John Stirrat

Prediction of Arrhythmic Events in Ischemic and Dilated Cardiomyopathy Patients Referred for Implantable Cardiac Defibrillator Evaluation of Multiple Scar Quantification Measures for Late Gadolinium Enhancement Magnetic Resonance Imaging

Background— Scar signal quantification using late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) identifies patients at higher risk of future events, both in ischemic cardiomyopathy (ICM) and nonischemic dilated cardiomyopathy (DCM). However, the ability of scar signal burden to predict events in such patient groups at the time of referral for implantable cardioverter-defibrillator (ICD) has not been well explored. This study evaluates the predictive use of multiple scar quantification measures in ICM and DCM patients being referred for ICD. Methods and Results— One hundred twenty-four consecutive patients referred for ICD therapy (59 with ICM and 65 with DCM) underwent a standardized LGE-CMR protocol with blinded, multithreshold scar signal quantification and, for those with ICM, peri-infarct signal quantification. Patients were followed prospectively for the primary combined outcome of appropriate ICD therapy, survived cardiac arrest, or sudden cardiac death. At a mean follow-up of 632 ± 262 days, 18 patients (15%) had suffered the primary outcome. Total scar was significantly higher among those suffering a primary outcome, a relationship maintained within each cardiomyopathy cohort (P<0.01 for all comparisons). Total scar was the strongest independent predictor of the primary outcome and demonstrated a negative predictive value of 86%. In the ICM subcohort, peri-infarct signal showed only a nonsignificant trend toward elevation among those having a primary end point. Conclusions— Myocardial scar quantification by LGE-CMR predicts arrhythmic events in patients being evaluated for ICD eligibility irrespective of cardiomyopathy etiology.

Interactive Hierarchical-Flow Segmentation of Scar Tissue From Late-Enhancement Cardiac MR Images

We propose a novel multi-region image segmentation approach to extract myocardial scar tissue from 3-D whole-heart cardiac late-enhancement magnetic resonance images in an interactive manner. For this purpose, we developed a graphical user interface to initialize a fast max-flow-based segmentation algorithm and segment scar accurately with progressive interaction. We propose a partially-ordered Potts (POP) model to multi-region segmentation to properly encode the known spatial consistency of cardiac regions. Its generalization introduces a custom label/region order constraint to Potts model to multi-region segmentation. The combinatorial optimization problem associated with the proposed POP model is solved by means of convex relaxation, for which a novel multi-level continuous max-flow formulation, i.e., the hierarchical continuous max-flow (HMF) model, is proposed and studied. We demonstrate that the proposed HMF model is dual or equivalent to the convex relaxed POP model and introduces a new and efficient hierarchical continuous max-flow based algorithm by modern convex optimization theory. In practice, the introduced hierarchical continuous max-flow based algorithm can be implemented on the parallel GPU to achieve significant acceleration in numerics. Experiments are performed in 50 whole heart 3-D LE datasets, 35 with left-ventricular and 15 with right-ventricular scar. The experimental results are compared to full-width-at-half-maximum and Signal-threshold to reference-mean methods using manual expert myocardial segmentations and operator variabilities and the effect of user interaction are assessed. The results indicate a substantial reduction in image processing time with robust accuracy for detection of myocardial scar. This is achieved without the need for additional region constraints and using a single optimization procedure, substantially reducing the potential for error.

Influence of pacing site characteristics on response to cardiac resynchronization therapy.

Background—Transmural scar occupying left ventricular (LV) pacing regions has been associated with reduced response to cardiac resynchronization therapy (CRT). However, spatial influences of lead tip delivery relative to scar at both pacing sites remain poorly explored. This study evaluated scar distribution relative to LV and right ventricular (RV) lead tip placement through coregistration of late gadolinium enhancement MRI and cardiac computed tomographic (CT) findings. Influences on CRT response were assessed by serial echocardiography. Methods and Results—Sixty patients receiving CRT underwent preimplant late gadolinium enhancement MRI, postimplant cardiac CT, and serial echocardiography. Blinded segmental evaluations of mechanical delay, percentage scar burden, and lead tip location were performed. Response to CRT was defined as a reduction in LV end-systolic volume ≥15% at 6 months. The mean age and LV ejection fraction were 64±9 years and 25±7%, respectively. Mean scar volume was higher among CRT nonresponders for both the LV (23±23% versus 8±14% [P=0.01]) and RV pacing regions (40±32% versus 24±30% [P=0.04]). Significant pacing region scar was identified in 13% of LV pacing regions and 37% of RV pacing regions. Absence of scar in both regions was associated with an 81% response rate compared with 55%, 25%, and 0%, respectively, when the RV, LV, or both pacing regions contained scar. LV pacing region dyssynchrony was not predictive of response. Conclusions—Myocardial scar occupying the LV pacing region is associated with nonresponse to CRT. Scar occupying the RV pacing region is encountered at higher frequency and seems to provide a more intermediate influence on CRT response.

Prevalence of Myocardial Fibrosis Patterns in Patients With Systolic Dysfunction Prognostic Significance for the Prediction of Sudden Cardiac Arrest or Appropriate Implantable Cardiac Defibrillator Therapy

Background—Late gadolinium enhancement-cardiac magnetic resonance is increasingly performed in patients with systolic dysfunction. Numerous patterns of fibrosis are commonly reported among this population. However, the relative prevalence and prognostic significance of these findings remains uncertain. Methods and Results—Three hundred eighteen consecutive patients referred for late gadolinium enhancement-cardiac magnetic resonance and a left ventricular ejection fraction <55% were followed up for the primary end point of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy. Late gadolinium enhancement images were blindly interpreted for the presence of 6 distinct pattern(s) of myocardial fibrosis in addition to signal threshold-based quantification of total fibrosis volume. The mean age and left ventricular ejection fraction of participants were 62.0±12.9 years and 32.6±11.9%, respectively. Any pattern of myocardial fibrosis was seen in 248 patients (78%) with ≥2 patterns present in 25% of patients. During follow-up (median of 467 days), 49 patients (15%) had a primary outcome. After adjustment for left ventricular ejection fraction, cardiomyopathy pathogenesis, and total fibrosis volume, the presence of a midwall striae pattern of fibrosis was an independent predictor of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy with a hazard ratio of 2.4 (95% confidence interval, 1.2–4.6; P=0.01); this finding is present in 30% of patients with nonischemic and 15% of patients with ischemic cardiomyopathy. Cumulative event rate was significantly higher among those with midwall striae, particularly among those with a left ventricular ejection fraction >35% (40% versus 6%; P=0.005). Conclusions—Patients with systolic dysfunction frequently demonstrate multiple patterns of myocardial fibrosis. Of these, a midwall striae pattern of fibrosis is the strongest independent predictor of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy.Background— Late gadolinium enhancement-cardiac magnetic resonance is increasingly performed in patients with systolic dysfunction. Numerous patterns of fibrosis are commonly reported among this population. However, the relative prevalence and prognostic significance of these findings remains uncertain. Methods and Results— Three hundred eighteen consecutive patients referred for late gadolinium enhancement-cardiac magnetic resonance and a left ventricular ejection fraction 35% (40% versus 6%; P =0.005). Conclusions— Patients with systolic dysfunction frequently demonstrate multiple patterns of myocardial fibrosis. Of these, a midwall striae pattern of fibrosis is the strongest independent predictor of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy.

Accuracy and reproducibility of semi-automated late gadolinium enhancement quantification techniques in patients with hypertrophic cardiomyopathy

BackgroundThe presence and extent of late gadolinium enhancement (LGE) has been associated with adverse events in patients with hypertrophic cardiomyopathy (HCM). Signal intensity (SI) threshold techniques are routinely employed for quantification; Full-Width at Half-Maximum (FWHM) techniques are suggested to provide greater reproducibility than Signal Threshold versus Reference Mean (STRM) techniques, however the accuracy of these approaches versus the manual assignment of optimal SI thresholds has not been studied. In this study, we compared all known semi-automated LGE quantification techniques for accuracy and reproducibility among patients with HCM.MethodsSeventy-six HCM patients (51 male, age 54 ±13 years) were studied. Total LGE volume was quantified using 7 semi-automated techniques and compared to expert manual adjustment of the SI threshold to achieve optimal segmentation. Techniques tested included STRM based thresholds of >2, 3, 4, 5 and 6 SD above mean SI of reference myocardium, the FWHM technique, and the Otsu-auto-threshold (OAT) technique. The SI threshold chosen by each technique was recorded for all slices. Bland-Altman analysis and intra-class correlation coefficients (ICC) were reported for each semi-automated technique versus expert, manually adjusted LGE segmentation. Intra- and inter-observer reproducibility assessments were also performed.ResultsFifty-two of 76 (68%) patients showed LGE on a total of 202 slices. For accuracy, the STRM >3SD technique showed the greatest agreement with manual segmentation (ICC =0.97, mean difference and 95% limits of agreement =1.6 ± 10.7 g) while STRM >6SD, >5SD, 4SD and FWHM techniques systematically underestimated total LGE volume. Slice based analysis of selected SI thresholds similarly showed the STRM >3SD threshold to most closely approximate manually adjusted SI thresholds (ICC =0.88). For reproducibility, the intra- and inter-observer reproducibility of the >3SD threshold demonstrated an acceptable mean difference and 95% limits of agreement of -0.5 ± 6.8 g and -0.9 ± 5.6 g, respectively.ConclusionsFWHM segmentation provides superior reproducibility, however systematically underestimates total LGE volume compared to manual segmentation in patients with HCM. The STRM >3SD technique provides the greatest accuracy while retaining acceptable reproducibility and may therefore be a preferred approach for LGE quantification in this population.

Stress Hypoperfusion and Tissue Injury in Hypertrophic Cardiomyopathy: Spatial Characterization Using High-Resolution 3-Tesla Magnetic Resonance Imaging

Background— Ischemia and tissue injury are common in patients with hypertrophic cardiomyopathy. Cardiovascular magnetic resonance imaging offers combined evaluations of each phenomenon at sufficiently high resolution to examine transmural spatial distribution. In this prospective cohort study, we examine the spatial distribution of stress perfusion abnormalities and tissue injury in patients with hypertrophic cardiomyopathy. Methods and Results— One hundred consecutive patients with hypertrophic cardiomyopathy underwent cardiovascular magnetic resonance imaging. Cine, stress perfusion, late gadolinium enhancement, and T2-weighted imaging techniques were used. Each was spatially coregistered according to predefined segmental and subsegmental models and was blindly analyzed for abnormalities using validated techniques. Spatial associations among stress perfusion, late gadolinium enhancement, and T2 imaging were made at segmental and subsegmental levels. Of the 100 patients studied, the phenotype was septal in 86 and apical in 14. Late gadolinium enhancement imaging was abnormal in 79 patients (79%). Eighty-six patients met prespecified safety criteria to undergo stress perfusion, and ischemia was identified in 46 patients (57%). T2 imaging was available in 81 patients and was abnormal in 19 (29%). The dominant distribution of all 3 findings was to segment with hypertrophy. Subsegmental analysis revealed geographic dominance of ischemia within the subendocardial zones. However, this zone was most commonly spared from late gadolinium enhancement and T2 abnormalities, typically seen in midwall and subepicardial zones. Conclusions— Inducible hypoperfusion is a common finding in hypertrophic cardiomyopathy and is typically identified within segments exhibiting imaging markers of tissue injury. However, the respective transmural dominance of these phenomena seems distinct. Alternate factors contributing to a regional susceptibility to tissue injury are deserving of further study.Background— Ischemia and tissue injury are common in patients with hypertrophic cardiomyopathy. Cardiovascular magnetic resonance imaging offers combined evaluations of each phenomenon at sufficiently high resolution to examine transmural spatial distribution. In this prospective cohort study, we examine the spatial distribution of stress perfusion abnormalities and tissue injury in patients with hypertrophic cardiomyopathy. Methods and Results— One hundred consecutive patients with hypertrophic cardiomyopathy underwent cardiovascular magnetic resonance imaging. Cine, stress perfusion, late gadolinium enhancement, and T2-weighted imaging techniques were used. Each was spatially coregistered according to predefined segmental and subsegmental models and was blindly analyzed for abnormalities using validated techniques. Spatial associations among stress perfusion, late gadolinium enhancement, and T2 imaging were made at segmental and subsegmental levels. Of the 100 patients studied, the phenotype was septal in 86 and apical in 14. Late gadolinium enhancement imaging was abnormal in 79 patients (79%). Eighty-six patients met prespecified safety criteria to undergo stress perfusion, and ischemia was identified in 46 patients (57%). T2 imaging was available in 81 patients and was abnormal in 19 (29%). The dominant distribution of all 3 findings was to segment with hypertrophy. Subsegmental analysis revealed geographic dominance of ischemia within the subendocardial zones. However, this zone was most commonly spared from late gadolinium enhancement and T2 abnormalities, typically seen in midwall and subepicardial zones. Conclusions— Inducible hypoperfusion is a common finding in hypertrophic cardiomyopathy and is typically identified within segments exhibiting imaging markers of tissue injury. However, the respective transmural dominance of these phenomena seems distinct. Alternate factors contributing to a regional susceptibility to tissue injury are deserving of further study.

The Prognostic Role of Late Gadolinium Enhancement Magnetic Resonance Imaging in Patients With Cardiomyopathy

Cardiovascular magnetic resonance imaging (CMRI) is currently considered part of standard care at many academic centres for the evaluation of patients with ischemic or nonischemic cardiomyopathy. While CMRI provides unparalleled diagnostic versatility for the assessment of myocardial function, perfusion, and tissue health, evidence supporting its prognostic value for the prediction of important cardiovascular events is now emerging. Given the low specificity of currently available clinical markers in patients with cardiomyopathy, more-robust biomarkers aimed at identifying those at high risk of sudden cardiac death and other relevant outcomes are desirable. Late gadolinium enhancement (LGE) CMRI offers the novel capacity to quantify the burden of myocardial fibrosis, a common pathophysiological end point of most cardiomyopathy states. As such, it has the potential to be a robust and ubiquitous marker of cardiovascular events related to the presence of advanced tissue disease. This review paper focuses on the evidence to date supporting LGE imaging as a tool for the prediction of future cardiovascular events in patients with ischemic and nonischemic cardiomyopathy.

A fast convex optimization approach to segmenting 3d scar tissue from delayed-enhancement cardiac MR images

We propose a novel multi-region segmentation approach through a partially-ordered ports (POP) model to segment myocardial scar tissue solely from 3D cardiac delayed-enhancement MR images (DE-MRI). The algorithm makes use of prior knowledge of anatomical spatial consistency and employs customized label ordering to constrain the segmentation without prior knowledge of geometric representation. The proposed method eliminates the need for regional constraint segmentations, thus reduces processing time and potential sources of error. We solve the proposed optimization problem by means of convex relaxation and introduce its duality: the hierarchical continuous max-flow (HMF) model, which amounts to an efficient numerical solver to the resulting convex optimization problem. Experiments are performed over ten DE-MRI data sets. The results are compared to a FWHM (full-width at half-maximum) method and the inter- and intra-operator variabilities assessed.

Model-Based Navigation of Left and Right Ventricular Leads to Optimal Targets for Cardiac Resynchronization Therapy A Single-Center Feasibility Study

Background—Left ventricular (LV) and right ventricular pacing site characteristics have been shown to influence response to cardiac resynchronization therapy (CRT). This study aimed to determine the clinical feasibility of image-guided lead delivery using a 3-dimensional navigational model displaying both LV and right ventricular (RV) pacing targets. Serial echocardiographic measures of clinical response and procedural metrics were evaluated. Methods and Results—Thirty-one consecutive patients underwent preimplant cardiac MRI with the generation of a 3-dimensional navigational model depicting optimal segmental targets for LV and RV leads. Lead delivery was guided by the model in matched views to intraprocedural fluoroscopy. Blinded assessment of final lead tip location was performed from postprocedural cardiac computed tomography. Clinical and LV remodeling response criteria were assessed at baseline, 3 months, and 6 months using a 6-minute hall walk, quality of life questionnaire, and echocardiography. Mean age and LV ejection fraction was 66±8 years and 26±8%, respectively. LV leads were successfully delivered to a target or adjacent segment in 30 of 31 patients (97%), 68% being nonposterolateral. RV leads were delivered to a target or adjacent segment in 30 of 31 patients (97%), 26% being nonapical. Twenty-three patients (74%) met standard criteria for response (LV end-systolic volume reduction ≥15%), 18 patients (58%) for super-response (LV end-systolic volume reduction ≥30%). LV ejection fraction improved at 6 months (31±8 versus 26±8%, P=0.04). Conclusions—This study demonstrates clinical feasibility of dual cardiac resynchronization therapy lead delivery to optimal targets using a 3-dimensional navigational model. High procedural success, acceptable procedural times, and a low rate of early procedural complications were observed. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01640769.

Right Ventricular Ejection Fraction Is Incremental to Left Ventricular Ejection Fraction for the Prediction of Future Arrhythmic Events in Patients With Systolic Dysfunction

Background— Left ventricular ejection fraction remains the primary risk stratification tool used in the selection of patients for implantable cardioverter defibrillator therapy. However, this solitary marker fails to identify a substantial portion of patients experiencing sudden cardiac arrest. In this study, we examined the incremental value of considering right ventricular ejection fraction for the prediction of future arrhythmic events in patients with systolic dysfunction using the gold standard of cardiovascular magnetic resonance. Methods and Results— Three hundred fourteen consecutive patients with ischemic cardiomyopathy or nonischemic dilated cardiomyopathy undergoing cardiovascular magnetic resonance were followed for the primary outcome of sudden cardiac arrest or appropriate implantable cardioverter defibrillator therapy. Blinded quantification of left ventricular and right ventricular (RV) volumes was performed from standard cine imaging. Quantification of fibrosis from late gadolinium enhancement imaging was incrementally performed. RV dysfunction was defined as right ventricular ejection fraction ⩽45%. Among all patients (164 ischemic cardiomyopathy, 150 nonischemic dilated cardiomyopathy), the mean left ventricular ejection fraction was 32±12% (range, 6–54%) with mean right ventricular ejection fraction of 48±15% (range, 7–78%). At a median of 773 days, 49 patients (15.6%) experienced the primary outcome (9 sudden cardiac arrest, 40 appropriate implantable cardioverter defibrillator therapies). RV dysfunction was independently predictive of the primary outcome (hazard ratio=2.98; P=0.002). Among those with a left ventricular ejection fraction >35% (N=121; mean left ventricular ejection fraction, 45±6%), RV dysfunction provided an adjusted hazard ratio of 4.2 (P=0.02). Conclusions— RV dysfunction is a strong, independent predictor of arrhythmic events. Among patients with mild to moderate LV dysfunction, a cohort greatly contributing to global sudden cardiac arrest burden, this marker provides robust discrimination of high- versus low-risk subjects.