Risk assessment in patients with symptomatic and asymptomatic pre-excitation.

AIMS: Controversy remains as to whether the exercise stress test (EST) is sufficient for risk evaluation in patients with pre-excitation. This study aims to clarify the usefulness of EST in risk stratification in both asymptomatic and symptomatic patients presenting with pre-excitation. METHODS AND RESULTS: This prospective study includes consecutive asymptomatic and symptomatic patients with pre-excitation referred for risk assessment. All participants performed an incremental EST (bicycle) prior to an electrophysiology study (EPS). Primary data from the EST included loss of pre-excitation during exercise, and primary data from the EPS included the measurement of accessory pathway effective refractory period (APERP), shortest pre-excited RR interval (SPERRI), and inducible arrhythmia with the use of a beta-adrenergic receptor agonist if deemed necessary. One hundred and sixty-four patients (59 asymptomatic, 105 symptomatic) completed an EST and EPS. Forty-five patients (27%) demonstrated low-risk findings on EST, of which 19 were asymptomatic and 26 were symptomatic. Six patients with low-risk EST findings had SPERRI/APERP ≤ 250 ms at EPS, and two of them were asymptomatic. The sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy of low-risk EST for excluding patients with SPERRI/APERP ≤ 250 ms were 40, 91, 87, 51, and 60%, respectively. The number of patients with inducible arrhythmia at EPS was similar in the asymptomatic (36, 69%) and symptomatic (73, 61%) groups. CONCLUSION: Sudden loss of pre-excitation during EST has a low NPV in excluding high-risk APs. The EPS with the use of isoproterenol should be considered to accurately assess the risk of patients with pre-excitation regardless of symptoms (ClinicalTrials.gov Identifier: NCT03301935).

Association between catheter ablation of atrial fibrillation and mortality or stroke.

OBJECTIVE: Catheter ablation of atrial fibrillation effectively reduces symptomatic burden. However, its long-term effect on mortality and stroke is unclear. We investigated if patients with atrial fibrillation who undergo catheter ablation have lower risk for all-cause mortality or stroke than patients who are managed medically. METHODS: We retrospectively included 5628 consecutive patients who underwent first-time catheter ablation for atrial fibrillation between 2008 and 2018 at three major Swedish electrophysiology units. Control individuals with an atrial fibrillation diagnosis but without previous stroke were selected from the Swedish National Patient Register, resulting in a control group of 48 676 patients. Propensity score matching was performed to produce two cohorts of equal size (n=3955) with similar baseline characteristics. The primary endpoint was a composite of all-cause mortality or stroke. RESULTS: Patients who underwent catheter ablation were healthier (mean CHA2DS2-VASc score 1.4±1.4 vs 1.6±1.5, p<0.001), had a higher median income (288 vs 212 1000 Swedish krona [KSEK]/year, p<0.001) and had more frequently received university education (45.1% vs 28.9%, p<0.001). Mean follow-up was 4.5±2.8 years. After propensity score matching, catheter ablation was associated with lower risk for the combined primary endpoint (HR 0.58, 95% CI 0.48 to 0.69). The result was mainly driven by a decrease in all-cause mortality (HR 0.51, 95% CI 0.41 to 0.63), with stroke reduction showing a trend in favour of catheter ablation (HR 0.75, 95% CI 0.53 to 1.07). CONCLUSIONS: Catheter ablation of atrial fibrillation was associated with a reduction in the primary endpoint of all-cause mortality or stroke. This result was driven by a marked reduction in all-cause mortality.

Low incidence of major complications after the first six hours post atrial fibrillation ablation: Is same-day discharge safe and feasible in most patients?

AIMS: This study evaluates the incidence of procedural complications related to catheter ablation of atrial fibrillation (AF) to assess the potential feasibility and safety of same-day discharge in a large cohort. METHODS: We performed an analysis of prospectively collected data of complications of all patients staying overnight after undergoing AF ablation between 2001 and 2020 at a tertiary center. Using medical records, we analyzed complications occurring intraprocedurally until 6 h postablation and between 6 h postablation and discharge the day after the ablation procedure. RESULTS: In 5414 AF ablations, we identified a total of 108 (2.0%) major complications occurring intraprocedural or before discharge. Most major complications occurred intraprocedurally or within 6 h after the procedure (n = 96, 1.8%). Twelve (0.2%) major complications occurred between 6 h Postablation and discharge. The most common of these major complications were congestive heart failure (n = 6) and transient ischemic attack (TIA, n = 4). During this time span, 61 (1.1%) minor complications occurred. Factors independently associated with major complications intraprocedurally and until discharge were body mass index (BMI) ≥ 30 kg/m2 (p = .009), significant valvular disease (p = .001), cardiomyopathy (p < .001), prior stroke or TIA (p = .014), first-time procedure versus repeat procedure (p = .013), cryoablation versus radiofrequency (p < .001), and procedure duration (p < .001). CONCLUSION: After AF ablation, very few complications occurred between 6 h postprocedure and discharge the next day. Therefore, same-day discharge is a safe option for a majority of patients.

Cryoablation of substrates adjacent to the atrioventricular node: acute and long-term safety of 1303 ablation procedures.

AIMS: Radiofrequency (RF) ablation is effective for ablation of atrial arrhythmias. However, RF ablation in the vicinity of the atrioventricular (AV) node is associated with a risk of inadvertent, irreversible high-grade AV block, depending on the type of substrate. Cryoablation is an alternative method. The objective was to investigate the acute and long-term risks of AV block during cryoablation. METHODS AND RESULTS: We studied 1303 consecutive cryoablations of substrates in the vicinity of the AV node in 1201 patients (median age 51 years, range 6-89 years) on acute and long-term impairment to the AV nodal conduction system. The arrhythmias treated were AV nodal reentrant tachycardias (n=1116), paraseptal and superoparaseptal accessory pathways (n=100), and focal atrial tachycardias (n=87). In 158 (12%) procedures, cryomapping (38 cases) or cryoablation (120 cases) were stopped due to transient AV block (first-degree AV block 74 cases, second-degree AV block 67 cases, and third-degree AV block 17 cases) after which another site was tested. Transient AV block occurred within seconds of mapping up to 3 min of ablation. The incidence of AV block was similar for different substrates. In most cases, AV nodal conduction was restored within seconds but in two cases transient AV block lasted 21 and 45 min, respectively. There were no cases of acute permanent AV blocks. No late AV blocks occurred during follow-up (mean 24 months, range 6-96 months). CONCLUSION: Cryoablation adjacent to the AV node carries a negligible risk of permanent AV block. Transient AV block during ablation is a benign finding.

Continuous warfarin therapy is safe and feasible in catheter ablation of atrial fibrillation.

OBJECTIVES: In the context of catheter ablation of atrial fibrillation, oral anticoagulant therapy has been traditionally replaced by bridging with heparin during the periprocedural period. We wanted to study the feasibility and safety of continuous warfarin therapy compared to traditional bridging therapy. DESIGN: The complication rates were compared retrospectively in a consecutive patient series. In the bridging group, warfarin was discontinued three days and low molecular weight heparin started one day prior to the procedure. Warfarin was reinitiated one day after and low molecular weight heparin was continued until the therapeutic INR target was reached. Patients on continuous therapy received warfarin throughout the periprocedural period. All patients received unfractionated heparin during the procedure. RESULTS: Three thromboembolic cerebrovascular events (1.9%) occurred in the bridging group (n = 157) and seven (0.82%) in the warfarin group (n = 850) (p = 0.142). The number of cardiac tamponades was one (0.64%) and four (0.47%), respectively (p = 0.786). Total number of severe bleeding and thromboembolic complications was more common in the bridging group: 9 (5.7%) versus 22 (2.6%); p = 0.036. In multivariate analysis, female gender, advanced age, and bridging therapy predicted complications. CONCLUSIONS: Continuous oral anticoagulant therapy is a safe and feasible alternative for bridging therapy in patients undergoing catheter ablation of atrial fibrillation.

Cryothermal vs. radiofrequency ablation as atrial flutter therapy: a randomized comparison.

AIMS: Radiofrequency (RF) ablation of the cavotricuspid isthmus (CTI) is an effective treatment for atrial flutter (AFL). However, RF may injure cardiac structures such as the atrio-ventricular node or the right coronary artery and is usually painful. This prospective, randomized study compares cryoablation (Cryo) with RF ablation regarding efficacy, safety, and perceived pain. METHODS AND RESULTS: One-hundred and fifty-three patients (78 Cryo; 75 RF) with CTI-dependent AFL--median age 65 years (range 34-82), 140 men (91%)--were randomized to Cryo or RF. Primary endpoint was demonstration of long-term efficacy defined as no symptomatic recurrence of AFL at the 6-month follow-up. Radiofrequency ablation was performed with a 3.5 mm open-irrigated-tip catheter and Cryo with a 9 F, 8 mm tip catheter. Ablation endpoint was bidirectional CTI block. Pain was evaluated with a visual analogue scale (VAS; 0-10). The acute success rate was 92% for Cryo and 95% for RF (P = 0.58). Procedural time was longer in the Cryo group (152 ± 54 min) than the RF group (116 ± 41 min) (P < 0.001). Cryoablation was considerably less painful compared with RF (mean VAS-Cryo 0.7 ± 1.2 vs. VAS-RF 4.6 ± 2.0; P < 0.001). Success rate at 6-month follow-up was 93% (73 of 78) for Cryo and 97% (73 of 75) for RF (P = 0.86). No major adverse events occurred in any group. CONCLUSION: Cryoablation of isthmus-dependent AFL is not inferior to RF but with significantly less procedure-related pain.

Manganese chloride tetrahydrate (CMC-001) enhanced liver MRI: evaluation of efficacy and safety in healthy volunteers.

OBJECT: To evaluate the efficacy of three dose levels of the oral hepatobiliary manganese-based magnetic resonance imaging (MRI) contrast agent CMC-001, and assess its safety profile and patient acceptability. MATERIALS AND METHODS: After ethics committee approval, 32 healthy volunteers (males/females: 18/14) were included. Liver MRI was performed before and 3 h after ingestion of 0.8, 0.4, and 0.2 g of CMC-001 on separate occasions. Liver-to-muscle signal intensity (SI) ratio from baseline to post-contrast and image quality was assessed. Adverse drug reactions/adverse events (ADRs/AEs) and clinico-laboratory tests were monitored. RESULTS: The increase in liver-to-muscle SI ratio was significantly higher after 0.8 g (0.696) compared to 0.4 g (0.458) and 0.2 g (0.223) (in all pair-wise comparisons, P < 0.0001). The overall image quality was superior after 0.8 g. ADRs/AEs were dose-related and predominantly of mild intensity. CONCLUSION: Liver MRI using 0.8 g CMC-001 has the highest efficacy and still acceptable ADRs and should therefore be preferred.

The ischemic preconditioning effect of adenosine in patients with ischemic heart disease.

INTRODUCTION: In vivo and in vitro evidence suggests that adenosine and its agonists play key roles in the process of ischemic preconditioning. The effects of low-dose adenosine infusion on ischemic preconditioning have not been thoroughly studied in humans. AIMS: We hypothesised that a low-dose adenosine infusion could reduce the ischemic burden evoked by physical exercise and improve the regional left ventricular (LV) systolic function. MATERIALS AND METHODS: We studied nine severely symptomatic male patients with severe coronary artery disease. Myocardial ischemia was induced by exercise on two separate occasions and quantified by Tissue Doppler Echocardiography. Prior to the exercise test, intravenous low-dose adenosine or placebo was infused over ten minutes according to a randomized, double blind, cross-over protocol. The LV walls were defined as ischemic if a reduction, no increment, or an increment of < 15% in peak systolic velocity (PSV) was observed during maximal exercise compared to the baseline values observed prior to placebo-infusion. Otherwise, the LV walls were defined as non-ischemic. RESULTS: PSV increased from baseline to maximal exercise in non-ischemic walls both during placebo (P = 0.0001) and low-dose adenosine infusion (P = 0.0009). However, in the ischemic walls, PSV increased only during low-dose adenosine infusion (P = 0.001), while no changes in PSV occurred during placebo infusion (P = NS). CONCLUSION: Low-dose adenosine infusion reduced the ischemic burden and improved LV regional systolic function in the ischemic walls of patients with exercise-induced myocardial ischemia, confirming that adenosine is a potential preconditioning agent in humans.

Preconditioning effects of adenosine in patients with severe coronary artery disease but preserved coronary flow reserve.

BACKGROUND: Adenosine plays a key role in different protective and adaptive responses to ischemia and has been suggested to induce ischemic preconditioning. AIM: To investigate whether a low-dose adenosine infusion reduces the ischemic burden induced by pharmacological stress without affecting the coronary flow reserve (CFR). MATERIALS AND METHODS: Myocardial ischemia was induced by dobutamine stress test and quantified by tissue Doppler echocardiography in 11 patients with advanced coronary artery disease. CFR was quantified during high-dose adenosine infusion by contrast echocardiography. Before the dobutamine stress test and contrast echocardiography, intravenous low-dose adenosine or placebo was infused over 15 min according to a randomized, double-blind, cross-over protocol. Echocardiographic left ventricular (LV) apical images and flow pattern of left anterior descending coronary artery (LAD) were obtained at baseline, during adenosine/placebo infusion, maximal, and recovery phases.Furthermore, the LV walls were categorized as ischemic or nonischemic according to a predefined ischemic threshold of at least 25% increment in peak systolic velocity (PSV)from baseline to maximal stress. CFR was measured as the ratio of peak/baseline of maximal diastolic velocity in the distal LAD. RESULTS: PSV increased both during placebo and adenosine infusions from baseline to maximal stress. However, in the ischemic walls, the PSV increased only during adenosine infusion, whereas no differences were observed in the nonischemic walls. There were no differences in blood pressure, heart rate, or regional CFR during placebo or adenosine infusion. CONCLUSION: Low-dose adenosine infusion improves regional LV systolic function in the ischemic walls, without any effect on CFR, suggesting that the observed improvement may be because of ischemic preconditioning.

Acute and long-term outcome of cryoablation therapy of typical atrioventricular nodal reentrant tachycardia.

AIMS: The purpose of this study was to evaluate the safety and efficacy of cryoablation in a large series of patients with typical (slow-fast) atrioventricular nodal reentrant tachycardia (AVNRT). METHODS AND RESULTS: Between 2003 and 2007, 312 patients with typical AVNRT--median age of 53 years (range 10-92), 200 women (64%)--underwent cryoablation, using exclusively a 6 mm tip catheter tip. Acute success was achieved in 309 of 312 patients (99%). The overall recurrence rate was 18 of 309 (5.8%) during a mean follow-up of 673 +/- 381 days. Sixteen of these patients (89%) were successfully reablated. The recurrence rate was 9% in patients with residual dual atrioventricular (AV) nodal pathway post-ablation compared with 4% in those with complete elimination of slow pathway conduction (P = 0.05). No patient developed permanent AV block. CONCLUSION: Cryoablation of AVNRT can be achieved with a high acute success rate and a reasonable recurrence rate at long-term follow-up. Complete abolition of slow pathway conduction seems to predict better late outcome.

Safety and efficacy of cryoablation of atrial tachycardia with high risk of ablation-related injuries.

AIMS: The purpose of this study was to evaluate the safety and efficacy of cryoablation as an alternative to radio frequency (RF) ablation in high-risk-located atrial tachycardia (AT). METHODS AND RESULTS: Between 2004 and 2007, 164 patients underwent catheter ablation due to AT at our institution. Twenty-six of these patients (22 women and 4 men), median age 58 years (range 14-76), were considered having high-risk-located AT and were treated by cryoablation. Seven patients had failed prior RF ablation due to high risk of complications. The AT foci distribution was: close to the AV node (n = 14), vicinity of the sinus node (n = 7), and crista terminalis adjacent to the phrenic nerve (n = 5). Cryomapping, using a 6 mm tip catheter, at -30 degrees C was performed before ablation with a goal temperature of -80 degrees C for 240 s. Acute success rate was achieved in 25/26 patients (96%). During a follow-up of 493 +/- 258 days, three patients had recurrences. Two of these underwent a second successful cryoablation procedure. Long-term success rate was 92%. Phrenic nerve palsy occurred in two patients with complete recovery after 1 day and 5 months, respectively. CONCLUSION: Cryoablation of high-risk-located AT foci is a safe and effective alternative to RF therapy.

beta-Endorphin modulates adenosine provoked chest pain in men, but not in women-a comparison between patients with ischemic heart disease and healthy volunteers.

INTRODUCTION: Increasing evidence suggests the existence of sex differences in pain perception. Adenosine, an early messenger for myocardial ischemia induces angina pectorislike symptoms in healthy volunteers and in patients with ischemic heart disease. AIMS: To study whether sex influences adenosine-provoked chest pain and the analgesic effect of the opioid receptor agonist beta-endorphin. MATERIALS AND METHODS: Twenty patients (10 male and 10 female) with significant coronary artery disease and 20 healthy volunteers (10 male and 10 female) were studied. Both the hand algometer and Borg CR-10 scale were used to estimate chest pain. Chest pain was provoked double-blind by injections of placebo, 1/3, 2/3, 3/3 of maximal tolerable dose of adenosine twice in randomized order. This procedure was repeated after bolus injection of beta-endorphin followed by infusion and repeated a third time after bolus injection of naloxone 0.8 mg. Central chest pain and physiologic responses were quantified using hemodynamic and psychophysical methods. RESULTS: Pain estimate by hand algometer and the Borg CR-10 scale was correlated (r=0.77, P<0.001). Both sexes reported a dose-dependent increase of adenosine-provoked chest pain with no differences for maximum tolerable dose of adenosine per kilogram. beta-Endorphin administration lowered adenosine-provoked pain in both male patients and male healthy volunteers (P=0.02) but not in women. Naloxone tended to increase the pain perception in male patients (P=0.052) and male healthy volunteers (P=0.054), but did not have any significant effect on pain modalities in female. CONCLUSIONS: In conclusion, women were resistant to beta-endorphin modulation of adenosine-provoked chest pain. In male patients, beta-endorphin induced analgesia.