Contributor: Chris Sobowale
Bleeding and thrombosis account for almost half of adverse events in patients with CF-LVADs.
Saeed et al analyzed 144 HeartMate II (HMII) CF-LVAD patients in a single center, retrospective study. Patients in the sildenafil groups were on sildenafil for pulmonary hypertension or right ventricular dysfunction for at least 30 days after discharge from CF-LVAD implant. Patients were divided into four groups:
- Low level hemolysis not on sildenafil (n=31)
- Low level hemolysis on sildenafil (n= 16)
- No low level hemolysis not on sildenafil n= (76)
- No low level hemolysis on sildenafil (n=21)
Bleeding and thrombosis are referred to collectively as hemocompatibility-related adverse events (HRASEs). So, what leads to HRASEs? Platelet activation / aggravation is augmented by hemolysis where extracellular free hemoglobin is generated. This is shown to reduce nitric oxide (NO) bioavailability, ultimately reducing cGMP formation. Hemolytic events occur in 15-35% of patients with CF-LVADs. Sildenafil (a phosphodiesterase-5 inhibitor) preserves cGMP, can it affect platelet activation / aggravation?
Low level hemolysis (LLH) was defined as lactate dehydrogenase (LDH) 400-700 U/L in HMII CF-LVAD patients at the time of discharge following HMII CF-LVAD implantation. All patients were on aspirin and warfarin with INR goal 2-3. The incidence of hemorrhagic and thrombotic events (device thrombosis and ischemic stroke) were tracked up to 365 days after discharge.
Hemorrhagic events were similar between all groups. Patients with LLH not on sildenafil had thrombotic events 12/31 (39%) in comparison to those with LLH on sildenafil 1/16 (6.3%). The adjusted hazard ratio for device thrombosis in LLH patients not on sildenafil vs LLH patients on sildenafil was 8.8 vs 1.7 (95% CI: 1.2-68.2, p=0.02). Ischemic stroke only occurred in patients with LLH not on sildenafil (n=5, 3% of entire cohort).
No study is perfect. This is a small, retrospective single center study. Treatment with sildenafil was based on non-standardized diagnosis of pulmonary hypertension or right ventricular dysfunction.