Objective criteria for septal fibrosis in non-ischemic dilated cardiomyopathy: validation for the prediction of future cardiovascular events.

BACKGROUND: Expert subjective reporting of mid-wall septal fibrosis on late gadolinium enhancement (LGE) images has been shown to predict major cardiovascular outcomes in patients with non-ischemic dilated cardiomyopathy (NIDCM). This study aims to establish objective criteria for non-experts to report clinically relevant septal fibrosis and compare its performance by such readers versus experts for the prediction of cardiovascular events. METHODS: LGE cardiovascular magnetic resonance (CMR) was performed in 118 consecutive patients with NIDCM (mean age 57 ± 14, 42 % female) and the presence of septal fibrosis scored by expert readers. CMR-naive readers performed signal threshold-based LGE quantification by referencing mean values of remote tissue and applying these to a pre-defined anatomic region to measure septal fibrosis. All patients were followed for the primary composite outcome of cardiac mortality or appropriate implantable cardioverter-defibrillator (ICD) therapy. RESULTS: The mean LVEF was 32 ± 12 %. At a median follow-up of 1.9 years, 20 patients (17 %) experienced a primary composite outcome. Expert visual scoring identified 55 patients with septal fibrosis. Non-expert septal fibrosis quantification was highly reproducible and identified mean septal fibrosis burden for three measured thresholds as follows; 5SD: 2.9 ± 3.6 %, 3SD: 6.9 ± 6.3 %, and 2SD: 11.1 ± 7.5 % of the left ventricular (LV) mass, respectively. By ROC analysis, optimal thresholds for prediction of the primary outcome were; 5SD: 2.74 % (HR 8.7, p < 0.001), 3SD: 6.63 % (HR 5.7, p = 0.001) and 2SD: 10.15 % (HR 6.1, p = 0.001). By comparison, expert visual scoring provided a HR of 5.3 (p = 0.001). In adjusted analysis, objective quantification by a novice reader (>5SD threshold) was the strongest independent predictor of the primary outcome (HR 8.7) and provided improved risk reclassification beyond LVEF alone (NRI 0.54, 95 % CI 0.16-0.92, p = 0.005). CONCLUSIONS: Novice readers were able to achieve superior risk prediction for future cardiovascular events versus experts using objective criteria for septal fibrosis in patients with NIDCM. Patients with a septal fibrosis burden >2.74 % of the LV mass (>5SD threshold) were at a 9-fold higher risk of cardiac death or appropriate ICD therapy versus those not meeting this criteria. As such, this study validates reproducible criteria applicable to all levels of expertise to identify NIDCM patients at high risk of future cardiovascular events.

Influence of phase correction of late gadolinium enhancement images on scar signal quantification in patients with ischemic and non-ischemic cardiomyopathy.

BACKGROUND: Myocardial fibrosis imaging using late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) has been validated as a quantitative predictive marker for response to medical, surgical, and device therapy. To date, all such studies have examined conventional, non-phase corrected magnitude images.  However, contemporary practice has rapdily adopted phase-corrected image reconstruction. We sought to investigate the existence of any systematic bias between threshold-based scar quantification performed on conventional magnitude inversion recovery (MIR) and matched phase sensitive inversion recovery (PSIR) images. METHODS: In 80 patients with confirmed ischemic (N = 40), or non-ischemic (n = 40) myocardial fibrosis, and also in a healthy control cohort (N = 40) without fibrosis, myocardial late enhancement was quantified using a Signal Threshold Versus Reference Myocardium technique (STRM) at ≥2, ≥3, and ≥5 SD threshold, and also using the Full Width at Half Maximal (FWHM) technique. This was performed on both MIR and PSIR images and values compared using linear regression and Bland-Altman analyses. RESULTS: Linear regression analysis demonstrated excellent correlation for scar volumes between MIR and PSIR images at all three STRM signal thresholds for the ischemic (N = 40, r = 0.96, 0.95, 0.88 at 2, 3, and 5 SD, p < 0.0001 for all regressions), and non ischemic (N = 40, r = 0.86, 0.89, 0.90 at 2, 3, and 5 SD, p < 0.0001 for all regressions) cohorts. FWHM analysis demonstrated good correlation in the ischemic population (N = 40, r = 0.83, p < 0.0001). Bland-Altman analysis demonstrated a systematic bias with MIR images showing higher values than PSIR for ischemic (3.3 %, 3.9 % and 4.9 % at 2, 3, and 5 SD, respectively), and non-ischemic (9.7 %, 7.4 % and 4.1 % at ≥2, ≥3, and ≥5 SD thresholds, respectively) cohorts. Background myocardial signal measured in the control population demonstrated a similar bias of 4.4 %, 2.6 % and 0.7 % of the LV volume at 2, 3 and 5 SD thresholds, respectively. The bias observed using FWHM analysis was -6.9 %. CONCLUSIONS: Scar quantification using phase corrected (PSIR) images achieves values highly correlated to those obtained on non-corrected (MIR) images. However, a systematic bias exists that appears exaggerated in non-ischemic cohorts. Such bias should be considered when comparing or translating knowledge between MIR- and PSIR-based imaging.

High-resolution 3-dimensional late gadolinium enhancement scar imaging in surgically corrected Tetralogy of Fallot: clinical feasibility of volumetric quantification and visualization.

BACKGROUND: The extent of surgical scarring in Tetralogy of Fallot (TOF) may be a marker of adverse outcomes and provide substrate for ventricular arrhythmia. In this study we evaluate the feasibility of high resolution three dimensional (3D) late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) for volumetric scar quantification in patients with surgically corrected TOF. METHODS: Fifteen consecutive patients underwent 3D LGE imaging with 3 Tesla CMR using a whole-heart, respiratory-navigated technique. A novel, signal-histogram based segmentation technique was tested for the quantification and modeling of surgical scar. Total scar volume was compared to the gold standard manual expert segmentation. The feasibility of segmented scar fusion to matched coronary CMR data for volumetric display was explored. RESULTS: Image quality sufficient for 3D scar segmentation was acquired in fourteen patients. Mean patient age was 32.2 ± 11.9 years (range 21 to 57 years) with mean right ventricle (RV) ejection fraction (EF) of 53.9 ± 9.2% and mean RV end diastolic volume of 117.0 ± 41.5 mL/m². The mean total scar volume was 11.1 ± 8.2 mL using semi-automated 3D segmentation with excellent correlation to manual expert segmentation (r = 0.99, bias = 0.89 mL, 95% CI -1.66 to 3.44). The mean segmentation time was significantly reduced using the novel semi-automated segmentation technique (10.1 ± 2.6 versus 45.8 ± 12.6 minutes). Excellent intra-observer and good inter-observer reproducibility was observed. CONCLUSION: 3D high resolution LGE imaging with semi-automated scar segmentation is clinically feasible among patients with surgically corrected TOF and shows excellent accuracy and reproducibility. This approach may offer a valuable clinical tool for risk prediction and procedural planning among this growing population.

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

BACKGROUND: The 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. METHODS: Seventy-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. RESULTS: Fifty-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. CONCLUSIONS: FWHM 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.

Intra-thoracic fat volume is associated with myocardial infarction in patients with metabolic syndrome.

BACKGROUND: Visceral adiposity is increased in those with Metabolic Syndrome (MetS) and atherosclerotic disease burden. In this study we evaluate for associations between intra-thoracic fat volume (ITFV) and myocardial infarction (MI) in patients with MetS. METHODS: Ninety-four patients with MetS, MI or both were identified from a cardiovascular CMR clinical registry. MetS was defined in accordance to published guidelines; where-as MI was defined as the presence of subendocardial-based injury on late gadolinium enhancement imaging in a coronary vascular distribution. A healthy control group was also obtained from the same registry. Patients were selected into the following groups: MetS+/MI- (N = 32), MetS-/MI + (N = 30), MetS+/MI + (N = 32), MetS-/MI- (N = 16). ITFV quantification was performed using signal threshold analysis of sequential sagittal CMR datasets (HASTE) and indexed to body mass index. RESULTS: The mean age of the population was 59.8 ± 12.5 years. MetS+ patients (N=64) demonstrated a significantly higher indexed ITFV compared to MetS- patients (p = 0.05). Patients in respective MetS-/MI-, MetS+/MI-, MetS-/MI+, and MetS+/MI + study groups demonstrated a progressive elevation in the indexed ITFV (22.3 ± 10.6, 28.6 ± 12.6, 30.6 ± 12.3, and 35.2 ± 1.4 ml/kg/m(2), (p = 0.002)). Among MetS+ patients those with MI showed a significantly higher indexed ITFV compared to those without MI (p = 0.02). CONCLUSIONS: ITFV is elevated in patients with MetS and incrementally elevated among those with evidence of prior ischemic myocardial injury. Accordingly, the quantification of ITFV may be a valuable marker of myocardial infarction risk among patients with MetS and warrants further investigation.

Safety and Efficacy of Percutaneous Gallstone Extraction in High-Risk Patients: An Alternative to Cholecystectomy or Long-Term Drainage?

BACKGROUND: Acute cholecystitis in nonsurgical candidates is often managed with cholecystostomy tube drainage. After symptom resolution, management options include cholecystectomy, long-term tube drainage, or tube removal. Percutaneous cholecystolithotomy (PCCL) can offer another therapeutic option for patients who are poor operative candidates. STUDY DESIGN: A retrospective study of PCCL performed between December 2000 and September 2017 was conducted. Demographic characteristics, procedure details, gallstone-related complications, procedure-related complications, readmission, and mortality data were collected. RESULTS: Seventy-five patients were identified (52.0% male, 48.0% female, mean ± SD age 75.6 ± 13.9 years). Mean ± SD follow-up time was 2.8 ± 3.7 years. Most of the patients (90.7%) had an American Society of Anesthesiologists physical status classification of 3 or 4. Eleven patients (14.7%) had failed earlier cholecystectomy. A total of 96 PCCL procedures were performed, and complete gallstone removal was achieved in 68 of 75 patients (90.7%), including all patients with previously aborted cholecystectomy. The 30-day and 90-day readmission rates were 4% and 8%, respectively. Three patients (3.9%) subsequently underwent cholecystectomy after PCCL. Ten (10.4%) procedure-related complications (Clavien-Dindo grade I and II) and 17 (22.7%) gallstone-related complications occurred during the follow-up period. Postprocedural choledocholithiasis occurred in 6 patients (8.0%). Recurrent gallstones developed in 5 patients (6.3%) (3 patients undergoing cholecystectomy and 2 patients treated with cholecystostomy tube). CONCLUSIONS: PCCL is a viable option for management of symptomatic gallbladder stones in high-risk surgical patients. There is a high technical success rate, even in patients with earlier failed cholecystectomy. Most patients (77.3%) avoided gallstone-related complications after the procedure.

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.

Contribution of mitral valve leaflet length and septal wall thickness to outflow tract obstruction in patients with hypertrophic cardiomyopathy.

We sought to examine whether elongation of the mitral valve leaflets in patients with hypertrophic cardiomyopathy (HCM) is synergistic to septal wall thickness (SWT) in the development of left ventricular outflow tract obstruction (LVOTO). HCM is a common genetic cardiac disease characterized by asymmetric septal hypertrophy and predisposition towards LVOTO. It has been reported that elongation of the mitral valve leaflets may be a primary phenotypic feature and contribute to LVOTO. However, the relative contribution of this finding versus SWT has not been studied. 152 patients (76 with HCM and 76 non-diseased age, race and BSA-matched controls) and 18 young, healthy volunteers were studied. SWT and the anterior mitral valve leaflet length (AMVLL) were measured using cine MRI. The combined contribution of these variables (SWT × AMVLL) was described as the Septal Anterior Leaflet Product (SALP). Peak LVOT pressure gradient was determined by Doppler interrogation and defined as "obstructive" if ≥ 30 mmHg. Patients with HCM were confirmed to have increased AMVLL compared with controls and volunteers (p < 0.01). Among HCM patients, both SWT and SALP were significantly higher in patients with LVOTO (N = 17) versus without. SALP showed modest improvement in predictive accuracy for LVOTO (AUC = 0.81) among the HCM population versus SWT alone (AUC = 0.77). However, in isolated patients this variable identified patients with LVOTO despite modest SWT. Elongation of the AMVLL is a primary phenotypic feature of HCM. While incremental contributions to LVOTO appear modest at a population level, specific patients may have dominant contribution to LVOTO. The combined marker of SALP allows for maintained identification of such patients despite modest increases in SWT.

Ventricular pacing site separation by cardiac computed tomography: validation for the prediction of clinical response to cardiac resynchronization therapy.

Cardiac Resynchronization Therapy (CRT) fails to provide benefit in up to one-third of patients. Maximizing the geographic separation of right and left ventricular pacing lead sites has been suggested as one way to improve response. Cardiac CT provides an opportunity to explore 3-dimensional inter-lead distance (ILD) measures for the prediction of CRT response. The objective of this study was to investigate associations between standardized measures of ILD by cardiac CT and echocardiographic response to CRT. Forty-two consecutive patients undergoing CRT had serial clinical and echocardiographic evaluations performed in addition to a post-procedural cardiac-gated CT with blinded measurement of direct and circumferential (via the myocardium) ILD measures. Clinical response to CRT, the primary clinical outcome, was defined as a ≥15% reduction in LVESV using echocardiography at 6-months. The mean age and ejection fraction was 63.6 ± 8.9 years and 25.2 ± 7.8%, respectively. The primary outcome occurred in 35 of 42 patients (83%). Both direct and circumferential CT-based ILD measures were associated with the primary outcome by univariate analysis. Receiver Operator Characteristic analysis identified Circumferential ILD to have the strongest predictive accuracy (AUC 0.78). Inter- and intra-observer reproducibility of CT-derived ILD measures was excellent. Circumferential ILD measures on cardiac CT are predictive of clinical response to CRT. Incorporation of these measures into the selection of optimal pacing targets, particularly from pre-procedural CT coronary vein imaging may be of therapeutic benefit and warrants further investigation.

Comparison of semi-automated scar quantification techniques using high-resolution, 3-dimensional late-gadolinium-enhancement magnetic resonance imaging.

The quantification and modeling of myocardial scar is of expanding interest for image-guided therapy, particularly in the field of arrhythmia management. Migration towards high-resolution, three-dimensional (3D) MRI techniques for spatial mapping of myocardial scar provides superior spatial registration. However, to date no systematic comparison of available approaches to 3D scar quantification have been performed. In this study we compare the reproducibility of six 3D scar segmentation algorithms for determination of left ventricular scar volume. Additionally, comparison to two-dimensional (2D) scar quantification and 3D manual segmentation is performed. Thirty-five consecutive patients with ischemic cardiomyopathy were recruited and underwent conventional 2D late gadolinium enhancement (LGE) and 3D isotropic LGE imaging (voxel size 1.3 mm(3)) using a 3 T scanner. 3D LGE datasets were analyzed using six semi-automated segmentation techniques, including the signal threshold versus reference mean (STRM) technique at >2, >3, >5 and >6 standard deviations (SD) above reference myocardium, the full width at half maximum (FWHM) technique, and an optimization-based technique called hierarchical max flow (HMF). The mean ejection fraction was 32.1 ± 12.7 %. Reproducibility was greatest for HMF and FWHM techniques with intra-class correlation coefficient values ≥0.95. 3D scar quantification and modeling is clinically feasible in patients with ischemic cardiomyopathy. While several approaches show acceptable reproducibility, HMF appears superior due to maintenance of accuracy towards manual segmentations.

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.

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.

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.

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.

Myocardial fibrosis and quality of life in patients with non-ischemic cardiomyopathy: a cardiovascular magnetic resonance imaging study.

Myocardial fibrosis (MF) is a common pathophysiologic endpoint in non-ischemic cardiomyopathy and may be identified by late gadolinium enhancement (LGE) MRI. While associated with future cardiovascular events in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) the influence of MF on interim quality of life (QOL) has not been explored. In this study we investigate for associations between MF and validated indices of QOL in patients with HCM and DCM. Ninety-eight patients with known cardiomyopathy (n = 56-HCM/n = 42-DCM) underwent LGE-MRI in addition to standardized testing for QOL using the disease-specific Minnesota Living With Heart Failure (MLWHF) and the generic SF-12 questionnaires. LGE-MRI images were blindly analyzed for the presence and volume of MF using validated techniques. All analyses were stratified according to cardiomyopathy sub-type. The mean age of the population was 56.8 ± 12.9 years. MF was identified in 82 % of patients with HCM and 74 % of patients with DCM with respective mean MF burdens of 20.0 and 13.7 % of the left ventricular mass (p = 0.008). QOL scores for those with HCM or DCM, as assessed by both MLWHF and SF-12, were not significantly different between those with versus those without MF, and showed no association with MF burden by quantitative signal analysis. In this study we identified no association between QOL and MF burden by LGE-MRI in patients with HCM or DCM. Therefore, the severity of underlying myocardial tissue disease, a recognized substrate for ventricular arrhythmia, cannot and should not be inferred from the patient's symptom status or QOL.

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.

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.

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.

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.