Abstract
Aims
Atrial fibrillation (AF) and heart failure (HF) often coexist. Catheter ablation has been reported to restore left ventricular (LV) function but patients benefit differently. This study ...investigated the correlation between left atrial (LA) fibrosis extent and LV ejection fraction (LVEF) recovery after AF ablation.
Methods and results
In this study, 103 patients 64 years, 69% men, 79% persistent AF, LVEF 33% interquartile range (IQR) (25–38) undergoing first time AF ablation were investigated. Identification of LA fibrosis and selection of ablation strategy were based on sinus rhythm voltage mapping. Continuous rhythm monitoring was used to assess ablation success. Improvement in post-ablation LVEF was measured as primary study endpoint. An absolute increase in post-ablation LVEF ≥10% was defined as ‘Super Response’. Left atrial fibrosis was present in 38% of patients. After ablation LVEF increased by absolute 15% (IQR 6–25) (P < 0.001). Left ventricular ejection fraction improvement was higher in patients without LA fibrosis 15% (IQR 10–25) vs. 10% (IQR 0–20), P < 0.001. An inverse correlation between LVEF improvement and the extent of LA fibrosis was found (R2 = 0.931). In multivariate analysis, the presence of LA fibrosis was the only independent predictor for failing LVEF improvement odds ratio 7.2 (95% confidence interval 2.2–23.4), P < 0.001. Echocardiographic ‘Super Response’ was observed in 55/64 (86%) patients without and 21/39 (54%) patients with LA fibrosis, respectively (P < 0.001).
Conclusion
Presence and extent of LA fibrosis predict LVEF response in HF patients undergoing AF ablation. The assessment of LA fibrosis may impact prognostic stratification and clinical management in HF patients with AF.
Graphical abstract
Objective
To evaluate the regulation of matrix metalloproteinase (MMP)-2 in diabetic cardiomyopathy.
Methods
Left ventricle (LV) function was determined by a micro-tip catheter in streptozotocin ...(STZ)-induced diabetic rats, 2 or 6 weeks (w) after STZ-application. LV total collagen, collagen type I and III content were immunohistologically analyzed and quantified by digital image analysis. LV collagen type I, III and MMP-2 mRNA expression was quantified by real-time RT-PCR. LV pro- and active MMP-2 levels were analyzed by zymography; Smad 7, membrane type (MT)1-MMP and tissue inhibitor metalloproteinase (TIMP)-2 protein levels by Western Blot.
Results
STZ-induced diabetes was associated with a time-dependent impairment of LV diastolic and systolic function. This was paralleled by a time-dependent increase in LV total collagen content, despite reduced LV collagen type I and III mRNA levels, indicating a role of post-transcriptional/post-translational changes of extracellular matrix regulation. Six weeks (w) after STZ-injection, MMP-2 mRNA expression and pro-MMP-2 levels were 2.7-fold (
P
< 0.005) and 1.3-fold (
P
< 0.05) reduced versus controls, respectively, whereas active MMP-2 was decreased to undetectable levels 6 w post-STZ. Concomitantly, Smad 7 and TIMP-2 protein levels were 1.3-fold (
P
< 0.05) and 10-fold (
P
< 0.005) increased in diabetics versus controls, respectively, whereas the 45 kDa form of MT1-MMP was undetectable in diabetics.
Conclusion
Under STZ-diabetic conditions, cardiac fibrosis is associated with a dysregulation in extracellular matrix degradation. This condition is featured by reduced MMP-2 activity, concomitant with increased Smad 7 and TIMP-2 and decreased MT1-MMP protein expression, which differs from mechanisms involved in dilated and ischemic heart disease.
The incidence of worsened clinical outcome due to high right ventricular (RV) pacing burden in patients with preserved left ventricular function remains controversial.
To investigate the impact of RV ...pacing on several echocardiographic and spiroergometric parameters.
In 60 pacemaker patients with preserved left ventricular ejection fraction (LVEF) serial echocardiographies and spiroergometries were performed over a time course of 12 months. Additionally, in 48 patients retrospective echocardiographic analyses of the LV- and RV function were carried out up to 24 months after pacemaker implantation.
The patients were divided into two groups: The high RV pacing burden group (hRVP: ≥ 40%) and the low RV pacing group (lRVP < 40%) according to the definitions in previous randomized MOST and DAVID trials. After a period of 12-month pacemaker therapy no changes to left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), LVEF, E/A-ratio; E/E'-ratio and tricuspid annular plane systolic excursion (TAPSE) could be revealed, independently of the RV pacing burden. Additionally, after 24-month long term follow-up there were no differences in LVEF and TAPSE in both groups. Accordingly, no relevant changes of peak exercise capacity, ventilatory anaerobic threshold or maximal oxygen consumption could be demonstrated independently of the RV pacing.
In pacemaker patients with preserved LVEF the burden of RV pacing has no adverse influence on several echocardiographic and spiroergometric surrogate parameters of pacemaker-induced cardiomyopathy after a follow-up of 12 to 24 month. Despite this, screening for pacemaker induced cardiomyopathy should be performed especially in the presence of new heart failure symptoms.
To describe the extent and distribution of low voltage zones (LVZ) in a large cohort of patients undergoing ablation for paroxysmal and persistent atrial fibrillation (AF), and to explore baseline ...predictors of LVZ in these patients.
Consecutive patients who underwent a bipolar voltage map guided AF ablation, were enrolled. Voltage maps were conducted for each patient using 3-dimensional electroanatomical mapping system and LVZ were defined as areas of bipolar voltage < 0.5 mV. A total of 539 patients (309 male, age 65 ± 10 years) were included. Low voltage zones was present in 58 out of 292 patients with paroxysmal and 134 out of 247 persistent AF (P < 0.001). The area of LVZ was larger in patients with persistent as compare to paroxysmal AF, 5 cm2 (IQR 3-18.6) vs. 12.1 cm2 (IQR 3.6-28.5), P = 0.026, respectively. In the multivariate analysis age (OR 1.07, 95%CI 1.05-1.10, P < 0.001), female gender (OR 2.18, 95%CI 1.38-3.43, P = 0.001), sinoatrial node dysfunction (OR 3.90, 95%CI 1.24-12.21, P = 0.020), larger surface area of left atrium pr. cm2 (OR 1.01, 95%CI 1.00-1.02, P = 0.016), and persistent AF (OR 5.03, 95%CI 3.20-7.90, P<0.001) were associated with presence of LVZ.
In a large cohort of patients undergoing ablation for AF, the prevalence of LVZ was higher and LVZ areas larger in patients with persistent as compared with paroxysmal AF. The most frequent localization of LVZ was anterior wall, septum and posterior wall. Presence of LVZ was associated with higher age, female gender, larger LA surface area, and sinoatrial node dysfunction.
Background
Renal denervation (RDN) can reduce cardiac sympathetic activity maintained by arterial hypertension (aHT). Its potential antiarrhythmic effect on rhythm outcome in patients with multi‐drug ...resistant aHT undergoing catheter ablation for atrial fibrillation (AF) is unclear.
Methods
The RDN+AF study was a prospective, randomized, two‐center trial. Patients with paroxysmal or persistent AF and uncontrolled aHT (mean systolic 24‐h ambulatory BP > 135 mmHg) despite taking at least three antihypertensive drugs were enrolled. Patients were 1:2 randomized to either RDN+AF ablation or AF‐only ablation. Primary endpoint was freedom from any AF episode > 2 min at 12 months assessed by implantable loop recorder (ILR) or 7d‐holter electrocardiogram. Secondary endpoints included rhythm outcome at 24 months, blood pressure control, periprocedural complications, and renovascular safety.
Results
The study randomized 61 patients (mean age 65 ± 9 years, 53% men). At 12 months, RDN+AF patients tended to have a greater decrease in ambulatory BPs but did not reach statistical significance. No differences in rhythm outcome were observed. Freedom from AF recurrence in the RDN+AF and AF‐only group measured 61% versus 53% p = .622 at 12 months and 39% versus 47% p = .927 at 24 months, respectively. Periprocedural complications occurred in 9/61 patients (15%). No patient died.
Conclusion
Among patients with multidrug‐resistant aHT and paroxysmal or persistent AF, concomitant RDN+AF ablation was not associated with better blood pressure control or rhythm outcome in comparison to AF‐only ablation and medical therapy.
To study device performance, arrhythmia recurrence characteristics, and methods of outcome assessment using a novel implantable cardiac monitor (ICM) in patients undergoing ablation for atrial ...fibrillation (AF).
In 419 consecutive patients undergoing first-time catheter ablation for symptomatic paroxysmal (n = 224) or persistent (n = 195) AF an ICM was injected at the end of the procedure. Telemedicine staff ensured full episode transmission coverage and manually evaluated all automatic arrhythmia episodes. Device detection metrics were calculated for ≥2, ≥6, and ≥10 min AF detection durations. Four methods of outcome assessment were studied: continuous recurrence analysis, discontinuous recurrence analysis, AF-burden analysis, and analysis of individual rhythm profiles. A total of 43 673 automatic AF episodes were transmitted over a follow-up of 15 ± 6 months. Episode-based positive predictive values changed significantly with longer AF detection durations (70.5% for ≥2 min, 81.8% for ≥6 min, and 85.9% for ≥10 min). Patients with exclusive short episode recurrences (≥2 to <6 min) were rare and their arrhythmia detection was clinically irrelevant. Different methods of outcome assessment showed a large variation (46-79%) in ablation success. Individual rhythm characteristics and subclinical AF added to this inconsistency. Analysis of AF-burden and individual rhythm profiles were least influenced and showed successful treatment in 60-70% of the patients.
We suggest AF detection duration >6 min and AF burden >0.1% as a standardized outcome definition for AF studies to come in the future.
The prognostic implication of right atrial (RA) and left atrial (LA) size for an immediate success of direct current cardioversion (DCCV) in atrial fibrillation (AF) remains unclear. This study aimed ...to compare RA and LA size for the prediction of DCCV success.
Between 2012 and 2018, 734 consecutive outpatients were screened for our prospective registry. Each eligible patient received a medical history, blood analysis, and transthoracic echocardiography with a focus on indexed RA (iRA) area and LA volume (iLAV) prior to DCCV with up to three biphasic shocks (200-300-360 J) or additional administration of amiodarone or flecainide to restore sinus rhythm.
We enrolled 589 patients, and DCCV was in 89% (n=523) successful. Mean age was 68 ± 10 years, and 40% (n=234) had New York heart association class >II. A prevalence of the male sex (64%, n=376) and of persistent AF (86%, n=505) was observed. Although DCCV success was associated with female sex (odds ratio OR, 1.88; 95% confidence interval CI, 1.06-3.65), with absence of coronary heart disease and normal left ventricular function (OR, 2.24; 95% CI, 1.26-4.25), with short AF duration (OR, 1.93; 95% CI, 1.05-4.04) in univariable regression, only iRA area remained a stable and independent predictor of DCCV success (OR, 0.27; 95% CI, 0.12-0.69; area under the curve 0.71), but not iLAV size (OR, 1.16; 95% CI, 1.05-1.56) in multivariable analysis.
iRA area is superior to iLAV for the prediction of immediate DCCV success in AF.
Until today, catheter interventional mapping and ablation of atrial fibrillation (AF) has been limited to the right and left atrial endocardium. We report feasibility, electrophysiological findings, ...and clinical outcome using a combined endo-/epicardial catheter approach for mapping and ablation of AF.
Fifty-nine patients with permanence of pulmonary vein isolation and further symptomatic recurrences of paroxysmal AF, persistent AF, or atrial tachycardia underwent reablation using biatrial endo-/epicardial mapping and ablation. Identification of arrhythmia substrates and selection of ablation strategy were based on sinus rhythm voltage mapping. Using continuous monitoring and a 3-month blanking period, freedom from AF/atrial tachycardia ≥2 minutes was defined as primary end point. In all patients, endo-/epicardial mapping and ablation was feasible using standard technologies of catheter access, 3-dimensional mapping, and radiofrequency ablation. Epicardial mapping and ablation did not add procedural risks. Exclusively epicardial low voltage substrates were found in 14% of the patients. For the first time, novel epicardial conduction abnormalities located in the epicardial fiber network were described in human AF patients (19% of the cohort). Epicardial ablation was needed in 80% of the patients. Over 23±10 months of follow-up freedom from arrhythmia recurrences measured 73%.
Catheter-based endo-/epicardial mapping and ablation of AF was feasible and safe. Epicardial mapping provided new insights into AF mechanisms. Epicardial ablation increased transmurality of ablation lesions. Clinical outcome in this cohort of complex AF patients was favorable, indicating potential further development of current AF treatment.
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