Eva Sammut

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.

Noninvasive Assessment of LV Contraction Patterns Using CMR to Identify Responders to CRT

OBJECTIVES Type II activation describes the U-shaped electrical activation of the left ventricle (LV) with a line of block in patients with left bundle branch block (LBBB). We sought to determine if a corresponding pattern of contraction could be identified using cardiac magnetic resonance (CMR) cine imaging and whether this predicted response to cardiac resynchronization therapy (CRT). BACKGROUND U-shaped LV electrical activation in LBBB has been shown to predict favorable response to CRT. It is not known if the degree of electromechanical coupling is such that the same is true for LV contraction patterns. METHODS A total of 52 patients (48% ischemic) scheduled for CRT implantation prospectively underwent pre-implantation CMR cine analysis using endocardial contour tracking software to generate time-volume curves and contraction propagation maps. These were analyzed to assess the contraction sequence of the LV. The effect of contraction pattern on CRT response in terms of reverse remodeling (RR) and clinical parameters (New York Heart Association functional class, 6-min walk distance and Heart Failure Questionnaire score) was assessed at 6 months. RESULTS Two types of contraction pattern were identified; homogenous spread from septum to lateral wall (type I, n = 27) and presence of block with a subsequent U-shaped contraction pattern (type II, n = 25). Rates of RR in those with a type 2 pattern were significantly greater at 6 months (80% vs. 26%, p < 0.001) as was mean increase in 6-min walk distance (126 ± 106 m vs. 55 ± 60 m; p = 0.004). CONCLUSIONS Cine CMR can identify a U-shaped pattern of contraction which predicts increased echocardiographic and clinical response rates to CRT in patients with LBBB.

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.

Analysis of passive cardiac constitutive laws for parameter estimation using 3D tagged MRI

An unresolved issue in patient-specific models of cardiac mechanics is the choice of an appropriate constitutive law, able to accurately capture the passive behavior of the myocardium, while still having uniquely identifiable parameters tunable from available clinical data. In this paper, we aim to facilitate this choice by examining the practical identifiability and model fidelity of constitutive laws often used in cardiac mechanics. Our analysis focuses on the use of novel 3D tagged MRI, providing detailed displacement information in three dimensions. The practical identifiability of each law is examined by generating synthetic 3D tags from in silico simulations, allowing mapping of the objective function landscape over parameter space and comparison of minimizing parameter values with original ground truth values. Model fidelity was tested by comparing these laws with the more complex transversely isotropic Guccione law, by characterizing their passive end-diastolic pressure–volume relation behavior, as well as by considering the in vivo case of a healthy volunteer. These results show that a reduced form of the Holzapfel–Ogden law provides the best balance between identifiability and model fidelity across the tests considered.

Prevalence of myocardial crypts in a large retrospective cohort study by cardiovascular magnetic resonance

BackgroundMyocardial crypts are discrete clefts or fissures in otherwise compacted myocardium of the left ventricle (LV). Recent reports suggest a higher prevalence of crypts in patients with hypertrophic cardiomyopathy (HCM) and also within small samples of genotype positive but phenotype negative relatives. The presence of a crypt has been suggested to be a predictor of gene carrier status. However, the prevalence and clinical significance of crypts in the general population is unclear. We aimed to determine the prevalence of myocardial crypts in a large cohort of subjects using clinical cardiovascular magnetic resonance (CMR).MethodsConsecutive subjects referred for clinical CMR during a 12-month period (n = 1020, age 52.6 ± 17, males: 61%) were included. Crypts were defined as >50% invagination into normal myocardium and their overall prevalence, location and shape was investigated and compared between different patient groups.ResultsThe overall prevalence of crypts was 64/1020 (6.3%). In a predefined ‘normal’ control group the prevalence was lower (11/306, 3.6%, p = 0.031), but were equally prevalent in ischemic heart disease (12/236, 5.1%, p = n/s) and the combined non-ischemic cardiomyopathy (NICM) groups (24/373; 6.4%, p = n/s). Within the NICM group, crypts were significantly more common in HCM (9/76, 11.7%, p = 0.04) and hypertensive CM subjects (3/11, 27%, p = 0.03). In patients referred for CMR for family screening of inherited forms of CM, crypts were significantly more prevalent (10/41, 23%, p < 0.001), including a smaller group with a first degree relative with HCM (3/9, 33%, p = 0.01).ConclusionMyocardial crypts are relatively common in the normal population, and increasingly common in HCM and hypertensive cardiomyopathy. Crypts are also more frequently seen in normal phenotype subjects referred because of a family history of an inherited cardiomyopathy and HCM specifically. It is uncertain what the significance of crypts are in this group, and because of variability in the imaging protocols used and their relative frequency within the normal population, should not be used to clinically stratify these patients. Prospective studies are required to confirm the clinical significance of myocardial crypts, as their significance remains unclear.

Left Ventricular Epicardial Electrograms Show Divergent Changes in Action Potential Duration in Responders and Nonresponders to Cardiac Resynchronization Therapy

Background—A consistent feature of electrophysiological remodeling in heart failure is ventricular action potential duration (APD) prolongation. However, the effect of reverse remodeling on APD during cardiac resynchronization therapy (CRT) has not been determined in these patients. We hypothesized (1) that CRT may alter APD and (2) that the effect of CRT on APD may be different in patients who exhibit a good hemodynamic response to CRT compared with those with a poor response. Methods and Results—Left ventricular (LV) activation recovery intervals, as a surrogate for APD, were measured from the LV epicardium in 13 patients at day 0, 6 weeks, and 6 months after CRT implant. Responders to CRT were defined as those demonstrating a ≥15% reduction in LV end-systolic volume at 6 months. The responder group had a significant reduction in LV activation recovery interval (mean, −13±12 ms; median, −16 ms; interquartile range, −2 to −19 ms) during right ventricular pacing at 6 months (P<0.05). Conversely, the nonresponders showed a significant increase in activation recovery interval (mean, +22 ms±16; median, 17 ms; interquartile range, 8 to 35 ms; P<0.05). One patient in each group was on amiodarone. Conclusions—In patients with heart failure, LV epicardial APD (activation recovery interval) altered during CRT. The effect on APD was opposite in patients showing a good hemodynamic response compared with nonresponders. The findings may provide an explanation for the persistent high incidence of arrhythmias in some patients with CRT and the additional mortality benefit observed in responders of CRT.

Studying Dynamic Myofiber Aggregate Reorientation in Dilated Cardiomyopathy Using In Vivo Magnetic Resonance Diffusion Tensor Imaging

Background—The objective of this study is to assess the dynamic alterations of myocardial microstructure and strain between diastole and systole in patients with dilated cardiomyopathy relative to healthy controls using the magnetic resonance diffusion tensor imaging, myocardial tagging, and biomechanical modeling. Methods and Results—Dual heart-phase diffusion tensor imaging was successfully performed in 9 patients and 9 controls. Tagging data were acquired for the diffusion tensor strain correction and cardiac motion analysis. Mean diffusivity, fractional anisotropy, and myocyte aggregate orientations were compared between both cohorts. Cardiac function was assessed by left ventricular ejection fraction, torsion, and strain. Computational modeling was used to study the impact of cardiac shape on fiber reorientation and how fiber orientations affect strain. In patients with dilated cardiomyopathy, a more longitudinal orientation of diastolic myofiber aggregates was measured compared with controls. Although a significant steepening of helix angles (HAs) during contraction was found in the controls, consistent change in HAs during contraction was absent in patients. Left ventricular ejection fraction, cardiac torsion, and strain were significantly lower in the patients compared with controls. Computational modeling revealed that the dilated heart results in reduced HA changes compared with a normal heart. Reduced torsion was found to be exacerbated by steeper HAs. Conclusions—Diffusion tensor imaging revealed reduced reorientation of myofiber aggregates during cardiac contraction in patients with dilated cardiomyopathy relative to controls. Left ventricular remodeling seems to be an important factor in the changes to myocyte orientation. Steeper HAs are coupled with a worsening in strain and torsion. Overall, the findings provide new insights into the structural alterations in patients with dilated cardiomyopathy.

Age-related changes in intraventricular kinetic energy: a physiological or pathological adaptation?

Measuring intracardiac kinetic energy using four-dimensionl flow cardiac magnetic resonance provides important information on the decline in the early diastolic kinetic energy of blood with aging. The decline is comparable with that seen in those with heart failure and may be a marker of cardiac function.

Effects of tracer arrival time on the accuracy of high-resolution (voxel-wise) myocardial perfusion maps from contrast-enhanced first-pass perfusion magnetic resonance

First-pass perfusion cardiac magnetic resonance (CMR) allows the quantitative assessment of myocardial blood flow (MBF). However, flow estimates are sensitive to the delay between the arterial and myocardial tissue tracer arrival time (tOnset) and the accurate estimation of MBF relies on the precise identification of tOnset. The aim of this study is to assess the sensitivity of the quantification process to tOnset at voxel level. Perfusion data were obtained from series of simulated data, a hardware perfusion phantom, and patients. Fermi deconvolution has been used for analysis. A novel algorithm, based on sequential deconvolution, which minimizes the error between myocardial curves and fitted curves obtained after deconvolution, has been used to identify the optimal tOnset for each region. Voxel-wise analysis showed to be more sensitive to tOnset compared to segmental analysis. The automated detection of the tOnset allowed a net improvement of the accuracy of MBF quantification and in patients the identification of perfusion abnormalities in territories that were missed when a constant user-selected tOnset was used. Our results indicate that high-resolution MBF quantification should be performed with optimized tOnset values at voxel level.