Ventricular Tachycardia Ablation in Severe Heart Failure: An International Ventricular Tachycardia Ablation Center Collaboration Analysis.

BACKGROUND: Ventricular tachycardia (VT) radiofrequency ablation has been associated with reduced VT recurrence and mortality, although it is typically not considered among New York Heart Association class IV (NYHA IV) heart failure patients. We compared characteristics and VT radiofrequency ablation outcomes of those with and without NYHA IV in the International VT Ablation Center Collaboration. METHODS AND RESULTS: NYHA II-IV patients undergoing VT radiofrequency ablation at 12 international centers were included. Clinical variables, VT recurrence, and mortality were analyzed by NYHA IV status using Kaplan-Meier analysis and Cox proportional hazard models. There were significant differences between NYHA IV (n=111) and NYHA II and III (n=1254) patients: NYHA IV had lower left ventricular ejection fraction; more had diabetes mellitus, kidney disease, cardiac resynchronization implantable cardioverter-defibrillator, and VT storm despite greater antiarrhythmic drug use (P<0.01). NYHA IV subjects required more hemodynamic support, were inducible for more and slower VTs, and were less likely to undergo final programmed stimulation. There was no significant difference in acute complications. In-hospital deaths, recurrent VT, and 1-year mortality were higher in the NYHA IV group, in the context of greater baseline comorbidities. Importantly, NYHA IV patients without recurrent VT had similar survival compared with NYHA II and III patients with recurrent VT (68% versus 73%). Early VT recurrence (≤30 days) was significantly associated with mortality, especially in NYHA IV patients. CONCLUSIONS: Despite greater baseline comorbidities, VT radiofrequency ablation can be safely performed among NYHA IV patients. Early VT recurrence is significantly associated with subsequent mortality regardless of NYHA status. Elimination of recurrent VT in NYHA IV patients may reduce mortality to a level comparable to NYHA II and III with arrhythmia recurrence.

Freedom from recurrent ventricular tachycardia after catheter ablation is associated with improved survival in patients with structural heart disease: An International VT Ablation Center Collaborative Group study.

BACKGROUND: The impact of catheter ablation of ventricular tachycardia (VT) on all-cause mortality remains unknown. OBJECTIVE: The purpose of this study was to examine the association between VT recurrence after ablation and survival in patients with scar-related VT. METHODS: Analysis of 2061 patients with structural heart disease referred for catheter ablation of scar-related VT from 12 international centers was performed. Data on clinical and procedural variables, VT recurrence, and mortality were analyzed. Kaplan-Meier analysis was used to estimate freedom from recurrent VT, transplant, and death. Cox proportional hazards frailty models were used to analyze the effect of risk factors on VT recurrence and mortality. RESULTS: One-year freedom from VT recurrence was 70% (72% in ischemic and 68% in nonischemic cardiomyopathy). Fifty-seven patients (3%) underwent cardiac transplantation, and 216 (10%) died during follow-up. At 1 year, the estimated rate of transplant and/or mortality was 15% (same for ischemic and nonischemic cardiomyopathy). Transplant-free survival was significantly higher in patients without VT recurrence than in those with recurrence (90% vs 71%, P<.001). In multivariable analysis, recurrence of VT after ablation showed the highest risk for transplant and/or mortality [hazard ratio 6.9 (95% CI 5.3-9.0), P<.001]. In patients with ejection fraction <30% and across all New York Heart Association functional classes, improved transplant-free survival was seen in those without VT recurrence. CONCLUSION: Catheter ablation of VT in patients with structural heart disease results in 70% freedom from VT recurrence, with an overall transplant and/or mortality rate of 15% at 1 year. Freedom from VT recurrence is associated with improved transplant-free survival, independent of heart failure severity.

Global and Regional Myocardial Innervation Before and After Ablation of Drug-Refractory Ventricular Tachycardia Assessed with 123I-MIBG.

UNLABELLED: Cardiac innervation is a critical component of ventricular arrhythmogenesis that can be noninvasively assessed with (123)I-MIBG. However, the effect of ventricular tachycardia (VT) ablation on global and regional left ventricular sympathetic innervation and clinical outcomes has not been previously assessed. METHODS: In this prospective, single-center feasibility study, 13 patients with cardiomyopathy (n = 9 ischemic, n = 4 nonischemic) who were scheduled to undergo ablation of drug-refractory VT underwent 15-min and 4-h (123)I-MIBG scans before and 6 mo after the ablation procedure. Planar and arrhythmia-specific 757-segment analysis of short-axis SPECT images was performed in all datasets. RESULTS: Global innervation assessed with heart-to-mediastinal ratio and washout rates was preserved in all patients at baseline (1.8 [continuous variables are expressed as median and quartile: Q1-Q3, 1.7-2.4] and 54% [Q1-Q3, 47%-67%]) and did not change significantly at the 6-mo follow-up (1.9 [Q1-Q3, 1.6-2.2], P = 0.9; and 56% [Q1-Q3, 41%-62%], P = 0.6). However, segmental analysis demonstrated that ischemic patients had larger areas of abnormal innervation at baseline (52.1% vs. 19.6%, P = 0.011) and at the 6-mo follow-up (56.7% vs. 27.5%, P = 0.011) than the nonischemic patients. Innervation defects affected 40% of the inferior segments in all ischemic cardiomyopathy patients, whereas they affected only 10% of inferior segments in 75% of nonischemic patients. When segmental data were further analyzed in denervated (DZ), transition (TZ), and normal (NZ) zones, there were changes in these designated innervation categories from baseline to the 6-mo follow-up for ischemic (19% DZ, 59% TZ, 22% NZ) and nonischemic (6% DZ, 45% TZ, 15% NZ) patients. In ischemic patients, relative changes were significantly greater in the TZ segments than in the DZ, which demonstrated the second highest proportional changes (P = 0.028). Receiver operating characteristic curves defined best cutoffs of DZ, TZ, and NZ as less than 30.5%, 30.6%-47.1%, and more than 47.1%, respectively. CONCLUSION: Patients with ischemic cardiomyopathy have larger areas of abnormal innervation than those with nonischemic cardiomyopathy. Although VT ablation did not change global innervation, a novel arrhythmia-specific segmental analysis demonstrated significant dynamic changes in innervation categories and allowed quantitative definitions of DZ, TZ, and NZ. These findings provide novel insights into the mechanics of sympathetic innervation in patients undergoing VT ablation and may have diagnostic and therapeutic implications.

Atrial fibrillation ablation in the era of cryoballoon and force-sensing catheters: freeze or burn?

OPINION STATEMENT: Atrial fibrillation can adversely affect the quality of life for many patients. Though antiarrhythmic drug therapy remains an option for the treatment of atrial fibrillation, the drugs are associated with numerous side effects. Atrial fibrillation ablation has been shown to be as efficacious as antiarrhythmic drug therapy. The field of atrial fibrillation ablations has evolved over time from utilizing radiofrequency energy to using cryoenergy. Newer technologies are being developed with efforts to improve outcomes in patients undergoing atrial fibrillation ablations. This article will highlight two such technologies: cryoballoon ablation catheters and contact force-sensing catheters. These novel catheters appear to be further revolutionizing this young field in electrophysiology.

Three-dimensional 123I-meta-iodobenzylguanidine cardiac innervation maps to assess substrate and successful ablation sites for ventricular tachycardia: feasibility study for a novel paradigm of innervation imaging.

BACKGROUND: Innervation is a critical component of arrhythmogenesis and may present an important trigger/substrate modifier not used in current ventricular tachycardia (VT) ablation strategies. METHODS AND RESULTS: Fifteen patients referred for ischemic VT ablation underwent preprocedural cardiac (123)I- meta-iodobenzylguanidine ((123)I-mIBG) imaging, which was used to create 3-dimensional (3D) innervation models and registered to high-density voltage maps. 3D (123)I-mIBG innervation maps demonstrated areas of complete denervation and (123)I-mIBG transition zone in all patients, which corresponded to 0% to 31% and 32% to 52% uptake. (123)I-mIBG denervated areas were ≈2.5-fold larger than bipolar voltage-defined scar (median, 24.6% [Q1-Q3, 18.3%-34.4%] versus 10.6% [Q1-Q3, 3.9%-16.4%]; P<0.001) and included the inferior wall in all patients, with no difference in the transition/border zone (11.4% [Q1-Q3, 9.5%-13.2%] versus 16.6% [Q1-Q3, 12.0%-18.8%]; P=0.07). Bipolar/unipolar voltages varied widely within areas of denervation (0.8 mV [Q1-Q3, 0.3-1.7 mV] and 4.0 mV [Q1-Q3, 2.9-5.6 mV]) and (123)I-mIBG transition zones (0.8 mV [Q1-Q3, 0.4-1.8 mV] and 4.6 mV [Q1-Q3, 3.2-6.3 mV]). Bipolar voltages in denervated areas and (123)I-mIBG transition zones were <0.5 mV, 0.5 to 1.5 mV, and >1.5 mV in 35%, 36%, and 29%, as well as 35%, 35%, and 30%, respectively (P>0.05). Successful ablation sites were within bipolar voltage-defined scar (7%), border zone (57%), and areas of normal voltage (36%), but all ablation sites were abnormally innervated (denervation/(123)I-mIBG transition zone in 50% each). CONCLUSIONS: (123)I-mIBG innervation defects are larger than bipolar voltage-defined scar and cannot be detected with standard voltage criteria. Thirty-six percent of successful VT ablation sites demonstrated normal voltages (>1.5 mV), but all ablation sites were within the areas of abnormal innervation. (123)I-mIBG innervation maps may provide critical information about triggers/substrate modifiers and could improve understanding of VT substrate and facilitate VT ablation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01250912.

Differences in quantitative assessment of myocardial scar and gray zone by LGE-CMR imaging using established gray zone protocols.

Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging is the gold standard for myocardial scar evaluation. Heterogeneous areas of scar ('gray zone'), may serve as arrhythmogenic substrate. Various gray zone protocols have been correlated to clinical outcomes and ventricular tachycardia channels. This study assessed the quantitative differences in gray zone and scar core sizes as defined by previously validated signal intensity (SI) threshold algorithms. High quality LGE-CMR images performed in 41 cardiomyopathy patients [ischemic (33) or non-ischemic (8)] were analyzed using previously validated SI threshold methods [Full Width at Half Maximum (FWHM), n-standard deviation (NSD) and modified-FWHM]. Myocardial scar was defined as scar core and gray zone using SI thresholds based on these methods. Scar core, gray zone and total scar sizes were then computed and compared among these models. The median gray zone mass was 2-3 times larger with FWHM (15 g, IQR: 8-26 g) compared to NSD or modified-FWHM (5 g, IQR: 3-9 g; and 8 g. IQR: 6-12 g respectively, p < 0.001). Conversely, infarct core mass was 2.3 times larger with NSD (30 g, IQR: 17-53 g) versus FWHM and modified-FWHM (13 g, IQR: 7-23 g, p < 0.001). The gray zone extent (percentage of total scar that was gray zone) also varied significantly among the three methods, 51 % (IQR: 42-61 %), 17 % (IQR: 11-21 %) versus 38 % (IQR: 33-43 %) for FWHM, NSD and modified-FWHM respectively (p < 0.001). Considerable variability exists among the current methods for MRI defined gray zone and scar core. Infarct core and total myocardial scar mass also differ using these methods. Further evaluation of the most accurate quantification method is needed.

Impact of ICD artifact burden on late gadolinium enhancement cardiac MR imaging in patients undergoing ventricular tachycardia ablation.

BACKGROUND: Cardiac magnetic resonance imaging (CMRI) is the gold standard for myocardial scar evaluation. Although ideal for substrate assessment in ventricular tachycardia (VT), most patients have an implantable cardioverter-defibrillator (ICD) at presentation for ablation. This study evaluates the ICD artifact burden during standard late gadolinium enhancement CMRI (LGE-CMRI) evaluation of myocardial scar in VT patients with ICDs. METHODS: Thirty-one patients with ICD and cardiomyopathy underwent LGE-CMRI using 1.5-T magnetic resonance scanner before VT ablation. Using the American Heart Association (AHA) 17-segment model, short-axis LGE series were analyzed for artifact burden localization and assessment. RESULTS: Preablation CMRI was performed in 31 patients with single chamber (n = 13), dual chamber (n = 11), and biventricular (n = 7) ICDs. Pre- and post-MRI ICD parameters were unchanged. All patients had susceptibility artifact and 51.6% (256 of 496) of segments were affected by artifact. The artifact area (178 ± 136 cm(2) ) resulted in an artifact burden of 54 ± 21% of the LV myocardial area (327 ± 15 cm(2) ). The anterior wall was most affected by artifact (89%) compared with 52%, 49%, and 23% in the lateral, septal, and inferior walls, respectively (P < 0.0001). The apical segments had more artifact burden (66%) than the mid (49%) and basal (44%) segments (P = 0.0005). Artifact area correlated with ICD-heart distance on anteroposterior chest radiograph (r = 0.42, P = 0.021) and body mass index (r = -0.48, P = 0.008). CONCLUSIONS: Current clinical LGE-CMRI scar imaging protocols produce ICD artifacts that affect >50% of the LV myocardium and correlate with the ICD-heart distance. This significantly limits the application of CMRI for image-guided VT ablation.

Safety of computed tomography in patients with cardiac rhythm management devices: assessment of the U.S. Food and Drug Administration advisory in clinical practice.

OBJECTIVES: To assess the safety of computed tomography (CT) imaging in patients with cardiac rhythm management (CRM) devices, which was subject to an advisory from the U.S. Food and Drug Administration (FDA) in 2008. BACKGROUND: The FDA warned about potential interference of CT imaging with CRM devices and made recommendations for clinical practice despite only limited evidence. METHODS: All 516 CT scans that involved direct radiation exposure of CRM devices (332 defibrillators, 184 pacemakers) at 2 large-volume centers between July 2000 and May 2010 were included. The primary outcome was a composite endpoint of death, bradycardia or tachycardia requiring termination of the scan or an immediate intervention, unplanned hospital admission, reprogramming of the device, inappropriate defibrillator shocks, or device replacement/revision thought to be due to CT imaging. Significant changes in device parameters were sought as a secondary outcome (control group 4:1 ratio). RESULTS: The main finding was that none of the CTs were associated with the primary outcome. With serial device interrogations, there were no differences in changes in battery voltage or lead parameters between devices exposed to radiation and their controls. Potentially significant changes in device parameters were observed in a small group of devices (both the CT group and control group), but no definitive link to CT was confirmed, and there were no associated clinical consequences. CONCLUSIONS: The findings suggest that the presence of CRM devices should not delay or result in cancellation of clinically indicated CT imaging procedures, and provide evidence that would be helpful when the FDA advisory is re-evaluated.

Cardiac sarcoidosis: electrophysiological outcomes on long-term follow-up and the role of the implantable cardioverter-defibrillator.

OBJECTIVES: The objectives of this study were to identify the predictors of life-threatening ventricular arrhythmias in patients with cardiac sarcoidosis (CS) and to evaluate the role of the implantable cardioverter-defibrillator (ICD) in this patient population. BACKGROUND: ICD implantation is a class IIA recommendation for patients with CS. However, some indications for ICD implantation in CS patients are still unclear and not enough data are available to establish predictors of malignant ventricular tachyarrhythmias in this group of patients. METHODS: We retrospectively identified all consecutive patients who were diagnosed with CS, during the period from March 2002 to April 2010. Cardiac rhythm devices were regularly interrogated and clinical data recorded during follow-up visits. RESULTS: Thirty-three patients (17 male) with CS were identified. The mean age was 53 ± 11. The mean left ventricular ejection fraction (LVEF) was 41 ± 18%. Thirty patients received an ICD. Twelve patients (36.3%) had sustained ventricular arrhythmias. Eleven patients received appropriate therapies and 9 patients received inappropriate shocks, representing 36.7% and 30.0% of the ICD population, respectively. Patients who received appropriate ICD therapies were younger with mean age 47.4 ± 7.8, and had a lower mean LVEF 33.0 ± 12.0 compared to those who did not receive ICD therapies (P = 0.0301 and 0.0341, respectively). There were no other demographic, clinical, electrocardiographic, electrophysiological, or imaging markers that predicted the future occurrence of appropriate ICD therapies in our cohort of patients. CONCLUSIONS: CS is strongly associated with malignant ventricular arrhythmias. No specific predictors of such tachyarrhythmias emerged, other than young age and low LVEF.

Impact of fluoroscopy unit on the accuracy of a magnet-based electroanatomic mapping and navigation system: an in vitro and in vivo validation study.

INTRODUCTION: During mapping and ablation procedures, the movement of large ferromagnetic items (i.e., fluoroscopic equipment) introduce heterogeneities in the electromagnetic field, which may affect the accuracy of electromagnet-based navigation. We aimed to assess the impact of common periprocedural fluoroscopic equipment movement on the accuracy of an electromagnet-based navigation system. METHODS AND RESULTS: The impact of fluoroscopic equipment movement on the accuracy of the Carto® 3 System (Biosense Webster, Inc., Diamond Bar, CA, USA) was assessed both in vitro (n = 20 patients, phantom model) and in vivo (n = 18 patients). Location recordings were obtained with unchanged catheter position for fluoroscopic equipment rotational movements (RMs) and maximal to closest distance (MD to CD) to phantom/patient. The effects of both single- and biplane fluoroscopy were assessed. In vitro, the movement of fluoroscopic equipment resulted in an average catheter location estimation error of 0.8 mm (interquartile range 0.3-1.3). The maximal location estimation errors with MD to CD movement and RM were 2.3 mm and 1.3 mm, respectively. Changing from single-plane to biplane setup resulted in an average location estimation change of 1.5 mm (maximum 2.1). Larger location changes were observed in vivo (2.9 mm vs 0.8 mm, P < 0.0001) with 28.7% of these exceeded 4 mm versus none of the in vitro measurements (P < 0.0001). CONCLUSION: Although fluoroscopy manipulation affected the accuracy of the Carto® 3 System, the in vitro data suggest that these inaccuracies are likely of limited clinical consequences. The larger in vivo inaccuracies are most likely due to nonferromagnetic interferences, such as respiratory or cardiac movements.

Assessment of ventricular tachycardia scar substrate by intracardiac echocardiography.

BACKGROUND: Intracardiac echocardiography (ICE) is increasingly used to guide complex ablation procedures. This study aimed to assess the scar substrate of ventricular tachycardia (VT) by ICE in patients undergoing VT ablation. METHODS: In 22 patients undergoing VT ablation (10 ischemic, 12 nonischemic), the Biosense CARTOSOUND module (Biosense Webster, Diamond Bar, CA, USA) was used for three-dimensional reconstruction of the ventricles. The characteristics and appearance with ICE imaging of voltage-defined scar zones (bipolar voltage <0.5 mV), border zones (0.5-1.5 mV), and normal myocardium (>1.5 mV) on electroanatomic maps were evaluated. The standard image analysis software Image J (National Institutes of Health, Bethesda, MD, USA) was used to analyze signal intensity (mean pixel signal intensity unit [SIU]) and heterogeneity (standard deviation of signal intensity in analyzed area) on ICE images. RESULTS: A total of 83 myocardial areas were analyzed from two-dimensional ICE images (15 scars, 31 border zones, and 37 normal). Voltage-defined scar zones had increased signal intensities compared to border zones (149 SIU vs 104 SIU, P < 0.0001) and normal myocardium (88 SIU, P < 0.0001). Border zones were more likely to have heterogeneous densities compared to normal myocardium (standard deviation of signal intensity 20 SIU vs 12 SIU, P < 0.0001). In receiver-operator characteristic analyses, signal intensity ≥ 137 SIU differentiated scar from nonscar zones (area under curve 0.91, P < 0.0001). Software-based color enhancement of areas with signal intensity ≥ 137 SIU allowed identification of the VT substrate in all 15 patients with voltage-defined scar zones. CONCLUSIONS: ICE provides important information about the VT anatomical substrate and may have potential to identify areas of scarred myocardium.

I passed out: now what?: general approach to the patient with syncope.

Syncope is the transient loss of consciousness and postural tone caused by transient cerebral hypoperfusion. It is a common problem that is often alarming to patients and their families. The differential diagnosis of the patient with transient loss of consciousness is broad and workup may be expensive. It is important to identify patients with life-threatening conditions and those with red flags indicating an increased risk of sudden death. An initial approach consisting of a careful history, physical examination, and electrocardiograms is essential. This review covers the general diagnostic approach to the patient with syncope.

MRI-Guided ventricular tachycardia ablation: integration of late gadolinium-enhanced 3D scar in patients with implantable cardioverter-defibrillators.

BACKGROUND: Substrate-guided ablation of ventricular tachycardia (VT) in patients with implanted cardioverter-defibrillators (ICDs) relies on voltage mapping to define the scar and border zone. An integrated 3D scar reconstruction from late gadolinium enhancement (LGE) MRI could facilitate VT ablations. METHODS AND RESULTS: Twenty-two patients with ICD underwent contrast-enhanced cardiac MRI with a specific absorption rate of <2.0 W/kg before VT ablation. Device interrogation demonstrated unchanged ICD parameters immediately before, after, or at 68±21 days follow-up (P>0.05). ICD imaging artifacts were most prominent in the anterior wall and allowed full and partial assessment of LGE in 9±4 and 12±3 of 17 segments, respectively. In 14 patients with LGE, a 3D scar model was reconstructed and successfully registered with the clinical mapping system (accuracy, 3.9±1.8 mm). Using receiver operating characteristic curves, bipolar and unipolar voltages of 1.49 and 4.46 mV correlated best with endocardial MRI scar. Scar visualization allowed the elimination of falsely low voltage recordings (suboptimal catheter contact) in 4.1±1.9% of <1.5-mV mapping points. Display of scar border zone allowed identification of excellent pace mapping sites, with only limited voltage mapping in 64% of patients. Viable endocardium of >2 mm resulted in >1.5-mV voltage recordings despite up to 63% transmural midmyocardial scar successfully ablated with MRI guidance. All successful ablation sites demonstrated LGE (transmurality, 68±26%) and were located within 10 mm of transition zones to 0% to 25% scar in 71%. CONCLUSIONS: Contrast-enhanced cardiac MRI can be safely performed in selected patients with ICDs and allows the integration of detailed 3D scar maps into clinical mapping systems, providing supplementary anatomic guidance to facilitate substrate-guided VT ablations.

Defibrillation threshold testing in patients with hypertrophic cardiomyopathy.

INTRODUCTION: Implantable cardioverter-defibrillators (ICDs) decrease sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). One of the vital aspects of ICD implantation is the demonstration that the myocardium can be reliably defibrillated, which is defined by the defibrillation threshold (DFT). We hypothesized that patients with HCM have higher DFTs than patients implanted for other standard indications. METHODS: We retrospectively reviewed the medical records of patients implanted with an ICD at the University of Maryland from 1996 to 2008. All patients with HCM who had DFTs determined were included. Data were compared to selected patients implanted for other standard indications over the same time period. All patients had a dual-coil lead with an active pectoral can system and had full DFT testing using either a step-down or binary search protocol. RESULTS: The study group consisted of 23 HCM patients. The comparison group consisted of 294 patients. As expected, the HCM patients were younger (49 ± 18 years vs 63 ± 12 years; P < 0.00001) and had higher left ventricular ejection fractions (66% vs 32%; P < 0.000001). The average DFT in the HCM group was 13.9 ± 7.0 Joules (J) versus 9.8 ± 5.1 J in the comparison group (P = 0.0004). In the HCM group, five of the 23 patients (22%) had a DFT ≥ 20 J compared to 19 of 294 comparison patients (6%). There was a significant correlation between DFT and left ventricle wall thickness in the HCM group as measured by echocardiography (r = 0.44; P = 0.03); however, there was no correlation between DFT and QRS width in the HCM group (r = 0.1; P = NS). CONCLUSIONS: Our results suggest that patients with HCM have higher DFTs than patients implanted with ICDs for other indications. More importantly, a higher percentage of HCM patients have DFTs ≥ 20 J and the DFT increases with increasing left ventricle wall thickness. These data suggest that DFT testing should always be considered after implanting ICDs in HCM patients.

Pacemaker/implantable cardioverter-defibrillator interaction.

We describe a case of pacemaker/implantable cardioverter-defibrillator (ICD) interaction in a single system causing failure to detect induced ventricular fibrillation (VF) in an 83-year-old man with ischemic cardiomyopathy. He underwent an ICD generator replacement due to battery depletion. In addition, a right atrial lead was placed to treat symptomatic bradycardia. Appropriate sensing and pacing parameters were observed in both leads during implant, and there was no cross-talk between the leads. A defibrillation threshold (DFT) test was performed (sense 1.5 mV, shock on T) with induction of VF that was not detected by the device, ultimately requiring an external defibrillation to terminate the arrhythmia. The device printout during testing showed atrial/ventricular lead cross-talk caused by the 1.1-J shock to induce VF, sensed beats in the noise window activating the noise suppression algorithm and preventing initial VF detection, and recurrent resetting of the automatic gain control due to ventricular sensing of the atrial pacing artifact preventing detection and perpetuating atrioventricular (AV) pacing at a rate of 60 bpm. In conclusion, pacemaker/ICD interaction can occur in a dual-chamber ICD system. This can be prevented by programming a shorter AV delay, increasing sensitivity (i.e., more sensitive value), and programming a pause before initiating pacing after an ICD discharge.

Left-sided atrial flutter originating in the coronary sinus after radiofrequency ablation of atrial fibrillation.

We describe a case of atypical atrial flutter presenting 1 year after radiofrequency ablation for atrial fibrillation (AF). Electrophysiologic study showed a reentry circuit involving the inferolateral aspect of the mitral annulus and the coronary sinus (CS); however, a mitral isthmus line did not terminate the arrhythmia. Participation of the proximal CS musculature in the circuit suggested a possible target for ablation. Radiofrequency energy applications from within the CS terminated the tachycardia. Mapping and ablation within the CS should be considered in patients with post-AF ablation arrhythmias, particularly when the mitral annulus appears to be involved in the tachycardia circuit.

Early improvement in cardiac tissue perfusion due to mesenchymal stem cells.

The underlying mechanism(s) of improved left ventricular function (LV) due to mesenchymal stem cell (MSC) administration after myocardial infarction (MI) remains highly controversial. Myocardial regeneration and neovascularization, which leads to increased tissue perfusion, are proposed mechanisms. Here we demonstrate that delivery of MSCs 3 days after MI increased tissue perfusion in a manner that preceded improved LV function in a porcine model. MI was induced in pigs by 60-min occlusion of the left anterior descending coronary artery, followed by reperfusion. Pigs were assigned to receive intramyocardial injection of allogeneic MSCs (200 million, approximately 15 injections) (n = 10), placebo (n = 6), or no intervention (n = 8). Resting myocardial blood flow (MBF) was serially assessed by first-pass perfusion magnetic resonance imaging (MRI) over an 8-wk period. Over the first week, resting MBF in the infarct area of MSC-treated pigs increased compared with placebo-injected and untreated animals [0.17 +/- 0.03, 0.09 +/- 0.01, and 0.08 +/- 0.01, respectively, signal intensity ratio of MI to left ventricular blood pool (LVBP); P < 0.01 vs. placebo, P < 0.01 vs. nontreated]. In contrast, the signal intensity ratios of the three groups were indistinguishable at weeks 4 and 8. However, MSC-treated animals showed larger, more mature vessels and less apoptosis in the infarct zones and improved regional and global LV function at week 8. Together these findings suggest that an early increase in tissue perfusion precedes improvements in LV function and a reduction in apoptosis in MSC-treated hearts. Cardiac MRI-based measures of blood flow may be a useful tool to predict a successful myocardial regenerative process after MSC treatment.

Chronic allopurinol administration ameliorates maladaptive alterations in Ca2+ cycling proteins and beta-adrenergic hyporesponsiveness in heart failure.

Xanthine oxidase (XO) activity contributes to both abnormal excitation-contraction (EC) coupling and cardiac remodeling in heart failure (HF). beta-Adrenergic hyporesponsiveness and abnormalities in Ca(2+) cycling proteins are mechanistically linked features of the HF phenotype. Accordingly, we hypothesized that XO influences beta-adrenergic responsiveness and expression of genes whose products participate in deranged EC coupling. We measured inotropic (dP/dt(max)), lusitropic (tau), and vascular (elastance; E(a)) responses to beta-adrenergic (beta-AR) stimulation with dobutamine in conscious dogs administered allopurinol (100 mg po daily) or placebo during a 4-wk induction of pacing HF. With HF induction, the decreases in both baseline and dobutamine-stimulated inotropic responses were offset by allopurinol. Additionally, allopurinol converted a vasoconstrictor effect to dobutamine to a vasodilator response and enhanced both lusitropic and preload reducing effects. To assess molecular correlates for this phenotype, we measured myocardial sarcoplasmic reticulum Ca(2+)-ATPase 2a (SERCA), phospholamban (PLB), phosphorylated PLB (P-PLB), and Na(+)/Ca(2+) transporter (NCX) gene expression and protein. Although SERCA mRNA and protein concentrations did not change with HF, both PLB and NCX were upregulated (P < 0.05). Additionally, P-PLB and protein kinase A activity were greatly reduced. Allopurinol ameliorated all of these molecular alterations and preserved the PLB-to-SERCA ratio. Preventing maladaptive alterations of Ca(2+) cycling proteins represents a novel mechanism for XO inhibition-mediated preservation of cardiac function in HF, raising the possibility that anti-oxidant therapies for HF may ameliorate transcriptional changes associated with adverse cardiac remodeling and beta-adrenergic hyporesponsiveness.