Background: Extreme preterm birth conveys an elevated risk of heart failure by young adulthood. Smaller biventricular chamber size, diastolic dysfunction, and pulmonary hypertension may contribute to reduced ventricular-vascular coupling. However, how hemodynamic manipulations may affect right ventricular (RV) function and coupling remains unknown. Methods: As a pilot study, 4D flow MRI was used to assess the effect of afterload reduction and heart rate reduction on cardiac hemodynamics and function. Young adults born premature were administered sildenafil (a pulmonary vasodilator) and metoprolol (a beta blocker) on separate days, and MRI with 4D flow completed before and after each drug administration. Endpoints include cardiac index (CI), direct flow fractions, and ventricular kinetic energy including E/A wave kinetic energy ratio. Results: Sildenafil resulted in a median CI increase of 0.24 L/min/m2 (P=0.02), mediated through both an increase in heart rate (HR) and stroke volume. Although RV ejection fraction improved only modestly, there was a significant increase (4% of end diastolic volume) in RV direct flow fraction (P=0.04), consistent with hemodynamic improvement. Metoprolol administration resulted in a 5-bpm median decrease in HR (P=0.01), a 0.37 L/min/m2 median decrease in CI (P=0.04), and a reduction in time-averaged kinetic energy (KE) in both ventricles (P<0.01), despite increased RV diastolic E/A KE ratio (P=0.04). Conclusions: Despite reduced right atrial workload, metoprolol significantly depressed overall cardiac systolic function. Sildenafil, however, increased CI and improved RV function, as quantified by the direct flow fraction. The preterm heart appears dependent on HR, but sensitive to RV afterload manipulations.
Age-associated changes in 4D flow CMR derived Tricuspid Valvular Flow and Right Ventricular Blood Flow Kinetic Energy