Atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) is associated with PV to left atrium reconduction. Effective lesion creation necessitates adequate contact force between the ...ablation catheter and myocardium.
The purpose of this study was to study the utility of contact force-guided ablation on immediate and long-term outcomes.
Seventy-five patients with highly symptomatic paroxysmal AF underwent wide circumferential PVI using an irrigated-tip radiofrequency catheter. In 25 patients, ablation was guided by real-time contact force measurements (CF group; SmartTouch, Biosense Webster). A control group of 50 patients underwent PVI using a standard nonforce sensing catheter (standard group; ThermoCool, Biosense Webster). After PVI, all patients underwent adenosine testing to unmask dormant conduction. Patients were followed up at 3, 6, and 12 months and by transtelephonic monitoring as well.
Dormant conduction was unmasked and subsequently eliminated in 4 PV pairs (8%; 16% of patients) in the CF group and 35 PV pairs (35%; 52% of patients) in the standard group (P = .0004 per PV pair; P = .0029 per patient). The single-procedure, off-antiarrhythmic drug freedom from recurrent atrial arrhythmias at 1 year was 88% in the CF group vs 66% in the standard group (P = .047). Procedure duration and fluoroscopy time were significantly longer in the CF group (P = .0038 and P = .0001, respectively).
The use of real-time contact force guidance results in a significant reduction in the prevalence of dormant conduction with improved long-term freedom from recurrent arrhythmias. The utility of a contact force-guided approach requires evaluation in a long-term prospective randomized study.
Although the benefits of cardiac resynchronization therapy are well established in selected patients with heart failure and a prolonged QRS duration, salutary effects in patients with narrow QRS ...complexes remain to be demonstrated.
The Evaluation of Resynchronization Therapy for Heart Failure (LESSER-EARTH) trial is a randomized, double-blind, 12-center study that was designed to compare the effects of active and inactive cardiac resynchronization therapy in patients with severe left ventricular dysfunction and a QRS duration <120 milliseconds. The trial was interrupted prematurely by the Data Safety and Monitoring Board because of futility and safety concerns after 85 patients were randomized. Changes in exercise duration after 12 months were no different in patients with and without active cardiac resynchronization therapy (-0.7 minutes 95% confidence interval (CI), -2.9 to 1.5 versus 0.8 minutes 95% CI, -1.2 to 2.9; P=0.31. Similarly, no significant differences were observed in left ventricular end-systolic volumes (-6.4 mL 95% CI, -18.8 to 5.9 versus 3.1 mL 95% CI, -9.2 to 15.5; P=0.28) and ejection fraction (3.3% 95% CI, 0.7-6.0 versus 2.1% 95% CI, -0.5 to 4.8; P=0.52). Moreover, cardiac resynchronization therapy was associated with a significant reduction in the 6-minute walk distance (-11.3 m 95% CI, -31.7 to 9.7 versus 25.3 m 95% CI, 6.1-44.5; P=0.01), an increase in QRS duration (40.2 milliseconds 95% CI, 34.2-46.2 versus 3.4 milliseconds 95% CI, 0.6-6.2; P<0.0001), and a nonsignificant trend toward an increase in heart failure-related hospitalizations (15 hospitalizations in 5 patients versus 4 hospitalizations in 4 patients).
In patients with a left ventricular ejection fraction ≤35%, symptoms of heart failure, and a QRS duration <120 milliseconds, cardiac resynchronization therapy did not improve clinical outcomes or left ventricular remodeling and was associated with potential harm.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00900549.
Introduction
Expert societies recently published strong recommendations to reduce the exposure of patients and staff to ionizing radiation (IR) during interventional and electrophysiology (EP) ...procedures. However, adherence to these guidelines remains difficult and the impact of implementing such recommendations is poorly characterized.
Methods and results
We conducted a single‐center cohort study to quantify radiation exposure over time in three EP laboratories at the Montreal Heart Institute during 5,546 consecutive procedures from 2012 to 2015 by 11 primary operators. Overall, 2,618 (47.2%) procedures were catheter‐based and 2,928 (52.8%) were device interventions. Interventions to reduce radiation exposure included educational initiatives to raise awareness (i.e., limiting cine acquisition, patient position, table height), slower frame rate, lower radiation dose per pulse, collimation, and integration with 3‐D mapping systems and/or MediGuide technology. An 85% reduction in IR exposure was observed from 2012 to 2015, with the mean dose‐area‐product (DAP) decreasing from 7.65 ± 0.05 Gy·cm2 to 1.15 ± 0.04 Gy·cm2 (P < 0.001). This was true for catheter‐based procedures (mean DAP 16.99 ± 0.08 to 2.00 ± 0.06 Gy·cm2, P < 0.001) and device interventions (mean DAP 4.18 ± 0.06 to 0.64 ± 0.05 Gy·cm2, P < 0.001). The median effective dose of IR recorded per quarter by 282 cervical dosimeters on EP staff decreased from 0.57 (IQR 0.18, 1.03) mSv in 2012 to 0.00 (IQR 0.00, 0.19) mSv in 2015, P < 0.001.
Conclusion
Enforcing good clinical practices with simple measures and low‐dose fluoroscopy settings are highly effective in reducing IR exposure in the EP lab. These promising results should encourage other EP labs to adopt similar protective measures.
Hemidiaphragmatic paralysis is the most frequent complication associated with cryoballoon ablation for atrial fibrillation. To date, no preventive strategy has proved effective.
We sought to assess ...the feasibility of diaphragmatic electromyography during cryoballoon ablation, explore the relationship between altered signals and phrenic nerve palsy, and define characteristic changes that herald hemidiaphragmatic paralysis.
Cryoballoon ablation was performed in the right superior pulmonary vein or superior vena cava in 16 mongrel dogs weighing 37.7 ± 2.4 kg, at sites determined by phrenic nerve capture. During ablation, the phrenic nerve was paced at 60 bpm from the superior vena cava while recording diaphragmatic compound motor action potentials (CMAPs) by esophageal decapolar catheters. Diaphragmatic excursion was monitored by fluoroscopy and abdominal palpation.
Before ablation, the CMAP amplitude was 592 (interquartile range 504, 566) μV, initial latency 21.5 ± 4.2 ms, peak latency 64.7 ± 21.1 ms, and duration 101.7 ± 13.3 ms. Hemidiaphragmatic paralysis was obtained in all dogs 62 ± 34 seconds into the cryoapplication. The CMAP amplitude decreased exponentially, with no patterned changes in latencies and duration. Discriminatory analyses by receiver-operating curve characteristics identified a 30% reduction in CMAP amplitude as the most predictive cutoff value for hemidiaphragmatic paralysis (c-statistic 0.965; P<.0001). This criterion presaged diaphragmatic paralysis, as detected by abdominal palpation, by 31 ± 23 seconds.
Diaphragmatic electromyographic signals could be reliably recorded during cryoballoon ablation. An exponential decrease in CMAP amplitude precedes diaphragmatic paralysis, with a 30% reduction yielding the best discriminatory potential. A promising safety margin was detected, which merits prospective validation.
BACKGROUND—Phrenic nerve palsy remains the most frequent complication associated with cryoballoon-based pulmonary vein (PV) isolation. We sought to characterize our experience using a novel ...monitoring technique for the prevention of phrenic nerve palsy.
METHODS AND RESULTS—Two hundred consecutive cryoballoon-based PV isolation procedures between October 2010 and October 2013 were studied. In addition to standard abdominal palpation during right phrenic nerve pacing from the superior vena cava, all patients underwent diaphragmatic electromyographic monitoring using surface electrodes. Cryoablation was terminated on any perceived reduction in diaphragmatic motion or a 30% decrease in the compound motor action potential (CMAP). During right-sided ablation, a ≥30% reduction in CMAP amplitude occurred in 49 patients (24.5%). Diaphragmatic motion decreased in 30 of 49 patients and was preceded by a 30% reduction in CMAP amplitude in all. In 82% of cases, this reduction in CMAP amplitude occurred during right superior PV isolation. The baseline CMAP amplitude was 946.5±609.2 mV and decreased by 13.8±13.8% at the end of application. This decrease was more marked in the 33 PVs with a reduction in diaphragmatic motion than in those without (40.9±15.3% versus 11.3±10.5%; P<0.001). In 3 cases, phrenic nerve palsy persisted beyond the end of the procedure, with all cases recovering within 6 months. Despite the shortened application all veins were isolated. At repeat procedure the right-sided PVs reconnected less frequently than the left-sided PVs in those with phrenic nerve palsy.
CONCLUSIONS—Electromyographic phrenic nerve monitoring using the surface CMAP is reliable, easy to perform, and offers an early warning to impending phrenic nerve injury.
Ablation Time and Active Cryoballoon Deflation
Introduction
Optimal cryoballoon ablation parameters for pulmonary vein (PV) isolation remain to be defined. We conducted a randomized preclinical ...trial to compare 2‐ versus 4‐minute ablation lesions and assess the safety of active (forced) cryoballoon deflation.
Methods and Results
Thirty‐two dogs underwent PV isolation with a second‐generation 23 mm cryoballoon catheter. The left superior (LSPV) and inferior (LIPV) PVs were randomized in a factorial design to (1) a single 2‐ versus 4‐minute cryoapplication, and (2) passive versus active cryoballoon deflation. Animals were survived for 30 days, after which histopathologic analysis was performed. Acute PV isolation was attained in 89.8% of PVs after a single application (93.8% LSPV, 85.2% LIPV; P = 0.2823). Mean time to PV isolation was 29.5 ± 18.5 seconds. Although 4‐minute lesions were associated with a thicker neointima than 2‐minute lesions (223.8 μm versus 135.6 μm; P = 0.007), no differences were observed in procedural characteristics (freezing temperature, rewarming time), rates of acute PV isolation, or the achievement of complete circumferentially transmural lesions at 30 days (78.7% overall; 86.2% for 2 minutes vs 70.0% for 4 minutes; P = 0.285). Active deflation was associated with faster balloon rewarming but not with significant differences in mean or maximum neointimal thickness.
Conclusion
A single application with the second‐generation cryoballoon catheter results in a high rate of PV isolation. The degree of vascular injury was not increased by active balloon deflation and no differences in acute efficacy or mature transmural circumferential lesions were observed with 2‐ versus 4‐minute applications.
Recent clinical and preclinical studies have demonstrated that cryothermal ablation using a balloon catheter (Artic Front®, Medtronic CryoCath LP, Pointe‐Claire, Canada) provides an effective means ...of achieving pulmonary vein isolation. This review explores the biophysics and biomechanics of cryoballoon ablation. Components of the cryoballoon catheter system are examined, mechanisms of cryothermal injury are summarized, and potential advantages of cryoballoon technology over standard radiofrequency ablation in isolating pulmonary veins are discussed. Practical aspects of biophysics and biomechanics relevant to the clinical electrophysiologist are emphasized, particularly with regards to the selection of the most appropriate cryoballoon catheter and minimizing peri‐procedural complications. (PACE 2012; 35:1162–1168)
Rationale
Atrial fibrillation (AF) is associated with an increased risk of thromboembolism. This risk is currently assessed with scoring systems based on clinical characteristics. However, these ...tools have limited prognostic performance. Circulating biomarkers are proposed for improved prediction of major clinical events and individualization of treatments in patients with AF.
Objective
The aim was to assess the cost-effectiveness of precision medicine (PM), i.e., the use of combined biomarkers and clinical variables, in comparison to standard of care (SOC) for risk stratification in a hypothetical cohort of AF patients at risk of stroke.
Methods
A Markov cohort model was developed to evaluate the costs and quality-adjusted life-years (QALYs) of PM compared to SOC, over 20 years using a Canadian healthcare system perspective.
Results
PM decreased the mean per-patient overall costs by 7% ($94,932 vs $102,057 Canadian dollars, respectively) and increased the QALYs by 12% (8.77 vs 7.68 QALYs, respectively). The calculated incremental cost-effectiveness ratio was negative, indicating that PM is an economically dominant strategy. These results were robust to one-way and probabilistic sensitivity analyses.
Conclusion
PM compared to SOC is economically dominant and is projected to generate cost savings.
Left ventricular (LV) pacing alone may theoretically avoid deleterious effects of right ventricular pacing.
In a multicenter, double-blind, crossover trial, we compared the effects of LV and ...biventricular (BiV) pacing on exercise tolerance and LV remodeling in patients with an LV ejection fraction ≤35%, QRS ≥120 milliseconds, and symptoms of heart failure. A total of 211 patients were recruited from 11 centers. After a run-in period of 2 to 8 weeks, 121 qualifying patients were randomized to LV followed by BiV pacing or vice versa for consecutive 6-month periods. The greatest improvement in New York Heart Association class and 6-minute walk test occurred during the run-in phase before randomization. Exercise duration at 75% of peak Vo(2) (primary outcome) increased from 9.3±6.4 to 14.0±11.9 and 14.3±12.5 minutes with LV and BiV pacing, respectively, with no difference between groups (P=0.4327). LV ejection fraction improved from 24.4±6.3% to 31.9±10.8% and 30.9±9.8% with LV and BiV pacing, respectively, with no difference between groups (P=0.4530). Reductions in LV end-systolic volume were likewise similar (P=0.6788). The proportion of clinical responders (≥20% increase in exercise duration) to LV and BiV pacing was 48.0% and 55.1% (P=0.1615). Positive remodeling responses (≥15% reduction in LV end-systolic volume) were observed in 46.7% and 55.4% (P=0.0881). Overall, 30.6% of LV nonresponders improved with BiV and 17.1% of BiV nonresponders improved with LV pacing.
LV pacing is not superior to BiV pacing. However, nonresponders to BiV pacing may respond favorably to LV pacing, suggesting a potential role as tiered therapy.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00901212.
Genetic causes of many familial arrhythmia syndromes remain elusive. In this study, whole‐exome sequencing (WES) was carried out on patients from three different families that presented with ...life‐threatening arrhythmias and high risk of sudden cardiac death (SCD). Two French Canadian probands carried identical homozygous rare variant in TECRL gene (p.Arg196Gln), which encodes the trans‐2,3‐enoyl‐CoA reductase‐like protein. Both patients had cardiac arrest, stress‐induced atrial and ventricular tachycardia, and QT prolongation on adrenergic stimulation. A third patient from a consanguineous Sudanese family diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT) had a homozygous splice site mutation (c.331+1G>A) in TECRL. Analysis of intracellular calcium (Ca2+i) dynamics in human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) generated from this individual (TECRLHom‐hiPSCs), his heterozygous but clinically asymptomatic father (TECRLHet‐hiPSCs), and a healthy individual (CTRL‐hiPSCs) from the same Sudanese family, revealed smaller Ca2+i transient amplitudes as well as elevated diastolic Ca2+i in TECRLHom‐hiPSC‐CMs compared with CTRL‐hiPSC‐CMs. The Ca2+i transient also rose markedly slower and contained lower sarcoplasmic reticulum (SR) calcium stores, evidenced by the decreased magnitude of caffeine‐induced Ca2+i transients. In addition, the decay phase of the Ca2+i transient was slower in TECRLHom‐hiPSC‐CMs due to decreased SERCA and NCX activities. Furthermore, TECRLHom‐hiPSC‐CMs showed prolonged action potentials (APs) compared with CTRL‐hiPSC‐CMs. TECRL knockdown in control human embryonic stem cell‐derived CMs (hESC‐CMs) also resulted in significantly longer APs. Moreover, stimulation by noradrenaline (NA) significantly increased the propensity for triggered activity based on delayed afterdepolarizations (DADs) in TECRLHom‐hiPSC‐CMs and treatment with flecainide, a class Ic antiarrhythmic drug, significantly reduced the triggered activity in these cells. In summary, we report that mutations in TECRL are associated with inherited arrhythmias characterized by clinical features of both LQTS and CPVT. Patient‐specific hiPSC‐CMs recapitulated salient features of the clinical phenotype and provide a platform for drug screening evidenced by initial identification of flecainide as a potential therapeutic. These findings have implications for diagnosis and treatment of inherited cardiac arrhythmias.
Synopsis
Mutations in the novel TECRL gene were identified in patients with malignant exercise‐induced arrhythmias. Increased triggered electrical activity upon stimulation in patient‐specific hiPSC‐CMs was rescued by the antiarrhythmic drug flecainide.
Trans‐2,3‐enoyl‐CoA reductase‐like (TECRL) is preferentially expressed in the heart.
Mutations in TECRL cause lethal arrhythmias in humans.
Cardiac defects in TECRL patients are characterized by overlapping features of long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT).
Cardiomyocytes differentiated from patient‐specific human induced pluripotent stem cells (hiPSCs) recapitulate the electrical abnormalities observed in TECRL patients.
Mutations in the novel TECRL gene were identified in patients with malignant exercise‐induced arrhythmias. Increased triggered electrical activity upon stimulation in patient‐specific hiPSC‐CMs was rescued by the antiarrhythmic drug flecainide.
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