Valvular cardiomyopathy in aortic valve regurgitation correlates with myocardial fibrosis

Objective: At the tissue level, disruption of the extracellular matrix network leads to irreversible cardiac fibrosis, which contributes to myocardial dysfunction. At the myocyte level, downregulation of beta-adrenoceptors (beta-AR) reduces adaptation to increased workload. The aim of our study was to analyse the correlation between myocardial fibrosis and beta-AR sensitivity in patients with aortic valve (AV) disease. Methods: A total of 92 consecutive patients who underwent elective AV surgery between 2017–2019 were included in our study (51 with aortic regurgitation (AR-group); 41 with aortic stenosis (AS-group) and left ventricular (LV) biopsies were obtained intraoperatively. In vitro force contractility testing was performed by measuring beta-AR sensitivity (−log EC50[ISO]). In parallel, a quantitative analysis of myocardial fibrosis burden was performed. Results: Mean age at the time of AV surgery was not statistically different in both groups (AR: 53.3 ± 15.3 years vs. AS: 58.7 ± 17.0 years; p = 0.116). The LV end-diastolic diameter was significantly enlarged in the AR-group when compared to the AS-group (59.4 ± 15.6 vs. 39.7 ± 21.2; p < 0.001). Analysis of beta-AR sensitivity (AR: −6.769 vs. AS: −6.659; p = 0.316) and myocardial fibrosis (AR: 8.9% vs. AS: 11.3%; p = 0.284) showed no significant differences between patients with AS and AR. There was no correlation between myocardial fibrosis and beta-AR sensitivity in the whole study cohort (R = 0.1987; p = 0.100) or in the AS-subgroup (R = 0.009; p = 0.960). However, significant correlation of fibrosis and beta-AR sensitivity was seen in AR-patients (R = 0.363; p = 0.023). Conclusion: More severe myocardial fibrosis was associated with reduced beta-AR sensitivity in patients presenting with AR but not with AS. Therefore, our results suggest that in patients with AR, cellular myocardial dysfunction is present and correlates with the extent of myocardial fibrosis in the myocardium

Left atrial strain predicts the rhythm outcome in patients with persistent atrial fibrillation undergoing left atrial cryoablation during minimally invasive mitral valve repair

ObjectivesPatients with atrial fibrillation (AF) have lower left atrial (LA) strain, which is a predictor for LA function. Here, we evaluated the prognostic value of LA strain to predict the rhythm outcome in patients with persistent AF undergoing LA cryoablation concomitant to minimally invasive mitral valve repair.MethodsBetween 01/2016 and 12/2020, 72 patients with persistent AF underwent LA cryoablation during minimally invasive mitral valve surgery. All patients received a complete LA lesion set and left atrial appendage (LAA) closure with a clip. All patients received preoperative transthoracic echocardiography (TTE) with LA and left ventricular strain measurements. Preoperative LA and LV strain analysis was correlated with postoperative rhythm outcome.ResultsThe mean age of the patients was 66.9 ± 7.2 years, of whom 42 (58%) were male patients. No major ablation-related complications occurred in any of the patients. Successful LAA closure was confirmed by intraoperative echocardiography in all patients. The 1-year survival rate was 97%. Freedom from AF at 12 months was 72% and 68% off antiarrhythmic drugs. Preoperative LA strain values were statistically significantly higher in patients with freedom from AF at 12 months of follow-up (12.7% ± 6.9% vs. 4.9% ± 4.1%, p = 0.006). Preoperative LV strain value was not associated with postoperative rhythm outcome. In multivariate logistic regression analysis, LA strain (p &lt; 0.001) and AF duration (p = 0.017) were predictors for freedom from AF at 12 months of follow-up.ConclusionsIn our study, LA strain analysis predicted the rhythm outcome in patients with persistent AF undergoing concomitant surgical AF ablation. In the future, LA strain might be a useful tool to guide decision-making on ablation strategies in patients with persistent AF

Prognostic impact of implantable cardioverter defibrillators and associated adverse events in patients with continuous flow left ventricular assist devices

ObjectivesImplantation of implantable cardioverter defibrillators (ICD) reduces the risk of all-cause mortality in symptomatic heart failure (HF) patients with severe left ventricular (LV) dysfunction. Nevertheless, the prognostic impact of ICD therapy in continuous flow left ventricular assist device (LVAD) recipients remains controversial.Methods162 consecutive HF patients, who underwent LVAD implantation at our institution between 2010 and 2019, were categorized according to the presence (n = 94, ICD-group) or absence (n = 68, Control-group) of ICDs. Apart from clinical baseline and follow-up parameters, adverse events (AEs) related to ICD therapy and overall survival rates were retrospectively analyzed.ResultsOut of 162 consecutive LVAD recipients 79 patients (48.8%) were preoperatively categorized as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile ≤2. The prevalence of severe HF symptoms and preoperative use of short-term circulatory support devices (54.4% vs. 13.8%, p &lt; 0.001) was higher within the Control-group, although baseline severity of LV and RV dysfunction was similar. Apart from an increased prevalence of perioperative right heart failure (RHF) within the Control-group (45.6% vs. 17.0%; p &lt; 0.001), procedural characteristics and perioperative outcome were similar. Overall-survival during a median follow-up of 14 (3.0–36.5) months was similar within both groups (p = 0.46). During the first 2 years after LVAD implantation 53 ICD-related AEs occurred within the ICD-group. Thereof, lead-dysfunction occurred in 19 patients and unplanned ICD-reintervention in 11 patients. Furthermore, in 18 patients appropriate shocks without loss of consciousness occurred, whereas inappropriate shocks occurred in 5 patients.ConclusionICD therapy in LVAD recipients was not associated with a survival benefit or reduced morbidity after LVAD implantation. Conservative ICD-programming seems to be justified to avoid ICD-related complications and „awake shocks” after LVAD implantation

Minimal access median sternotomy for aortic valve replacement in elderly patients

BACKGROUND: We report our clinical experience with a approach for aortic valve replacement (AVR) via minimal access skin incision and complete median sternotomy. This approach was used in patients with higher age and multiple co-morbidities, facilitating an easy access with short bypass and cross clamp times. It was especially performed in patients asking for an excellent cosmetic result, who did not qualifying for minimally-invasive AVR via partial upper sternotomy. METHODS: AVR via minimal-access median sternotomy, was performed in 58 patients between 01/2009 and 11/2011. Intra- and postoperative data including cross clamp time, cardiopulmonary bypass time, mortality, stroke, pacemaker implantation, re-operation for bleeding, ventilation time, ICU and hospital stay, wound infection, sternal dehiscence or fracture and 30 day mortality were collected. RESULTS: Mean patients age was 76.1 +/−9.4 years, 72% were female. Minimal-access AVR could be performed with a mean length of midline skin incision of 7.8 cm. Aortic cross-clamping time was 54.6 +/−6.3 min, cardiopulmonary bypass time 71.2+/−11.3 min and time of surgery 154.1 +/−26.8 min. Re-operation for bleeding had to be performed in 1 case (1.7%). There were no strokes or pacemaker implantations needed. Mean ventilation time was 4.5 h, ICU stay was 2 days and mean length of hospital stay was 6 days. 6 months follow up showed mortality of 0% and no sternal dehiscence or wound infection was observed. CONCLUSION: Minimal-access AVR via complete median sternotomy can be performed safely,in this elderly patient cohort without adding additional operative risk compared to conventional AVR. By avoidiance of large skin incisions this approach combines excellent cosmetic results with fast surgery time and excellent postoperative recovery

A Network-Based Multi-Target Computational Estimation Scheme for Anticoagulant Activities of Compounds

BACKGROUND: Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. METHODOLOGY: We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. CONCLUSIONS: This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by combining network efficiency analysis with scoring function from molecular docking

Successful extracorporeal membrane oxygenation weaning after cardiac resynchronization therapy device implantation in a patient with end-stage heart failure.

We present the case of a 46-year old male with end-stage heart failure due to ethyltoxic cardiomyopathy. The patient did not meet the criteria for heart transplantation and declined left ventricular assist device implantation. We decided to conduct cardiac resynchronization therapy defibrillator (CRT-D) implantation. Under general anaesthesia for CRT-D implantation, cardiac function worsened. Due to deteriorating haemodynamics, CRT-D implantation was aborted and emergent veno-arterial extracorporeal membrane oxygenation (ECMO) implantation was performed. Subsequent weaning from ECMO was not possible. We decided to proceed with CRT-D implantation while still on ECMO support. With biventricular stimulation, cardiac function improved promptly and the patient could be weaned from ECMO the same day

Complete Left-Atrial Lesion Set versus Pulmonary Vein Isolation Only in Patients with Paroxysmal AF Undergoing CABG or AVR

Background and Objectives: In patients with paroxysmal atrial fibrillation (AF) undergoing CABG or aortic valve surgery, many surgeons are not willing to open the left atrium to perform a complete left-sided Cox-Maze lesion set. Pulmonary vein isolation (PVI) is often favored in those patients. We investigated the outcome of patients with isolated pulmonary vein isolation compared to those receiving an extended left atrial (LA) lesion set. Materials and Methods: Between 2003 and 2016, 817 patients received concomitant surgical AF ablation in our institution. A total of 268 patients with paroxysmal AF were treated by surgical ablation concomitant to AVR or CABG. Of those, 86 patients underwent a complete left-sided lesion set, while 182 patients were treated with an isolated pulmonary vein isolation. The primary endpoint was freedom from atrial fibrillation at 12 months&rsquo; follow-up. Results: There were no statistically significant differences regarding baseline characteristics. No major ablation-related complications were observed in any of the groups. In the PVI group, three patients (1.6%) had an intraoperative stroke, while two (2.3%) patients experienced a stroke in the LA ablation group (p = 0.98). In-hospital mortality was 3.4% in the PVI group, and 2.8% in the extended LA group (p = 0.33). Freedom from AF at 12 months&rsquo; follow-up was 76% in the extended LA ablation group and 70% in the PVI group, showing no statistically significant difference (p = 0.32). Conclusion: Surgical AF ablation concomitant to CABG or AVR in patients with paroxysmal AF is safe and effective. There was no statistically significant difference between the compared lesion sets in terms of freedom from AF, survival or stroke rate after 12 months

Impact of phosphodiesterases PDE3 and PDE4 on 5-hydroxytryptamine receptor4-mediated increase of cAMP in human atrial fibrillation

Atrial fibrillation (AF)-associated remodeling includes contractile dysfunction whose reasons are only partially resolved. Serotonin (5-HT) increases contractile force and causes arrhythmias in atrial trabeculae from patients in sinus rhythm (SR). In persistent atrial fibrillation (peAF), the force responses to 5-HT are blunted and arrhythmic effects are abolished. Since force but not arrhythmic responses to 5-HT in peAF could be restored by PDE3 + PDE4 inhibition, we sought to perform real-time measurements of cAMP to understand whether peAF alters PDE3 + PDE4-mediated compartmentation of 5-H