Kenneth C. Bilchick

Cardiac Magnetic Resonance Assessment of Dyssynchrony and Myocardial Scar Predicts Function Class Improvement Following Cardiac Resynchronization Therapy

OBJECTIVES We tested a circumferential mechanical dyssynchrony index (circumferential uniformity ratio estimate [CURE]; 0 to 1, 1 = synchrony) derived from magnetic resonance-myocardial tagging (MR-MT) for predicting clinical function class improvement following cardiac resynchronization therapy (CRT). BACKGROUND There remains a significant nonresponse rate to CRT. MR-MT provides high quality mechanical activation data throughout the heart, and delayed enhancement cardiac magnetic resonance (DE-CMR) offers precise characterization of myocardial scar. METHODS MR-MT was performed in 2 cohorts of heart failure patients with: 1) a CRT heart failure cohort (n = 20; left ventricular ejection fraction of 0.23 +/- 0.057) to evaluate the role of MR-MT and DE-CMR prior to CRT; and 2) a multimodality cohort (n = 27; ejection fraction of 0.20 +/- 0.066) to compare MR-MT and tissue Doppler imaging septal-lateral delay for assessment of mechanical dyssynchrony. MR-MT was also performed in 9 healthy control subjects. RESULTS MR-MT showed that control subjects had highly synchronous contraction (CURE 0.96 +/- 0.01), but tissue Doppler imaging indicated dyssynchrony in 44%. Using a cutoff of <0.75 for CURE based on receiver-operator characteristic analysis (area under the curve: 0.889), 56% of patients tested positive for mechanical dyssynchrony, and the MR-MT CURE predicted improved function class with 90% accuracy (positive and predictive values: 87%, 100%); adding DE-CMR (% total scar <15%) data improved accuracy further to 95% (positive and negative predictive values: 93%, 100%). The correlation between CURE and QRS duration was modest in all cardiomyopathy subjects (r = 0.58, p < 0.001). The multimodality cohort showed a 30% discordance rate between CURE and tissue Doppler imaging septal-lateral delay. CONCLUSIONS The MR-MT assessment of circumferential mechanical dyssynchrony predicts improvement in function class after CRT. The addition of scar imaging by DE-CMR further improves this predictive value.

Bundle-Branch Block Morphology and Other Predictors of Outcome After Cardiac Resynchronization Therapy in Medicare Patients

Background— Clinical trials of cardiac resynchronization therapy (CRT) have enrolled a select group of patients, with few patients in subgroups such as right bundle-branch block (RBBB). Analysis of population-based outcomes provides a method to identify real-world predictors of CRT outcomes. Methods and Results— Medicare Implantable Cardioverter-Defibrillator Registry (2005 to 2006) data were merged with patient outcomes data. Cox proportional-hazards models assessed death and death/heart failure hospitalization outcomes in patients with CRT and an implantable cardioverter-defibrillator (CRT-D). The 14 946 registry patients with CRT-D (median follow-up, 40 months) had 1-year, 3-year, and overall mortality rates of 12%, 32%, and 37%, respectively. New York Heart Association class IV heart failure status (1-year hazard ratio [HR], 2.23; 3-year HR, 1.98; P<0.001) and age ≥80 years (1-year HR, 1.74; 3-year HR, 1.75; P<0.001) were associated with increased mortality both early and late after CRT-D. RBBB (1-year HR, 1.44; 3-year HR, 1.37; P<0.001) and ischemic cardiomyopathy (1-year HR, 1.39; 3-year HR, 1.44; P<0.001) were the next strongest adjusted predictors of both early and late mortality. RBBB and ischemic cardiomyopathy together had twice the adjusted hazard for death (HR, 1.99; P<0.001) as left BBB and nonischemic cardiomyopathy. QRS duration of at least 150 ms predicted more favorable outcomes in left BBB but had no impact in RBBB. A secondary analysis showed lower hazards for CRT-D compared with standard implantable cardioverter-defibrillators in left BBB compared with RBBB. Conclusions— In Medicare patients, RBBB, ischemic cardiomyopathy, New York Heart Association class IV status, and advanced age were powerful adjusted predictors of poor outcome after CRT-D. Real-world mortality rates 3 to 4 years after CRT-D appear higher than previously recognized.

Incidence and time course of early recovery of pulmonary vein conduction after catheter ablation of atrial fibrillation

Background: Although it is well recognized that recovery of pulmonary vein (PV) conduction is common among patients who fail atrial fibrillation (AF) ablation, little is known about the precise time course of recurrence.

Impact of Mechanical Activation, Scar, and Electrical Timing on Cardiac Resynchronization Therapy Response and Clinical Outcomes

OBJECTIVES Using cardiac magnetic resonance (CMR), we sought to evaluate the relative influences of mechanical, electrical, and scar properties at the left ventricular lead position (LVLP) on cardiac resynchronization therapy (CRT) response and clinical events. BACKGROUND CMR cine displacement encoding with stimulated echoes (DENSE) provides high-quality strain for overall dyssynchrony (circumferential uniformity ratio estimate [CURE] 0 to 1) and timing of onset of circumferential contraction at the LVLP. CMR DENSE, late gadolinium enhancement, and electrical timing together could improve upon other imaging modalities for evaluating the optimal LVLP. METHODS Patients had complete CMR studies and echocardiography before CRT. CRT response was defined as a 15% reduction in left ventricular end-systolic volume. Electrical activation was assessed as the time from QRS onset to LVLP electrogram (QLV). Patients were then followed for clinical events. RESULTS In 75 patients, multivariable logistic modeling accurately identified the 40 patients (53%) with CRT response (area under the curve: 0.95 [p < 0.0001]) based on CURE (odds ratio [OR]: 2.59/0.1 decrease), delayed circumferential contraction onset at LVLP (OR: 6.55), absent LVLP scar (OR: 14.9), and QLV (OR: 1.31/10 ms increase). The 33% of patients with CURE <0.70, absence of LVLP scar, and delayed LVLP contraction onset had a 100% response rate, whereas those with CURE ≥0.70 had a 0% CRT response rate and a 12-fold increased risk of death; the remaining patients had a mixed response profile. CONCLUSIONS Mechanical, electrical, and scar properties at the LVLP together with CMR mechanical dyssynchrony are strongly associated with echocardiographic CRT response and clinical events after CRT. Modeling these findings holds promise for improving CRT outcomes.

Impact of the CHA2DS2-VASc score on anticoagulation recommendations for atrial fibrillation.

BACKGROUND The Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus, Stroke (CHADS(2)) score is used to predict the need for oral anticoagulation for stroke prophylaxis in patients with atrial fibrillation. The Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus, Stroke, Vascular disease, Age 65-74 years, Sex category (CHA(2)DS(2)-VASc) schema has been proposed as an improvement. Our objective is to determine how adoption of the CHA(2)DS(2)-VASc score alters anticoagulation recommendations. METHODS Between 2004 and 2008, 1664 patients were seen at the University of Virginia Atrial Fibrillation Center. We calculated the CHADS(2) and CHA(2)DS(2)-VASc scores for each patient. The 2006 American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines for atrial fibrillation management were used to determine anticoagulation recommendations based on the CHADS(2) score, and the 2010 European Society of Cardiology guidelines were used to determine anticoagulation recommendations based on the CHA(2)DS(2)-VASc score. RESULTS The average age was 62±13 years, and 34% were women. Average CHADS(2) and CHA(2)DS(2)-VASc scores were 1.1±1.1 and 1.8±1.5, respectively (P<.0001). The CHADS(2) score classified 33% as requiring oral anticoagulation. The CHA(2)DS(2)-VASc score classified 53% as requiring oral anticoagulation. For women, 31% had a CHADS(2) score ≥ 2, but 81% had a CHA(2)DS(2)-VASc score ≥ 2 (P = .0001). Also, 32% of women with a CHADS(2) score of zero had a CHA(2)DS(2)-VASc score ≥ 2. For men, 25% had a CHADS(2) score ≥ 2, but 39% had a CHA(2)DS(2)-VASc score ≥ 2 (P<.0001). CONCLUSION Compared with the CHADS(2) score, the CHA(2)DS(2)-VASc score more clearly defines anticoagulation recommendations. Many patients, particularly older women, are redistributed from the low- to high-risk categories.

Real-time fast strain-encoded magnetic resonance imaging to evaluate regional myocardial function at 3.0 Tesla: Comparison to conventional tagging

To compare the utility of the real‐time technique fast strain‐encoded magnetic resonance imaging (fast‐SENC) for the quantification of regional myocardial function to conventional tagged magnetic resonance imaging (MRI).

Sonication of Explanted Cardiac Rhythm Management Devices for the Diagnosis of Pocket Infections and Asymptomatic Bacterial Colonization

Background: Correct diagnosis of the causative organism is critical for the treatment of pacemaker and defibrillator pocket infections. No gold standard for this exists, although swab and tissue cultures are frequently used. The purpose of this study was to determine the value of ultrasonication of explanted generators in the diagnosis of pocket infections and asymptomatic bacterial colonization.

Impact of Heart Rhythm Status on Registration Accuracy of the Left Atrium for Catheter Ablation of Atrial Fibrillation

Introduction: Registration accuracy is of crucial importance to the successful use of image integration technique to facilitate atrial fibrillation (AF) ablation. It is well known that a patients heart rhythm can switch from sinus rhythm (SR) to AF or vice versa during an AF ablation procedure. However, the impact of the heart rhythm change on the accuracy of left atrium (LA) registration has not been studied.

Physiology of biventricular pacing

Biventricular pacing (cardiac resynchronization therapy [CRT]) has been shown to be a very effective therapy for patients with heart failure and dyssynchrony, with improved survival now shown in a recent trial. Electrical dyssynchrony, usually quantified by the duration of the QRS complex, is distinct from mechanical dyssynchrony. Intraventricular mechanical dyssynchrony is most commonly manifest by decreased septal work with concomitant early lateral wall prestretch and subsequent inefficient late contraction. Intraventricular dyssynchrony appears to be more predictive of response to CRT than interventricular dyssynchrony. Mechanical left ventricular dyssynchrony also is associated with regional molecular derangements in connexin-43, stress response kinases, and tumor necrosis factor-α. These molecular derangements may lead to abnormalities in conduction velocity and action potential duration, which may predispose to ventricular arrhythmia. Biventricular pacing corrects abnormal regional wall stresses and results in electrical, mechanical, and molecular left ventricular remodeling.

MR Cine DENSE Dyssynchrony Parameters for the Evaluation of Heart Failure: Comparison With Myocardial Tissue Tagging

OBJECTIVES We sought to assess the effectiveness of automated mechanical dyssynchrony (MD) parameters based on regional heterogeneity of strain (circumferential [CURE], longitudinal [LURE], and radial uniformity ratio estimates) relative to parameters based on regional time to peak contraction with cardiac magnetic resonance (CMR) cine DENSE (Displacement Encoding with Stimulated Echoes) validated with myocardial tissue tagging (MTT) strain data. BACKGROUND Dyssynchrony measures based on the Fourier transformation (FT) of regional strain, such as CURE (previously evaluated in cardiac resynchronization therapy candidates), directly assess MD and yield straightforward global dyssynchrony indexes; however, performance relative to the 12-segment standard deviation of time to peak strain (SD12) or maximal regional delay in time to peak strain is unknown. METHODS Cine DENSE and MTT were obtained with CMR (1.5-T Siemens Avanto, Siemens, Erlangen, Germany) in 13 canines: 3 normal control subjects, 5 with tachycardia pacing-induced heart failure (HF) and left bundle branch ablation (LBBB-HF), and 5 with HF and narrow QRS (NQRS-HF). Strain and dyssynchrony parameters were determined with both CMR methods. RESULTS Both HF groups had reduced peak strains and left ventricular ejection fraction compared with normal cases. There was strong agreement between cine DENSE and MTT on the basis of intraclass correlation coefficients (CURE: 0.99, 95% CI: 0.96 to 1.00; LURE: 0.92, 95% CI: 0.77 to 0.98; circumferential strain [E(CC)]: 0.95, 95% CI: 0.72 to 0.99; longitudinal strain [E(LL)]: 0.82, 95% CI: 0.42 to 0.97). The FT-based metrics (scale 0 to 1), in particular CURE, discriminated highly between LBBB-HF and NQRS-HF groups (median difference): CURE: 0.60, 95% CI: 0.43 to 0.76; LURE: 0.39, 95% CI: 0.19 to 0.58; radial uniformity ratio estimate: 0.22, 95% CI: 0.04 to 0.40). In contrast, relative confidence intervals for group differences in time-to-peak parameters were wide, indicating less consistent discrimination (median difference): SD12-E(CC): 52.5, 95% CI: -4.0 to 109.2; SD12-E(LL): 40.9, 95% CI: -5.3 to 87.1; SD12-radial strain: 42.0, 95% CI: 0.4 to 83.6). Correlations between FT-based and time-to-peak parameters were significant (CURE/SD12-E(CC): r = -0.62, p = 0.03; LURE/SD12-E(LL): r = -0.76, p = 0.005) but not as tight as correlations between time-to-peak parameters. CONCLUSIONS Automated FT-based circumferential, radial, and longitudinal dyssynchrony measures compare favorably with time-to-peak parameters. Cine DENSE was effective for this application and validated with MTT. Further clinical evaluation in cardiac resynchronization therapy candidates with CMR or other imaging modalities is warranted.