Aims To assess the hemodynamic effects of organic vs. inorganic nitrate administration among patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results We assessed carotid and aortic pressure-flow relations non-invasively before and after the administration of 0.4 mg of sublingual-nitroglycerin (NTG; n=26), and in a separate sub-study, in response to 12.9 mmol of inorganic nitrate (n=16). NTG did not consistently reduce wave reflections arriving at the proximal aorta (change in real part of reflection coefficient, 1st harmonic:-0.09; P=0.01; 2nd harmonic:-0.045, P=0.16; 3rd harmonic:+0.087; P=0.05), but produced profound vasodilation in the carotid territory, with a significant reduction in systolic blood pressure (133.6 vs 120.5 mmHg; P=0.011) and a marked reduction in carotid bed vascular resistance (19580 vs. 13078 dynes·s/cm5; P=0.001) and carotid characteristic impedance (3440 vs. 1923 dynes·s/cm5; P=0.002). Inorganic nitrate, in contrast, consistently reduced wave reflections across the first 3 harmonics (change in real part of reflection coefficient, 1st harmonic: -0.12; P=0.03; 2nd harmonic:-0.11, P=0.01; 3rd harmonic:-0.087; P=0.09) and did not reduce blood pressure, carotid bed vascular resistance or carotid characteristic impedance (P=NS). Conclusions NTG produces marked vasodilation in the carotid circulation, with a pronounced reduction in blood pressure and inconsistent effects on central wave reflections. Inorganic nitrate, in contrast, produces consistent reductions in wave reflections, and unlike NTG, it does so without significant hypotension or cerebrovascular dilatation. These hemodynamic differences may underlie the different effects on exercise capacity and side effect profile of inorganic vs. organic nitrate in HFpEF.

Organic nitrates, but not inorganic nitrates, increase the amount of hydraulic energy transmitted into the carotid artery in subjects with HFpEF. These findings may have implications for the adverse effect profiles of these agents (such as the differential incidence of headaches) and for the pulsatile hemodynamic stress of the brain microvasculature in this patient population.

Intraventricular pressure differences (IVPDs) govern left ventricular (LV) efficient filling and are a significant determinant of LV diastolic function. Our primary aim is to assess the performance of available methods (color M-mode (CMM) and 1D/2D MRI-based methods) to determine IVPDs from intracardiac flow measurements. Performance of three methods to calculate IVPDs was first investigated via an LV computational fluid dynamics (CFD) model. CFD velocity data were derived along a modifiable scan line, mimicking ultrasound/MRI acquisition of 1D (IVPD/IVPD) and 2D (IVPD) velocity-based IVPD information. CFD pressure data (IVPD) was used as a ground truth. Methods were also compared in a small cohort (n = 13) of patients with heart failure with preserved ejection fraction (HFpEF). In silico data showed a better performance of the IVPD approach: RMSE values for a well-aligned scan line were 0.2550 mmHg (IVPD), 0.0798 mmHg (IVPD), and 0.2633 mmHg (IVPD). In vivo data exhibited moderate correlation between techniques. Considerable differences found may be attributable to different timing of measurements and/or integration path. CFD modeling demonstrated an advantage using 2D velocity information to compute IVPDs, and therefore, a 2D MRI-based method should be favored. However, further studies are needed to support the clinical significance of MRI-based computation of IVPDs over CMM.