Background: Right ventricular (RV) dysfunction is recognized as a cardinal prognostic marker in systolic heart failure patients. Conflicting data exist on the interaction of RV function and left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT). This prospective monocentric trial was set up to assess the predictive value of baseline RV function and corresponding RV-pulmonary artery (PA) coupling on LV reverse remodeling after CRT. Methods: 110 patients with a CRT indication were prospectively enrolled. RV function and RV-PA interaction were analyzed at baseline using echocardiographic and invasive pressure-volume loop catheter approach. The primary endpoint was reverse LV remodeling (CRT-responder) defined as a reduction in LV end-systolic volume of >= 15% at 6 months. Results: Responders had higher RV-PA coupling ratios (single-beat end-systolic elastance/PA elastance: Ees/Ea) at baseline, which corresponded to smaller RVs with better ejection fraction and lower afterload. After multivariate adjustment, the baseline Ees/Ea remained an independent predictor for LV response (OR 14.0 [1.5-130.8], p = 0.021). Normal coupling (Ees/Ea >= 1) was associated with higher responder rates (RR) (86%). Progressive uncoupling was associated with lower LV-RR (Ees/Ea <= 1-0.5: 57%, and Ees/Ea < 0.5: 32%, p < 0.001), corresponded with higher degrees of LV impairment and severity of mitral regurgitation, and was independently associated with an adverse outcome. Conclusions: A higher baseline RV-PA coupling, reflecting a lower degree of LV-induced pulmonary hypertension and secondary RV-dysfunction, is associated with an improved LV-reverse remodeling and is independently associated with better prognosis. The value of RV-PA ratio as potential guide for CRT patient selection warrants further investigation. (C) 2018 Elsevier B.V. All rights reserved.\

Purpose: Animal-based studies have shown that oestrogen protects against vascular injury, atherosclerosis and cardiac hypertrophy. The underlying mechanism is very complex and includes antiapoptotic, antiproliferative effects of oestrogen, as well as the regulation of the components of the renin-angiotensin-system (RAS). Postmenopausal women have a very high risk to suffer from stroke during atrial fibrillation. In this study, we addressed basic questions regarding oestrogen effects on the atrial myocardium with the special focus on interactions between oestrogen, member of RAS, and RAS-associated downstream effectors. Methods: Right atrial appendages were obtained from 40 patients undergoing heart surgery for coronary artery bypass graft or mitral/aortic valve replacement. Human atrial tissue slices were prepared and cultivated for up to 24h in the presence of 17 beta oestradiol (E2) in the concentrations 1, 10, and 100 nM. The molecular changes were studied at the transcriptional level using real time-PCR (n=10) and immunoblots (n=6). Results: The analyses on the expression of oestrogen receptors alpha (ERα) and beta (ERβ) revealed that ERα is a dominant receptor in the atrial tissue. In the postmenopausal women (age 72±8, n=14) the amounts of Eα- and Eβ-mRNAs remained at the similar level than in men (age 69±5, n=10). The exposure to E2 caused a dose-dependent activation of MAP kinases, which indicated involvement of Eα in the oestrogen signalling. Furthermore, the treatment with E2 resulted in the significant downregulation of ACE-mRNA (75±8% vs. 100% control, p<0.05) and an increase in the ACE2-mRNA (137±16%; p<0.05). This shift in the regulation was dose-dependent and most clearly at the highest concentration of E2. Additionally, an inhibitory effect on the expression of intracellular adhesion molecule (ICAM-1) was observed. E2 caused a decrease in the ICAM-1 mRNA (75±12% vs. 100% of control, p<0.05) and protein level (42±9% vs. 100% of control, p<0.05). Moreover, E2 affected the expression of pro-oxidative LOX-1 by 30% at the-mRNA (p<0.05) and by 44% at the protein level (p<0.01). The possible participation of NF-κB signalling was monitored by phosphorylation status of inhibitory molecule I-κB. No activation of NF-κB in atrial tissue accompanied the treatment with E2. Conclusions: Our study demonstrates that oestrogen administration might achieve protective effects on the atrial tissue by downregulation of ACE. These findings may help to explain why in particular postmenopausal women are prone to the development of structural and prothrombogenic atrial alterations.

HAS-BLED would allow clinicians to make an informed assessment of their individual patient's potential risk for bleeding per se (rather than guesswork) to be balanced against the stroke risk when management options are being considered. 108

Activated factor X (FXa) is an important player in the coagulation cascade responsible for thrombin generation, which is activated during atrial fibrillation. Increasing evidence suggests that FXa influences cell signalling in various cell types by activating protease-activated receptors (PARs). It is so far not known if molecular effects of FXa affect atrial signal transduction. To study the effects of FXa, human atrial tissue slices were cultivated with FXa up to 24h. Additionally, rapid pacing was applied at 4Hz to resemble atrial fibrillation. The inhibitory impact of FXa antagonist (Rivaroxaban), protease-activated receptor 1 antagonist (SCH79797), and protease-activated receptor 2 antagonist (GB83) were analysed under experimental conditions. The exposure of atrial tissue to FXa resulted in the 1.7 fold upregulation of PAR2-mRNA, activation of MAP kinases (ERK1/2) and NF-κB signalling. Furthermore FXa increased the expression of adhesion molecule ICAM-1 (1.82 ± 0.20), chemokine IL-8 (1.94 ± 0.20), as well as prothrombotic molecule PAI-1 (1.52 ± 0.17). The combination of rapid pacing and FXa caused significant upregulation of PAR1 (2.82 ± 0.22), PAR2 (2.66 ± 0.40), ICAM-1 (2.13 ± 0.25), IL-8 (2.22 ± 0.24), LOX-1 (2.59 ± 0.35), and PAI-1 (2.65 ± 0.52) at the mRNA level. Rivaroxaban and GB83 prevented upregulation of PARs, ICAM-1, LOX-1, IL-8, and activation of MAP kinases. The elevation in the expression of PAI-1 was hindered in the presence of SCH79797, or Rivaroxaban. The present study indicates that FXa mediates inflammatory signalling in atrial tissue. Importantly, FXa and tachyarrhythmia act synergistically to increase expression of protease-activated receptors and inflammatory mediators. Rivaroxaban prevented effectively FXa-induced molecular effects in human atrial tissue particularly during rapid pacing.

Background One-lung ventilation (OLV) results in alveolar proinflammatory effects, whereas their extent may depend on administration of anesthetic drugs. The current study evaluates the effects of different volatile anesthetics compared with an intravenous anesthetic and the relationship between pulmonary and systemic inflammation in patients undergoing open thoracic surgery. Methods Sixty-three patients scheduled for elective open thoracic surgery were randomized to receive anesthesia with 4 mg · kg⁻¹ · h⁻¹ propofol (n = 21), 1 minimum alveolar concentration desflurane (n = 21), or 1 minimum alveolar concentration sevoflurane (n = 21). Analgesia was provided by remifentanil (0.25 μg · kg⁻¹ · min⁻¹). After intubation, all patients received pressure-controlled mechanical ventilation with a tidal volume of approximately 7 ml · kg ideal body weight, a peak airway pressure lower than 30 cm H₂O, a respiratory rate adjusted to a Paco2 of 40 mmHg, and a fraction of inspired oxygen lower than 0.8 during OLV. Fiberoptic bronchoalveolar lavage of the ventilated lung was performed immediately after intubation and after surgery. The expression of inflammatory cytokines was determined in the lavage fluids and serum samples by multiplexed bead-based immunoassays. Results Proinflammatory cytokines increased in the ventilated lung after OLV. Mediator release was more enhanced during propofol anesthesia compared with desflurane or sevoflurane administration. For tumor necrosis factor-α, the values were as follows: propofol, 5.7 (8.6); desflurane, 1.6 (0.6); and sevoflurane, 1.6 (0.7). For interleukin-8, the values were as follows: propofol, 924 (1680); desflurane, 390 (813); and sevoflurane, 412 (410). (Values are given as median [interquartile range] pg · ml⁻¹). Interleukin-1β was similarly reduced during volatile anesthesia. The postoperative serum interleukin-6 concentration was increased in all patients, whereas the systemic proinflammatory response was negligible. Conclusions OLV increases the alveolar concentrations of proinflammatory mediators in the ventilated lung. Both desflurane and sevoflurane suppress the local alveolar, but not the systemic, inflammatory responses to OLV and thoracic surgery.

Cardiovascular diseases (CVD) and, in particular, coronary artery disease (CAD) are the leading causes of death in developed countries, especially in the elderly population. Males exhibit a higher risk for cardiovascular events than women. The pericardial fluid (PF) is in direct contact with the epicardial sections of the coronary arteries and the perimyocardium. A systematic analysis of gender-specific or age-related differences in angiotensin-related pathways like bradykinin metabolism however, has not been performed in the PF so far. Therefore, the amounts of angiotensin-converting enzyme (ACE) and the rate of the degradation of bradykinin (BK) and the amounts/activity of major BK-degrading enzymes, aminopeptidase N (APN) and dipeptidyl-aminopeptidase IV (DPIV), were assessed in the pericardial fluid (PF) of 44 patients undergoing coronary artery bypass grafting. We found BK being degraded within the PF. Interestingly, there was an age-dependent decrease in the amounts of ACE protein in women. In elderly women, ACE/APN and ACE/DPIV ratios were substantially reduced to 41.4% or 29.4% respectively (p<0.05). In contrast, an age-dependent decline of ACE protein and ACE/protease ratios were not found in men. In men and women, total BK degradation correlated with age (r=0.5; p=0.021) further supporting a switch in BK metabolising enzymes in elderly women. Thus, we can show age- and gender-dependent differences in BK metabolism within the PF in patients with coronary artery disease. The present finding that the expression of ACE is lowest in elderly women, despite the presence of similar BK degradation, might help to explain the potentially reduced therapeutic effects of ACE inhibitors in elderly women.

BACKGROUND:Atrial fibrillation (AF) is associated with oxidative stress within the fibrillating atrial myocardium. Experimental studies suggest that reduced levels of nitric oxide (NO) caused by down-regulation of the NO synthase (eNOS) contribute to the development of prothrombotic endocardial remodeling in AF. This study was designed to determine the endocardial expression of eNOS in atrial tissue samples from patients with and without AF.METHODS:Tissue microarrays were used to analyze right atrial tissue specimens obtained from 234 patients (38 with AF; 196 with sinus rhythm) for differences in atrial eNOS expression. In selected patients, immunohistological results were confirmed by Western blotting.RESULTS:Immunohistochemical analyses showed that eNOS is expressed by endocardial cells and myocytes. However, endocardial expression of eNOS was not independently related to AF per se. There was no difference between paroxysmal and persistent AF. Clinical factors like gender (P=.05) and coronary artery disease (P=.06) were associated with down-regulation of eNOS. Interestingly, diabetes mellitus (P=.02) was associated with an up-regulation of endocardial eNOS, whereas other risk factors for thromboembolic events did not influence eNOS levels. Multivariable analysis showed that eNOS expression is influenced by interactions between diabetes mellitus and AF (P=.09) as well as by interactions between gender and AF (P=.04). Lowest levels of eNOS were found in women with AF.CONCLUSION:AF does not independently effect atrial eNOS expression in humans. Due to the nonuniform regulation of endocardial eNOS expression, it appears unlikely that down-regulation of eNOS is a final common pathway for the development of prothrombotic endocardial remodeling, since classical risk factors for thromboembolic events do not reduce endocardial eNOS protein.

BACKGROUND:Preoperative carotid sonography with consecutive preventive strategies might reduce stroke risk during cardiac surgery. Since routine sonography in all patients may be unfeasible, an approach to examine preselected patients was investigated.METHODS:A prognostic model predicting carotid disease was developed using the clinical data of 1,768 routinely examined patients. It recommended 1,018 of 4,814 patients of a following collective for selective sonography. Patients recommended for preoperative sonography were compared to those selected in clinical practice.RESULTS:Besides the evaluated predictor variables, a history of syncope/cardiogenic shock and of pulmonary disease was associated with patient selection for sonography in clinical practice, even though both variables were not associated with severe carotid disease. In patients who underwent sonography, although this was not recommended by the prognostic model, severe carotid disease was estimated lower than what was actually detected, suggesting a change in relative relevance of predicting variables along with the change in frequencies of patients' cardiovascular characteristics.CONCLUSION:Prognostic models for selective screening before cardiac surgery may require reevaluation over time, especially when baseline characteristics used for prediction have changed. Criteria used in clinical practice to select patients for screening may differ from those recommended by investigational studies.

Background. Self-management improves oral anticoagulation control. Here we provide data of a preplanned interim analysis of very low-dose early self-controlled anticoagulation.Methods. In a prospective, randomized, multicenter trial, 1,137 patients performed low-dose international normalized ratio (INR) self-management with a target INR range of 1.8. to 2.8 for aortic valve replacement recipients and 2.5 to 3.5 for mitral or double valve replacement recipients for the first six postoperative months. Thereafter, 379 patients continued to achieve the aforementioned INR target range (LOW group), whereas the INR target value was set at 2.0 (range, 1.6 to 2.1) for the remaining patients with aortic valve replacement and 2.3 (range, 2.0 to 2.5) for the remaining patients with mitral valve or double valve replacement. One half of this latter group had to check their INR values once a week (VL1 group) the other half twice a week (VL2 group). Patients were followed up for 24 months.Results. Beyond study month six, the incidence of thromboembolic events that required hospital admission was 0.58%, 0.0%, and 0.58% in the LOW, VL1, and VL2 groups, respectively (p = 0.368). The incidence of bleeding events per patient-year was 1.16%, 1.07%, and 0.58% in the LOW, VL1, and VL2 groups, respectively (p = 0.665). Mortality rate did not differ among study groups.Conclusions. Data demonstrate the efficacy and safety of very low-dose INR self-management. (Ann Thorac Surg 2010;90:1487-94) (C) 2010 by The Society of Thoracic Surgeons

L’échographie carotidienne préopératoire avec des stratégies préventives pourrait réduire le risque d’AVC pendant la chirurgie cardiaque. Puisque l’échographie systématique chez tous les malades n’est pas réalisable, une approche d’examen sélectif a été étudiée. Un modèle pronostique prévoyant l’atteinte carotidienne a été développé à partir des données cliniques de 1.768 patients examinés en routine. Il préconisait l’échographie sélective chez 1.018 de 4.814 malades d’un collectif de suivi. Les malades recommandés pour l’échographie préopératoire étaient comparés à ceux choisis dans la pratique clinique. A côté des variables prédictives évaluées, une histoire de syncope/choc cardiogénique et de maladie pulmonaire était associée au choix des malades pour l’échographie en pratique clinique, même si les deux variables n’étaient pas associées à des lésions carotidiennes graves. Chez les malades qui ont eu une échographie, bien qu’elle n’ait pas été recommandée par le modèle pronostique, les lésions carotidiennes graves étaient estimées moindres que ce qui a été détecté réellement, ce qui suggère un changement de la pertinence relative des variables prédictives avec le changement des fréquences des caractéristiques cardio-vasculaires des patients. Les modèles pronostiques pour le dépistage sélectif avant chirurgie cardiaque doivent être réévalués avec le temps, particulièrement quand les caractéristiques de base utilisées pour la prévision changent. Les critères utilisés en pratique clinique pour choisir les malades à examiner peuvent différer de ceux recommandés par les études cliniques.

Objective: The implantation of cardiac resynchronization/defibrillation devices (CRT-Ds) increasingly is used in patients with congestive heart failure and left bundle-branch block. There are no data on the effects of anesthesia and surgery on outcome after implantation.Design: A retrospective, observational study; postoperative survey.Setting: University hospital.Participants: Three hundred forty-one patients (258 men/83 women, 63 +/- 9 years) with congestive heart failure and left bundle-branch block who underwent CRT-D implantation in 1996 to 2005.Measurements and Main Results: Perioperative data were retrieved from the patients' records. Cardiologists caring for the patients were contacted to obtain information on current New York Heart Association (NYHA) status and mortality after CRT-D implantation. Preoperatively, 45 patients were classified as NYHA II, 246 as NYHA III, and 50 as NYHA IV. CRT was performed via thoracotomy in 100 and transvenously in 241 cases. General anesthesia (propofol or sevoflurane and remifentanil) was performed in 273 and local anesthesia (lidocaine) in 68 patients. Hypotension occurred mainly during general anesthesia (43% v 4%). The 30-day mortality was 0%. The postoperative survey started in 2006 and was completed by 215 patients. The mean survival time was 77 months; 151 patients survived the study period. Outcome was not influenced by local and general anesthesia. Presence of preoperative NYHA class >II (odds ratio [OR] = 1.6, confidence interval [CI] = 0.5-5.1), mitral regurgitation (OR = 2.5, CI = 1.2-5.5), and serum creatinine >1.1 mg/dL (OR = 3.0, CI = 1.5-6.2) resulted in an inferior prognosis.Conclusions: In patients with severely impaired cardiac function, general anesthesia for the implantation of a biventricular pacing device can be used with justifiable risk. The method of anesthesia did not influence outcome. (C) 2010 Elsevier Inc. All rights reserved.

Detection of dyssynchrony is primarily performed by EKG and/or tissue Doppler echocardiography, sampling the heart in selected basal segments. Limited approaches for dyssynchrony have been performed by cardiovascular MRI (CMR).

Objective: An elastic ventricular restraint device has been developed for patients with heart failure who remain symptomatic despite treatment with standard therapies. The safety and efficacy of this device are under clinical investigation. Six-month data for the first 51 patients treated worldwide are reported. We hypothesize that the Paracor HeartNet device (Paracor Medical, Sunnyvale, Calif), placed through a minithoracotomy in patients with severe dilated cardiomyopathy, improves clinical and functional status.Methods: Fifty-one patients with an ejection fraction of 35% or less, with a New York Heart Association class II or III, and receiving optimal medical therapy for at least 3 months, were selected at 15 sites (3 in Europe, 12 in the United States) to undergo implantation of the HeartNet device through a minithoracotomy. Patients were evaluated at baseline and at 6-month follow-up by echocardiography, the 6-minute walk test, cardiopulmonary exercise testing (partial oxygen pressure in mixed venous blood), New York Heart Association class, and (in the United States) the Minnesota Living with Heart Failure questionnaire.Results: The average age was 52 years (30-73 years), with a preponderance of men and nonischemic cause of heart failure. Implantation was accomplished in 50 of 51 patients (98%). Adverse events included 2 in-hospital deaths secondary to pulmonary complications (4%), additional pulmonary complications in 7 patients (14%), arrhythmia in 14 patients (27%), epicardial laceration in 2 patients (4%), and empyema in 1 patient (2%). Six-month data demonstrated significant improvement in the 6-minute walk test (+65.7, P = .002) and Minnesota Living with Heart Failure scores (-15.7, P = .002) and improvement in echocardiographic findings.Conclusion: The Paracor HeartNet device can be reliably implanted in patients with heart failure and marked reduction of left ventricular function. These data suggest a functional and clinical benefit, with a trend toward reverse remodeling, and support the conduct of a randomized controlled pivotal trial.

Accumulating evidence links calcium-overload and oxidative stress to atrial remodeling during atrial fibrillation (AF). Furthermore, atrial remodeling appears to increase atrial thrombogeneity, characterized by increased expression of adhesion molecules. The aim of this study was to assess mitochondrial dysfunction and oxidative stress-activated signal transduction (nuclear factor-kappa B [NF-kappa B], lectin-like oxidized low-density lipoprotein receptor [LOX-1], intercellular adhesion molecule-1 [ICAM-1], and hemeoxgenase-1 [HO-1]) in atrial tissue during AF. Ex vivo atrial tissue from patients with and without AF and, additionally, rapid pacing of human atrial tissue slices were used to study mitochondrial structure by electron microscopy and mitochondrial respiration. Furthermore, quantitative reverse transcription polymerase chain reaction (RTPCR), immunoblot analyses, gel-shift assays, and enzyme-linked immunosorbent assay (ELISA) were applied to measure nuclear amounts of NF-kappa B target gene expression. Using ex vivo atrial tissue samples from patients with AF we demonstrated oxidative stress and impaired mitochondrial structure and respiration, which was accompanied by nuclear accumulation of NF-kappa B and elevated expression levels of the adhesion molecule ICAM-1 and the oxidative stress-induced markers HO-1 and LOX-1. All these changes were reproduced by rapid pacing for 24 hours of human atrial tissue slices. Furthermore, the blockade of calcium inward current with verapamil effectively prevented both the mitochondrial changes and the activation of NF-kappa B signaling and target gene expression. The latter appeared also diminished by the antioxidants apocynin and resveratrol (an inhibitor of NF-kappa B), or the angiotensin II receptor type 1 antagonist, olmesartan. This study demonstrates that calcium inward current via L-type calcium channels contributes to oxidative stress and increased expression of oxidative stress markers and adhesion molecules during cardiac tachyarrhythmia.

We present the case of successful resection of a giant aneurysm of the LAD presenting with recurrent severe haemoptysis in a 72-year old man. He was admitted to a regional hospital with fever, recurrent bloody sputum, weight loss and left sided chest pain, and developed respiratory failure requiring ventilation. Investigations are summarised and reviewed and the diagnosis was eventually reached by TTE, CT and MRI scans, confirmed by coronary angiography. Successful emergency surgery to resect the aneurysm and put a vein graft to the LAD is described. The presentation and management of coronary giant aneurysm is reviewed.

Cardiovascular mortality accounts for about 50% of all deaths in rheumatoid arthritis, which appears to be mainly related to an increased prevalence of ischemic heart disease [ 1 Caplan A. Certain unusual radiological appearances in the chest of coalminers suffering from rheumatoid arthritis. Thorax. 1953; 8: 29-37 Crossref PubMed Scopus (215) Google Scholar , 2 Rimal B. Greenberg A.K. Rom W.N. Basic pathogenetic mechanisms in silicosis: current understanding. Curr Opin Pulm Med. 2005; 11: 169-173 Crossref PubMed Scopus (231) Google Scholar , 3 Kitas G. Banks M.J. Bacon P.A. Cardiac involvement in rheumatoid disease. Clin Med. 2001; 1: 18-21 Crossref PubMed Scopus (78) Google Scholar , 4 Messner E.M. Foster C.S. Destructive corneal and scleral disease associated with rheumatoid arthritis. Medical and surgical management. Cornea. 1995; 14: 408-417 Crossref PubMed Scopus (73) Google Scholar ]. Although commonly found at autopsy, myocardial and valvular involvement in rheumatoid arthritis is rarely clinically apparent. The association of rheumatoid arthritis with pneumoconiosis caused by inhalation of silica and non-asbestos silicate minerals is referred to as Caplan's syndrome [ [1] Caplan A. Certain unusual radiological appearances in the chest of coalminers suffering from rheumatoid arthritis. Thorax. 1953; 8: 29-37 Crossref PubMed Scopus (215) Google Scholar ]. Although rheumatoid arthritis is relatively common in the general population, Caplan's syndrome is rare. This report describes an extended, unique manifestation of Caplan's syndrome.