Atrial fibrillation symptom reduction and improved quality of life following the hybrid convergent procedure: a CONVERGE trial subanalysis.

Background: CONVERGE was a prospective, multicenter, randomized controlled trial that evaluated the safety of Hybrid Atrial Fibrillation Convergent (HC) and compared its effectiveness to endocardial catheter ablation (CA) for the treatment of persistent atrial fibrillation (PersAF) and longstanding PersAF (LSPAF). In 2020, we reported that CONVERGE met its primary safety and effectiveness endpoints. The primary objective of the present study is to report CONVERGE trial results for quality of life (QOL) and Class I/III anti-arrhythmic drug (AAD) utilization following HC. Methods: Eligible patients had drug-refractory symptomatic PersAF or LSPAF and a left atrium diameter ≤6.0 cm. Enrolled patients were randomized 2:1 to receive HC or CA. Atrial Fibrillation Severity Scale (AFSS) and the 36-Item Short Form Health Survey (SF-36) were assessed at baseline and 12 months; statistical comparison was performed using paired t-tests. AAD utilization at baseline through 12 and 18 months post-procedure was evaluated; statistical comparison was performed using McNemar's tests. Results: A total of 153 patients were treated with either HC (n=102) or CA (n=51). Of the 102 HC patients, 38 had LSPAF. AFSS and SF-36 Mental and Physical Component scores were significantly improved at 12 months versus baseline with HC overall and for the subset of LSPAF patients treated with either HC or CA. The proportion of HC patients (n=102) who used Class I /III AADs at 12 and 18 months was significantly less (33.3% and 36.3%, respectively) than baseline (84.3%; P<0.001). In LSPAF patients who underwent HC (n=38), AADs use was 29.0% through 18 months follow-up versus 71.1% at baseline (P<0.001). Conclusions: HC reduced AF symptoms, significantly improved QOL, and reduced AAD use in patients with PersAF and LSPAF. ClinicalTrialsgov Identifier: NCT01984346.

Hybrid epicardial-endocardial ablation for long-standing persistent atrial fibrillation: A subanalysis of the CONVERGE Trial.

Background: Favorable clinical outcomes are difficult to achieve in long-standing persistent atrial fibrillation (LSPAF) with catheter ablation (CA). The CONVERGE (Convergence of Epicardial and Endocardial Ablation for the Treatment of Symptomatic Persistent Atrial FIbrillation) trial evaluated the effectiveness of hybrid convergent (HC) ablation vs endocardial CA. Objective: The study sought to evaluate the safety and effectiveness of HC vs CA in the LSPAF subgroup from the CONVERGE trial. Methods: The CONVERGE trial was a prospective, multicenter, randomized trial that enrolled 153 patients at 27 sites. A post hoc analysis was performed on LSPAF patients. The primary effectiveness was freedom from atrial arrhythmias off new or increased dose of previously failed or intolerant antiarrhythmic drugs (AADs) through 12 months. The primary safety endpoint was major adverse event incidence through 30 days with HC. Key secondary effectiveness measures included (1) percent of patients achieving ≥90% AF burden reduction vs baseline and (2) AF freedom. Results: Sixty-five patients (42.5% of total enrollment) had LSPAF; 38 in HC and 27 in CA. Primary effectiveness was 65.8% (95% confidence interval [CI] 50.7%-80.9%) with HC vs 37.0% (95% CI 5.1%-52.4%) with CA (P = .022). Through 18 months, these rates were 60.5% (95% CI 50.0%-76.1%) with HC vs 25.9% (95% CI 9.4%-42.5%) with CA (P = .006). Secondary effectiveness rates were higher than CA with HC at 12 and 18 months. Freedom from atrial arrhythmias off AADs was 52.6% (95% CI 36.8%-68.5%) and 47.4% (95% CI 31.5%-63.2%) with HC at 12 and 18 months vs 25.9% (95% CI 9.4%-42.5%) and 22.2% (95% CI 6.5%-37.9%) with CA, respectively (12 months: P = .031; 18 months: P = .038). Three (7.9%) major adverse events occurred within 30 days of HC. Conclusion: Post hoc analysis demonstrated effectiveness and acceptable safety of HC compared with CA in LSPAF.

Hybrid Convergent Procedure for the Treatment of Persistent and Long-Standing Persistent Atrial Fibrillation: Results of CONVERGE Clinical Trial.

BACKGROUND: The limited effectiveness of endocardial catheter ablation (CA) for persistent and long-standing persistent atrial fibrillation (AF) treatment led to the development of a minimally invasive epicardial/endocardial ablation approach (Hybrid Convergent) to achieve a more comprehensive lesion set with durable transmural lesions. The multicenter randomized controlled CONVERGE trial (Convergence of Epicardial and Endocardial Ablation for the Treatment of Symptomatic Persistent AF) evaluated the safety of Hybrid Convergent and compared its effectiveness to CA for persistent and long-standing persistent AF treatment. METHODS: One-hundred fifty-three patients were randomized 2:1 to Hybrid Convergent versus CA. Primary effectiveness was freedom from AF/atrial flutter/atrial tachycardia absent new/increased dosage of previously failed/intolerant class I/III antiarrhythmic drugs through 12 months. Primary safety was major adverse events through 30 days. CONVERGE permitted left atrium size up to 6 cm and imposed no limits on AF duration, making it the only ablation trial to substantially include long-standing persistent-AF, that is, 42% patients with long-standing persistent-AF. RESULTS: Of 149 evaluable patients at 12 months, primary effectiveness was achieved in 67.7% (67/99) patients with Hybrid Convergent and 50.0% (25/50) with CA (P=0.036) on/off previously failed antiarrhythmic drugs and in 53.5% (53/99) versus 32.0% (16/50; P=0.0128) respectively off antiarrhythmic drugs. At 18 months using 7-day Holter, 74.0% (53/72) Hybrid Convergent and 55% (23/42) CA patients experienced ≥90% AF burden reduction. A total of 2.9% (3/102) patients had primary safety events within 7 days, and 4.9% (5/102) between 8 and 30 days postprocedure. No deaths, cardiac perforations, or atrioesophageal fistulas occurred. All but one primary safety event resolved. CONCLUSIONS: The Hybrid Convergent procedure has superior effectiveness compared to the CA for the treatment of persistent and long-standing persistent atrial fibrillation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01984346.

Predictors of early mortality in implantable cardioverter-defibrillator recipients.

AIMS: Multiple trials have shown that implantable cardioverter defibrillators (ICDs) prolong survival in secondary and primary prevention populations. However, in spite of the efficacy of these devices in terminating life-threatening arrhythmias, total mortality remains high. METHODS AND RESULTS: We evaluated 1703 patients (mean age: 67 +/- 12 years, 82% male) with conventional ICD indications, who were enrolled and followed between 2001 and 2004 at 128 US centres. Patients were followed for up to a year, and vital status was obtained for 1655 patients (97%, median follow-up: 377 days). There were 183 deaths within 1 year of ICD implantation (1-year mortality rate: 16%). Predictors of mortality included a history of atrial fibrillation (AF, P < 0.0001), diabetes (P = 0.0001), failure to use cholesterol-lowering medications (P < 0.001), use of digitalis and derivatives (P < 0.0001), use of diuretics (P < 0.0001), low body mass index (BMI, P < 0.0001), increasing age (P < 0.0001), low left ventricular ejection fraction (P < 0.0001), low activity hours (P < 0.0001), elevated resting heart rate (P = 0.014), low mean arterial pressure (MAP, P = 0.007), and poor functional status (New York Heart Association class, P < 0.0001). In multivariate modelling, AF (P < or = 0.001), diabetes (P = 0.004), BMI (P = 0.001), MAP (P = 0.040), and functional class (P = 0.006) predicted mortality. CONCLUSION: In this population undergoing ICD implantation, poor functional status, low MAP, diabetes, low BMI, and AF were strongly associated with death within a year.

A randomized trial of the effect of automated ventricular capture on device longevity and threshold measurement in pacemaker patients.

BACKGROUND: An automatic capture (AC) algorithm adjusts ventricular pacing output to capture the ventricle while optimizing output to 0.5 V above threshold. AC maintains this output and confirms capture on a beat-to-beat basis in bipolar and unipolar pacing and sensing. OBJECTIVE: To assess the AC algorithm and its impact on device longevity. METHODS: Patients implanted with a pacemaker were randomized 1:1 to have the AC feature on or off for 12 months. Two threshold tests were conducted at each visit- automatic threshold and manual threshold. Average ventricular voltage output and projected device longevity were compared between AC on and off using nonparametric tests. RESULTS: Nine hundred ten patients were enrolled and underwent device implantation. Average ventricular voltage output was 1.6 V for the AC on arm (n = 444) and 3.1 V for the AC off arm (n = 446) (P < 0.001). Projected device longevity was 10.3 years for AC on and 8.9 years for AC off (P < 0.0001), or a 16% increase in longevity for AC on. The proportion of patients in whom there was a difference between automatic threshold and manual threshold of

Identification of preferential sites of parasympathetic input to the atrioventricular node in man.

OBJECTIVES: The effects of subthreshold stimulation performed at various sites in the perinodal and posteroseptal space on atrioventricular (AV) nodal conduction were investigated. BACKGROUND: The identification of specific or preferential sites of parasympathetic innervation to the AV node is suggested by observations made in both the animal and clinical laboratories. Pathologic studies of the parasympathetic innervation to the AV node show it is made up of serpiginous fibers traveling at highly specific sites within the myocardium endocardially towards the compact AV node. METHODS: We utilized endocardial subthreshold stimulation to selectively identify and characterize AV nodal inputs. Fourteen patients (age: 56 +/- 4 years) undergoing electrophysiologic testing with or without radiofrequency ablation for supraventricular tachycardia were studied. A steerable quadripolar catheter was positioned in 3 to 9 locations in the region between the site recording the His bundle electrogram and the coronary sinus (CS) os under flouroscopic and electroanatomic guidance. We mapped anterosuperior sites at or near sites with His potential recordings, and up to 2 mm inferior to the His bundle recording, posteroseptal sites included the CS os and sites along the posterior, superior, and inferior border of the CS. Atrial pacing was performed at a cycle length 50 ms longer than Wenckebach cycle length. Subthreshold stimulation was applied at a frequency of 10 Hz and 20 Hz delivered to the distal electrode pair. AH and HV intervals were recorded before and during subthreshold stimulation. AH prolongation was defined as a reproducible increase in AH interval by >10 ms from a stable baseline AH interval. RESULTS: Eight of 14 patients demonstrated prolongation of AV conduction at a mean of 1.75 +/- 0.2 sites. Mean AH prolongation was 56.4 +/- 13.0 ms (p = 0.02) from baseline. AH prolongation was achieved 15.4 +/- 1.8 mm below the His bundle recording in 7 patients, at the site of the His bundle recording in 3 patients, and along the posterior CS os border in 3 patients. CONCLUSION: Subthreshold stimulation prolongs AV nodal conduction only at specific sites within the triangle of Koch, suggesting discrete parasympathetic endocardial inputs into the AV nodal region.

Long-term outcome of patients after successful radiofrequency ablation for typical atrial flutter.

The aim of the study was to determine the long-term freedom from atrial arrhythmias after radiofrequency ablation of atrial flutter and to determine the factors associated with recurrent arrhythmias. Radiofrequency ablation has emerged as the preferred treatment for recurrent, typical atrial flutter. Although the short-term results after radiofrequency ablation of atrial flutter have been widely reported, there is insufficient data on long-term outcome with respect to the occurrence of atrial arrhythmias in patients after successful ablation. The first 108 patients to undergo successful ablation for typical atrial flutter at the authors' institutions were followed prospectively until the occurrence of typical atrial flutter, atrial fibrillation, atypical atrial flutter, or death. Several prespecified clinical and procedural factors were tested using univariate and multivariate analysis as predictors of arrhythmia recurrence. Patients were followed for a minimum of 3 years and a maximum of 8 years, or until the first arrhythmia recurrence (average duration 17 +/- 17 months). Recurrences of typical atrial flutter were usually observed within the first 6 months (73%, n = 16), with the remainder (27%, n = 6) occurring between 6 months and 2 years, and none were observed later. Freedom from recurrence of typical atrial flutter was 80% at 1 year (95% CIs 72-89%), 73% at 2 years (CIs 63-83%), and 73% at 5 years (CIs 63-83%). By contrast, freedom from occurrence of atrial fibrillation or atypical atrial flutter progressively declined over time; 80% at 1 year (CIs 71-88%), 59% at 2 years (CIs 48-70%), and 33% at 5 years (CIs 19-48%). A history of atrial fibrillation or atypical atrial flutter prior to ablation was associated with an increased risk of occurrence during follow-up (relative risk 3.4, CIs 1.5-8.1, P < 0.05). Freedom from occurrence of any atrial arrhythmia was only 27% at 5 years (CIs 15-40%). After successful ablation of typical atrial flutter, recurrence of typical flutter is relatively uncommon and usually occurs early. However, there is a progressive occurrence of atrial fibrillation and/or atypical flutter during follow-up so that many patients require further antiarrhythmic or additional ablative therapy. Radiofrequency ablation of typical atrial flutter should be considered a palliative procedure for most patients and only one component of the long-term care of the patient with atrial tachyarrhythmias.

Cerebral blood flow velocity declines before arterial pressure in patients with orthostatic vasovagal presyncope.

OBJECTIVES: We studied hemodynamic changes leading to orthostatic vasovagal presyncope to determine whether changes of cerebral artery blood flow velocity precede or follow reductions of arterial pressure. BACKGROUND: Some evidence suggests that disordered cerebral autoregulation contributes to the occurrence of orthostatic vasovagal syncope. We studied cerebral hemodynamics with transcranial Doppler recordings, and we closely examined the temporal sequence of changes of cerebral artery blood flow velocity and systemic arterial pressure in 15 patients who did or did not faint during passive 70 degrees head-up tilt. METHODS: We recorded photoplethysmographic arterial pressure, RR intervals (electrocardiogram) and middle cerebral artery blood flow velocities (mean, total, mean/RR interval; Gosling's pulsatility index; and cerebrovascular resistance [mean cerebral velocity/mean arterial pressure, MAP]). RESULTS: Eight men developed presyncope, and six men and one woman did not. Presyncopal patients reported light-headedness, diaphoresis, or a sensation of fatigue 155 s (range: 25 to 414 s) before any cerebral or systemic hemodynamic change. Average cerebral blood flow velocity (CBFV) changes (defined by an iterative linear regression algorithm) began 67 s (range: 9 to 198 s) before reductions of MAP. Cerebral and systemic hemodynamic measurements remained constant in nonsyncopal patients. CONCLUSIONS: Presyncopal symptoms and CBFV changes precede arterial pressure reductions in patients with orthostatic vasovagal syncope. Therefore, changes of cerebrovascular regulation may contribute to the occurrence of vasovagal reactions.

Clinical and electrophysiologic effects of calcium channel blockers in patients receiving ibutilide.

BACKGROUND: Ibutilide is indicated for the acute termination of atrial fibrillation and atrial flutter. Recent work concludes that ibutilide activates a late inward sodium current that is blocked by nifedipine. Because calcium channel blockers are commonly used in patients with atrial fibrillation, it is important to exclude an antagonistic effect on ibutilide in the clinical setting. METHODS: We performed a retrospective electrocardiographic (ECG) review of patients enrolled in 3 clinical trials of ibutilide (2 atrial fibrillation conversion protocols and 1 ventricular tachycardia suppression protocol) to determine clinical efficacy and ECG effects of ibutilide in patients receiving and not receiving calcium channel blockers. Calcium channel blockers were administered as clinically indicated. A meta-analysis of the effects of calcium channel blockers on the conversion efficacy of atrial fibrillation and atrial flutter by ibutilide was also performed for studies in the literature. RESULTS: One hundred thirty patients were included in the ECG analysis (106 from atrial fibrillation protocols and 24 from the ventricular tachycardia protocol). Sixty-eight of the 130 patients were taking calcium channel blockers at the time of ibutilide administration. There were no differences in the QT or QTc intervals, conversion rate for atrial fibrillation or atrial flutter, or suppression of ventricular tachycardia between patients taking and not taking calcium channel blockers. In the meta-analysis of 4 studies, there was no difference in the conversion rates between patients taking (52%, n = 221) and not taking (45%, n = 402) calcium channel blockers (P =.09). CONCLUSIONS: In the clinical setting, the concomitant use of calcium channel blockers does not alter the ECG effects or efficacy of ibutilide for the treatment of atrial or ventricular arrhythmias.