Background:

Bleeding and vascular complications are the most frequent procedure-related complications following transcatheter aortic valve implantation (TAVI). Several studies have shown increased morbidity and mortality rates in patients with major bleeding complications. 

In patients undergoing cardiac surgery, protamine administration for antagonization of systemic anticoagulation with heparin has become standard care, as it has shown to reduce the risk of postoperative bleeding. 

However, data regarding the efficacy of protamine administration in the prevention of bleeding complications and its safety regarding thromboembolic complications in TAVI patients is scarce.

Objectives:

The aim of this prospective observational study was to evaluate whether protamine administration for heparin reversal after the procedure reduces the rate of bleeding complications, and whether this might affect the outcome of the patients.

Methods 

Our study cohort included 873 consecutive patients undergoing TAVI with next-generation transcatheter heart valves, of whom 677 (77.5%) received protamine for heparin reversal. Standard access management included vessel preclosure with one Prostar or two Proglide devices, manual compression, and if necessary percutaneous transluminal angioplasty (PTA) or implantation of a covered nitinol stent-graft. The indication for protamine administration was left to the discretion of the operator. The primary endpoint of the study was a composite of 30-day all-cause mortality, life-threatening as well as major bleeding. Key secondary end points included one-year all-cause mortality and VARC-2 defined stroke and myocardial infarction at 30 days. 

Results:

The mean age of our study population was 81 (±6.1) years; 50.2% were of female gender. The primary endpoint of the study occurred less frequently in the protamine administration group (3.2%) as compared with the control group (8.7%, p=0.03). This result was mainly driven by lower rates of life-threatening and major bleeding in the protamine group (0.1% vs 2.6%, p=0.003; 1.0% vs 4.1%, p=0.008, respectively), as presented in Figure 1. Accordingly, a red blood cell transfusion was needed more frequently in the control cohort than in the protamine group (11.7% vs 7.2%, p=0.05; Figure 2). Furthermore, protamine administration resulted in a significantly shorter hospital stay (11.1±5.8 vs 12.7±7.8 days, p=0.05). 

In the overall cohort, VARC-2–defined stroke was observed in 1.9% and myocardial infarction in 0.2% of patients, with no significant difference between the groups (p=0.08, p=1.0, respectively). In multivariate analysis, only protamine administration (OR: 0.24 [95% CI: 0.10 - 0.58], p=0.001) and acute kidney injury (OR: 5.82 [95% CI: 2.02 - 16.77], p=0.001) were independently associated with the primary end point. 

Conclusion:

Protamine administration resulted in significantly lower rates of life-threatening and major bleeding complications as compared to patients without heparin reversal. Patients with protamine administration had significantly shorter hospital stays (delta 1.6 days). Occurrence of stroke and myocardial infarction was not increased by protamine administration.