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Objectives: To evaluate differences in coronary microvascular function approximately 12 years after delivery between women who had had early- (EO-PE) or late- (LO-PE) onset pre-eclampsia and those who had had a normotensive pregnancy, and to assess the relationship between microvascular function and myocardial deformation at follow-up in these women.Methods: This was a case-control study of 88 women who had delivered at the Department of Gynecology and Obstetrics, Randers Regional Hospital, Randers, Denmark, between 1998 and 2008. Coronary flow velocity reserve (CFVR) was assessed by Doppler echocardiography approximately 12 years after delivery. Women were grouped according to whether the pregnancy had been complicated by EO-PE (n = 29) or LO-PE (n = 20), or had been normotensive (controls) (n = 39). Study groups were matched for maternal age and time since delivery. CFVR at follow-up was compared between the study groups. Regression analysis was used to assess the association between gestational age at onset of PE and CFVR. The association between left ventricular global longitudinal strain (LV-GLS) and CFVR at follow-up was also evaluated.Results: Resting coronary flow velocity assessed 12 years after delivery was comparable between the study groups (P = 0.55), whereas peak hyperemic flow velocity was significantly lower in the EO-PE group than in the LO-PE group (P < 0.01) and controls (P < 0.0001). As such, mean CFVR at follow-up was significantly lower in the EO-PE group than in the LO-PE group (P < 0.01) and controls (P < 0.0001). CFVR was < 2.5 in 48% of women in the EO-PE group, 25% of those in the LO-PE group and 8% of controls (P < 0.01). There was a significant positive association between gestational age at diagnosis of PE and CFVR at 12-year follow-up (β1 = 1.8 (95% CI, 0.8-2.9); P < 0.01). This relationship remained significant after adjustment for cardiovascular risk factors, namely mean arterial blood pressure, glycated hemoglobin level, body mass index, low-density lipoprotein cholesterol level and smoking status (P < 0.05). There was a significant association between LV-GLS and CFVR in women who had had PE (β1 = -1.5 (95% CI, -2.2 to -0.9); R2  = 0.33, P < 0.0001).Conclusions: Low gestational age at onset of PE, both as a continuous variable and when categorized as early onset, was associated with decreased CFVR 12 years after delivery. Nearly 50% of women who had had EO-PE had CFVR < 2.5 at follow-up. Reduced CFVR in women who had had PE was associated with subclinical myocardial dysfunction in terms of reduced LV-GLS. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background: Wild-type transthyretin amyloid (ATTRwt) cardiomyopathy is increasingly recognized in the development of heart failure. The link between cardiac performance, hemodynamics, and mitochondrial function in disease stages of ATTRwt has not previously been studied but may provide new insights into the pathophysiology and clinical performance of the patients., Methods and Results: The study investigated 47 patients diagnosed with ATTRwt at Aarhus University Hospital, Denmark. Patients were stratified according to the disease stages of the National Amyloidosis Centre (NAC) as NAC I with low levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) (NAC I-L, n=14), NAC I with high levels NT-proBNP (NAC I-H, n=20), and NAC II-III (n=13). Exercise testing with simultaneous right heart catheterization was performed in all patients. Endomyocardial biopsies were collected from the patients and the mitochondrial oxidative phosphorylation capacity was assessed. All NAC disease groups, even in the NAC I-L group, a significant abnormal increase in biventricular filling pressures were noted during exercise while the filling pressures was normal or near normal at rest. The inotropic response to exercise was reduced with diminished increase in cardiac output which was significantly more pronounced in the NAC I-H (Diff. -2.4, 95% CI (-4.2: -0.7), P =0.00) and the NAC II-III group (Diff: -3.1 L/min, 95% CI (-5.2: -1.1), P =0.00) compared with the NAC I-L group. The pulmonary artery wedge pressure to cardiac output ratio at peak exercise was significantly different between NAC I-L and NAC II-III (Diff: 1.6 mm Hg*min/L, 95% CI (0.01:3.3, P =0.04)). Patients with ATTRwt had a reduced oxidative phosphorylation capacity which correlated to left ventricular mass but not to cardiac output capacity., Conclusions: An abnormal restrictive left ventricle and right ventricle response to exercise was demonstrated, even present in patients with early-stage ATTRwt. In more advanced disease stages a progressive impairment of the pressure-flow relationship was noted. The myocyte energetics is deranged but not associated to the contractile reserve or restrictive filling characteristics in ATTRwt.

Background Despite correction of the atrial septal defect (ASD), patients experience atrial fibrillation frequently and have increased morbidity and mortality. We examined physical capacity, cardiac performance, and invasive hemodynamics in patients with corrected ASD. Methods and Results Thirty-eight corrected patients with isolated secundum ASD and 19 age-matched healthy controls underwent right heart catheterization at rest and during exercise with simultaneous expired gas assessment and echocardiography. Maximum oxygen uptake was comparable between groups (ASD 32.7±7.7 mL O 2 /kg per minute, controls 35.2±7.5 mL O 2 /kg per minute, P =0.3), as was cardiac index at both rest and peak exercise. In contrast, pulmonary artery wedge v wave pressures were increased at rest and peak exercise (rest: ASD 14±4 mm Hg, controls 10±5 mm Hg, P =0.01; peak: ASD 25±9 mm Hg, controls 14±9 mm Hg, P =0.0001). The right atrial v wave pressures were increased at rest but not at peak exercise. The transmural filling pressure gradient (TMFP) was higher at peak exercise among patients with ASD (10±6 mm Hg, controls 7±3 mm Hg, P =0.03). One third of patients with ASD demonstrated an abnormal hemodynamic exercise response defined as mean pulmonary artery wedge pressure ≥25 mm Hg and/or mean pulmonary artery pressure ≥35 mm Hg at peak exercise. These patients had significantly elevated peak right and left atrial a wave pressures, right atrial v wave pressures, pulmonary artery wedge v wave pressures, and transmural filling pressure compared with both controls and patients with ASD with a normal exercise response. Conclusions Patients with corrected ASD present with elevated right and in particular left atrial pressures at rest and during exercise despite preserved peak exercise capacity. Abnormal atrial compliance and systolic atrial function could predispose to the increased long-term risk of atrial fibrillation. Registration Information clinicaltrials.gov. Identifier: NCT03565471.

Midbrain dopaminergic (DAergic) neurons are a heterogeneous cell group, composed of functionally distinct cell populations projecting to the basal ganglia, prefrontal cortex and limbic system. Despite their functional significance, the midbrain population of DAergic neurons is sparse, constituting only 20 000-30 000 neurons in mice, and development of novel tools to identify these cells is warranted. Here, a bacterial artificial chromosome mouse line [Dat1-enhanced green fluorescent protein (eGFP)] from the Gene Expression Nervous System Atlas (GENSAT) that expresses eGFP under control of the dopamine transporter (DAT) promoter was characterized. Confocal microscopy analysis of brain sections showed strong eGFP signal reporter in midbrain regions and striatal terminals that co-localized with the DAergic markers DAT and tyrosine hydroxylase (TH). Thorough quantification of co-localization of the eGFP reporter signal with DAT and TH in the ventral midbrain showed that a vast majority of eGFP-expressing neurons are DAergic. Importantly, expression profiles also revealed DAergic heterogeneity when comparing substantia nigra and ventral tegmental area. Dat1-eGFP mice showed neither change in synaptosomal DA uptake nor altered levels of DAT and TH in both striatum and midbrain. No behavioural difference between Dat1-eGFP and wild-type was found, suggesting that the strain is not aberrant. Finally, cell populations highly enriched in DAergic neurons can be obtained from postnatal mice by fluorescence-activated cell sorting and the sorted neurons can be cultured in vitro. The current investigation demonstrates that eGFP expression in this mouse line is selective for DAergic neurons, suggesting that the Dat1-eGFP mouse strain constitutes a promising tool for delineating new aspects of DA biology., (© 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)