Complication rates following ventricular tachycardia ablation in ischaemic and non-ischaemic cardiomyopathies: a systematic review.

BACKGROUND: Catheter ablation of ventricular tachycardia (VT) is associated with potential major complications, including mortality. The risk of acute complications in patients with ischaemic cardiomyopathy (ICM) and non-ischaemic cardiomyopathy (NICM) has not been systematically evaluated. METHODS: PubMed was searched for studies of catheter ablation of VT published between September 2009 and September 2019. Pre-specified primary outcomes were (1) rate of major acute complications, including death, and (2) mortality rate. RESULTS: A total of 7395 references were evaluated for relevance. From this, 50 studies with a total of 3833 patients undergoing 4319 VT ablation procedures fulfilled the inclusion criteria (mean age 59 years; male 82%; 2363 [62%] ICM; 1470 [38%] NICM). The overall major complication rate in ICM cohorts was 9.4% (95% CI, 8.1-10.7) and NICM cohorts was 7.1% (95% CI, 6.0-8.3). Reported complication rates were highly variable between studies (ICM I2 = 90%; NICM I2 = 89%). Vascular complications (ICM 2.5% [95% CI, 1.9-3.1]; NICM 1.2% [95% CI, 0.7-1.7]) and cerebrovascular events (ICM 0.5% [95% CI, 0.2-0.7]; NICM, 0.1% [95% CI, 0-0.2]) were significantly higher in ICM cohorts. Acute mortality rates in the ICM and NICM cohorts were low (ICM 0.9% [95% CI, 0.5-1.3]; NICM 0.6% [95% CI, 0.3-1.0]) with the majority of overall deaths (ICM 75%; NICM 80%) due to either recurrent VT or cardiogenic shock. CONCLUSION: Overall acute complication rates of VT ablation are comparable between ICM and NICM patients. However, the pattern and predictors of complications vary depending on the underlying cardiomyopathy.

Relationship between sodium channel function and clinical phenotype in SCN5A variants associated with Brugada syndrome.

The identification of a pathogenic SCN5A variant confers an increased risk of conduction defects and ventricular arrhythmias (VA) in Brugada syndrome (BrS). However, specific aspects of sodium channel function that influence clinical phenotype have not been defined. A systematic literature search identified SCN5A variants associated with BrS. Sodium current (INa ) functional parameters (peak current, decay, steady-state activation and inactivation, and recovery from inactivation) and clinical features (conduction abnormalities [CA], spontaneous VA or family history of sudden cardiac death [SCD], and spontaneous BrS electrocardiogram [ECG]) were extracted. A total of 561 SCN5A variants associated with BrS were identified, for which data on channel function and clinical phenotype were available in 142. In the primary analysis, no relationship was found between any aspect of channel function and CA, VA/SCD, or spontaneous BrS ECG pattern. Sensitivity analyses including only variants graded pathogenic or likely pathogenic suggested that reduction in peak current and positive shift in steady-state activation were weakly associated with CA and VA/SCD, although sensitivity and specificity remained low. The relationship between in vitro assessment of channel function and BrS clinical phenotype is weak. The assessment of channel function does not enhance risk stratification. Caution is needed when extrapolating functional testing to the likelihood of variant pathogenicity.

Early experience of thoracoscopic vs. catheter ablation for atrial fibrillation.

AIMS: Video-assisted thoracoscopic surgery (VATS) ablation has been advocated as a treatment option for non-paroxysmal atrial fibrillation (AF) in recent guidelines. Real-life data on its safety and efficacy during a centre's early experience are sparse. METHODS AND RESULTS: Thirty patients (28 persistent/longstanding persistent AF) underwent standalone VATS ablation for AF by an experienced thoracoscopic surgeon, with the first 20 cases proctored by external surgeons. Procedural and follow-up outcomes were collected prospectively, and compared with 90 propensity-matched patients undergoing contemporaneous catheter ablation (CA). Six (20.0%) patients undergoing VATS ablation experienced ≥1 major complication (death n = 1, stroke n = 2, conversion to sternotomy n = 3, and phrenic nerve injury n = 2). This was significantly higher than the 1.1% major complication rate (tamponade requiring drainage n = 1) seen with CA (P < 0.001). Twelve-month single procedure arrhythmia-free survival rates without antiarrhythmic drugs were 56% in the VATS and 57% in the CA cohorts (P = 0.22), and 78% and 80%, respectively given an additional CA and antiarrhythmic drugs (P = 0.32). CONCLUSION: During a centre's early experience, VATS ablation may have similar success rates to those from an established CA service, but carry a greater risk of major complications. Those embarking on a programme of VATS AF ablation should be aware that complication and success rates may differ from those reported by selected high-volume centres.

Ablation index, a novel marker of ablation lesion quality: prediction of pulmonary vein reconnection at repeat electrophysiology study and regional differences in target values.

AIMS: Force-Time Integral (FTI) is commonly used as a marker of ablation lesion quality during pulmonary vein isolation (PVI), but does not incorporate power. Ablation Index (AI) is a novel lesion quality marker that utilizes contact force, time, and power in a weighted formula. Furthermore, only a single FTI target value has been suggested despite regional variation in left atrial wall thickness. We aimed to study AI's and FTI's relationships with PV reconnection at repeat electrophysiology study, and regional threshold values that predicted no reconnection. METHODS AND RESULTS: Forty paroxysmal atrial fibrillation patients underwent contact force-guided PVI, and the minimum and mean AI and FTI values for each segment were identified according to a 12-segment model. All patients underwent repeat electrophysiology study at 2 months, regardless of symptoms, to identify sites of PV reconnection. Late PV reconnection was seen in 53 (11%) segments in 25 (62%) patients. Reconnected segments had significantly lower minimum AI [308 (252-336) vs. 373 (323-423), P < 0.0001] and FTI [137 (92-182) vs. 228 (157-334), P < 0.0001] compared with non-reconnected segments. Minimum AI and FTI were both independently predictive, but AI had a smaller P value. Higher minimum AI and FTI values were required to avoid reconnection in anterior/roof segments than for posterior/inferior segments (P < 0.0001). No reconnection was seen where the minimum AI value was ≥370 for posterior/inferior segments and ≥480 for anterior/roof segments. CONCLUSION: The minimum AI value in a PVI segment is independently predictive of reconnection of that segment at repeat electrophysiology study. Higher AI and FTI values are required for anterior/roof segments than for posterior/inferior segments to prevent reconnection.

Novel Extravascular Defibrillation Configuration With a Coil in the Substernal Space: The ASD Clinical Study.

OBJECTIVES: This study assessed the defibrillation efficacy of the substernal-lateral electrode configuration. BACKGROUND: Subcutaneous implantable cardioverter-defibrillators (ICDs) are regarded as alternatives to transvenous ICDs in certain subjects. However, substantially higher shock energy of up to 80 J may be required. Proposed is a new defibrillation method of placing the shock coil into the substernal space. METHODS: This prospective, nonrandomized, feasibility study was conducted in subjects scheduled for midline sternotomy or implant of ICD. A blunted end tunneling tool was used to insert a defibrillation lead behind the sternum using a percutaneous subxiphoid approach. A skin patch electrode was placed on the left mid-axillary line at the fourth to fifth intercostal space. After ventricular fibrillation induction, a single 35-J shock was delivered between the lead and skin patch. RESULTS: Sixteen subjects (12 males, 4 females; mean age: 61.6 ± 11.8 years) were enrolled. The mean lead placement time was 11.1 ± 6.6 min. Of the 14 subjects with successfully induced ventricular fibrillation episodes, 13 subjects (92.9%) had successful defibrillation. The 1 failure was associated with high and lateral shock coil placement. Mean ventricular fibrillation duration was 18.4 ± 5.6 s with a shock impedance of 98.1 ± 19.3 ohms. Of the 11 subjects with coil-patch electrograms, the average R-wave amplitude during sinus rhythm was 3.0 ± 1.4 mV. CONCLUSIONS: These preliminary data demonstrate that substernal defibrillation is feasible and successful defibrillation can be achieved with the shock energy available in current transvenous ICDs. This may open new alternatives to extravascular ICD therapy.

Pulmonary Vein Re-Isolation as a Routine Strategy Regardless of Symptoms: The PRESSURE Randomized Controlled Trial.

OBJECTIVES: The goal of this study was to determine whether a strategy of early re-isolation of pulmonary vein (PV) reconnection in all patients, regardless of symptoms, would reduce the recurrence of atrial fibrillation (AF) and improve quality of life. BACKGROUND: Lasting pulmonary vein isolation (PVI) remains elusive. PV reconnection is strongly linked to the recurrence of arrhythmia. METHODS: A total of 80 patients with paroxysmal AF were randomized 1:1 after contact force-guided PVI to receive either standard care or undergo a repeat electrophysiology study after 2 months regardless of symptoms (repeat study). At the initial procedure, PVI was demonstrated by entrance/exit block and adenosine administration after a minimum 20-min wait. At the repeat study, all sites of PV reconnection were re-ablated. Patients recorded electrocardiograms daily and whenever symptomatic for 12 months using a handheld monitor. Recurrence was defined as ≥30 s of atrial tachyarrhythmia (AT) after a 3-month blanking period. The Atrial Fibrillation Effect on Quality-of-Life Questionnaire was completed at baseline and at 6 and 12 months. RESULTS: All 40 patients randomized to repeat study attended for this after 62 ± 6 days, of whom 25 (62.5%) had reconnection of 41 (26%) PVs. There were no complications related to these procedures. Subjects recorded a total of 32,203 electrocardiograms (380 [335 to 447] per patient) during 12.6 (12.2 to 13.2) months of follow-up. AT recurrence was significantly lower for the repeat study group (17.5% vs. 42.5%; p = 0.03), as was AT burden (p = 0.03). Scores on the Atrial Fibrillation Effect on Quality-of-Life Questionnaire were higher in the repeat study group at 6 months (p < 0.001) and 12 months (p = 0.02). CONCLUSIONS: A strategy of routine repeat assessment with re-isolation of PV reconnection improved freedom from AT recurrence, AT burden, and quality of life compared with current standard care. (The Effect of Early Repeat Atrial Fibrillation [AF] on AF Recurrence [PRESSURE]; NCT01942408).

Reablated Sites of Acute Reconnection After Pulmonary Vein Isolation Do Not Predict Sites of Late Reconnection at Repeat Electrophysiology Study.

INTRODUCTION: Acute reconnection of pulmonary veins (PVs) is frequently seen in the waiting period following pulmonary vein isolation (PVI). There are concerns that reablation at these sites may not be durably effective due to tissue edema caused by the initial ablation. We aimed to prospectively study the relationship between acute and late reconnection. METHODS AND RESULTS: Wide-area circumferential PVI was performed in 40 paroxysmal AF patients. Spontaneous reconnection was assessed after a minimum 20-minute waiting period, with adenosine administered to unmask dormant reconnection. All sites of acute reconnection were ablated to reisolate the PV. All 40 patients then underwent repeat electrophysiology study after 2 months, regardless of symptoms, to identify late reconnection. Sites of acute and late reconnection were compared according to a 12-segment PVI model. Acute reconnection was seen in 28 (6%) PVI segments in 20 (50%) patients, affecting 24/160 (15%) PVs. All were successfully reisolated. At repeat electrophysiology study, 51 (11%) PVI segments were reconnected in 25 (62%) patients, affecting 41 (25%) PVs. The proportion of PVI segments with and without acute reconnection exhibiting late reconnection at repeat study was no different (14% vs. 10%, P = 0.524). There was also no difference in late reconnection between PVI circles or patients with and without acute reconnection. CONCLUSION: Most PVI segments that undergo further ablation for acute reconnection show persistent isolation at repeat electrophysiology study, and the rate of late reconnection for these segments is no different to that for segments that did not acutely reconnect. This implies that effective reablation is delivered at these sites.

Recurrence of atrial tachyarrhythmia during the second month of the blanking period is associated with more extensive pulmonary vein reconnection at repeat electrophysiology study.

BACKGROUND: Current guidelines recommend a 3-month blanking period after pulmonary vein isolation (PVI) as early recurrence of atrial tachyarrhythmia (ERAT) may be due to transient proarrhythmic factors. However, studies have suggested that these factors resolve by 1 month. PV reconnection (PVrc) is strongly associated with postblanking AT recurrence in paroxysmal atrial fibrillation. We hypothesized that ERAT occurring beyond 4 weeks after PVI is associated with PVrc at repeat electrophysiology study. METHODS AND RESULTS: Forty patients with paroxysmal atrial fibrillation underwent mandatory repeat electrophysiology study 2 months after PVI, regardless of symptoms, to document the number of reconnected PVs. Antiarrhythmic drugs, including ß-blockers, were discontinued 4 weeks after PVI. Patients were instructed to record a 30-second ECG everyday between the 2 procedures using a portable monitor, with additional recordings for symptoms. ERAT was defined as ≥30 seconds of AT. Patients recorded a total of 3293 ECGs. Four (10%) patients had ERAT in the first 4 weeks (M1) only, 2 (5%) in month 2 (M2) only, and 11 (28%) in both. PVrc of 1 PV was identified in 12 (30%) patients and of >1 PV in 13 (32%) patients. ERAT in M2 was associated with PVrc, whereas M1 was not (11/13 [85%] versus 0/4 [0%]; P=0.006). M2 ERAT was strongly associated with PVrc of >1 PV (10/13 [77%] versus 3/27 [11%] without M2 ERAT; P<0.0001). CONCLUSIONS: ERAT occurring beyond 4 weeks after PVI is associated with PVrc and particularly of PVrc of >1 PV. ERAT confined to M1 is unrelated to underlying PVrc. The relationship between ERAT beyond 4 weeks after PVI and postblanking AT recurrence merits further investigation.

A novel marker to predict early recurrence after atrial fibrillation ablation: the ablation effectiveness quotient.

INTRODUCTION: Inability to predict clinical outcome despite acutely successful pulmonary vein isolation (PVI) remains the Achilles' heel of atrial fibrillation ablation (AFA). Arrhythmia recurrence is frequently due to recovery of radiofrequency (RF) ablation lesions believed to be complete at the original procedure. OBJECTIVES: We hypothesized that a high ratio between post-AFA levels of serum high sensitivity cardiac troponin T (HScTnT), a highly specific marker of acute myocardial injury, and duration of RF application (the ablation effectiveness quotient, AEQ) would indicate effective ablation and correlate with early clinical success. METHODS: We prospectively measured HScTnT levels in 60 patients (42 [70%] male, 22 [37%] with paroxysmal AF [PAF], mean age 62.5 ± 10.6 years) 12-18 hours after AFA and calculated the AEQ for each. Patients were followed-up with ECGs and Holter monitors for recurrence of atrial tachyarrhythmia (AT). RESULTS: Early recurrence of AT within 6 months occurred in 22 (37%). AT recurrence was not significantly related to left atrial size or comorbidities, nor to RF time or HScTnT level. Mean AEQ was significantly lower in those with recurrence than those without (0.35 ± 0.14 ng/L/s vs. 0.45 ± 0.18 ng/L/s), P = 0.02. Subgroup analysis showed this finding was due to patients with PAF in whom early significance was maintained to one year, with an AEQ >0.4 ng/L/s having 75% sensitivity and 90% specificity in predicting freedom from AT. CONCLUSION: A high AEQ correlates well with freedom from AT in patients with PAF in both the short and medium term. If confirmed in further studies, AEQ may become a useful marker of risk of AT post-AFA.

Fractionation of electrograms is caused by colocalized conduction block and connexin disorganization in the absence of fibrosis as AF becomes persistent in the goat model.

BACKGROUND: Electrogram fractionation and atrial fibrosis are both thought to be pathophysiological hallmarks of evolving persistence of atrial fibrillation (AF), but recent studies in humans have shown that they do not colocalize. The interrelationship and relative roles of fractionation and fibrotic change in AF persistence therefore remain unclear. OBJECTIVE: The aim of the study was to examine the hypothesis that electrogram fractionation with increasing persistence of AF results from localized conduction slowing or block due to changes in atrial connexin distribution in the absence of fibrotic change. METHODS: Of 12 goats, atrial burst pacemakers maintained AF in 9 goats for up to 3 consecutive 4-week periods. After each 4-week period, 3 goats underwent epicardial mapping studies of the right atrium and examination of the atrial myocardium for immunodetection of connexins 43 and 40 (Cx43 and Cx40) and quantification of connective tissue. RESULTS: Despite refractoriness returning to normal in between each 4-week period of AF, there was a cumulative increase in the prevalence of fractionated atrial electrograms during both atrial pacing (control and 1, 2, and 3 months period of AF 0.3%, 1.3% ± 1.5%, 10.6% ± 2%, and 17% ± 5%, respectively; analysis of variance, P < .05) and AF (0.3% ± 0.1%, 2.3% ± 1.2%, 14% ± 2%, and 23% ± 3%; P < .05) caused by colocalized areas of conduction block during both pacing (local conduction velocity <10 cm/s: 0.1% ± 0.1%, 0.3% ± 0.6%, 6.5% ± 3%, and 6.9% ± 4%; P < .05) and AF (1.5% ± 0.5%, 2.7% ± 1.1%, 10.1% ± 1.2%, and 13.6% ± 0.4%; P < .05), associated with an increase in the heterogeneity of Cx40 and lateralization of Cx43 (lateralization scores: 1.75 ± 0.89, 1.44 ± 0.31, 2.85 ± 0.96, and 2.94 ± 0.31; P < .02), but not associated with change in connective tissue content or net conduction velocity. CONCLUSION: Electrogram fractionation with increasing persistence of AF results from slow localized conduction or block associated with changes in atrial connexin distribution in the absence of fibrotic change.

Perturbed atrial calcium handling in an ovine model of heart failure: potential roles for reductions in the L-type calcium current.

Heart failure (HF) is commonly associated with reduced cardiac output and an increased risk of atrial arrhythmias particularly during ß-adrenergic stimulation. The aim of the present study was to determine how HF alters systolic Ca(2+) and the response to ß-adrenergic (ß-AR) stimulation in atrial myocytes. HF was induced in sheep by ventricular tachypacing and changes in intracellular Ca(2+) concentration studied in single left atrial myocytes under voltage and current clamp conditions. The following were all reduced in HF atrial myocytes; Ca(2+) transient amplitude (by 46% in current clamped and 28% in voltage clamped cells), SR dependent rate of Ca(2+) removal (kSR, by 32%), L-type Ca(2+) current density (by 36%) and action potential duration (APD90 by 22%). However, in HF SR Ca(2+) content was increased (by 19%) when measured under voltage-clamp stimulation. Inhibiting the L-type Ca(2+) current (ICa-L) in control cells reproduced both the decrease in Ca(2+) transient amplitude and increase of SR Ca(2+) content observed in voltage-clamped HF cells. During ß-AR stimulation Ca(2+) transient amplitude was the same in control and HF cells. However, ICa-L remained less in HF than control cells whilst SR Ca(2+) content was highest in HF cells during ß-AR stimulation. The decrease in ICa-L that occurs in HF atrial myocytes appears to underpin the decreased Ca(2+) transient amplitude and increased SR Ca(2+) content observed in voltage-clamped cells.

Improving safety in catheter ablation for atrial fibrillation: a prospective study of the use of ultrasound to guide vascular access.

INTRODUCTION: The most frequent complications of AF ablation (AFA) are related to vascular access, but there is little evidence as to how these can be minimized. METHODS: Consecutive patients undergoing AFA at a high-volume center received either standard care (Group S) or routine ultrasound-guided vascular access (Group U). Vascular complications were assessed before hospital discharge and by means of postal questionnaire 1 month later. Outcome measures were BARC 2+ bleeding complications, postprocedural pain, and prolonged bruising. RESULTS: Patients in Group S (n = 146) and U (n = 163) were well matched at baseline. Follow-up questionnaires were received from 92.6%. Patients in Group U were significantly less likely to have a BARC 2+ bleed, 10.4% versus 19.9% P = 0.02, were less likely to suffer groin pain after discharge (27.1% vs. 42.8%; P = 0.006) and were less likely to experience prolonged local bruising (21.5% vs. 40.4%; P = 0.001). Multivariable logistic regression analysis revealed a significant association of vascular complications with nonultrasound guided access (OR 3.12 95%CI 1.54-5.34; P = 0.003) and increasing age (OR 1.05 95%CI 1.01-1.09; P = 0.02). CONCLUSION: Routine use of ultrasound-guided vascular access for AFA is associated with a significant reduction in bleeding complications, postprocedural pain, and prolonged bruising when compared to standard care.

Age-related divergent remodeling of the cardiac extracellular matrix in heart failure: collagen accumulation in the young and loss in the aged.

The incidence of heart failure (HF) increases with age. This study sought to determine whether aging exacerbates structural and functional remodeling of the myocardium in HF. HF was induced in young (~18 months) and aged sheep (>8 years) by right ventricular tachypacing. In non-paced animals, aging was associated with increased left ventricular (LV) end diastolic internal dimensions (EDID, P<0.001), reduced fractional shortening (P<0.01) and an increase in myocardial collagen content (P<0.01). HF increased EDID and reduced fractional shortening in both young and aged animals, although these changes were more pronounced in the aged (P<0.05). Age-associated differences in cardiac extracellular matrix (ECM) remodeling occurred in HF with collagen accumulation in young HF (P<0.001) and depletion in aged HF (P<0.05). MMP-2 activity increased in the aged control and young HF groups (P<0.05). Reduced tissue inhibitor of metalloproteinase (TIMP) expression (TIMPs 3 and 4, P<0.05) was present only in the aged HF group. Secreted protein acidic and rich in cysteine (SPARC) was increased in aged hearts compared to young controls (P<0.05) while serum procollagen type I C-pro peptide (PICP) was increased in both young failing (P<0.05) and aged failing (P<0.01) animals. In conclusion, collagen content of the cardiac ECM changes in both aging and HF although; whether collagen accumulation or depletion occurs depends on age. Changes in TIMP expression in aged failing hearts alongside augmented collagen synthesis in HF provide a potential mechanism for the age-dependent ECM remodeling. Aging should therefore be considered an important factor when elucidating cardiac disease mechanisms.

Impaired ß-adrenergic responsiveness accentuates dysfunctional excitation-contraction coupling in an ovine model of tachypacing-induced heart failure.

Reduced inotropic responsiveness is characteristic of heart failure (HF). This study determined the cellular Ca2+ homeostatic and molecular mechanisms causing the blunted ß-adrenergic (ß-AR) response in HF.We induced HF by tachypacing in sheep; intracellular Ca2+ concentration was measured in voltage-clamped ventricular myocytes. In HF, Ca2+ transient amplitude and peak L-type Ca2+ current (ICa-L) were reduced (to 70 ± 11% and 50 ± 3.7% of control, respectively, P <0.05) whereas sarcoplasmic reticulum (SR) Ca2+ content was unchanged. ß-AR stimulation with isoprenaline (ISO) increased Ca2+ transient amplitude, ICa-L and SRCa2+ content in both cell types; however, the response of HF cells was markedly diminished (P <0.05).Western blotting revealed an increase in protein phosphatase levels (PP1, 158 ± 17% and PP2A, 188 ± 34% of control, P <0.05) and reduced phosphorylation of phospholamban in HF (Ser16, 30 ± 10% and Thr17, 41 ± 15% of control, P <0.05). The ß-AR receptor kinase GRK-2 was also increased in HF (173 ± 38% of control, P <0.05). In HF, activation of adenylyl cyclase with forskolin rescued the Ca2+ transient, SR Ca2+ content and SR Ca2+ uptake rate to the same levels as control cells in ISO. In conclusion, the reduced responsiveness of the myocardium to ß-AR agonists in HF probably arises as a consequence of impaired phosphorylation of key intracellular proteins responsible for regulating the SR Ca2+ content and therefore failure of the systolic Ca2+ transient to increase appropriately during ß-AR stimulation.

Effects of angiotensin receptor blockade on atrial electrical remodelling and the 'second factor' in a goat burst-paced model of atrial fibrillation.

Atrial fibrillation (AF) is self-perpetuating, via mechanisms of acute electrical remodelling and 'second factors' acting over a longer time course. Renin-angiotensin system (RAS) blockade may inhibit AF self-perpetuation. We evaluated the effects of RAS blockade with candesartan in a burst-paced goat model of lone AF in which both mechanisms are known to operate. Bioactivity of oral candesartan was demonstrated in 10 goats by inhibition of the pressor effect of angiotensin II. The effects of candesartan on electrical remodelling were assessed in 12 placebo and 12 candesartan-treated goats in a 28-day burst pacing protocol. To assess the effects of candesartan on second factors (structural remodelling), 16 goats underwent further 28-day periods of burst pacing (two periods in 16 goats, three periods in eight goats) each separated by periods of sinus rhythm sufficient for electrical remodelling to reverse. There was a progressive rise in angiotensin levels in both groups. Candesartan (0.5 mg/kg/day) achieved a 76% blunting of the pressor effect of angiotensin II and had no effect on electrical remodelling; the half time for fall of atrial effective refractory period (AERP) was 22.3 ± 4.9 h (placebo) and 22.0 ± 3.2 h (candesartan) (p = ns). Candesartan had no effect on AF stability, which progressively increased over successive 28-day periods (ANOVA p < 0.05). Candesartan had no effect on atrial electrical remodelling or the operation of 'second factors' in a goat model of lone AF. These findings suggest that any benefits of RAS blockade in patients with AF are unlikely to be due to direct effects on atrial remodelling.

Safety and acceptability of implantation of internal cardioverter-defibrillators under local anesthetic and conscious sedation.

BACKGROUND: Implantation and testing of implantable defibrillators (ICDs) using local anesthetic and conscious sedation is widely practiced; however, some centers still use general anesthesia. We assessed safety and patient acceptability for implantation of defibrillators using local anesthetic and conscious sedation. METHODS: The records of 500 consecutive device implants from two UK cardiac centers implanted under local anesthetic and conscious sedation from January 1996 to December 2004 were reviewed. Procedure time, left ventricular ejection fraction (LVEF) sedative dosage (midazolam), analgesic dosage (fentanyl or diamorphine), requirement for drug reversal, and respiratory support were recorded. Patient acceptability of the procedure was also assessed. RESULTS: Of 500 implants examined, 387 were ICDs, 88 were biventricular ICDs, and 25 were generator changes. Patients with biventricular-ICDs had significantly longer (mean +/- SD) procedure times 129.7 +/- 7.6 minutes versus 63.3 +/- 32.3 minutes; P < 0.0001 and lower LVEF 24.4 +/- 8.4% versus 35.7 +/- 15.4%; P < 0.0001. There were no differences in the doses (mean +/- SD) of midazolam 8.9 +/- 3.5 mg versus 8.0 +/- 3.1 mg; P = NS, diamorphine 4.3 +/- 2.0 mg versus 3.8 +/- 1.7 mg; P = NS or fentanyl 94.4 +/- 53.7 mcg versus 92.2 +/- 48.6 mcg; P = NS, between the two groups. There were no deaths or tracheal intubations in either group. Acceptability was available for 373 of 500 (75%) patients, 41 of 373 (11%) described "discomfort," but from these 41 patients only 14 of 373 (3.8%) declined a second procedure under the same conditions. CONCLUSIONS: Implantation of defibrillators under local anesthetic and sedation is safe and acceptable to patients. General anesthesia is no longer routinely required for implantation of defibrillators.