Pulmonary Vein Isolation with a Novel Size-Adjustable Cryo-Balloon Catheter: A Tailored Ablation Protocol.

Background: Pulmonary vein isolation (PVI) is a common therapeutic approach for symptomatic atrial fibrillation (AF). Among various techniques, cryo-balloon (CB) PVI is widely adopted, but, to date, established CB systems have had fixed balloon sizes. A novel size-adjustable CB, allowing balloon size adjustments during ablation, lacks sufficient data on optimal utilization in patient care. This study aims to systematically investigate this feature with a tailored ablation protocol. Methods: Our single-center prospective study included patients with paroxysmal or persistent atrial fibrillation undergoing first-time PVI with the size-adjustable CB from July 2023 to February 2024. Ablation was performed using the balloon size that provided better occlusion. The ablation protocol involved an initial occlusion test with the small balloon size (28 mm). If optimal occlusion (occlusion level 4) could not be achieved, an attempt with the larger balloon (31 mm) was initiated. Ablation was conducted using the balloon configuration that provided better occlusion of the pulmonary vein ostium. Results: Our prospective study includes 50 patients (median age [interquartile range, IQR]: 72 [65; 79] years, 24 [48.0%] females, and 35 [70.0%] patients with paroxysmal AF). The median procedure duration (IQR) was 77 (65; 96) minutes, and the median fluoroscopy time (IQR) was 17.7 (12.5; 22.0) min. PVI was successfully accomplished in each treated pulmonary vein (PV), with 87.4% of PVs isolated during the first freeze. The large balloon configuration was used to isolate 16.8% of PVs. Conclusions: The utilization of the size-adjustable CB, combined with the presented tailored ablation workflow, appears to facilitate effective and efficient pulmonary vein isolation. The use of a larger balloon configuration appears beneficial in isolating a significant proportion of the PVs.

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 < 0.001) and longer fluoroscopy time (18.9 vs. 14.5 min, p < 0.001). 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.

Atrial Fibrillation Ablation with a Novel Fully 3D-Mapping-Integrated Multi-Electrode Radiofrequency Balloon Catheter.

Pulmonary vein isolation (PVI), as the cornerstone of atrial fibrillation (AF) ablation, has emerged a widely used therapy for patients suffering from AF. To improve PVI efficiency, single-shot catheters (SSCs) have been developed. Regrettably, SSCs are not integrated into 3D-mapping technology. In that regard, a novel radiofrequency balloon catheter (RFBC, Heliostar, Biosense Webster) with full integration into 3D-mapping technology has been developed. The aim of this study was to assess operative and follow-up outcomes of the RFBC in AF patients. In this monocentric prospective registry, patients with a first-time PVI using the RFBC were included. Follow-up visits were scheduled 3, 6, 12 and 24 months after ablation and in case of symptoms. A total of 171 patients (36.8% female) were included, with a mean age of 68.5 ± 10.2 years. Among them, 63 patients (36.8%) presented with persistent AF. Notably, no major periprocedural complications were observed. The mean follow-up period was 287 ± 157 days. In the Kaplan-Meier analysis, the estimated recurrence-free survival after 12 months was 81.8%. Based on our data, PVI with the fully 3D-mapping-integrated RFBC seems to be safe and effective and to have a favorable 12-month outcome in patients with paroxysmal and persistent AF.

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.

Novel cryoballoon ablation system for pulmonary vein isolation: multicenter assessment of efficacy and safety-ANTARCTICA study.

AIMS: Pulmonary vein isolation (PVI) either by balloon devices or radiofrequency forms the cornerstone of invasive atrial fibrillation (AF) treatment. Although equally effective cryoballoon (CB)-based PVI offers shorter procedure duration and a better safety profile. Beside the worldwide established Arctic Front Advance system, a novel CB device, POLARx, was recently introduced. This CB incorporates unique features, which may translate into improved efficacy and safety. However, multicentre assessment of periprocedural efficacy and safety is lacking up to date. METHODS AND RESULTS: A total of 317 patients with paroxysmal or persistent AF were included and underwent POLARx CB-based PVI in 6 centres from Germany and Italy. Acute efficacy and safety were assessed in this prospective multicenter observational study. In 317 patients [mean age: 64 ± 12 years, 209 of 317 (66%) paroxysmal AF], a total of 1256 pulmonary veins (PVs) were identified and 1252 (99,7%) PVs were successfully isolated utilizing mainly the short tip POLARx CB (82%). The mean minimal CB temperature was -57.9 ± 7°C. Real-time PVI was registered in 72% of PVs. The rate of serious adverse events was 6.0% which was significantly reduced after a learning curve of 25 cases (9.3% vs. 3.0%, P = 0.018). The rate of recurrence-free survival after mean follow-up of 226 ± 115 days including a 90-day blanking period was 86.1%. CONCLUSION: In this large multicentre assessment, the novel POLARx CB shows a promising efficacy and safety profile after a short learning curve.

Substrate-based ablation of atypical atrial flutter in patients with atrial cardiomyopathy.

Background: Standard therapy of atypical atrial flutter (AFL) aims at deploying ablation lines between two non-conducting anatomical structures, thereby creating a line of block within the re-entry circuit. We have developed an ablation strategy, where we incorporate voltage information as a surrogate for atrial fibrosis from the electro-anatomical map (EAM) during AFL ablation procedures to create individualized, substrate-based ablation lines along the area of most pronounced low-voltage within the reentry-circuit. Objective: The aim of this study was to evaluate acute procedural success and long-term outcome of a substrate-based ablation (SBA) strategy in comparison to a standard anatomically based ablation (ABA) strategy for the ablation of atypical AFL. Methods: Patients that underwent ablation for AFL at our institution were included. SBA procedures were compared to ABA procedures. Endpoints were acute termination of AFL and recurrence of the index AFL or any other AFL during follow-up. Results: We included 47 patients, 24 individuals (51.1%) in the SBA group and 23 patients (48.9%) in the ABA group. Most patients had signs of atrial cardiomyopathy, namely enlarged left atrial diameter (LAD) and extended amount of left atrial low-voltage areas (LVA). Termination of AFL occurred in 27 of 29 (93.1%) AFL in the SBA group and in 28 of 31 (90.3%) AFL in the ABA group (p = 0.99). Freedom from recurrence of any atypical AFL after 2.5 years was 21.5% in the ABA group compared to 48.8% in the SBA group (p = 0.047). Conclusion: Substrate-based ablation is as effective as an anatomically-based ablation in the acute termination of AFL but yields better rhythm outcome with less recurrence of AFL in patients with atrial cardiomyopathy.

Predicting Phrenic Nerve Palsy in Patients Undergoing Atrial Fibrillation Ablation With the Cryoballoon-Does Sex Matter?

Background: Phrenicus nerve palsy (PNP) is a typical complication during pulmonary vein isolation (PVI) using the cryoballoon with the ominous potential to counteract the clinical benefit of restored sinus rhythm. According to current evidence incidence of PNP is about 5-10% of patients undergoing Cryo-PVI and is more frequent during ablation of the RSPV compared to the RIPV. However, information on patient specific characteristics predicting PNP and long-term outcome of patients suffering from this adverse event is sparse. Aim of the Study: To evaluate procedural and clinical characteristics of AF patients with PNP during cryoballoon PVI compared to patients without PNP. Methods and Results: Between 2013 and 2019 we included 632 consecutive AF patients undergoing PVI with the cryoballoon in our study. 84/632 (13.3%) patients experienced a total number of 89 PNP during the ablation procedure. 75/89 (84%) cryothermal induced PNP recovered until the end of the procedure (transient PNP, tPNP), whereas 14/89 (16%) PNP hold beyond the end of the procedure (non-transient PNP, ntPNP). Using multivariate logistic regression, we found that sex and BMI are strong and independent predictors of cryothermal induced non-transient PNP during cryoballoon PVI with an odds ratio of 3.9 (CI: 95%, 1.1-14.8, p = 0.04) for female gender. Interestingly, all patients (14/14, 100%) with a non-transient PNP experienced complete PNP resolution after a mean recovery time of 68 ± 79 days. Conclusion: Our data indicate for the first time, that female sex and lower BMI are independent predictors for non-transient PNP caused by cryoballoon PVI. Fortunately, during follow up all PNP patients resolved completely with a median recovery time of 35 days.

Catheter ablation for atrial fibrillation in HFpEF patients-A propensity-score-matched analysis.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are both common conditions associated with high morbidity and mortality, especially if they coexist. Catheter ablation (CA) for AF has been shown recently to induce reverse remodeling and improve symptoms in HFpEF patients. The aim of this study was to compare outcomes of AF patients with HFpEF, who either underwent CA for AF or received medical therapy only. METHODS AND RESULTS: We included all AF patients with HFpEF according to current guidelines treated at our hospital between 2013 and 2018. Out of 6614 AF patients, we identified 127 with confirmed HFpEF. After applying propensity score matching to balance patient groups, 43 patients treated by CA and 43 patients receiving medical treatment were compared. Patients in the CA group underwent a mean of 1.5 ± 0.8 ablation procedures. Arrhythmia recurrence occurred significantly less frequently in the CA group (hazard ratio [HR]: 0.47; 95% CI: 0.25-0.87; p = .016). The primary endpoint, a composite of heart failure hospitalization and death, was reduced significantly by CA compared to medical therapy (HR: 0.30; 95% CI: 0.13-0.67; p = .003). This was driven by a decrease in heart failure hospitalization. Clinical and echocardiographic parameters of HFpEF improved significantly only after CA. Remarkably, reassessment of diagnostic HFpEF criteria at the end of follow-up demonstrated HFpEF resolution in 15 out of 43 patients (35%) treated by CA and only 4 out of 43 patients (9%) treated medically (p = .008). CONCLUSION: Catheter ablation for AF in HFpEF patients in comparison to medical therapy decreases heart failure hospitalization, heart failure symptoms, and improves diastolic function. AF ablation should be considered in patients with HFpEF and concomitant AF.

Immunoadsorption for heart failure is associated with normalization of iron metabolism.

AIMS: In heart failure (HF) patients, early stages are associated with increased iron levels, whereas iron deficiency is a common feature of chronic HF. We investigated the acute and long-term changes in iron metabolism in HF patients after immunoadsorption treatment and intravenous immunoglobulin (IVIG) administration. METHODS AND RESULTS: Twenty-seven patients with HF with reduced ejection fraction (HFrEF) received a single cycle of immunoadsorption followed by IVIG administration. Left ventricular ejection fraction (LVEF) and iron biomarker (ferritin, hepcidin and interleukin-6) were evaluated at baseline, after immunoadsorption and during long-term follow-up of 29.3 months. LVEF improved significantly after immunoadsorption treatment from baseline 27% to 43% at long-term follow-up. Ferritin decreased from baseline 300.2 to 201.3 ng/mL (p < 0.0001) during immunoadsorption treatment and normalized during long-term to 207.9 ng/mL. Hepcidin showed a V-shaped course, with a significant decrease after immunoadsorption and normalization during long-term. Interleukin-6 levels showed no relevant inflammation. CONCLUSIONS: Our data suggest that initial high serum ferritin and hepcidin levels indicate elevated iron levels characteristic of early stages of HFrEF, without inflammation. Normalization of hepcidin and ferritin was paralleled by restoration of systolic cardiac function after immunoadsorption treatment, without development of iron deficiency, as usually observed in chronic HF.

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 (tSpO2) and transcutaneous carbon-dioxide (tpCO2) measurements. We enrolled 125 consecutive patients, 67 patients underwent cryoballoon atrial fibrillation ablation and 58 patients had an EAM and radiofrequency ablation procedure. Mean procedure duration of EAM procedures was significantly longer (p < 0.001) and propofol doses as well as morphine equivalent doses of administered opioids were significantly higher in EAM patients compared to cryoballoon patients (p < 0.001). Cryoballoon patients display higher tpCO2 levels compared to EAM patients at 30 min (cryoballoon: 51.1 ± 7.0 mmHg vs. EAM: 48.6 ± 6.2 mmHg, p = 0.009) and at 60 min (cryoballoon: 51.4 ± 7.3 mmHg vs. EAM: 48.9 ± 6.6 mmHg, p = 0.07) procedure duration. Mean arterial pressure was significantly higher after 60 min (cryoballoon: 84.7 ± 16.7 mmHg vs. EAM: 76.7 ± 13.3 mmHg, p = 0.017) in cryoballoon PVI compared to EAM procedures. Regarding respiratory and hemodynamic safety endpoints, no significant difference was detected regarding hypercapnia, hypoxia and episodes of hypotension. Despite longer procedure duration and deeper sedation requirement, conscious sedation in EAM procedures appears to be as safe as conscious sedation in cryoballoon ablation procedures regarding hemodynamic and respiratory safety endpoints.

Continuous transcutaneous carbon-dioxide monitoring to avoid hypercapnia in complex catheter ablations under conscious sedation.

BACKGROUND: Ablation of complex cardiac arrhythmias requires an immobilized patient. For a successful and safe intervention and for patient comfort, this can be achieved by conscious sedation. Administered sedatives and analgesics have respiratory depressant side effects and require close monitoring. We investigated the feasibility and accuracy of additional, continuous transcutaneous carbon-dioxide partial pressure (tpCO2) measurement during conscious sedation in complex electrophysiological catheter ablation procedures. METHOD: We evaluated the accuracy and additional value of continuous tpCO2 detection by application of a Severinghaus electrode in comparison to arterial and venous blood gas analyses. RESULTS: We included 110 patients in this prospective observational study. Arterial pCO2 (paCO2) and tpCO2 showed good correlation throughout the procedures (r = 0.60-0.87, p < 0.005). Venous pCO2 (pvCO2) were also well correlated to transcutaneous values (r = 0.65-0.85, p < 0.0001). Analyses of the difference of pvCO2 and tpCO2 measurements showed a tolerance within <10 mmHg in up to 96-98% of patients. Hypercapnia (pCO2 < 70 mmHg) was detected more likely and earlier by continuous tpCO2 monitoring compared to half-hourly pvCO2 measurements. CONCLUSION: Continuous tpCO2 monitoring is feasible and precise with good correlation to arterial and venous blood gas carbon-dioxide analysis during complex catheter ablations under conscious sedation and may contribute to additional safety.

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.

Pulmonary vein isolation with the cryoballoon in obese atrial fibrillation patients - Does weight have an impact on procedural parameters and clinical outcome?

INTRODUCTION: Obesity is a known risk factor for the incidence and prevalence of atrial fibrillation (AF). Pulmonary vein isolation (PVI) is an established therapeutic option for AF patients, however clinical benefit of AF ablation remains controversial in overweight and obese patients. We investigated the impact of overweight and obesity in AF patients undergoing cryoballoon PVI on procedural characteristics and clinical outcome. METHODS: We included consecutive patients undergoing cryoballoon PVI at Ulm University Medical center. Normal weight was defined as a body mass index (BMI) of 18.5-24.9 kg/m2, overweight as a BMI of 25.0-29.9 kg/m2 and obesity as a BMI of ≥30.0 kg/m2. RESULTS: Evaluating 600 patients, mean age was 66.3±10.8 years and 43% patients were female. 41% of the patients were classified as overweight and 34% as obese. Regarding procedural characteristics, overweight and obese patients had longer fluoroscopy area dose product (p<0.001) and obese patients a higher fluoroscopy time (p<0.05). Analyses of ablation related procedural characteristics revealed no relevant differences regarding number and duration of ablation, time to isolation and nadir temperature. Importantly, recurrence of atrial arrhythmia was statistically not different comparing normal weight, overweight and obese patients. CONCLUSION: Besides higher radiation exposure, cryoballoon PVI in overweight and obese patients is as safe and efficient as in normal weight patients. It is reasonable to proceed with cryoballoon PVI on overweight and obese patients as would be done in normal weight patients, since this might encourage overweight and obese patients to exercise.

Atrial fibrillation ablation in heart failure patients: improved systolic function after cryoballoon pulmonary vein isolation.

AIMS: Atrial fibrillation (AF) and heart failure (HF) are the most common cardiac diseases and often coexist leading to increased mortality and morbidity compared with AF patients without HF. As shown previously, AF ablation using radio frequency (RF) in HF patients leads to a reduction of AF burden, an increase of left ventricular ejection fraction (LVEF) and consequently to reduced hospitalization and mortality. Previous AF ablation studies on HF patients have been liberal about additional targets beyond pulmonary vein isolation (PVI). Thus, the aim of this study was to assess systematically the impact of a straightforward PVI-only strategy on LVEF, NYHA functional class, and cardiovascular hospitalization rate in HF patients. METHODS AND RESULTS: Out of 414 consecutive patients undergoing PVI, only with the cryoballoon 113 patients with reduced LVEF [mean: 38.4 ± 10.8%, reduced ejection fraction (rEF) group] and 301 patients with normal LVEF (>55%) at baseline were identified [normal ejection fraction (nEF) group]. Remarkably, even though freedom from arrhythmia recurrence after 1 year was significantly lower in the rEF group (64.9%) compared with the nEF group (71.2%, P = 0.036), mean LVEF improved from 38.4 ± 10.8% to 52.5 ± 17.2% (P < 0.001) after cryoballoon ablation in the rEF group. Accordingly, HF-related symptoms as well as hospitalization rate declined significantly in the rEF group during follow-up compared with baseline. CONCLUSIONS: The results of the present study suggest that catheter ablation restricted to a straightforward PVI-only strategy using the cryoballoon leads to improved left ventricular ejection fraction as well as improvement of NYHA functional class and increased freedom from cardiovascular rehospitalization.

Restoration of sinus rhythm by pulmonary vein isolation improves heart failure with preserved ejection fraction in atrial fibrillation patients.

AIMS: Atrial fibrillation (AF) in patients suffering from heart failure with preserved ejection fraction (HFpEF) is associated with increased symptoms and higher morbidity and mortality. Effective treatment strategies for this patient population have not yet been established. METHODS AND RESULTS: We analysed clinical outcomes and echocardiographic parameters of patients with AF and HFpEF who underwent pulmonary vein isolation (PVI). Out of 374 PVI patients, we identified 35 patients suffering from concomitant HFpEF. Freedom from atrial tachyarrhythmia (AT) after 1 year was 80%. Heart failure symptoms assessed by New York Heart Association class significantly improved from 2.7 ± 0.7 to 1.7 ± 0.9 (P < 0.001). We observed regression of diastolic dysfunction by echocardiography 12 months after the index procedure. Moreover, 15 patients (42.9%) experienced complete resolution of HFpEF after a single ablation procedure. Multivariate logistic regression revealed absence of AT recurrence as an independent predictor of recovery from HFpEF (hazard ratio 11.37, 95% confidence interval 1.70-75.84, P = 0.009). Furthermore, resolution of HFpEF by achieving freedom from AT recurrence by PVI, including multiple procedures, led to a significant reduction of hospitalizations. CONCLUSION: Our results suggest that restoration of sinus rhythm by PVI in HFpEF patients with concomitant AF induces reverse remodelling, improvement of symptoms, resolution of HFpEF and subsequently decrease of hospitalizations. Randomized controlled trials are warranted to confirm our results.

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.

Impact of atrial rhythm on pulmonary vein signals in cryoballoon ablation - Sinus rhythm predicts real-time observation of pulmonary vein isolation.

PURPOSE: Real-time observation of pulmonary vein (PV) potentials with a spiral mapping catheter has emerged as a key electrogram-based procedural parameter to estimate lesion quality and titrate cryoenergy application during PV isolation (PVI) with the cryoballoon. Whether correct PV electrogram interpretation and thus PVI real-time observation rate depends on atrial rhythm during cryoballoon PVI is unknown. We compared observation rates of time-to PV isolation (TTI) during sinus rhythm (SR group) and during atrial fibrillation (AFib group) in cryoballoon PVI. METHODS: We prospectively included 157 consecutive patients undergoing cryoballoon PVI and compared the incidence of PVI real-time recording of each pulmonary vein during SR and in AFib. RESULTS: Overall PVI real-time observation rate was 82.1% (491/598 PV) with significantly higher TTI observation rate in the SR group (315/365 PV, 86.3%) compared to the AFib group (176/233 PV, 75.5%; p < 0.001). Per vein analysis demonstrated that only TTI observation rate in the left superior pulmonary vein (LSPV) was significantly higher during SR (85/92, 92.4%) compared to AFib (37/54, 68.5%; p < 0.001). Regression analysis revealed that atrial rhythm is a strong and independent predictor of PVI real-time observation in the LSPV with an odds ratio of 4.98 (95%-CI: 1.86-13.34, p = 0.001) to detect TTI during SR. CONCLUSIONS: Our results demonstrate that correct interpretation of PV electrograms and thus PVI real-time observation is more likely in SR than in AFib. Hence, cardioversion of patients in AFib at the beginning of the procedure should be considered to yield higher PVI real-time observation rates facilitating TTI guided cryoenergy titration.

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.

Therapeutic Chemical Screen Identifies Phosphatase Inhibitors to Reconstitute PKB Phosphorylation and Cardiac Contractility in ILK-Deficient Zebrafish.

Patients with inherited dilated cardiomyopathy (DCM) often suffer from severe heart failure based on impaired cardiac contractility leading to increased morbidity and mortality. Integrin-linked kinase (ILK) as a part of the cardiac mechanical stretch sensor was found to be an essential genetic regulator of cardiac contractility. Integrin-linked kinase localizes to z-disks and costameres in vertebrate hearts and regulates the activity of the signaling molecule protein kinase B (PKB/Akt) by controlling its phosphorylation. Despite identification of several potential drug targets in the ILK signaling pathway, pharmacological treatment strategies to restore contractile function in ILK-dependent cardiomyopathies have not been established yet. In recent years, the zebrafish has emerged as a valuable experimental system to model human cardiomyopathies as well as a powerful tool for the straightforward high-throughput in vivo small compound screening of therapeutically active substances. Using the ILK deficient zebrafish heart failure mutant main squeeze (msq), which shows reduced PKB phosphorylation and thereby impaired cardiac contractile force, we identified here, in an automated small compound screen, the protein phosphatase inhibitors calyculin A and okadaic acid significantly restoring myocardial contractile function by reconstituting PKB phosphorylation in msq ILK-deficient zebrafish embryos.