Jason S. Bradfield

Safety and efficacy of renal denervation as a novel treatment of ventricular tachycardia storm in patients with cardiomyopathy

BACKGROUND Modulation of the autonomic nervous system has been used to treat refractory ventricular tachycardia (VT). Renal artery denervation (RDN) is under investigation for the treatment of sympathetic-driven cardiovascular diseases. OBJECTIVE The purpose of this study was to report the largest case series to date using RDN as adjunctive therapy for refractory VT in patients with underlying cardiomyopathy. METHODS Four patients with cardiomyopathy (2 nonischemic, 2 ischemic) with recurrent VT despite maximized antiarrhythmic therapy and prior endocardial (n = 2) or endocardial/epicardial (n = 2) ablation underwent RDN ± repeat VT ablation. RDN was performed spirally along each main renal artery with either a nonirrigated (6 W at 50°C for 60 seconds) or an open irrigated ablation catheter (10-12 W for 30-60 seconds). Renal arteriography was performed before and after RDN. RESULTS RDN was well tolerated acutely and demonstrated no clinically significant complications during follow-up of 8.8 ± 2.6 months (range 5.0-11.0 months). No hemodynamic deterioration or worsening of renal function was observed. The number of VT episodes was decreased from 11.0 ± 4.2 (5.0-14.0) during the month before ablation to 0.3 ± 0.1 (0.2-0.4) per month after ablation. All VT episodes occurred in the first 4 months after ablation (2.6 ± 1.5 months). The responses to RDN were similar for ischemic and nonischemic patients. CONCLUSION This case series provides promising preliminary data on the safety and effectiveness of RDN as an adjunctive therapy in the treatment of patients with cardiomyopathy and VT resistant to standard interventions.

Epicardial ablation of ventricular tachycardia: An institutional experience of safety and efficacy

BACKGROUND Epicardial ablation has been shown to be a useful adjunct for treatment of ventricular tachycardia (VT). OBJECTIVE To report the trends, safety, and efficacy of epicardial mapping and ablation at a single center over an 8-year period. METHODS Patients referred for VT ablation (June 2004 to July 2011) were divided into 3 groups: ischemic cardiomyopathy (ICM), nonischemic cardiomyopathy (NICM), and idiopathic ventricular arrhythmias (VA). Patients with scar-mediated VT who underwent combined epicardial and endocardial (epi-endo) mapping and ablation were compared with those who underwent endocardial-only (endo-only) ablation with regard to patient characteristics, acute procedural success, 6- and 12-month clinical outcomes. RESULTS Among 144 patients referred for VT ablation, 95 patients underwent 109 epicardial procedures (94% access rate). Major complications were seen in 8 patients (8.8%) with pericardial bleeding (>80 cm(3)) in 6 cases (6.7%), although no tamponade, surgical intervention, or procedural mortality was seen. Patients with ICM who underwent a combined epi-endo ablation had improved freedom from VT compared with those who underwent endo-only ablation at 12 months (85% vs 56%; P = .03). In patients with NICM, no differences were seen between those who underwent epi-endo ablation and those who underwent endo-only ablation at 12 months (36% vs 33%; P = 1.0). In idiopathic VA, only 2 of 17 patients were successfully ablated from the epicardium. CONCLUSIONS In this large tertiary single-center experience, complication rates are acceptably low and improved clinical outcomes were associated with epi-endo ablation in patients with ICM. Patients with NICM represent a growing referred population, although clinical recurrence remains high despite epicardial ablation. Epicardial ablation has a low yield in idiopathic VA.

Functional pace-mapping responses for identification of targets for catheter ablation of scar-mediated ventricular tachycardia.

Background— Myocardial scars harbor areas of slow conduction and display abnormal electrograms. Pace-mapping at these sites can generate a 12-lead ECG morphological match to a targeted ventricular tachycardia (VT), and in some instances, multiple exit morphologies can result. At times, this can also result in the initiation of VT, termed pace-mapped induction (PMI). We hypothesized that in patients undergoing catheter ablation of VT, scar substrates with multiple exit sites (MES) identified during pace-mapping have improved freedom from recurrent VT, and PMI of VT predicts successful sites of termination during ablation. Methods and Results— High-density mapping was performed in all subjects to delineate scar (0.5–1.5 mV). Sites with abnormal electrograms were tagged, stimulated (bipolar 10 mA at 2 ms), and targeted for ablation. MES was defined as >1 QRS morphology from a single pacing site. PMI was defined as initiation of VT during pace-mapping (400–600 ms). In a 2-year period, 44 consecutive patients with scar-mediated VT underwent mapping and ablation. MES were observed during pace-mapping in 25 patients (57%). At 9 months, 74% of patients who exhibited MES during pace-mapping had no recurrence of VT compared with 42% of those without MES observed (P=0.024), with an overall freedom from VT of 61%. Thirteen patients (30%) demonstrated PMI, and termination of VT was seen in 95% (18/19) of sites where ablation was performed. Conclusions— During pace-mapping, electrograms that exhibit MES and PMI may be specific for sites critical to reentry. These functional responses hold promise for identifying important sites for catheter ablation of VT.

Impact of local ablation on interconnected channels within ventricular scar: mechanistic implications for substrate modification.

Background— The extent to which channels within scar are interconnected is not known. The objective of the study was to evaluate the impact of local ablation of late potentials (LPs) on adjacent and remote areas of slow conduction with simultaneous multipolar mapping. Methods and Results— Analysis was performed on consecutive patients referred for ablation of scar-mediated ventricular tachycardia with double ventricular access. Ablation was performed targeting the earliest of LPs visualized on the multipolar catheter, and the impact on later LPs was recorded. In 21 patients, a multipolar catheter placed within scar visualized spatially distinct LPs. Among 39 radiofrequency applications, ablation at earlier LPs had an effect on neighboring and remote LPs in 31 (80%), with delay in 8 (21%), partial elimination in 9 (23%), and complete elimination in 14 (36%). The mean distance where an ablation impact was detected was 17.6±14.7 mm (range, 2–50 mm). Among all patients, 9.7±7.8 radiofrequency applications were delivered to homogenize the targeted scar region with a mean number of 23±12 LPs targeted. Conclusions— Ablation can eliminate neighboring and remote areas of slow conduction, suggesting that channels within scar are frequently interconnected. This is the first mechanistic demonstration to show that ablation can modify electrical activity in regions of scar outside of the known radius of an radiofrequency lesion. The targeting of relatively earlier LPs can expedite scar homogenization without the need for extensive ablation of all LPs.Background—The extent to which channels within scar are interconnected is not known. The objective of the study was to evaluate the impact of local ablation of late potentials (LPs) on adjacent and remote areas of slow conduction with simultaneous multipolar mapping. Methods and Results—Analysis was performed on consecutive patients referred for ablation of scar-mediated ventricular tachycardia with double ventricular access. Ablation was performed targeting the earliest of LPs visualized on the multipolar catheter, and the impact on later LPs was recorded. In 21 patients, a multipolar catheter placed within scar visualized spatially distinct LPs. Among 39 radiofrequency applications, ablation at earlier LPs had an effect on neighboring and remote LPs in 31 (80%), with delay in 8 (21%), partial elimination in 9 (23%), and complete elimination in 14 (36%). The mean distance where an ablation impact was detected was 17.6±14.7 mm (range, 2–50 mm). Among all patients, 9.7±7.8 radiofrequency applications were delivered to homogenize the targeted scar region with a mean number of 23±12 LPs targeted. Conclusions—Ablation can eliminate neighboring and remote areas of slow conduction, suggesting that channels within scar are frequently interconnected. This is the first mechanistic demonstration to show that ablation can modify electrical activity in regions of scar outside of the known radius of an radiofrequency lesion. The targeting of relatively earlier LPs can expedite scar homogenization without the need for extensive ablation of all LPs.

Catheter Ablation Utilizing Remote Magnetic Navigation: A Review of Applications and Outcomes

The utilization of the NIOBE™ magnetic navigation system (MNS, Stereotaxis, St. Louis, MO, USA) has increased significantly since the first published report in 2002. There has been much enthusiasm for this technology as a means to reduce radiation exposure to the patient and physician alike, and potentially decrease risks associated with catheter manipulation by less experienced operators. However, there are limited data regarding the acute, intermediate, and long‐term results and procedural characteristics from ablation procedures utilizing this system. We present a review of the outcomes and procedural data available to date.

Effect of Exposure to Cigarette Smoke on Carotid Artery Intimal Thickening: The Role of Inducible NO Synthase

Objective—We investigated the role of inducible NO synthase (iNOS) in intimal thickening with exposure to cigarette smoke (CS). Methods and Results—Intimal thickening in wild-type (WT) and iNOS-deficient (iNOS−/−) mice subjected to CS exposure was induced by placement of a cuff around the carotid artery. CS exposure in WT mice was associated with increased arterial iNOS expression, superoxide production, activator protein-1 (AP-1) activation, and serum NO. Intimal thickening 21 days after cuff placement was significantly greater in mice exposed to CS compared with air (0.023±0.013 mm2 versus 0.009±0.008 mm2; P<0.05). iNOS inhibitor mercaptoethylguanidine-treated WT mice exposed to CS had reduced iNOS activity and intimal thickening (0.006±0.005 mm2; P<0.05). Intimal thickening was significantly less in iNOS−/− mice compared with WT mice (0.006±0.005 mm2; P<0.01) and was not augmented with CS (0.002±0.002 mm2). The aryl hydrocarbon receptor (AhR) was detected in arteries in vivo and in smooth muscle cells (SMCs) in vitro. CS condensate treatment of SMCs increased AhR binding to the core xenobiotic-responsive element of the iNOS promoter and increased iNOS expression. Conclusions—Increased arterial expression of iNOS, mediated at least in part by AhR signaling, may be an important mechanism by which CS increases carotid intimal thickening. CS exposure in mice was associated with increased arterial iNOS expression, superoxide production, AP-1 activation, serum NO expression, and intimal thickening. Inhibition or deletion of iNOS abrogated the effects of CS.

Cardiac involvement in sarcoidosis: Evolving concepts in diagnosis and treatment

Clinically evident sarcoidosis involving the heart has been noted in at least 2 to 7% of patients with sarcoidosis, but occult involvement is much higher (> 20%). Cardiac sarcoidosis is often not recognized antemortem, as sudden death may be the presenting feature. Cardiac involvement may occur at any point during the course of sarcoidosis and may occur in the absence of pulmonary or systemic involvement. Sarcoidosis can involve any part of the heart, with protean manifestations. Prognosis of cardiac sarcoidosis is related to extent and site(s) of involvement. Most deaths due to cardiac sarcoidosis are due to arrhythmias or conduction defects, but granulomatous infiltration of the myocardium may be lethal. The definitive diagnosis of isolated cardiac sarcoidosis is difficult. The yield of endomyocardial biopsies is low; treatment of cardiac sarcoidosis is often warranted even in the absence of histologic proof. Radionuclide scans are integral to the diagnosis. Currently, 18F-fluorodeoxyglucose positron emission tomography/computed tomography and gadolinium-enhanced magnetic resonance imaging scans are the key imaging modalities to diagnose cardiac sarcoidosis. The prognosis of cardiac sarcoidosis is variable, but mortality rates of untreated cardiac sarcoidosis are high. Although randomized therapeutic trials have not been done, corticosteroids (alone or combined with additional immunosuppressive medications) remain the mainstay of treatment. Because of the potential for sudden cardiac death, implantable cardioverter-defibrillators should be placed in any patient with cardiac sarcoidosis and serious ventricular arrhythmias or heart block, and should be considered for cardiomyopathy. Cardiac transplantation is a viable option for patients with end-stage cardiac sarcoidosis refractory to medical therapy.

Low referral rate for prophylactic implantation of cardioverter-defibrillators in a tertiary care medical center.

Background: Implantable cardioverter‐defibrillators (ICDs) for primary prevention became standard of care after the publication of the second Multicenter Automatic Defibrillator Implantation Trial (MADIT‐II) and Sudden Cardiac Death in Heart Failure Trial (SCD‐HeFT).

Relationship Between Sinus Rhythm Late Activation Zones and Critical Sites for Scar-Related Ventricular Tachycardia Systematic Analysis of Isochronal Late Activation Mapping

Background—It is not known whether the most delayed late potentials are functionally most specific for scar-related ventricular tachycardia (VT) circuits. Methods and Results—Isochronal late activation maps were constructed to display ventricular activation during sinus rhythm over 8 isochrones. Analysis was performed at successful VT termination sites and prospectively tested. Thirty-three patients with 47 scar-related VTs where a critical site was demonstrated by termination of VT during ablation were retrospectively analyzed. In those who underwent mapping of multiple surfaces, 90% of critical sites were on the surface that contained the latest late potential. However, only 11% of critical sites were localized to the latest isochrone (87.5%–100%) of ventricular activation. The median percentage of latest activation at critical sites was 78% at a distance from the latest isochrone of 18 mm. Sites critical to reentry were harbored in regions with slow conduction velocity, where 3 isochrones were present within a 1-cm radius. Ten consecutive patients underwent ablation prospectively guided by isochronal late activation maps, targeting concentric isochrones outside of the latest isochrone. Elimination of the targeted VT was achieved in 90%. Termination of VT was achieved in 6 patients at a mean ventricular activation percentage of 78%, with only 1 requiring ablation in the latest isochrone. Conclusions—Late potentials identified in the latest isochrone of activation during sinus rhythm are infrequently correlated with successful ablation sites for VT. The targeting of slow conduction regions propagating into the latest zone of activation may be a novel and promising strategy for substrate modification.

Coupling interval variability differentiates ventricular ectopic complexes arising in the aortic sinus of valsalva and great cardiac vein from other sources: mechanistic and arrhythmic risk implications.

OBJECTIVES The objective of this study was to determine whether premature ventricular contractions (PVCs) arising from the aortic sinuses of Valsalva (SOV) and great cardiac vein (GCV) have coupling interval (CI) characteristics that differentiate them from other ectopic foci. BACKGROUND PVCs occur at relatively fixed CI from the preceding normal QRS complex in most patients. However, we observed patients with PVCs originating in unusual areas (SOV and GCV) in whom the PVC CI was highly variable. We hypothesized that PVCs from these areas occur seemingly randomly because of the lack of electrotonic effects of the surrounding myocardium. METHODS Seventy-three consecutive patients referred for PVC ablation were assessed. Twelve consecutive PVC CIs were recorded. The ΔCI (maximum - minimum CI) was measured. RESULTS We studied 73 patients (age 50 ± 16 years, 47% male). The PVC origin was right ventricular (RV) in 29 (40%), left ventricular (LV) in 17 (23%), SOV in 21 (29%), and GCV in 6 (8%). There was a significant difference between the mean ΔCI of RV/LV PVCs compared with SOV/GCV PVCs (33 ± 15 ms vs. 116 ± 52 ms, p < 0.0001). A ΔCI of >60 ms demonstrated a sensitivity of 89%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 94%. Cardiac events were more common in the SOV/GCV group versus the RV/LV group (7 of 27 [26%] vs. 2 of 46 [4%], p < 0.02). CONCLUSIONS ΔCI is more pronounced in PVCs originating from the SOV or GCV. A ΔCI of 60 ms helps discriminate the origin of PVCs before diagnostic electrophysiological study and may be associated with increased frequency of cardiac events.