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.

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.

The effect of second-generation cryoablation without electrical mapping in persistent AF using continuous monitoring.

BACKGROUND: Second-generation cryoballoon ablation is safe and effective in patients with persistent atrial fibrillation (AF). The aim of this study is to report the real long-term AF burden and freedom from AF post-cryoablation using continuous monitoring, and to assess whether intraoperative confirmation of pulmonary vein isolation using electrical mapping is necessary. METHODS: A total of 33 patients (mean age 75.7 ± 5.6 years, 16 men) with persistent AF who underwent second-generation cryoablation without electrical mapping were reviewed. All patients had a cardiac implantable device and were followed up for a mean of 755 ± 170 days. RESULTS: AF burden significantly decreased from 67.51% ± 34.90% to 18.28% ± 26.65% at 1-year follow-up, and this reduction was maintained at final follow-up (18.26% ± 23.70%, p < 0.001). Continuous monitoring revealed a freedom from AF rate of 33% and 24% at 1-year and full follow-up, respectively. Patients who remained in persistent AF at final follow-up had a trend towards higher pre-ablation AF burden (81.6% ± 29.7% vs 57.3% ± 36.4%, p = 0.08). CONCLUSION: Second-generation cryoablation without confirming pulmonary vein isolation using electrical mapping is effective leading to significant reductions in AF burden based on continuous beat-to-beat monitoring at 1-year and long-term follow-up.

The hemodynamic effects of a central iliac arteriovenous anastomosis at 6 months in patients with resistant and uncontrolled hypertension.

A central iliac arteriovenous anastomosis, termed the "coupler" (ROX Medical), results in a significant reduction in blood pressure (BP) in hypertensive patients. This study assessed functional and hemodynamic changes induced by the device. Twenty-one patients with resistant and/or uncontrolled hypertension underwent stress echocardiography and cardiopulmonary exercise testing (CPET) at baseline and 6 months post-coupler implantation. End points were selected to best evaluate cardiac function including Doppler stroke volume (SV), septal and lateral E/E', and right ventricular systolic velocity S' (RV S'). CPET VO2 peak demonstrated total cardiopulmonary performance. SV increased from 76.4 SD12.2 mL to 92.1 SD22.7 mL 6 months post-coupler insertion; P = .002. No changes in RV S', septal or lateral E/E', or VO2 peak were observed. Five patients experienced increased diuretic requirement ≥3 times baseline. RV S' fell from 19.0 SD1.87 cm/s to 16.80 SD3.43 cm/s in these patients (P > .05). A significant increase in SV 6 months post-coupler insertion was observed. In patients with increased diuretic requirement, the device was associated with a lower RV S' suggesting occult RV dysfunction as the mechanism of this pre-specified adverse outcome.

Results of the first investigator-initiated randomized clinical trial of nMARQTM, PVACTM, and thoracoscopic ablation for paroxysmal atrial fibrillation.

Aims: To investigate the effect of minimally invasive thoracoscopic surgical ablation and nMARQ irrigated multi-electrode phased radiofrequency (RF) ablation to treat paroxysmal atrial fibrillation (AF) compared with PVAC multi-electrode phased RF ablation, with beat-to-beat device-derived Holter monitoring throughout the study duration. Methods and results: An investigator-initiated prospective trial of patients with paroxysmal AF randomized (1:1:1) to initial surgical, nMARQ or PVAC ablation. All patients had continuous beat-to-beat monitoring with an ILR or pacemaker to evaluate and document AF recurrence. There was a strong trend (P = 0.050) toward difference in AF outcome, with surgical AF ablation more efficacious than catheter ablation. At one year, the proportion of patients with less than 1% AF burden after one procedure and off all antiarrhythmic drugs was 63, 56, and 90% for PVAC, nMARQ and surgical ablations respectively. There were significantly more repeat ablations in the catheter ablation groups (P = 0.008): 25% PVAC, 27% nMARQ, 0% surgery. However, 7 of 20 (35%) of patients undergoing surgical ablation suffered a procedural complication, including two sternotomies for bleeding and one death. This was higher than for catheter ablation (P < 0.001). Surgical ablation took longer to perform (P < 0.001) and had a longer hospital admission (P < 0.001) than catheter ablation. Conclusion: Surgical AF ablation required significantly fewer repeat procedures than catheter ablation, and there was a clear trend towards improved arrhythmia outcome. However, it was associated with a significantly higher rate of procedural complications. Surgical ablation for paroxysmal AF is promising, however more prospective outcome data is required. Clinical Trial Registration: NCT01504451, http://clinicaltrials.gov/show/NCT01504451.

Structural cure for reflex syncope?

The ROX Coupler is a device that allows creation of a central arteriovenous anastomosis at the iliac level. The device has been shown to improve exercise capacity in patients with chronic obstructive pulmonary disease and is CE marked for the treatment of resistant and uncontrolled hypertension. Reflex syncope is a challenging clinical condition with limited proven therapeutic options. We describe the resolution of symptoms and tilt table response of a patient who underwent insertion of a ROX Coupler to treat hypertension, and also incidentally had pre-existing vasodepressor syncope.

Relationship of indices of inflammation and thrombogenesis to arrhythmia burden in paroxysmal atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with a high risk of stroke. The contribution of arrhythmia to events is clear in sustained forms of AF, but in paroxysmal AF, presently available data have yet to identify what proportion of time spent in AF (ie, arrhythmia burden [AFB]) is of clinical relevance. We aimed to assess this relationship using surrogate blood markers for the hypercoagulable state associated with AF. METHODS: One hundred twenty-one consecutive outpatients (mean age 74.7 +/- 7.8 years; 73 [60.3%] men) with pacemakers capable of arrhythmia detection were recruited. AFB was assessed over a 1-month period and classified as AFB = 0%, 0.1% to 10%, 10.1% to 50%, or > 50%. RESULTS: Baseline characteristics and comorbidities were comparable between groups. There were no significant differences in levels of soluble E-selectin (sE-selectin), von Willebrand factor (vWf), high-sensitivity C-reactive protein, interleukin-6, soluble P-selectin (sP-selectin), or tissue factor (TF) across the four patient groups. Levels of plasma brain natriuretic peptide (BNP) were approximately twofold greater in the group with the highest AFB (P < .001). Following a stepwise multiple linear regression analysis, age was a significant predictor of vWf (P = .010), sP-selectin (P = .042), and BNP (P = .012). Left ventricular fractional shortening was predictive of BNP (P = .001) and sE-selectin (P = .012). Anticoagulation was a predictor of vWf levels (P = .005), and hypertension was predictive of TF (P < .001). CONCLUSION: Given no appreciable difference in levels of prothrombotic markers in relation to AFB in this study, it is plausible that these abnormalities do, in fact, relate to underlying risk factors, and that such patients should be anticoagulated if risk factors dictate. Thus, AFB per se should probably not influence the decision to anticoagulate, but rather the presence of AF combined with clinical risk scoring should remain the predominant tool for stroke risk assessment.

A cardiac sonographer led follow up clinic for heart valve disease.

INTRODUCTION: This study describes the effect of introducing a cardiac sonographer led follow up clinic for patients with stable heart valve disease. The 2 years before and after the instigation of the valve clinic were audited. MATERIALS AND METHODS: The clinic was conducted in a single centre and undertaken in the cardiology department of a district general hospital. 382 patients, with 397 clinically significant valve lesions, but for whom surgery was not yet indicated but follow up required, were seen in a cardiac sonographer run clinics. These patients no longer attended a medical follow up clinic unless there was clinical or echocardiographic deterioration. Effectiveness was judged by the percentage treated according to current best practice guidelines, the number of echocardiograms performed and the number of hospital out patient visits attended. In addition mortality data for the subjects in the clinic was collected. RESULTS: The proportion followed up according to best practice guidelines rose from 157 (41%) to 354 (92%) (p<0.01). The total number of echocardiograms performed fell from 807 to 550. Total number of out patient visits fell from 998 to 31. 11 patients died in the two year study period, none from progressive valve disease. DISCUSSION: This study demonstrates that a protocol driven sonographer led heart valve disease follow up clinic, significantly improved the quality of follow up while bringing about a major reduction in out patients visits, without compromising patient safety.

Pacemaker implantation in a patient with paroxysmal atrial fibrillation and left pneumonectomy.

Paroxysmal atrial fibrillation is a common occurrence in patients following thoracic surgery and in some patients remains refractory to medical therapy. New pacemaker devices are available with atrial preventative and termination pacing algorithms designed to reduce arrhythmia recurrences. This report describes the implantation of such a device in a patient following pneumonectomy and the subsequent effect on atrial arrhythmia burden.

How do we diagnose syncope?

INTRODUCTION: The Eastbourne Syncope Assessment Study aims to increase diagnostic yield in unexplained syncope while reducing investigational costs. The initial study phase was a retrospective analysis of every presentation to the Eastbourne General Hospital (a busy nontertiary center in the United Kingdom serving a population of 250,000; 24% are older than 65 years) with syncope for the year 1998. METHODS AND RESULTS: A total of 1,334 cases with syncopal codes were identified. Six hundred sixty patients (mean age 64 years) had actually suffered an episode of syncope. Forty percent had recurrent syncope, with a mean of 4.7 previous episodes. Twenty-nine percent of syncope cases remained undiagnosed. Forty-four percent were diagnosed as vasovagal, 12% neurologic, 6% due to an arrhythmia, 2% drug related, and 2% due to hemorrhage. Thirteen different types of investigation were undertaken, with an overall total of 3,264 investigations performed at a cost of Pound Sterling 104,285. Diagnosis was achieved by history and examination alone in 61% of cases. Excluding history and examination, the most cost-effective diagnostic tools were the 7-day patient-activated recorder (R test) and tilt testing (Pound Sterling 260 and Pound Sterling 401 per diagnosis, respectively). Investigations also were graded by their relative diagnostic power. Hospital admission alone accounted for 67% of the cost of investigating syncope. CONCLUSION: In syncope, diagnostic rates can be improved and investigational costs reduced by concentrating on the most specific, sensitive, and cost-effective investigations and by minimizing hospital stay. Such a protocol currently is under investigation at our institution.