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

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

Intermittent Fasting and Metabolic Health

Given the ongoing strain that the obesity epidemic has placed on public health outcomes, new and effective approaches to weight control are needed. One approach to improving weight and metabolic outcomes is intermittent fasting, which consists of multiple different timing schedules for temporary food avoidance, including alternate-day fasting, other similar full-day fasting patterns, and time-restricted feeding (where the day’s food is consumed over a 6-h period, allowing for 18 h of fasting). These feeding schedules have favorable metabolic effects by intermittently inducing the metabolism of fatty acids to ketones. The regimens overall lead to a decrease in weight and have been linked to improvements in dyslipidemia and blood pressure. While more research is needed on longer-term outcomes and this approach should be avoided in particular health conditions, intermittent fasting should be considered as an option for individuals who have a pattern of unhealthy weight gain using standard eating patterns