RESUMO
Impaired primary hemostasis and dysregulated angiogenesis, known as a two-hit hypothesis, are associated with gastrointestinal (GI) bleeding in patients with continuous-flow left ventricular assist devices (CF-LVADs). Exercise is known to influence hemostasis and angiogenesis in healthy individuals; however, little is known about the effect in patients with CF-LVADs. The objective of this prospective observational study was to determine whether acute exercise modulates two-hit hypothesis mediators associated with GI bleeding in patients with a CF-LVAD. Twenty-two patients with CF-LVADs performed acute exercise either on a cycle ergometer for approximately 10 minutes or on a treadmill for 30 minutes. Blood samples were taken pre- and post-exercise to analyze hemostatic and angiogenic biomarkers. Acute exercise resulted in an increased platelet count (p < 0.00001) and platelet function (induced by adenosine diphosphate, p = 0.0087; TRAP-6, p = 0.0005; ristocetin, p = 0.0009). Additionally, high-molecular-weight vWF multimers (p < 0.00001), vWF collagen-binding activity (p = 0.0012), factor VIII (p = 0.034), angiopoietin-1 (p = 0.0026), and vascular endothelial growth factor (p = 0.0041) all increased after acute exercise. This pilot work demonstrates that acute exercise modulated two-hit hypothesis mediators associated with GI bleeding in patients with CF-LVADs.
RESUMO
BACKGROUND: Spot urinary sodium concentration (UNa) is advocated in guidelines to assess diuretic response and titrate dosage in acute heart failure (AHF). However, no randomised controlled trial data exists to support this approach. We performed a prospective pilot trial to investigate the feasibility of this approach. METHODS: 60 patients with AHF (n = 30 in each arm) were randomly assigned to titration of loop diuretics for the first 48 hours of admission according to UNa levels (intervention arm) or based on clinical signs and symptoms of congestion (standard care arm). Diuretic insufficiency was defined as UNa < 50 mmol/L. Endpoints relating to diuretic efficacy, safety and AHF outcomes were evaluated. RESULTS: UNa-guided therapy patients experienced less acute kidney injury (20% vs 50%, p = 0.01) and a tendency towards less hypokalaemia (serum K+<3.5 mmol, 7% vs 27%, p = 0.04), with greater weight loss (3.3 kg vs 2.1 kg, p = 0.01). They reported a greater reduction in the clinical congestion score (-4.7 vs -2.6, p < 0.01) and were more likely to report marked symptom improvement (40% vs 13.3%, p = 0.04) at 48 hours. There was no difference in the length of hospital stay (median LOS: 8 days in both groups, p = 0.98), 30-day mortality or readmission rate. CONCLUSION: UNa-guided titration of diuretic therapy in AHF is feasible and safer than titration based on clinical signs and symptoms of congestion, with more effective decongestion at 48 hours. Further large-scale trials are needed to determine if the superiority of this approach translates into improved patient outcomes.