Long-term outcome of surgical cryoablation for refractory ventricular tachycardia in patients with non-ischemic cardiomyopathy.

Aims: Limited data exist on the long-term outcome of patients (pts) with non-ischemic cardiomyopathy (NICM) and ventricular tachycardia (VT) refractory to conventional therapies undergoing surgical ablation (SA). We aimed to investigate the long-term survival and VT recurrence in NICM pts with VT refractory to radiofrequency catheter ablation (RFCA) who underwent SA. Methods and results: Consecutive pts with NICM and VT refractory to RFCA who underwent SA were included. VT substrate was characterized in the electrophysiology lab and targeted by RFCA. During SA, previous RFCA lesions/scars were identified and targeted with cryoablation (CA; 3 min/lesion; target -150 °C). Follow-up comprised office visits, ICD interrogations and the social security death index. Twenty consecutive patients with NICM who underwent SA (age 53 ± 16 years, 18 males, LVEF 41 ± 20%; dilated CM = 9, arrhythmogenic right ventricular CM = 3, hypertrophic CM = 2, valvular CM = 4, and mixed CM = 2) were studied. Percutaneous mapping/ablation in the electrophysiology lab was performed in 18 and 2 pts had primary SA. During surgery, 4.9 ± 4.0 CA lesions/pt were delivered to the endocardium (2) and epicardium (11) or both (7). VT-free survival was 72.5% at 1 year and over 43 ± 31 months (mos) (range 1-83mos), there was only one arrhythmia-related death. There was a significant reduction in ICD shocks in the 3-mos preceding SA vs. the entire follow-up period (6.6 ± 4.9 vs. 2.3 ± 4.3 shocks/pt, P = 0.001). Conclusion: In select pts with NICM and VT refractory to RFCA, SA guided by pre-operative electrophysiological mapping and ablation may be a therapeutic option.

Distinct Electrocardiographic Form of Idiopathic Ventricular Arrhythmia Originating From the Left Bundle Branch.

Most premature ventricular contractions (PVCs) arise from the right or left ventricular outflow tract. Some VPCs originate near the His-bundle region. However, there remains a paucity of information on PVCs originating directly from the cardiac conduction system. We describe 2 cases with idiopathic frequent PVCs that were mapped directly to the left bundle branch itself. We also provide an anatomic-based mapping and ablation approach for management of these uncommon and challenging arrhythmias. In both cases we were able to either eliminate or significantly suppress the ectopic source by applying radiofrequency at this location without causing any significant impairment of the atrioventricular conduction.

Use of a novel endoscopic catheter for direct visualization and ablation in an ovine model of chronic myocardial infarction.

BACKGROUND: Defining the arrhythmogenic substrate is essential for successful ablation of scar-related ventricular tachycardia. The visual characteristics of endocardial ischemic scar have not been described in vivo. The goal of this study was (1) to quantify the visual characteristics of normal tissue, scar border zone, and dense scar in vivo with the use of a novel endoscopic catheter that allows direct endocardial visualization and (2) to correlate visual attributes of myocardial scar with bipolar voltage. METHODS AND RESULTS: Percutaneous transient balloon occlusion (150 minutes) of the mid left anterior descending coronary artery was performed in an ovine model. Animals survived for 41.5±0.7 days. Detailed bipolar voltage maps of the left ventricle were acquired with the use of NavX. Video snapshots of the endocardium were acquired at sites distributed throughout the left ventricle. Visual tissue characteristics of normal (>1.5 mV), border (0.5-1.5 mV), and dense scar (<0.5 mV) were quantified with the use of image processing. Radiofrequency lesions (10-20 W, 30 seconds) were delivered under direct visualization. Mean white-threshold pixel area was lowest in normal tissue (189 969±41 478 pixels(2)), intermediate in scar border zone (255 979±36 016 pixels(2)), and highest in dense scar (324 452±30 152 pixels(2); P<0.0001 for all pairwise comparisons). Tissue whiteness, characteristic of scar, was inversely correlated with bipolar voltage (P<0.0001). During radiofrequency lesions, there was a significant increase in white-thresholded pixel area of the visual field after ablation (average increase, 85 381±52 618 pixels(2); P<0.001). CONCLUSIONS: Visual characteristics of chronic infarct scar in vivo observed with the use of a novel endoscopic catheter correlate with bipolar electrogram voltage. Irrigated radiofrequency lesions in normal endocardial tissue and postinfarction zone can be visualized and quantified with the use of image processing. This technology shows promise for visually based delivery of radiofrequency lesions for the treatment of scar-based ventricular tachycardia.

Comparison of epicardial cryoablation and irrigated radiofrequency ablation in a Swine infarct model.

UNLABELLED: Epicardial Cryoablation in Swine. INTRODUCTION: Cryoablation is an alternative to radiofrequency (RF) energy used in some ablation procedures. Its role and effectiveness compared to irrigated RF in epicardial tissue and epicardial substrates is not yet fully established. METHODS AND RESULTS: Using a swine chronic infarct model, we compared RF lesions produced by an open-irrigated 3.5 mm tip catheter with those produced by an 8 mm tip cryocatheter in epicardial infarct border zone, epicardial normal tissue, and normal endocardium. In the infarct border zone, cryolesions were larger than RF lesions in maximum diameter (9.3 ± 2.9 mm vs 6.2 ± 2 mm, P < 0.001) and volume (171.7 ± 173.1 mm(3) vs 77 ± 53.5 mm(3) , P = 0.021). In normal epicardial tissue, cryolesions were larger in maximum diameter (11.2 ± 4.3 mm vs 7.7 ± 3.1 mm, P = 0.012), depth (5.8 ± 1.6 mm vs 4.7 ± 1.4 mm, P = 0.034), and volume (274.7 ± 242.2 mm(3) vs 112 ± 102.9 mm(3) , P = 0.002). In normal endocardium, no significant differences were found. CONCLUSIONS: Epicardial cryoablation with an 8 mm tip cryocatheter led to larger lesion volume in infarcted myocardium compared to a 3.5 mm irrigated RF catheter. This is likely related to a combination of cryoadherence, more efficient energy delivery with horizontal orientation, and lack of warming by circulating blood. Cryoablation merits further investigation as a modality for treating ventricular tachycardia of epicardial origin in humans. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1016-1023, September 2012).

Importance of the Interventricular Septum as Part of the Ventricular Tachycardia Substrate in Nonischemic Cardiomyopathy.

OBJECTIVES: This study sought to characterize septal substrate in patients with nonischemic left ventricular cardiomyopathy (NILVCM) undergoing ventricular tachycardia (VT) ablation. BACKGROUND: The interventricular septum is an important site of VT substrate in NILVCM. METHODS: The authors studied 95 patients with NILVCM and VT. Electroanatomic mapping using standard bipolar (<1.5 mV) and unipolar (<8.3 mV) low-voltage criteria identified septal scar location and size. Analysis of unipolar voltage was performed and scars quantified using graded unipolar cutoffs from 4 to 8.3 mV were correlated with delayed gadolinium-enhanced cardiac magnetic resonance (DE-CMR), performed in 57 patients. RESULTS: Detailed LV endocardial mapping (mean 262 ± 138 points) showed septal bipolar and unipolar voltage abnormalities (VAs) in 44 (46%) and 79 (83%) patients, most commonly with basal anteroseptal involvement. Of the 59 patients in whom the septum was targeted, bipolar and unipolar septal VAs were seen in 36 (61%) and 54 (92%). Of the 35 with CMR-defined septal scar, bipolar and unipolar septal VAs were seen in 18 (51%) and 31 (89%). In 12 patients without CMR septal scar, 6 (50%) had isolated unipolar septal VAs on electroanatomic mapping, a subset of whom the septum was targeted for ablation (44%). In the graded unipolar analysis, the optimal cutoff associated with magnetic resonance imaging septal scar was 4.8 mV (sensitivity 75%, specificity 70%; area under the curve: 0.75; 95% confidence interval: 0.60 to 0.90). CONCLUSIONS: Septal substrate by unipolar or bipolar voltage mapping in patients with NILVCM and VT is common. A unipolar voltage cutoff of 4.8 mV provides the best correlation with DE-CMR. A subset of patients with septal VT had normal DE-CMR or endocardial bipolar voltage with abnormal unipolar voltage.

Cardiac magnetic resonance imaging and electroanatomic voltage discordance in non-ischemic left ventricle ventricular tachycardia and premature ventricular depolarizations.

PURPOSE: Magnetic resonance imaging (MRI) with late gadolinium enhancement is commonly performed in patients with non-ischemic LV ventricular tachycardia/ventricular premature depolarizations (non-ischemic LV-VT/VPDs) to define VT substrate prior to catheter ablation. We investigated the prevalence of abnormal voltage and VT localized to areas of the myocardium not reported to have late gadolinium enhancement (LGE) on routine pre-procedural MRI and sought to determine if quantitative MRI analysis could reduce this discordance. METHODS: Patients with non-ischemic LV-VT/VPD who underwent LV endocardial mapping with VT/VPD ablation and either septal or free wall MRI-voltage discordance were studied. Electroanatomic maps were analyzed post-procedure for areas of electrogram-defined scar and VT localized to areas without reported LGE. Discordant segments were then analyzed offline using delayed signal intensity of >2 and >5 standard deviations above normal myocardium. RESULTS: Of 90 consecutive patients, 32 (36%) patients with septal (n = 16), free wall (n = 14) or both (n = 2) MRI-voltage + mismatch were identified. All discordant segments demonstrated unipolar voltage abnormalities with 12 patients (6 septal and 6 free wall) also showing low bipolar voltage but no LGE at signal intensity >5 standard deviations. Eleven patients (5 septum, 6 free wall) had VT localized to discordant areas. Ninety-three percent of patients in the septal group (26/48 segments) and 89% of patients in the free wall group (9/13 segments) had a concordant response established by using a signal intensity cutoff of >2 standard deviations. CONCLUSIONS: MRI-voltage discordance was identified in 36% of patients with non-ischemic LV-VT/VPD who underwent VT ablation. In 12% of patients, VT was targeted in areas of abnormal voltage not suggested by routine qualitative MRI. Quantitative MRI analysis using a lower signal intensity threshold increased the sensitivity for detecting areas of clinically relevant VT substrate.

In vitro expression studies of a novel mutation delta299 in a patient affected with apparent mineralocorticoid excess.

Apparent mineralocorticoid excess syndrome (AME) is an autosomal recessive disorder that results in low renin hypertension and other characteristic clinical features. Typical patients present with severe hypertension, hypokalemia, and undetectable aldosterone. Most patients also have low birth weight, failure to thrive, and nephrocalcinosis. The 11betahydroxysteroid dehydrogenase type 2 (11betaHSD2) defect is documented by demonstrating a failure to convert cortisol to cortisone. Here, we report a patient with typical phenotypic features of AME who does not carry any of the previously described mutations in the HSD11B2 gene. This female patient from a consanguineous Pakistani family presented at age 9 yr. She had a low birth weight compared with her siblings and presented with hypertension (225/120 mm Hg), low plasma renin activity, hypokalemic metabolic alkalosis, suppressed aldosterone, and bilateral nephrocalcinosis. Echocardiogram did not reveal left ventricular hypertrophy, and baseline ophthalmological evaluation did not demonstrate hypertensive retinopathy. However, at age 12 yr, she developed mild to moderate hypertensive retinopathy. Biochemical analysis showed an elevated urinary cortisol to cortisone metabolites ratio (tetrahydrocortisol and 5alpha-tetrahydrocortisol/tetrahydrocortisone) of 28 (normal, 0.66-2.44). She had a cortisol secretion rate of 0.43 mg/d (normal, 5-25 mg/d). Sequence analysis of the HSD11B2 gene revealed a novel homozygous delta299 mutation in exon 5. In vitro expression in Chinese hamster ovary cells revealed that this mutation resulted in no activity.

Sudden cardiac death in patients with nonischemic cardiomyopathy.

Sudden cardiac death (SCD) is an important cause of mortality worldwide. Although SCD is most often associated with coronary heart disease, the risk of SCD in patients without ischemic heart disease is well-established. Nonischemic cardiomyopathies, including idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy represent three unique disease entities that have been shown to be highly associated with SCD and ventricular arrhythmias. A variety of risk stratification tools have been investigated, although the optimal strategy remains unknown. Identification of the arrhythmogenic substrate and treatment of ventricular arrhythmias in these subgroups can be challenging. Herein, we aim to discuss the current understanding of the anatomic and electrophysiologic substrate underlying ventricular arrhythmias and highlight features that may be associated with a higher risk of SCD in these 3 conditions.

Characterization of trans-septal activation during septal pacing: criteria for identification of intramural ventricular tachycardia substrate in nonischemic cardiomyopathy.

BACKGROUND: Identification of intramural basal-septal ventricular tachycardia (VT) substrate is challenging in nonischemic cardiomyopathy. We sought to (1) characterize normal/abnormal trans-septal right ventricular (RV) to left ventricular activation; (2) assess the effect of opposite RV pacing on left ventricular septal bipolar electrograms (EGMs); and (3) establish criteria for the identification of intramural septal VT substrate. METHODS AND RESULTS: Endocardial activation mapping and local EGM assessment of the left interventricular septum was performed during RV basal septal pacing in 40 patients undergoing VT ablation with no evidence of septal scar (group 1, n=14) and with septal scar (group 2, n=26) defined by low septal unipolar voltage (<8.3 mV) and delayed enhancement on cardiac MRI with/without abnormal bipolar voltage (<1.5 mV) in sinus rhythm. Left ventricular trans-septal activation time was prolonged in Group 2 compared with Group 1 (55.3±33.0 versus 25.7±8.8 ms; P=0.003). In 6 group 2 patients, left ventricular septal breakthrough was displaced to the scar border. During RV pacing, group 2 had fractionated (8.8%), late (2.8%), and split (5.7%) EGMs not seen in group 1. Trans-septal activation >40 ms (sensitivity 60%, specificity 100%; P<0.001) and EGM duration >95 ms during pacing (sensitivity 22%, specificity 91%; P<0.001) identified septal scar (13/26 pts). CONCLUSIONS: In patients with nonischemic cardiomyopathy, VT and septal scar, delayed transmural conduction time (>40 ms) and fractionated, late, split, and wide (>95 ms) bipolar EGMs during RV basal pacing identify intramural VT substrate. In select cases, the basal septum appears compartmentalized as the stimulated wavefront is rerouted to the scar border.

Mechanisms of cardiac arrhythmias.

Cardiac arrhythmias are prevalent among humans across all age ranges and may occur in the setting of underlying heart disease as well as in structurally normal hearts. While arrhythmias are widely varied in their clinical presentations, they possess shared electrophysiologic properties at the cellular level. The 3 main mechanisms responsible for cardiac arrhythmias are automaticity, triggered activity, and reentry. Although identifying the specific mechanism may at times be challenging for the clinician and require invasive electrophysiologic study, differentiating and understanding the underlying mechanism may be critical to the development of an appropriate diagnosis and treatment strategy.

Sinus rhythm electrocardiogram identification of basal-lateral ischemic versus nonischemic substrate in patients with ventricular tachycardia.

PURPOSE: Sinus rhythm (SR) electrocardiogram (ECG) features in patients with nonischemic cardiomyopathy (NICM) and ventricular tachycardia (VT) have been described. ECG characteristics that distinguish nonischemic VT substrate from prior myocardial infarction (MI) have yet to be determined. We aimed to identify ECG differences between patients with basal-inferolateral scar due to NICM versus prior MI. METHODS: SR/atrial-paced ECGs from patients who underwent VT ablation with endocardial/epicardial basal-inferolateral nonischemic scar (n = 25) were compared to patients with inferior/inferolateral MI (n = 30). Surface QRS complexes in each lead were analyzed. Patients with bundle branch block or ventricular pacing were excluded. The best diagnostic algorithm was determined by multivariate analysis then validated prospectively. RESULTS: The NICM group had smaller R amplitude in leads I, II, and III (p ≤ 0.05 for all), greater S amplitude in leads II, III, and V6 (p ≤ 0.001 for all) and S/R ratio in lead V6 (p = 0.001). Inferior Q waves were uncommon in NICM (24 % vs. 87 %, p < 0.001). Lateral QRS fragmentation was uncommon (20 %) but only found in NICM. A three-step algorithm was derived with 100 % sensitivity and 77 % specificity for NICM. In the validation cohort (n = 51), ICM was appropriately excluded in 93 % of the cases of NICM (91 % interobserver agreement) by the algorithm. CONCLUSIONS: Lateral lead QRS fragmentation, absence of inferior Q waves, and lead V6 S/R ratio ≥0.25 on the SR ECG distinguishes patients with basal-lateral scar due to NICM from those with prior MI. These findings demonstrate the value of the surface ECG in identifying unique scar-based VT substrate.

Layered activation of epicardial scar in arrhythmogenic right ventricular dysplasia: possible substrate for confined epicardial circuits.

BACKGROUND: Ventricular tachycardia ablation in arrhythmogenic right ventricular dysplasia (ARVD) is more successful when including epicardial ablation. Scarring may cause independent, layered epicardial activation and promote epicardially confined ventricular tachycardia circuits. We aimed to characterize transmural right ventricular activation in ARVD patients and to compare this with reference patients without structural heart disease. METHODS AND RESULTS: Eighteen ARVD patients underwent detailed endocardial and epicardial sinus rhythm electroanatomic mapping. Bipolar activation was annotated at the sharpest intrinsic deflection including late potentials and compared with 6 patients with normal hearts. Total scar area was larger on the epicardium (97±78 cm(2)) than the endocardium (57±44 cm(2); P=0.04), with significantly more isolated potentials. Total epicardial activation time was longer than endocardial (172±54 versus 99±27 ms; P<0.01), and both were longer than in reference patients. Earliest endocardial site was the right ventricular anteroseptum in 17 of 18 ARVD patients versus 5 of 6 controls (P=0.446), and latest endocardial site was in the outflow tract in 13 of 18 ARVD patients versus 4 of 6 controls and tricuspid annulus in 5 of 18 ARVD patients versus 2 of 6 controls (P=1.00). In reference patients, epicardial activation directly opposite endocardial sites occurred in 5.2±1.9 ms, suggesting direct transmural activation. In contrast, ARVD patients had major activation delay to the epicardium with laminar central scar activation from the scar border, not by direct transmural spread from the endocardium. CONCLUSIONS: Transmural right ventricular activation is modified by ARVD scarring with a delayed epicardial activation sequence suggestive of independent rather than direct transmural activation. This may predispose ventricular tachycardia circuits contained entirely within the epicardium in ARVD and explains observations on the need for direct epicardial ablation to eliminate ventricular tachycardia.

Long-term follow-up of patients with cardiac sarcoidosis and implantable cardioverter-defibrillators.

BACKGROUND: Ventricular tachyarrhythmias are an important cause of morbidity and mortality in cardiac sarcoidosis. To date, the prevalence and incidence of ventricular tachycardia/ventricular fibrillation (VT/VF) in this population remain unknown. OBJECTIVES: To determine the prevalence and incidence of ventricular tachyarrhythmias in patients with cardiac sarcoidosis and to identify the clinical attributes associated with appropriate implantable cardioverter-defibrillator (ICD) therapies. METHODS: We studied 45 patients with ICDs, biopsy-proven systemic sarcoidosis, and cardiac involvement, as evidenced by histopathology, cardiac magnetic resonance imaging, and/or (18)F-fluoro-2-deoxyglucose-positron emission tomography imaging. Device logs and medical records were retrospectively reviewed. RESULTS: Appropriate ICD therapies for VT/VF were observed in 37.8% of the patients with an incidence of 15% per year. Inappropriate ICD therapies occurred in 13.3% of the patients. Longer ICD follow-up (4.5 ± 3.1 years vs 1.5 ± 1.5 years; P = .001), depressed left ventricular ejection fraction (35.5% ± 15.5% vs 50.9% ± 15.5%; P = .002), and complete heart block (47.1% vs 17.9%; P = .048) were associated with appropriate ICD therapy. While there was no significant difference in the total number of shocks/antitachycardia pacing-terminated events between primary (n = 29) and secondary (n = 16) prevention groups, there was a trend toward more events in the secondary prevention arm after 2 years. CONCLUSIONS: Ventricular tachyarrhythmias requiring ICD therapy were common in patients with cardiac sarcoidosis, with an estimated incidence rate of 15% per year. Longer follow-up, left ventricular systolic dysfunction, and complete heart block were associated with VT/VF. Patients with primary prevention ICDs had high rates of appropriate ICD therapy but not as high as did secondary prevention patients. In the absence of reliable risk stratification techniques, consideration should be given to prophylactic ICD implantation in patients with cardiac sarcoidosis.

The V(2) transition ratio: a new electrocardiographic criterion for distinguishing left from right ventricular outflow tract tachycardia origin.

OBJECTIVES: We sought to develop electrocardiography (ECG) criteria for distinguishing left ventricular outflow tract (LVOT) from right ventricular outflow tract (RVOT) origin in patients with idiopathic outflow tract ventricular tachycardia (OTVT) and lead V(3) R/S transition. BACKGROUND: Several ECG criteria have been proposed for differentiating left from right OTVT origin; ventricular tachycardias (VTs) with left bundle branch block and V(3) transition remain a challenge. METHODS: We analyzed the surface ECG pattern of patients with OTVT with a precordial transition in lead V(3) who underwent successful catheter ablation. Sinus and VT QRS morphologies were measured in limb and precordial leads with electronic calipers. The V(2) and V(3) transition ratios were calculated by computing the percentage R-wave during VT (R/R+S)(VT) divided by the percentage R-wave in sinus rhythm (R/R+S)(SR). RESULTS: We retrospectively analyzed ECGs from 40 patients (mean age 44 ± 14 years, 21 female) with outflow tract premature ventricular contractions (PVCs)/VT. Patients with structural heart disease, paced rhythms, and bundle branch block during sinus rhythm were excluded. The V(2) transition ratio was significantly greater for LVOT PVCs compared with RVOT PVCs (1.27 ± 0.60 vs. 0.23 ± 0.16; p < 0.001) and was the only independent predictor of LVOT origin. In 21 prospective cases, a V(2) transition ratio ≥0.60 predicted an LVOT origin with 91% accuracy. A PVC precordial transition occurring later than the sinus rhythm transition excluded an LVOT origin with 100% accuracy. CONCLUSIONS: The V(2) transition ratio is a novel electrocardiographic measure that reliably distinguishes LVOT from RVOT origin in patients with lead V(3) precordial transition. This measure might be useful for counseling patients and planning an ablation strategy.

Mecanismos de las arritmias cardiacas / Mechanisms of cardiac arrhythmias

En la especie humana, las arritmias cardiacas son muy prevalentes en todos los grupos de edad y pueden darse tanto en el contexto de una cardiopatía subyacente como en corazones estructuralmente normales. Aunque las formas de presentación clínica de las arritmias son muy diversas, en las células comparten propiedades electrofisiológicas comunes. Los 3 mecanismos principales de las arritmias cardiacas son las alteraciones en el automatismo, la actividad desencadenada y la reentrada. Aunque la identificación del mecanismo específico a veces pueda resultar difícil para el clínico y requerir un estudio electrofisiológico invasivo, diferenciar y comprender el mecanismo subyacente puede ser crucial para desarrollar una correcta estrategia diagnóstica y terapéutica (AU)

Cardiac arrhythmias are prevalent among humans across all age ranges and may occur in the setting of underlying heart disease as well as in structurally normal hearts. While arrhythmias are widely varied in their clinical presentations, they possess shared electrophysiologic properties at the cellular level. The 3 main mechanisms responsible for cardiac arrhythmias are automaticity, triggered activity, and reentry. Although identifying the specific mechanism may at times be challenging for the clinician and require invasive electrophysiologic study, differentiating and understanding the underlying mechanism may be critical to the development of an appropriate diagnosis and treatment strategy (AU)