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IntroductionCatheter ablation of persistent AF has not been consistently successful in terminating AF or preventing arrhythmia recurrences. Non-invasive Electrocardiographic Imaging (ECGI) can help to understand recurrences by mapping the mechanisms of pre-ablation AF and comparing them with the patterns of recurrent arrhythmias in the same patient.MethodsSeventeen persistent AF patients underwent ECGI before their first catheter ablation. Time-domain activation maps and phase progression maps were obtained on the bi-atrial epicardium. Location of arrhythmogenic drivers were annotated on the bi-atrial anatomy. Activation and phase movies were examined to understand the wavefront dynamics during AF. Eight patients recurred within 12 months of ablation and underwent a follow-up ECGI. Driver locations and movies were compared for pre- and post-ablation AF.ResultsA total of 243 focal drivers were mapped during pre-ablation AF. 62% of the drivers were mapped in the left atrium (LA). The pulmonary vein region harbored most of the drivers (43%). 35% of the drivers were mapped in the right atrium (RA). 59% (10/17) and 53% (9/17) of patients had repetitive sources in the left pulmonary veins (LPV) and left atrial appendage (LAA), and the lower half of RA, respectively. All patients had focal drivers. 29% (5/17) of patients had macro-reentry waves. 24% (4/17) of patients had rotors. Activation patterns during persistent AF varied from single macro-reentry to complex activity with multiple simultaneous wavefronts in both atria, resulting in frequent wave collisions. A total of 76 focal driver activities were mapped in 7/8 patients during recurrence. 59% of the post-ablation AF drivers were mapped in the LA. The pulmonary vein region harbored 50% of total drivers. 39% of sources were mapped in the RA. AF complexity remained similar post-ablation. 58% (44/76) of pre-ablation sources persisted during recurrence. 38% (3/8) of patients had macro-reentry and one patient had rotors.ConclusionECGI provides patient-specific information on mechanisms of persistent AF and recurrent arrhythmia. More than half pre-ablation sources repeated during post-ablation recurrence. This study provides direct evidence for drivers that persist days and months after the ablation procedure. Patient-tailored bi-atrial ablation is needed to successfully target persistent AF and prevent recurrence. ECGI can potentially predict recurrence and assist in choice of therapy.

Introduction Point-by-point 3-dimensional (3D) electroanatomic mapping (EAM) is used to guide catheter ablation of premature ventricular complexes (PVCs). Due to the differences in the spatial excursion of the cardiac chambers during cardiac cycles in PVCs vs sinus rhythm, the 3D location registration during PVCs is shifted relative to sinus rhythm. In this study, we describe our strategy to adjust for this displacement in real-time during PVC mapping. Methods and results We report 21 patients who underwent catheter ablation of 23 unique PVCs using Carto 3. After mapping the earliest site for each PVC, we reregistered its 3D location to a sinus rhythm beat in real-time, and used this to guide ablation lesion delivery. The PVC earliest location was spatially displaced from the successful ablation lesion in sinus rhythm by average 6.7 (range 3.3-13.0) mm. Offline, we subsequently analyzed 25 unique chamber maps and 606 PVC points. For each point, we reregistered the 3D location to a preceding sinus beat. The PVC points were displaced from sinus rhythm location by average 4.4 (0.3-13.7) mm. The maximally displaced point for each chamber was 7.7 (4.7-13.7) mm. The general direction of shift during PVC was leftward and inferior relative to sinus rhythm. Conclusions During electroanatomic mapping of PVCs using the Carto 3 system, points mapped during PVCs are spatially displaced relative to their location in sinus rhythm. Electrophysiologists should recognize this phenomenon and account for the shift to guide accurate delivery of ablation lesions.

Introduction: Guidelines favor patient selection by left bundle branch block (LBBB) with QRS width ≥150 ms for cardiac resynchronization therapy (CRT). Predicting CRT response in patients with QRS width 120 to 149 ms or non-LBBB remains difficult. Left ventricular (LV) global longitudinal strain (GLS) and systolic stretch index (SSI) have shown to characterize the ventricular substrate responsive to CRT. However, the potential application of longitudinal left atrial (LA) strain remains unclear. Hypothesis: Baseline LA strain has prognostic value in CRT patients with intermediate ECG criteria. Methods: We studied 195 patients who underwent CRT based on routine indications: ejection fraction ≤35% and QRS width ≥120 ms. GLS was assessed using the 3 standard apical views. Radial SSI was derived from the mid LV short axis view. Peak longitudinal LA strain was derived from the 2 and 4-chamber apical view. The predefined combined clinical endpoint was death, heart transplant or left ventricular assist device over 4 years after CRT. Results: LA strain was feasible in 162 (83%) of the CRT candidates: QRS duration 156 ± 26 ms, 39.5% had LBBB with QRS ≥ 150ms, 60.5% had intermediate ECG criteria. High peak longitudinal strain (>median, 10.1%) was associated with favorable event-free survival (pmedian, 8.4%) had similar outcome to those with Class I indications for CRT. Multivariable analysis revealed that LA strain had independent prognostic value (hazard ratio 0.9 per LA strain %, p < 0.001) even after adjusted for other clinical, electrophysiological and echocardiographic covariates including QRS morphology and duration, GLS and SSI. Conclusions: Peak LA strain had important prognostic value in candidates for CRT. Prognostic value of LA strain was additive to LV strain characteristics and most significant in CRT patients with intermediate ECG criteria for CRT.

Background Guidelines favor patient selection by left bundle branch block (LBBB) with QRS width ≥150 ms for cardiac resynchronization therapy (CRT). However, predicting response to CRT patients with QRS width 120 to 149 ms or non-LBBB remains difficult. Speckle tracking left atrial (LA) strain is a novel means to assess cardiac function, however its applications to CRT patients remains unclear. Purpose To test the hypothesis that baseline LA strain has prognostic value in CRT patients with intermediate ECG criteria. Methods We studied 195 patients with heart failure (HF) who underwent CRT based on routine indications: ejection fraction ≤35% and QRS width ≥120 ms. GLS was assessed using the 3 standard apical views. LA longitudinal strain was based on 12 segments from the 2 and 4-chamber apical view. Peak LA strain, a measure associated with the reservoir function of the LA, was defined as the average of peak longitudinal strain from all segments. The predefined combined clinical endpoint was death, heart transplant or left ventricular assist device (LVAD) over 4 years after CRT. Results LA strain was feasible in 162 (83%) of the candidates for CRT: age 64±11 years, 72% male, QRS duration 156±26 ms, 39.5% had LBBB with QRS ≥150ms, 60.5% had intermediate ECG criteria. Median LA strain was 11.0% [1.3% - 36.8%]. High LA peak strain was associated with more favorable event-free survival and Low LA Peak strain was associated with worse clinical outcome following CRT (FIGURE, p Conclusions Baseline peak LA strain had important prognostic value in HF patients who are candidates for CRT. Prognostic value of LA strain was most significant in CRT patients with intermediate ECG criteria (QRS 120 to 149ms or non-LBBB) and has promise for clinical applications. LA strain and clinical outcome after CRT Funding Acknowledgement Type of funding source: None

Familial hypercholesterolaemia (FH) is a dominant and highly penetrant monogenic disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL)-cholesterol concentration and, if untreated, leads to premature atherosclerosis and coronary artery disease (CAD). There are approximately 100,000 people with FH in Australia. However, an overwhelming majority of those affected remain undetected and inadequately treated, consistent with FH being a leading challenge for public health genomics. To further address the unmet need, we provide an updated guidance, presented as a series of systematically collated recommendations, on the care of patients and families with FH. These recommendations have been informed by an exponential growth in published works and new evidence over the last 5 years and are compatible with a contemporary global call to action on FH. Recommendations are given on the detection, diagnosis, assessment and management of FH in adults and children. Recommendations are also made on genetic testing and risk notification of biological relatives who should undergo cascade testing for FH. Guidance on management is based on the concepts of risk re-stratification, adherence to heart healthy lifestyles, treatment of non-cholesterol risk factors, and safe and appropriate use of LDL-cholesterol lowering therapies, including statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors and lipoprotein apheresis. Broad recommendations are also provided for the organisation and development of health care services. Recommendations on best practice need to be underpinned by good clinical judgment and shared decision making with patients and families. Models of care for FH need to be adapted to local and regional health care needs and available resources. A comprehensive and realistic implementation strategy, informed by further research, including assessments of cost-benefit, will be required to ensure that this new guidance benefits all Australian families with or at risk of FH.

Background: Case studies have suggested the efficacy of catheter-free, electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia (VT) using stereotactic body radiation therapy, although prospective data are lacking. Methods: We conducted a prospective phase I/II trial of noninvasive cardiac radioablation in adults with treatment-refractory episodes of VT or cardiomyopathy related to premature ventricular contractions (PVCs). Arrhythmogenic scar regions were targeted by combining noninvasive anatomic and electric cardiac imaging with a standard stereotactic body radiation therapy workflow followed by delivery of a single fraction of 25 Gy to the target. The primary safety end point was treatment-related serious adverse events in the first 90 days. The primary efficacy end point was any reduction in VT episodes (tracked by indwelling implantable cardioverter defibrillators) or any reduction in PVC burden (as measured by a 24-hour Holter monitor) comparing the 6 months before and after treatment (with a 6-week blanking window after treatment). Health-related quality of life was assessed using the Short Form-36 questionnaire. Results: Nineteen patients were enrolled (17 for VT, 2 for PVC cardiomyopathy). Median noninvasive ablation time was 15.3 minutes (range, 5.4–32.3). In the first 90 days, 2/19 patients (10.5%) developed a treatment-related serious adverse event. The median number of VT episodes was reduced from 119 (range, 4–292) to 3 (range, 0–31; P P =0.008). Quality of life improved in 5 of 9 Short Form-36 domains at 6 months. Conclusions: Noninvasive electrophysiology-guided cardiac radioablation is associated with markedly reduced ventricular arrhythmia burden with modest short-term risks, reduction in antiarrhythmic drug use, and improvement in quality of life. Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02919618.

Learning objectives Cardiac resynchronisation therapy (CRT) is an established treatment for heart failure patients with left ventricular dysfunction complicated by left ventricular (LV) conduction delay. In patients who are candidates for CRT, the LV stroke volume is diminished both by cardiomyopathy and by a dyssynchronous contraction pattern caused by conduction delay (figure 1). Left bundle branch block (LBBB) is the category of LV conduction delay in cardiomyopathy patients where CRT is most effective as a therapy. Although other patterns of LV conduction delay may also respond to CRT, the pathophysiology of dyssynchrony tied to LV conduction delay is best understood by examination of the constellation of cardiomyopathy and LBBB. By stimulation of opposing sides of the left ventricle (figure 1), a more synchronised contraction can be achieved, and the LV stroke volume can be augmented to achieve clinically meaningful improvements in heart failure outcomes. Beyond the acute haemodynamic effects of CRT that improve heart failure symptoms, long-term beneficial changes at the myocardial cellular and transcriptional level lead to LV reverse remodelling and a direct impact on the natural history of systolic heart failure. Because of this, CRT is now routinely used in patients whose heart failure symptoms are mild to avoid progression of their cardiomyopathy and heart failure symptoms. Despite two decades for evolution of CRT implantation techniques and technology, CRT has been plagued with a non-response rate in the range of 30% that has varied little over time. Recent developments, particularly with multisite LV …

Point-by-point 3D electroanatomic mapping is used to guide catheter ablation of PVCs. Due to differences in the spatial excursion of the cardiac chambers during cardiac cycles in PVCs versus sinus rhythm, 3D location registration during PVCs may be shifted relative to sinus rhythm. In this study, we

Background— Phase analysis of cardiac arrhythmias, particularly atrial fibrillation, has gained interest because of the ability to detect organized stable drivers (rotors) and target them for therapy. However, the lack of methodology details in publications on the topic has resulted in ongoing debate over the phase mapping technique. By comparing phase maps and activation maps, we examined advantages and limitations of phase mapping. Methods and Results— Seven subjects were enrolled. We generated phase maps and activation maps from electrocardiographic imaging–reconstructed epicardial unipolar electrograms. For ventricular signals, phase was computed with (1) pseudoempirical mode decomposition detrending and (2) a novel Moving Average (MVG) detrending approach. For atrial fibrillation signals, MVG was modified to incorporate dynamic cycle length (DCL) changes (MVG-DCL). Phase maps were visually analyzed to study phase singularity points and rotors. Results show that phase is sensitive to cycle length choice, a limitation that was addressed by the MVG-DCL algorithm. MVG-DCL was optimal for atrial fibrillation analysis. Phase maps helped to highlight high-curvature wavefronts and rotors. However, for some activation patterns, phase generated nonrotational singularity points and false rotors. Conclusions— Phase mapping computes singularity points and visually highlights rotors. As such, it can help to provide a clearer picture of the spatiotemporal activation characteristics during atrial fibrillation. However, it is advisable to incorporate electrogram characteristics and the time-domain activation sequence in the analysis, to prevent misinterpretation and false rotor detection. Therefore, for mapping complex arrhythmias, a combined time-domain activation and phase mapping with variable cycle length seems to be the most reliable method.

Introduction Implantable cardioverter defibrillator (ICD) recipients who suffer from posttraumatic stress disorder (PTSD) are known to be associated with significant cardiac-specific mortality. Clinical observations suggest that PTSD is frequently undetected in ICD recipients followed up at electrophysiology (EP) outpatient clinics. Early recognition of PTSD is important to reduce the risk of serious manifestations on patient outcomes. Methods All ICD recipients aged 19 years or older at the Washington University School of Medicine (WASHU) EP clinic, a large urban EP clinic, were invited to participate in the project. An informed consent letter with an attached primary care: posttraumatic stress disorder (PC: PTSD) survey was offered to the participants who met the inclusion criteria. Those who completed the survey were included in the project. Individuals with positive survey result were offered a referral to mental health services. Comparisons between PTSD and non-PTSD patients were done using a two-sample t-test for continuous variables. Using Fisher's exact test, PTSD prevalence was compared to the study by Ladwig et al in which prevalence was determined as the proportion of patients with positive findings of PTSD ( n = 38/147). All analyses were conducted using SAS v9.4. The proportion of patients having PTSD was determined and an exact 95% confidence interval was evaluated based on the binomial distribution. Results Using a convenience sample, 50 ICD recipients (33 males and 17 females) were enrolled. The project had a 30-day outcome period. Nine (18%) of the 50 participants had positive PC: PTSD findings and all these nine participants were referred to a mental health specialist. The current project demonstrated an 18% (9/50) PTSD prevalence rate when compared to a 26% (38/147) prevalence rate in the study by Ladwig et al ( P = 0.34). Although this project did not demonstrate 20% PTSD prevalence rate, as hypothesized, the 18% PTSD prevalence rate is consistent with previous research. Conclusion The prevalence of PTSD noted in the current project is consistent with previous research and validates underrecognition of PTSD in ICD patients. Offering a referral to all ICD recipients at EP clinic visits with a positive PC: PTSD screening to a mental health specialist is an important step in reducing the risk of serious manifestations on patient outcomes.

Background— Cardiac memory refers to the observation that altered cardiac electrical activation results in repolarization changes that persist after the restoration of a normal activation pattern. Animal studies, however, have yielded disparate conclusions, both regarding the spatial pattern of repolarization changes in cardiac memory and the underlying mechanisms. The present study was undertaken to produce 3-dimensional images of the repolarization changes underlying long-term cardiac memory in humans. Methods and Results— Nine adult subjects with structurally normal hearts and dual-chamber pacemakers were enrolled in the study. Noninvasive electrocardiographic imaging was used before and after 1 month of ventricular pacing to reconstruct epicardial activation and repolarization patterns. Eight subjects exhibited cardiac memory in response to ventricular pacing. In all subjects, ventricular pacing resulted in a prolongation of the activation recovery interval (a surrogate for action potential duration) in the region close to the site of pacemaker-induced activation from 228.4±7.6 ms during sinus rhythm to 328.3±6.2 ms during cardiac memory. As a consequence, increases are observed in both apical-basal and right-left ventricular gradients of repolarization, resulting in a significant increase in the dispersion of repolarization. Conclusions— These results demonstrate that electrical remodeling in response to ventricular pacing in human subjects results in action potential prolongation near the site of abnormal activation and a marked dispersion of repolarization. This dispersion of repolarization is potentially arrhythmogenic and, intriguingly, was less evident during continuous right ventricular pacing, suggesting the novel possibility that continuous right ventricular pacing at least partially suppresses pacemaker-induced cardiac memory.

Evaluation of: Weerasooriya R, Khairy P, Litalien J et al. Catheter ablation for arial fibrillation; are results maintained at 5 years of follow-up? J. Am. Coll. Cardiol. 57, 160–166 (2011).Atrial fibrillation is the most common arrhythmia faced in clinical practice with a substantial impact on morbidity, mortality, and heathcare expenditures. Patients with atrial fibrillation in which a rhythm control strategy is desired to improve quality of life have had limited options. The discovery of the role of pulmonary vein triggers has led to the development of catheter ablation techniques that have shown promising short-term success rates. Long-term outcomes were until recently, lacking. These results confirm the inherently recurrent nature of atrial fibrillation and the need for multiple procedures to achieve reasonable long-term successful maintenance of sinus rhythm.

Background:Conventional insertion of implantable cardioverter-defibrillator (ICD) includes an evaluation of the defibrillation threshold (DFT). Implanting an ancillary defibrillation lead in the azygos vein has been introduced as a therapeutic option in patients with “high” DFT. This study reports the efficacy and stability of azygos defibrillation coils implanted for elevated DFTs. Methods:This is a retrospective review of seven consecutive patients with right and left pectoral, single- and dual-chamber, and biventricular ICDs and elevated DFTs, in whom an azygos defibrillation coil was introduced. Results:Addition of an azygos defibrillator lead achieved a satisfactory safety margin during single energy defibrillation efficacy testing in four out of seven patients, with success at maximum device output in two patients. No satisfactory safety margin was achieved in the remaining patient, despite the further addition of a subcutaneous defibrillation coil. No change in lead position was observed over a mean radiographic follow-up of 8 months. No complications were noted during a mean follow-up of 14 months, including no deaths, and no ICD shocks. Conclusion:Implanting a defibrillation coil into the azygos vein is feasible and safe. In a majority of patients with failed defibrillation efficacy testing, adding an azygos coil achieves success on repeat testing. Therefore, this technique is one option for lowering the defibrillation threshold in patients who fail DFT testing of their ICD.

Background: Patients with ischemic cardiomyopathy (ICM) who have monomorphic ventricular tachycardia (VT) induced by programmed ventricular stimulation (PVS) are at increased risk of sudden cardiac death (SCD). Among a primary prevention population, the prognostic significance of induced polymorphic ventricular arrhythmias is unknown. Methods:A total of 105 consecutive patients who received an implantable cardioverter-defibrillator (ICD) for primary prevention of SCD in the setting of ICM and non-sustained VT were retrospectively evaluated. Seventy-five patients (group I) had induction of monomorphic VT and 30 patients (group II) had a sustained ventricular arrhythmia other than monomorphic VT (ventricular flutter, ventricular fibrillation, and polymorphic VT) induced during PVS. Results:Baseline characteristics were similar between group I and group II except for ejection fraction (25% vs. 31%, P = 0.0001) and QRS duration (123 milliseconds vs. 109 milliseconds, P = 0.04). Sixteen of 75 (21.3%) patients in group I and 6 of 30 (20%) patients in group II received appropriate ICD therapy (P = 0.88). Survival free from ICD therapy was similar between groups (P = 0.54). There was a trend toward increased all-cause mortality among patients in group I by Kaplan-Meier analysis (P = 0.08). However, when adjusted for age, EF, and QRS duration mortality was similar (P = 0.45). Conclusions:There is no difference in rates of appropriate ICD discharge or mortality between patients dichotomized by type of rhythm induced during PVS. These results suggest that patients in this population who have inducible VF or sustained polymorphic VT have similar rates of subsequent clinical ventricular tachyarrhythmias as those with inducible monomorphic VT.

PURPOSE: To provide additional insight into factors that may be associated with the need for target vessel revascularization (TVR) following de novo renal artery stenting during long-term follow-up. METHODS: A retrospective chart and database review was conducted to analyze the progress of all patients with de novo symptomatic renal artery stenosis who underwent stent-supported angioplasty under the auspices of the Single Operator, Single Center, Renal Stent Retrospective Study (SOCRATES). The records review identified 782 patients who were enrolled in the study between 1993 and 2004; after excluding 34 (4.5%) patients (lost to follow-up or inadequate data), 748 consecutive patients (412 women; mean age 70.7+/-9.7 years, range 37-92) were suitable for longitudinal analysis. The need for TVR was based on strict clinical criteria (> or =20% rise in serum creatinine, worsening hypertension, and/or recurrent flash pulmonary edema), and all patients underwent multidisciplinary evaluation before stenting and during follow-up. RESULTS: Follow-up spanned a mean 45.8+/-26.5 months. TVR was needed in 88 (10.03%) of 877 arteries and was best predicted by patient age < or =67 years (OR 2.91, p=0.0001), stent diameter < or =5.0 mm (OR 2.31, p=0.001), solitary functioning kidney (OR 2.01, p=0.048), history of lower extremity peripheral artery disease (OR 1.87, p=0.008), and antecedent history of stroke (OR 1.73, p=0.026). CONCLUSION: Renal artery stenting appears to be durable, with only 10% of stented arteries requiring TVR during clinically-based long-term follow-up. Arteries with a final stent diameter < or =5.0 mm were more than twice as likely to need TVR, as were patients with a solitary kidney. The authors acknowledge that clinical recurrence is not a surrogate for ultrasound surveillance after renal artery stenting, so prospective controlled trials will be needed to determine risk factors for restenosis.

Background Cigarette smoking is a known risk factor for sudden cardiac death (SCD). It is unknown whether smoking status affects implantable cardioverter-defibrillator (ICD) therapy. Objective The primary end point was appropriate ICD therapy according to smoking status. Methods A total of 105 consecutive patients who underwent ICD implantation for primary prevention of SCD were retrospectively analyzed. All patients had an abnormal response to programmed ventricular stimulation performed for nonsustained ventricular tachycardia in the setting of ischemic cardiomyopathy between January 1999 and December 2003. Results Among the 105 patients, 6 (37.5%) of 16 current smokers, 14 (25.9%) of 54 former smokers, and 2 (5.7%) of 35 of never smokers received an appropriate ICD therapy ( P = .02). Kaplan-Meier analysis for survival free of appropriate ICD therapy comparing never smokers with both current smokers ( P = .002) and former smokers ( P = .01) demonstrated statistically significant differences by log rank over a mean follow-up of 21.8 ± 13.7 months. Cox regression analysis found that current smoking was associated with an increased risk of appropriate therapy (hazard ratio 7.36; 95% confidence interval 1.42–38.10; P = .02) as was former smoking (hazard ratio 5.42; 95% confidence interval 1.20–24.47; P = .03). There was no difference in inappropriate therapy between groups ( P = .12). Conclusions Cigarette smoking is an independent predictor of appropriate ICD therapy in a primary prevention population. While outcomes differences among current smokers, former smokers, and never smokers are demonstrable, the effect of smoking cessation on ICD therapy requires further study.

Background A novel magnetic guidance system has been developed that allows the operator to remotely navigate an electrophysiology mapping/ablation catheter to precise locations in the heart for treatment of tachyarrhythmias. To date, this new technology has not been directly compared with the conventional approach. Objective To compare the use of the magnetic guidance system to the conventional approach for ablation of atrioventricular nodal reentry tachycardia. Methods Between November 2002 and October 2004, 28 patients with atrioventricular nodal reentry tachycardia treated with the magnetic guidance system were retrospectively compared with 28 matched control patients. Results Patients treated using the magnetic guidance system had similar procedure durations and fluoroscopy times compared with the matched controls. The only statistically significant difference between the groups was a longer time between insertion of the ablation catheter and placement of the first radiofrequency lesion in the magnetic guidance system cohort (23.3 ± 12.0 vs. 10.5 ± 13.9, p=0.001), possibly due to the research protocol. However, there was a trend toward a shorter total time that radiofrequency energy was applied in the magnetic guidance system cohort (5.2 ± 4.5 vs. 8.0 ± 7.2, p=0.087). There were no major complications or recurrences after at least 3 months of follow-up among the patients treated with the magnetic guidance system. Conclusion The magnetic guidance system appears to have similar, and possibly improved, clinical efficacy compared with conventional catheter navigation for the treatment of atrioventricular nodal reentrant tachycardia.

Background: Cardiac resynchronization therapy (CRT) improves functional outcomes in patients with severe systolic heart failure. Whether the effects of CRT on left ventricular (LV) diastolic function and clinical outcomes are influenced by the cause as either ischemic or nonischemic cardiomyopathy (CM) has not been well established. Methods: A total of 57 patients (age 60 11 years; 25% women; LV ejection fraction 25 5%) were studied before and 4 2 months after CRT by echocardiography. Heart failure cause was ischemic CM in 19 and nonischemic CM in 38. Measurements of LV systolic and diastolic function were determined by 2-dimensional and Doppler echocardiography with Doppler tissue imaging of regional myocardial velocities. Clinical outcome events were assessed at long-term follow-up and included hospitalization for heart failure exacerbation, heart transplantation, or cardiac-related death. Results: There were significant increases in LV ejection fraction, reductions in end-systolic volumes, and improved LV systolic dyssynchrony in both groups. However, significant improvements in LV diastolic function were observed only in the patients with nonischemic CM. Clinical events occurred in 53% of the ischemic group versus 26% of the nonischemic group (P < .05) after 20 11 months of CRT. Univariate and multivariate analysis revealed that Doppler-estimated LV filling pressures were predictors of clinical outcome events. Conclusions: After CRT patients with ischemic CM exhibit lack of improvement in LV diastolic function despite favorable effects on LV systolic performance. The Doppler-derived LV filling indices may be an important predictor of long-term clinical outcomes after CRT. (J Am Soc Echocardiogr 2006;19:307-313.)

Defibrillation Energy Requirements of CRT-D Patients. Objectives: While defibrillation energy requirements (DERs) have been extensively studied in patients receiving conventional defibrillators, the DERs of patients receiving cardiac resynchronization therapy with defibrillation capability (CRT-D) devices have not been well described. The purpose of this analysis was to characterize DERs (defined as true threshold or the presence of appropriate safety margins) in patients undergoing implant of a CRT-D and to determine whether DERs in this population were similar to those reported for patients undergoing implantation of conventional defibrillators. Methods: Data were analyzed retrospectively from the VENTAK CHF/CONTAK CD biventricular pacing study. An appropriate safety margin of at least 10 J was verified with at least two successful conversions with 21 J or less. Multivariate logistic regression was performed to determine baseline predictors of failed DER testing. Results: Of 501 patients enrolled, 444 (89%) had successful DER test outcomes. Of the remaining 57 patients, 34 converted with energies >21J, and 23 had their testing terminated prematurely or were not tested, primarily due to patient condition. Larger left ventricular internal dimension in diastole (P = 0.003) and prolonged procedure time (P = 0.01) were significant predictors of higher energy requirements. Few significant complications arose from DER testing. Conclusions: DER testing can be accomplished safely and successfully in the majority of CRT-D patients. However, safety margins cannot be ascertained in a significant number of these patients. Left ventricular inner diameter in diastole (LVIDd) and prolonged procedure time may predict higher DERs, and could be used to anticipate the need for a high-energy device or inclusion of a subcutaneous array.

BACKGROUND Atrioventricular (AV) delay optimization can be an important determinant of the response to cardiac resynchronization therapy (CRT) in patients with medically refractory heart failure and a ventricular conduction delay. OBJECTIVES The purpose of this study was to compare two Doppler echocardiographic methods of AV delay optimization after CRT. METHODS Forty consecutive patients (age 59 12 years) with severe heart failure, New York Heart Association class 3.1 0.4, QRS duration 177 23 ms, and left ventricular ejection fraction 26% 6% referred for CRT were studied using two-dimensional Doppler echocardiography. In each patient, the acute improvement in stroke volume with CRT in response to two methods of AV delay optimization was compared. In the first method, the AV delay that produced the largest increase in the aortic velocity time integral (VTI) derived from continuous-wave Doppler (aortic VTI method) was measured. In the second method, the AV delay that optimized the timing of mitral valve closure to occur simultaneously with the onset of left ventricular systole was calculated from pulsed Doppler mitral waveforms at a short and long AV delay interval (mitral inflow method). RESULTS The optimized AV delay determined by the aortic VTI method resulted in an increase in aortic VTI of 19% 13% compared with an increase of 12% 12% by the mitral inflow method (P .001). The optimized AV delay by the aortic VTI method was significantly longer than the optimized AV delay calculated from the mitral inflow method (119 34 ms vs 95 24 ms, P .001). There was no correlation in the AV delay determined by the two methods (r 0.03). CONCLUSION AV delay optimization by Doppler echocardiography for patients with severe heart failure treated with a CRT device yields a greater systolic improvement when guided by the aortic VTI method compared with the mitral inflow method.

Background Ablation of atrial fibrillation (AF) remains a challenging procedure fraught with significant risks and technical difficulties. A magnetically guided catheter system has been developed that potentially addresses many of these challenges. Fully remote controlled electrical isolation of pulmonary veins was performed in canines, facilitated by a three-dimensional computed tomogram (CT) that depicted the anatomic relationships of the pulmonary veins and the left atrium. Objective The purpose of this study was to evaluate the feasibility of pulmonary vein isolation with a novel remote controlled magnetically guided catheter. Methods CT scans were obtained in seven healthy male canines. A 7-Fr irrigated magnetic catheter was advanced transseptally to the left atrium. A magnetic guidance system was used to control the orientation of the catheter tip. A mechanical device advanced or retracted the catheter as needed. Pulmonary venography was performed and compared with the CT scan. The CT scan was used as a visual reference to set the magnetic field vectors. Radiofrequency energy was delivered through the irrigated magnetic catheter to isolate the superior pulmonary veins, as judged by elimination of pulmonary vein potentials. Results The isolation procedure was successful in all 14 pulmonary veins, and there was no evidence of stenosis at 80–100 days postprocedure. Conclusions These results demonstrate that remote controlled catheter ablation is safe and effective for segmental pulmonary vein isolation. This technology could facilitate curative ablation of AF in humans and reduce the occupational hazards to the operator of prolonged procedures and radiation exposure.

Background Invasive studies have shown that cardiac resynchronization therapy (CRT) acutely improves left ventricular (LV) systolic performance and lowers filling pressures in a majority of patients with medically-refractory severe heart failure. Measurements included LV volume, ejection fraction, PWD early (E-wave) and atrial (A-wave) velocities, diastolic filling time (DFT), and DTI early diastolic mitral annular velocity (Em) at the lateral and septal annulus; PWD mitral E-wave/Em and E/FP were calculated to estimate LV filling pressures. Results Immediately after CRT, LV volumes decreased and LVEF increased significantly. PWD mitral E-wave velocity decreased and E-wave duration and DFT increased significantly; mitral E/FP ratio also decreased significantly, consistent with a decrease in LV filling pressure. Patients with a pre-CRT mitral E/A ratio >1 (n = 20), demonstrated improvements in LV diastolic filling and lower filling pressures whereas those with an E/A ratio ≤1 (n = 21) did not show significant changes in diastolic indices. Conclusions The acute effects of CRT include echocardiographic evidence of reduced LV volumes and increased LVEF with improved diastolic filling and lower filling pressures; LV relaxation is not significantly altered. The benefits in diastolic function are dependent on the PWD-determined LV filling characteristics prior to CRT.

OBJECTIVES The purpose of this study was to determine if AV delay optimization with continuouswave Doppler aortic velocity-time integral (VTI) is clinically superior to an empiric program in patients treated with cardiac resynchronization therapy (CRT) for severe heart failure. BACKGROUND The impact of AV delay programming on clinical outcomes associated with CRT is unknown. METHODS A randomized, prospective, single-blind clinical trial was performed to compare two methods of AV delay programming in 40 patients with severe heart failure referred for CRT. Patients were randomized to either an optimized AV delay determined by Doppler echocardiography (group 1, n 20) or an empiric AV delay of 120 ms (group 2, n 20) with both groups programmed in the atriosynchronous biventricular pacing (VDD) mode. Optimal AV delay was defined as the AV delay that yielded the largest aortic VTI at one of eight tested AV intervals (between 60 and 200 ms). New York Heart Association (NYHA) functional classification and quality-of-life (QOL) score were compared 3 months after randomization. RESULTS Immediately after CRT initiation with AV delay programming, VTI improved by 4.0 1.7 cm vs 1.8 3.6 cm (P .02), and ejection fraction (EF) increased by 7.8 6.2% vs 3.4 4.4% (P .02) in group 1 vs group 2, respectively. After 3 months, NYHA classification improved by 1.0 0.5 vs 0.4 0.6 class points (P .01), and QOL score improved by 23 13 versus 13 11 points (P .03) for group 1 vs group 2, respectively. CONCLUSIONS Echocardiography-guided AV delay optimization using the aortic Doppler VTI improves clinical outcomes at 3 months compared to an empiric AV delay program of 120 ms.

Objectives We evaluated in humans the safety and efficacy of a novel magnetic guidance system (MGS) for electrophysiological mapping, pacing, and ablation. Background Catheter ablation of atrial fibrillation and other complex arrhythmias requires precise catheter manipulation and stabilization. We have shown in animals that the MGS can precisely manipulate a mapping catheter within the heart with an external magnetic field rather than manual catheter control. Methods Thirty-one adults referred for diagnostic electrophysiology studies were enrolled in a prospective trial of the MGS. The magnetic catheter was navigated to preselected sites in the right atrium (RA) and right ventricle (RV) in the first 20 patients. Electrograms were recorded at each target site, and pacing thresholds were measured. In a subset of five patients, RA and RV electrograms and stimulation thresholds were recorded with both a standard ablation catheter and the magnetic catheter. Eleven additional patients were recruited for supraventricular tachycardia (SVT) mapping, and seven of these underwent ablation. Results Navigation was successful in 200 of 202 predetermined right-sided navigation targets and 13 of 13 targets in the left atria. Pacing thresholds and electrogram amplitudes in the RA and RV were not significantly different between the standard and magnetic catheters. The SVT mapping with the magnetic catheter was successful in 13 patients, including 4 with left-sided accessory pathways. The MGS was used for successful ablation of SVT in seven of seven patients. There were no procedural complications. Conclusions These results demonstrate that the MGS can be used for intracardiac mapping, pacing, and ablation safely and effectively.

Background— Ablation of complex arrhythmias would be greatly facilitated by more precise control of ablation catheters. A feasibility study was performed in animals to evaluate a novel magnetic guidance system (MGS) that generates a magnetic field to control the movement and position of a magnetic ablation catheter. Methods and Results— The MGS is composed of a digital biplanar fluoroscope within an array of superconducting electromagnets that surround the torso of the experimental animal and a computer control system that generates a composite magnetic field for directional catheter deflection. Magnetic catheter navigation was performed in dogs and pigs (20 to 30 kg). A 7F magnetic ablation catheter was used for intracardiac navigation and radiofrequency ablation. The performance of a standard 7F deflectable catheter was not affected by the MGS. The magnetic catheter was navigated successfully to 51 predefined targets throughout the heart in 6 animals. In 5 animals, the magnetic catheter, guided by a 3D computed tomogram, was successfully navigated to all pulmonary veins. Navigation accuracy was estimated as Conclusions— These results demonstrate that the MGS can navigate and stabilize an ablation catheter at endocardial targets. Linear or focal radiofrequency ablation with the magnetic catheter is not compromised by the magnetic field. This technology provides precise control of endocardial catheters.

Ventricular contraction is achieved by the coordinated electrical activation of the ventricles through the action of the cardiac conduction system. In the presence of left bundle branch block (LBBB) or interventricular conduction delay (IVCD), the ventricular contraction pattern is desynchronized and the stroke volume is reduced as a consequence. In patients with congestive heart failure (CHF) due to systolic dysfunction, the presence of LBBB or IVCD further degrades ventricular function, contributing directly to the severity of their CHF symptoms. Cardiac resynchronization therapy (CRT) through biventricular pacing relieves CHF symptoms and improves functional status in patients with medically refractory heart failure due to left ventricular systolic dysfunction and LBBB or IVCD. The benefits of CRT are due to improvement in the ventricular activation sequence, resulting in a more coordinated and efficient ventricular contraction. In addition to symptomatic benefits, available data support the hypothesis that CRT alters the natural history of CHF in patients with intraventricular conduction delay.

Background. A decline in the R wave voltage obtained from surface electrocardiograms once correlated with cardiac allograft rejection. With cyclosporine therapy, however, these electrocardiographic findings became inconsistent, occurring only during severe rejection episodes. Despite cyclosporine use, intramyocardial unipolar peak-to-peak amplitudes obtained from plunge electrodes are reported to be highly sensitive and specific for diagnosing rejection. These reports are based on heterotopic grafts, which atrophy over time, making long-term voltage changes during rejection difficult to interpret. The purpose of this study was to use analysis of unipolar peak-to-peak amplitudes as a prospective monitoring tool for diagnosing orthotopic cardiac allograft rejection. Methods. Ten adult mongrel dogs underwent orthotopic heart transplantation with the attachment of four intramyocardial leads. The unipolar peak-to-peak amplitudes were measured daily and compared with endomyocardial biopsy results. Results. We found that intramyocardial unipolar peak-to-peak amplitude analysis had a sensitivity and a specificity of 100% for diagnosing rejection. We also found that as the number of myocardial leads increased, the sensitivity of detecting rejection also increased. Conclusions. We conclude that unipolar peak-to-peak amplitude analysis is an accurate noninvasive means for early detection of cardiac allograft rejection in an orthotopic model. Its success should allow less frequent, more selective use of endomyocardial biopsy.

Atrial fibrillation (AF) is a common cause of stroke. In the US nearly 800,000 people suffer stroke each year and about 130,000 die as a result. Stroke care accounts for an estimated US$34 billion in health care expenditures in the US each year. Among all strokes, AF is the cause in 15–20 % of cases. The incidence of AF in the US has grown steadily over time to a current estimate of 6.1 million with the condition. With the anticipated growth in the worldwide AF population, the need for effective new therapeutic strategies for stroke prevention is clear.

Atrial fibrillation (AF) affects more than six million people in the U.S. alone. It has been estimated to cause nearly 40% of all strokes in patients older than 70 years of age [(1)][1]. Billions of health care dollars are spent each year on the care of patients with this arrhythmia and its sequalae

Background— Various mechanisms of atrial fibrillation (AF) have been demonstrated experimentally. Invasive methods to study these mechanisms in humans have limitations, precluding continuous mapping of both atria with sufficient resolution. In this article, we present continuous biatrial epicardial activation sequences of AF in humans using noninvasive electrocardiographic imaging (ECGI). Methods and Results— In the testing phase, ECGI accuracy was evaluated by comparing ECGI with coregistered CARTO images during atrial pacing in 6 patients. Additionally, correlative observations from catheter mapping and ablation were compared with ECGI in 3 patients. In the study phase, ECGI maps during AF in 26 patients were analyzed for mechanisms and complexity. ECGI noninvasively imaged the low-amplitude signals of AF in a wide range of patients (97 procedural success). Spatial accuracy for determining initiation sites from pacing was 6 mm. Locations critical to maintenance of AF identified during catheter ablation were identified by ECGI; ablation near these sites restored sinus rhythm. In the study phase, the most common patterns of AF were multiple wavelets (92), with pulmonary vein (69) and non–pulmonary vein (62) focal sites. Rotor activity was seen rarely (15). AF complexity increased with longer clinical history of AF, although the degree of complexity of nonparoxysmal AF varied widely. Conclusions— ECGI offers a noninvasive way to map epicardial activation patterns of AF in a patient-specific manner. The results highlight the coexistence of a variety of mechanisms and variable complexity among patients. Overall, complexity generally increased with duration of AF.

Quantitative ECG Analysis. Introduction: Optimal atrial tachyarrhythmia management is facilitated by accurate electrocardiogram interpretation, yet typical atrial flutter (AFl) may present without sawtooth F-waves or RR regularity, and atrial fibrillation (AF) may be difficult to separate from atypical AFl or rapid focal atrial tachycardia (AT). We analyzed whether improved diagnostic accuracy using a validated analysis tool significantly impacts costs and patient care. Methods and Results: We performed a prospective, blinded, multicenter study using a novel quantitative computerized algorithm to identify atrial tachyarrhythmia mechanism from the surface ECG in patients referred for electrophysiology study (EPS). In 122 consecutive patients (age 60 ± 12 years) referred for EPS, 91 sustained atrial tachyarrhythmias were studied. ECGs were also interpreted by 9 physicians from 3 specialties for comparison and to allow healthcare system modeling. Diagnostic accuracy was compared to the diagnosis at EPS. A Markov model was used to estimate the impact of improved arrhythmia diagnosis. We found 13% of typical AFl ECGs had neither sawtooth flutter waves nor RR regularity, and were misdiagnosed by the majority of clinicians (0/6 correctly diagnosed by consensus visual interpretation) but correctly by quantitative analysis in 83% (5/6, P = 0.03). AF diagnosis was also improved through use of the algorithm (92%) versus visual interpretation (primary care: 76%, P < 0.01). Economically, we found that these improvements in diagnostic accuracy resulted in an average cost-savings of $1,303 and 0.007 quality-adjusted-life-years per patient. Conclusions: Typical AFl and AF are frequently misdiagnosed using visual criteria. Quantitative analysis improves diagnostic accuracy and results in improved healthcare costs and patient outcomes. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1251-1259, November 2010)

Background: The programmed atrioventricular delay (AVD) is an important determinant of the response in left ventricular (LV) systolic performance during cardiac resynchronization therapy (CRT). It is not well established if the optimal AVD for CRT may be influenced by the LV diastolic filling pattern. Methods: Thirty patients were studied pre- and post-CRT at programmed AVD of 60–160 ms. Doppler measurements included the aortic and mitral velocity time integral (VTI), mitral early (E) and late diastolic filling (A) wave velocities, E- and A-wave VTI, and diastolic filling time (DFT). The optimal AVD for each of the Doppler variables was defined by the maximal improvement compared to pre-CRT. Patients were grouped by the pre-CRT mitral inflow pattern as impaired relaxation (IR, mitral E/A ≤1, n = 15) or pseudonormalized/restrictive filling (PNF/RF, mitral E/A >1, n = 15). Results: The percentage of improvement in aortic VTI was greater in the PNF/RF group (P = 0.03). Mitral E-wave velocity decreased in the PNF/RF group (P < 0 .001), E-wave VTI increased in both groups (P < 0 .05) and A-wave VTI increased in the PNF/RF group. DFT increased in both groups. The optimal AVD that maximized aortic VTI was longer than the AVD that improved DFT. Conclusions: The effects of various programmed AVD during CRT on the response in LV stroke volume and diastolic filling are influenced by the pre-CRT LV filling characteristics. AVD optimization based on maximizing DFT is shorter compared to the aortic VTI method.

Introduction: Chronic kidney disease (CKD) has been independently associated with increased cardiovascular mortality. Little is known about the benefit of implantable cardioverter defibrillator (ICD) therapy for prevention of sudden death in this large, high-risk population. We sought to evaluate the impact of CKD on survival in patients who received an ICD for primary prevention of sudden death. Methods and Results: In this retrospective study of patients who underwent ICD implantation for primary prevention of sudden death, patients were stratified by CKD, defined as serum creatinine ≥2 mg/dL or dialysis use. Primary endpoint was mortality. CKD was identified in 35 of 229 patients (15.3%). There were 33 deaths during a follow-up period of 18.0 ± 15.2 months: 17 of 35 CKD patients and 16 of 194 patients without CKD (48.6% vs 8.2%, P < 0.00001 by log-rank). One-year survival for patients with and without CKD was 61.2% and 96.3%, respectively. Cox regression analysis controlling for age, sex, comorbidities, ejection fraction, and medications proved CKD to be the strongest independent predictor of death (hazard ratio 10.5; 95% confidence interval 4.8–23.1; P = 0.0001). This risk was dependant on severity of CKD; a 10 mL/min reduction in creatinine clearance was associated with a 55% increase in hazard of death (P < 0.0001). Conclusions: In patients receiving an ICD for primary prevention of sudden death, CKD significantly reduced long-term survival. This poor prognosis may limit the impact of primary prevention ICD therapy in this patient population.

The effects of left ventricular (LV) lead placement for cardiac resynchronization therapy (CRT) on LV remodeling and dyssynchrony are not well defined. Sixty-one patients (age 60 +/- 11 years, 76% men) were evaluated by echocardiography before and 4 +/- 2 months after CRT and grouped by the LV lead placement (lateral, posterolateral, or anterolateral). Echocardiographic measurements included LV volumes and LV ejection fraction. Tissue Doppler imaging was used to assess for inter- and intraventricular systolic and diastolic dyssynchrony. Analysis of variance was used to determine the effect of the LV lead placement on echocardiographic variables after CRT. The LV lead was placed in a lateral cardiac vein in 33 patients (54%), posterolateral in 15 (25%), and anterior in 13 (21%). Lateral LV lead placement was associated with significantly smaller LV volumes compared with the posterolateral lead placement (p0.01). Diastolic dyssynchrony improved significantly with lateral lead placement compared with the anterior lead location (p0.05). Improvement in LV ejection fraction and inter- and intraventricular systolic dyssynchrony was similar among the 3 groups. In conclusion, in patients undergoing CRT, a lateral lead location resulted in greater reverse LV remodeling and improved diastolic dyssynchrony compared with other lead placement locations.

with heart failure, in whom risk of all-cause mortality and sudden death mortality is markedly increased, betaadrenergic antagonists are part of the standard of care, which is defined by randomized prospective clinical trials to pharmacologically extend longevity. A meta-analysis of 23 beta-blocker trials in patients with heart failure demonstrated that the protective effect associated with these drugs was proportional to the heart rate reduction and not related to the dose of the beta-blocker. 7 Ivabradine is a new agent with a direct effect on the funny current (If,) which is an important determinant of the pacemaker potential and periodicity in the sinoatrial node. A randomized prospective trial of ivabradine in patients with heart failure demonstrated a reduction in the primary composite end point of cardiovascular death and heart failure hospital admissions associated with ivabradine treatment. 8 Both reports provide strong evidence of a direct connection between an improvement in cardiovascular outcomes and a pharmacological effect on the resting heart rate. In this issue of HeartRhythm, Teodorescu et al 9 provide more evidence for an important link between resting heart rate and sudden death risk in patients with known coronary artery disease. For their case-control analysis, they identified 378 cases of sudden cardiac death older than 35 years that had prior electrocardiograms (ECGs) available for analysis. Cases were identified from the ongoing Oregon Sudden Unexpected Death Study. The control cases were chosen from the same geographic region and sex and age matched to cases. All the control patients also had coronary artery disease. Resting heart rate was defined by a 12-lead ECG identified from medical records before the sudden death event. The patient characteristics in the 2 groups were remarkable for a number of statistically significant asymmetries. Among cases, diabetes mellitus, chronic obstructive pulmonary disease, chronic renal insufficiency, and severe left ventricular systolic dysfunction (LVSD) were more prevalent. Among heart rate-modulating drugs, only digoxin and beta2-agonists were more commonly used among cases. After adjustment for major comorbidities such as diabetes, pulmonary, and renal disease as well as the effects of heart rate-modulating drugs, the authors found a 26% increase in risk associated with each 10-beats/min increase in resting heart rate. Subsequent adjustment for the impact of LVSD attenuated this relationship to a minor degree. Digoxin use had the strongest predictive value for sudden death, but only 12 controls were on the drug as opposed to 62 controls, of

ObjectivesTo determine the short-term effects of cardiac resynchronization therapy (CRT) on measurements of left ventricular (LV) diastolic function in patients with severe heart failure.BackgroundCardiac resynchronization therapy improves systolic performance; however, the effects on diastolic function by load-dependent pulsed-wave Doppler transmitral indices has been variable.MethodsFifty patients with severe heart failure were evaluated by two-dimensional Doppler echocardiography immediately prior to and 4 ± 1 month after CRT. Measurements included LV volumes and ejection fraction (EF), pulsed-wave Doppler (PWD)-derived transmitral filling indices (E- and A-wave velocities, E/A ratio, deceleration time [DT], diastolic filling time [DFT], and isovolumic relaxation time). Tissue Doppler imaging was used for measurements of systolic and diastolic (Em) velocities at four mitral annular sites; mitral E-wave/Em ratio was calculated to estimate LV filling pressure. Color M-mode flow propagation velocities were also obtained.ResultsAfter CRT, LV volumes decreased significantly (p < 0.001) and LVEF increased >5% in 28 of 50 patients (56%) and were accompanied by reduction in PWD mitral E-wave velocity and E/A ratio (both p < 0.01), increased DT and DFT (both p < 0.01), and lower filling pressures (i.e., E-wave/Em septal; p < 0.01). Patients with LVEF response ≤5% after CRT had no significant changes in measurements of diastolic function; LV relaxation (i.e., Em velocities) worsened in this group.ConclusionsIn heart failure patients receiving CRT, improvement in LV diastolic function is coupled to the improvement in LV systolic function.

The Fidelis lead recall is the latest in a series of device recalls that have challenged clinicians with regard to appropriate patient management strategies. Medtronic (Minneapolis, Minnesota) recalled the Sprint Fidelis 6949 implantable cardioverter-defibrillator (ICD) lead in 2007 after 665 lead

The consequence of synchronous, rapid activation of the left ventricle (LV) by the cardiac conduction system is an efficient economy of energy expenditure for the work of ejection during the cardiac cycle. In the failing heart with concomitant conduction system disease, this economy is disrupted