Process optimization for atrial fibrillation ablation.

AIMS: In the light of an increasing prevalence of atrial fibrillation (AF) and growing evidence for the superiority of early invasive rhythm control, the demand for ablation therapy is rising. Accordingly, ablation centres will have to maximize their capacity by either adding electrophysiology laboratory resources or optimizing process management. In order to optimize process management, we applied "Lean Six Sigma" method to a single ablation center. We compared procedural parameters, acute efficacy and safety of cryoballoon pulmonary vein isolation (cryoPVI) before and after modifications. METHODS AND RESULTS: Patients (n = 713) undergoing cryoPVI (108 before and 605 after process optimization) were analysed. Within 3 years of process optimization, electrophysiology laboratory occupancy time (150.7 ± 44.4 vs. 94 ± 22.1 min, P < 0.001), procedure time (84.5 ± 21-47.4 ± 12 min, P < 0.001), left-atrial dwell time (53.9 ± 18.4-31.9 ± 9.9 min, P < 0.001), and fluoroscopy time (15.8 ± 5.1 vs. 6.2 ± 2.8 min, P < 0.001) decreased. Contrast dye use (116 ± 35 vs. 27 ± 15 mL, P < 0.001) and radiation dose (893 ± 1078 vs. 253 ± 249 cGy cm2, P < 0.001) were reduced by ∼77 and ∼72%, respectively. There was no difference in safety endpoint occurrence (3.7 vs. 1.5%, P = 0.11). CONCLUSION: The process optimization of cryoPVI for AF therapy using the 'Lean Six Sigma' method significantly increases efficiency without compromising patient safety.

Age-related regulation and region-specific distribution of ion channel subunits promoting atrial fibrillation in human left and right atria.

AIMS: Age-induced changes and electrical remodelling are important components of the atrial fibrillation (AF) substrate. To study regional distribution and age-dependent changes in gene expression that may promote AF in human atria. METHODS AND RESULTS: Human left atrial (LA) and right atrial (RA) tissue samples were obtained from donor hearts unsuitable for transplantation and from patients undergoing mitral valve repair. Atrial fibrillation was mimicked in vitro by tachypacing of human atrial tissue slices. Ionic currents were studied by the whole-cell patch-clamp technique; gene expression was analysed by real-time qPCR and immunoblotting. Both healthy RA and RA from older patients showed greater CACNA1c mRNA and CaV1.2 protein expression than LA. No age-dependent changes of Kir2.1 expression in both atria were seen. Remodelling occurred in a qualitatively similar manner in RA and LA. IK1 and Kir2.1 protein expression increased with AF. MiR-1, miR-26a, and miR-26b were down-regulated with AF in both atria. ICa,L was decreased. CACNA1c and CACNA2b expression decreased and miR-328 increased in RA and LA during AF. Ex vivo tachypacing of human atrial slices replicated these findings. There were age-dependent increases in miR-1 and miR-328, while miR-26a decreased with age in atrial tissues from healthy human donor hearts. CONCLUSION: Features of electrical remodelling in man occur in a qualitatively similar manner in both human atria. Age-related miR-328 dysregulation and reduced ICa,L may contribute to increased AF susceptibility with age.

The early repolarization pattern: Echocardiographic characteristics in elite athletes.

BACKGROUND: The electrocardiographic early repolarization (ER) pattern is associated with idiopathic ventricular fibrillation and increased long-term cardiovascular mortality. Whether structural cardiac aberrations influence the phenotype is unclear. Since ER is particularly common in athletes, we evaluated its prevalence and investigated predisposing echocardiographic characteristics and cardiopulmonary exercise capacity in a cohort of elite athletes. METHODS: A total of 623 elite athletes (age 21 ± 5 years) were examined during annual preparticipation screening from 2006 until 2012 including electrocardiography, echocardiography, and exercise testing. ECGs were analyzed with focus on ER. All athletes participated in a clinical follow-up. RESULTS: The prevalence of ER was 17% (108/623). ER-positive athletes were predominantly male (71%, 77/108), showed a lower heart rate (57.1 ± 9.3 bpm versus 60.0 ± 11.2 bpm; p = 0.015) and a higher lean body mass compared to ER-negative participants (88.1% ± 5.6% versus 86.5% ± 6.3%; p = 0.015). Echocardiographic measurements and cardiopulmonary exercise capacity in male and female athletes with and without ER largely showed similar results. Only the notching ER subtype (n = 15) was associated with an increased left atrial diameter (OR 7.01, 95%CI 1.65-29.83; p = 0.008), a higher left ventricular mass (OR 1.02, 95%CI 1.00-1.03; p = 0.038) and larger relative heart volume (OR 1.01, 95%CI 1.00-1.01; p = 0.01). During a follow-up of 7.4 ± 1.5 years, no severe cardiovascular event occurred in the study sample. CONCLUSIONS: In elite athletes presence of ER is not associated with distinct alterations in echocardiography and cardiopulmonary exercise. Athletes presenting with ER are rather male, lean with a low heart rate.

Large-Scale Analysis of Determinants, Stability, and Heritability of High-Density Lipoprotein Cholesterol Efflux Capacity.

OBJECTIVE: Cholesterol efflux capacity (CEC) has emerged as a biomarker of coronary artery disease risk beyond plasma high-density lipoprotein (HDL) cholesterol (HDL-C) level. However, the determinants of CEC are incompletely characterized. We undertook a large-scale family-based population study to identify clinical, biochemical, and HDL particle parameter determinants of CEC, characterize reasons for the discordancy with HDL-C, quantify its heritability, and assess its stability over 10 to 12 years. APPROACHES AND RESULTS: CEC was quantified in 1988 individuals from the GRAPHIC (Genetic Regulation of Arterial Pressure of Humans in the Community) cohort, comprising individuals from 2 generations from 520 white nuclear families. Serum lipid and lipoprotein levels were determined by ultracentrifugation or nuclear magnetic resonance and HDL particle size and number quantified by nuclear magnetic resonance. Ninety unrelated individuals had repeat CEC measurements in samples collected after 10 to 12 years. CEC was positively correlated with HDL-C (R=0.62; P<0.0001). Among clinical and biochemical parameters, age, systolic blood pressure, alcohol consumption, serum albumin, triglycerides, phospholipids, and lipoprotein(a) were independently associated with CEC. Among HDL particle parameters, HDL particle number, particle size, and apolipoprotein A-II level were independently associated with CEC. Serum triglyceride level partially explained discordancy between CEC and HDL-C. CEC measurements in samples collected 10 to 12 years apart were strongly correlated (r=0.73; P<0.0001). Heritability of CEC was 0.31 (P=3.89×10-14) without adjustment for HDL-C and 0.13 (P=1.44×10-3) with adjustment. CONCLUSIONS: CEC is a stable trait over time, is influenced by specific clinical, serum, and HDL particle parameters factors beyond HDL-C, can be maintained in persons with a low plasma HDL-C by elevated serum triglyceride level, and is modestly independently heritable.

Cryoballoon vs. radiofrequency ablation for paroxysmal atrial fibrillation: an updated meta-analysis of randomized and observational studies.

AIMS: Radiofrequency (RF) ablation represents a standard of care for pulmonary vein isolation in patients with drug-refractory paroxysmal atrial fibrillation (AF). In this setting, cryoballoon (CB) ablation has emerged as alternative therapy. However, the efficacy and safety of CB vs. RF ablation in patients with paroxysmal AF remain a matter of debate. METHODS AND RESULTS: We searched electronic scientific databases for studies of CB vs. RF ablation in patients with paroxysmal AF. Aggregate data were pooled to perform a meta-analysis. The primary efficacy and safety outcomes were the recurrence of any atrial arrhythmia and procedure-related complications, respectively. A total of 6473 participants from 10 studies (CB, n = 2232 vs. RF, n = 4241) were studied. After a median follow-up of 16 months, the risk of any atrial arrhythmia recurrence (risk ratio, RR 95% confidence interval [95% CI] = 1.01 [0.90-1.14], P = 0.83) and procedure-related complications (RR [95% CI] = 0.92 [0.66-1.28], P = 0.61) were comparable between CB vs. RF ablation. Cryoballoon ablation led to a higher risk of persistent phrenic nerve palsy (RR [95% CI] = 13.60 [3.87-47.81], P < 0.01) and a lower risk of cardiac tamponade (RR [95% CI] = 0.48 [0.25-0.89], P = 0.02) compared with RF ablation. There was a trend of statistically significant interaction between the type of CB and the duration of ablation (P for interaction = 0.09). CONCLUSION: In patients with paroxysmal AF, ablation therapy with CB is associated with efficacy and safety comparable to that of RF. Second-generation CB catheters seem to reduce procedure duration. Further studies are warranted to disclose the impact of second-generation CB catheters compared with RF for ablation of paroxysmal AF.

Ultra-sensitive troponin I is an independent predictor of incident coronary heart disease in the general population.

Troponins are sensitive markers of myocardial injury and predictive of cardiovascular events, but conventional assays fail to detect slightly elevated troponins in a considerable proportion of the general population. Using a novel ultrasensitive assay, we explored the relationship of troponin levels with the incidence of coronary heart disease (CHD) in a case-cohort sample (mean age 52.5 ± 0.2 years, 51.5% women) comprising 803 CHD cases and 1942 non-cases. Ultrasensitive troponin I was detectable in 99.9% of available case-cohort samples. In an age- and sex-adjusted model, individuals in the highest quartile of the troponin distribution had a more than threefold increased risk for CHD events compared to those in the bottom quartile [hazard ratio, HR, 3.11; 95% confidence interval (CI) 2.15-4.49]. In a model adjusting for cardiovascular risk factors including C-reactive protein, cystatin C and N-terminal pro brain natriuretic peptide, individuals in the highest troponin I quartile still showed a hazard ratio of 2.58 (95% CI 1.66-4.00) for incident CHD as compared to those in the lowest quartile. Ultrasensitive troponin I was detectable in almost all individuals of a study sample reflecting middle-aged to elderly European general population. Ultrasensitive troponin concentrations exhibit an independent, graded, positive relation with incident CHD.

Irrigated-tip catheters for radiofrequency ablation of right-sided accessory pathways in adolescents.

BACKGROUND: Catheter ablation of right-sided accessory pathways (APs) has lower success and higher recurrence rates compared to left-sided substrates. Irrigated-tip catheter (ITC) ablation might offer an advantage in this setting but data about its use in patients below 18 years are scarce. The aim of this study was to compare an ITC approach to conventional catheter ablation. METHODS: A retrospective analysis of all patients <18 years undergoing radiofrequency ablation (RFA) for right-sided APs from 2004 to 2014 at our institution was performed. Patients either underwent an ITC approach in combination with 3-D mapping (Group 1; n  =  53) or a conventional non-ITC approach (Group 2; n  =  52). Study endpoints were acute procedural success, safety, and recurrence rate. A total of 105 mostly adolescent patients (56.2% male; median age 14 years) with 107 right-sided APs were included. RESULTS: The prevailing anatomic AP locations were right posteroseptal (44.9%), right anterior/anterolateral (24.3%), and right lateral (13.1%). Acute success (94.3% vs 94.2%) did not differ between the groups. One major complication (pericardial effusion) occurred in the non-ITC group. Overall, freedom from AP recurrence was 94% at 4 years in the ITC group, and 81% at 4 years in the non-ITC group (P  =  0.04). CONCLUSIONS: The use of ITCs in combination with 3-D mapping system for ablation of right-sided APs in adolescents has a high acute success rate, is safe, and associated with a significantly reduced recurrence rate compared to a non-ITC/conventional approach. It might be considered as alternative approach in this age group.

Autotaxin activity has a high accuracy to diagnose intrahepatic cholestasis of pregnancy.

BACKGROUND & AIMS: Intrahepatic cholestasis of pregnancy (ICP) is defined by pruritus, elevated total fasting serum bile salts (TBS) and transaminases, and an increased risk of adverse fetal outcome. An accurate diagnostic marker is needed. Increased serum autotaxin correlates with cholestasis-associated pruritus. We aimed at unraveling the diagnostic accuracy of autotaxin in ICP. METHODS: Serum samples and placental tissue were collected from 44 women with uncomplicated pregnancies and 105 with pruritus and/or elevated serum transaminases. Autotaxin serum levels were quantified enzymatically and by Western blotting, autotaxin gene expression by quantitative PCR. RESULTS: Serum autotaxin was increased in ICP (mean ± SD: 43.5 ± 18.2 nmol ml(-1)min(-1), n=55, p<0.0001) compared to other pruritic disorders of pregnancy (16.8 ± 6.7 nmol ml(-1)min(-1), n=33), pre-eclampsia complicated by HELLP-syndrome (16.8 ± 8.9 nmol ml(-1)min(-1), n=17), and pregnant controls (19.6 ± 5.7 nmol ml(-1)min(-1), n=44). Longitudinal analysis during pregnancy revealed a marked rise in serum autotaxin with onset of ICP-related pruritus. Serum autotaxin was increased in women taking oral contraceptives. Increased serum autotaxin during ICP was not associated with increased autotaxin mRNA in placenta. With a cut-off value of 27.0 nmol ml(-1)min(-1), autotaxin had an excellent sensitivity and specificity in distinguishing ICP from other pruritic disorders or pre-eclampsia/HELLP-syndrome. Serum autotaxin displayed no circadian rhythm and was not influenced by food intake. CONCLUSIONS: Increased serum autotaxin activity represents a highly sensitive, specific and robust diagnostic marker of ICP, distinguishing ICP from other pruritic disorders of pregnancy and pregnancy-related liver diseases. Pregnancy and oral contraception increase serum autotaxin to a much lesser extent than ICP.

Atrial Tachycardias Following Persistent Atrial Fibrillation Ablation: Predictors of Recurrence After the Repeat Ablation.

BACKGROUND: Repeat procedures after persistent atrial fibrillation (AF) ablation are frequently performed for secondary atrial tachycardias (AT). Predictors of AT recurrence after the first repeat ablation have not yet been studied. METHODS: We investigated predictors of AT recurrence in 117 patients who underwent ablation for secondary AT arising after a previous ablation for persistent AF using the Cox proportional hazards model. RESULTS: Acute ablation success rate was 94%. Over a follow-up period of 12 months, 61 patients (53%) were free from AT recurrence. Of the assessed predictors of AT recurrence, the number of ablated AT forms (>1 vs. 1) was significantly associated with AT recurrence (hazard ratio 2.01, 95% CI 1.18-3.43, P = 0.01). Other variables including left atrial diameter, AT mechanism, or the characteristics of previous AF ablation did not have significant influence on AT recurrence (P>0.05). Men had a tendency toward fewer AT recurrences than women (OR 0.60, 95% CI 0.34-1.05, P = 0.07). During a second AT ablation procedure, 19 (49%) patients were identified to have a recurrence of the previously ablated AT, whereas in 20 patients (51%) a new AT form was diagnosed. CONCLUSION: Ablation of atrial tachycardias following persistent AF ablation has a high acute success rate. However, a substantial number of patients develop new onset AT during follow-up. The occurrence of multiple AT forms during the repeat ablation procedure was the only predictive factor for AT recurrence.

Sensor-Based Electromagnetic Navigation (Mediguide®): How Accurate Is It? A Phantom Model Study.

BACKGROUND: Data about localization reproducibility as well as spatial and visual accuracy of the new MediGuide® sensor-based electroanatomic navigation technology are scarce. We therefore sought to quantify these parameters based on phantom experiments. METHODS AND RESULTS: A realistic heart phantom was generated in a 3D-Printer. A CT scan was performed on the phantom. The phantom itself served as ground-truth reference to ensure exact and reproducible catheter placement. A MediGuide® catheter was repeatedly tagged at selected positions to assess accuracy of point localization. The catheter was also used to acquire a MediGuide®-scaled geometry in the EnSite Velocity® electroanatomic mapping system. The acquired geometries (MediGuide®-scaled and EnSite Velocity®-scaled) were compared to a CT segmentation of the phantom to quantify concordance. Distances between landmarks were measured in the EnSite Velocity®- and MediGuide®-scaled geometry and the CT dataset for Bland-Altman comparison. The visualization of virtual MediGuide® catheter tips was compared to their corresponding representation on fluoroscopic cine-loops. Point localization accuracy was 0.5 ± 0.3 mm for MediGuide® and 1.4 ± 0.7 mm for EnSite Velocity®. The 3D accuracy of the geometries was 1.1 ± 1.4 mm (MediGuide®-scaled) and 3.2 ± 1.6 mm (not MediGuide®-scaled). The offset between virtual MediGuide® catheter visualization and catheter representation on corresponding fluoroscopic cine-loops was 0.4 ± 0.1 mm. CONCLUSIONS: The MediGuide® system shows a very high level of accuracy regarding localization reproducibility as well as spatial and visual accuracy, which can be ascribed to the magnetic field localization technology. The observed offsets between the geometry visualization and the real phantom are below a clinically relevant threshold.

Dissociated pulmonary vein activity after pulmonary vein isolation for paroxysmal atrial fibrillation: a predictor for recurrence?

BACKGROUND: The role of dissociated pulmonary vein (DPV) activity after pulmonary vein isolation (PVI) is still poorly defined. We evaluated electrophysiological features and clinical impact on long-term outcome of DPV activity. METHODS: A total of 243 patients (mean age 63 ± 11 years; 63% males) undergoing PVI for paroxysmal atrial fibrillation (AF) were included. DPV activity was defined as a residual low frequency irregular PV rhythm. Patients were divided into Group 1 (presence of DPV activity; n = 65) or Group 2 (absence of DPV activity; n = 178). RESULTS: Of 936 isolated PVs, 112 PVs (12%) showed DPV activity. DPV activity was observed more frequently in PVs identified as AF triggers (P = 0.026). During follow-up (mean 12 ± 7 months), 15 of 65 patients of Group 1 (23%) and 57 of 178 patients of Group 2 (32%) had an arrhythmia recurrence (P = 0.23). At linear regression analysis, no independent predictor for clinical recurrence was identified. During the repeat ablation, 62 of 72 patients (86%) showed a recovered PV conduction without difference between the 2 groups. Clinically, all patients of Group 1 with PV reconnection (n = 13/15) had a recurrence of paroxysmal AF. In Group 2, 5 of 52 patients with reconnected PV developed non-PV related arrhythmias. CONCLUSION: DPV activity occurred in 12% of PVs after PVI and was observed more frequently in PVs identified as AF triggers. DPV activity was not predictive for AF recurrence during follow-up. PV-left atrium reconnection involving PVs with DPV activity leads to AF.

The relation of red blood cell fatty acids with vascular stiffness, cardiac structure and left ventricular function: the Framingham Heart Study.

Polyunsaturated fatty acids have been associated with beneficial influences on cardiovascular health. However, the underlying mechanisms are not clear, and data on the relations of polyunsaturated fatty acids to subclinical disease measures such as vascular stiffness and cardiac function are sparse and inconclusive. In a large community-based cohort, we examined the relations of omega-3 and other fatty acids to a comprehensive panel of vascular function measures (assessing microvascular function and large artery stiffness), cardiac structure and left ventricular function. Red blood cell (RBC) membrane fatty acid composition, a measure of long-term fatty acid intake, was assessed in participants of the Framingham Offspring Study and Omni cohorts and related to tonometry-derived measures of vascular stiffness and to a panel of echocardiographic traits using partial correlations. Up to n=3055 individuals (56% women, mean age 66 years) were available for analyses. In age- and sex-adjusted models, higher RBC omega-3 content was moderately associated (p≤0.002) with several measures of vascular stiffness and function in a protective direction. However, after multivariable adjustment, only an association of higher RBC omega-3 content with lower carotid-femoral pulse wave velocity (a measure of aortic stiffness) remained significant (r = -0.06, p=0.002). In secondary analyses, higher linoleic acid, the major nutritional omega-6 fatty acid, was associated with smaller left atrial size, even after multivariable adjustment (r = -0.064, p<0.001). In conclusion, in our cross-sectional community-based study, we found several associations consistent with the notion of protective effects of omega-3 and linoleic acid. The clinical significance of these modest associations remains to be elucidated.

Genetic associations with lipoprotein subfractions provide information on their biological nature.

Adverse levels of lipoproteins are highly heritable and constitute risk factors for cardiovascular outcomes. Hitherto, genome-wide association studies revealed 95 lipid-associated loci. However, due to the small effect sizes of these associations large sample numbers (>100 000 samples) were needed. Here we show that analyzing more refined lipid phenotypes, namely lipoprotein subfractions, can increase the number of significantly associated loci compared with bulk high-density lipoprotein and low-density lipoprotein analysis in a study with identical sample numbers. Moreover, lipoprotein subfractions provide novel insight into the human lipid metabolism. We measured 15 lipoprotein subfractions (L1-L15) in 1791 samples using (1)H-NMR (nuclear magnetic resonance) spectroscopy. Using cluster analyses, we quantified inter-relationships among lipoprotein subfractions. Additionally, we analyzed associations with subfractions at known lipid loci. We identified five distinct groups of subfractions: one (L1) was only marginally captured by serum lipids and therefore extends our knowledge of lipoprotein biochemistry. During a lipid-tolerance test, L1 lost its special position. In the association analysis, we found that eight loci (LIPC, CETP, PLTP, FADS1-2-3, SORT1, GCKR, APOB, APOA1) were associated with the subfractions, whereas only four loci (CETP, SORT1, GCKR, APOA1) were associated with serum lipids. For LIPC, we observed a 10-fold increase in the variance explained by our regression models. In conclusion, NMR-based fine mapping of lipoprotein subfractions provides novel information on their biological nature and strengthens the associations with genetic loci. Future clinical studies are now needed to investigate their biomedical relevance.

Catheter ablation for atrial fibrillation in elderly patients: an updated meta-analysis of comparative studies.

BACKGROUND: Age is a relevant risk factor for the development of atrial fibrillation (AF) and is associated with increased recurrence rates in the setting of rhythm-control. Catheter ablation is increasingly advocated in elderly despite conflicting data regarding its efficacy and safety in this patient cohort. Therefore, we aimed to analyze currently available evidence regarding catheter ablation for AF in patients ≥75 years compared to younger patients. METHODS: We performed a systematic literature search and meta-analysis on efficacy and safety of catheter ablation in patients ≥75 years with AF. Primary efficacy and safety endpoints were: first recurrence of atrial arrhythmia following first-time ablation and occurrence of death, stroke, or any procedure-related complication. Secondary outcomes included procedure and fluoroscopy time. RESULTS: We identified 301 potentially relevant studies of which 39 underwent detailed analysis. A total of 19 studies (MINORS score ≥13) reporting on 108,419 patients (101,844 <75 years, 6,575 ≥75 years) undergoing first-time catheter ablation for AF were included. Risk of arrhythmia recurrence following catheter ablation (39% vs. 32%; RR [95% CI] 1.24 [1.09-1.41]; P=0.001) and occurrence of safety endpoints (10.8% vs. 8.5%; RR [95% CI] 1.64 [1.53-1.76], P<0.00001) were significantly higher in patients ≥ 75 years compared to younger patients. There was no difference concerning procedure (P=0.33) or fluoroscopy time (P=0.91) between younger and elderly patients. CONCLUSION: In patients ≥75 years of age catheter ablation for AF has higher risk of arrhythmia recurrence and is associated with an increased risk of procedure-related complications and safety endpoint occurrence compared to younger patients.

Pulmonary Vein Isolation or Pace & Ablate in Elderly Patients with Persistent Atrial Fibrillation (ABLATE versus PACE) - Rationale, Methods and Design.

Age is a major risk-factor for atrial fibrillation (AF) and associated hospitalizations. With increasing emphasis on rhythm-control, pulmonary-vein isolation (PVI) is often suggested, even to elderly patients (≥75 years). Efficacy of PVI aiming at rhythm-control is limited in persistent AF. Pacemaker implantation with atrioventricular-node ablation may represent a reasonable alternative, with the aim of controlling symptoms and improving quality-of-life in elderly patients. In this investigator-initiated, randomized, multicenter trial, we test the hypothesis that pacemaker-implantation and atrioventricular-node (AVN) ablation provides superior symptom-control over PVI in elderly patients with symptomatic persistent AF, without any increase in adverse-event profile. In the "ABLATE versus PACE" (NCT04906668) prospective, open-label superiority trial 196 elderly patients with normal ejection fraction and symptomatic persistent AF despite guideline-indicated medical therapy, will be randomized to either cryoballoon-PVI (ABLATE) or dual-chamber pacemaker implantation with subsequent AVN ablation (PACE), and followed for a minimum of 12 months. The primary efficacy outcome is a composite endpoint of rehospitalization for atrial arrhythmia or cardiac decompensation/ heart failure, (outpatient) electrical cardioversion or upgrade to cardiac resynchronization therapy due to worsening of left-ventricular ejection fraction ≤35%. Secondary endpoints include death from any cause, stroke, quality of life or procedure-related complications. Sample-size is designed to achieve 80% power for the primary endpoint (two-tailed alpha of 5%). "ABLATE versus PACE" will determine whether pacemaker implantation and AVN ablation can improve symptom-control in elderly patients with persistent AF over PVI without increasing safety endpoints.

Angiotensin Receptor-Neprilysin Inhibitor Is Associated With Improved Cardiac Autonomic Function in Heart Failure.

BACKGROUND: Heart failure with reduced ejection fraction is associated with potentially deleterious imbalance of the cardiac autonomic nervous system. Sacubitril/valsartan (angiotensin receptor-neprilysin inhibitor [ARNI]) reduces cardiovascular mortality and hospitalization for heart failure with reduced ejection fraction. Whether ARNI affects the cardiac autonomic nervous system has not been studied. METHODS AND RESULTS: This investigator-initiated, prospective, single-center cohort study compared heart rate (HR) variability, HR, deceleration capacity, and periodic repolarization dynamics as noninvasive measures of the cardiac autonomic nervous system before and after initiation of ARNI therapy. Patients underwent standardized 12-lead Holter-ECG, echocardiography and laboratory testing before and 3 months after start of therapy. End points were changes in HR variability (SD of normal-to-normal intervals, mean square of differences between consecutive R-R intervals), HR, deceleration capacity, and periodic repolarization dynamics as well as ventricular function and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Of 63 patients with heart failure with reduced ejection fraction enrolled, 48 (76.2%) patients were still on ARNI at follow-up. SD of normal-to-normal intervals increased from 25 to 36 milliseconds (P<0.001), mean square of differences between consecutive R-R intervals increased from 12 to 19 milliseconds (P<0.001), HR decreased from 73±9 bpm to 67±4 bpm, (P<0.001), and deceleration capacity increased from 2.1 to 4.4 milliseconds (P<0.001). A trend for periodic repolarization dynamics reduction was observed (5.6 deg2 versus 4.7 deg2, P=0.09). Autonomic changes were accompanied by increased left ventricular ejection fraction (29±6% versus 40±8%, P<0.001) and reduced NT-proBNP (3548 versus 685 ng/L, P<0.001). Correlation analysis showed a significant relationship between volume-unloading (as evidenced by NT-proBNP reduction) and autonomic improvement. CONCLUSIONS: Three months of ARNI therapy resulted in a significant increase in cardiac parasympathetic tone. The improvement in autonomic properties may be mediated by "volume unloading" and likely contributes to the beneficial effects of ARNI in heart failure with reduced ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04587947.

Pulmonary Vein Isolation in Elderly Patients ≥ 75 Years: A Propensity Score-Matched Analysis With Focus on Differences Among Atrial Fibrillation Types.

BACKGROUND: Age is a major risk factor for development of atrial fibrillation (AF) and associated with increased recurrence rates in the setting of rhythm control. Current data tend to support catheter ablation in elderly patients, but uncertainties exist regarding efficacy and safety of ablation in elderly patients. METHODS: This was a prospective single-centre observational study with propensity score matching (PSM) to investigate the influence of age on efficacy and safety of cryoballoon ablation (CBA) stratified by age (< 75 years vs ≥ 75 years) and AF phenotype (paroxysmal vs persistent). Primary efficacy endpoint was recurrence of atrial arrhythmia after a 90-day blanking period. Safety endpoints were death, stroke, or procedure-associated complications. RESULTS: Consecutive patients (n = 953) underwent CBA for first-time AF ablation. Median follow-up was 18 months. By means of PSM, 268 matches were formed. At 1 year, primary efficacy endpoint occurred in 22.4% of young vs 33.2% of elderly patients, including both AF phenotypes (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.47-0.90; P = 0.01). AF relapse occurred in 19.7% of young vs 28.5% of elderly patients with paroxysmal (HR, 0.63; 95% CI, 0.40-0.99; P = 0.046) compared with 25.9% (30 of 116, young) vs 38.8% (45 of 116, elderly) patients with persistent AF (HR, 0.62; 95% CI, 0.39-0.97; P = 0.038). No difference was observed regarding the incidence of safety endpoints between young and elderly patients (P = 0.38). CONCLUSIONS: CBA is associated with higher recurrence rates in elderly (≥ 75 years) than in younger patients, with highest recurrence rates in elderly patients with persistent AF.

Zero-fluoro atrioventricular-nodal reentrant tachycardia ablation.

BACKGROUND: Atrioventricular-nodal reentrant tachycardia (AVNRT) is a common supraventricular tachycardia, particularly in younger patients. The treatment of choice is radiofrequency catheter ablation (RFCA), traditionally necessitating ionizing radiation for catheter guidance. OBJECTIVE: The authors aimed to demonstrate the feasibility and safety of zero-fluoroscopy RFCA of AVNRT using EnSite™ NavX™ as a three-dimensional (3D) electroanatomical mapping system (EAM). METHODS: The authors retrospectively analyzed 68 patients that underwent AVNRT-RFCA. One group was a priori allocated to conventional fluoroscopy mapping (convFluoro, n = 30). In 38 cases, the electrophysiologist chose to use 3D-EAM for ablation. Of these patients, 20 could be ablated without fluoroscopy use (zeroFluoro). In 18 cases that were initially intended as 3D-EAM, additional fluoroscopy use was necessary due to difficult anatomic conditions (convertedFluoro). Procedure duration, fluoroscopy duration and dose, as well as complications were analyzed. RESULTS: Procedure duration was similar for the convFluoro and zeroFluoro groups (74 ± 24 min vs. 80 ± 26 min, p = ns). The convertedFluoro group showed longer procedure duration compared to the convFluoro group (94 ± 30 min vs. 74 ± 24 min, p < 0.05). The use of 3D-EAM significantly reduced fluoroscopy duration comparing the convFluoro with the convertedFluoro group (12 ± 9 min vs. 7 ± 6 min, p < 0.05). The difference in fluoroscopy dose between convFluoro and convertedFluoro did not reach significance (169 ± 166 cGycm2 vs. 134 ± 137 cGycm2, p = ns). In zeroFluoro cases, no radiation was used at all. 3D-EAM-guided RFCA was primarily successful in all patients. Overall, there were only few minor complications in the different groups. No major complications occurred. CONCLUSION: Zero-fluoro RFCA in patients with AVNRT is feasible and safe. 3D-EAM can reduce radiation exposure in the majority of patients without prolonging procedure duration or increasing complications.

Frame-rate reduction to reduce radiation dose for cardiac device implantation is safe.

Background: Radiation exposure to patient and surgeon during cardiac implantable electrical device (CIED) procedures remains a substantial health hazard to date. Advanced technical options for radiation dose reduction often pose considerable financial hurdles. We propose a near-zero cost, low-effort modification to a clinical x-ray system significantly reducing radiation dose during CIED implantation. Objective: We aim to evaluate a reduced frame rate protocol in CIED implantation for complication rates and reduction in radiation exposure. Methods: Starting May 2019, the frame rate during CIED implantations at our hospital was halved from 7.5 frames/s to 3.8 frames/s, and no further technical changes were made. During the following year, 264 patients were operated using this protocol and retrospectively compared with 231 cases implanted in the year before the protocol change, totaling 495 cases. Of these, 17%, 63%, and 19% were single-chamber, dual-chamber, or resynchronization devices, respectively. Incidence of complication prior to hospital discharge was considered the primary endpoint of the analysis. Radiation dose and procedural parameters were secondary endpoints. Results: There was no increase in complications with the reduced frame rate protocol. Regression analysis further supported that the reduced frame rate radiation protocol was not associated with complication rates. Radiation exposure measured as dose area product was significantly reduced by ∼62% (median 369 [interquartile range 154-1207] cGy·cm2 via the reduced frame rate protocol vs median 970 [interquartile range 400-1906] cGy·cm2 with the standard frame rate; P < 0.01). Conclusion: A reduction of frame rate during CIED implantation is safe in terms of complication incidence and effective in terms of reducing radiation exposure.

Cryoballoon pulmonary vein isolation for atrial fibrillation in obese patients: A non-inferiority analysis.

Background: Patients with obesity are at higher risk of developing atrial fibrillation (AF) and benefit from radiofrequency ablation. Potentially, cryoballoon ablation (CBA) may be equally effective and safe in such patients. Methods: We conducted a prospective, single-center study to investigate whether CBA for pulmonary vein isolation is as effective and safe in obese patients as it is in non-obese controls. Primary efficacy endpoint was recurrence of AF, atrial flutter or atrial tachycardia after a 90-day blanking period. Safety endpoints were death, stroke or procedure-associated complications. Conduction of a subgroup analysis regarding the impact of additional diabetes was predefined in case the primary efficacy endpoint was met. The study was event driven and powered for noninferiority. Results: A total of 949 patients underwent CBA (251 obese with mean body-mass-index 33.5 ± 3 kg/m2 and 698 non-obese with mean body-mass-index 25.3 ± 3 kg/m2) during a 5-year recruitment period. Median follow-up was 15 months. The primary efficacy endpoint occurred in 78/251 obese and 247/698 non-obese patients (12-months Kaplan-Meier event-rate estimates, hazard ratio 0.79; 95% confidence interval [CI], 0.58 to 1.07; log-rank P = 0.0002 for noninferiority). No differences were observed in safety end point occurrence (P = 0.78). The occurrence of primary efficacy end point was found to be unaffected by the presence of diabetes in the prespecified subgroup analysis (log-rank P = 0.57). Conclusion: CBA is effective and safe in obese and DM patients. Weighing the high cardiovascular risk of obese patients against a reduction of cardiovascular events by early rhythm control, CBA should be offered to this patient population.