortality rate was similar for BAV and TAV patients.</p><p dir="ltr">Study III investigated all-cause mortality, heart failure, and reinfection among patients who underwent surgery for aortic valve IE. It compared patients who had a new permanent pacemaker implanted (n = 168; 8%) with those who did not (n = 2007; 92%). There was no difference in all-cause mortality between patients who received a pacemaker and those who did not (HR 1.2, 95% CI: 0.9 to 1.6). Heart failure (HR 1.4, 95% CI: 0.9 to 2.3) and reinfection (HR 0.9, 95% CI: 0.5 to 1.5) were also similar.</p><p dir="ltr">Study IV investigated survival, loss of life expectancy, heart failure, and recurrent IE in patients undergoing surgery for aortic valve IE. It compared female patients (n = 502; 19%) with male patients (n = 2083; 81%). Thirty-day mortality was similar (age-adjusted OR 1.1, 95% CI 0.8 to 1.6). After adjustments, females had 4% (95% CI: 0.2% to 7.9%) higher survival than male patients at 15 years. Matched loss of life expectancy ranged from 16 years (95% CI: 9 to 22) for 50-year-old females undergoing surgery in year 2000 to 2 years (95% CI: 0.95 to 3) for 80- year-old male patients undergoing surgery in year 2020. There was no difference in heart failure or recurrent IE between female and male patients.</p><p dir="ltr">Study V investigated 30-day mortality, survival conditional on 30-day survival, heart failure, stroke, and recurrent prosthetic valve endocarditis (PVE) in patients who underwent surgery for aortic valve IE. It compared patients with PVE (n = 685; 26%) with patients with native valve endocarditis (NVE; n = 1900; 74%). Thirty-day mortality was higher among PVE than NVE patients (12% vs. 6%; adjusted OR 1.8, 95% CI: 1.2 to 2.6). At 10 years, survival was similar for PVE and NVE (conditional survival difference: - 3.8%, 95% CI: - 8.3% to 0.7%). There was no difference in heart failure, stroke, or recurrent PVE.</p><p dir="ltr">Conclusions: I) While intravenous drug users managed surgery well, they had poor long-term outcomes. Strategies to handle addiction and reinfection should be prioritized when managing these patients. II) A high proportion of NVE patients have BAV. Reassuringly, the prognosis for these patients was better than for those with TAV despite higher rates of abscess formation. Prior BAV did not impact long-term outcomes in PVE patients. III) New implantation of pacemaker at the time of IE surgery was not associated with adverse long-term outcomes in patients. Although pacemaker need suggests more advanced disease, our study suggests that it does not importantly jeopardize lifesaving surgery for IE. IV) IE was shown to have substantial long-term impact. Loss of life expectancy was up to 16 years and particularly accentuated in younger patients. Female patients were older, had higher surgical risk, and lower income than male patients, but after adjustments, survival was better. Clinicians should be aware of sex differences IE patients to achieve early diagnosis and better optimize preoperative patient care. V) Severity of disease and higher operative risk among PVE patients as compared with NVE patients was reflected in lower 30- day survival. Importantly, PVE patients who survived the postoperative period had a similar prognosis to NVE patients. Given the poor prognosis of these patients otherwise, our results suggest that clinicians should not be afraid to refer and perform surgery in patients with very complex PVE disease.</p><h3>List of scientific papers</h3><p dir="ltr">I. <b>Bearpark L,</b> Sartipy U, Franco-Cereceda A, Glaser N. Surgery for Endocarditis in Intravenous Drug Users. The Annals of Thoracic Surgery. Volume 112, Issue 2, 573-581. <a href="https://doi.org/10.1016/j.athoracsur.2020.09.013" rel="noreferrer" target="_blank">https://doi.org/10.1016/j.athoracsur.2020.09.013</a></p><p dir="ltr">II. <b>Bearpark LO</b><b>F</b>, Sartipy U, Franco-Cereceda A, Glaser N. Surgery for Endocarditis in Patients with Bicuspid Aortic Valves. Annals of Cardiothoracic Surgery. 2022, Volume 11, Issue 4:448-458. <a href="https://doi.org/10.21037/acs-2022-bav-fs-0062" rel="noreferrer" target="_blank">https://doi.org/10.21037/acs-2022-bav-fs-0062</a></p><p dir="ltr">III. <b>Bearpark LO</b><b>F</b>, Dismorr M, Franco-Cereceda A, Sartipy U, Glaser N. Implications of Pacemaker Implantation After Aortic Valve Surgery for Endocarditis: A Nationwide Study. European Journal of Cardio-Thoracic Surgery. Volume 67, Issue 4, April 2025, ezaf125. <a href="https://doi.org/10.1093/ejcts/ezaf125" rel="noreferrer" target="_blank">https://doi.org/10.1093/ejcts/ezaf125</a></p><p dir="ltr">IV. <b>Bearpark LO</b><b>F</b>, Dismorr M, Franco-Cereceda A, Sartipy S, Glaser N. Sex-based Differences After Aortic Valve Surgery for Infective Endocarditis: A SWEDEHEART Study of Outcomes and Loss of Life Expectancy. [Submitted]</p><p dir="ltr">V. <b>Bearpark L,</b> Dismorr M, Franco-Cereceda A, Sartipy S, Glaser N. Survival Following Aortic Valve Surgery for Prosthetic Valve Endocarditis: A SWEDEHEART Study. [Submitted]</p>