Jason G. Andrade

The Clinical Profile and Pathophysiology of Atrial Fibrillation Relationships Among Clinical Features, Epidemiology, and Mechanisms

Atrial fibrillation (AF) is the most common arrhythmia (estimated lifetime risk, 22%-26%). The aim of this article is to review the clinical epidemiological features of AF and to relate them to underlying mechanisms. Long-established risk factors for AF include aging, male sex, hypertension, valve disease, left ventricular dysfunction, obesity, and alcohol consumption. Emerging risk factors include prehypertension, increased pulse pressure, obstructive sleep apnea, high-level physical training, diastolic dysfunction, predisposing gene variants, hypertrophic cardiomyopathy, and congenital heart disease. Potential risk factors are coronary artery disease, kidney disease, systemic inflammation, pericardial fat, and tobacco use. AF has substantial population health consequences, including impaired quality of life, increased hospitalization rates, stroke occurrence, and increased medical costs. The pathophysiology of AF centers around 4 general types of disturbances that promote ectopic firing and reentrant mechanisms, and include the following: (1) ion channel dysfunction, (2) Ca(2+)-handling abnormalities, (3) structural remodeling, and (4) autonomic neural dysregulation. Aging, hypertension, valve disease, heart failure, myocardial infarction, obesity, smoking, diabetes mellitus, thyroid dysfunction, and endurance exercise training all cause structural remodeling. Heart failure and prior atrial infarction also cause Ca(2+)-handling abnormalities that lead to focal ectopic firing via delayed afterdepolarizations/triggered activity. Neural dysregulation is central to atrial arrhythmogenesis associated with endurance exercise training and occlusive coronary artery disease. Monogenic causes of AF typically promote the arrhythmia via ion channel dysfunction, but the mechanisms of the more common polygenic risk factors are still poorly understood and under intense investigation. Better recognition of the clinical epidemiology of AF, as well as an improved appreciation of the underlying mechanisms, is needed to develop improved methods for AF prevention and management.

Efficacy and safety of cryoballoon ablation for atrial fibrillation: A systematic review of published studies

Further-more, the procedure is complex, time consuming, andhighly dependent on operator competency given the diffi-culties associated with creating contiguous curvilinear le-sions with focal ablation. As such, considerable effort hasbeen directed toward deriving more effective and saferapproaches.Balloon-based ablation systems potentially offer a sim-pler and faster means of achieving pulmonary vein isolation(PVI) that, theoretically, is less reliant on operator dexterity.Concurrently, cryothermal energy offers advantages overRF energy, including increased catheter stability, less endo-thelial disruption with lower thromboembolic risk, and min-imal tissue contraction with healing, an observation thoughtto result in less esophageal damage and PVS.

Cardiac Resynchronization Therapy in Patients With Heart Failure and a QRS Complex <120 Milliseconds The Evaluation of Resynchronization Therapy for Heart Failure (LESSER-EARTH) Trial

Background— 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. Methods and Results— 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). Conclusions— 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. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00900549.Background —While the benefits of cardiac resynchronization therapy (CRT) 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. Methods and Results —The LESSER-EARTH trial is a randomized, double-blind, 12-center study that was designed to compare the effects of active versus inactive CRT therapy in patients with severe left ventricular dysfunction and a QRS duration <120 ms. The trial was prematurely interrupted by the Data Safety and Monitoring Board due to 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 CRT [-0.7 (-2.9, 1.5) minutes versus +0.8 (-1.2, 2.9) minutes, P =0.31]. Similarly, no significant differences were observed in left ventricular end-systolic volumes [-6.4 (-18.8, 5.9) mL versus +3.1 (-9.2, 15.5) mL, P =0.28] and ejection fraction [+3.3% (0.7%, 6.0%) versus +2.1% (-0.5%, 4.8%), P =0.52]. Moreover, CRT was associated with a significant reduction in the 6-minute walk distance [-11.3 (-31.7, 9.7) meters versus +25.3 (6.1, 44.5) meters, P =0.01], an increase in QRS duration [40.2 (34.2, 46.2) ms versus 3.4 (0.6, 6.2) ms, P <0.0001], and a non-significant trend towards an increase in heart failure-related hospitalizations (15 hospitalizations in 5 patients versus 4 hospitalizations in 4 patients). Conclusions —In patients with a left ventricular ejection fraction ≤35%, symptoms of heart failure, and a QRS duration <120 ms, CRT did not improve clinical outcomes or left ventricular remodelling, and was associated with potential harm. Clinical Trial Registration Information —ClinicalTrials.gov. Identifier: [NCT00900549][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00900549&atom=%2Fcirculationaha%2Fearly%2F2013%2F02%2F05%2FCIRCULATIONAHA.112.001239.atom

Adenosine-guided pulmonary vein isolation for the treatment of paroxysmal atrial fibrillation: an international, multicentre, randomised superiority trial

BACKGROUND Catheter ablation is increasingly used to manage atrial fibrillation, but arrhythmia recurrences are common. Adenosine might identify pulmonary veins at risk of reconnection by unmasking dormant conduction, and thereby guide additional ablation to improve arrhythmia-free survival. We assessed whether adenosine-guided pulmonary vein isolation could prevent arrhythmia recurrence in patients undergoing radiofrequency catheter ablation for paroxysmal atrial fibrillation. METHODS We did this randomised trial at 18 hospitals in Australia, Europe, and North America. We enrolled patients aged older than 18 years who had had at least three symptomatic atrial fibrillation episodes in the past 6 months, and for whom treatment with an antiarrhythmic drug failed. After pulmonary vein isolation, intravenous adenosine was administered. If dormant conduction was present, patients were randomly assigned (1:1) to additional adenosine-guided ablation to abolish dormant conduction or to no further ablation. If no dormant conduction was revealed, randomly selected patients were included in a registry. Patients were masked to treatment allocation and outcomes were assessed by a masked adjudicating committee. Patients were followed up for 1 year. The primary outcome was time to symptomatic atrial tachyarrhythmia after a single procedure in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT01058980. FINDINGS Adenosine unmasked dormant pulmonary vein conduction in 284 (53%) of 534 patients. 102 (69·4%) of 147 patients with additional adenosine-guided ablation were free from symptomatic atrial tachyarrhythmia compared with 58 (42·3%) of 137 patients with no further ablation, corresponding to an absolute risk reduction of 27·1% (95% CI 15·9-38·2; p<0·0001) and a hazard ratio of 0·44 (95% CI 0·31-0·64; p<0·0001). Of 115 patients without dormant pulmonary vein conduction, 64 (55·7%) remained free from symptomatic atrial tachyarrhythmia (p=0·0191 vs dormant conduction with no further ablation). Occurrences of serious adverse events were similar in each group. One death (massive stroke) was deemed probably related to ablation in a patient included in the registry. INTERPRETATION Adenosine testing to identify and target dormant pulmonary vein conduction during catheter ablation of atrial fibrillation is a safe and highly effective strategy to improve arrhythmia-free survival in patients with paroxysmal atrial fibrillation. This approach should be considered for incorporation into routine clinical practice. FUNDING Canadian Institutes of Health Research, St Jude Medical, Biosense-Webster, and M Lachapelle (Montreal Heart Institute Foundation).

Pulmonary vein isolation using “contact force” ablation: The effect on dormant conduction and long-term freedom from recurrent atrial fibrillation—A prospective study

BACKGROUND 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. OBJECTIVE The purpose of this study was to study the utility of contact force-guided ablation on immediate and long-term outcomes. METHODS 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. RESULTS 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). CONCLUSION 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.

Pulmonary vein isolation using a second-generation cryoballoon catheter: a randomized comparison of ablation duration and method of deflation.

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.

Clinical Experience With a Novel Electromyographic Approach to Preventing Phrenic Nerve Injury During Cryoballoon Ablation in Atrial Fibrillation

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.

Incidence and Significance of Early Recurrences of Atrial Fibrillation After Cryoballoon Ablation Insights From the Multicenter Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) Trial

Background—Early recurrence of atrial fibrillation (ERAF) is common after radiofrequency catheter ablation for AF. We sought to determine the incidence and prognostic significance of ERAF after cryoballoon ablation. Moreover, the benefit of early reablation for ERAF after cryoballoon ablation is undetermined. Methods and Results—The Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) trial randomized 245 patients with paroxysmal AF to medical therapy versus cryoballoon-based pulmonary vein ablation. Patients were followed for 12 months. ERAF was defined as any recurrence of AF >30 seconds during the first 3 months of follow-up. Late recurrence (LR) was defined as any recurrence of AF >30 seconds between 3 and 12 months. Of the 163 patients randomized to cryoablation, 84 patients experienced ERAF (51.5%). The only significant factor associated with ERAF was male sex (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.03–4.61; P=0.041). LR was observed in 41 patients (25.1%), and was significantly related to ERAF (55.6% LR with ERAF versus 12.7% without ERAF; P<0.001). Among patients with ERAF, only current tobacco use (HR, 3.84; 95% CI, 1.82–8.11; P<0.001) was associated with LR. Conversely, early reablation was associated with greater freedom from LR (3.3% LR with early reablation versus 55.6% without; HR, 0.04; 95% CI, 0.01–0.32; P=0.002). Conclusions—ERAF after cryoballoon ablation occurs in ≈50% of patients and is strongly associated with LR. Early reablation for ERAF is associated with excellent long-term freedom from recurrent AF.

Facilitated cardiac recovery in fulminant myocarditis: pediatric use of the Impella LP 5.0 pump

We describe the successful use of the Impella LP 5.0 intracardiac microaxial pump (Abiomed, Danvers, MA) in a 13-year-old boy with fulminant biopsy-proven viral myocarditis. The patient, who previously was in refractory cardiogenic shock despite increasing inotropic and vasopressor support, immediately stabilized after Impella LP 5.0 implantation and was successfully bridged to a full recovery. Months later, he remains completely well, with no intracardiac or peripheral vascular sequelae of the procedure. In carefully selected pediatric patients the Impella may be a beneficial form of temporary mechanical circulatory support for fulminant cardiogenic shock.

Exploration of Association of 1,25-OH2D3 with Augmentation Index, a Composite Measure of Arterial Stiffness

BACKGROUND AND OBJECTIVES Abnormalities in mineral metabolism [calcium, phosphate, and immunoreactive parathyroid hormone (PTH)] and vitamin D have been linked to increases in central arterial stiffness. Central arterial stiffness can be measured using noninvasive technologies, including augmentation index (AIx), a composite measure of arterial stiffness. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS In 131 outpatients identified from individual cardiac or kidney disease clinics, we examined conventional demographic and laboratory risk factors, vitamin D levels (1,25-OH2D3 and 25-OHD3), and markers of inflammation or endothelial function [C-reactive peptide (hsCRP), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), and IL-6] in relationship to AIx. RESULTS The median eGFR was significantly different between clinics (range 25-81 ml/min). Subjects with higher phosphate or MMP-9 levels were found to have a higher AIx (P = 0.02 and 0.07, respectively). Lower 1,25-OH2D3 levels or reduced eGFR were associated with higher AIx (P = 0.002 and 0.005, respectively). The associations between 1,25-OH2D3 and phosphate levels and AIx were observed for values within the normal range. No association was noted for calcium, iPTH, 25-OHD3, or hsCRP and AIx. Adjusting for potential confounders [eGFR, calcium, phosphate, and (log) iPTH] the association of lower 1,25-OH2D3 with AIx remained statistically significant. CONCLUSION This exploratory study demonstrates a significant association between AIx and 1,25-OH2D3 in a diverse group with cardiac, kidney disease, or both. These increasing understanding of the role of vitamin D in vascular health lends a context to these findings and raises questions as to additional modifiable risk factors in complex patients. Further studies are required.