Incidence of MRI-detected brain lesions and neurocognitive function after electrical cardioversion in anticoagulated patients with persistent atrial fibrillation.

BACKGROUND: After electrical cardioversion (eCV) in patients with atrial fibrillation (AF), the risk for clinically apparent cerebral thromboembolism is increased in the subsequent weeks. To date, there is little evidence on the incidence of acute brain lesions (ABL) detected with cerebral magnetic resonance imaging (MRI) after eCV, in particular in patients treated with the Non-Vitamin K Antagonist oral anticoagulants (NOAC). AIMS: The aim of this pilot study was to evaluate the incidence of MRI-detected ABL, as well as the neuro-cognitive function after eCV in patients with persistent AF using NOACs as compared to phenprocoumon. METHODS AND RESULTS: 50 consecutive patients with persistent AF (mean age 69.6±3.5years, 26 male) were evaluated in this prospective study. Cerebral 3Tesla MRI and neuro-cognitive assessment using the National Institutes of Health Stroke Scale (NIHSS) score and the Montreal Cognitive Assessment Test (MoCA) were performed in all patients within 24h before eCV and after a median follow-up duration of 14days (Q1: 13, Q3: 19days). Patients were treated with an OAC for at least 4weeks after eCV and according to the CHA2DS2-Vasc-score thereafter. Thirty-nine patients were treated with NOACs (Dabigatran 10/50 [20%], Apixaban 21/50 [42%] and Rivaroxaban 8/50 [16]) and 11/50 patients with Phenprocoumon (22%). No patient developed ABL on cerebral MRI at the 2-week follow-up. Neurological as well as cognitive function were similar before and 2weeks after eCV (NIHSS-score: p=0.35; MoCa score: p=0.21). CONCLUSION: Electrical CV in patients with persistent AF, in particular when treated with NOACs, carries a low risk for the development of MRI-detected ABL or neurocognitive decline. CLINICAL TRIALS REGISTRATION: GermanClinicalTrialsRegister number: DRKS00010460.

Molecular imaging in cardiovascular diseases.

UNLABELLED: Cardiovascular diseases remain the leading cause of morbidity and mortality in industrialized and developing countries. In clinical practice, the in-vivo identification of atherosclerotic lesions, which can lead to complications such as heart attack or stroke, remains difficult. Imaging techniques provide the reference standard for the detection of clinically significant atherosclerotic changes in the coronary and carotid arteries. The assessment of the luminal narrowing is feasible, while the differentiation of stable and potentially unstable or vulnerable atherosclerotic plaques is currently not possible using non-invasive imaging. With high spatial resolution and high soft tissue contrast, magnetic resonance imaging (MRI) is a suitable method for the evaluation of the thin arterial wall. In clinical practice, native MRI of the vessel wall already allows the differentiation and characterization of components of atherosclerotic plaques in the carotid arteries and the aorta. Additional diagnostic information can be gained by the use of non-specific MRI contrast agents. With the development of targeted molecular probes, that highlight specific molecules or cells, pathological processes can be visualized at a molecular level with high spatial resolution. In this review article, the development of pathophysiological changes leading to the development of the arterial wall are introduced and discussed. Additionally, principles of contrast enhanced imaging with non-specific contrast agents and molecular probes will be discussed and latest developments in the field of molecular imaging of the vascular wall will be introduced. KEY POINTS: Molecular magnetic resonance imaging has great potential to improve the in vivo characterization of atherosclerotic plaques. Based on the molecular information is feasible to enable a better differentiation of stable and unstable (vulnerable) atherosclerotic plaques.

Molecular imaging in cardiovascular diseases.

Cardiovascular diseases remain the leading cause of morbidity and mortality in industrialized and developing countries. In clinical practice, the in-vivo identification of atherosclerotic lesions, which can lead to complications such as heart attack or stroke, remains difficult. Imaging techniques provide the reference standard for the detection of clinically significant atherosclerotic changes in the coronary and carotid arteries. The assessment of the luminal narrowing is feasible, while the differentiation of stable and potentially unstable or vulnerable atherosclerotic plaques is currently not possible using non-invasive imaging. With high spatial resolution and high soft tissue contrast, magnetic resonance imaging (MRI) is a suitable method for the evaluation of the thin arterial wall. In clinical practice, native MRI of the vessel wall already allows the differentiation and characterization of components of atherosclerotic plaques in the carotid arteries and the aorta. Additional diagnostic information can be gained by the use of non-specific MRI contrast agents. With the development of targeted molecular probes, that highlight specific molecules or cells, pathological processes can be visualized at a molecular level with high spatial resolution. In this review article, the development of pathophysiological changes leading to the development of the arterial wall are introduced and discussed. Additionally, principles of contrast enhanced imaging with non-specific contrast agents and molecular probes will be discussed and latest developments in the field of molecular imaging of the vascular wall will be introduced.

Induced differentiation of acute myeloid leukemia cells by activation of retinoid X and liver X receptors.

Use of all-trans retinoic acid (ATRA) as a differentiation agent has been limited to acute promyelocytic leukemia (APL) as non-APL leukemias are insensitive to ATRA. We recently demonstrated that the rexinoid, bexarotene, induces differentiation and therapeutic responses in patients with refractory AML. Rexinoids bind and activate retinoid X receptors (RXRs); however, rexinoids alone are incapable of activating retinoic acid receptor (RAR)/RXR complexes, suggesting that myeloid differentiation can occur independent of RAR. In this study, we demonstrate that rexinoid differentiation of AML cells is RAR independent and requires the expression of PU.1. Because of the promiscuousness of RXR with other nuclear receptors, myeloid differentiation by bexarotene with other nuclear receptor ligands was explored. Bexarotene cooperated with ATRA to enhance differentiation in some AML cell lines; however, the combination of bexarotene with the PPARγ agonist rosiglitazone did not. In contrast, bexarotene combined with liver X receptor (LXR) agonists, T0901317 or GW3965, induced potent differentiation and cytotoxicity in AML cell lines and primary human AML cells, but not in normal progenitor cells. These results suggest that RXR/LXR-regulated gene expression in normal cells is deregulated in AML cells and identifies a potential role for these agonists in differentiation therapy of non-APLs.

High prevalence of cardiac parvovirus B19 infection in patients with isolated left ventricular diastolic dysfunction.

BACKGROUND: The etiology of left ventricular (LV) isolated diastolic dysfunction often remains unclear. In the present study, we report a strong association between parvovirus B19 (PVB19) genomes and isolated LV diastolic dysfunction. METHODS AND RESULTS: In 70 patients (mean+/-SD age, 43+/-11 years) admitted with exertional dyspnea and/or reduced exercise tolerance despite preserved LV systolic contractility (ejection fraction=68%), isolated diastolic dysfunction was clinically suspected. Patients with classic risk factors for diastolic dysfunction such as hypertension, coronary heart disease, diabetes mellitus, or pulmonary disease had been excluded. Diastolic function was assessed by echocardiography and LV and RV catheterization. Endomyocardial biopsies (EMBs) were analyzed for the presence of storage or infiltrative diseases or myocarditis, including molecular screening for cardiotropic virus genomes. In a substudy of 24 patients who reported atypical angina, coronary endothelial function was additionally investigated with a coronary Doppler flow-wire technique. In 37 of 70 patients (53%), isolated diastolic dysfunction was confirmed as the cause of their clinical symptoms. No evidence for cardiac storage or infiltrative diseases was found in these cases, but in 35 of 37 of these patients (95%), cardiotropic virus genomes were detected in EMBs (P<0.001). PVB19 was the most frequent pathogen in 31 of 37 patients (84%). In a subgroup of 10 patients with diastolic dysfunction and coexisting endothelial dysfunction, all 10 (100%) were PVB19 positive. CONCLUSIONS: PVB19 genomes were predominant in patients with unexplained, isolated diastolic dysfunction. A strong association with the incidence of endothelial dysfunction was obvious, consistent with the hypothesis that PVB19-induced endothelial dysfunction may be a possible pathomechanism underlying diastolic dysfunction.

Methohexital impairs osmoregulation. Studies in conscious and anesthetized volume-expanded dogs.

BACKGROUND: Anesthetic agents influence central regulations. This study investigated the effects of methohexital anesthesia on renal and hormonal responses to acute sodium and water loading in dogs in the absence of surgical stress. METHODS: Fourteen experiments (two in each dog) were performed in seven well-trained, chronically tracheotomized beagle dogs kept in highly standardized environmental and dietary conditions (2.5 mmol sodium and 91 ml water/kg body weight daily). Experiments lasted 3 h, while the dogs were conscious (7 experiments) or, after 1 h control, while they were anesthetized (7 experiments) with methohexital (initial dose 6.6 mg/kg body weight and maintenance infusion 0.34 mg.min-1.kg-1 body weight) over a period of 2 h. In both experiments, extracellular volume expansion was performed by intravenous infusion of a balanced isoosmolar electrolyte solution (0.5 ml.min-1.kg-1 body weight). Normal arterial blood gases were maintained by controlled mechanical ventilation. In another five dogs the same protocol was used, and vasopressin (0.05 mU.min-1.kg-1 body weight) was infused intravenously during methohexital anesthesia. RESULTS: Values are given as means. During methohexital anesthesia, mean arterial pressure decreased from 108 to 101 mmHg, and heart rate increased from 95 to 146 beats/min. Renal sodium excretion decreased; urine volume increased; and urine osmolarity decreased from 233 to 155 mosm/l, whereas plasma osmolarity increased from 301 to 312 mosm/l because of an increase in plasma sodium concentration from 148 to 154 mmol/l. Plasma renin activity, plasma aldosterone concentration, plasma atrial natriuretic peptide, and plasma antidiuretic hormone concentrations (range 1.8-2.8 pg/ml) did not change in either protocol. In the presence of exogenous vasopressin (antidiuretic hormone 3.3 pg/ml), water diuresis did not occur, and neither plasma osmolarity nor the plasma concentration of sodium changed. CONCLUSIONS: Methohexital may impair osmoregulation by inhibiting adequate pituitary antidiuretic hormone release in response to an osmotic challenge.