Long Term outcomes of percutaneous atrial fibrillation ablation in patients with continuous monitoring.

INTRODUCTION: There is limited data using continuous monitoring to assess outcomes of atrial fibrillation (AF) ablation. This study assessed long-term outcomes of AF ablation in patients with implantable cardiac devices. METHODS: 207 patients (mean age 68.1 ± 9.5, 50.3% men) undergoing ablation for symptomatic AF were followed up for a mean period of 924.5 ± 636.7 days. Techniques included The Pulmonary Vein Ablation Catheter (PVAC) (59.4%), cryoablation (17.4%), point by point (14.0%) and The Novel Irrigated Multipolar Radiofrequency Ablation Catheter (nMARQ) (9.2%). RESULTS: 130 (62.8%) patients had paroxysmal AF (PAF) and 77 (37.2%) persistent AF. First ablation and repeat ablation reduced AF burden significantly (relative risk 0.91, [95% CI 0.89 to 0.94]; P <0.0001 and 0.90, [95% CI, 0.86-0.94]; P <0.0001). Median AF burden in PAF patients reduced from 1.05% (interquartile range [IQR], 0.1%-8.70%) to 0.10% ([IQR], 0%-2.28%) at one year and this was maintained out to four-years. Persistent AF burden reduced from 99.9% ([IQR], 51.53%-100%) to 0.30% ([IQR], 0%-77.25%) at one year increasing to 87.3% ([IQR], 4.25%-100%) after four years. If a second ablation was required, point-by-point ablation achieved greater reduction in AF burden (relative risk, 0.77 [95% CI, 0.65-0.91]; P <0.01). CONCLUSION: Ablation reduces AF burden both acutely and in the long-term. If a second ablation was required the point-by-point technique achieved greater reductions in AF burden than "single-shot" technologies. Persistent AF burden increased to near pre ablation levels by year 4 suggesting a different mechanism from PAF patients where this increase did not occur.

A trial of three non-invasive blood pressure monitors compared with invasive blood pressure assessment in atrial fibrillation and sinus rhythm.

OBJECTIVE: To investigate the accuracy of three non-invasive blood pressure (BP) devices in atrial fibrillation (AF) compared with invasive arterial BP. METHODS: One hundred patients aged 45-90 years, 63% male (50 in AF and 50 age matched controls in sinus rhythm [SR]) were identified with arterial lines measuring beat-to-beat BP fluctuation. Non-invasive BP measurements utilising the manual sphygmomanometer (MS), PulseCor R6.5 (PC) and automated sphygmomanometer (AS) were taken simultaneously with invasive BP in a randomised sequence. This was repeated three times in each patient. RESULTS: In SR differences in systolic BP (SBP) for MS, AS and PC were -0.34 mm Hg (95% CI -2.31 to 1.63; P = .733), -3.80 mm Hg (95% CI -5.73 to -1.87; P = .0001) and -3.90 mm Hg (95% CI -5.90 to -1.90; P = .0001) and for diastolic BP (DBP) were 6.02 mm Hg (95% CI 4.39-7.64; P < .0001), 8.95 mm Hg (95% CI 7.36-10.55; P < .0001) and 7.54 mm Hg (95% CI 5.89-9.18; P < .0001), respectively. In AF mean differences in SBP for MS, AS and PC were -7.33 mm Hg (95% CI -9.11 to -5.55; P < .0001), -5.29 mm Hg (95% CI -7.08 to -3.50; P < .0001) and -5.75 mm Hg (95% CI -7.54 to -3.96; P < .0001) respectively and for DBP were 5.28 mm Hg (95% CI 4.03-6.54; P < .0001), 6.26 mm Hg (95% CI 5.00-7.52; P < .0001) and 6.89 mm Hg (95% CI 5.64-8.15; P < .0001) respectively. CONCLUSIONS: The MS is accurate in SR because of direct assessment of Korotkoff sounds. Non-invasive BP assessment in AF is significantly less accurate. These findings have important prognostic and therapeutic implications.

Central arteriovenous anastomosis for the treatment of patients with uncontrolled hypertension (the ROX CONTROL HTN study): a randomised controlled trial.

BACKGROUND: Hypertension contributes to cardiovascular morbidity and mortality. We assessed the safety and efficacy of a central iliac arteriovenous anastomosis to alter the mechanical arterial properties and reduce blood pressure in patients with uncontrolled hypertension. METHODS: We enrolled patients in this open-label, multicentre, prospective, randomised, controlled trial between October, 2012, and April, 2014. Eligible patients had baseline office systolic blood pressure of 140 mm Hg or higher and average daytime ambulatory blood pressure of 135 mm Hg or higher systolic and 85 mm Hg or higher diastolic despite antihypertensive treatment. Patients were randomly allocated in a 1:1 ratio to undergo implantation of an arteriovenous coupler device plus current pharmaceutical treatment or to maintain current treatment alone (control). The primary endpoint was mean change from baseline in office and 24 h ambulatory systolic blood pressure at 6 months. Analysis was by modified intention to treat (all patients remaining in follow-up at 6 months). This trial is registered with ClinicalTrials.gov, number NCT01642498. FINDINGS: 83 (43%) of 195 patients screened were assigned arteriovenous coupler therapy (n=44) or normal care (n=39). Mean office systolic blood pressure reduced by 26·9 (SD 23·9) mm Hg in the arteriovenous coupler group (p<0·0001) and by 3·7 (21·2) mm Hg in the control group (p=0·31). Mean systolic 24 h ambulatory blood pressure reduced by 13·5 (18·8) mm Hg (p<0·0001) in arteriovenous coupler recipients and by 0·5 (15·8) mm Hg (p=0·86) in controls. Implantation of the arteriovenous coupler was associated with late ipsilateral venous stenosis in 12 (29%) of 42 patients and was treatable with venoplasty or stenting. INTERPRETATION: Arteriovenous anastomosis was associated with significantly reduced blood pressure and hypertensive complications. This approach might be a useful adjunctive therapy for patients with uncontrolled hypertension. FUNDING: ROX Medical.

Are implantable cardiac monitors the 'gold standard' for atrial fibrillation detection? A prospective randomized trial comparing atrial fibrillation monitoring using implantable cardiac monitors and DDDRP permanent pacemakers in post atrial fibrillation ablation patients.

AIMS: Implantable devices are widely accepted, but not proven, to be the most reliable monitoring method to assess atrial fibrillation (AF) therapies. We compared REVEAL(®)XT implantable cardiac monitors (ICMs) and permanent pacemakers (PPMs). METHODS AND RESULTS: Fifty patients with paroxysmal AF were randomized to ICM or PPM implant 6 weeks prior to pulmonary vein isolation. Permanent pacemakers were programmed to monitoring only (ODO). Device downloads were performed at 0, 3, 6, 9, and 12 months. All patients underwent 7-day external loop recorder. Device ECGs and EGMs were compared for AF burden. A total of 20 744 and 11 238 arrhythmia episodes were identified in the ICM and PPM groups, respectively. Correct identification of AF was significantly better in the PPM group (97 vs. 55% P < 0.001). In the ICM group, 26% of ECGs were un-interpretable. Sensitivity and specificity for each episode of AF was significantly better in the PPM group (100 vs. 79% and 98 vs. 66%, respectively, P < 0.001). The positive predictive value for the detection of any AF was significantly better in the PPM than the ICM (100 vs. 58%, P = 0.03). The negative predictive value for the absence of all AF was not significantly different between the PPM and ICM (100% vs. 92%, P = 0.76). CONCLUSION: Permanent pacemakers Holters are the most accurate method of evaluating arrhythmia burden and the therapeutic efficacy of novel AF therapies. ICM has a high degree of artefact, which reduces its specifity and sensitivity. Despite the deficiencies of ICM monitoring the negative predictive value of the ICM is satisfactory if zero AF burden is the aim of therapy.

First clinical trial of specific IKACh blocker shows no reduction in atrial fibrillation burden in patients with paroxysmal atrial fibrillation: pacemaker assessment of BMS 914392 in patients with paroxysmal atrial fibrillation.

AIMS: To assess the efficacy of BMS 914392 on atrial fibrillation (AF) burden reduction in 20 patients with pacemakers and paroxysmal atrial fibrillation (PAF). BMS 914392 is a potent, selective, oral inhibitor of the IKACh current and has been shown to suppress AF, whilst having no effect on the ventricular refractory period. This is the first efficacy study of BMS 914392 in patients with PAF. METHODS AND RESULTS: The study was a four-way, crossover, double-blind design. A total of 20 patients with PAF and dual-chamber pacemakers were recruited. The pacemakers allowed beat-to-beat monitoring. Anti-arrhythmic drugs were withdrawn. Patients received low-dose (10 mg OD), medium-dose (10 mg TDS), and high-dose (20 mg TDS) BMS 914392 or placebo for 3 weeks before being crossed to the next phase. Patients underwent a washout period, four treatment phases and a final washout phase. Atrial fibrillation burden was downloaded from their pacemakers at the end of each study phase. BMS 914392 did not reduce AF burden when compared with placebo (10 mg OD P = 0.56, 10 mg TDS P = 0.22, 20 mg TDS P = 0.23). Heart rate and corrected QT (QTc) were not affected by BMS 914392. Adverse event (AE) rates did not differ from placebo in any of the treatment groups, with no serious AEs recorded. CONCLUSION: BMS 914932 has not been shown to reduce AF burden in patients with PAF and pacemakers using beat-to-beat pacemaker monitoring throughout the study. BMS 914392 was well tolerated and did not affect QTc or reduce heart rate. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01356914.

A randomized comparison of retrograde left-sided versus anterograde right-sided ablation of the atrioventricular junction.

BACKGROUND: Catheter ablation of the atrioventricular node (AVN) is an effective treatment for patients with symptomatic atrial fibrillation. This study compares the success rate, procedure time, radiation time, and complication rates of retrograde left-sided (LSA) and anterograde right-sided (RSA) AVN ablation in a randomised controlled trial. METHODS: Thirty-one patients undergoing AVN ablation were randomized to either LSA (15 patients) or RSA (16 patients). Crossover occurred after six unsuccessful radiofrequency (RF) applications. RESULTS: The LSA cohort had a mean age of 77.00 ± 5.17 and the RSA cohort was 79.44 ± 6.08 (p = .0240). There were five crossovers from LSA to RSA and there was one crossover from RSA to LSA. There was no significant difference in ablation time between LSA and RSA (210.40 ± 179.77 vs. 192.19 ± 130.29 seconds, p = .748). There was no significant difference in procedure time, fluoroscopy time, radiation dose, or number of RF applications between the two groups. There was 1 (6.67%) serious adverse event in the LSA group and 1 (6.25%) in the RSA group due to femoral hematomas requiring blood transfusion or intervention. There was no significant difference in patient-reported discomfort between LSA and RSA (16.43 ± 20.67 vs. 17.87 ± 28.08, p = .877). The study was stopped before full recruitment due to futility. CONCLUSIONS: Retrograde LSA of the AVN does not reduce RF applications, procedure time, or radiation exposure compared with conventional RSA and cannot be recommended as a first-line clinical approach.

A randomized sham-controlled study of pulmonary vein isolation in symptomatic atrial fibrillation (The SHAM-PVI study): Study design and rationale.

INTRODUCTION: Pulmonary vein (PV) isolation has been shown to reduce atrial fibrillation (AF) burden and symptoms in patients. However, to date previous studies have been unblinded raising the possibility of a placebo effect to account for differences in outcomes. HYPOTHESIS & METHODS: The objective of this study is to compare PV isolation to a sham procedure in patients with symptomatic AF. The SHAM-PVI study is a double blind randomized controlled clinical trial. 140 patients with symptomatic paroxysmal or persistent AF will be randomized to either PV isolation (with cryoballoon ablation) or a sham procedure (with phrenic nerve pacing). All patients will receive an implantable loop recorder. The primary outcome is total AF burden at 6 months postrandomisation (excluding the 3 month blanking period). Key secondary outcomes include (1) time to symptomatic and asymptomatic atrial tachyarrhythmia (2) total atrial tachyarrhythmia episodes and (3) patient reported outcome measures. RESULTS: Enrollment was initiated in January 2020. Through April 2023 119 patients have been recruited. Results are expected to be disseminated in 2024. CONCLUSION: This study compares PV isolation using cryoablation to a sham procedure. The study will estimate the effect of PV isolation on AF burden.

Interatrial septal puncture without the use of fluoroscopy-reducing ionizing radiation in left atrial ablation procedures.

Ablation for atrial fibrillation is now widespread and may involve the delivery of relatively high doses of ionizing radiation to both patients and operators. Until now, atrial septal puncture has mandated the use of either fluoroscopy or additional expensive imaging modalities for its safe deployment. We describe a novel technique using the EnSite NavX three-dimensional imaging system for visualization of the transseptal needle throughout the puncture-without the need for either fluoroscopy or additional imaging. This may be important in reducing the need for fluoroscopy for left atrial ablation procedures.

Central Iliac Arteriovenous Anastomosis for Uncontrolled Hypertension: One-Year Results From the ROX CONTROL HTN Trial.

Creation of a central iliac arteriovenous anastomosis using a novel nitinol coupler device results in an immediate, significant reduction of blood pressure (BP). We present efficacy and safety findings at 12 months post-coupler insertion. This open-label, multicenter, prospective, randomized trial enrolled patients with a baseline office systolic BP ≥140 mm Hg and average daytime ambulatory BP ≥135/85 mm Hg. Subjects were randomly allocated to coupler implantation and continuing previous pharmacotherapy or to maintain previous treatment alone. At 12 months, 39 patients who had coupler therapy were included in the intention-to-treat analysis. Office-based systolic BP reduced by 25.1±23.3 mm Hg (baseline, 174±18 mm Hg; P<0.0001) post-coupler placement, and office diastolic BP reduced by 20.8±13.3 mm Hg (baseline, 100±13 mm Hg; P<0.0001). Mean 24-hour ambulatory BP reduced by 12.6±17.4/15.3±9.7 mm Hg (P<0.0001 for both). In a prespecified subset of patients who failed to respond adequately to prior renal denervation, coupler therapy led to highly significant reduction in office systolic/diastolic BP (30.7/24.1 mm Hg) and significant reduction in 24-hour ambulatory systolic/diastolic BP (12.4/14.4 mm Hg) at 12 months (n=9). After coupler therapy, 14 patients (33%) developed ipsilateral venous stenosis; all were treated successfully with venous stenting. These findings confirm the importance of arterial mechanics in the pathophysiology of hypertension and support the clinical use of a central iliac arteriovenous anastomosis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01642498.

Effect of Arteriovenous Anastomosis on Blood Pressure Reduction in Patients With Isolated Systolic Hypertension Compared With Combined Hypertension.

BACKGROUND: Options for interventional therapy to lower blood pressure (BP) in patients with treatment-resistant hypertension include renal denervation and the creation of an arteriovenous anastomosis using the ROX coupler. It has been shown that BP response after renal denervation is greater in patients with combined hypertension (CH) than in patients with isolated systolic hypertension (ISH). We analyzed the effect of ROX coupler implantation in patients with CH as compared with ISH. METHODS AND RESULTS: The randomized, controlled, prospective ROX Control Hypertension Study included patients with true treatment-resistant hypertension (office systolic BP ≥140 mm Hg, average daytime ambulatory BP ≥135/85 mm Hg, and treatment with ≥3 antihypertensive drugs including a diuretic). In a post hoc analysis, we stratified patients with CH (n=31) and ISH (n=11). Baseline office systolic BP (177±18 mm Hg versus 169±17 mm Hg, P=0.163) and 24-hour ambulatory systolic BP (159±16 mm Hg versus 154±11 mm Hg, P=0.463) did not differ between patients with CH and those with ISH. ROX coupler implementation resulted in a significant reduction in office systolic BP (CH: -29±21 mm Hg versus ISH: -22±31 mm Hg, P=0.445) and 24-hour ambulatory systolic BP (CH: -14±20 mm Hg versus ISH: -13±15 mm Hg, P=0.672), without significant differences between the two groups. The responder rate (office systolic BP reduction ≥10 mm Hg) after 6 months was not different (CH: 81% versus ISH: 82%, P=0.932). CONCLUSIONS: Our data suggest that creation of an arteriovenous anastomosis using the ROX coupler system leads to a similar reduction of office and 24-hour ambulatory systolic BP in patients with combined and isolated systolic hypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01642498.

Safe sedation in modern cardiological practice.

Safe sedation is fundamental to many modern cardiological procedures, and following the publication of the report on safe sedation by the Academy of Medical Royal Colleges, this report discusses sedation specifically in cardiological practice. The major areas within cardiology that use sedation are cardioversion, catheter ablation particularly of atrial fibrillation, transoesophageal echocardiography, implantable device (cardiovascular implantable electronic device) procedures and other procedures such as transcatheter aortic valve replacement. There is increasing demand for cardiological sedation but there is wide geographical variation in its use and there are also growing data to support non-anaesthetists giving sedation. The use of benzodiazepines, particularly for short procedures, is common, but even here good record-keeping and audit together with an understanding of the continuum of sedation and having appropriately trained staff and the necessary facilities are vital. Nurse administration of propofol may be appropriate for some procedures in cardiology that require at least moderate sedation. Appropriate training is essential and the use of capnography and target controlled infusion pumps for propofol administration is recommended.

Causes of death in patients with rheumatoid arthritis: comparison with siblings and matched osteoarthritis controls.

OBJECTIVE: Survival of patients with rheumatoid arthritis (RA) is reduced when compared to the general population. We assessed differences in causes and age of death between patients with RA and their siblings. Comparisons were also made with a control group of subjects with lower limb osteoarthritis (OA). METHODS: A population of 257 patients with RA studied in 1991 was compared to 371 of their same-sex siblings and 485 patients with hip and knee OA who were also attending the department at this time. Death certificates were obtained and compared. RESULTS: Among patients with RA, 54% (139/257) were deceased, compared to 28% (105/371) of the siblings and 32% (154/485) of OA patients (RA vs siblings or OA, p < 0.05). There were more deaths due to ischemic heart disease (IHD) in both the RA and OA groups compared to those expected; ratio observed/expected, 1.66 (95% CI 1.01, 2.79) and 1.96 (95% CI 1.21, 3.25), respectively, but not for siblings: observed/expected = 1.05 (95% CI 0.53, 2.08). There was a significant deficit in cancer related deaths in RA patients, observed/expected = 0.62 (95% CI 0.36, 1.03). CONCLUSION: Significantly more patients with RA had died than in either of the comparator populations. RA and OA patients died more frequently of IHD than the siblings. The RA population had a 40% reduced rate of cancer related deaths than expected and compared to their siblings.

Surface atrial frequency analysis in patients with atrial fibrillation: assessing the effects of linear left atrial ablation.

INTRODUCTION: Our group has shown previously that measurements of atrial frequency can be obtained from surface 12-lead ECG recordings of patients during atrial fibrillation (AF), using a combination of principal component and Fourier transform algorithms. Such measurements are reproducible over time and change with drug manipulation of the arrhythmia. AIMS: To determine whether linear left atrial ablation, using a combination of "roof" and "mitral isthmus" lines results in changes in surface atrial frequency during AF and to assess the contribution of each individual line when sited sequentially. METHODS AND RESULTS: Computerized recordings from 26 patients, who had undergone linear ablation procedures for AF, were reviewed. The atrial signal was extracted from the 12-lead ECG data by principal component analysis and the main frequency component identified using Fourier analysis. Atrial frequency before and after these two standard ablation lines was compared. Atrial frequency decreased significantly after the combination of roof and mitral isthmus lines (5.66 vs 5.15 Hz) and when either roof (5.61 vs 5.13 Hz) or mitral isthmus (5.89 vs 5.75 Hz) lines were sited first. However, only the roof line led to a significant reduction in atrial frequency when sited second (5.64 vs 5.49 Hz). CONCLUSIONS: Measurements of atrial frequency can be obtained from surface 12-lead ECG recordings during AF and change as predicted in response to linear left atrial ablation. This technique may be useful in assessing antiarrhythmic treatments for AF.

P wave morphology during spontaneous and paced pulmonary vein activity: differences between patients with atrial fibrillation and normal controls.

P wave morphology (PWM) has been used to predict the location of ectopic foci responsible for triggering atrial fibrillation (AF). With bi-atrial mapping, this study examined PWM during spontaneous ectopy and during pulmonary vein (PV) pacing, comparing the results with published algorithms in 40 AF patients and 15 controls. PWM during PV pacing is similar to spontaneous ectopy, if performed at similar coupling intervals. PWM during ectopic activity from the PVs is affected by cycle length and the presence of underlying atrial electrical and structural abnormalities. Changes in PWM during decremental pacing were observed in 5% of controls but in over 25% of persistent AF patients. The algorithms are accurate in over 90% of controls and paroxysmal AF patients with normal atria, but less than 60% in those with persistent AF or electrical or structural atrial abnormalities. The accuracy of non-invasive localization of arrhythmogenic PV is limited.

Evolution of ventricular function during permanent pacing from either right ventricular apex or outflow tract following AV-junctional ablation for atrial fibrillation.

AIMS: To compare acute and chronic ventricular function between patients, without cardiac failure, paced at either right ventricular apex or outflow tract. METHODS: Twenty patients. 10 paced apically and 10 in the outflow tract, underwent two radionuclide ventriculograms. Eight parameters of systolic or diastolic function were compared at each assessment, as were changes within each group over time. RESULTS: No differences were identified in systolic function between pacing sites 6 weeks after pacing or 23 weeks later. Peak filling rate was lower (P=0.04) at the second assessment with outflow tract pacing. No other diastolic differences were identified. Between assessments, time to peak filling rate prolonged (P=0.04) with apical pacing, while left ventricular area reduced (P=0.04) and peak filling rate decreased (P=0.04) with outflow tract pacing. Septal motion was better preserved with outflow tract pacing. No other parameter changed over time. ECG measures were similar at 14.7 months. CONCLUSIONS: No major differences were identified in systolic function between pacing sites. Some systolic parameters were better preserved with outflow tract pacing and diastolic function deteriorated subtly over time in both groups. Right ventricular pacing adversely affects left ventricular function.