Jayanthi N. Koneru

The utility of 12-lead Holter monitoring in patients with permanent atrial fibrillation for the identification of nonresponders after cardiac resynchronization therapy.

OBJECTIVES This study sought to determine the incidence of ineffective capture using 12-lead Holter monitoring and to assess whether this affects response to cardiac resynchronization therapy (CRT). BACKGROUND Cardiac resynchronization therapy is used in patients with atrial fibrillation (AF), prolonged QRS duration, and heart failure in the setting of ventricular dysfunction. The percentage of ventricular pacing is used as an indicator of adequate biventricular (BiV) pacing. Although device counters show a high pacing percentage, there may be ineffective capture because of underlying fusion and pseudo-fusion beats. METHODS We identified 19 patients (age 72 +/- 8 years, ejection fraction 18 +/- 5%), with permanent AF who underwent CRT. All patients received digoxin, beta-blockers, and amiodarone for rate control; device interrogation showed >90% BiV pacing. Patients had a 12-lead Holter monitor to assess the presence of effective (>90% fully paced beats/24 h) pacing. At 12 months post-CRT, the New York Heart Association functional class was reassessed and an echocardiogram was obtained and compared with pre-CRT. RESULTS Only 9 (47%) patients had effective pacing. The other 10 (53%) patients had 16.4 +/- 4.6% fusion and 23.5 +/- 8.7% pseudo-fusion beats. Long-term responders (> or =1 New York Heart Association functional class improvement) to CRT had a significantly higher percentage of fully paced beats (86.4 +/- 17.1% vs. 66.8 +/- 19.1%; p = 0.03) than nonresponders. CONCLUSIONS Pacing counters overestimate the degree of effective BiV pacing in patients with permanent AF undergoing CRT therapy. Only patients with complete capture responded clinically to CRT. These findings have important implications for the application of CRT to patients with permanent AF and heart failure.

Long-term clinical outcomes of focal impulse and rotor modulation for treatment of atrial fibrillation: A multicenter experience

BACKGROUND New approaches to ablation of atrial fibrillation (AF) include focal impulse and rotor modulation (FIRM). Studies of this technology with short-term follow-up have shown favorable outcomes. OBJECTIVE The purpose of this study was to characterize the long-term results of FIRM ablation in a cohort of patients treated at 2 academic medical centers. METHODS All FIRM-guided ablation procedures (n = 43) at UCLA Medical Center and Virginia Commonwealth University Medical Center performed between January 2012 and October 2013 were included for analysis. During AF, FIRM software constructed phase maps from unipolar atrial electrograms to identify putative AF sources. These sites were targeted for ablation, along with pulmonary vein isolation in 77% of patients. RESULTS AF was paroxysmal in 56%, and 67% had prior AF ablation. All patients had rotors identified (mean 2.6 ± 1.2 per patient, 77% in LA). Prespecified acute procedural end-point was achieved in 47% of patients (n = 20): AF termination in 4, organization in 7, >10% slowing of AF cycle length in 9. Acute complications occurred in 4 patients (9.3%). At 18 ± 7 months of follow-up, 37% were free from documented recurrent AF after a 3-month blanking period; 21% were free from documented atrial tachyarrhythmias and off antiarrhythmic drugs. Multivariate analysis did not reveal any significant predictors of AF recurrence, including pattern of AF, acute procedural success, or prior failed ablation. CONCLUSION Long-term clinical results after FIRM ablation in this cohort of patients showed poor efficacy, different from previously published studies. Randomized studies are needed to evaluate the efficacy and clinical utility of this ablation approach for treating AF.

Histopathologic characterization of chronic radiofrequency ablation lesions for pulmonary vein isolation.

OBJECTIVES This study describes the histopathologic and electrophysiological findings in patients with recurrence of atrial fibrillation (AF) after pulmonary vein (PV) isolation who underwent a subsequent surgical maze procedure. BACKGROUND The recovery of PV conduction is commonly responsible for recurrence of AF after catheter-based PV isolation. METHODS Twelve patients with recurrent AF after acutely successful catheter-based antral PV isolation underwent a surgical maze procedure. Full-thickness surgical biopsy specimens were obtained from the PV antrum in areas of visible endocardial scar. Before biopsy, intraoperative epicardial electrophysiological recordings were taken from each PV using a circular mapping catheter. RESULTS Twenty-two PVs were biopsied from the 12 patients 8 ± 11 months after ablation. Eleven of the 22 specimens (50%) revealed transmural scar, and 11 (50%) showed viable myocardium with or without scar. Each biopsy specimen demonstrated evidence of injury, most commonly endocardial thickening (n = 21 [95%]) and fibrous scar (n = 18 [82%]). Seven of the 22 specimens (32%) showed conduction block at surgery. Transmural scar was more likely to be seen in the biopsy specimens from the PVs with conduction block than in specimens from the PVs showing reconnection. However, viable myocardium alone or mixed with scar was seen in 2 specimens from PVs with conduction block. CONCLUSIONS PVs showing electrical reconnection after catheter-based antral ablation frequently reveal anatomic gaps or nontransmural lesions at the sites of catheter ablation. Nontransmural lesions are noted in some PVs with persistent conduction block, suggesting that lesion geometry may influence PV conduction. The histological findings show that nontransmural ablation can produce a dynamic cellular substrate with features of reversible injury. Delayed recovery from injury may explain late recurrences of AF after PV isolation.

Value of the Signal-Averaged Electrocardiogram in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

BACKGROUND Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited disease that causes structural and functional abnormalities of the right ventricle (RV). The presence of late potentials as assessed by the signal-averaged electrocardiogram (SAECG) is a minor task force criterion. OBJECTIVE The purpose of this study was to examine the diagnostic and clinical value of the SAECG in a large population of genotyped ARVC/D probands. METHODS We compared the SAECGs of 87 ARVC/D probands (age 37 ± 13 years, 47 males) diagnosed as affected or borderline by task force criteria without using the SAECG criterion with 103 control subjects. The association of SAECG abnormalities was also correlated with clinical presentation, surface ECG, ventricular tachycardia (VT) inducibility at electrophysiologic testing, implantable cardioverter-defibrillator therapy for VT, and RV abnormalities as assessed by cardiac magnetic resonance imaging (cMRI). RESULTS Compared with controls, all three components of the SAECG were highly associated with the diagnosis of ARVC/D (P <.001). They include the filtered QRS duration (97.8 ± 8.7 ms vs 119.6 ± 23.8 ms), low-amplitude signal (24.4 ± 9.2 ms vs 46.2 ± 23.7 ms), and root mean square amplitude of the last 40 ms of the QRS (50.4 ± 26.9 μV vs 27.9 ± 36.3 μV). The sensitivity of using SAECG for diagnosis of ARVC/D was increased from 47% using the established 2 of 3 criteria (i.e., late potentials) to 69% by using a modified criterion of any 1 of 3 criteria, while maintaining a high specificity of 95%. Abnormal SAECG as defined by this modified criterion was associated with a dilated RV volume and decreased RV ejection fraction detected by cMRI (P <.05). SAECG abnormalities did not vary with clinical presentation or reliably predict spontaneous or inducible VT and had limited correlation with ECG findings. CONCLUSION Using 1 of 3 SAECG criteria contributed to increased sensitivity and specificity for the diagnosis of ARVC/D. This finding is incorporated in the recent modification of the task force criteria.

Characteristics of Ventricular Tachycardia Ablation in Patients With Continuous Flow Left Ventricular Assist Devices

Background—Left ventricular assist devices (LVADs) are increasingly used as a bridge to cardiac transplantation or as destination therapy. Patients with LVADs are at high risk for ventricular arrhythmias. This study describes ventricular arrhythmia characteristics and ablation in patients implanted with a Heart Mate II device. Methods and Results—All patients with a Heart Mate II device who underwent ventricular arrhythmia catheter ablation at 9 tertiary centers were included. Thirty-four patients (30 male, age 58±10 years) underwent 39 ablation procedures. The underlying cardiomyopathy pathogenesis was ischemic in 21 and nonischemic in 13 patients with a mean left ventricular ejection fraction of 17%±5% before LVAD implantation. One hundred and ten ventricular tachycardias (VTs; cycle lengths, 230–740 ms, arrhythmic storm n=28) and 2 ventricular fibrillation triggers were targeted (25 transseptal, 14 retrograde aortic approaches). Nine patients required VT ablation <1 month after LVAD implantation because of intractable VT. Only 10/110 (9%) of the targeted VTs were related to the Heart Mate II cannula. During follow-up, 7 patients were transplanted and 10 died. Of the remaining 17 patients, 13 were arrhythmia-free at 25±15 months. In 1 patient with VT recurrence, change of turbine speed from 9400 to 9000 rpm extinguished VT. Conclusions—Catheter ablation of VT among LVAD recipients is feasible and reasonably safe even soon after LVAD implantation. Intrinsic myocardial scar, rather than the apical cannula, seems to be the dominant substrate.

Atrioesophageal fistula formation with cryoballoon ablation is most commonly related to the left inferior pulmonary vein.

BACKGROUND Collateral damage has been reported with use of the cryoballoon for pulmonary vein isolation. OBJECTIVE The purpose of this study was to determine the incidence and characteristics associated with atrioesophageal fistula (AEF) after cryoballoon use. METHODS Cases of AEF reported with use of the cryoballoon since 2011 were collected from the Manufacturer and User Facility Device Experience (MAUDE) database, publications, and the manufacturers database. Lowest balloon temperatures were compared with matched control patients undergoing cryoballoon ablation without AEF formation. Location of AEF was compared with AEF associated with radiofrequency ablation. RESULTS A total of 11 cases of AEF were identified from a worldwide experience that exceed 120,000 cases. Mean age was 60 (range 31-78 years), and 80% of patients were male. Although mean lowest balloon temperatures were no different between patients with AEF and those with no AEF (-58.5°C ± 7.2°C vs -56°C ± 2.6°C, P = NS), balloon inflation times were longer in patients with AEF (238.8 ± 54.8 seconds vs 178.1 ± 37.5 seconds in the non-AEF group, P ≤.001) All cases of AEF for which location was identified occurred in relation to the left pulmonary veins. The left inferior pulmonary vein (LIPV) was involved in 8 of 10 patients with cryoballoon compared to 0 of 11 patients in the radiofrequency group (P <.05). Mortality for cryoballoon-associated AEF was 64%. CONCLUSION AEF after cryoballoon use is rare (<1 in 10,000) and most commonly was identified near the LIPV. Proximity of the esophagus to the LIPV and evidence of esophageal luminal cooling should be considered indications to limit cryoablation at this vein.

Quetiapine, QTc interval prolongation, and torsade de pointes: a review of case reports

Recently, both the manufacturer of quetiapine and the US Food and Drug Administration warned healthcare providers and patients about quetiapine-induced QTc interval prolongation and torsade de pointes (TdP) when using this drug within the approved labeling.  We reviewed the case-report literature and found 12 case reports of QTc interval prolongation in the setting of quetiapine administration. There were no cases of quetiapine-induced TdP or sudden cardiac death (SCD) among patients using quetiapine appropriately and free of additional risk factors for QTc interval prolongation and TdP. Among the 12 case reports risk factors included female sex (nine cases), coadministration of a drug associated with QTc interval prolongation (eight cases), hypokalemia or hypomagnesemia (six cases) quetiapine overdose (five cases), cardiac problems (four cases), and coadministration of cytochrome P450 3A4 inhibitors (two cases). There were four cases of TdP. As drug-induced TdP is a rare event, prospective studies to evaluate the risk factors associated with QTc prolongation and TdP are difficult to design, would be very costly, and would require very large samples to capture TdP rather than its surrogate markers. Furthermore, conventional statistical methods may not apply to studies of TdP, which is rare and an ‘outlier’ manifestation of QTc prolongation. We urge drug manufacturers and regulatory agencies to periodically publish full case reports of psychotropic drug-induced QTc interval prolongation, TdP, and SCD so that clinicians and investigators may better understand the clinical implications of prescribing such drugs as quetiapine.

Quetiapine and the need for a thorough QT/QTc study

The Food and Drug Administration (FDA) directed AstraZeneca in 2011 to add a warning to the labeling of the atypical antipsychotic agent quetiapine (Seroquel) about quetiapine-induced QTc interval prolongation and the potential for drug-induced torsade de pointes (TdP). This warning was updated the following year. Rather than relying on a thorough QT/QTc (TQT) study, this update was based on postmarketing reports of patients (1) overdosing on quetiapine, (2) having severe hypokalemia, or (3) receiving drugs associated with QTc interval prolongation such as (1) class I-A or class III antiarrhythmics, (2) certain antipsychotics (eg, ziprasidone, chlorpromazine, thioridazine), (3) certain antibiotics (eg, gatifloxacin, moxifloxacin), or (4) any other classes of drugs linked to QTc interval prolongation (eg, pentamidine, L-methadyl acetate, methadone). Interestingly, of the 3095 patients, 2 (0.06%) developed QTc interval prolongation of more than 500 milliseconds in quetiapine premarketing trials. They were older women with dementia. There was no link between quetiapine dose and QTc interval prolongation. Here, we evaluate available information on quetiapine in respect of QTc inteval prolongation and TdP, taking into account both information from preclinical experimental studies and human data. A striking feature of the latter is a lack of information from ‘‘thorough QT’’ (TQT) studies. We argue that TQT data for quetiapine would be invaluable in reaching an integrated assessment of its cardiac risk.

LAA ligation using the LARIAT suture delivery device: Tips and tricks for a successful procedure☆

intracranial bleeding (the most serious complication) to increased propensity for mechanical injury (the least serious complication). The resumption of OAC in patients who have suffered a life-threatening complication due to OAC is associated with a much higher risk of such events in the future. Alternative treatment options for this subset of patients include surgical and percutaneous catheter–based exclusion of the left atrial appendage (LAA). Of these, the percutaneous catheter–based LAA ligation procedure with the LARIAT suture delivery device (SentreHEART, Inc, Redwood City, CA) is an option that uses a combined endocardial and epicardial approach for LAA closure. It is technically feasible and has been shown to produce complete and long-term closure of the LAA. 3–5 We provide a step-bystep approach to LAA ligation with the LARIAT suture delivery device. This article provides useful hands-on information on a successful procedure with the LARIAT device but is not a substitute for proctoring—a necessity for the initial cases. A flow diagram of the steps involved in the procedure is depicted in Figure 1, and an overview of these steps is depicted in Figure 2 and Online Supplemental Movie 1. Preprocedural planning Patient selection On the basis of the published data, we consider performing this procedure in patients with AF who have risk factors for stroke and contraindications to OAC (Table 1). The percutaneous LAA ligation procedure requires the LARIAT device to be freely mobile within the pericardial space; therefore, prior open heart surgery is an absolute contraindication. A clinical history of severe pericarditis, epicardial VT ablation, uremia, pectus excavatum, and severe obesity are relative contraindications.

Methadone, QTc interval prolongation and torsade de pointes: Case reports offer the best understanding of this problem

We reviewed the literature and found 31 adult cases and 1 newborn case of methadone-associated QTc interval prolongation and/or torsade de pointes (TdP). Parametric statistics may not be useful in studying this issue because methadone-associated TdP is a very rare event and, hence, “an extreme outlier” consistent with scalable randomness. We may have to rely upon narrative medicine in the form of case reports with all its limitations and hazards to provide our best understanding. We report risk factors for methadone-associated QTc interval prolongation and TdP based on review of published case reports. We believe both drug manufacturers and the FDA would better serve our patients and inform clinicians if they more readily reported drug-induced outliers such as methadone-associated TdP using a case report format.