Background Inorganic nitrate (NO3−), abundant in certain vegetables, is converted to nitrite by bacteria in the oral cavity. Nitrite can be converted to nitric oxide (NO) in the setting of hypoxia. We tested the hypothesis that NO3− supplementation improves exercise capacity in HFpEF via specific adaptations to exercise. Methods Seventeen subjects participated in this randomized, double-blind, cross-over study comparing a single-dose of NO3-rich beetroot juice (NO3−:12.9 mmoles) versus an identical nitrate-depleted placebo. Subjects performed supine-cycle maximal-effort cardiopulmonary exercise tests, with measurements of cardiac output (CO) and skeletal muscle oxygenation. We also assessed skeletal muscle oxidative function. Study endpoints included exercise efficiency (total work/total oxygen consumed), peak VO2, total work performed, vasodilatory reserve, forearm mitochondrial oxidative function, and augmentation index (a marker of arterial wave reflections, measured via radial arterial tonometry). Results Supplementation increased plasma NO-metabolites (median 326 μM versus 10 μM; P=0.0003), peak VO2 (12.6±3.7 vs. 11.6±3.1 mL O2/min/kg; P=0.005), and total work performed (55.6±35.3 vs. 49.2±28.9 kJ; P=0.04). However, efficiency was unchanged. NO3− led to greater reductions in SVR (−42.4±16.6 vs. −31.8±20.3%; P=0.03) and increases in CO (121.2±59.9 vs. 88.7±53.3%; P=0.006) with exercise. NO3− reduced aortic augmentation index (132.2±16.7 vs. 141.4±21.9%, P=0.03) and tended to improve mitochondrial oxidative function. Conclusion NO3− increased exercise capacity in HFpEF by targeting peripheral abnormalities. Efficiency did not change due to parallel increases in total work and VO2. NO3− increased exercise vasodilatory and cardiac output reserves. NO3− also reduced arterial wave reflections, which are linked to left ventricular diastolic dysfunction and remodeling.

Abstract-Effective arterial elastance (E A ) was proposed as a lumped parameter that incorporates pulsatile and resistive afterload and is increasingly being used in clinical studies. Theoretical modeling studies suggest that E A is minimally affected by pulsatile load, but little human data are available. We assessed the relationship between E A and arterial load determined noninvasively from central pressure-flow analyses among middle-aged adults in the general population (n=2367) and a diverse clinical population of older adults (n=193). In a separate study, we investigated the sensitivity of E A to changes in pulsatile load induced by isometric exercise (n=73). The combination of systemic vascular resistance and heart rate predicted 95.6% and 97.8% of the variability in E A among middle-aged and older adults, respectively. E A demonstrated a quasi-perfect linear relationship with the ratio of systemic vascular resistance/heart period (middle-aged adults, R=0.972; older adults, R=0.99; P<0.0001). Aortic characteristic impedance, total arterial compliance, reflection magnitude, and timing accounted together for <1% of the variability in E A in either middle-aged or older adults. Despite pronounced changes in pulsatile load induced by isometric exercise, changes in E A were not independently associated with changes pulsatile load but were rather a nearly perfect linear function of the ratio of systemic vascular resistance/ heart period (R=0.99; P<0.0001). Our findings demonstrate that E A is simply a function of systemic vascular resistance and heart rate and is negligibly influenced by (and insensitive to) changes in pulsatile afterload in humans. Its current interpretation as a lumped parameter of pulsatile and resistive afterload should thus be reassessed.

Background Heterogeneity in the underlying processes that contribute to heart failure with preserved ejection fraction ( HF p EF ) is increasingly recognized. Diabetes mellitus is a frequent comorbidity in HF p EF , but its impact on left ventricular and arterial structure and function in HF p EF is unknown. Methods and Results We assessed the impact of diabetes mellitus on left ventricular cellular and interstitial hypertrophy (assessed with cardiac magnetic resonance imaging, including T1 mapping pregadolinium and postgadolinium administration), arterial stiffness (assessed with arterial tonometry), and pulsatile arterial hemodynamics (assessed with in‐office pressure‐flow analyses and 24‐hour ambulatory monitoring) among 53 subjects with HF p EF (32 diabetic and 21 nondiabetic subjects). Despite few differences in clinical characteristics, diabetic subjects with HFpEF exhibited a markedly greater left ventricular mass index (78.1 [95% CI , 70.4–85.9] g versus 63.6 [95% CI , 55.8–71.3] g; P =0.0093) and indexed extracellular volume (23.6 [95% CI , 21.2–26.1] mL/m 2 versus 16.2 [95% CI , 13.1–19.4] mL/m 2 ; P =0.0008). Pronounced aortic stiffening was also observed in the diabetic group (carotid‐femoral pulse wave velocity, 11.86 [95% CI , 10.4–13.1] m/s versus 8.8 [95% CI , 7.5–10.1] m/s; P =0.0027), with an adverse pulsatile hemodynamic profile characterized by increased oscillatory power (315 [95% CI , 258–373] mW versus 190 [95% CI , 144–236] mW; P =0.0007), aortic characteristic impedance (0.154 [95% CI , 0.124–0.183] mm Hg/mL per second versus 0.096 [95% CI , 0.072–0.121] mm Hg/mL per second; P =0.0024), and forward (59.5 [95% CI , 52.8–66.1] mm Hg versus 40.1 [95% CI , 31.6–48.6] mm Hg; P =0.0010) and backward (19.6 [95% CI , 16.2–22.9] mm Hg versus 14.1 [95% CI , 10.9–17.3] mm Hg; P =0.0169) wave amplitude. Abnormal pulsatile hemodynamics were also evident in 24‐hour ambulatory monitoring, despite the absence of significant differences in 24‐hour systolic blood pressure between the groups. Conclusions Diabetes mellitus is a key determinant of left ventricular remodeling, arterial stiffness, adverse pulsatile...

There is controversy regarding the utility of left ventricular (LV) mechanics assessed by featuretracking (FT)-SSFP, a readily implementable technique in clinical practice. In particular, whether LV mechanics assessed by FT-SSFP predicts outcomes in subjects with heart failure (HF) with reduced ejection fraction (HFrEF), with preserved ejection fraction (HFpEF), or without HF is unknown. We aimed to assess whether LV mechanics measured with FT-SSFP cine MRI predicts adverse outcomes. We prospectively enrolled 612 adults without HF (n=402), with HF with reduced ejection fraction (HFrEF; n=113), or HFpEF (n=97) and assessed LV strain using FT-SSFP cine MRI. Over a median follow-up of 39.5 months, 75 participants had a HF admission, and 85 died. In Cox proportional hazards models, lower global longitudinal (Standardized Hazard Ratio: 1.56, 95% CI=1.22 to 2.00, p=0.0004), circumferential (Standardized HR: 1.46, 95% CI=1.08 to 1.95, p=0.0123), and radial strain (Standardized HR: 0.59, 95% CI=0.43-0.83, p=0.0019) were independently associated with the composite endpoint, after adjustment for HF status, LV ejection fraction (LVEF), age, sex, ethnicity, body mass index, systolic and diastolic blood pressure, hypertension, diabetes, coronary artery disease and glomerular filtration rate. Furthermore, global longitudinal strain stratified the risk of adverse outcomes across tertiles better than LVEF. In analyses that included only participants with a preserved LVEF, systolic radial, circumferential and longitudinal strain were independently predictive of adverse outcomes. We conclude that LV longitudinal, circumferential and radial strain measured using FT-SSFP cine

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Objectives: Treating white spot lesions (WSL) to create a sound and esthetically pleasing enamel surface is a question yet to be fully answered. The objective of this randomized controlled trial was to measure and compare the degree of regression of WSL during orthodontic treatment achieved by using three commercially available materials. Methods: A single-blinded randomized prospective clinical trial, comprising 80 patients categorized into four groups (one control group and three experimental groups, with 20 subjects per group) using block randomization, was conducted. Group A (control group): Colgate strong toothpaste; and experiments groups were Group B: GC tooth mousse, Group C: Phos-Flur mouthwash and Group D: SHY-NM. Subjects were instructed to use the designated dentifrice/mouthwash and photographs were taken at baseline, third and sixth months, and white spot lesions were reassessed in the maxillomandibular anterior teeth. Results: All the three groups had shown an improvement in WSL. But Group B has shown the greatest difference in mean values of decalcification index (DI) scores. Conclusion: All three commercially available products showed a regression of WSL over a 6-month duration. GC tooth mousse proved to be the most effective means of treating WSL over other regimens.