Mosaic loss of Y chromosome in monocytes is associated with lower survival after transcatheter aortic valve replacement.

AIMS: Mosaic loss of Y chromosome (LOY) in blood cells is the most common acquired mutation, increases with age, and is related to cardiovascular disease. Loss of Y chromosome induces cardiac fibrosis in murine experiments mimicking the consequences of aortic valve stenosis, the prototypical age-related disease. Cardiac fibrosis is the major determinant of mortality even after transcatheter aortic valve replacement (TAVR). It was hypothesized that LOY affects long-term outcome in men undergoing TAVR. METHODS AND RESULTS: Using digital PCR in DNA of peripheral blood cells, LOY (Y/X ratio) was assessed by targeting a 6 bp sequence difference between AMELX and AMELY genes using TaqMan. The genetic signature of monocytes lacking the Y chromosome was deciphered by scRNAseq. In 362 men with advanced aortic valve stenosis undergoing successful TAVR, LOY ranged from -4% to 83.4%, and was >10% in 48% of patients. Three-year mortality increased with LOY. Receiver operating characteristic (ROC) curve analysis revealed an optimal cut-off of LOY >17% to predict mortality. In multivariate analysis, LOY remained a significant (P < 0.001) independent predictor of death during follow-up. scRNAseq disclosed a pro-fibrotic gene signature with LOY monocytes displaying increased expression of transforming growth factor (TGF) ß-associated signaling, while expression of TGFß-inhibiting pathways was down-regulated. CONCLUSION: This is the first study to demonstrate that LOY in blood cells is associated with profoundly impaired long-term survival even after successful TAVR. Mechanistically, the pro-fibrotic gene signature sensitizing the patient-derived circulating LOY monocytes for the TGFß signaling pathways supports a prominent role of cardiac fibrosis in contributing to the effects of LOY observed in men undergoing TAVR.

Clonal haematopoiesis in chronic ischaemic heart failure: prognostic role of clone size for DNMT3A- and TET2-driver gene mutations.

AIMS: Somatic mutations of the epigenetic regulators DNMT3A and TET2 causing clonal expansion of haematopoietic cells (clonal haematopoiesis; CH) were shown to be associated with poor prognosis in chronic ischaemic heart failure (CHF). The aim of our analysis was to define a threshold of variant allele frequency (VAF) for the prognostic significance of CH in CHF. METHODS AND RESULTS: We analysed bone marrow and peripheral blood-derived cells from 419 patients with CHF by error-corrected amplicon sequencing. Cut-off VAFs were optimized by maximizing sensitivity plus specificity from a time-dependent receiver operating characteristic (ROC) curve analysis from censored data. 56.2% of patients were carriers of a DNMT3A- (N = 173) or a TET2- (N = 113) mutation with a VAF >0.5%, with 59 patients harbouring mutations in both genes. Survival ROC analyses revealed an optimized cut-off value of 0.73% for TET2- and 1.15% for DNMT3A-CH-driver mutations. Five-year-mortality was 18% in patients without any detected DNMT3A- or TET2 mutation (VAF < 0.5%), 29% with only one DNMT3A- or TET2-CH-driver mutations above the respective cut-off level and 42% in patients harbouring both DNMT3A- and TET2-CH-driver mutations above the respective cut-off levels. In carriers of a DNMT3A mutation with VAF ≥ 1.15%, 5-year mortality was 31%, compared with 18% mortality in those with VAF < 1.15% (P = 0.048). Likewise, in patients with TET2 mutations, 5-year mortality was 32% with VAF ≥ 0.73%, compared with 19% mortality with VAF < 0.73% (P = 0.029). CONCLUSION: The present study defines novel threshold levels for clone size caused by acquired somatic mutations in the CH-driver genes DNMT3A and TET2 that are associated with worse outcome in patients with CHF.

A Novel Method to Predict Mortality and Length of Stay after Transfemoral Transcatheter Aortic Valve Implantation.

Background and Objectives: We tested if a novel combination of predictors could improve the accuracy of outcome prediction after transfemoral transcatheter aortic valve implantation (TAVI). Materials and Methods: This prospective study recruited 169 participants (49% female; median age 81 years). The primary endpoint was midterm mortality; secondary endpoints were acute Valve Academic Research Consortium (VARC)-3 complication rate and post-TAVI in-hospital length of stay (LoS). EuroSCORE II (ESII), comorbidities (e.g., coronary artery disease), eGFR (estimated glomerular filtration rate; based on cystatin C), hemoglobin, creatinine, N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) levels and patient-reported outcome measures (PROMs, namely EuroQol-5-Dimension-5-Levels, EQ5D5L; Kansas City Cardiomyopathy Questionnaire, KCCQ; clinical frailty scale, CFS) at baseline were tested as predictors. Regression (uni- and multi-variate Cox; linear; binary logistic) and receiver operating characteristic (ROC)-curve analysis were applied. Results: Within a median follow-up of 439 (318-585) days, 12 participants died (7.1%). Independent predictors of mortality using multivariate Cox regression were baseline eGFR (p = 0.001) and KCCQ (p = 0.037). Based on these predictors, a Linear Prediction Score (LPS1) was calculated. The LPS1-area under the curve (AUC)-value (0.761) was significantly higher than the ESII-AUC value (0.597; p = 0.035). Independent predictors for LoS > 6 days (the median LoS) were eGFR (p = 0.028), NTproBNP (p = 0.034), and EQ5D5L values (p = 0.002); a respective calculated LPS2 provided an AUC value of 0.677 (p < 0.001). Eighty participants (47.3%) experienced complications. Male sex predicted complications only in the univariate analysis. Conclusions: The combination of KCCQ and eGFR can better predict midterm mortality than ES II alone. Combining eGFR, NTproBNP, and EQ5D5L can reliably predict LoS after TAVI. This novel method improves personalized TAVI risk stratification and hence may help reduce post-TAVI risk.

Patients at Intermediate Surgical Risk Undergoing Isolated Interventional or Surgical Aortic Valve Implantation for Severe Symptomatic Aortic Valve Stenosis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is increasingly being used for treatment of severe aortic valve stenosis in patients at intermediate risk for surgical aortic valve replacement (SAVR). Currently, real-world data comparing indications and clinical outcomes of patients at intermediate surgical risk undergoing isolated TAVR with those undergoing SAVR are scarce. METHODS: We compared clinical characteristics and outcomes of patients with intermediate surgical risk (Society of Thoracic Surgeons score 4%-8%) who underwent isolated TAVR or conventional SAVR within the prospective, all-comers German Aortic Valve Registry. RESULTS: A total of 7613 patients at intermediate surgical risk underwent isolated TAVR (n=6469) or SAVR (n=1144) at 92 sites in Germany between 2012 and 2014. Patients treated by TAVR were significantly older (82.5±5.0 versus 76.6±6.7 years, P<0.001) and had higher risk scores (logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation]: 21.2±12.3% versus 14.2±9.5%, P<0.001; Society of Thoracic Surgeons score: 5.6±1.1 versus 5.2±1.0, P<0.001). Multivariable analyses revealed that advanced age, coronary artery disease, New York Heart Association class III/IV, pulmonary hypertension, prior cardiac decompensation, elective procedure, arterial occlusive disease, no diabetes mellitus, and a smaller aortic valve area were associated with performing TAVR instead of SAVR (all P<0.001). Unadjusted in-hospital mortality rates were equal for TAVR and SAVR (3.6% versus 3.6%, P=0.976), whereas unadjusted 1-year mortality was significantly higher in patients after TAVR (17.5% versus 10.8%, P<0.001). After propensity score matching, the difference in 1-year mortality between patients with TAVR and SAVR was no longer significant (17.1% versus 15.7%, P=0.59). CONCLUSIONS: Patients at intermediate risk undergoing TAVR differ significantly from those treated with SAVR with regard to age and baseline characteristics. Isolated TAVR and SAVR were associated with an in-hospital mortality rate of 3.6%. In the propensity score analysis, there was no significant difference in 1-year mortality between patients with TAVR and SAVR.

Five-year experience with pulmonary vein isolation using the second-generation cryoballoon for treatment of persistent atrial fibrillation.

INTRODUCTION: We analyzed the procedural experience and clinical outcome after pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) gained over 5 years using the second-generation cryoballoon (CB-Adv). METHODS AND RESULTS: For this retrospective study, we enrolled 281 patients undergoing PVI at our institution between 2012 and 2016. The analyzed period was divided into 5 calendar years. Follow-up data, including Holter electrocardiography recordings, were collected during outpatient clinic visits. The impact of several variables on outcome was evaluated by means of univariate and multivariate analyses and Cox proportional hazards regression models. The median procedure and fluoroscopy times over the years were 90 (72 of 114) and 15 (11 of 21) minutes, respectively. A continuous decline in complication rates and fluoroscopy and procedure times was observed in each subsequent year. During mid-term follow-up (33 [25 of 48] months), 178 (63.3%) patients were AF, atrial flutter, or atrial tachycardia free. Multivariate analysis revealed left atrial area (hazard ratio [HR] = 1.05; P < 0.001), female sex (HR = 2.53; P < 0.001), and common ostium (HR = 1.93; P < 0.001) as significant predictors of outcome. The overall 1-year success rate was 76.2%. A gradual decrease in the 1-year success rate (from 90.5% in 2012 to 67.9% in 2016) was mainly related to a steady increase of left atrial area in the entire cohort with successive years of the study. CONCLUSIONS: PVI using CB-Adv in patients with persistent AF is accompanied by a learning curve and facilitates a satisfactory outcome, followed by the proper selection of patients.

Second-generation cryoballoon ablation for treatment of persistent atrial fibrillation: Three-year outcome and predictors of recurrence after a single procedure.

INTRODUCTION: Data on long-term outcomes of cryoballoon (CB) ablation for treatment of persistent atrial fibrillation (AF) are sparse. Here, we report the first 3-year follow-up results and predictors of success for catheter ablation using the second-generation CB in patients with persistent AF. METHODS AND RESULTS: For this prospective observational study, we enrolled 101 patients ablated with the second-generation CB at our institution. The endpoint was the first documented recurrence (> 30 seconds) of AF, atrial flutter, or atrial tachycardia after a 3-month blanking period. Follow-up data were collected during outpatient clinic visits and included Holter-ECG recordings. The impact of several variables on recurrence was evaluated by means of univariate and multivariate analyses and Cox proportional hazards regression models. After a median follow-up of 37 (31 of 42) months, recurrence was documented in 30 patients (29.7%). The median procedure and fluoroscopy times were 120 (102 of 147) and 20 (16 of 27) minutes, respectively. Phrenic nerve palsy occurred in 2.0% of the patients. Among the 30 patients who experienced recurrence, 16 underwent repeat ablation in radiofrequency technique. Cox regression analysis showed that left atrial area > 21 cm2 and AF history duration > 2 years independently predicted recurrence. CONCLUSIONS: Sinus rhythm was maintained in a substantial proportion of patients even 3 years after CB ablation. Patients with a nonenlarged left atrium and short AF history had the best outcome.

Ice or fire? Comparison of second-generation cryoballoon ablation and radiofrequency ablation in patients with symptomatic persistent atrial fibrillation and an enlarged left atrium.

INTRODUCTION: We aimed to compare arrhythmia recurrence rates after second-generation cryoballoon (CB-Adv) ablation and radiofrequency (RF) ablation in patients with symptomatic persistent atrial fibrillation (AF) and left atrial (LA) enlargement. METHODS AND RESULTS: Persistent AF patients with LA enlargement were compared using a propensity-score-matching algorithm, and 111 patients treated with CB-Adv ablation and 111 patients treated with RF ablation were selected. The primary endpoint was the first documented >30-second arrhythmia recurrence after a 3-month blanking period. Median LA area was comparable between the RF and CB-Adv groups (24.2 vs. 24.0 cm2 , P = 0.49). In addition to pulmonary vein isolation, roof lines (RLs) with bidirectional conduction block were created in 48 patients in the CB-Adv group and 49 patients in the RF group. Midterm outcome after single procedure is characterized by arrhythmia recurrences in 47 patients in the RF group and 32 patients in the CB-Adv group (P = 0.20). There were no differences in the number of AF recurrences in the two groups (38 vs. 32, P = 0.66), but there were more instances of LA tachycardia (LAT) in the RF group than in the CB-Adv group (11 vs. 0, P < 0.01). LAT recurrence in RF patients was associated with RL creation (9 with vs. 2 without, P < 0.01). Among patients in whom a RL was created, arrhythmia-free survival was lower in the RF group than in the CB-Adv group (44.9% vs. 79.2%, P < 0.01). CONCLUSIONS: Arrhythmia recurrence rates in the two groups during midterm follow-up were comparable. RL creation during CB-Adv ablation resulted in acceptable outcomes.

PLAAF score as a novel predictor of long-term outcome after second-generation cryoballoon pulmonary vein isolation.

Aims: Predictors of atrial arrhythmia recurrence have not been described in a long-term follow-up study of patients undergoing pulmonary vein isolation (PVI) using the cryoballoon technique. We aimed to evaluate the efficacy of a second-generation cryoballoon and identify pre-procedural predictors of 3-year outcome after PVI. Methods and results: For this observational cohort study, we enrolled 440 patients ablated at our institution with a second-generation cryoballoon. The endpoint was the first documented recurrence (>30 s) of atrial fibrillation (AF), atrial flutter, or atrial tachycardia after a 3-month blanking period. The impact of several pre-existing variables on clinical outcome was evaluated by univariate and multivariate analyses using the Cox proportional hazards regression model. The PLAAF (persistent AF, left atrial area, abnormal PV anatomy, AF history, female gender) score was defined to predict outcome. After a median follow-up of 36 months (interquartile range 25/75-27/42), the endpoint was achieved in 95 of 440 (21.6%) patients. Cox regression analysis showed that persistent AF, left atrial (LA) area, abnormal PV anatomy, AF history, and female gender independently predicted recurrence. The calculated optimal cut-offs for LA area and AF history were 21 cm2 and 3 years, respectively. Patients with a PLAAF score of 0 showed the best outcome, with an arrhythmia-free survival of 86.7%. Conclusion: PVI using the cryoballoon technique shows acceptable long-term results depending on predictors described by the new PLAAF score, which may facilitate patient selection for PVI.

Safety and feasibility of percutaneous skin closure using purse-string suture compared with compression bandage after pulmonary vein isolation.

INTRODUCTION: This observational study was designed to analyze the safety and feasibility of percutaneous skin closure using a purse-string suture and compare it with the use of a compression bandage after pulmonary vein isolation. METHODS AND RESULTS: A total of 407 patients undergoing pulmonary vein isolation (217 with radiofrequency and 190 with cryoballoon ablation) were treated with either purse-string sutures or compression bandages. The purse-string suture was applied after ablation before withdrawal of the sheaths. Patients were on bed rest for 6 hours prior to suture removal, which was accomplished 18-24 h after ablation. The compression bandage was applied after sheath withdrawal and was removed after 12 hours of bed rest. We analyzed the occurrence of any vascular or thromboembolic complication as well as hospital costs and hospital stay length after ablation. The incidence of vascular complications after compression bandage was higher than after purse-string suture in the cryoballoon and radiofrequency group (P < 0.05, respectively). The hospital costs were lower and hospital stay was shorter in both radiofrequency (4.921 ± 3.145 vs. 5.802 ± 4.006 Euro; 2.34 ± 1.32 vs. 2.98 ± 1.57 days, P < 0.05) and cryoballoon groups (4.705 ± 3.091 vs. 5.661 ± 3.563 Euro; 2.14 ± 1.37 vs. 2.61 ± 1.55 days, P < 0.05) in patients treated with a purse-string suture. CONCLUSIONS: Percutaneous skin closure with a purse-string suture has the clinical impact to reduce vascular complications, hospital costs, and hospital stay length after pulmonary vein isolation.

Release kinetics of inflammatory biomarkers in a clinical model of acute myocardial infarction.

RATIONALE: Inflammation in the setting of acute myocardial infarction (MI) has been linked to risk stratification; however, the release kinetics of inflammatory biomarkers in patients with acute MI has been difficult to establish. OBJECTIVE: The aim of this study was to determine the kinetics of changes in the levels of several biomarkers specifically linked to inflammation after transcoronary ablation of septal hypertrophy, a procedure that mimics acute MI. METHODS AND RESULTS: We analyzed release kinetics of C-reactive protein, high-sensitivity C-reactive protein, interleukin-6, soluble CD40 ligand, and peripheral blood leukocyte subsets in patients (n=21) undergoing transcoronary ablation of septal hypertrophy. Blood samples were collected before transcoronary ablation of septal hypertrophy and at various times after transcoronary ablation of septal hypertrophy. Serum levels of C-reactive protein were increased at 24 hours (1.0 mg/dL [interquartile range [IQR], 0.7-1.75] versus 0.2 mg/dL [IQR, 0.1-1.05] at baseline [BL]; P<0.001), whereas high-sensitivity C-reactive protein increased as early as 8 hours (2.68 mg/L [IQR, 1.23-11.80] versus 2.17 mg/L [IQR, 1.15-5.06] at BL; P=0.002). Interleukin-6 was significantly increased at 45 minutes (2.59 pg/mL [IQR, 1.69-5.0] versus 1.5 pg/mL [IQR, 1.5-2.21] at BL; P=0.002), and soluble CD40 ligand was significantly decreased at 60 minutes (801.6 pg/mL [IQR, 675.0-1653.5] versus 1750.0 pg/mL [IQR, 1151.0-2783.0] at BL; P=0.016). Elevated counts of polymorphonuclear neutrophils were detectable at 15 minutes, with a significant increase at 2 hours (6415 cells/µL [IQR, 5288-7827] versus 4697 cells/µL [IQR, 2892-5620] at BL; P=0.004). Significant monocytosis was observed at 24 hours (729 cells/µL [IQR, 584-1344] versus 523 cells/µL [IQR, 369-701] at BL; P=0.015). CONCLUSIONS: Interleukin-6 and neutrophil granulocytes showed a continuous rise at all prespecified time points after induction of MI. Our results provide valuable additional evidence of the diagnostic value of inflammatory biomarkers in the setting of early acute MI.

The slope of the initial temperature drop predicts acute pulmonary vein isolation using the second-generation cryoballoon.

AIMS: There is no objective, early indicator of occlusion quality, and efficacy of cryoballoon pulmonary vein isolation. As previous experience suggests that the initial cooling rate correlates with these parameters, we investigated the slope of the initial temperature drop as an objective measure. METHODS AND RESULTS: A systematic evaluation of 523 cryoapplications in 105 patients using a serial ROC-AUC analysis was performed. We found the slope of a linear regression of the temperature-time function to be a good predictor (PPV 0.9, specificity 0.72, sensitivity 0.71, and ROC-AUC 0.75) of acute isolation. It also correlated with nadir temperatures (P< 0.001, adjusted R2= 0.43), predicted very low nadir temperatures, and varied according to visual occlusion grades (ANOVA P< 0.001). CONCLUSIONS: About 25 s after freeze initiation, the temperature-time slope predicts important key characteristics of a cryoablation, such as nadir temperature. The slope is the only reported predictor to actually precede acute isolation and thus to support decisions about pull-down manoeuvres or aborting a cryoablation early on. It is also predictive of very low nadir temperatures and phrenic nerve palsy and thus may add to patient safety.

Cryoballoon ablation of persistent atrial fibrillation: feasibility and safety of left atrial roof ablation with generation of conduction block in addition to antral pulmonary vein isolation.

AIMS: Although the generation of linear lesions by ablation improves success rates in patients with persistent atrial fibrillation (AF), the procedure has been considered unsuitable for cryoablation balloon catheter technologies. We developed a technique for linear ablations, using second-generation cryoballoon technology. METHODS AND RESULTS: This was a single-arm, prospective study in 76 patients with persistent AF treated consecutively at our centre. Cryoablation was performed using a 28 mm second-generation cryoballoon. The first cryoenergy application was performed in close proximity to the position during isolation of the left superior pulmonary vein (PV). Sequential overlapping freezes were applied along the left atrial (LA) roof by slight clockwise rotation of the sheath in combination with slight retraction of the sheath and incremental advancement of the cryoballoon, until reaching the original position for right superior PV isolation. The acute endpoint was the creation of a roofline, defined as complete conduction block across the LA roof >120 ms and ascending activation across the posterior LA wall. Acute success in roofline generation was achieved in 88% of patients, applying on average five (median 4-6) freezes with nadir temperature of -40°C (-36 to -44°C). In five patients, conduction block could not be achieved. No phrenic nerve injuries occurred during roofline generation. CONCLUSION: Generation of linear roofline lesions is possible with the second-generation cryoballoon. The technique can be used in combination with PV isolation to treat persistent AF with good acute success rates, short procedure times, and acceptable safety concerns. If validated by further studies, the method would be an appealing alternative to radiofrequency ablation techniques.

Plasma microRNA-21 for the early prediction of acute kidney injury in patients undergoing major cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is a complication after major cardiac surgery that is associated with higher rates of morbidity and mortality. MicroRNA-21 (miR-21) has been described as an early biomarker for AKI. We investigated whether miR-21 is predictive of AKI and long-term mortality after cardiac surgery. METHODS: Consecutive patients (n = 115) undergoing major cardiac surgery were included. Serum creatinine was measured prior to, 4 h after, and 1, 4 and 7 days after extracorporeal circulation. Diagnosis of post-operative AKI was made in accordance with the international Kidney Disease: Improving Global Outcomes definition of AKI. Serum cystatin C and miR-21 were measured prior to and 4 h after surgery. miR-21 was determined by quantitative RT-PCR and was normalized to miRNA-39 from Caenorhabditis elegans. The median follow-up time was 2.9 years. RESULTS: AKI occurred in 36.5% (n = 42) of all patients. Baseline miR-21 was significantly lower in patients developing cardiac surgery-associated AKI (CSA-AKI) than in patients without CSA-AKI [0.27 (interquartile range, IQR, 0.14-0.30) versus 0.44 (IQR 0.25-0.75); P < 0.01]. Baseline miR-21 predicted CSA-AKI Stage 2/3 with an area under the curve of 0.701 [95% confidence interval (CI) 0.59-0.82; P = 0.007]. Baseline miR-21 <0.31 showed a hazard ratio of 3.11 (95% CI: 1.33-11.26) for CSA-AKI Stage 2/3. Patients with AKI Stage 2/3 had a significantly higher mortality (50 versus 10%; P = 0.0001) and dialysis rate (27 versus 11%; P = 0.038) within the 2.9-year follow-up. CONCLUSIONS: Our results indicate that miR-21 has the potential to identify patients at higher risk for CSA-AKI. This predictive value might be helpful in pre-procedural risk assessment and peri-procedural diagnosis and treatment.

Clinical impact of a novel three-dimensional electrocardiographic imaging for non-invasive mapping of ventricular arrhythmias-a prospective randomized trial.

AIMS: ECVUE™ technology, a novel, three-dimensional, non-invasive mapping system, offers a unique arrhythmia characterization and localization. We sought to evaluate the clinical impact of this system in routine clinical mapping and ablation of ventricular arrhythmias (VAs). METHODS AND RESULTS: Patients with monomorphic premature ventricular contractions with or without monomorphic ventricular tachycardia were enrolled prospectively and randomized into two groups: ventricular ectopy localization using either 12-lead electrocardiogram (ECG) algorithms or with ECVUE™, followed by conventional guided ablation. Forty-two patients were enrolled in the study. The ECVUE™ system accurately identified both the chamber and sub-localized the VA origin in 20 of 21 (95.2%) patients. In contrast, using 12-lead ECG algorithms, the chamber was accurately diagnosed in 16 of 21 (76.2%) patients, while the arrhythmia origin in only 8 of 21 (38.1%), (P = 0.001 vs. ECVUE™). Acute success in ablation was achieved in all patients. Regarding the number of radiofrequency-energy applications (in total 2 vs. 4, P = 0.005) in the ECVUE™ arm, ablation was more precise than the ECG group which used standard of care activation and pace mapping-guided ablation. Three months success in ablation was 95.2% for the ECVUE™ and 100% for the ECG group (P = ns). Time to ablation was 35.3 min in the conventional arm and 24.4 min in ECVUE Group, (P = 0.035). The X-ray radiation exposure was 3.21 vs. 0.39 mSv, P = 0.001 for the ECVUE™ group and ECG group. CONCLUSION: ECVUE™ technology offers a clinically useful tool to map VAs with high accuracy and more targeted ablations superior to the body surface ECG but had significantly higher radiation exposure due to computed tomography scan.

The Impact of Left Atrial Surface Area and the Second Generation Cryoballoon on Clinical Outcome of Atrial Fibrillation Cryoablation.

AIMS: In this observational study, we examine the significance of the left atrial (LA) surface area and compare the clinical usage of the Arctic Front Advance (CBA) versus Arctic Front (CB) cryoballoon with the intent to investigate the impact of each in terms of long-term freedom from atrial fibrillation (AF) for patients with nonvalvular AF. METHODS: Pulmonary vein isolation (PVI) was performed while using a cryoballoon ablation catheter in conjunction with an intraluminal circular diagnostic mapping catheter, Achieve. The consecutive patients ablated with CBA were matched with patients previously ablated with CB, using propensity score matching. The primary endpoint of this observational single-center retrospective study was the first observation of electrocardiogram-documented recurrence of atrial arrhythmias lasting >30 seconds. RESULTS: The patient demographic data were similar in the CBA- and CB-group (N = 188 patients each group). In all patients in the CBA-group and in 95% of the patients in the CB group, acute procedural PVI of all veins was achieved with the single usage of a 28-mm cryoballoon. The one-year freedom from atrial arrhythmias was significantly better in the CBA- versus the CB-group of patients, 90% versus 64%, respectively. During 15-month clinical follow-up in CBA group, patients with LA area above 23 cm(2) were more likely to experience recurrence of AF (23%) than patients with LA area below 23 cm(2) (7%). CONCLUSIONS: Comparing one-year outcomes, the CBA is superior to the CB with regards to maintenance of normal sinus rhythm. When using the CBA catheter, an enlarged LA is associated with a higher recurrence of arrhythmia.

Learning curve in cryoballoon ablation of atrial fibrillation: eight-year experience.

BACKGROUND: We analyzed the procedural experience cryoballoon ablation (CBA) of atrial fibrillation (AF) gained over 8 years in a high-volume centre to understand the influence of the learning curve on feasibility, safety and clinical outcome. METHODS AND RESULTS: In 424 patients (62% male) with drug-refractory AF, CBA was performed between 2005 and 2012. The analyzed period was divided into 8 calendar years. The endpoint of the study was arrhythmia recurrence after the 3-month blanking period in the 1-year follow-up since the index procedure, in the absence of anti-arrhythmic drugs class I and III. A combined AF type, Left Atrium size, Renal insufficiency, MEtabolic syndrome, cardiomyopathy (ALARMEc) risk score was calculated for each patient. The overall 1-year success rate of a single CBA was 73%. Continuous increase in 1-year success rate was observed with successive years of the study. The gradual improvement in outcome was related to gradual fall in ALARMEc risk score in successive patients. A continuous decrease in fluoroscopy and procedure time was observed in each subsequent year. CONCLUSIONS: CBA, followed by the proper selection of patients, facilitates a satisfactory outcome, especially in patients at an early stage of PV-trigger-dependent AF. Still, as with each new technology, it requires completion of a learning curve.

Score associated with the outcome after multiple ablation procedures in patients with atrial fibrillation.

BACKGROUND: Catheter ablation (CA) of atrial fibrillation (AF) is now established therapeutic option. Multiple procedures (MPs) are often needed to achieve the satisfactory outcome. The aim of the study was to assess the outcome after MPs in AF patients categorized to risk-score groups. METHODS: We followed a cohort of consecutive 911 (69% male; median 59 years) patients with AF (58% paroxysmal) who had CAAF performed. ALARMEC (Atrial fibrillation type, Left Atrium size, Renal insufficiency, MEtabolic syndrome, cardiomyopathy) risk score was calculated for each patient. The end point was maintenance of sinus rhythm at the follow-up of 60 months. RESULTS: We performed 1,199 CAAF procedures. One, two, and three procedures were performed in 663 (73%), 208 (23%), and 40 (4%) patients, respectively. Outcome after the first procedure (56%) was improved with MPs (76%). MPs > 2 were performed in 1%, 3%, 5%, 6%, and 10% patients with ALARMEC score of 0, 1, 2, 3, and 4, respectively. MPs were successful in 89%, 86%, 81%, 65%, and 43% of patients with ALARMEC score of 0, 1, 2, 3, and 4, respectively. Outcome in 174 (19%) patients on antiarrhythmic drugs (AADs) was 85%, 68%, 75%, 44%, and 39% in ALARMEC score: 0, 1, 2, 3, and 4, respectively. Outcome in 737 (81%) patients without AAD was 90%, 85%, 80%, 77%, and 69% in ALARMEC score of 0, 1, 2, 3, and 4, respectively. CONCLUSION: The moderate success rate after index procedure of CAAF can be further improved with multiple ones and AAD.

Personalised preinterventional risk stratification of mortality, length of stay and hospitalisation costs in transcatheter aortic valve implantation using a machine learning algorithm: a pilot trial.

INTRODUCTION: Risk stratification based on Euroscore II (ESII) is used in some centres to assist decisions to perform transcatheter aortic valve implant (TAVI) procedures. ESII is a generic, non-TAVI-specific metric, and its performance fades for mortality at follow-up longer than 30 days. We investigated if a TAVI-specific predictive model could achieve improved predictive preinterventional accuracy of 1-year mortality compared with ESII. PATIENTS AND METHODS: In this prospective pilot study, 284 participants with severe symptomatic aortic valve stenosis who underwent TAVI were enrolled. Standard clinical metrics (American Society of Anesthesiology (ASA), New York Heart Association and ESII) and patient-reported outcome measures (EuroQol-5 Dimension-Visual Analogue Scale, Kansas City Cardiomyopathy Questionnaire and Clinical Frailty Scale (CFS)) were assessed 1 day before TAVI. Using these data, we tested predictive models (logistic regression and decision tree algorithm (DTA)) with 1-year mortality as the dependent variable. RESULTS: Logistic regression yielded the best prediction, with ASA and CFS as the strongest predictors of 1-year mortality. Our logistic regression model score showed significantly better prediction accuracy than ESII (area under the curve=0.659 vs 0.800; p=0.002). By translating our results to a DTA, cut-off score values regarding 1-year mortality risk emerged for low, intermediate and high risk. Treatment costs and length of stay (LoS) significantly increased in high-risk patients. CONCLUSIONS AND SIGNIFICANCE: A novel TAVI-specific model predicts 1-year mortality, LoS and costs after TAVI using simple, established, transparent and inexpensive metrics before implantation. Based on this preliminary evidence, TAVI team members and patients can make informed decisions based on a few key metrics. Validation of this score in larger patient cohorts is needed.

Pulmonary Vein Isolation Followed by Biatrial Ablation of Rotational Activity in Patients with Persistent Atrial Fibrillation: Results of the Cryo-Vest Study.

Background and Aims: Noninvasive mapping allows the identification of patient-specific atrial rotational activity (RA) that might play a key role in the perpetuation of persistent atrial fibrillation (PsAF). So far, the impact of pulmonary vein isolation by cryoballoon (Cryo-PVI) on RA is unclear. Moreover, the long-term effect of periprocedural termination of AF during the ablation procedure is controversial. Methods: Noninvasive electrocardiographic mapping with a 252-electrode vest was performed in 42 patients with PsAF. After the first analysis, Cryo-PVI was performed. The RA was analyzed again and then targeted by radiofrequency catheter ablation. The primary clinical endpoint was periprocedural termination of AF. The secondary endpoint was freedom from any atrial arrhythmia >30 s during a 12-month follow-up. Results: In 33 patients (79%), right atrial RA was identified leading to biatrial ablation, and nine patients (21%) had left atrial RA only. Twelve patients (28.6%) converted from AF to sinus rhythm (SR) (Group A). Thirteen patients (30.9%) converted to atrial tachycardia (AT) (Group B). In 17 patients (40.5%), AF was not terminated by ablation (Group C). After a mean follow-up time of 13.8 months, 26 patients were free from AF and AT (61.9%). In terms of rhythm, control Group A (75%) and B (83.3%) showed higher success rates than Group C (33.3%) (p < 0.01). Cryo-PVI had no substantial impact on RA. Conclusions: The RA-based ablation approach showed acceptable success rates. Periprocedural termination of AF had a positive predictive impact on the outcome. No difference was observed between conversion to SR or to AT. Cryo-PVI had no impact on RA.