Muzahir H. Tayebjee

Characterization of fractionated atrial electrograms critical for maintenance of atrial fibrillation: a randomized, controlled trial of ablation strategies (the CFAE AF trial).

Background— Whether ablation of complex fractionated atrial electrograms (CFAE) modifies atrial fibrillation (AF) by eliminating drivers or atrial debulking remains unknown. This randomized study aimed to determine the effect of ablating different CFAE morphologies compared with normal electrograms (ie, debulking normal tissue) on the cycle length of persistent AF (AFCL).nnMethods and Results— After pulmonary vein isolation left and right atrial CFAE were targeted, until termination of AF or abolition of CFAE before DC cardioversion. Ten-second electrograms were classified according to a validated scale, with grade 1 being most fractionated and grade 5 normal. Patients were randomly assigned to have CFAE grades eliminated sequentially, from grade 1 to 5 (group 1) or grade 5 to 1 (group 2). An increase in AFCL (mean of left and right atrial appendage) ≥5 ms after a lesion was regarded as significant. CFAE (n=968) were targeted in 20 patients. AFCL increased after targeting 51±35% of grade 1 CFAE, 30±15% grade 2, 12±5% grade 3, 33±12% grade 4, and 8±15% grade 5 CFAE ( P <0.01 for grades 1, 2, and 4 versus 5; 3 versus 5, not significant). The proportion of lesions causing AFCL prolongation was unaffected by the order in which CFAE were targeted.nnConclusions— Targeting CFAE is not simply atrial debulking. Ablating certain grades of CFAE increases AFCL, suggesting they are more important in maintaining AF.nnClinical Trial Registration— URL: . Unique identifier: [NCT00894400][1].nn [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00894400&atom=%2Fcircae%2F4%2F5%2F622.atomBackground— Whether ablation of complex fractionated atrial electrograms (CFAE) modifies atrial fibrillation (AF) by eliminating drivers or atrial debulking remains unknown. This randomized study aimed to determine the effect of ablating different CFAE morphologies compared with normal electrograms (ie, debulking normal tissue) on the cycle length of persistent AF (AFCL). Methods and Results— After pulmonary vein isolation left and right atrial CFAE were targeted, until termination of AF or abolition of CFAE before DC cardioversion. Ten-second electrograms were classified according to a validated scale, with grade 1 being most fractionated and grade 5 normal. Patients were randomly assigned to have CFAE grades eliminated sequentially, from grade 1 to 5 (group 1) or grade 5 to 1 (group 2). An increase in AFCL (mean of left and right atrial appendage) ≥5 ms after a lesion was regarded as significant. CFAE (n=968) were targeted in 20 patients. AFCL increased after targeting 51±35% of grade 1 CFAE, 30±15% grade 2, 12±5% grade 3, 33±12% grade 4, and 8±15% grade 5 CFAE (P<0.01 for grades 1, 2, and 4 versus 5; 3 versus 5, not significant). The proportion of lesions causing AFCL prolongation was unaffected by the order in which CFAE were targeted. Conclusions— Targeting CFAE is not simply atrial debulking. Ablating certain grades of CFAE increases AFCL, suggesting they are more important in maintaining AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00894400.

Target Organ Damage in Hypertension: Pathophysiology and Implications for Drug Therapy

Hypertension is a well known risk factor for cardiovascular and cerebrovascular events such as heart attacks and strokes. In addition, it is associated with earlier changes in organ systems in the body, such as left ventricular hypertrophy (LVH), proteinuria and renal failure, retinopathy and vascular dementia which are grouped under the term target organ damage (TOD). There are many processes involved in the pathogenesis of TOD and these include endothelial activation, platelet activation, increased thrombogenesis, changes in the renin aldosterone angiotensin system (RAAS), and collagen turnover. All these changes work hand in hand and lead to the production of hypertensive TOD. In this review, we aim to provide an overview of the recent advances in pathophysiology of hypertensive TOD, and examine how these changes lead to the production of TOD. A better understanding of these pathogenic processes would help us better devise treatment strategies in preventing the dreaded complications associated with hypertension.

Impact of angiotensin-converting enzyme-inhibitors and angiotensin receptor blockers on long-term outcome of catheter ablation for atrial fibrillation

AIMSnWe hypothesized that modulation of the renin-angiotensin-aldosterone system (RAAS) improves success following catheter ablation for atrial fibrillation (AF).nnnMETHODS AND RESULTSnWe examined a prospective registry of consecutive patients undergoing catheter ablation of paroxysmal or persistent AF between November 2004 and December 2008. Patients were divided based on whether they were taking RAAS modulators at the time of their first procedure and examined on an intention to treat basis. There were 419 patients (222 paroxysmal and 197 persistent AF) who underwent 1.8 ± 0.9 procedures. Median follow-up from the last procedure was 1.7 (range 0.9-5.0) years. There were 142 patients on RAAS modulators; they were older, more likely to suffer from hypertension, diabetes, coronary disease, or left ventricular impairment. Overall, sinus rhythm was maintained in 73.2% of those taking RAAS modulators vs. 77.6% of those taking none (P = 0.304). Multivariate analysis showed no impact of RAAS modulators [hazard ratios (HR): 1.97, CI: 0.56-6.89, P = 0.290] but also no effect of hypertension, ischaemic heart disease, left ventricular impairment, or diabetes that should have confounded results (persistent AF was found to predict failure; HR: 0.34, CI: 0.14-0.84, P = 0.020). Subgroup analysis of patients with risk factors for developing AF (hypertension, coronary artery disease, left ventricular impairment, or diabetes) found no benefit in this context, with sinus rhythm maintained in 73.2% of those taking RAAS modulators compared with 69.9% of those taking none (P = 0.574).nnnCONCLUSIONnModulation of the RAAS does not appear to affect maintenance of sinus rhythm following catheter ablation of AF.

Impact of variant pulmonary vein anatomy and image integration on long-term outcome after catheter ablation for atrial fibrillation.

AIMSnTo investigate the impact of variant pulmonary vein (PV) anatomy and the use of three-dimensional image integration (3D-II) on long-term efficacy of catheter ablation for atrial fibrillation (AF).nnnMETHODSnConsecutive procedures from 2002 to 2007 were analysed from a prospective database. All patients underwent wide area circumferential ablation, with linear lesions added and complex fractionated electrograms targeted for persistent AF. Imaging was segmented on Carto to assess PV anatomy.nnnRESULTSnThree hundred and fifty patients underwent 1.9 ± 0.9 procedures. The mean age was 57 ± 11 years, 73% males, and 55% paroxysmal AF. Freedom from AF/atrial tachycardia was 42% for paroxysmal AF and 20% for persistent AF at 3.1 years after the first procedure, or 86 and 66%, respectively, at 2.5 years after the last procedure. The Kaplan-Meier analysis showed a trend towards improved single-procedure efficacy with 3D-II (8.9% difference, P = 0.087) and a reduction in the number of procedures per patient from 2.1 ± 1.1 to 1.8 ± 0.9 (P < 0.0001). The use of 3D-II improved single-procedure efficacy with Carto (13.3% difference, P = 0.018), but not with Ensite NavX. Variant PV anatomy was identified in 28% and was associated with a lower single-procedure efficacy (10.0% difference, P = 0.024) but with no effect on final outcome. Multivariate analysis confirmed the impact of 3D-II [hazard ratio (HR) for recurrence of AF 0.67, P = 0.020] and variant PV anatomy (HR 1.37, P = 0.044).nnnCONCLUSIONnThe use of 3D-II improves single-procedure efficacy of PV isolation for AF. Variant PV anatomy was associated with a lower single-procedure success rate.

Point-by-Point Radiofrequency Ablation Versus the Cryoballoon or a Novel Combined Approach: A Randomized Trial Comparing 3 Methods of Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation (The Cryo Versus RF Trial).

Catheter ablation of paroxysmal AF using the Cryoballoon (CRYO) has yielded similar success rates to conventional wide encirclement using radiofrequency catheter ablation (RFCA), but randomized data are lacking. Pilot data suggested a high success rate with a combined approach (COMBINED) using wide encirclement with RFCA followed by 2 CRYO applications to each vein. We compared these 3 strategies in a randomized controlled trial.

A randomised comparison of Cartomerge vs. NavX fusion in the catheter ablation of atrial fibrillation: The CAVERN Trial

PurposeIntegration of a 3D reconstruction of the left atrium into cardiac mapping systems can aid catheter ablation of atrial fibrillation (AF). The two most widely used systems are NavX Fusion and Cartomerge. We aimed to compare the clinical efficacy of these systems in a randomised trial.MethodsPatients undergoing their first ablation were randomised to mapping using either NavX fusion or CartoMerge. Pulmonary vein isolation by wide area circumferential ablation was performed for paroxysmal AF with additional linear and fractionated potential ablation for persistent AF. Seven-day Holter monitoring was used for confirmation of sinus rhythm maintenance at 6xa0months.ResultsNinety-seven patients were randomised and underwent a procedure. There was no difference in the primary endpoint of freedom from arrhythmia at 6xa0months (51% in the Cartomerge group vs. 48% in the NavX Fusion group, pu2009=u20090.76). 3D image registration was faster with Cartomerge (24 vs. 33xa0min, pu2009=u20090.0001), used less fluoroscopic screening (11 vs. 15xa0min, pu2009=u20090.039) with a lower fluoroscopic dose (840 vs. 1,415xa0mGyCm2, pu2009=u20090.043). There was a strong trend to lower ablation times in the Cartomerge group, overall RF time (3,292xa0s vs. 4,041, pu2009=u20090.07). Distance from 3D lesion to 3D image shell was smaller in the Cartomerge group (2.7u2009±u20091.9 vs. 3.3u2009±u20093.7xa0mm, pu2009<u20090.001).ConclusionsCartomerge appears to be faster and uses less fluoroscopy to achieve registration than NavX Fusion, but overall procedural times and clinical outcomes are similar.

Pulmonary vein isolation with radiofrequency ablation followed by cryotherapy: a novel strategy to improve clinical outcomes following catheter ablation of paroxysmal atrial fibrillation.

INTRODUCTIONnPulmonary vein (PV) isolation for atrial fibrillation (AF) often requires repeat procedures due to PV reconnection. We hypothesized that wide area cicumferential ablation using radiofrequency energy (RFA) followed by ostial PV ablation with a cryoablation balloon would reduce the rate of AF recurrence compared with either approach alone.nnnMETHODS AND RESULTSnA retrospective study compared outcomes in the first 25 consecutive patients undergoing PV isolation for paroxysmal AF using the combined approach, to consecutive controls using either approach alone. Demographic and procedural data were collected from a prospective database. Kaplan-Meier curves were used to analyse AF free survival and curves were compared using the log-rank test. Twenty-five patients were included in each group. There were no major complications. Minor complications included two transient phrenic nerve palsies and a haematoma in both the combined groups and the cryoablation alone groups. In the RFA group the only complication was a grounding plate burn. Follow-up was 2.2 years in the RFA group, 1.0 years in the cryoablation group, and 1.4 years in the combined group. All recurrences but one occurred within one year. Freedom from AF was significantly greater in the combined group (80%) compared with the RFA alone group (52%) and the cryoablation alone group (56%, both P < 0.05).nnnCONCLUSIONnThe combined approach was safe and increased single procedure efficacy of PV isolation for AF compared with either technique alone.

Characterization of Fractionated Atrial Electrograms Critical for Maintenance of Atrial FibrillationClinical Perspective: A Randomized, Controlled Trial of Ablation Strategies (The CFAE AF Trial)

Background— Whether ablation of complex fractionated atrial electrograms (CFAE) modifies atrial fibrillation (AF) by eliminating drivers or atrial debulking remains unknown. This randomized study aimed to determine the effect of ablating different CFAE morphologies compared with normal electrograms (ie, debulking normal tissue) on the cycle length of persistent AF (AFCL).nnMethods and Results— After pulmonary vein isolation left and right atrial CFAE were targeted, until termination of AF or abolition of CFAE before DC cardioversion. Ten-second electrograms were classified according to a validated scale, with grade 1 being most fractionated and grade 5 normal. Patients were randomly assigned to have CFAE grades eliminated sequentially, from grade 1 to 5 (group 1) or grade 5 to 1 (group 2). An increase in AFCL (mean of left and right atrial appendage) ≥5 ms after a lesion was regarded as significant. CFAE (n=968) were targeted in 20 patients. AFCL increased after targeting 51±35% of grade 1 CFAE, 30±15% grade 2, 12±5% grade 3, 33±12% grade 4, and 8±15% grade 5 CFAE ( P <0.01 for grades 1, 2, and 4 versus 5; 3 versus 5, not significant). The proportion of lesions causing AFCL prolongation was unaffected by the order in which CFAE were targeted.nnConclusions— Targeting CFAE is not simply atrial debulking. Ablating certain grades of CFAE increases AFCL, suggesting they are more important in maintaining AF.nnClinical Trial Registration— URL: . Unique identifier: [NCT00894400][1].nn [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00894400&atom=%2Fcircae%2F4%2F5%2F622.atomBackground— Whether ablation of complex fractionated atrial electrograms (CFAE) modifies atrial fibrillation (AF) by eliminating drivers or atrial debulking remains unknown. This randomized study aimed to determine the effect of ablating different CFAE morphologies compared with normal electrograms (ie, debulking normal tissue) on the cycle length of persistent AF (AFCL). Methods and Results— After pulmonary vein isolation left and right atrial CFAE were targeted, until termination of AF or abolition of CFAE before DC cardioversion. Ten-second electrograms were classified according to a validated scale, with grade 1 being most fractionated and grade 5 normal. Patients were randomly assigned to have CFAE grades eliminated sequentially, from grade 1 to 5 (group 1) or grade 5 to 1 (group 2). An increase in AFCL (mean of left and right atrial appendage) ≥5 ms after a lesion was regarded as significant. CFAE (n=968) were targeted in 20 patients. AFCL increased after targeting 51±35% of grade 1 CFAE, 30±15% grade 2, 12±5% grade 3, 33±12% grade 4, and 8±15% grade 5 CFAE (P<0.01 for grades 1, 2, and 4 versus 5; 3 versus 5, not significant). The proportion of lesions causing AFCL prolongation was unaffected by the order in which CFAE were targeted. Conclusions— Targeting CFAE is not simply atrial debulking. Ablating certain grades of CFAE increases AFCL, suggesting they are more important in maintaining AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00894400.

Characterization of Fractionated Atrial Electrograms Critical for Maintenance of Atrial FibrillationClinical Perspective

Background— Whether ablation of complex fractionated atrial electrograms (CFAE) modifies atrial fibrillation (AF) by eliminating drivers or atrial debulking remains unknown. This randomized study aimed to determine the effect of ablating different CFAE morphologies compared with normal electrograms (ie, debulking normal tissue) on the cycle length of persistent AF (AFCL).nnMethods and Results— After pulmonary vein isolation left and right atrial CFAE were targeted, until termination of AF or abolition of CFAE before DC cardioversion. Ten-second electrograms were classified according to a validated scale, with grade 1 being most fractionated and grade 5 normal. Patients were randomly assigned to have CFAE grades eliminated sequentially, from grade 1 to 5 (group 1) or grade 5 to 1 (group 2). An increase in AFCL (mean of left and right atrial appendage) ≥5 ms after a lesion was regarded as significant. CFAE (n=968) were targeted in 20 patients. AFCL increased after targeting 51±35% of grade 1 CFAE, 30±15% grade 2, 12±5% grade 3, 33±12% grade 4, and 8±15% grade 5 CFAE ( P <0.01 for grades 1, 2, and 4 versus 5; 3 versus 5, not significant). The proportion of lesions causing AFCL prolongation was unaffected by the order in which CFAE were targeted.nnConclusions— Targeting CFAE is not simply atrial debulking. Ablating certain grades of CFAE increases AFCL, suggesting they are more important in maintaining AF.nnClinical Trial Registration— URL: . Unique identifier: [NCT00894400][1].nn [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00894400&atom=%2Fcircae%2F4%2F5%2F622.atomBackground— Whether ablation of complex fractionated atrial electrograms (CFAE) modifies atrial fibrillation (AF) by eliminating drivers or atrial debulking remains unknown. This randomized study aimed to determine the effect of ablating different CFAE morphologies compared with normal electrograms (ie, debulking normal tissue) on the cycle length of persistent AF (AFCL). Methods and Results— After pulmonary vein isolation left and right atrial CFAE were targeted, until termination of AF or abolition of CFAE before DC cardioversion. Ten-second electrograms were classified according to a validated scale, with grade 1 being most fractionated and grade 5 normal. Patients were randomly assigned to have CFAE grades eliminated sequentially, from grade 1 to 5 (group 1) or grade 5 to 1 (group 2). An increase in AFCL (mean of left and right atrial appendage) ≥5 ms after a lesion was regarded as significant. CFAE (n=968) were targeted in 20 patients. AFCL increased after targeting 51±35% of grade 1 CFAE, 30±15% grade 2, 12±5% grade 3, 33±12% grade 4, and 8±15% grade 5 CFAE (P<0.01 for grades 1, 2, and 4 versus 5; 3 versus 5, not significant). The proportion of lesions causing AFCL prolongation was unaffected by the order in which CFAE were targeted. Conclusions— Targeting CFAE is not simply atrial debulking. Ablating certain grades of CFAE increases AFCL, suggesting they are more important in maintaining AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00894400.

Distinguishing far-field appendage from local pulmonary vein signal in the left upper pulmonary vein during atrial tachycardia.

A 52-year-old man with drug-refractory paroxysmal atrial fibrillation (AF) underwent an AF ablation procedure comprising wide area encirclement of leftand right-sided pulmonary veins, and ablation of a tricuspid valve isthmus line. At the end of the case all pulmonary veins were isolated and bidirectional block was achieved across the tricuspid isthmus. He represented after 2 months with symptoms relating to a documented atrial tachycardia. He underwent a repeat procedure. Ablation and pulmonary vein (PV) catheters were introduced to the left atrium and a decapolar catheter was placed within the coronary sinus. Placement of the PV catheter within the left upper pulmonary vein (LUPV) confirmed reconnection of this vein. Two distinct bipolar signals were identified within the vein (see Fig. 1, Signals A and B). These change as the PV catheter is advanced into the vein. Explain the change in signal timing, determine whether the tachycardia originates from the vein, and identify which signal represents a local pulmonary vein electrogram and which is the far-field signal.