Echocardiographic prediction of outcome after cardiac resynchronization therapy: conventional methods and recent developments

Echocardiography plays an important role in patient assessment before cardiac resynchronization therapy (CRT) and can monitor many of its mechanical effects in heart failure patients. Encouraged by the highly variable individual response observed in the major CRT trials, echocardiography-based measurements of mechanical dyssynchrony have been extensively investigated with the aim of improving response prediction and CRT delivery. Despite recent setbacks, these techniques have continued to develop in order to overcome some of their initial flaws and limitations. This review discusses the concepts and rationale of the available echocardiographic techniques, highlighting newer quantification methods and discussing some of the unsolved issues that need to be addressed

Presence of mechanical dyssynchrony in duchenne muscular dystrophy

<p>Abstract</p> <p>Background</p> <p>Cardiac dysfunction in boys with Duchenne muscular dystrophy (DMD) is a leading cause of death. Cardiac resynchronization therapy (CRT) has been shown to dramatically decrease mortality in eligible adult population with congestive heart failure. We hypothesized that mechanical dyssynchrony is present in DMD patients and that cardiovascular magnetic resonance (CMR) may predict CRT efficacy.</p> <p>Methods</p> <p>DMD patients (n = 236) were stratified into 4 groups based on age, diagnosis of DMD, left ventricular (LV) ejection fraction (EF), and presence of myocardial fibrosis defined as positive late gadolinum enhancement (LGE) compared to normal controls (n = 77). Dyssynchrony indices were calculated based on timing of CMR derived circumferential strain (e_cc). The calculated indices included cross-correlation delay (XCD), uniformity of strain (US), regional vector of variance (RVV), time to maximum strain (TTMS) and standard deviation (SD) of TTMS. Abnormal XCD value was defined as > normal + 2SD. US, RVV, TTMS and SD were calculated for patients with abnormal XCD.</p> <p>Results</p> <p>There was overall low prevalence of circumferential dyssynchrony in the entire DMD population; it increased to 17.1% for patients with abnormal EF and to 31.2% in the most advanced stage (abnormal EF with fibrosis). All but one DMD patient with mechanical dyssynchrony exhibited normal QRS duration suggesting absence of electrical dyssynchrony. The calculated US and RVV values (0.91 ± 0.09, 1.34 ± 0.48) indicate disperse rather than clustered dyssynchrony.</p> <p>Conclusion</p> <p>Mechanical dyssynchrony is frequent in boys with end stage DMD-associated cardiac dysfunction. It is associated with normal QRS complex as well as extensive lateral fibrosis. Based on these findings, it is unlikely that this patient population will benefit from CRT.</p

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

ObjectivesWe 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).BackgroundCardiac 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.MethodsDogs 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.ResultsLeft bundle branch block and RBBB induced similar QRS widening, and LV function (ejection fraction, maximum time derivative of LV pressure [dP/dtmax]) 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/dtmax, 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.ConclusionsLess 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

Noninvasive Multi-Modality Studies of Cardiac Electrophysiology, Mechanics, and Anatomical Substrate in Healthy Adults, Arrhythmogenic Cardiomyopathy, and Heart Failure

Heart disease is a leading cause of death and disability and is a major contributor to healthcare costs. Many forms of heart disease are caused by abnormalities in the electrical function of heart muscle cells or the cardiac conduction system. Electrocardiographic Imaging (ECGI) is a noninvasive modality for imaging cardiac electrophysiology. By combining recordings of the voltage distribution on the torso surface with anatomical images of the heart-torso geometry, ECGI reconstructs voltages on the epicardium. This thesis applies ECGI to novel studies of human heart function and disease and explores new combinations of ECGI with additional imaging modalities. ECGI was applied in combination with late gadolinium enhancement (LGE) scar imaging MRI in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). ARVC carries a high risk of sudden cardiac death, and the hallmark feature of ARVC is the progressive replacement of healthy myocardium with fibrous and fatty tissue. By combining ECGI and LGE in ARVC patients we found that there are signs of conduction abnormalities before structural abnormalities can be detected in ARVC patients. Electrical and structural abnormalities in ARVC patients co-localized. We also found that PVCs, potential triggers for arrhythmia, originated in regions of structural and electrical abnormalities. ECGI was applied in combination with speckle tracking echocardiography (STE) to longitudinally image heart failure patients undergoing cardiac resynchronization therapy (CRT). STE is an echocardiographic technique for measuring strain (contraction) in the heart. CRT is a highly effective treatment for heart failure, however, around 30% of patients do not respond to the treatment. ECGI was more effective for predicting response to CRT than the current standard ECG criteria or STE indices. The timing of peak contraction in STE did not accurately reflect the electrical activation sequence. CRT caused improvements in contraction that persisted even when pacing was disabled. CRT prolonged repolarization at the site of the LV pacing lead, which may increase the risk of arrhythmia in CRT patients. The above studies contribute novel observations of human disease physiology and demonstrate the clinical feasibility and effectiveness of ECGI for noninvasive assessment of ARVC and CRT

Gated 99mTc-tetrofosmin SPECT and gated 18F-FDG PET for the assessment of left ventricular myocardial dyssynchrony and its impact of the left ventricular function

Globally, cardiovascular disease (CVD) is the leading cause of mortality. Coronary artery disease (CAD) is one of the most prevalent types of CVD and annually accounts for around half of all CVD deaths. Therefore, CAD is one of the main contributors to massive health, and health-economic, burdens. A major factor in the morbidity and mortality of CAD is Left Ventricular Mechanical Dyssynchrony (LVMD). LVMD can also be used as a measure of disease burden and, potentially, clinical outcome Currently, the non-invasive standard test within nuclear medicine diagnostic imaging for patients with CAD is ECG-gated myocardial perfusion scintigraphy (MPS). Another well-recognized non-invasive imaging technique for myocardial metabolic imaging (MMI) is ECG-gated 18Ffluorodeoxyglucose PET (FDG-PET). Several computer software packages are currently available to provide phase analysis of ECG-gated MPS imaging and also ECG-gated FDG PET for the evaluation of LVMD. For our analyses we used Quantitative Gated SPECT (QGS, Cedars-Sinai, Los Angeles, California). Phase analysis of LVMD in patients with heart failure (HF) provides an additional tool to select patients for cardiac resynchronization therapy (CRT). The results of LVMD phase analysis of MPS and FDG-PET leads to a better selection of patients for CRT improving both treatment efficacy and cost efficiency. In our joint publication we investigated the performance of gated FDG PET phase analysis as compared to gated MPS as well as looked at possible cut-off values for FDG PET to define dyssynchrony. We analyzed the phase analysis parameters Bandwidth (BW), Phase Standard Deviation (Phase SD), and Entropy between SPECT and PET datasets. Based on the results we could only find moderate agreement between SPECT and PET to identify dyssynchrony. Entropy was the best single PET parameter to predict dyssynchrony. The optimized cut-off value for Entropy was 63%. In my first author publication we further investigated the relationship between LVMD and LV function. We were able to show that LVMD is linked to significantly higher end diastolic volume (EDV) and end systolic volume (ESV) as well as a significantly reduced left ventricular ejection fraction (LVEF) for MPS and gated FDG PET imaging. Additionally, we validated that the increasing severity of LVMD is associated with increasing EDV and ESV as well as a decreasing LVEF. The association was strongest for the dyssynchrony parameter Entropy. Both studies show that phase analysis results of QGS for gated MPS and gated FDG-PET not only assess LVMD but also demonstrate a good correlation with LV function. Furthermore, we demonstrated that the methods cannot be used interchangeably, even though in principle both measure the same parameters. Establishing reference ranges and cut-off values is difficult due to the lack of an external gold standard. There is, however, limitation for both studies. Neverteless, this novel approach of objective analysis of dyssynchrony, is a great way forward to dive deeper into the phase analysis of both imaging techniques and thus to expand the clinical efficiency of these methods

Three-dimensional mapping of mechanical activation patterns, contractile dyssynchrony and dyscoordination by two-dimensional strain echocardiography: Rationale and design of a novel software toolbox

<p>Abstract</p> <p>Background</p> <p>Dyssynchrony of myocardial deformation is usually described in terms of variability only (e.g. standard deviations SD's). A description in terms of the spatio-temporal distribution pattern (vector-analysis) of dyssynchrony or by indices estimating its impact by expressing dyscoordination of shortening in relation to the global ventricular shortening may be preferential. Strain echocardiography by speckle tracking is a new non-invasive, albeit 2-D imaging modality to study myocardial deformation.</p> <p>Methods</p> <p>A post-processing toolbox was designed to incorporate local, speckle tracking-derived deformation data into a 36 segment 3-D model of the left ventricle. Global left ventricular shortening, standard deviations and vectors of timing of shortening were calculated. The impact of dyssynchrony was estimated by comparing the end-systolic values with either early peak values only (early shortening reserve ESR) or with all peak values (virtual shortening reserve VSR), and by the internal strain fraction (ISF) expressing dyscoordination as the fraction of deformation lost internally due to simultaneous shortening and stretching. These dyssynchrony parameters were compared in 8 volunteers (NL), 8 patients with Wolff-Parkinson-White syndrome (WPW), and 7 patients before (LBBB) and after cardiac resynchronization therapy (CRT).</p> <p>Results</p> <p>Dyssynchrony indices merely based on variability failed to detect differences between WPW and NL and failed to demonstrate the effect of CRT. Only the 3-D vector of onset of shortening could distinguish WPW from NL, while at peak shortening and by VSR, ESR and ISF no differences were found. All tested dyssynchrony parameters yielded higher values in LBBB compared to both NL and WPW. CRT reduced the spatial divergence of shortening (both vector magnitude and direction), and improved global ventricular shortening along with reductions in ESR and dyscoordination of shortening expressed by ISF.</p> <p>Conclusion</p> <p>Incorporation of local 2-D echocardiographic deformation data into a 3-D model by dedicated software allows a comprehensive analysis of spatio-temporal distribution patterns of myocardial dyssynchrony, of the global left ventricular deformation and of newer indices that may better reflect myocardial dyscoordination and/or impaired ventricular contractile efficiency. The potential value of such an analysis is highlighted in two dyssynchronous pathologies that impose particular challenges to deformation imaging.</p

Assessment of distribution and evolution of Mechanical dyssynchrony in a porcine model of myocardial infarction by cardiovascular magnetic resonance

BACKGROUND: We sought to investigate the relationship between infarct and dyssynchrony post- myocardial infarct (MI), in a porcine model. Mechanical dyssynchrony post-MI is associated with left ventricular (LV) remodeling and increased mortality. METHODS: Cine, gadolinium-contrast, and tagged cardiovascular magnetic resonance (CMR) were performed pre-MI, 9 ± 2 days (early post-MI), and 33 ± 10 days (late post-MI) post-MI in 6 pigs to characterize cardiac morphology, location and extent of MI, and regional mechanics. LV mechanics were assessed by circumferential strain (eC). Electro-anatomic mapping (EAM) was performed within 24 hrs of CMR and prior to sacrifice. RESULTS: Mean infarct size was 21 ± 4% of LV volume with evidence of post-MI remodeling. Global eC significantly decreased post MI (-27 ± 1.6% vs. -18 ± 2.5% (early) and -17 ± 2.7% (late), p &lt; 0.0001) with no significant change in peri-MI and MI segments between early and late time-points. Time to peak strain (TTP) was significantly longer in MI, compared to normal and peri-MI segments, both early (440 ± 40 ms vs. 329 ± 40 ms and 332 ± 36 ms, respectively; p = 0.0002) and late post-MI (442 ± 63 ms vs. 321 ± 40 ms and 355 ± 61 ms, respectively; p = 0.012). The standard deviation of TTP in 16 segments (SD16) significantly increased post-MI: 28 ± 7 ms to 50 ± 10 ms (early, p = 0.012) to 54 ± 19 ms (late, p = 0.004), with no change between early and late post-MI time-points (p = 0.56). TTP was not related to reduction of segmental contractility. EAM revealed late electrical activation and greatly diminished conduction velocity in the infarct (5.7 ± 2.4 cm/s), when compared to peri-infarct (18.7 ± 10.3 cm/s) and remote myocardium (39 ± 20.5 cm/s). CONCLUSIONS: Mechanical dyssynchrony occurs early after MI and is the result of delayed electrical and mechanical activation in the infarct

Cardiac MR Elastography: Comparison with left ventricular pressure measurement

Purpose of the Study: To compare magnetic resonance elastography (MRE) with ventricular pressure changes in an animal model. Methods: Three pigs of different cardiac physiology (weight, 25 to 53 kg; heart rate, 61 to 93 bpm; left ventricular [LV] end-diastolic volume, 35 to 70 ml) were subjected to invasive LV pressure measurement by catheter and noninvasive cardiac MRE. Cardiac MRE was performed in a short-axis view of the heart and applying a 48.3-Hz shear-wave stimulus. Relative changes in LV-shear wave amplitudes during the cardiac cycle were analyzed. Correlation coefficients between wave amplitudes and LV pressure as well as between wave amplitudes and LV diameter were determined. Results: A relationship between MRE and LV pressure was observed in all three animals (R-square [greater than or equal to] 0.76). No correlation was observed between MRE and LV diameter (R-square [less than or equal to] 0.15). Instead, shear wave amplitudes decreased 102 +/- 58 ms earlier than LV diameters at systole and amplitudes increased 175 +/- 40 ms before LV dilatation at diastole. Amplitude ratios between diastole and systole ranged from 2.0 to 2.8, corresponding to LV pressure differences of 60 to 73 mmHg. Conclusion: Externally induced shear waves provide information reflecting intraventricular pressure changes which, if substantiated in further experiments, has potential to make cardiac MRE a unique noninvasive imaging modality for measuring pressure-volume function of the heart

3D cine DENSE MRI: ventricular segmentation and myocardial stratin analysis

Includes abstract. Includes bibliographical references