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Background: The prognostic importance of left atrial (LA) dysfunction is increasingly recognized. Magnetic Resonance Imaging (MRI) can provide excellent visualization of the left atrial wall. We aimed to study the association of LA dysfunction measured using feature-tracking MRI with incident adverse cardiovascular events among subjects with or without HF at baseline. Methods and Results: We prospectively studied 640 adults without HF (n=419), HF with preserved ejection fraction (HFpEF, n=101), or HF with reduced ejection fraction (HFrEF, n=120). We measured phasic LA function by volumetric and feature-tracking methods to derive longitudinal strain. The composite outcome of incident heart failure hospitalization or death was adjudicated over a median follow-up of 37.1 months. Measures of LA phasic function were more prominently impaired in subjects with HFrEF, than among subjects with HFpEF. In unadjusted Cox proportional hazards models, all measures of phasic LA function and volumes (maximum, minimum and diastatic) were associated with the composite outcome. However, in analyses that adjusted for clinical risk factors, heart failure status, maximum LA volume, left ventricular (LV) mass and LV ejection fraction, measures of conduit and reservoir LA function, but not booster-pump function, were associated with the composite outcome. The strongest associations were observed for conduit longitudinal strain (Standardized Hazard ratio=0.66; 95%CI=0.49–0.88, P=0.004), conduit strain rate (Standardized HR=1.59; 95%CI=1.16–2.16, P=0.0035), and reservoir strain (Standardized HR=0.68; 95%CI=0.52–0.89, P=0.0055). Conclusions: Phasic LA function measured using MRI feature-tracking is independently predictive of the risk of incident HF admission or death, even after adjusting for LA volume and LV remodeling.

These findings may help nuclear medicine physicians when comparing images performed at different time points, when using FDG uptake in internal reference regions as a relative indicator of FDG uptake in a specific lesion, and when reading a delayed FDG PET imaging.

CKD is associated with increased (inactive) dp-ucMGP, a vitamin K-dependent inhibitor of vascular calcification, which correlates with large artery stiffness. Further studies are needed to assess whether vitamin K2 supplementation represents a suitable therapeutic strategy to prevent or reduce arterial stiffening in CKD.

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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...

BackgroundWave reflections, which are increased in patients with heart failure with preserved ejection fraction, impair diastolic function and promote pathologic myocardial remodeling. Organic nitrates reduce wave reflections acutely, but whether this is sustained chronically or affected by hydralazine coadministration is unknown.Methods and ResultsWe randomized 44 patients with heart failure with preserved ejection fraction in a double‐blinded fashion to isosorbide dinitrate (ISDN; n=13), ISDN+hydralazine (ISDN+hydral; n=15), or placebo (n=16) for 6 months. The primary end point was the change in reflection magnitude (RM; assessed with arterial tonometry and Doppler echocardiography). Secondary end points included change in left ventricular mass and fibrosis, measured with cardiac magnetic resonance imaging, and the 6‐minute walk distance. ISDN reduced aortic characteristic impedance (mean baseline=0.15 [95% CI, 0.14–0.17], 3 months=0.11 [95% CI, 0.10–0.13], 6 months=0.10 [95% CI, 0.08–0.12] mm Hg/mL per second; P=0.003) and forward wave amplitude (Pf, mean baseline=54.8 [95% CI, 47.6–62.0], 3 months=42.2 [95% CI, 33.2–51.3]; 6 months=37.0 [95% CI, 27.2–46.8] mm Hg, P=0.04), but had no effect on RM (P=0.64), left ventricular mass (P=0.33), or fibrosis (P=0.63). ISDN+hydral increased RM (mean baseline=0.39 [95% CI, 0.35–0.43]; 3 months=0.31 [95% CI, 0.25–0.36]; 6 months=0.44 [95% CI, 0.37–0.51], P=0.03), reduced 6‐minute walk distance (mean baseline=343.3 [95% CI, 319.2–367.4]; 6 months=277.0 [95% CI, 242.7–311.4] meters, P=0.022), and increased native myocardial T1 (mean baseline=1016.2 [95% CI, 1002.7–1029.7]; 6 months=1054.5 [95% CI, 1036.5–1072.3], P=0.021). A high proportion of patients experienced adverse events with active therapy (ISDN=61.5%, ISDN+hydral=60.0%; placebo=12.5%; P=0.007).Conclusions ISDN, with or without hydralazine, does not exert beneficial effects on RM, left ventricular remodeling, or submaximal exercise and is poorly tolerated. ISDN+hydral appears to have deleterious effects on RM, myocardial remodeling, and submaximal exercise. Our findings do not support the routine use of these vasodilators in patients with heart failure with preserved ejection fraction.Clinical Trial Registration URL: www.clinicaltrials.gov. Unique identifier: NCT01516346.