Extent Of Scar Research Articles

A novel composite type I collagen scaffold with micropatterned porosity regulates the entrance of phagocytes in a severe model of spinal cord injury.

Traumatic spinal cord injury (SCI) is a damage to the spinal cord that results in loss or impaired motor and/or sensory function. SCI is a sudden and unexpected event characterized by high morbidity and mortality rate during both acute and chronic stages, and it can be devastating in human, social and economical terms. Despite significant progresses in the clinical management of SCI, there remain no effective treatments to improve neurological outcomes. Among experimental strategies, bioengineered scaffolds have the potential to support and guide injured axons contributing to neural repair. The major aim of this study was to investigate a novel composite type I collagen scaffold with micropatterned porosity in a rodent model of severe spinal cord injury. After segment resection of the thoracic spinal cord we implanted the scaffold in female Sprague-Dawley rats. Controls were injured without receiving implantation. Behavioral analysis of the locomotor performance was monitored up to 55days postinjury. Two months after injury histopathological analysis were performed to evaluate the extent of scar and demyelination, the presence of connective tissue and axonal regrowth through the scaffold and to evaluate inflammatory cell infiltration at the injured site. We provided evidence that the new collagen scaffold was well integrated with the host tissue, slightly ameliorated locomotor function, and limited the robust recruitment of the inflammatory cells at the injury site during both the acute and chronic stage in spinal cord injured rats. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1040-1053, 2017.

Electroanatomic Correlates of Depolarization Abnormalities in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.

Epsilon waves and other depolarization abnormalities in the right precordial leads are thought to represent delayed activation of the right ventricular outflow tract in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). However, no study has directly correlated cardiac electrical activation with the surface ECG findings in ARVD/C. Thirty ARVD/C patients (mean age 32.7 ± 11.2years, 16 men) underwent endocardial and epicardial electroanatomical activation mapping in sinus rhythm. Twelve-lead ECGs were classified into 5 patterns: (1) normal QRS (11 patients); (2) terminal activation delay (TAD) (3 patients); (3) incomplete right bundle branch block (IRBBB) (5 patients); (4) epsilon wave (5 patients); (5) complete right bundle branch block (CRBBB) (6 patients). Timing of local ventricular activation and extent of scar was then correlated with surface QRS. Earliest endocardial and epicardial RV activation occurred on the mid anteroseptal wall in all patients despite the CRBBB pattern on ECG. Total RV activation times increased from normal QRS to prolonged TAD, IRBBB, epsilon wave, and CRBBB, respectively (103.9 ± 5.6, 116.3 ± 6.5, 117.8 ± 2.7, 146.4 ± 16.3, and 154.3 ± 6.3, respectively, P < 0.05). The total epicardial scar area (cm(2) ) was similar among the different ECG patterns. Median endocardial scar burden was significantly higher in patients with epsilon waves even compared with patients with CRBBB (34.3 vs. 11.3 cm(2) , P < 0.01). Timing of epsilon wave corresponded to activation of the subtricuspid region in all patients. We found that epsilon waves are often associated with severe conduction delay and extensive endocardial scarring in addition to epicardial disease. The timing of epsilon waves on surface ECG correlated with electrical activation of the sub-tricuspid region.

Evidence-based approach to the treatment of hidradenitis suppurativa/acne inversa, based on the European guidelines for hidradenitis suppurativa.

Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease characterized by painful, recurrent nodules and abscesses that rupture and lead to sinus tracts and scarring. To date, an evidence-based therapeutic approach has not been the standard of care and this is likely due to the lack of evidence based treatment guidelines. The purpose of this study was to promote a holistic evidence-based approach which implemented Level of Evidence and Strength of Recommendation for the treatment of HS. Based upon the European Dermatology Forumguidelines for the management of HS, evidence-based approach was explored for the treatment of HS. The diagnosis of HS should be made by a dermatologist or other healthcare professional with expert knowledge in HS. All patients should be offered adjuvant therapy as needed (pain management, weight loss, tobacco cessation, treatment of super infections, and application of appropriate dressings). The treating physician should be familiar with disease severity scores, especially Hurley staging, physician global assessment and others. The routine use of patient’reported outcomesincluding DLQI, itch and pain assessment (Visual Analogue Scale) is strongly recommended. The need for surgical intervention should be assessed in all patients depending upon type and extent of scarring, and an evidence-based surgical approach should be implemented. Evidence-based medical treatment of mild disease consists of topical Clindamycin 1 % solution/gel b.i.d. for 12 weeks or Tetracycline 500 p.o. b.i.d. for 4 months (LOE IIb, SOR B), for more widespread disease. If patient fails to exhibit response to treatment or for a PGA of moderate-to-severe disease, Clindamycin 300 p.o. b.i.d. with Rifampicin 600 p.o. o.d. for 10 weeks (LOE III, SOR C) should be considered. If patient is not improved, then Adalimumab 160 mg at week 0, 80 mg at week 2; then 40 mg subcutaneously weekly should be administered (LOE Ib, SOR A). If improvement occurs then therapy should be maintained as long as HS lesions are present. If the patient fails to exhibit response, then consideration of second or third line therapy is required. A growing body of evidence is being published to guide the treatment of HS. HS therapy should be based upon the evaluation of the inflammatory components as well as the scarring and should be directed by evidence-based guidelines. Treatment should include surgery as well as medical treatment. Future studies should include benefit risk ratio analysis and long term assessment of efficacy and safety, in order to facilitate long term evidence based treatment and rational pharmacotherapy.

Ventricular Tachycardia and Sudden Cardiac Death in Connective Tissue Diseases: Can Cardiovascular Magnetic Resonance Play a Role?

Ventricular tachycardia (VT) and sudden cardiac death (SCD) are deleterious manifestations of cardiac involvement in connective tissue diseases (CTD). In rheumatoid arthritis (RA), the commonest cause of SCD is coronary artery disease that may lead to acute coronary syndrome and VT. In systemic lupus erythematosus (SLE), VT is due either to coronary artery disease or to acute myocarditis. VT/SCD can be also assessed in polymyostis (PM) and dermatomyositis (DM). Finally, VT was described in 7-13%, while SCD in 5-21% of unselected SSc patients. Cardiovascular magnetic resonance (CMR) has been already used as screening tool in CTDs, because of its capability to evaluate noninvasively and without radiation, function, inflammation, perfusion defects and fibrosis. Apart of the impaired ventricular function, which can be by itself a predisposing factor for VT/SCD, the commonest causes that can potentially lead to VT/SCD in CTDs are myocarditis, coronary artery disease with ischemic type fibrosis, microvascular disease, nonischemic type fibrosis and heart failure. The detection of perfusion defects by CMR can be served as a tool to select those patients, who should undergo x ray coronary angiography and/or angioplasty. The location and extent of myocardial scar can guide further electrophysiologic study and/or intervention. On the other hand, in those with myocarditis, microvascular disease and/or heart failure, a modification in both cardiac and rheumatic medication may be recommended after evaluation of CMR findings. CMR in CTDs with VT/SCD may guide risk stratification, rheumatic and cardiac therapeutic decision making and therefore it should be included as a reliable adjunct in the evaluation of these patients.

Myocardial strain assessment by cine cardiac magnetic resonance imaging using non-rigid registration

AimsTo evaluate a novel post-processing method for assessment of longitudinal mid-myocardial strain in standard cine cardiac magnetic resonance (CMR) imaging sequences. Methods and resultsCine CMR imaging and tagged cardiac magnetic resonance imaging (TMRI) were performed in 15 patients with acute myocardial infarction (AMI) and 15 healthy volunteers served as control group. A second group of 37 post-AMI patients underwent both cine CMR and late gadolinium enhancement (LGE) CMR exams. Speckle tracking echocardiography (STE) was performed in 36 of these patients. Cine CMR, TMRI and STE were analyzed to obtain longitudinal strain. LGE-CMR datasets were analyzed to evaluate scar extent. Comparison of peak systolic strain (PSS) measured from CMR and TMRI yielded a strong correlation (r=0.86, p<0.001). PSS measured from CMR and STE correlated well (r=0.75, p<0.001). A cutoff longitudinal PSS value of −13.14% differentiated non-infarction from any infarcted myocardium, with a sensitivity of 93% and a specificity of 89% (area under curve (AUC) 0.95). PSS value of −9.39% differentiated non-transmural from transmural infarcted myocardium, with a sensitivity of 75% and a specificity of 67% (AUC 0.78). ConclusionThe present study showed a novel off-line post-processing method for segmental longitudinal strain analysis in mid-myocardium layer based on cine CMR data. The method was found to be highly correlated with strain measurements obtained by TMRI and STE. This tool allows accurate discrimination between different transmurality states of myocardial infarction.

Abstract 14586: Total Scar Burden Predicts Cardiac Resynchronization Therapy (CRT) Response Beyond Left Bundle Branch Block (LBBB) and QRS Duration (QRSd) and Regardless of the Type of Cardiomyopathy (CM)

Introduction: Prior studies have demonstrated that up to 30% of patients do not benefit from CRT and that response may be affected by the extent and location of myocardial scar. We sought to determine the predictive value of the scar burden on CRT response after controlling for the type of cardiomyopathy (Ischemic=ICM vs. Non-Ischemic=NICM), the presence of LBBB and QRSd. Methods: We reviewed 71 pts (49% NICM, age 71 +/- 11, 34% women) who underwent cardiac MRI (CMR) pre-CRT. Total and lateral wall % scar were measured and pre-CRT ECG features (LBBB and QRSd) were noted. The change in EF on echo &gt;6 months post-CRT was calculated and a positive response was defined as a ≥10% increase in left ventricular ejection fraction (EF). The relationship between LBBB, QRSd, total and lateral scar % and change in EF were investigated using Pearson (r) correlation. Hierarchical multiple regression was used to assess the ability of total and lateral scar burden to predict CRT response after controlling for the type of CM, the presence of LBBB and QRSd. Results: Mean EF pre-CRT was 23.6%+/-8 and correlated significantly with EF by CMR (mean =24.4 +/-10; r = 0.5, p&lt;0.01). LBBB was present in 52% of pts and mean QRSd was 152ms. A positive response to CRT was noted in 52% of pts. The change in EF correlated significantly with the presence of LBBB (0.31; p=0.01), QRSd (0.27; p=0.03); total scar % (-0.39; p&lt;0.01) and lateral scar % (-0.28;p=0.02). After controlling for the type of CM, and presence of LBBB and QRSd, total scar % was still significantly predictive of the response to CRT [R squared change (tot scar) = 0.06, F change (1,63) = 16, p=0.01] - see table 1. With lateral scar, the same analysis was not significant [R squared change (lat scar)=0.04, F change (1,62)=3.5 p=0.06] Conclusion: Assessment of total scar burden provides incremental predictive value to CRT response after controlling for the type of CM (ICM vs. NICM), the presence of LBBB and QRSd.

Abstract 13980: Cardiac Magnetic Resonance Imaging Quantification of Myocardial Ischemia and Necrosis Using a Novel Risk Prediction Model Allows for Better Risk Stratification in Coronary Artery Disease

Background: Cardiac magnetic resonance imaging (CMR) provides information about inducible myocardial ischemia and necrosis in one single examination in coronary artery disease (CAD) patients. Both variables have been shown to correlate with prognosis. However, there is no consensus on how to assess and quantify these two variables. Hypothesis: Objective of the present prospective study in consecutive patients was to provide a simple algorithm for quantification of ischemia and necrosis and to test for risk stratification models. Methods: Patients with known or suspected CAD referred for adenosine-stress CMR were consecutively enrolled from 2003 to 2007. Examination was conducted on a 1.5-T whole-body scanner. Reversible ischemia was diagnosed by adenosine stress first pass perfusion imaging. Myocardial necrosis was assessed by late gadolinium enhancement (LGE). In a semiautomatic approach, extent of reversible ischemia and scar was quantified and reported as percentage of the left ventricle. Primary endpoint was defined as cardiac death, non-fatal myocardial infarction and stroke. Results: The study cohort consisted of 845 patients. Median age was 64 years, 271 patients were women. During a median follow-up period of 3.8 years 61 primary endpoints occurred. Statistical analysis yielded a ≥6% optimal threshold for reversible ischemia to predict a primary endpoint (univariate hazard ratio 4.91, p&lt;.0001). Similarly, thresholds for extent of myocardial necrosis were defined (LGE &gt;15% and ≤33%: univariate hazard ratio 2.75, p&lt;.0001; LGE &gt;33%: univariate hazard ratio 16.27, p&lt;.0001). The risk prediction model containing both, quantified ischemia and necrosis, proved to be superior in comparison to the dichotomous model (ischemia present: yes/no; necrosis present: yes/no) on multivariate testing (increase in χ 2 -values: 45.004 to 61.545; increase in integrated discrimination improvement: .02269 to .03187; net reclassification index for optimal model: .25593, p=.001). Conclusion: CMR cut-off values for quantification of myocardial ischemia (≥6%) and necrosis (&gt;15% and &gt;33%) have been found which allow for better risk stratification in CAD patients. The combination of both has been shown to yield the superior risk stratification model.

Abstract 13561: The Emerging Role of Stress Speckle Tracking in Viability World

Introduction: Speckle-tracking echocardiography has recently emerged as a quantitative ultrasound technique for accurately evaluating myocardial function by analyzing the motion of speckles identified. Speckle-tracking obtained under stress may offer an opportunity to improve the detection of dynamic regional abnormalities and myocardial viability. Objective: To evaluate stress speckle tracking as tool to detect myocardial viability in comparison to cardiac MRI in post-STEMI patients. Methods: 71 patients were prospectively enrolled in our 18-month’s study. Dobutamin stress echocardiography was performed 4 days post-infaction accompanied with automated functional imaging (Speckle tracking) analysis of left ventricle during rest and then during low dose stress. All patients underwent a follow up stress echocardiography at 6 weeks with speckle tracking analysis. Cardiac MRI took place concomitantly at 4 days post-infarction and 6 weeks. We carried out an assessment of re-admission with acute coronary syndrome (ACS) after one year of enrollment. Results: Investigating strain rate obtained with stress speckle tracking after revascularization predicted the extent of myocardial scar, determined by contrast-enhanced magnetic resonance imaging. A good correlation was found between the global strain and total infarct size (R 0.75, p&lt; 0.001). Furthermore, a clear inverse relationship was found between the segmental strain and the transmural extent of infarction in each segment. ( R -0.69, p&lt;0.01). Meanwhile it provided 81.82% sensitivity and 82.6% specificity to detect transmural from non-transmural infaction at a cut-off value of -10.15. Global stress strain rate showed 80% sensitivity and 77.5% specificity at a cut-off value of -9.1 to predict hospital re-admission with ACS. A cut-off value of -8.4 had shown a 69.23% sensitivity and 73.5% specificity to predict the re-admission related to other cardiac symptoms . Conclusion: Strain rate obtained from speckle tracking during stress is a novel method of detecting myocardial viability after STEMI .Moreover it carries a promising role in post-myocardial infarction risk stratification with a reasonable prediction of reversible cardiac-related hospital re-admission.

RELATIONSHIP OF ELECTRICAL MARKERS OF SUDDEN CARDIAC ARREST RISK AND CHARACTERISTICS OF MYOCARDIAL SCAR

Left ventricular ejection fraction (LVEF) is the standard method used to identify patients at risk for sudden cardiac arrest (SCA) after myocardial infarction (MI). Yet, electrical markers and myocardial scar appear to provide more accurate information on SCA risk. We assessed the relationships between two established electrical markers, Holter-based T-wave alternans (TWA) and Heart Rate Turbulence (HRT) with scar, as assessed using late gadolinium-enhanced cardiac magnetic resonance imaging (LGE-CMR), in post-MI patients with a range of LVEF values to assess the correlation between these measures. Consecutive patients in sinus rhythm and no contraindication to CMR-LGE were enrolled 3 to 15 months after MI. HRT slope and maximal TWA were measured from 24-hour high-resolution ECG recordings (SEER12) and commercial software (MARS, GE Healthcare). CMR-LGE imaging was used to assess the extent, location and characteristics of myocardial scar (LV percent at 5-SD) using a 1.5 Tesla scanner and CVI42 software (Circle Cardiovascular Imaging). Electrical and scar data were independently assessed and compared using variance least squares regression, t-tests and the non-parametric test of trend. The 99 patients enrolled included 83 participants in the Risk Estimation Following Infarction Noninvasive Evaluation-ICD efficacy (REFINE-ICD) study (LVEF 36 to 50%) and others with an LVEF < 35% (n = 6) or > 50% (n = 10). Median LVEF was 42% (inter-quartile range 38% to 45%). Most were male (87%), their mean age was 61 years, 76% had recent documented ST-Elevation MI and 25% had a history of multiple MI events. A linear relationship between TWA and the extent of myocardial scar was observed (p = 0.002). Yet, maximal mean TWA values only tended to be higher in the 32 patients with anterior transmural scar (55 μV) vs. the 68 others (51 μV; p = 0.09). Further, maximal TWA was not related to the number of regions with scar (p = 0.2). No significant linear relationship between HRT slope and scar burden was observed (p = 0.6). Further, no significant relationship between HRT slope and scar was found in terms of transmurality (p = 0.6), location (p = 0.3) or the number of regions affected (p = 0.4). These data indicate that TWA is weakly associated, and HRT is not associated with myocardial scar extent and location among patients with prior myocardial infarction. Accordingly, electrical versus CMR-based markers of risk appear poorly correlated and offer independent insight into arrhythmogeneisis among this patient population.

Noninvasive electrocardiographic imaging of chronic myocardial infarct scar

BackgroundMyocardial infarction (MI) scar constitutes a substrate for ventricular tachycardia (VT), and an accurate delineation of infarct scar may help to identify reentrant circuits and thus facilitate catheter ablation. One of the recent advancements in characterization of a VT substrate is its volumetric delineation within the ventricular wall by noninvasive electrocardiographic imaging. This paper compares, in four specific cases, epicardial and volumetric inverse solutions, using magnetic resonance imaging (MRI) with late gadolinium enhancement as a gold standard. MethodsFor patients with chronic MI, who presented at Glasgow Western Infirmary, delayed-enhancement MRI and 120-lead body surface potential mapping (BSPM) data were acquired and 4 selected cases were later made available to a wider community as part of the 2007 PhysioNet/Computers in Cardiology Challenge. These data were used to perform patient-specific inverse solutions for epicardial electrograms and morphology-based criteria were applied to delineate infarct scar on the epicardial surface. Later, the Rochester group analyzed the same data by means of a novel inverse solution for reconstructing intramural transmembrane potentials, to delineate infarct scar in three dimensions. Comparison of the performance of three specific inverse-solution algorithms is presented here, using scores based on the 17-segment ventricular division scheme recommended by the American Heart Association. ResultsThe noninvasive methods delineating infarct scar as three-dimensional (3D) intramural distribution of transmembrane action potentials outperform estimates providing scar delineation on the epicardial surface in all scores used for comparison. In particular, the extent of infarct scar (its percentage mass relative to the total ventricular mass) is rendered more accurately by the 3D estimate. Moreover, the volumetric rendition of scar border provides better clues to potential targets for catheter ablation. ConclusionsElectrocardiographic inverse solution providing transmural distribution of ventricular action potentials is a promising tool for noninvasively delineating the extent and location of chronic MI scar. Further validation on a larger data set with detailed gold-standard data is needed to confirm observations reported in this study.

MRI Evaluation of Radiofrequency, Cryothermal, and Laser Left Atrial Lesion Formation in Patients with Atrial Fibrillation.

Catheter ablation utilizing radiofrequency (RF), Cryothermal (Cryo), or Laser energy is effective for treatment of atrial fibrillation (AF). Late gadolinium enhancement magnetic resonance imaging (LGE-MRI) has been used to estimate the burden of left atrial (LA) fibrosis, but no data exist regarding structural changes following each modality. We sought to compare the baseline to postprocedure change in LA scar burden following RF, Cryo, or Laser ablation for treatment of AF. Seventeen patients with AF underwent initial pulmonary vein (PV) isolation (PVI) using RF (n = 7), Cryo (n = 5), and Laser (n = 5). LGE-MRI was performed prior to and at 24 hours and 3 months after PVI. In a linear mixed-effects model, accounting for intrapatient clustering of data and interpatient differences in baseline scar, LGE extent was significantly increased at 24 hours postablation (+14.6 ± 1.9% of LA myocardium, P < 0.001), and remained stable from 24 hours to 3 months (+0.12 ± 1.9%, P = 0.951). There was no statistically significant difference between the postablation scar extent among ablation modalities when compared to RF (Cryo +4.5 ± 3.0%, P = 0.123; Laser -3.2 ± 3.0%, P = 0.291). The PV antral LGE intensity was increased by 25.1 ± 3.8% (P<0.001) 24 hours after ablation and additionally increased by 8.1 ± 3.8 at 3 months (P = 0.033). Radiofrequency, Cryo, and laser ablation result in increased LGE extent and intensity at 24 hours and 3 months postablation. No statistically significant difference was noted in the extent of fibrosis induced by any modality.

Relationship of quantitative parameters of myocardial perfusion SPECT and ventricular arrhythmia in patients receiving cardiac resynchronization therapy.

Ventricular arrhythmia is the major cause of sudden cardiac death for patients with heart failure, including those receiving implantation of cardiac resynchronization therapy (CRT). The purpose of this study was to assess the value of myocardial perfusion SPECT (MPS) in predicting ventricular arrhythmia for patients with CRT. Fifty-one patients (35 males, mean age 64 ± 12 years) who had received CRT for at least 6 months were enrolled for resting gated MPS. Three main quantitative parameters of MPS, including extent of myocardial scar, left ventricular ejection fraction (LVEF) and LV dyssynchrony (phase SD), were generated by Emory Cardiac Toolbox. Using the recorded ventricular arrhythmia in the device, including ventricular tachycardia (VT) and ventricular fibrillation (VF), as the primary end point, the value of quantitative parameters of MPS in predicting the development of VT/VF was assessed. Twenty (39 %) of the 51 patients developed VT/VF during the follow-up (15.3 ± 12.7 months). The patients with VT/VF had significantly lower LVEF (24 ± 12 vs. 36 ± 17 %, p < 0.005), larger scar areas (36 ± 19 vs. 22 ± 12 %, p < 0.05) and larger phase SD (57° ± 20° vs. 43° ± 17°, p < 0.01). When categorizing the patients by the median values of LVEF, scar and phase SD, univariate regression analysis showed that lower LVEF (<29 %), larger scar (>23 %) and larger phase SD (>50°) were related to the development of VT/VF (p = 0.006, 0.011 and 0.064, respectively). However, only LVEF was marginally significant as an independent predictor of VT//VF on multivariate regression analysis (p = 0.0573). Survival analysis with Kaplan-Meier curves showed that the survival probability for VT/VF in those with LVEF >29 %, scar areas <23 % and phase SD < 50° was significantly better than in the others (HR 5.16, 95 % CI 1.20-22.16) by log-rank test (χ (2) = 5.9894, p = 0.014). Lower LVEF, larger scar and/or more dyssynchrony assessed by MPS were related to the development of ventricular arrhythmia for patients with CRT, and further defibrillator implantation may be considered for these patients.

Distribution of Hypertrophy and Late Gadolinium Enhancement in Children and Adolescents with Hypertrophic Cardiomyopathy.

While well characterized in adult patients, the pattern of hypertrophy and the extent of myocardial scarring in hypertrophic cardiomyopathy (HCM) are insufficiently known. The aim of this study was to assess the hypertrophy patterns and the prevalence and clinical significance of scars in the hearts of young patients with HCM. A retrospective analysis of the imaging findings of 38 children (aged 12.83 ± 2 years, 30 males) with HCM who underwent cardiac magnetic resonance imaging (CMR) was performed. In addition to left ventricular mass and volumes, the examinations were assessed for the pattern of hypertrophy and presence of late gadolinium enhancement (LGE). A myocardial signal intensity ≥6 standard deviations above the mean of normal myocardium defined positive LGE. Left ventricular mass index averaged 110 ± 34 g/m(2) . Nineteen children (50%) had diffuse septal, 13 (34%) diffuse concentric and 6 (16%) isolated basal hypertrophy. Seven children (18%) had LGE. Patients with LGE had a greater left ventricular mass index than those without (136 ± 34 g/m(2) vs. 104 ± 31 g/m(2) , P = .025). The only two patients who presented with an episode of aborted sudden cardiac death had LGE (P = .03). The most common hypertrophy pattern in children with HCM was diffuse septal hypertrophy. The incidence of LGE observed is lower than that reported in adults. The presence of LGE appears to confer a risk for adverse events.

The relationship between transmurality of ischemic scars and the heart rate of ventricular tachycardia

Aims. The relationship between the heart rate of ventricular tachycardia (VT) and the transmurality of ischemic scars was assessed by a new semiautomatic coordinate-based analysis of late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) images. Methods and results. Twenty patients assessed by LGE-CMR before implantation of implantable cardioverter defibrillator (ICD) with verified VT during the first year following ICD implantation were included. Scar was defined by pixels with a signal intensity ≥ 50% of maximum signal intensity. All pixels were assigned a coordinate position between endo- and epicardium (λ) and the angle of the heart axis (φ). Based upon the λ and φ values, multiple scar features were computed for all scarred areas. These features were correlated to VT heart rate across the complete range of transmurality. The strongest correlation with univariate regression was found between VT heart rate and the sum of transmurality when the maximum transmurality of these features was ≥ 90% (R-square = 0.47). In multiple regressions analysis, the strongest relationship with VT heart rate was found with a maximum transmurality ≥ 90% and by a combination of scar size, transmurality, and endocardial extent of infarction (R-square = 0.64). Conclusion. Transmurality is the strongest predictor of VT heart rate both in univariate and multivariate models. The strongest relationships were found at a transmurality level > 90%.

Macrophage-derived osteopontin induces reactive astrocyte polarization and promotes re-establishment of the blood brain barrier after ischemic stroke

Infarcted regions of the brain after stroke are segregated from the intact brain by scar tissue comprising both fibrous and glial components. The extent and quality of scarring is influenced by inflammation. The matricellular glycoprotein osteopontin (OPN) is strongly induced in myeloid cells after stroke and may contribute to repair of ischemic brain lesions. To elucidate the role of OPN in scar formation, we induced photothrombotic brain infarction, characterized by circumscribed cortical infarctions with a well-defined border zone toward the intact brain parenchyma. The cellular source and functional role of OPN was addressed by studies in OPN null (OPN(-/-) ) mice, wild-type mice depleted of hematogenous monocytes/macrophages by clodronate-filled liposome treatment, and CCR2(-/-) bone marrow chimeric mice characterized by impaired hematogenous macrophage influx into the infarctions. OPN was mainly produced by hematogenous macrophages infiltrating into the inner border zone of the infarcts whereas astrocyte activation occurred in the outer border zone. In OPN(-/-) as well as macrophage-depleted mice, reactive astrocytes failed to properly extend processes from the periphery toward the center of the infarctions. This was associated with incomplete coverage of neovessels by astrocytic endfeet and persistent leakiness of the damaged blood brain barrier. In conclusion, OPN produced by hematogenous macrophages induces astrocyte process extension toward the infarct border zone, which may contribute to repair of the ischemic neurovascular unit.

Global and regional myocardial deformation mechanics of microvascular obstruction in acute myocardial infarction: a three dimensional speckle-tracking imaging study

Microvascular obstruction (MVO) and transmural infarct size are prognostic factors after acute myocardial infarction (AMI). We assessed the value of myocardial deformation patterns using 3D speckle tracking imaging (3DSTI) in detecting myocardial and microvascular damage after AMI. One hundred patients with first ST-segment elevation MI from the REMI Study were prospectively included. Transthoracic echocardiography with 3DSTI and CMR were performed within 72 h after revascularization therapy. Global (3DG) and segmental (3DS) values of LV longitudinal (LS), circumferential and radial area strain were obtained. Late gadolinium enhancement (LGE) and MVO was quantified as transmural (>50%) or non-transmural (<50%). Predictive performance was assessed by area under the receiver operating curve characteristic (AUC). Mean LVEFCMR was 45.8 ± 9.2 % with 22.2 ± 12.7% transmural LGE. MVO was present in 55 patients (MVO transmural extent 11.4 ± 11.8%). In global analysis, all 3DG strain values were correlated with LVEFCMR and infarct size, with the best correlation obtained for 3DGAS (r = -0.678; p < 0.0001). All 3DG strain values, with the exception of LS, were significantly different between patients with and without MVO. In segmental analysis, all 3DS strain values were significantly lower in transmurally infarcted segments than in non-infarcted segments, and all 3DS values except 3DSRS were significantly lower in non-transmural infarcted segments than in non-infarcted segments. The best 3DS strain for detecting non-viable segments with MVO (MVO > 75%) was 3DSAS [AUC 0.867 (0.849-0.884), 78.0% sensitivity and 81.1% specificity for 3DSAS = -16.1%]. Importantly, 3DSRS and 3DSAS were associated with an increase in diagnostic accuracy of both transmural LGE and MVO over 3DSLS (all increase in AUC > 0.04, all p < 0.01). The newly developed 3DSTI, especially 3DSAS, is a sensitive and reproducible tool to predict and quantify the transmural extent of scar. This new early imaging strategy improve the prediction of MVO while enabling to assess the success of reperfusion and the risk of late systolic remodeling in STEMI.

Pain after Hernia Surgery Must Be Avoided and Hopefully Treated.

PAIN AFTER HERNIA SURGERY MUST BE AVOIDED AND HOPEFULLY TREATED © Springer-Verlag 2014 P5:04 QUICK HOT SPOT: SYSTEMATIC PATHOLOGICAL ASSESSMENT OF EXPLANTED HERNIA MESHES REVEALS IMPORTANT INFORMATION OF MESH-BODY INTERACTIONS V Iakovlevl , G Iakovleva2, R Bendavid3 1St, Michael's Hospital, University of Toronto, Toronto, CANADA 2Markham StoujJVille Hospital, Markham, CANADA JShouldice Hospital, Richmond Hill, CANADA Purpose: Polypropylene meshes, introduced in the late 50's, spread to other anatomical sites over the decades of use and presently are employed in millions of surgeries worldwide. Up to 10% of meshes are excised for complications or recurrence generating a large, but underutilized pool of study material. There is a surprising lack of studies based on the meshes explanted from the patients. Paradoxically, in the presence of abundant material from humans most conclusions of mesh-body interactions are based on animal studies. We aimed to standardize pathological examination of explanted meshes and correlate histological findings with clinical presentations. Methods: Consecutive specimens of explanted polypropylene hernia meshes received at the pathology department within last two years were examined according to a predefined protocol. Out of 32 available specimens 13 were ventral and 19 inguinal hernia meshes. Median age was 61 years (range 24-82), 12 female and 20 male patients. For ventral hernias 2 were removed for migration into the bladder and fallopian tube, 4 for infection and 7 for recurrence. For groin meshes 7 were excised for pain and 12 for recurrence. The following microscopic parameters were assessed: mesh deformation, extent of fibrous encapsulation, nerve density and ingrowth, degree and type of inflammation, edema, vascular thrombosis, fat necrosis, attachment to muscle, and polypropylene degradation. Subjective parameters were scored independently by two pathologists. Two-tailed T-test and Pearson correlation were calculated to assess the significance of associations. Results: In relation to reason for excision, the most significant finding was higher density of nerve branches ingrown into the meshes removed for pain compared to those removed for other complications (p < 0.001). Connection with striated muscle showed less pronounced, but significant association with pain (p = 0.05). Meshes removed for pain also showed trends of more exuberant foreign body type inflammation (p = 0.15) and edema in the scar inhabiting the mesh (p = 0.12). The amount of scarring with bridging fibrosis and the degree of foreign body reaction tended to be reduced in meshes with a longer period since implantation (correlation = -0.4 for both parameters). Polypropylene material showed a layer of degradation forming a sheath around the mesh filaments. The layer was detectable by its ability to trap histological dyes in the microcracks and become stained in the microscopic sections, however the stainable layer retained optical properties of polypropylene in polarized light. Conclusions: We observed several important findings and associations related to mesh complications. One of the main findings related to pain is innervation within the tissue ingrown into the mesh. The innervated tissue is exposed to all regular pain mechanisms including nerve entrapment, compression by edema, inflammatory and other mechanisms. Histologically, mechanical nerve irritation of entrapped nerves is likely the leading mechanism while connection to striated muscle, edema and foreign body reaction appear to contribute in the development of pain. In relation to the body reaction to the mesh, the extent of scarring and foreign body inflammation tend to become reduced over time, however the change is mild. Knitted polypropylene meshes remain encapsulated in scar and retain the ability to trigger foreign body reaction many years after implantation. We also found that polypropylene used in mesh manufacturing degrades while exposed to the body environment and the clinical impact of polypropylene degradation needs to be studied further. Overall, the explant specimens, mostly neglected over the decades contain primary information of the mesh-body interactions. A standardized systematic examination of explanted mesh specimens can help our understanding of the mechanisms of complications and build a body of knowledge needed for further technical developments and treatment strategies in the field of hernia repair.

Regional ejection fraction and regional area strain for left ventricular function assessment in male patients after first-time myocardial infarction.

In this work, we present a method to assess left ventricle (LV) regional function from cardiac magnetic resonance (CMR) imaging based on the regional ejection fraction (REF) and regional area strain (RAS). CMR scans were performed for 30 patients after first-time myocardial infarction (MI) and nine age- and sex-matched healthy volunteers. The CMR images were processed to reconstruct three-dimensional LV geometry, and the REF and RAS in a 16-segment model were computed using our proposed methodology. The method of computing the REF was tested and shown to be robust against variation in user input. Furthermore, analysis of data was feasible in all patients and healthy volunteers without any exclusions. The REF correlated well with the RAS in a nonlinear manner (quadratic fit-R(2) = 0.88). In patients after first-time MI, the REF and RAS were significantly reduced across all 16 segments (REF: p < 0.05; RAS: p < 0.01). Moreover, the REF and RAS significantly decreased with the extent of transmural scar obtained from late gadolinium-enhanced CMR images. In addition, we show that the REF and RAS can be used to identify regions with compromised function in the patients with preserved global ejection fraction with reasonable accuracy (more than 78%). These preliminary results confirmed the validity of our approach for accurate analysis of LV regional function. Our approach potentially offers physicians new insights into the local characteristics of the myocardial mechanics after a MI.

SCAR LOCATION, BUT NOT TOTAL SCAR BURDEN, PREDICTS ARRHYTHMIA FREE SURVIVAL IN HEART FAILURE PATIENTS WITH IMPLANTABLE DEFIBRILLATOR

Heart failure patients with ischemic cardiomyopathy are at increased risk of ventricular arrhythmias. We evaluated if the location and extent of myocardial scar correlate with risk of ventricular arrhythmias and mortality in patients with reduced left ventricular ejection fraction and concomitant

PREVALENCE OF MYOCARDIAL SCAR IN WOMEN WITH SIGNS AND SYMPTOMS OF ISCHEMIA BUT NO OBSTRUCTIVE CORONARY ARTERY DISEASE: A REPORT FROM THE WOMEN’S ISCHEMIA SYNDROME EVALUATION

Moderated Poster ContributionsStable Ischemic Heart Disease Moderated Poster Theater, Poster Hall B1Sunday, March 15, 2015, 10:00 a.m.-10:10 a.m.Session Title: Ischemia in Women without Obstructive Coronary Artery DiseaseAbstract Category: 26. Stable Ischemic Heart Disease: ClinicalPresentation Number: 1205M-05Authors: May Bakir, Janet Wei, Louise Thomson, John Petersen, Quanlin Li, Erika Jones, Puja Mehta, Chrisandra Shufelt, Daniel Berman, Eileen Handberg, Sheryl Kelsey, George Sopko, Carl Pepine, C. Noel Bairey Merz, Cedars-Sinai Medical Center, Los Angeles, CA, USABackground: Women with signs and symptoms of ischemia and no obstructive coronary artery disease (CAD) have an elevated major adverse cardiac event rate. We evaluated the presence, extent and distribution of scar using cardiac magnetic resonance imaging (CMRI) late gadolinium enhancement (LGE) in the Women’s Ischemia Syndrome Evaluation.methods: Women (n=344) with signs and symptoms of ischemia and no obstructive CAD underwent 1.5T CMRI LGE. Scans were read blindly for presence and segmental distribution of LGE. Scar size was quantified using Pie Medical Imaging software. LGE type was defined as ischemic when subendocardial or transmural and localized to a coronary artery distribution, and non-ischemic when mid-myocardial or epicardial. Fisher’s exact and two sample t-tests were used for statistical analysis.results: LGE was present in 20 (5.8%) women, including 15 (75%) with ischemic LGE. Women with non-ischemic LGE (n=5) had larger scar size compared to women with ischemic LGE (Table). There were no significant differences in cardiac risk factors among women with no LGE, ischemic LGE, or non-ischemic LGE, and there was no significant correlation between LGE presence and cardiac risk factors.Conclusion: Women with signs and symptoms of ischemia and no obstructive CAD have a 5.8% prevalence of myocardial scar detected by CMRI, with a predominant ischemic LGE pattern. These findings demonstrate that these women can develop irreversible myocardial injury, which may be clinically under-diagnosed.No LGE(n=324)Ischemic LGE(n=15)Non-ischemic LGE(n=5)Age 54 ± 11 years 55 ± 8 years 37 ± 15 yearsBody Mass Index 30 ± 8 32 ± 11 35 ± 7Hypertension 40% 31% 75%Diabetes 11% 14% 50%Dyslipidemia 20% 10% 33%Family History of Coronary Artery Disease 48% 21% 50%Scar pattern n/a4 LAD6 LCX4 RCA1 LAD and RCA3 patchy epicardial1 midmyocardial ASH1 RV insertion pointsScar size n/a 4.83 ± 3.12g* 9.57 ± 6.10g*ASH= asymmetric septal hypertrophy, LAD= left anterior descending artery, LCX= left circumflex artery, LGE= late gadolinium enhancement, RCA= right coronary artery, RV= right ventricular*p=0.0034