Simon P. Fynn

An Entirely Subcutaneous Implantable Cardioverter–Defibrillator

BACKGROUND Implantable cardioverter-defibrillators (ICDs) prevent sudden death from cardiac causes in selected patients but require the use of transvenous lead systems. To eliminate the need for venous access, we designed and tested an entirely subcutaneous ICD system. METHODS First, we conducted two short-term clinical trials to identify a suitable device configuration and assess energy requirements. We evaluated four subcutaneous ICD configurations in 78 patients who were candidates for ICD implantation and subsequently tested the best configuration in 49 additional patients to determine the subcutaneous defibrillation threshold in comparison with that of the standard transvenous ICD. Then we evaluated the long-term use of subcutaneous ICDs in a pilot study, involving 6 patients, which was followed by a trial involving 55 patients. RESULTS The best device configuration consisted of a parasternal electrode and a left lateral thoracic pulse generator. This configuration was as effective as a transvenous ICD for terminating induced ventricular fibrillation, albeit with a significantly higher mean (+/-SD) energy requirement (36.6+/-19.8 J vs. 11.1+/-8.5 J). Among patients who received a permanent subcutaneous ICD, ventricular fibrillation was successfully detected in 100% of 137 induced episodes. Induced ventricular fibrillation was converted twice in 58 of 59 patients (98%) with the delivery of 65-J shocks in two consecutive tests. Clinically significant adverse events included two pocket infections and four lead revisions. After a mean of 10+/-1 months, the device had successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. CONCLUSIONS In small, nonrandomized studies, an entirely subcutaneous ICD consistently detected and converted ventricular fibrillation induced during electrophysiological testing. The device also successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. (ClinicalTrials.gov numbers, NCT00399217 and NCT00853645.)

Targeted left ventricular lead placement to guide cardiac resynchronization therapy: the TARGET study: a randomized, controlled trial.

OBJECTIVES This study sought to assess the impact of targeted left ventricular (LV) lead placement on outcomes of cardiac resynchronization therapy (CRT). BACKGROUND Placement of the LV lead to the latest sites of contraction and away from the scar confers the best response to CRT. We conducted a randomized, controlled trial to compare a targeted approach to LV lead placement with usual care. METHODS A total of 220 patients scheduled for CRT underwent baseline echocardiographic speckle-tracking 2-dimensional radial strain imaging and were then randomized 1:1 into 2 groups. In group 1 (TARGET [Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy]), the LV lead was positioned at the latest site of peak contraction with an amplitude of >10% to signify freedom from scar. In group 2 (control) patients underwent standard unguided CRT. Patients were classified by the relationship of the LV lead to the optimal site as concordant (at optimal site), adjacent (within 1 segment), or remote (≥2 segments away). The primary endpoint was a ≥15% reduction in LV end-systolic volume at 6 months. Secondary endpoints were clinical response (≥1 improvement in New York Heart Association functional class), all-cause mortality, and combined all-cause mortality and heart failure-related hospitalization. RESULTS The groups were balanced at randomization. In the TARGET group, there was a greater proportion of responders at 6 months (70% vs. 55%, p = 0.031), giving an absolute difference in the primary endpoint of 15% (95% confidence interval: 2% to 28%). Compared with controls, TARGET patients had a higher clinical response (83% vs. 65%, p = 0.003) and lower rates of the combined endpoint (log-rank test, p = 0.031). CONCLUSIONS Compared with standard CRT treatment, the use of speckle-tracking echocardiography to the target LV lead placement yields significantly improved response and clinical status and lower rates of combined death and heart failure-related hospitalization. (Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy [TARGET] study); ISRCTN19717943).

Electrophysiological and electrocardiographic characteristics of focal atrial tachycardia originating from the pulmonary veins: acute and long-term outcomes of radiofrequency ablation.

Background—The objective of this study was to describe the electrophysiological characteristics, anatomic distribution, and long-term outcome after focal ablation (RFA) of pulmonary vein (PV) atrial tachycardia (AT). Both atrial fibrillation (AF) and AT may be due to a rapidly firing focus in the PVs. Whether these represent two aspects of the same process is unknown. Methods and Results—Twenty-seven patients with 28 PV(16%) ATs of a consecutive series of 172 undergoing RFA for focal AT are reported. The mean age was 39±16 years, with symptoms for 9±14 years resistant to 1.7±0.8 medications. AT occurred spontaneously or with isoproterenol in all patients and was not inducible with PES in any. The distribution of PV ATs was right superior PV, 11; left superior PV, 11; left inferior PV, 5; and right inferior PV, 1; 26of 28 foci (93%) were ostial. RFA was successful in 28 of 28 PV ATs acutely. RFA was focal in 25 of 28, with PV isolation of a single target vein in 3. There were 4 recurrences at a mean of 3.3 months. Repeat RFA was performed in all 4 and successful in 3 of 4. All but one recurrence occurred from the same site. Long-term success was achieved in 26 of 27 (96%) patients at mean follow-up of 25±22 months. No patients have had subsequent development of AF or AT from a different site. Conclusions—PV AT has a distribution similar to PV AF, with a propensity to upper veins. However, the majority of foci are ostial, and only a small percentage occur from deep in the PV. Focal RFA is associated with high long-term success, with freedom from both AT from other sites and from AF. PV AT is a localized process and therefore may be different from PV AF.

Reversal of atrial electrical remodeling after cardioversion of persistent atrial fibrillation in humans.

BACKGROUND Although atrial electrical remodeling has been studied extensively in animal models, the reversibility of this phenomenon after termination of clinical atrial fibrillation (AF) has not been demonstrated. We aimed to examine this important question of reversibility by using AF cycle length (AFCL) and coupling intervals of atrial premature beats after cardioversion as measures of atrial refractoriness. METHODS AND RESULTS We measured AFCL at the right atrial appendage and distal coronary sinus before attempting internal cardioversion in 39 patients with persistent AF. Patients were monitored by daily transtelephonic recordings after discharge and admitted rapidly for repeat internal cardioversion if there was spontaneous AF recurrence. Measurements of AFCL were repeated immediately before repeat cardioversions in the 17 patients who had recurrence of AF. There was an increase in AFCL from the initial cardioversion to that measured at the time of first AF recurrence at both the right atrial appendage (161+/-22 vs 167+/-26 ms, P=0.05) and distal coronary sinus (162+/-20 vs 168+/-22 ms, P=0.01) sites. The magnitude of increase in AFCL was positively correlated with duration of sinus rhythm before AF recurrence (r=0.524, P=0.001). Other measures of refractoriness (shortest coupling interval of atrial premature beats and directly measured refractory periods after cardioversion) also increased from initial to subsequent cardioversions. CONCLUSIONS These findings demonstrate that changes in atrial electrophysiology associated with chronic AF in humans are reversible after cardioversion and that the extent of this reversal is dependent on the duration of sinus rhythm after cardioversion.

Ablation of Persistent Atrial Fibrillation Using Multielectrode Catheters and Duty-Cycled Radiofrequency Energy

OBJECTIVES The purpose of this study was to assess the efficacy and safety of a novel, multielectrode, duty-cycled radiofrequency ablation (RFA) system for long-standing persistent atrial fibrillation (AF). BACKGROUND RFA for persistent AF remains a lengthy and challenging procedure. METHODS In 5 European centers, 50 patients with long-standing persistent AF underwent RFA. A circular pulmonary vein (PV) ablation catheter was used for PV isolation. Complex fractionated atrial electrograms were targeted at the interatrial septum using a multiarray septal ablation catheter and in the left atrium using a multiarray ablation catheter. RESULTS During a mean total procedure time of 155 +/- 40 min, complete PV isolation and complex fractionated atrial electrogram ablation were achieved in all patients. In 50% of patients, redo ablation was performed using the same strategy and technology. There were no device-related adverse events. At 6 months, a 7-day Holter electrocardiogram showed >80% AF reduction in 40 of 50 patients (80%), and 32 of 50 (64%) were off antiarrhythmic drugs. At 20 +/- 4 months after the last procedure, 31 of 47 patients (66%) had a >80% reduction in AF burden, with 21 patients (45%) free of AF and off antiarrhythmic drugs. CONCLUSIONS This initial 50-patient multicenter study demonstrates a 80% short-term and 66% success rate at 20 months, with a low complication rate and a relatively short procedure time in patients with persistent AF using 3 anatomically specific multielectrode ablation catheters and low-energy duty-cycled radiofrequency energy.

Repetitive 4-Week Periods of Atrial Electrical Remodeling Promote Stability of Atrial Fibrillation Time Course of a Second Factor Involved in the Self-Perpetuation of Atrial Fibrillation

Background—Episodes of atrial fibrillation (AF) are known to cause both a rapid reduction in atrial refractoriness (atrial electrical remodeling) and a more delayed increase in AF stability thought to be due to a so-called “second factor.” The aim of this study was to quantify the effects and time course of such a factor on AF stability in the chronic goat model. Methods and Results—AF was maintained in 6 goats by burst atrial pacing for 3 consecutive 4-week periods separated a mean of 6±2.1 days of sinus rhythm. Six days of sinus rhythm was just sufficient for refractoriness changes to reverse fully in all goats. Atrial effective refractory period, AF inducibility, and duration of individual episodes of AF were assessed at regular intervals. There was a progressive reduction from month 1 to 2 to 3 in the mean duration of burst pacing required to induce individual episodes of AF of 60 seconds (178±251, 110±102, and 21±30 hours), 1 hour (229±224, 136±104, and 68±51 hours), and 24 hours (277±218, 192±190, and 102±75 hours; P <0.03). The frequency with which AF was induced during extrastimulus pacing increased progressively from 16.7% in month 1 to 31.7% in month 2 and 46.9% in month 3 (P <0.001). Conclusions—Sequential 4-week periods of atrial fibrillation result in a progressive increase in AF stability independent of baseline atrial refractory period. This finding suggests the presence of a second factor in the self-perpetuation of AF with a time course comparable to that of AF-induced ultrastructural changes in the atria.

Left ventricular lead placement in cardiac resynchronization therapy: where and how?

Cardiac resynchronization therapy (CRT) offers proven benefit to patients with refractory symptomatic chronic heart failure (New York Heart Association Class III or IV), severe left ventricular (LV) systolic dysfunction (LV ejection fraction <35%), and LV dyssynchrony (QRS width >120 ms). Cardiac resynchronization therapy has the potential to improve survival and functional capacity, reduce hospital admissions, and promote LV reverse remodelling. Although difficult to truly evaluate, up to 30% of patients do not attain symptomatic benefit. Factors associated with a poor outcome include inappropriate patient selection, inadequate device programming, presence of myocardial scar, and suboptimal LV lead placement. Left ventricular dyssynchrony is an important determinant of CRT response, although at present no reliable single measure to identify patients beyond QRS width has been identified. In this review, we discuss the effect of LV lead placement to pace the region of maximal dyssynchrony, the impact of total scar burden on response, and the relationship between LV lead position and localized scar. Consideration is also given to prospectively defining placement of the LV lead including surgical epicardial lead positioning.

Effect of Low-Amplitude Two-Dimensional Radial Strain at Left Ventricular Pacing Sites on Response to Cardiac Resynchronization Therapy

BACKGROUND Left ventricular (LV) lead placement to areas of scar has detrimental effects on response to cardiac resynchronization therapy (CRT). Speckle-tracking radial two-dimensional strain offers assessment of the extent of regional myocardial deformation. The aim of this study was to assess the impact of LV lead placement at areas of low-amplitude strain on CRT response. METHODS The optimal cutoff of radial strain amplitude at the LV pacing site associated with an unfavorable CRT response was determined in a derivation group (n = 65) and then tested in a second consecutive validation group (n = 75) of patients with heart failure. Patients had concordant LV leads if placed at the most delayed site, and dyssynchrony was defined as anteroseptal to posterior delay ≥ 130 msec. CRT response was defined as a ≥15% reduction in LV end-systolic volume at 6 months. RESULTS In the derivation group, a derived cutoff for radial strain amplitude of <9.8% defined low-amplitude segments (LAS) and had a high specificity but low sensitivity for predicting LV reverse remodeling, suggesting a strong negative predictive value. In the validation group, compared with patients without LAS at the LV pacing site, in patients with LAS (n = 16), CRT response was significantly lower (62.7% vs 31.3%, P < .05). By multivariate analysis, LV lead concordance and the absence of an LAS at the LV pacing site but not dyssynchrony were significantly related to CRT response. CONCLUSION LV lead placement over segments with two-dimensional radial strain amplitudes <9.8% is associated with poor outcomes of CRT.

Clinical evaluation of a policy of early repeated internal cardioversion for recurrence of atrial fibrillation.

Early Repeated Cardioversion for AF Recurrence. Introduction: The clinical value of cardioversion (CV) of persistent atrial fibrillation (AF) is limited by the high rate of early AF recurrence, which may be related to the persistence of atrial electrical remodeling. We examined the hypothesis that the likelihood of maintaining sinus rhythm after CV of persistent AF is significantly enhanced by a policy of early repeated CV.

Pulmonary veins: anatomy, electrophysiology, tachycardia, and fibrillation.

Recent years have seen an enormous amount of experimental and clinical research into role of the pulmonary veins (PVs) in atrial fibrillation (AF). Advanced imaging techniques have confirmed the findings of earlier postmortem studies and added further dimension to our knowledge of PV anatomy. Such work is vital for an effective approach to successful ablation of AF. Detailed mapping studies suggest that reentry within the PVs is most likely responsible for their arrhythmogenicity, although focal or triggered activity cannot be excluded. Further work also implicates the posterior left atrium in the genesis of AF. Investigation into the interplay between the PVs and left atrium has led to a reevaluation of the mechanisms underlying AF and suggests that the PVs may play a role in both the initiation and maintenance of this arrhythmia. In order for electrophysiologists to further develop the technical approach to ablation of AF and improve the clinical outcomes, these crucial issues must be resolved.