Circumferential Uniformity Ratio Estimate Research Articles

Cardiac magnetic resonance defines mechanisms of sex-based differences in outcomes following cardiac resynchronization therapy.

BackgroundMechanisms of sex-based differences in outcomes following cardiac resynchronization therapy (CRT) are poorly understood.ObjectiveTo use cardiac magnetic resonance (CMR) to define mechanisms of sex-based differences in outcomes after CRT and describe distinct CMR-based phenotypes of CRT candidates based on sex and non-ischemic/ischemic cardiomyopathy type.Materials and methodsIn a prospective study, sex-based differences in three short-term CRT response measures [fractional change in left ventricular end-systolic volume index 6 months after CRT (LVESVI-FC), B-type natriuretic peptide (BNP) 6 months after CRT, change in peak VO2 6 months after CRT], and long-term survival were evaluated with respect to 39 baseline parameters from CMR, exercise testing, laboratory testing, electrocardiograms, comorbid conditions, and other sources. CMR was also used to quantify the degree of left-ventricular mechanical dyssynchrony by deriving the circumferential uniformity ratio estimate (CURE-SVD) parameter from displacement encoding with stimulated echoes (DENSE) strain imaging. Statistical methods included multivariable linear regression with evaluation of interaction effects associated with sex and cardiomyopathy type (ischemic and non-ischemic cardiomyopathy) and survival analysis.ResultsAmong 200 patients, the 54 female patients (27%) pre-CRT had a smaller CMR-based LVEDVI (p = 0.04), more mechanical dyssynchrony based on the validated CMR CURE-SVD parameter (p = 0.04), a lower frequency of both late gadolinium enhancement (LGE) and ischemic cardiomyopathy (p < 0.0001), a greater RVEF (p = 0.02), and a greater frequency of LBBB (p = 0.01). After categorization of patients into four groups based on cardiomyopathy type (ischemic/non-ischemic cardiomyopathy) and sex, female patients with non-ischemic cardiomyopathy had the lowest CURE-SVD (p = 0.003), the lowest pre-CRT BNP levels (p = 0.01), the lowest post-CRT BNP levels (p = 0.05), and the most favorable LVESVI-FC (p = 0.001). Overall, female patients had better 3-year survival before adjustment for cardiomyopathy type (p = 0.007, HR = 0.45) and after adjustment for cardiomyopathy type (p = 0.009, HR = 0.67).ConclusionCMR identifies distinct phenotypes of female CRT patients with non-ischemic and ischemic cardiomyopathy relative to male patients stratified by cardiomyopathy type. The more favorable short-term response and long-term survival outcomes in female heart failure patients with CRT were associated with lower indexed CMR-based LV volumes, decreased presence of scar associated with prior myocardial infarction and ICM, and greater CMR-based dyssynchrony with the CURE-SVD.

Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging

BackgroundThe lack of dystrophin in cardiomyocytes in Duchenne muscular dystrophy (DMD) is associated with progressive decline in cardiac function eventually leading to death by 20–40 years of age. The aim of this prospective study was to determine rate of progressive decline in left ventricular (LV) function in Duchenne muscular dystrophy (DMD) over 5 years.MethodsShort axis cine and grid tagged images of the LV were acquired in individuals with DMD (n = 59; age = 5.3–18.0 years) yearly, and healthy controls at baseline (n = 16, age = 6.0–18.3 years) on a 3 T MRI scanner. Grid-tagged images were analyzed for composite circumferential strain (ℇcc%) and ℇcc% in six mid LV segments. Cine images were analyzed for left ventricular ejection fraction (LVEF), LV mass (LVM), end-diastolic volume (EDV), end-systolic volume (ESV), LV atrioventricular plane displacement (LVAPD), and circumferential uniformity ratio estimate (CURE). LVM, EDV, and ESV were normalized to body surface area for a normalized index of LVM (LVMI), EDV (EDVI) and ESV (ESVI).ResultsAt baseline, LV ℇcc% was significantly worse in DMD compared to controls and five of the six mid LV segments demonstrated abnormal strain in DMD. Longitudinal measurements revealed that ℇcc% consistently declined in individuals with DMD with the inferior segments being more affected. LVEF progressively declined between 3 to 5 years post baseline visit. In a multivariate analysis, the use of cardioprotective drugs trended towards positively impacting cardiac measures while loss of ambulation and baseline age were associated with negative impact. Eight out of 17 cardiac parameters reached a minimal clinically important difference with a threshold of 1/3 standard deviation.ConclusionThe study shows a worsening of circumferential strain in dystrophic myocardium. The findings emphasize the significance of early and longitudinal assessment of cardiac function in DMD and identify early biomarkers of cardiac dysfunction to help design clinical trials to mitigate cardiac pathology. This study provides valuable non-invasive and non-contrast based natural history data of cardiac changes which can be used to design clinical trials or interpret the results of current trials aimed at mitigating the effects of decreased cardiac function in DMD.

Cardiac Magnetic Resonance Assessment of Response to Cardiac Resynchronization Therapy and Programming Strategies

ObjectivesThe objective was to determine the feasibility and effectiveness of cardiac magnetic resonance (CMR) cine and strain imaging before and after cardiac resynchronization therapy (CRT) for assessment of response and the optimal resynchronization pacing strategy. BackgroundCMR with cardiac implantable electronic devices can safely provide high-quality right ventricular/left ventricular (LV) ejection fraction (RVEF/LVEF) assessments and strain. MethodsCMR with cine imaging, displacement encoding with stimulated echoes for the circumferential uniformity ratio estimate with singular value decomposition (CURE-SVD) dyssynchrony parameter, and scar assessment was performed before and after CRT. Whereas the pre-CRT scan constituted a single “imaging set” with complete volumetric, strain, and scar imaging, multiple imaging sets with complete strain and volumetric data were obtained during the post-CRT scan for biventricular pacing (BIVP), LV pacing (LVP), and asynchronous atrial pacing modes by reprogramming the device outside the scanner between imaging sets. Results100 CMRs with a total of 162 imaging sets were performed in 50 patients (median age 70 years [IQR: 50-86 years]; 48% female). Reduction in LV end-diastolic volumes (P = 0.002) independent of CRT pacing were more prominent than corresponding reductions in right ventricular end-diastolic volumes (P = 0.16). A clear dependence of the optimal CRT pacing mode (BIVP vs LVP) on the PR interval (P = 0.0006) was demonstrated. The LVEF and RVEF improved more with BIVP than LVP with PR intervals ≥240 milliseconds (P = 0.025 and P = 0.002, respectively); the optimal mode (BIVP vs LVP) was variable with PR intervals <240 milliseconds. A lower pre-CRT displacement encoding with stimulated echoes (DENSE) CURE-SVD was associated with greater improvements in the post-CRT CURE-SVD (r = −0.69; P < 0.001), LV end-systolic volume (r = −0.58; P < 0.001), and LVEF (r = −0.52; P < 0.001). ConclusionsCMR evaluation with assessment of multiple pacing modes during a single scan after CRT is feasible and provides useful information for patient care with respect to response and the optimal pacing strategy.

The Prognostic Value of Left Ventricular Mechanical Dyssynchrony Derived from Cardiac MRI in Patients with Idiopathic Dilated Cardiomyopathy.

To investigate the prognostic value of mechanical dyssynchrony evaluated by deformable registration algorithm (DRA) analysis of cardiac MRI (CMR) in patients with idiopathic dilated cardiomyopathy (DCM). This secondary analysis of a prospective study (clinical trial no. ChiCTR1800017058) enrolled 409 patients (mean age, 48 years ± 14:300 men) with idiopathic DCM who underwent CMR between June 2012 and September 2018. Mechanical dyssynchrony was measured as standard deviation of time-to-peak (sdTTP) and uniformity ratio estimate (URE) indexes by DRA strain analysis. The primary endpoint included all-cause mortality and heart transplantation. The secondary endpoint included primary endpoint, aborted sudden cardiac death, and heart failure readmission. Cox regression analyses and Kaplan-Meier survival analysis were performed to identify the association between variables and outcomes. During a median follow-up of 25.1 months, 57 and 132 patients reached primary and secondary endpoints, respectively. Most URE indexes were significantly lower in patients reaching primary endpoint. In multivariable analysis, circumferential URE (CURE) at apical level was independently associated with primary endpoints (hazard ratio, 0.307 [95% CI: 0.106, 0.883]; P = .03) and secondary endpoints (hazard ratio, 0.452 [95% CI: 0.209, 0.979]; P = .04), whereas most sdTTP measures were not. Furthermore, among patients with left ventricular ejection fraction of less than 35% or presence of late gadolinium enhancement, those with CURE at apical level of less than 0.917 had a significantly higher rate of adverse outcomes. URE indexes were more predictive of prognostic outcomes compared with sdTTP measurements; the CURE at apical level was an independent predictor of adverse cardiac events in patients with DCM.Keywords: Heart, Outcomes Analysis, MR-ImagingClinical trial registration no. ChiCTR1800017058 Supplemental material is available for this article. See also commentary by Rajiah and François in this issue.© RSNA, 2021.

Abstract 15116: The Prognostic Value of Left Ventricular Mechanical Dyssynchrony in Patients With Idiopathic Dilated Cardiomyopathy

Backgrounds: The mechanical dyssynchrony has been commonly observed in idiopathic dilated cardiomyopathy (DCM) patients, and several cardiac magnetic resonance (CMR) imaging techniques were used to evaluate the mechanical dyssynchrony. Standard deviation of time-to-peak (T2Psd) and uniformity ratio estimate (URE) indices are two widely used parameters to reflect the incoordinate movement of the left ventricle. However, the prognostic value of mechanical dyssynchrony in DCM patients is not clear. Methods and Results: We prospectively enrolled 402 DCM patients undergoing CMR imaging between Jun 2012 to Sep 2018. Mechanical dyssynchrony was measured as T2Psd and URE indices by CMR deformable registration algorithm (DRA) analysis. The primary endpoint was defined as all-cause mortality and heart transplantation, and the secondary endpoint was a combination of primary endpoint, aborted sudden cardiac death, and heart failure readmission. Univariate and multivariate Cox regression analyses were performed to identify the association between variables and outcome. Survival curves were obtained by Kaplan-Meier survival analysis and compared by log-rank test. During a median follow-up of 25.1 months (IQR: 16.2-41.6), there were 57 patients reached primary endpoints, and secondary endpoints occurred in 132 patients. Circumferential uniformity ratio estimate (CURE) at basal, mid and apical level, radial uniformity ratio estimate (RURE)at mid and apical level and longitudinal uniformity ratio estimate (LURE) were significantly worse in patients with primary endpoint compared to patients without primary endpoint. While no significant differences were observed regarding the T2Psd value between patients with and without primary endpoints. In multivariate analysis, CURE at apical level was independently associated with primary endpoints (HR 0.214, P=0.005) and secondary endpoints (HR 0.402, P=0.018). Furthermore, among patients with LVEF &lt;35% or presence of LGE, those with decreased CURE at apical level (&lt;0.917) showed a significantly higher rate of adverse outcome. Conclusion: The CURE at apical level is an independent predictor of adverse cardiac events in DCM patients. Compared with T2Psd, URE index is a better predictor of adverse events.

CMR DENSE and the Seattle Heart Failure Model Inform Survival and Arrhythmia Risk After CRT

ObjectivesThis study sought to determine if combining the Seattle Heart Failure Model (SHFM-D) and cardiac magnetic resonance (CMR) provides complementary prognostic data for patients with cardiac resynchronization therapy (CRT) defibrillators. BackgroundThe SHFM-D is among the most widely used risk stratification models for overall survival in patients with heart failure and implantable cardioverter-defibrillators (ICDs), and CMR provides highly detailed information regarding cardiac structure and function. MethodsCMR Displacement Encoding with Stimulated Echoes (DENSE) strain imaging was used to generate the circumferential uniformity ratio estimate with singular value decomposition (CURE-SVD) circumferential strain dyssynchrony parameter, and the SHFM-D was determined from clinical parameters. Multivariable Cox proportional hazards regression was used to determine adjusted hazard ratios and time-dependent areas under the curve for the primary endpoint of death, heart transplantation, left ventricular assist device, or appropriate ICD therapies. ResultsThe cohort consisted of 100 patients (65.5 [interquartile range 57.7 to 72.7] years; 29% female), of whom 47% had the primary clinical endpoint and 18% had appropriate ICD therapies during a median follow-up of 5.3 years. CURE-SVD and the SHFM-D were independently associated with the primary endpoint (SHFM-D: hazard ratio: 1.47/SD; 95% confidence interval: 1.06 to 2.03; p = 0.02) (CURE-SVD: hazard ratio: 1.54/SD; 95% confidence interval: 1.12 to 2.11; p = 0.009). Furthermore, a favorable prognostic group (Group A, with CURE-SVD <0.60 and SHFM-D <0.70) comprising approximately one-third of the patients had a very low rate of appropriate ICD therapies (1.5% per year) and a greater (90%) 4-year survival compared with Group B (CURE-SVD ≥0.60 or SHFM-D ≥0.70) patients (p = 0.02). CURE-SVD with DENSE had a stronger correlation with CRT response (r = −0.57; p < 0.0001) than CURE-SVD with feature tracking (r = −0.28; p = 0.004). ConclusionsA combined approach to risk stratification using CMR DENSE strain imaging and a widely used clinical risk model, the SHFM-D, proved to be effective in this cohort of patients referred for CRT defibrillators. The combined use of CMR and clinical risk models represents a promising and novel paradigm to inform prognosis and device selection in the future.

Cardiac Magnetic Resonance Left Ventricular Mechanical Uniformity Alterations for Risk Assessment After Acute Myocardial Infarction

BackgroundDespite limitations as a stand‐alone parameter, left ventricular (LV) ejection fraction is the preferred measure of myocardial function and marker for postinfarction risk stratification. LV myocardial uniformity alterations may provide superior prognostic information after acute myocardial infarction, which was the subject of this study.Methods and ResultsConsecutive patients with acute myocardial infarction (n=1082; median age: 63 years; 75% male) undergoing cardiac magnetic resonance at a median of 3 days after infarction were included in this multicenter observational study. Circumferential and radial uniformity ratio estimates were derived from cardiac magnetic resonance feature tracking as markers of mechanical uniformity alterations (values between 0 and 1 with 1 reflecting perfect uniformity). The clinical end point was the 12‐month rate of major adverse cardiac events, consisting of all‐cause death, reinfarction, and new congestive heart failure. Patients with major adverse cardiac events (n=73) had significantly impaired circumferential uniformity ratio estimates (0.76 [interquartile range: 0.67–0.86] versus 0.84 [interquartile range: 0.76–0.89]; P<0.001) and radial uniformity ratio estimates (0.69 [interquartile range: 0.60–0.79] versus 0.76 [interquartile range: 0.67–0.83]; P<0.001) compared with patients without events. Although uniformity estimates did not provide independent prognostic information in the overall cohort, a circumferential uniformity ratio estimate below the median of 0.84 emerged as an independent predictor of outcome in postinfarction patients with LV ejection fraction >35% (n=959), even after adjustment for established risk factors (hazard ratio: 1.99; 95% CI, 1.06–3.74; P=0.033 in multivariable Cox regression analysis). In contrast, LV ejection fraction was not associated with adverse events in this subgroup of patients with acute myocardial infarction.ConclusionsCardiac magnetic resonance–derived estimates of mechanical uniformity alterations are novel markers for risk assessment after acute myocardial infarction, and the circumferential uniformity ratio estimate provides independent prognostic information for patients with preserved or only moderately reduced LV ejection fraction.

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

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. 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. 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. 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. 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.

Electromechanical and scar characteristics at left ventricular lead implant site in the context of overall dyssynchrony with cine DENSE predict cardiac resynchronization therapy outcomes

Background In clinical patients undergoing cardiac resynchronization therapy (CRT), myocardial properties (mechanical, electrical, and scar-mediated) at the left ventricular (LV) lead position (LVLP) and overall LV dyssynchrony (circumferential uniformity ratio estimate [CURE, 0-1]) are of interest with respect to CRT outcomes. We sought to define the relative importance of these factors for CRT response in a clinical CMR study with longitudinal follow-up.

Quantification of left ventricular dyssynchrony in patients with systolic dysfunction: a comparison of circumferential strain MR-tagging metrics.

To define which circumferential strain MR-tagging metrics of left intraventricular dyssynchrony better identifies patients with systolic dysfunction against control subjects. One hundred fifty subjects were studied: (i) controls with ejection fraction (EF) > 55% (n = 84), (ii) patients with EF ≤ 55% not eligible for cardiac resynchronization therapy (CRT) (n = 52), and (iii) patients eligible for CRT according to the ESC guidelines (n = 14). Tagging cine MR-based circumferential filtered strain curves were extracted. Six dyssynchrony indices were studied: standard deviation (SD) of peak strain (SD_Ecc_ES), SD of time-to-peak (SD_TTP), strain delay index (LIM), regional variance vector (RVV), circumferential uniformity ratio estimate (CURE), and uniformity of strain TTP (US_TTP). All metrics show significant differences between the three groups (ANOVA, P < 10(-4) ) and are correlated with EF. Significantly higher AUC values of ROC curves between patients with normal vs. decreased EF were obtained with SD_TTP (0.998) and CURE (0.995). Agreement among different methods was fair to good (kappa 0.32 to 0.89). Interobserver variability was best for CURE (1.2%) and US_TTP (0.8%) while more than 3-times larger for other metrics. SD_TTP and CURE are the most discriminant dyssynchrony metrics for systolic dysfunction. However, taking into account the method's variability argues in favor of indices of uniformity of the strain, ie, CURE and US_TTP.

Principle component analysis of myocardial strain to quantify left ventricular dyssynchrony

Background Cardiac resynchronization therapy (CRT) is effective for selected heart failure (HF) patients, but is associated with a 30-40% nonresponse rate. Identification of CRT responders may be improved with myocardial strain imaging. The circumferential uniformity ratio estimate (CURE ) measures mechanical dyssynchrony by Fourier series fitting of myocardial strains over space, but requires user interaction to define a range of cardiac phases over which CURE is calculated (time dependence). We hypothesize that principal component analysis (PCA) can quantify dyssynchrony in myocardial strain in a data-driven, time-independent manner that does not require any subjective user assessments of strain data.

Abstract 18768: Comparison of Displacement-Based and Radial Uniformity Ratio Estimate Dyssynchrony Metrics in Serial Echocardiography of Post-Infarct Mice

Background: Many of the existing dyssynchrony metrics rely on myocardial strain measurements, including circumferential uniformity ratio estimate (CURE) and related metrics such as RURE. Since strain is a derivative of displacement, amplification of noise in strain calculations due to noisy displacement data is common, thus compromising strain-based dyssynchrony metrics. We propose a novel displacement-based dyssynchrony metric, called Dyskinesia Index (DI), that is sensitive and consistent in detecting left ventricular (LV) dyssynchrony, particularly dyskinesia. Methods: Long-axis (LA) cines of 7 C57BL/6 mice were captured with a 30MHz ultrasound transducer. Baseline (B) data were acquired prior to myocardial infarction (MI) induced by a 1-hr occlusion of the LAD followed by reperfusion. Thereafter, cines were acquired at 2, 4, 7, 14 and 28 days post-MI. Displacements were quantified using speckle tracking on the LA cines. DI was determined using Fourier analysis of radial displacement distributed along the endocardial wall, and is the square root of the ratio of the zero-order power term to the sum of zero-order and a scaled first order power terms. Results: In Fig. 1, DI is compared to RURE at B and at 5 time-points post-MI. DI values at B are consistently close to 1 (0.96±0.01), and decrease significantly early after MI due to dyskinesia, reaching a minimum at D4 (0.64±0.08). After the first week, motion in the infarct zone becomes more akinetic due to scar formation and DI values partially recover to a plateau late after MI. ANOVA reveals significant differences between B and all post-MI time-points (p &lt; 0.05). In contrast, RURE is less sensitive to dyskinesia at D4 and post-MI estimates are only significant from B for after D4 (p &lt; 0.05). Conclusion: Strain-based measures of dyssynchrony are error-susceptible without proper filtering of displacement data. DI has been shown to work well in ultrasound B-mode images, where image artifacts can degrade displacement data.

Basic Science of Cardiac Resynchronization Therapy

Electromechanical dyssynchrony can markedly worsen heart failure (HF) morbidity and mortality, independent of traditional risk factors.1–4 Depending on the metric used, current estimates of the prevalence of dyssynchrony vary from 25–30% in patients with HF (based on QRS widening) up to 60%, based on tissue Doppler or MRI measures of dyssynchronous contraction of the left ventricle (LV).5,6 Cardiac resynchronization therapy (CRT) or biventricular pacing has emerged as a promising option to treat patients with HF and dyssynchronous contraction.7–9 The past few decades have seen the rise of pharmacotherapy, primarily through agents that antagonize the effect of excessive concentrations of circulating neurohormones, yet, HF-related morbidity and mortality remain high.3–6 Biventricular stimulation has been demonstrated to improve contractile performance in patients with mechanical dyssynchrony acutely and chronically while also prolonging long-term survival—something not yet achieved by drug therapy.10 Although the clinical and mechanical effectiveness of CRT are well described, 30% of patients do not benefit from CRT and clinical criteria to identify CRT nonresponders remain elusive8,11,12 Currently, the most widely used predictor of reverse remodeling is the presence of marked mechanical dyssynchrony before CRT, as indexed by the width of the QRS.13 Mechanical dyssynchrony seems important, yet imaging-based measures have not predicted response well14 and even improvement in dyssynchrony after initiation of CRT only weakly predicts chronic response.15 Limited understanding of the molecular mechanisms underlying reverse cardiac remodeling induced by CRT has hampered the selection of potential responders. In this review, we focus on the electrophysiological aspects and molecular networks underlying the benefits of CRT. We will review how CRT homogenizes regional differences in stress kinase signaling and electric remodeling and then review its global effect on myocyte function and its …

A Study of Mechanical Optimization Strategy for Cardiac Resynchronization Therapy Based on an Electromechanical Model

An optimal electrode position and interventricular (VV) delay in cardiac resynchronization therapy (CRT) improves its success. However, the precise quantification of cardiac dyssynchrony and magnitude of resynchronization achieved by biventricular (BiV) pacing therapy with mechanical optimization strategies based on computational models remain scant. The maximum circumferential uniformity ratio estimate (CURE) was used here as mechanical optimization index, which was automatically computed for 6 different electrode positions based on a three-dimensional electromechanical canine model of heart failure (HF) caused by complete left bundle branch block (CLBBB). VV delay timing was adjusted accordingly. The heart excitation propagation was simulated with a monodomain model. The quantification of mechanical intra- and interventricular asynchrony was then investigated with eight-node isoparametric element method. The results showed that (i) the optimal pacing location from maximal CURE of 0.8516 was found at the left ventricle (LV) lateral wall near the equator site with a VV delay of 60 ms, in accordance with current clinical studies, (ii) compared with electrical optimization strategy of E RMS, the LV synchronous contraction and the hemodynamics improved more with mechanical optimization strategy. Therefore, measures of mechanical dyssynchrony improve the sensitivity and specificity of predicting responders more. The model was subject to validation in future clinical studies.

Ventricular Dilation and Electrical Dyssynchrony Synergistically Increase Regional Mechanical Nonuniformity But Not Mechanical Dyssynchrony

Background— Heart failure (HF) in combination with mechanical dyssynchrony is associated with a high mortality rate. To quantify contractile dysfunction in patients with HF, investigators have proposed several indices of mechanical dyssynchrony, including percentile range of time to peak shortening (WTpeak), circumferential uniformity ratio estimate (CURE), and internal stretch fraction (ISF). The goal of this study was to compare the sensitivity of these indices to 4 major abnormalities responsible for cardiac dysfunction in dyssynchronous HF: dilation, negative inotropy, negative lusitropy, and dyssynchronous activation. Methods and Results— All combinations of these 4 major abnormalities were included in 3D computational models of ventricular electromechanics. Compared with a nonfailing heart model, ventricles were dilated, inotropy was reduced, twitch duration was prolonged, and activation sequence was changed from normal to left bundle branch block. In the nonfailing heart, CURE, ISF, and WTpeak were 0.97±0.004, 0.010±0.002, and 78±1 milliseconds, respectively. With dilation alone, CURE decreased 2.0±0.07%, ISF increased 58±47%, and WTpeak increased 31±3%. With dyssynchronous activation alone, CURE decreased 15±0.6%, ISF increased 14-fold (±3), and WTpeak increased 121±4%. With the combination of dilation and dyssynchronous activation, CURE decreased 23±0.8%, ISF increased 20-fold (±5), and WTpeak increased 147±5%. Conclusions— Dilation and left bundle branch block combined synergistically decreased regional cardiac function. CURE and ISF were sensitive to this combination, but WTpeak was not. CURE and ISF also reflected the relative nonuniform distribution of regional work better than WTpeak. These findings might explain why CURE and ISF are better predictors of reverse remodeling in cardiac resynchronization therapy.

Left ventricular dyssynchrony in patients with left bundle branch block and patients after myocardial infarction: integration of mechanics and viability by cardiac magnetic resonance

To quantify left ventricular (LV) dyssynchrony in patients with left bundle branch block (LBBB) and in patients after myocardial infarction (MI) applying an accelerated three-dimensional (3D) tagging cardiac magnetic resonance (CMR) technique, and to combine dyssynchrony information with viability data obtained by late gadolinium enhancement (LGE) CMR. Thirty-two patients (59 +/- 11 years) after first MI (Pats(MI)), 10 patients (63 +/- 10 years) with LBBB (ejection fraction < 40%; Pats(LBBB<40)), 13 patients (63 +/- 11) with LBBB (ejection fraction >or= 40%; Pats(LBBB >or=40 )), and 15 healthy controls (53 +/- 10 years) underwent 3D tagging CMR and LGE imaging at 1.5 T. As a measure of mechanical LV dyssynchrony, the standard deviation of T(max) over the LV, the circumferential uniformity ratio estimate (CURE) index, and a segmental-based circumferential systolic dyssynchrony index (SDI) were calculated. All three parameters detected significantly increased circumferential dyssynchrony in patients compared with controls. The CURE and SDI showed a good correlation (r = 0.93, P < 0.0001) and detected most severe dyssynchrony in Pats(LBBB<40) (P < 0.001 vs. controls, P < 0.005 vs. Pats(MI)). Systolic dyssynchrony index additionally allowed integration of localized viability information to yield SDI(viable) which was highest in Pats(LBBB<40). Dyssynchrony patterns in the LV can be quantified globally and regionally by 3D tagging CMR. Combination of viability and dyssynchrony information allows for a comprehensive dyssynchrony quantification in patients with LBBB or post-MI. Future studies are required to test the value of the method to predict responsiveness to resynchronization.

Usefulness of Left Ventricular Dyssynchrony After Acute Myocardial Infarction, Assessed by a Tagging Magnetic Resonance Image Derived Metric, as a Determinant of Ventricular Remodeling

Development of left ventricular (LV) remodeling after acute myocardial infarction (AMI) is a serious medical complication. We investigated the correlation of LV dyssynchrony after AMI with LV remodeling using magnetic resonance-myocardial tagging (MR-MT) derived dyssynchrony index (circumferential uniformity ratio estimate [CURE]). Forty-three patients diagnosed with ST-elevation AMI were analyzed. After treatment with primary percutaneous intervention, cardiac magnetic resonance imaging was performed to obtain a cine image, a delayed enhancement image, and an MR-MT image. CURE as a dyssynchrony index was calculated from the MR-MT image using HARP software (CURE 0 to 1 = dyssynchrony to synchrony). After 6 months, follow-up cardiac magnetic resonance imaging was performed to assess degree of LV remodeling. Sixteen patients (37%) had an increased LV end-systolic volume (ESV) >15% compared with baseline. The baseline LV dyssynchrony index, CURE, was significantly associated with ESV at 6 months (r = -0.49, p <0.001) and weakly correlated with change in ESV (percentage) compared with baseline values (r = -0.26, p = 0.08). Multivariate analysis showed that CURE was associated only with change in ESV (beta -0.39, p = 0.03). Subgroup analysis for patients with nonviable myocardium (infarct thickness >75%, n = 31) showed that this correlation was stronger (beta -0.52, p = 0.006), suggesting that CURE could predict progression of LV remodeling in patients with AMI and nonviable myocardium. LV dyssynchrony immediately after AMI is an important determinant of LV remodeling. In conclusion, the MR-MT dyssynchrony index, CURE, might be useful for prediction of LV remodeling in patients with AMI.

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

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). 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. 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. 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. 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.

Abstract 2713: Comparison of MRI Myocardial Tissue Tagging and Tissue Doppler Imaging for Assessment of Mechanical Dyssynchrony

Background: Echocardiographic (EC) indices of mechanical dyssynchrony (MD) are based largely upon longitudinal strain, whereas magnetic resonance imaging myocardial tissue tagging (MRI-MT) assessment is based on circumferential strain, the latter being the primary direction of myocardial contraction. Methods: We sought to compare cardiac MRI studies with an EC protocol using 2D imaging, tissue Doppler imaging (TDI), and M-mode in 32 subjects. Absolute strain, time to peak strain in 6 segments, TDI septal-to-lateral delay (SLD; MD if ≥ 70 ms), and M-mode septal-to-posterior wall motion delay (SPWMD; MD if ≥ 130 ms) were measured and compared to the MRI-MT-based CURE (circumferential uniformity ratio estimate, CURE; 0 –1, 0 = asynchrony, 1 = perfect synchrony; MD if &lt; 0.75), which recently has been shown to predict clinical CRT response. Results: The 8 control subjects (normal QRSd; CURE 0.975 ± 0.01; SLD 26 ± 27 ms) had less MD by MRI-MT (p = 0.0001) and TDI (p = 0.04) as compared to 24 subjects with ejection fraction ≤ 35% (QRSd 135 ≤ 35 ms; CURE 0.695 ± 0.17; SLD 59 ± 39 ms). There was a moderate correlation between TDI and MRI-MT (R = 0.62), with a discordance rate of 22% overall and 25% in cardiomyopathy subjects, in some cases due to abnormal CURE with normal SLD and, in others, normal CURE with abnormal SLD. The M-mode assay (SPWMD) could not be assessed in 10 patients with septal akinesis (AK), although there was MD by TDI and MRI-MT in most of these subjects. In the patients without AK, the discordance rate between TDI and M-mode was 33%. Conclusions: MRI-MT assessment of circumferential strain and MD is complementary to TDI with a good correlation, but also a significant discordance rate.

Diminished Left Ventricular Dyssynchrony and Impact of Resynchronization in Failing Hearts With Right Versus Left Bundle Branch Block

We compared mechanical dyssynchrony and the impact of cardiac resynchronization therapy (CRT) in failing hearts with a pure right (RBBB) versus left bundle branch block (LBBB). Cardiac resynchronization therapy is effective for treating failing hearts with conduction delay and discoordinate contraction. Most data pertain to LBBB delays. With RBBB, the lateral wall contracts early so that biventricular (BiV) pre-excitation may not be needed. Furthermore, the magnitude of dyssynchrony and impact of CRT in pure RBBB versus LBBB remains largely unknown. Dogs with tachypacing-induced heart failure combined with right or left bundle branch radiofrequency ablation were studied. Basal dyssynchrony and effects of single and BiV CRT on left ventricular (LV) function were assessed by pressure-volume catheter and tagged magnetic resonance imaging, respectively. Left bundle branch block and RBBB induced similar QRS widening, and LV function (ejection fraction, maximum time derivative of LV pressure [dP/dt(max)]) was similarly depressed in failing hearts with both conduction delays. Despite this, mechanical dyssynchrony was less in RBBB (circumferential uniformity ratio estimate [CURE] index: 0.80 +/- 0.03 vs. 0.58 +/- 0.09 for LBBB, p < 0.04; CURE 0-->1 is dyssynchronous-->synchronous). Cardiac resynchronization therapy had correspondingly less effect on hearts with RBBB than those with LBBB (i.e., 5.5 +/- 1.1% vs. 29.5 +/- 5.0% increase in dP/dt(max), p < 0.005), despite similar baselines. Furthermore, right ventricular-only pacing enhanced function and synchrony in RBBB as well or better than did BiV, whereas LV-only pacing worsened function. Less mechanical dyssynchrony is induced by RBBB than LBBB in failing hearts, and the corresponding impact of CRT on the former is reduced. Right ventricular-only pacing may be equally efficacious as BiV CRT in hearts with pure right bundle branch conduction delay.