Tom Jackson

Myocardial tissue characterization by cardiac magnetic resonance imaging using T1 mapping predicts ventricular arrhythmia in ischemic and non-ischemic cardiomyopathy patients with implantable cardioverter-defibrillators

BACKGROUND Diffuse myocardial fibrosis may provide a substrate for the initiation and maintenance of ventricular arrhythmia. T1 mapping overcomes the limitations of the conventional delayed contrast-enhanced cardiac magnetic resonance (CE-CMR) imaging technique by allowing quantification of diffuse fibrosis. OBJECTIVE The purpose of this study was to assess whether myocardial tissue characterization using T1 mapping would predict ventricular arrhythmia in ischemic and non-ischemic cardiomyopathies. METHODS This was a prospective longitudinal study of consecutive patients receiving implantable cardioverter-defibrillators in a tertiary cardiac center. Participants underwent CMR myocardial tissue characterization using T1 mapping and conventional CE-CMR scar assessment before device implantation. The primary end point was an appropriate implantable cardioverter-defibrillator therapy or documented sustained ventricular arrhythmia. RESULTS One hundred thirty patients (71 ischemic and 59 non-ischemic) were included with a mean follow-up period of 430 ± 185 days (median 425 days; interquartile range 293 days). At follow-up, 23 patients (18%) experienced the primary end point. In multivariable-adjusted analyses, the following factors showed a significant association with the primary end point: secondary prevention (hazard ratio [HR] 1.70; 95% confidence interval [95% CI] 1.01-1.91), noncontrast T1(_native) for every 10-ms increment in value (HR 1.10; CI 1.04-1.16; 90-ms difference between the end point-positive and end point-negative groups), and Grayzone(_2sd-3sd) for every 1% left ventricular increment in value (HR 1.36; CI 1.15-1.61; 4% difference between the end point-positive and end point-negative groups). Other CE-CMR indices including Scar(_2sd), Scar(_FWHM), and Grayzone(_2sd-FWHM) were also significantly, even though less strongly, associated with the primary end point as compared with Grayzone(_2sd-3sd). CONCLUSION Quantitative myocardial tissue assessment using T1 mapping is an independent predictor of ventricular arrhythmia in both ischemic and non-ischemic cardiomyopathies.

Mechanistic insights into the benefits of multisite pacing in cardiac resynchronization therapy: The importance of electrical substrate and rate of left ventricular activation.

BACKGROUND Multisite pacing (MSP) of the left ventricle is proposed as an alternative to conventional single-site LV pacing in cardiac resynchronization therapy (CRT). Reports on the benefits of MSP have been conflicting. A paradigm whereby not all patients derive benefit from MSP is emerging. OBJECTIVE We sought to compare the hemodynamic and electrical effects of MSP with the aim of identifying a subgroup of patients more likely to derive benefit from MSP. METHODS Sixteen patients with implanted CRT systems incorporating a quadripolar LV pacing lead were studied. Invasive hemodynamic and electroanatomic assessment was performed during the following rhythms: baseline (non-CRT); biventricular (BIV) pacing delivered via the implanted CRT system (BIV(implanted)); BIV pacing delivered via an alternative temporary LV lead (BIV(alternative)); dual-vein MSP delivered via 2 LV leads; MultiPoint Pacing delivered via 2 vectors of the quadripolar LV lead. RESULTS Seven patients had an acute hemodynamic response (AHR) of <10% over baseline rhythm with BIV(implanted) and were deemed nonresponders. AHR in responders vs nonresponders was 21.4% ± 10.4% vs 2.0% ± 5.2% (P < .001). In responders, neither form of MSP provided incremental hemodynamic benefit over BIV(implanted). Dual-vein MSP (8.8% ± 5.7%; P = .036 vs BIV(implanted)) and MultiPoint Pacing (10.0% ± 12.2%; P = .064 vs BIV(implanted)) both improved AHR in nonresponders. Seven of 9 responders to BIV(implanted) had LV endocardial activation characterized by a functional line of block during intrinsic rhythm that was abolished with BIV pacing. All these patients met strict criteria for left bundle branch block (LBBB). No nonresponders exhibited this line of block or met strict criteria for LBBB. CONCLUSION Patients not meeting strict criteria for LBBB appear most likely to derive benefit from MSP.

Beneficial Effect on Cardiac Resynchronization From Left Ventricular Endocardial Pacing Is Mediated by Early Access to High Conduction Velocity Tissue: Electrophysiological Simulation Study

Background—Cardiac resynchronization therapy (CRT) delivered via left ventricular (LV) endocardial pacing (ENDO-CRT) is associated with improved acute hemodynamic response compared with LV epicardial pacing (EPI-CRT). The role of cardiac anatomy and physiology in this improved response remains controversial. We used computational electrophysiological models to quantify the role of cardiac geometry, tissue anisotropy, and the presence of fast endocardial conduction on myocardial activation during ENDO-CRT and EPI-CRT. Methods and Results—Cardiac activation was simulated using the monodomain tissue excitation model in 2-dimensional (2D) canine and human and 3D canine biventricular models. The latest activation times (LATs) for LV endocardial and biventricular epicardial tissue were calculated (LVLAT and TLAT), as well the percentage decrease in LATs for endocardial (en) versus epicardial (ep) LV pacing (defined as %dLV=100×(LVLATep−LVLATen)/LVLATep and %dT=100×(TLATep−TLATen)/TLATep, respectively). Normal canine cardiac anatomy is responsible for %dLV and %dT values of 7.4% and 5.5%, respectively. Concentric and eccentric remodeled anatomies resulted in %dT values of 15.6% and 1.3%, respectively. The 3D biventricular-paced canine model resulted in %dLV and %dT values of −7.1% and 1.5%, in contrast to the experimental observations of 16% and 11%, respectively. Adding fast endocardial conduction to this model altered %dLV and %dT to 13.1% and 10.1%, respectively. Conclusions—Our results provide a physiological explanation for improved response to ENDO-CRT. We predict that patients with viable fast-conducting endocardial tissue or distal Purkinje network or both, as well as concentric remodeling, are more likely to benefit from reduced ATs and increased synchrony arising from endocardial pacing.

Optimized Left Ventricular Endocardial Stimulation Is Superior to Optimized Epicardial Stimulation in Ischemic Patients With Poor Response to Cardiac Resynchronization Therapy: A Combined Magnetic Resonance Imaging, Electroanatomic Contact Mapping, and Hemodynamic Study to Target Endocardial Lead Placement

Objectives The purpose of this study was to identify the optimal pacing site for the left ventricular (LV) lead in ischemic patients with poor response to cardiac resynchronization therapy (CRT). Background LV endocardial pacing may offer benefit over conventional CRT in ischemic patients. Methods We performed cardiac magnetic resonance, invasive electroanatomic mapping (EAM), and measured the acute hemodynamic response (AHR) in patients with existing CRT systems. Results In all, 135 epicardial and endocardial pacing sites were tested in 8 patients. Endocardial pacing was superior to epicardial pacing with respect to mean AHR (% change in dP/dtmax vs. baseline) (11.81 [-7.2 to 44.6] vs. 6.55 [-11.0 to 19.7]; p = 0.025). This was associated with a similar first ventricular depolarization (Q-LV) (75 ms [13 to 161 ms] vs. 75 ms [25 to 129 ms]; p = 0.354), shorter stimulation–QRS duration (15 ms [7 to 43 ms] vs. 19 ms [5 to 66 ms]; p = 0.010) and shorter paced QRS duration (149 ms [95 to 218 ms] vs. 171 ms [120 to 235 ms]; p < 0.001). The mean best achievable AHR was higher with endocardial pacing (25.64 ± 14.74% vs. 12.64 ± 6.76%; p = 0.044). Furthermore, AHR was significantly greater pacing the same site endocardially versus epicardially (15.2 ± 10.7% vs. 7.6 ± 6.3%; p = 0.014) with a shorter paced QRS duration (137 ± 22 ms vs. 166 ± 30 ms; p < 0.001) despite a similar Q-LV (70 ± 38 ms vs. 79 ± 34 ms; p = 0.512). Lack of capture due to areas of scar (corroborated by EAM and cardiac magnetic resonance) was associated with a poor AHR. Conclusions In ischemic patients with poor CRT response, biventricular endocardial pacing is superior to epicardial pacing. This may reflect accessibility to sites that cannot be reached via coronary sinus anatomy and/or by access to more rapidly conducting tissue. Furthermore, guidance to the optimal LV pacing site may be aided by modalities such as cardiac magnetic resonance to target delayed activating sites while avoiding scar.

A U-shaped type II contraction pattern in patients with strict left bundle branch block predicts super-response to cardiac resynchronization therapy.

BACKGROUND New criteria to define strict left bundle branch block (LBBB) on the basis of pathophysiological principles predict response to cardiac resynchronization therapy (CRT). Heterogeneous activation and contraction patterns have been identified in patients with classical LBBB. Cardiac magnetic resonance (CMR) imaging has demonstrated that a U-shaped (type II) contraction predicts reverse remodeling post-CRT. A homogeneous spread of (type I) contraction is less predictive. OBJECTIVES The purpose of this study was to investigate contraction patterns among patients with strict LBBB and to test whether a type II contraction pattern better predicts CRT response and super-response. METHODS Thirty-seven patients with strict LBBB (QRS duration ≥140 ms for men and ≥130 ms for women with mid-QRS notching or slurring in ≥2 contiguous leads) underwent cine CMR imaging pre-CRT with an analysis of their contraction patterns by using endocardial contour tracking software. Patients were evaluated for reverse remodeling 6 months postimplantation. RESULTS Nineteen patients (51%) had a type II contraction pattern. A total of 25 patients (68%) of the cohort reverse remodeled. In the type II contraction group, all 19 patients (100%) reverse remodeled as compared with 6 patients (33%) in the type I contraction group (P < .01). Super-response was achieved in 21 patients (57%) of the total cohort: 5 patients with a type I contraction pattern (28%) and 16 patients with a type II contraction pattern (84%) (P < .01). CONCLUSION Patients with strict LBBB who are guideline indicated for CRT have heterogeneous contraction patterns derived from cine CMR. A type II contraction pattern is strongly predictive for reverse remodeling and super-response. This questions whether strict LBBB criteria alone are sufficient to reliably predict a positive response to CRT.

Focal But Not Diffuse Myocardial Fibrosis Burden Quantification Using Cardiac Magnetic Resonance Imaging Predicts Left Ventricular Reverse Modeling Following Cardiac Resynchronization Therapy.

Many heart failure patients with dyssynchrony do not reverse remodel (RR) in response to cardiac resynchronization therapy (CRT). The presence of focal and diffuse interstitial myocardial fibrosis may explain this high nonresponse rate. T1 mapping is a new cardiac magnetic resonance imaging (CMR) technique that overcomes the limitations of conventional contrast CMR and provides reliable quantitative assessment of diffuse myocardial fibrosis. The study tested the hypothesis that focal and diffuse fibrosis quantification would correlate with a lack of left ventricular (LV) RR to CRT.

Comparison of delayed transvenous reimplantation and immediate surgical epicardial approach in pacing-dependent patients undergoing extraction of infected permanent pacemakers.

BACKGROUND Pacemaker infection in pacing-dependent patients is challenging. After extraction, temporary pacing usually is utilized before delayed reimplantation (after an appropriate course of antibiotics), resulting in prolonged hospital stays. A single combined procedure of epicardial (EPI) pacemaker implantation and system extraction may prevent this. OBJECTIVE The purpose of this study was to evaluate the feasibility and safety of these 2 approaches by comparing clinical outcome for both strategies over 1 year. METHODS In center 1, 80 consecutive pacemaker-dependent patients underwent extraction with an externalized pacemaker and delayed implantation on the contralateral side (ENDO group). In center 2, 80 consecutive patients had 2 epicardial ventricular leads surgically implanted with extraction of the infected pacemaker during the same procedure (EPI group). Patients were followed-up for 12 months. RESULTS One hundred sixty pacing-dependent patients were successfully implanted and extracted (ENDO group 71 ± 13 years vs EPI group 73 ± 14, P = NS). In the EPI group, 2 patients developed significant pericardial bleeding. In-hospital mortality was 0% in the ENDO group and 2.5% in the EPI group. Total hospitalization time was 15 ± 7 days in the ENDO group vs 9 ± 6 days in the EPI group (P <.001). At 1 year, no infection recurrences occurred in either group, and mortality was equal (5% in each group). Median 1-year pacing thresholds were lower in the ENDO vs the EPI group (0.8 ± 0.6 V vs 1.1 ± 0.6 V, P = .02). CONCLUSION The ENDO and EPI strategies had an excellent success rate and low risk of complications. A single procedure using surgical epicardial lead implantation was associated with a shorter duration of hospital stay.

Cost-Effectiveness Analysis of Quadripolar Versus Bipolar Left Ventricular Leads for Cardiac Resynchronization Defibrillator Therapy in a Large, Multicenter UK Registry

Objectives The objective of this study was to evaluate the cost-effectiveness of quadripolar versus bipolar cardiac resynchronization defibrillator therapy systems. Background Quadripolar left ventricular (LV) leads for cardiac resynchronization therapy reduce phrenic nerve stimulation (PNS) and are associated with reduced mortality compared with bipolar leads. Methods A total of 606 patients received implants at 3 UK centers (319 Q, 287 B), between 2009 and 2014; mean follow-up was 879 days. Rehospitalization episodes were costed at National Health Service national tariff rates, and EQ-5D utility values were applied to heart failure admissions, acute coronary syndrome events, and mortality data, which were used to estimate quality-adjusted life-year differences over 5 years. Results Groups were matched with regard to age and sex. Patients with quadripolar implants had a lower rate of hospitalization than those with bipolar implants (42.6% vs. 55.4%; p = 0.002). This was primarily driven by fewer hospital readmissions for heart failure (51 [16%] vs. 75 [26.1%], respectively, for quadripolar vs. bipolar implants; p = 0.003) and generator replacements (9 [2.8%] vs. 19 [6.6%], respectively; p = 0.03). Hospitalization for suspected acute coronary syndrome, arrhythmia, device explantation, and lead revisions were similar. This lower health-care utilization cost translated into a cumulative 5-year cost saving for patients with quadripolar systems where the acquisition cost was <£932 (US

Comprehensive use of cardiac computed tomography to guide left ventricular lead placement in cardiac resynchronization therapy

1,398) compared with bipolar systems. Probabilistic sensitivity analysis results mirrored the deterministic calculations. For the average additional price of £1,200 (US

Current concepts relating coronary flow, myocardial perfusion and metabolism in left bundle branch block and cardiac resynchronisation therapy

1,800) over a bipolar system, the incremental cost-effective ratio was £3,692 per quality-adjusted life-year gained (US