Saturation recovery-prepared magnetic resonance angiography for assessment of left atrial and esophageal anatomy

Objectives:Magnetic resonance angiography (MRA) has been established as an important imaging method in cardiac ablation procedures. In pulmonary vein (PV) isolation procedures, MRA has the potential to minimize the risk of severe complications, such as atrio-esophageal fistula, by providing detailed information on esophageal position relatively to cardiac structures. However, traditional non-gated, first-pass (FP) MRA approaches have several limitations, such as long breath-holds, non-uniform signal intensity throughout the left atrium (LA), and poor esophageal visualization. The aim of this observational study was to validate a respiratory-navigated, ECG-gated (EC), saturation recovery-prepared MRA technique for simultaneous imaging of LA, LA appendage, PVs, esophagus, and adjacent anatomical structures.Methods:Before PVI, 106 consecutive patients with a history of AF underwent either conventional FP-MRA (n = 53 patients) or our new EC-MRA (n = 53 patients). Five quality scores (QS) of LA and esophagus visibility were assessed by two experienced readers. The non-parametric Mann–Whitney U-test was used to compare QS between FP-MRA and EC-MRA groups, and linear regression was applied to assess clinical contributors to image quality.Results:EC-MRA demonstrated significantly better image quality than FP-MRA in every quality category. Esophageal visibility using the new MRA technique was markedly better than with the conventional FP-MRA technique (median 3.5 [IQR 1] vs median 1.0, p < 0.001). In contrast to FP-MRA, overall image quality of EC-MRA was not influenced by heart rate.Conclusion:Our ECG-gated, respiratory-navigated, saturation recovery-prepared MRA technique provides significantly better image quality and esophageal visibility than the established non-gated, breath-holding FP-MRA. Image quality of EC-MRA technique has the additional advantage of being unaffected by heart rate.Advances in knowledge:Detailed information of cardiac anatomy has the potential to minimize the risk of severe complications and improve success rates in invasive electrophysiological studies. Our novel ECG-gated, respiratory-navigated, saturation recovery-prepared MRA technique provides significantly better image quality of LA and esophageal structures than the traditional first-pass algorithm. This new MRA technique is robust to arrhythmia (tachycardic, irregular heart rates) frequently observed in AF patients.     

Inducible nitric oxide synthase expression and cardiomyocyte dysfunction during sustained moderate ischemia in pigs

In acute myocardial ischemia, regional blood flow and function are proportionally reduced. With prolongation of ischemia, function further declines at unchanged blood flow. We studied the involvement of an inflammatory signal cascade in such progressive dysfunction and whether dysfunction is intrinsic to cardiomyocytes. In 10 pigs, ischemia was induced by adjusting inflow into the cannulated left anterior coronary artery to reduce coronary arterial pressure to 45 mm Hg (ISCH); 4 pigs received the inducible nitric oxide synthase (iNOS) inhibitors aminoguanidine or L-N(6)-(1-iminoethyl)-lysine during ISCH (ISCH+iNOS-Inhib); 6 pigs served as controls (SHAM). Anterior (AW) and posterior (PW) systolic wall thickening (sonomicrometry) were measured. After 6 hours, nitric oxide (NO) synthase (NOS) protein expression, NOS activity, and NO metabolites (nitrite/nitrate/nitroso species) were quantified in biopsies isolated from AW and PW. Cardiomyocyte shortening and intracellular calcium (Indo-1 acetoxymethyl ester) were measured without and with the NOS substrate L-arginine (100 micromol/L). In ISCH, AW wall thickening decreased from 42+/-4% (baseline) to 16+/-3% (6 hours). Wall thickening remained unchanged in ISCH-PW and SHAM-AW/PW. NOS2 (iNOS) protein expression and activity, but not NOS3 (endothelial NO synthase), were increased in ISCH-AW and ISCH-PW. iNOS expression correlated with increased nitrite contents. Cardiomyocyte shortening was reduced in ISCH-AW versus SHAM-AW (4.4+/-0.3% versus 5.6+/-0.3%). L-Arginine reduced cardiomyocyte shortening further in ISCH-AW (to 2.8+/-0.2%) and ISCH-PW (3.4+/-0.4% versus 5.4+/-0.4%) but not in SHAM or in ISCH+iNOS-Inhib; intracellular [Ca(2+)] remained unchanged. With L-arginine, in vitro AW cardiomyocyte shortening correlated with in vivo AW wall thickening (r=0.72). In conclusion, sustained regional ischemia induces myocardial iNOS expression in pigs, which contributes to contractile dysfunction at the cardiomyocyte level.     

Recent advances in the understanding of the role of nitric oxide in cardiovascular homeostasis

Nitric oxide synthases (NOS) are the enzymes responsible for nitric oxide (NO) generation. To date, 3 distinct NOS isoforms have been identified: neuronal NOS (NOS1), inducible NOS (NOS2), and endothelial NOS (NOS3). Biochemically, NOS consists of a flavin-containing reductase domain, a heme-containing oxygenase domain, and regulatory sites. NOS catalyse an overall 5-electron oxidation of one Nomega-atom of the guanidino group of L-arginine to form NO and L-citrulline. NO exerts a plethora of biological effects in the cardiovascular system. The basal formation of NO in mitochondria by a mitochondrial NOS seems to be one of the main regulators of cellular respiration, mitochondrial transmembrane potential, and transmembrane proton gradient. This review focuses on recent advances in the understanding of the role of enzyme and enzyme-independent NO formation, regulation of NO bioactivity, new aspects of NO on cardiac function and morphology, and the clinical impact and perspectives of these recent advances in our knowledge on NO-related pathways.     

Nitric oxide/cGMP signalling mediates the cardioprotective action of adrenomedullin in reperfused myocardium

We demonstrated previously that adrenomedullin (AM), when given during early reperfusion, limited infarct size in rat heart. The present study was undertaken to provide direct evidence of the NO-dependency of AM’s cardioprotective action by assessing NO biosynthesis and involvement of the soluble guanylyl cyclase (sGC) pathway. Perfused hearts from male CD-1 mice were subjected to 30-min left coronary occlusion and 60-min reperfusion. Infarct size was determined by tetrazolium staining. AM 10 nM was administered from 20 min after coronary occlusion until 10 min after reperfusion. Coronary effluent was analysed for NO₂ ⁻ and NO₃ ⁻, and myocardial samples were analysed for NO₂ ⁻, NO₃ ⁻, nitroso-adducts and cGMP concentration. To examine the role of NO/sGC signalling in the infarct-limiting action of AM, further hearts received the sGC inhibitor ODQ 2 μM. AM treatment stimulated NO synthesis, indicated by increased NO₂ ⁻ efflux in coronary effluent throughout reperfusion (summarised as area under curve, AM 29.2 ± 3.9 vs. control 14.4 ± 2.8 μmol min² mL⁻¹, P < 0.05). AM limited infarct size (35.4 ± 2.7 vs. 12.2 ± 2.3%, P < 0.01), associated with a 2.45-fold increase (P < 0.05) in myocardial cGMP concentration at 10 min after reperfusion. ODQ abolished the infarct size-limiting effect of AM (28.9 ± 4.3%). These data provide the first evidence that AM increases NO bioavailability in intact murine myocardium and confirm that the NO/sGC/cGMP pathway is central to the cytoprotective action of AM against ischaemia–reperfusion injury.     

Impaired endothelial progenitor cell function predicts age-dependent carotid intimal thickening

Objectives  We investigated whether qualitative or quantitative alterations of the endothelial progenitor cell (EPC) pool predict age-related structural vessel wall changes. Background  We have previously shown that age-related endothelial dysfunction is accompanied by qualitative rather than quantitative changes of EPCs. Animal studies suggest that impaired EPC functions lead to accelerated arterial intimal thickening. Methods  Intima-media thickness (IMT) was measured in the common carotid artery in our previously published groups of younger (25 ± 1 years, n = 20) and older (61 ± 2 years, n = 20) healthy non-smoking volunteers without arterial hypertension, hypercholesterolemia, and diabetes mellitus. Endothelial progenitor cells (EPCs, KDR⁺/CD34⁺ and KDR⁺/CD133⁺) were counted in peripheral blood using flow cytometry. In ex vivo expanded EPCs, the function was determined as chemotaxis to VEGF, proliferation, and survival. Results  We observed thicker IMT in older as compared to younger subjects (0.68 ± 0.03 mm Vs. 0.48 ± 0.02 mm, P < 0.001). Importantly, there were significant inverse univariate correlations between IMT, EPC chemotaxis, and survival (r = −0.466 P < 0.05; r = −0.463, P < 0.01). No correlation was observed with numbers of circulating EPCs. Multivariate regression analysis revealed that age, mean arterial pressure and migration of EPCs were independent predictors of IMT (R ² = 0.58). Conclusion  Impaired EPC function may lead to accelerated vascular remodeling due to chronic impairment of endothelial maintenance. Returned for 1. Revision: 13 December 2007 1. Revision received: 16 June 2008 Returned for 2. Revision: 20 June 2008 2. Revision received: 17 July 2008     

Lifestyle modification programs protecting cardiovascular health in Germany and Sweden. A qualitative interview study

A large amount of evidence, including neurohumoral, inflammatory, and metabolic physiological adaptations, emphasize the importance of the individual lifestyle as a public health concern. The related burden of chronic diseases in the European Union, which could be minimized by appropriate lifestyles, requires consistent transfer of evidence-based prevention guidelines. Due to the epidemiologic importance of cardiovascular diseases and innovative health-promoting strategies in Sweden, a comparative analysis between German and Swedish practices preventing cardiovascular events in high-risk populations is presented in this paper. This qualitative analysis demonstrates that lifestyle-related risk and protective factors based on smoking, physical activity, nutrition, and psychosocial determinants are of growing importance in cardiac death prevention. Especially in Sweden, behavioral prevention is joined by condition prevention. In Germany, intersectoral rehabilitation concepts improve patient adherence to behavioral recommendations but interdisciplinary communication between different health experts needs to be improved. The health-promoting hospital composes a health professional??s interface, which is based on the understanding that behavioral risk factors are not only highly interrelated, but also require sophisticated healthcare delivery to optimize health management effectiveness.     

Central retinal artery occlusion as a first sign of atrial fibrillation: A 3‐year retrospective single‐center analysis

BackgroundCentral retinal artery occlusion ((C)RAO) is known to be associated with stroke and/or atrial fibrillation (AF). Nevertheless, patients often present at the ophthalmologist initially and it is unknown how many of these receive an adequate cardiological/neurological work‐up (CWU/NWU), including a 24 h‐Holter‐ECG.HypothesisHypothesis of this study was that patients with (C)RAO do not undergo CWU on regular basis and that new‐onset AF is more often detected in patients with CWU.Methods and resultsWe performed a retrospective analysis of n = 292 consecutive patients who presented at an ophthalmology department with the diagnosis of (C)RAO during a 3‐year period. After excluding patients with known AF, meeting exclusion criteria, inability to comply with the protocol, missed land phoneline, or death during follow‐up a total of 174 patients were enrolled; mean follow‐up was 20 ± 12 months. The CHA₂DS₂‐VASc score of the cohort was 5.3 ± 1.4. Our analysis revealed that only 50.6% of patients received a CWU including a single Holter‐ECG after the index‐event. In 12.6% cases new‐onset AF was diagnosed, while the rate was higher in patients with CWU compared to patients without CWU (18.2 vs. 7.0%; p = 0.26). Evaluation of oral anticoagulation (OAC) therapy showed that only 66% of patients with AF were treated according to guidelines.ConclusionOnly half of patients with (C)RAO underwent CWU. Despite minimal monitoring, rate of new diagnosed AF was high. Our results confirm that (C)RAO identifies a high‐risk population for AF. These results illustrate the importance to implement standardized CWU in (C)RAO patients presenting at the ophthalmologist.