Use of Cardiac Biomarkers for Monitoring Improvement of Left Ventricular Function by Immunoadsorption Treatment in Dilated Cardiomyopathy

Immunoadsorption and subsequent administration of intravenous immunoglobulin (IVIG) have shown beneficial effects on cardiac function and symptoms in patients with dilated cardiomyopathy. Biomarkers play an emerging role in disease monitoring and outcome prediction of heart failure (HF) patients. We aimed to analyze cardiac biomarkers as predictor for improvement of left ventricular (LV) function after immunoadsorption treatment in dilated cardiomyopathy (DCM). Thirty-one patients with dilated cardiomyopathy on optimized HF pharmacotherapy received a single cycle of immunoadsorption for five days followed by IVIG administration. Left ventricular ejection fraction (LVEF) and heart failure biomarkers (hs troponin T, hs troponin I, NT-proBNP and sST2) were evaluated before treatment, after the last cycle of immunoadsorption and during a median follow-up of 30.5 months. We correlated HF biomarkers before immunoadsorption and acute changes of HF biomarkers by immunoadsorption with LV improvement during the long-term follow-up. LV function improved significantly after immunoadsorption from 28.0 to 42.0% during the long-term follow-up (p < 0.0001). Evaluation of biomarker levels showed a significant decrease for hs troponin I (from 9.2 to 5.5 ng/L, p < 0.05) and NT-proBNP (from 789.6 to 281.2 pg/mL, p < 0.005). Correlation of biomarker levels before immunoadsorption and LVEF at the long-term follow-up show good results for hs troponin T (r = −0.40, r2 = 0.16, p < 0.05), hs troponin I (r = −0.41, r2 = 0.17, p < 0.05) and sST2 (r = −0.46, r2 = 0.19, p < 0.05). Correlation of biomarker levels before immunoadsorption and the individual increase in LV function was significant for hs troponin T (r = −0.52, r2 = 0.27, p < 0.005) and hs troponin I (r = −0.53, r2 = 0.29, p < 0.005). To imply a tool for monitoring outcome immediately after immunoadsorption treatment, we investigated the correlation of acute changes of biomarker levels by immunoadsorption treatment and individual increase in LV function. A drop in hs troponin T (r = −0.41, r2 = 0.17, p < 0.05) and hs troponin I (r = −0.53, r2 = 0.28, p < 0.005) levels demonstrate a good correlation to improvement in LVEF during the long-term follow-up. Conclusion: Hs troponin T and I levels correlate with LV function improvement during long-term follow-up. Acute decrease of troponins by immunoadsorption treatment is paralleled by individual improvement of LVEF at the long-term follow-up. Thus, troponins could serve as a monitoring tool for the improvement of LV function after immunoadsorption treatment in dilated cardiomyopathy

Add-on Immunoadsorption Shortly-after Optimal Medical Treatment Further Significantly and Persistently Improves Cardiac Function and Symptoms in Recent-Onset Heart Failure—A Single Center Experience

Background: Immunoadsorption and intravenous immunoglobulin (IVIG) administration may have beneficial effects in patients with dilated cardiomyopathy with end-stage heart failure. We investigated the effect of immunoadsorption with subsequent IVIG administration on cardiac function and symptoms in patients on optimal medical treatment (OMT) for heart failure (HF) with recent-onset cardiomyopathy during long-term follow-up. Methods: Thirty-five patients with recent-onset of HF symptoms received intensive guideline-recommended medical HF therapy for 5.2 months. Subsequently, all patients received a single cycle of immunoadsorption for five days followed by IVIG administration. During the 29-month follow-up period, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF) and N-terminal pro brain natriuretic peptide (NT-proBNP) were evaluated. Changes in quality of life (QoL) were assessed using the Minnesota Living with HF Questionnaire. Results: Three months after immunoadsorption, NYHA functional class improved from 2.0 to 1.5 (p < 0.005) and LVEF significantly increased from 27.0% to 39.0% (p < 0.0001). Long-term follow-up of 29 months showed stable NYHA functional class and a further moderate increase in LVEF from 39.0% to 42.0% (p < 0.0001) accompanied by a significant improvement in NT-proBNP and QoL scores. Conclusion: Immunoadsorption followed by IVIG administration further enhances LVEF, HF symptoms, QoL and biomarkers in patients with recent-onset HF on OMT

Genetic compensation prevents myopathy and heart failure in an in vivo model of Bag3 deficiency.

Mutations in the molecular co-chaperone Bcl2-associated athanogene 3 (BAG3) are found to cause dilated cardiomyopathy (DCM), resulting in systolic dysfunction and heart failure, as well as myofibrillar myopathy (MFM), which is characterized by protein aggregation and myofibrillar disintegration in skeletal muscle cells. Here, we generated a CRISPR/Cas9-induced Bag3 knockout zebrafish line and found the complete preservation of heart and skeletal muscle structure and function during embryonic development, in contrast to morpholino-mediated knockdown of Bag3. Intriguingly, genetic compensation, a process of transcriptional adaptation which acts independent of protein feedback loops, was found to prevent heart and skeletal muscle damage in our Bag3 knockout model. Proteomic profiling and quantitative real-time PCR analyses identified Bag2, another member of the Bag protein family, significantly upregulated on a transcript and protein level in bag3-/- mutants. This implied that the decay of bag3 mutant mRNA in homozygous bag3-/- embryos caused the transcriptional upregulation of bag2 expression. We further demonstrated that morpholino-mediated knockdown of Bag2 in bag3-/- embryos evoked severe functional and structural heart and skeletal muscle defects, which are similar to Bag3 morphants. However, Bag2 knockdown in bag3+/+ or bag3+/- embryos did not result in (cardio-)myopathy. Finally, we found that inhibition of the nonsense-mediated mRNA decay (NMD) machinery by knockdown of upf1, an essential NMD factor, caused severe heart and skeletal muscle defects in bag3-/- mutants due to the blockade of transcriptional adaptation of bag2 expression. Our findings provide evidence that genetic compensation might vitally influence the penetrance of disease-causing bag3 mutations in vivo

Comparison between a Novel Radiofrequency-Balloon and a Standard Cryo-Balloon in Pulmonary Vein Isolation: A Propensity-Score-Matched Analysis

Background/Objectives: Single-shot devices are important tools for efficient pulmonary vein isolation (PVI) in atrial fibrillation (AF). In addition to the standard cryo-balloon (CB) catheter, a novel multi-electrode radiofrequency balloon-catheter (RFB, Heliostar, Biosense Webster, Irvine, CA, USA) with 3D-mapping-integration is available. Currently, there is no evidence allowing for a direct comparison between RFB-PVI and CB-PVI in a matched population. The study aimed to assess the procedural data, safety profiles, and outcomes of RFB-PVI versus CB-PVI. Methods: In this prospective registry study, symptomatic AF patients undergoing first-time PVI from January 2019 to April 2023, using RFB or CB, were included, with patients matched in a 1:2 ratio to reduce potential confounders. Results: The results from 171 consecutive RFB patients and 342 matched CB patients showed comparable recurrence-free survival after 12 months (81.3% RFB vs. 76.8% CB, p = 0.359). The RFB group had a longer procedure duration (88 vs. 73 min, p p Conclusions: In conclusion, the novel RFB system enables efficient and safe PVI, which is broadly comparable to the established CB system. However, the 3D-mapping integration in RFB did not reduce fluoroscopy time compared to CB

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08 août 19391939/08/08 (A48,N9520).Appartient à l’ensemble documentaire : Aquit

Impact of re-definition of paroxysmal and persistent atrial fibrillation in the 2012 and 2016 European Society of Cardiology atrial fibrillation guidelines on outcomes after pulmonary vein isolation

Purpose!#!In the 2016 European Society of Cardiology (ESC) guidelines for the management of atrial fibrillation (AF), the definition of AF type has been modified compared with the 2010 guidelines and its 2012 focused update. We compared the difference of single procedure outcomes using the definitions before and after 2016 on a cohort of patients with AF undergoing AF ablation.!##!Methods!#!Consecutive AF ablation patients with paroxysmal or persistent AF were retrospectively reclassified applying the 2010, 2012, and 2016 ESC definitions on AF type.!##!Results!#!We included a total of 628 patients. Applying the 2010 ESC AF guidelines definition, 68% of patients were paroxysmal while according to the 2016 ESC AF guidelines, the proportion increased to 87%. Applying the 2010 ESC guidelines definition, recurrence rates of paroxysmal and persistent AF patients differ significantly (log-rank p < 0.001). Applying the 2012 focused update and the 2016 ESC AF guidelines, recurrence rates do not differ significantly. In a cox regression model applying the 2010 guidelines, persistent AF is the only independent predictor of AF recurrence in our cohort. However, when applying the 2016 guidelines, persistent AF is no longer a predictor of AF recurrence.!##!Conclusions!#!The revised definition of AF types in the 2016 ESC AF guidelines leads to a marked shift from persistent to paroxysmal AF. It appears that the old definition provided a better separator to predict rhythm outcome after AF ablation

Safety of conscious sedation in electroanatomical mapping procedures and cryoballoon pulmonary vein isolation

Immobilization of patients during electrophysiological procedures, to avoid complications by patients' unexpected bodily motion, is achieved by moderate to deep conscious sedation using benzodiazepines and propofol for sedation and opioids for analgesia. Our aim was to compare respiratory and hemodynamic safety endpoints of cryoballoon pulmonary vein isolation (PVI) and electroanatomical mapping (EAM) procedures. Included patients underwent either cryoballoon PVI or EAM procedures. Sedation monitoring included non-invasive blood pressure measurements, transcutaneous oxygen saturation (tSp

Incidence of Long-Term Pulmonary Vein Reconnection after a 2-Minute Cryoballoon Freeze for Pulmonary Vein Isolation—Invasive Insights of TTI-Dependent Cryoenergy Titration

Introduction: The optimal freeze duration in cryoballoon pulmonary vein isolation (PVI) is unknown. TTI-based titration of cryoenergy allows individualized freeze duration and has emerged as a favorable ablation strategy in PV cryoablation. In a recent study, we demonstrated that omission of a bonus freeze and reduction in freeze duration to a minimum of 2 min in the case of short TTI led to comparable arrhythmia recurrence rates. Whereas clinical outcome seems to be comparable to fixed freeze duration, evidence of long-term PV reconnection rates in patients undergoing TTI-based cryoballoon ablation is sparse. Aim of the study: To evaluate the procedural efficacy of a single 2-min freeze for PVI, we assessed PV conduction recovery after cryoballoon PVI with a TTI-guided titration of freeze duration compared to a fixed ablation protocol. Methods and Results: We included consecutive patients with atrial fibrillation (AF) recurrence undergoing a second ablation procedure after the initial cryoballoon procedure. The second AF ablation procedure was performed by the 3D-mapping system and radiofrequency ablation technique. A total of 219 patients (age: 66.2 ± 10.8 years, 53% female, paroxysmal AF: 53%) treated with the TTI-guided protocol (174 patients, 685 PV) or fixed protocol (45 patients, 179 PV) showed comparable total reconnection rates (TTI: 36.9% vs. fixed: 31.8%, p = 0.21). The PV reconnection rate was not statistically different for PVs treated with a 2-min freeze in case of short TTI, compared to longer freeze duration. Interestingly, the PV reconnection rate was lower in LIPVs treated with the fixed protocol (13% vs. 31%, p = 0.029). In the TTI group, 17 out of 127 patients (15%) had durable isolation of all PVs, whereas in 8 out of 40 patients (20%) in the fixed group, all PVs were still isolated (p = 0.31). Conclusions: overall reconnection rate was not different using a TTI-guided ablation protocol compared to a fixed ablation protocol, whereas the LIPV reconnection rate was significantly lower in patients treated with a fixed ablation protocol

Angiopoietin 2 mediates microvascular and hemodynamic alterations in sepsis

Septic shock is characterized by increased vascular permeability and hypotension despite increased cardiac output. Numerous vasoactive cytokines are upregulated during sepsis, including angiopoietin 2 (ANG2), which increases vascular permeability. Here we report that mice engineered to inducibly overexpress ANG2 in the endothelium developed sepsis-like hemodynamic alterations, including systemic hypotension, increased cardiac output, and dilatory cardiomyopathy. Conversely, mice with cardiomyocyte-restricted ANG2 overexpression failed to develop hemodynamic alterations. Interestingly, the hemodynamic alterations associated with endothelial-specific overexpression of ANG2 and the loss of capillary-associated pericytes were reversed by intravenous injections of adeno-associated viruses (AAVs) transducing cDNA for angiopoietin 1, a TIE2 ligand that antagonizes ANG2, or AAVs encoding PDGFB, a chemoattractant for pericytes. To confirm the role of ANG2 in sepsis, we i.p. injected LPS into C57BL/6J mice, which rapidly developed hypotension, acute pericyte loss, and increased vascular permeability. Importantly, ANG2 antibody treatment attenuated LPS-induced hemodynamic alterations and reduced the mortality rate at 36 hours from 95% to 61%. These data indicate that ANG2-mediated microvascular disintegration contributes to septic shock and that inhibition of the ANG2/TIE2 interaction during sepsis is a potential therapeutic target