Very Premature Bioprosthetic and Valve Repair Degeneration in Sickle Cell Disease Patients

Background: Cardiovascular impairment is a leading cause of premature mortality in patients with sickle cell disease (SCD). Valvular heart disease frequently affects SCD patients, yet data addressing underlying etiologies and management strategies are limited. Although previous study suggested that open-heart surgery could be performed on SCD patients with acceptable risk (PMID: 20026775), it involved a small number of patients and a short follow-up period. Long-term outcomes following valvular heart surgery in SCD patients remain largely unknown. While bioprosthetic valves typically degenerate over 10-15 years in the general population, accumulating evidence indicates that chronic inflammation may play a pivotal role in their early degeneration. Based on our local experience and considering unique hemodynamic conditions, along with chronic hemolysis-induced inflammation in SCD, we hypothesized that these patients could be prone to premature valve repair and bioprosthetic degeneration.

Purpose: The aim of this study was to evaluate the long-term evolution of surgical valve repair and bioprosthetic implantation in SCD patients.

Method: We conducted a retrospective single center study, including all SCD patients (SS, Sβ0 and SC) that had open heart surgery in Henri Mondor teaching hospital (Creteil, France) between 2007 and 2019. Our investigation focused on patients that underwent heart valve surgeries with as primary objective the assessment of time until severe valvular degeneration diagnosed on echocardiography with an indication of reintervention retained by the Heart Team surgical staff. Patients which presented very premature valvular degeneration (<5 years) were then compared to the one for whom it was delayed or absent. Secondary objectives included the evaluation of surgical indications and risk, per and post-operative course along with 30-days mortality.

Results:

Between 2007 and 2019, 20 open heart surgeries were performed on SCD patients in our institution. Mean age was 38±14 years, 47 % were men and a large majority were homozygous sickle cell patients (>90%). Among them, 17 (85%) were valvular surgeries, including 14 (82%) valve repair or bioprosthetic replacement and 3 (18%) mechanical valves. The main etiologies were severe regurgitations due to rheumatism valvular disease (71%) or functional mechanism (18%). Among these patients, 6 (35%) had history of cardiac surgery, 6 (35%) had chronic kidney disease and 8 (47%) showed echocardiography signs of pulmonary hypertension. Mean left ventricular ejection fraction (LVEF) was at 53±10 % with 6 (35%) below 50%. The median estimated risk of in-hospital death after cardiac surgery evaluated with EuroSCORE II was 3.7% [2.5; 5.4], with 18% at low risk (≤2%); 53% moderate (2-5%) and 29% at high risk (>5%). No patient died during surgery and all but one received blood transfusion. ICU median stay was 4 [3; 11] days with 30-day mortality rate of 12%. Amongst the 13/14 (93%) patients that underwent valve repair or bioprosthetic implantation and survived past the 30-day period, 6 (46%) showed severe degeneration, diagnosed at a median of 3.9 [3.0; 6.6] years after surgery. This led to interventional valvular management for 5 patients (83%), including 3 mechanical valve replacement and 2 percutaneous procedures while one patient died before surgery. Patients that presented premature degeneration were younger, with a trend toward higher level of bilirubin, AST and HbS, suggesting deeper hemolysis. Notably, patients that initially underwent mechanical valvular replacement showed no sign of valvular degeneration after 12 years of follow-up. Among the 3 patients that showed early severe bioprosthetic degeneration and underwent mechanical prothesis implantation: 2 showed no sign of valvular degeneration at 4- and 7-years post-surgery. The third patient died 1 year after his 3^rd open heart valvular surgery within 3 years, following two consecutive premature bioprosthetic degeneration.

Conclusion: Valvular disease management by open-heart surgery is possible for SCD patients, with an acceptable postoperative risk. However, these patients are exposed to premature and severe valve repair or bioprosthetic degeneration, leading to early cardiac reintervention. These results provide crucial information for guiding prosthesis selection in young SCD patients with an indication for heart valve surgery.

Bartolucci:Innovhem: Other: Founder; Addmedica: Consultancy, Other: member advisory board; Emmaus: Consultancy; Novartis: Consultancy, Other: member advisory board and member steering commitee; Roche: Consultancy; Bluebird: Consultancy; Pfizer: Consultancy; JazzPharma: Consultancy. Habibi:Theravia: Honoraria; Novartis: Consultancy. De Luna:Vertex: Consultancy; Pfizer: Other: Sponsor HEMOPROVE trial NCT05199766.