Non-invasive intraventricular pressure differences estimated with cardiac MRI in subjects without heart failure and with heart failure with reduced and preserved ejection fraction.

Objective: Non-invasive assessment of left ventricular (LV) diastolic and systolic function is important to better understand physiological abnormalities in heart failure (HF). The spatiotemporal pattern of LV blood flow velocities during systole and diastole can be used to estimate intraventricular pressure differences (IVPDs). We aimed to demonstrate the feasibility of an MRI-based method to calculate systolic and diastolic IVPDs in subjects without heart failure (No-HF), and with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Methods: We studied 159 subjects without HF, 47 subjects with HFrEF and 32 subjects with HFpEF. Diastolic and systolic intraventricular flow was measured using two-dimensional in-plane phase-contrast MRI. The Euler equation was solved to compute IVPDs in diastole (mitral base to apex) and systole (apex to LV outflow tract). Results: Subjects with HFpEF demonstrated a higher magnitude of the early diastolic reversal of IVPDs (-1.30 mm Hg) compared with the No-HF group (-0.78 mm Hg) and the HFrEF group (-0.75 mm Hg; analysis of variance p=0.01). These differences persisted after adjustment for clinical variables, Doppler-echocardiographic parameters of diastolic filling and measures of LV structure (No-HF=-0.72; HFrEF=-0.87; HFpEF=-1.52 mm Hg; p=0.006). No significant differences in systolic IVPDs were found in adjusted models. IVPD parameters demonstrated only weak correlations with standard Doppler-echocardiographic parameters. Conclusions: Our findings suggest distinct patterns of systolic and diastolic IVPDs in HFpEF and HFrEF, implying differences in the nature of diastolic dysfunction between the HF subtypes.

Effect of organic and inorganic nitrates on cerebrovascular pulsatile power transmission in patients with heart failure and preserved ejection fraction.

OBJECTIVE: Increased penetration of pulsatile power to the brain has been implicated in the pathogenesis of age-related cognitive dysfunction and dementia, a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). However, there is a lack of knowledge on the effects of organic and inorganic nitrates administration in this population on the power carried by pressure and flow waves traveling through the proximal aorta and penetrating the carotid artery into the brain microvasculature. APPROACH: We assessed aortic and carotid hemodynamics non-invasively in two sub-studies: (1) at baseline and after administration of 0.4 mg of sublingual nitroglycerine (an organic nitrate; n = 26); and (2) in a randomized controlled trial of placebo (PB) versus inorganic nitrate administration (beetroot-juice (BR), 12.9 mmol NO3; n = 16). MAIN RESULTS: Wave and hydraulic power analysis demonstrated that NTG increased total hydraulic power (from 5.68% at baseline to 8.62%, P = 0.001) and energy penetration (from 8.69% to 11.63%; P = 0.01) from the aorta to the carotid, while inorganic nitrate administration did not induce significant changes in aortic and carotid wave power (power: 5.49%PB versus 6.25%BR, P = 0.49; energy: 8.89%PB versus 10.65%BR, P = 0.27). SIGNIFICANCE: 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.

Assessment of methodologies to calculate intraventricular pressure differences in computational models and patients.

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 (IVPDCMM/IVPD1D MRI) and 2D (IVPD2D MRI) velocity-based IVPD information. CFD pressure data (IVPDCFD) 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 IVPD2D MRI approach: RMSE values for a well-aligned scan line were 0.2550 mmHg (IVPD1D MRI), 0.0798 mmHg (IVPD2D MRI), and 0.2633 mmHg (IVPDCMM). 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.

Effects of organic and inorganic nitrate on aortic and carotid haemodynamics in heart failure with preserved ejection fraction.

AIMS: To assess the haemodynamic 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 (n = 26), and in a separate sub-study, in response to 12.9 mmoL of inorganic nitrate (n = 16). Nitroglycerin 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 vasodilatation 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 (19 580 vs. 13 078 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 three 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: Nitroglycerin produces marked vasodilatation 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 nitroglycerin, it does so without significant hypotension or cerebrovascular dilatation. These haemodynamic differences may underlie the different effects on exercise capacity and side effect profile of inorganic vs. organic nitrate in HFpEF.