A Novel Visually Guided Radiofrequency Balloon Ablation Catheter for Pulmonary Vein Isolation: One-Year Outcomes of the Multicenter AF-FICIENT I Trial.

[Figure: see text].

Decreases in cardiac catheter laboratory workload during the COVID-19 level 4 lockdown in New Zealand.

An increase in coronavirus disease (COVID-19) infections prompted Level 4 lockdown throughout New Zealand from 25 March 2020. We have investigated trends in coronary and electrophysiology (EP) procedures before and during this lockdown. The number of acute procedures for ST elevation myocardial infarction remained stable. In contrast, the number of in-patient angiograms and percutaneous intervention procedures fell by 53% compared with the previous 4 weeks in 2020 and by 56% compared with the corresponding period in 2019. Further study is required to determine the reasons for these trends.

Therapy From a Novel Substernal Lead: The ASD2 Study.

OBJECTIVES: The ASD2 (Acute Extravascular Defibrillation, Pacing, and Electrogram) study evaluated the ability to adequately sense, pace, and defibrillate patients with a novel implantable cardioverter-defibrillator (ICD) lead implanted in the substernal space. BACKGROUND: Subcutaneous ICDs are an alternative to a transvenous defibrillator system when transvenous implantation is not possible or desired. An alternative extravascular system placing a lead under the sternum has the potential to reduce defibrillation energy and the ability to deliver pacing therapies. METHODS: An investigational lead was inserted into the substernal space via a minimally invasive subxiphoid access, and a cutaneous defibrillation patch or subcutaneous active can emulator was placed on the left mid-axillary line. Pacing thresholds and extracardiac stimulation were evaluated. Up to 2 episodes of ventricular fibrillation were induced to test defibrillation efficacy. RESULTS: The substernal lead was implanted in 79 patients, with a median implantation time of 12.0 ± 9.0 min. Ventricular pacing was successful in at least 1 vector in 76 of 78 patients (97.4%), and 72 of 78 (92.3%) patients had capture in ≥1 vector with no extracardiac stimulation. A 30-J shock successfully terminated 104 of 128 episodes (81.3%) of ventricular fibrillation in 69 patients. There were 7 adverse events in 6 patients causally (n = 5) or possibly (n = 2) related to the ASD2 procedure. CONCLUSIONS: The ASD2 study demonstrated the ability to pace, sense, and defibrillate using a lead designed specifically for the substernal space.

Penetrance and expressivity of the R858H CACNA1C variant in a five-generation pedigree segregating an arrhythmogenic channelopathy.

BACKGROUND: Isolated cardiac arrhythmia due to a variant in CACNA1C is of recent knowledge. Most reports have been of singleton cases or of quite small families, and estimates of penetrance and expressivity have been difficult to obtain. We here describe a large pedigree, from which such estimates have been calculated. METHODS: We studied a five-generation family, in which a CACNA1C variant c.2573G>A p.Arg858His co-segregates with syncope and cardiac arrest, documenting electrocardiographic data and cardiac symptomatology. The reported patients/families from the literature with CACNA1C gene variants were reviewed, and genotype-phenotype correlations are drawn. RESULTS: The range of phenotype in the studied family is wide, from no apparent effect, through an asymptomatic QT interval prolongation on electrocardiography, to episodes of presyncope and syncope, ventricular fibrillation, and sudden death. QT prolongation showed inconsistent correlation with functional cardiology. Based upon analysis of 28 heterozygous family members, estimates of penetrance and expressivity are derived. CONCLUSIONS: These estimates of penetrance and expressivity, for this specific variant, may be useful in clinical practice. Review of the literature indicates that individual CACNA1C variants have their own particular genotype-phenotype correlations. We suggest that, at least in respect of the particular variant reported here, "arrhythmogenic channelopathy" may be a more fitting nomenclature than long QT syndrome.

High-Resolution Infrared Thermography of Esophageal Temperature During Radiofrequency Ablation of Atrial Fibrillation.

BACKGROUND: Catheter ablation for atrial fibrillation has potential to cause esophageal thermal injury. Esophageal temperature monitoring during ablation is commonly used; however, it has not eliminated thermal injuries, possibly because conventional sensors have poor spatial sampling and response characteristics. To enhance understanding of temperature dynamics that may underlie esophageal injury, we tested a high-resolution, intrabody, infrared thermography catheter to continuously image esophageal temperatures during ablation. METHODS AND RESULTS: Atrial fibrillation ablation patients were instrumented with a flexible, 9F infrared temperature catheter inserted nasally (n=8) or orally (n=8) into the esophagus adjacent to the left atrium. Ablation was performed while the infrared catheter continuously recorded surface temperatures from 7680 points per second circumferentially over a 6-cm length of esophagus. Physicians were blinded to temperature data. Endoscopy was performed within 24 hours to document esophageal injury. Thermal imaging showed that most patients (10/16) experienced ≥1 events where peak esophageal temperature was >40°C. Three patients experienced temperatures >50°C; and 1 experienced >60°C. Analysis of temperature data for each subject's maximum thermal event revealed high gradients (2.3±1.4°C/mm) and rates of change (1.5±1.3°C/s) with an average length of esophageal involvement of 11.0±5.4 mm. Endoscopy identified 3 distinct thermal lesions, all in patients with temperatures >50°C; all resolved within 2 weeks. CONCLUSIONS: Infrared thermography provided dynamic, high-resolution mapping of esophageal temperatures during cardiac ablation. Esophageal thermal injury occurred with temperatures >50°C and was associated with large spatiotemporal gradients. Additional studies are warranted to determine the relationships between thermal parameters and esophageal injury.

Longevity of the Subcutaneous Implantable Defibrillator: Long-Term Follow-Up of the European Regulatory Trial Cohort.

BACKGROUND: The recent advent of subcutaneous implantable cardioverter defibrillators (S-ICDs) has provided investigators with a safe and effective new therapy in patients at risk of sudden cardiac death. At present, no data are available with regard to the longevity of these new devices. This study evaluated the longevity of the S-ICD system. METHODS AND RESULTS: All patients enrolled in the European Regulatory Trial were included in the analysis. During follow-up, time and causes of device replacement or explantation were assessed and categorized. Device longevity was estimated using Kaplan-Meier analysis. Fifty-five patients were followed for a median of 5.8 years. During follow-up, 26 (47%) patients underwent device replacement and 5 (9%) underwent device explantation. Median time to replacement was 5.0 years (Q1-Q3, 4.4-5.6 years). Replacement was caused by battery depletion in 25 patients (92%), of which 5 within 1.5 years because of premature battery depletion, and by infection in 1 patient (2%). Replacement for a transvenous ICD system was required in 4 patients (7%) because of ineffective defibrillation in 1 (0.003 per patient-year), need for resynchronization therapy in 2 (0.01 per patient-year), and for antibradycardia pacing in 1 (0.003 per patient-year). At 5 years follow-up, 71% of devices were still in service. CONCLUSIONS: This study provides the first estimate of S-ICD system longevity since its introduction in clinical practice. Median longevity of the first generation S-ICD system was 5.0 years. The majority of devices were replaced because of battery depletion. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01117792.

Human muscle sympathetic nerve responses to urocortin-2 in health and stable heart failure.

Sympatholytic and vasodilator drugs have been of major therapeutic benefit in patients with heart failure (HF). Urocortin-2 (Ucn2) is a small corticotrophin-related peptide distributed throughout the cardiovascular system which inhibits cardiac sympathetic nerve activity (CSNA) and is also a powerful vasodilator. This study analysed the effects of a 60-min infusion of Ucn2 (25 µg) on muscle sympathetic nerve activity (MSNA) recorded from the lower limb in eight healthy men and four men with stable HF. During Ucn2 infusion, mean arterial pressure fell to a nadir of 84 ± 2 compared to 95 ± 2 mmHg during placebo (P = 0.001) and heart rate increased to a maximum of 74 ± 1 compared to 64 ± 1 b.p.m. (P < 0.001). Total peripheral resistance fell by 23 ± 4% compared with an increase of 23 ± 4% (P < 0.001) and cardiac output increased by 22 ± 4 compared to 4 ± 4% (P = 0.001). The MSNA burst frequency increased by 9 ± 2 compared to 1 ± 2 burst/min (P = 0.005) and burst area/min by 133 ± 7 vs 107 ± 7% (P = 0.01). Burst incidence and baroreflex sensitivity were not significantly altered. Qualitatively similar changes were observed in stable HF patients. Ucn2-induced vasodilatation increased MSNA in humans, as opposed to the decrease in CSNA we observed in sheep. Therefore, if Ucn2 has a central inhibitory effect on MSNA, it was over-run by off-loading the cardiovagal baroreflex. Alternatively, CSNA may be less responsive to baroreflex off-loading than MSNA.

Effects of AV delay and VV delay on left atrial pressure and waveform in ambulant heart failure patients: insights into CRT optimization.

BACKGROUND: We hypothesized that left atrial pressure (LAP) obtained by a permanent implantable sensor is sensitive to changes in cardiac resynchronization therapy (CRT) settings and could guide CRT optimization to improve the response rate. We investigated the effect of CRT optimization on LAP and its waveform parameters in ambulant heart failure (HF) patients. METHODS: CRT optimization was performed in eight ambulant HF patients, using echocardiography as reference. LAP waveform was acquired at each of eight atrioventricular (AV) intervals and five inter-ventricular (VV) intervals. Selected waveform parameters were also evaluated for their sensitivity to CRT changes and agreement with echocardiography-guided optimal settings. RESULTS: Optimal AV and VV intervals varied considerably between patients. All patients exhibited significant changes in waveform morphology with AV optimization. Optimal AV delay determined from echocardiography ranged between 140 ms and 225 ms. Mean LAP tended to be lower at optimal setting 14 ± 3 mmHg compared to shorter (<100 ms) or longer (>160 ms) AV settings (P = 0.16). There were clear trends to smaller peak a-wave (P = 0.11) and gentler positive a-slope (P = 0.15) and positive v-slope (P = 0.09) with longer AV delays. Mean LAP and negative v-wave slope correlated well with echo-guided optimal setting, r = 0.91 (P = 0.001) and 0.79 (P = 0.03), respectively. No significant effects on LAP or waveform were seen during VV optimization. CONCLUSIONS: LAP and its waveform changes considerably with AV optimization. There is good agreement between echo-guided optimal setting and LAP. LAP could provide an objective guide to CRT optimization. (Clinical Trial Registry information: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00632372).

Comparative pathology of an implantable left atrial pressure sensor.

A left atrial pressure (LAP) monitoring system was developed for guiding the management of patients with heart failure. The LAP sensor is implanted into the left atrium via transseptal catheterization and affixed to the interatrial septum by nitinol anchors. The long-term safety of permanent implantation of the LAP sensor in patients was evaluated based on the comparative pathology in animals. Tissue specimens of the LAP sensor from 7 patients, 49 canines, and 14 ovine were examined for thrombosis and tissue overgrowth. Implant duration ranged from 22 to 1,686 days. Gross examination showed minimal-to-moderate tissue overgrowth with no evidence of migration, erosion, or perforation. There was no excessive host-to-device reaction or active thrombogenesis in any of the subjects that followed the antithrombotic therapy protocol. Micro-computed tomography scanning confirmed the structural integrity of the device. Low vacuum scanning electron microscopy and histology showed neoendocardial tissue overgrowth with no inflammation or fibrin. The pathology of both animal models was found to closely approximate the pathology in humans and favorably supports the long-term safety of the device.

Urocortin-2 infusion in acute decompensated heart failure: findings from the UNICORN study (urocortin-2 in the treatment of acute heart failure as an adjunct over conventional therapy).

OBJECTIVES: The purpose of this study is to investigate the effects of urocortin-2 as adjunct therapy in acute decompensated heart failure (ADHF). BACKGROUND: Urocortin-2 produced favorable integrated effects in experimental heart failure but there are no equivalent human data. We describe the first therapeutic study of urocortin-2 infusion in ADHF. METHODS: Fifty-three patients with ADHF were randomly assigned to 5 ng/kg/min of urocortin-2 or placebo infusion for 4 h as an adjunct therapy. Changes in vital signs, plasma neurohormonal and renal indices during treatment were compared using repeated-measures analysis of covariance. Ten patients in each arm underwent more detailed invasive hemodynamic evaluation. RESULTS: Urocortin-2 produced greater falls in systolic blood pressure compared to placebo (16 ± 5.8 mm Hg, p < 0.001) with nonsignificant increases in heart rate (5.7 ± 3.8 beats/min, p = 0.07) and increased cardiac output (2.1 ± 0.4 l/min vs. -0.1 ± 0.4 l/min, p < 0.001) associated with a 47% reduction in calculated total peripheral resistance (p = 0.015). Falls in pulmonary artery and pulmonary capillary wedge pressures did not differ significantly between groups. Urocortin-2 reduced urine volume and creatinine clearance during infusion but these returned to above baseline level in the 8 h after infusion. Plasma renin activity rose briefly with urocortin-2 coinciding with reductions in blood pressure (p < 0.001). B-type natriuretic peptide levels fell significantly over 24 h with urocortin-2 (p < 0.01) but not with placebo. CONCLUSIONS: Urocortin-2 infusion in ADHF markedly augmented cardiac output without significant reflex tachycardia. Renal indices fell transiently concurrent with urocortin-2-induced reductions in blood pressure. Further investigations are required to uncover the full potential of urocortin-2 in treating ADHF.

Subcutaneous chronic implantable defibrillation systems in humans.

The recent introduction of subcutaneous implantable cardioverter defibrillator (S-ICD) has raised attention about the potential of this technology for clinical use in daily clinical practice. We review the methods and results of the four studies conducted in humans for approval of this innovative technology for daily practice. Two studies using a temporary S-ICD system (acute human studies) were conducted to search for an appropriate lead configuration and energy requirements. For this purpose, 4 S-ICD configurations were tested in 78 patients at the time of transvenous (TV)-ICD implantation. The optimal configuration was tested in 49 more patients to comparatively assess the subcutaneous defibrillation threshold (S-DFT) versus the standard TV-ICD. Long-term implants were evaluated in 55 patients using an implanted system (chronic human study). The acute humans studies led to an optimal S-ICD configuration comprising a parasternal electrode and left anterolateral thoracic pulse generator. Both configurations successfully terminated 98% of induced ventricular fibrillation (VF), but significantly higher energy levels were required with S-ICD than with TV-ICD systems (36.6 ± 19.8 J vs. 11.1 ± 8.5 J). In the chronic study, all 137 VF episodes induced at time of implant were detected with a 98% conversion rate. Two pocket infections and four lead revisions were required during 10 ± 1 months of follow-up. During this period, survival was 98%, and 12 spontaneous ventricular tachyarrhythmias were detected and treated by the device. These data show that the S-ICD systems here consistently detected and converted VF induced at time of implant as well as sustained ventricular tachyarrhythmias occurring during follow-up (248).

Surgical radiofrequency ablation for atrial fibrillation: the Christchurch, New Zealand experience.

AIMS: To report the long-term results following surgical radiofrequency ablation (RFA) for atrial fibrillation as an adjunct to other cardiac surgery at Christchurch Hospital. METHODS: A retrospective observational audit review of outcomes. The sample population included all patients identified as having undergone surgical RFA for atrial fibrillation at Christchurch Hospital, between the first procedure performed on 2 July 2001 and 28 January 2009. RESULTS: A total of 44 patients underwent surgical RFA between 2 July 2001 and 28 January 2009. Postoperatively there were three deaths prior to discharge (7%). Pacemakers were required in four patients (9%), and two patients subsequently underwent catheter ablation for atrial arrhythmias. In the immediate postoperative period only three patients remained in atrial fibrillation. At last follow-up up to 102 months from surgery (45 plus or minus 29 months), 27 patients had developed persistent atrial fibrillation and four persistent atrial flutter. Persisting long-term benefit was seen in seven patients (18%, 7/38); five patients were in stable sinus rhythm, one had paroxysmal atrial fibrillation and one paroxysmal atrial flutter. CONCLUSIONS: Whilst the procedure was effectively acutely, the recurrence of atrial fibrillation was high and development of new atrial flutter common over long-term follow-up.

Pulmonary vein ablation for atrial fibrillation: the Christchurch, New Zealand experience.

AIMS: To report the long-term results following percutaneous pulmonary vein ablation (PVA) for atrial fibrillation (AF) at Christchurch Hospital. METHODS: A retrospective observational audit review of outcomes. The sample population included all patients identified as having undergone percutaneous radiofrequency ablation of multiple pulmonary veins at Christchurch Hospital, from the first procedure performed on 29 September 2001 until 15 December 2009. RESULTS: A total of 187 patients underwent pulmonary vein ablation. The patient population was predominantly younger (mean age 51) and male (83%) with no important comorbidity. Following a single procedure only, the chance of remaining free of AF at 12 months was 0.74 for patients with paroxysmal AF (PAF) and 0.60 for patients with persistent AF (PsAF). 52 patients (28%) underwent a repeat procedure within 12 months of their index ablation owing to early recurrence of AF. 5-year survival free of clinical AF when analysed following these early repeat procedures, if required, was 0.74 and 0.56 for PAF and PsAF patients respectively. Complications occurred following 6% of procedures and were serious in 2.5%. New atrial flutter developed in 6% of patients. CONCLUSIONS: PVA is an effective treatment for AF, with better outcomes in patients with paroxysmal atrial fibrillation. However, as it carries a significant risk, we recommend that its application be reserved for patients with highly symptomatic, medication-refractory disease.

Prediction of cardiac rhythm 1 year following cardioversion for atrial fibrillation.

BACKGROUND: There is little recent information regarding outcome and its determinants following cardioversion (CV) for atrial fibrillation (AF) or flutter. This study aims to help improve prediction of cardiac rhythm outcome following CV for AF. METHODS: Cardiac rhythm at 6 weeks and 12 months was documented following elective (EC; n=496) or immediate (IC; n=52) cardioversion for AF or atrial flutter in a single referral centre. RESULTS: 65 and 58% of IC patients remained in sinus rhythm (SR) 6 weeks and 1 year after CV (respectively) compared with 43% and 30% in EC patients (P<0.001). Independent positive predictors of SR 6 weeks after cardioversion included amiodarone therapy (OR 2.04 [1.28-3.33], P<0.01) and atrial flutter (OR 1.85 [1.09-3.13], P<0.05). Negative predictors included the need for >1 shock to achieve SR (OR 1.61 [1.12-2.37], P=0.011) and arrhythmia duration, (OR 0.96 [0.95-0.97], P<0.001). At 1 year, amiodarone, duration of arrhythmia and the need for >1 shock remained independent predictors of rhythm. CONCLUSIONS: The number of shocks required to achieve SR is a newly demonstrated independent predictor of rhythm outcome after elective CV.

Serial Doppler echocardiography and tissue Doppler imaging in the detection of elevated directly measured left atrial pressure in ambulant subjects with chronic heart failure.

OBJECTIVES: This study sought to determine the accuracy of Doppler echocardiography and tissue Doppler imaging (TDI) measurements in detecting elevated left atrial pressure (LAP) in ambulant subjects with chronic heart failure using directly measured LAP as the reference. BACKGROUND: Echocardiographic indexes including the ratio of transmitral to annular early diastolic velocities (E/e') may identify raised invasively measured left ventricular filling pressures when tested in cross-sectional studies in some populations. The accuracy of these indexes when measured sequentially remains untested. We determined the accuracy of Doppler echocardiography and TDI measurements in detecting elevated directly measured LAP in ambulant subjects with stable chronic heart failure. METHODS: Fifteen patients with New York Heart Association functional class II to III heart failure and a permanently implanted direct LAP monitoring device underwent serial echocardiography. Simultaneous resting mean LAP, Doppler mitral inflow, mitral annular TDI, and pulmonary venous inflow velocities were obtained on each occasion. Receiver-operator characteristic curve analysis was used to compare the accuracy of the Doppler variables to detect an elevated device LAP ≥15 and ≥20 mm Hg. RESULTS: The patients (13 men, mean age: 71 years, mean left ventricular ejection fraction: 32 ± 12%) underwent 60 simultaneous echocardiographic studies and LAP measurements with a median of 4 (1 to 7) studies per patient. Mean LAP was 16.9 (range 5 to 39 mm Hg) at echocardiography (n = 60). E/e' had the greatest accuracy for detection of LAP ≥15 mm Hg with an area beneath the receiver-operator characteristic curve >0.9. In comparison, area under the curve for mitral E velocity and mitral E/A were 0.77 and 0.76, respectively (p < 0.008 vs. E/e' medial and average). CONCLUSIONS: Single and serial measurements of mitral inflow and mitral annular TDI velocities (E/e') can reliably detect raised directly measured LAP in ambulant subjects with compensated chronic heart failure. (Hemodynamically Guided Home Self-Therapy in Severe Heart Failure Patients [HOMEOSTASIS]; NCT00547729).

Symptoms and signs associated with syncope in young people with primary cardiac arrhythmias.

BACKGROUND: It is often reported that clinical symptoms are useful in differentiating cardiac from non-cardiac syncope. Studies in the young are rare. This study was designed to capture the symptoms and signs reported by patients with cardiac syncope before the patients or their attending clinicians knew the final diagnosis. METHODS: Retrospective case-note review of 35 consecutive unrelated gene-positive probands with a proven cardiac channelopathy. RESULTS: The presentation leading to diagnosis of cardiac channelopathy was resuscitated sudden cardiac death in 7 patients; syncope in 20; collapse with retained consciousness in 2; palpitations in 1 and an incidental finding in 5. For the 20 patients with syncope (LQTS 18, Brugada syndrome 2), median age at presentation was 13.9 years (1.8 day to 40.8 years). Of the 17 patients able to describe the onset of syncope, 11 (65%) had at least one symptom prior to collapse, though none reported nausea. Dizziness or lightheadedness was the most frequent symptom, being experienced by 8 (47%). Nine (of 20) patients (45%) had witnessed seizure-like activity and 8 (40%) had urinary incontinence. Nineteen patients were capable of describing the post-syncopal period, of whom 15 (79%) reported symptoms, the most common (12; 65%) being drowsiness or exhaustion. CONCLUSIONS: Cardiac syncope in the young frequently presents with symptoms and signs that are typically associated with other causes of transient loss of consciousness, including vasovagal syncope and seizure disorders. The presence of symptoms may not be as helpful in differentiating arrhythmic from non-arrhythmic events as is often supposed. A thorough history, appropriate investigations and a high index of suspicion remain essential in the assessment of syncope.