Scar Volume Research Articles

The relative importance of ischaemia and scar in the genesis of ventricular arrhythmia in ischaemic cardiomyopathy

Abstract Background Ventricular arrhythmias are a leading cause of death in patients with ischaemic cardiomyopathy (ICM). Ischaemia and scar are thought to contribute to arrhythmogenesis; as scar is considered fixed, strategies to reduce ischaemia such as revascularisation are undertaken to attempt to reduce risk, despite limited evidence behind this practice. Purpose The study rationale was to understand the relative contributions of ischaemia and scar on the genesis of arrhythmia in an ICM population, by undertaking a detailed assessment of arrhythmic substrate in a highly characterised population and secondly by validating these findings in a large cohort. Methods We assessed the relationship between scar, ischaemic burden and impact of ischaemia modulation via revascularisation on the arrhythmic substrate (study 1) and major arrhythmic events (study 2). S1: Patients were eligible for enrolment if they had an LVEF≤40%, extensive coronary disease (BCIS Jeopardy Score (JS) ≥6) and were due to undergo CABG or PCI. Arrhythmic substrate was characterised by the LV activation recovery interval (ARI) dispersion recorded by electrocardiographic imaging (ECGi). Scar and ischaemic burden were assessed via stress perfusion cardiac magnetic resonance (pCMR) imaging, calculated as a percentage of total LV myocardial volume. ECGi and pCMR were repeated 3 months post revasc. S2: Arrhythmia data were collected from device interrogation reports and blinded core lab analyses performed of CMR scans and angiograms of patients enrolled in the REVIVED-BCIS2 trial. Extent of revasc (quantified by change in JS/baseline JS) was used to estimate change in ischaemic burden. The primary outcome was death or aborted sudden death. Results S1: 30 patients were recruited; age 67±10 years, 87% male, BMI 28±5. Baseline LV ARI dispersion at rest was correlated with scar burden (r=0.37, p=0.04) but not ischaemic burden (r=0.25,p=0.21). Changes in metrics are shown(Table 1). Ischaemic burden reduced after revascularisation. Delta ischaemic burden was correlated with delta LV ARI dispersion (r=0.51, p=0.007 unadjusted). S2: Data was collected on 479 patients from REVIVED-BCI2 who underwent CMR; age 69±9 yrs, 88% male, BMI 28±6, LVEF 26±8%. 237 were randomised to PCI and 242 to OMT; no difference in rates of all-cause death, CV death, aborted sudden death, appropriate device therapy or arrhythmia was identified between the groups. Scar burden was associated with death or aborted sudden death, extent of revascularisation was not(Figure 1). Conclusion In our studies, the volume of scar was strongly related to both the arrhythmic substrate and occurrence of arrhythmic events. Whilst ischaemia reduction affected the arrhythmic substrate, this did not translate to a reduction in clinical events. These findings suggest that scar burden, rather than ischaemia reduction by revascularisation, should be the focus of risk stratification and therapeutic decision making in patients with ICM.Table 1Figure 1

Improved wear and corrosion resistance of magnesium AZ80 alloy prepared by laser surface remelting

Laser surface remelting (LSR) is a laser-based surface treatment method. In the LSR process, microstructural defects such as cracks and porosity are suppressed in addition to grain refinement, and the mechanical properties are improved. The present research investigated the effects of LSR parameters on the microstructure, wear, and corrosion behavior of Mg AZ80 alloy. The results showed that in LSR, the coarse-grained (29.8 μm) structure of AZ80 was transformed into a fine-grained structure (3.1 μm) with no microstructural defects. The evaporation of Mg during LSR and the formation of Al-rich and Mg-poor phases are the most important challenges in the surface treatment of AZ80. This limitation was solved by optimizing the LSR parameters, which included a gas flow rate of 2 L min−1, pulse duration of 3 ms, scanning speed of 3 mm s−1, pulse frequency of 8 Hz, and heat input of 64 J mm−1. The prevention of Mg evaporation was associated with the elimination of porosity and cracks, reducing of the solidification range, and uniform distribution of β-Mg17Al12 precipitation phases in α-Mg refined grains. The tribological behavior of the laser-treated region showed that the COF, depth of the wear scar, wear rate, and wear volume loss were reduced by 18%, 48%, 37%, and 66%, respectively, compared to AZ80. This result is attributed to the refinement of α-Mg grains and the uniform distribution of β-Mg17Al12 in the laser-treated region. The results of the polarization curves of the corrosion test in 3.5 wt% NaCl solution showed that the optimal laser-treated region with the lowest corrosion current density (34.68 × 10−6 μA.cm−2) and highest self-corrosion potential (1.425 V) exhibited the highest corrosion resistance. A slight change in the breakdown potential current slope in the laser-treated region indicates the formation of a protective film on the surface after the completion of LSR, which increases corrosion resistance.

Silencing siRNA microneedle patches versus silicone sheets in reducing post-surgical scars: a randomized single-blinded intra-individually controlled clinical trial.

A common complication of wounds is exuberant growth of fibrotic scar tissue, which can lead to hypertrophic scars or keloids. There are currently no treatments with good evidence for preventing excessive scar tissue formation. In this study, we explored the use of microneedle patches containing siRNA inhibiting SPARC mRNA in reducing the volume of post-surgical scars. We aim to compare the differences in the volume of post-surgical scars between daily application of siRNA-embedded dissolving microneedle patches and silicone sheets. The primary study outcome measure was the 3D volume of scar elevation.Our hypothesis was that scar formation in the half of the wound treated with siRNA microneedle patches will be lesser, as reflected by a smaller 3D volume, as compared to the half treated with silicone sheets. This was an 8-week, single-blinded intra-individually controlled randomised trial in a tertiary dermatological centre. Patients with two-week-old post-operative wounds were recruited. Each half of the scar was randomly assigned to the microneedle patch or silicone sheet. Three-dimensional (3D) volumes were obtained from the scars via a high-resolution scanner at day 0, 30 and 60. At day 30, scars treated with the microneedle patches had a lower geometric mean volume of 0.79mm3 when compared to scars treated with silicone sheets, with a difference in mean percentage volume reduction of 10.70%.At day 60, scars treated with the microneedle patches had a statistically significant lower volume (8.88mm3) when compared to the side treated with silicone sheets (12.77mm3, p=0.005), with a difference in mean percentage reduction of 9.66%. Additionally, there was also a statistically significant difference between the percentage reduction in scar volume, compared to baseline, on the side treated with microneedle patches (mean=83.78%) compared to the side treated with silicone sheets (mean=74.11%). There was a significantly greater reduction in the volume of post-surgical scars on the side treated with microneedle patches compared to the side treated with silicone sheets. This demonstrates the use of transdermal gene silencing technology for scar inhibition and that siRNA microneedle patches can be an effective and safe modality in the reduction of scar tissue formation. Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12622000558729, https://www.anzctr.org.au.

Clinical Significance of Myocardial Injury in Patients Hospitalized for COVID-19: A Prospective, Multicenter, Cohort Study

BackgroundHospitalized COVID-19 patients with troponin elevation have a higher prevalence of cardiac abnormalities than control individuals. However, the progression and impact of myocardial injury on COVID-19 survivors remain unclear. ObjectivesThis study sought to evaluate myocardial injury in COVID-19 survivors with troponin elevation with baseline and follow-up imaging and to assess medium-term outcomes. MethodsThis was a prospective, longitudinal cohort study in 25 United Kingdom centers (June 2020 to March 2021). Hospitalized COVID-19 patients with myocardial injury underwent cardiac magnetic resonance (CMR) scans within 28 days and 6 months postdischarge. Outcomes were tracked for 12 months, with quality of life surveys (EuroQol-5 Dimension and 36-Item Short Form surveys) taken at discharge and 6 months. ResultsOf 342 participants (median age: 61.3 years; 71.1% male) with baseline CMR, 338 had a 12-month follow-up, 235 had a 6-month CMR, and 215 has baseline and follow-up quality of life surveys. Of 338 participants, within 12 months, 1.2% died; 1.8% had new myocardial infarction, acute coronary syndrome, or coronary revascularization; 0.8% had new myopericarditis; and 3.3% had other cardiovascular events requiring hospitalization. At 6 months, there was a minor improvement in left ventricular ejection fraction (1.8% ± 1.0%; P < 0.001), stable right ventricular ejection fraction (0.4% ± 0.8%; P = 0.50), no change in myocardial scar pattern or volume (P = 0.26), and no imaging evidence of continued myocardial inflammation. All pericardial effusions (26 of 26) resolved, and most pneumonitis resolved (95 of 101). EuroQol-5 Dimension scores indicated an overall improvement in quality of life (P < 0.001). ConclusionsMyocardial injury in severe hospitalized COVID-19 survivors is nonprogressive. Medium-term outcomes show a low incidence of major adverse cardiovascular events and improved quality of life. (COVID-19 Effects on the Heart; ISRCTN58667920)

Needle-free jet injector treatment with bleomycin is efficacious in patients with severe keloids: a randomized, double-blind, placebo-controlled trial.

Severe keloids are difficult to treat. Corticosteroid injections with needles are painful and associated with frequent recurrences. Therefore, more effective, safe and patient friendly alternative treatments are urgently needed. To assess the efficacy, tolerability, and patient satisfaction of intralesional bleomycin treatment using a needle-free electronic pneumatic jet injector (EPI) in severe keloids. Patients with severe keloids were included in this double-blind, randomized placebo-controlled trial with split-lesion design. Three EPI treatments with bleomycin or saline, were administered every four weeks in respectively the intervention and control side. Outcome measures were change in scar volume assessed by 3D-imaging, Patient and Observer Scar Assessment Scale (POSAS), skin perfusion with laser speckle contrast imaging (LSCI), spilled volume, procedure related pain, adverse events, and patient satisfaction. Fourteen patients (9 female, 5 men) were included. The estimated mean keloid volume was significantly reduced with 20% after EPI-assisted bleomycin, compared to a slight increase of 3% in the control side (p<0.01). The estimated mean POSAS patient and observer scores decreased with respectively 26% and 28% (p = 0.02; p = 0.03). LSCI showed no significant change in perfusion. EPI treatment was preferred over previous needle injections in 85% of patients. The estimated mean spilled volume after EPI was around 50%, and NRS pain scores were moderate. Adverse events included bruising, hyperpigmentation, and transient superficial necrosis. Three EPI-assisted bleomycin treatments are efficacious and well-tolerated in severe keloids. Moreover, EPI treatment was preferred by most patients and may serve as a patient-friendly alternative treatment.

Septal late enhancement by cardiac CT is associated with repeat ablation in nonischemic cardiomyopathy patients.

Scar substrate in nonischemic cardiomyopathy (NICM) patients is often difficult to identify. Advances in cardiac imaging, especially using late iodine-enhanced computed tomography (LIE-CT), allow better characterization of scars giving rise to ventricular tachycardia (VT). Currently, there are limited data on clinical correlates of CT-derived scar substrates in NICM. We sought assess the relationship between scar location on LIE-CT and outcomes after radiofrequency catheter ablation (RFCA) in NICM patients with VT. From 2020 to 2022, consecutive patients with NICM undergoing VT RFCA with integration of cardiac CT scar modeling (inHeart, Pessac, France) were included at two US tertiary care centers. The CT protocol included both arterial-enhanced imaging for anatomical modeling and LIE-CT for scar assessment. The distribution of substrate on CT was analyzed in relation to patient outcomes, with primary endpoints being VT recurrence and the need for repeat ablation procedure. Sixty patients were included (age 64 ± 12 years, 90% men). Over a median follow-up of 120 days (interquartile range [IQR]: 41-365), repeat ablation procedures were required in 32 (53%). VT recurrence occurred in 46 (77%), with a median time to recurrence of 40 days (IQR: 8-65). CT-derived total scar volume positively correlated with intrinsic QRS duration (r = .34, p = 0.008). Septal scar was found on CT in 34 (57%), and lateral scar in 40 (7%). On univariate logistic regression, septal scar was associated with increased odds of repeat ablation (odds ratio [OR]: 2.9 [1.0-8.4]; p = 0.046), while lateral scar was not (OR: 0.9 [0.3-2.7]; p = 0.855). Septal scar better predicted VT recurrence when compared to lateral scar, but neither were statistically significant (septal scar OR: 3.0 [0.9-10.7]; p = 0.078; lateral scar OR: 1.7 [0.5-5.9]; p = 0.391). In this tertiary care referral population, patients with NICM undergoing VT catheter ablation with septal LIE-CT have nearly threefold increased risk of need for repeat ablation.

Fractional Radiofrequency and Oral Isotretinoin-A Prospective Randomized Controlled Split-Face Trial Comparing Concurrent Versus Delayed Fractional Radiofrequency Treatment for Acne Scars.

Therapeutic dogma has been to treat acne scars no less than 6 months after isotretinoin (ITN) cessation. To evaluate the safety and efficacy of fractional radiofrequency (FRF) in patients treated concurrently with ITN. We conducted a prospective randomized control 3-arm comparative trial to evaluate the treatment of acne scars. Patients received one of three treatment options: (A) ITN and FRF concurrent treatment, (B) ITN monotherapy, and (C) FRF 6 months post-ITN treatment. Patients in the FRF cohorts received three monthly sessions. Patients were followed for adverse effects up to 6-9 months post-FRF treatment. Final cosmesis was scored by three independent dermatologists using two scales: the Echelle d'Evaluation Clinique des Cicatrices d'Acne (ECCA) and an internal 5-point investigator's scale, indicating the percentage of improvement. Subjective analyses by patients were also assessed. Objective and subjective analyses revealed improvement in the ITN-FRF cohort, which was superior to the delayed FRF cohort and the ITN monotherapy cohort. Specifically, the concurrently treated cohort (ITN-FRF) had a significant reduction in acne scar volume from baseline mean (151.1 ± 44.7 to 97.0 ± 31.2, p < 0.005), outperforming both the delayed FRF and monotherapy ITN treatment cohorts, respectively (155.4 ± 37.8 to 122.0 ± 46.2, 144.6 ± 82.8 to 132.4 ± 62.7). Additionally, the concurrently treated cohort demonstrated improved ECCA scores (36.8 ± 15.5), significantly better than the ITN monotherapy cohort (101.5 ± 20.1, p < 0.01). Limited patient sample size: 38 patients completed the study; mostly Fitzpatrick Type II-III skin; photographic assessments utilized. Per our prospective trial, concurrent treatment of ITN-FRF is superior to delayed FRF treatment 6 months post-ITN cessation.

Scar tissue characterization to predict arrhythmia recurrence in patients undergoing ventricular tachycardia ablation: cardiac computed tomography compared with cardiac magnetic resonance

Abstract Background The role of imaging in evaluating patients undergoing ventricular tachycardia (VT) ablation is crucial for planning, procedural success, and clinical outcomes. In daily practice, cardiac computed tomography (CCT) assessing wall thinning and late iodine uptake (LI) and cardiac magnetic resonance (CMR) assessing late-gadolinium enhancement (LGE) are most commonly implemented. However, data comparing the two imaging modalities for scar tissue characterization is scarce. Aims To compare the performance of both imaging modalities for scar tissue characterization in ischemic (ICM) and non-ischemic (NICM) patients undergoing VT ablation and predict procedural outcomes. Methods In a retrospective analysis, consecutive patients undergoing both CCT and LGE-CMR before scheduled VT ablation were included. The presence and extent of scar was assessed by means of each imaging modality using dedicated softwares (MUSIC and ADAS). To compare scar distribution and agreement between the two modalities, a scar classification scheme was used for all 17 AHA segments: 0 points (no scar present), 1 point (scar &amp;lt;50% of total segment area), 2 points (scar representing 50-99% of total segment area) or 3 points (scar present in 100% of the segment area).&amp;lt;scar&amp;lt;100%)&amp;gt;&amp;lt;scar&amp;lt;100%&amp;gt; Results 36 patients (67±10 years; 97% male; LVEF 39±10%; 72% ischemic) undergoing CCT and LGE-CMR before scheduled VT ablation were included. In the ICM group, mean detected scar burden was higher than in the NICM group on LGE-CMR (total volume: 62.3±32.9g vs. 32.8±9.5g, p&amp;lt;0.001), using wall thinning model (WT)(mean scar area 69.0±45.6 cm2 vs. 23.4±23.6cm2, p=0.005) as well as LI (dense scar area: 39.2±28.1 cm2 vs. 11.0±6.3 cm2 , p=0.005). The absolute score difference per segment and patient between CCT and LGE-CMR was calculated and summed for all patients divided by the number of patients. Differences were more pronounced for NICM compared to ICM and LGE-CMR showed better concordance to LI than WT in both NICMP and ICM (Figure). Total procedure time was 205±68 min (ablation time 28±16 min; fluoroscopy time 15 ± 12 min). During a follow-up period of 19±7 months, 87 sustained VT episodes in 12 patients (33%) were documented. Three patients (8%) underwent a second VT ablation and one patient (3%) died during follow-up. In ICM, total scar volume on LGE-CMR and scar area on LI showed numerically higher predictive value for VT recurrence than total scar area by means of WT (AUC: LGE 0.76, LI 0.78 and WT 0.65 respectively), while in NICM scar characterization by means of WT yielded higher performance to predict VT recurrence than LI or LGE-CMR (AUC: LGE 0.67, LI 0.58, WT 0.83 respectively). Conclusions In patients undergoing VT ablation, both LGE-CMR and CCT are valuable for scar tissue characterization. Late iodine uptake on CCT showed a high concordance with LGE-CMR in both NICM and ICM.&amp;lt;/scar&amp;lt;100%&amp;gt;&amp;lt;/scar&amp;lt;100%)&amp;gt;

Resurfacing of atrophic facial acne scars with a multimodality CO2 and 1570 nm laser system.

Scarring is one of the most prevalent long-term complications of acne vulgaris and has cosmetic, psychological, and social burdens. Contemporary management programs integrate multiple modalities to best address the multiple factors underlying their development and persistence. This work assessed the impact of sequential multimodal laser therapy on acne scar geometrics and texture. Adult patients (n = 16) with Fitzpatrick skin type II-IV and presenting with facial acne scars, underwent three combination ablative (CO2), and nonablative (1570 nm) laser treatment sessions at two-month intervals. Treatment was delivered using a ProScan Hybrid applicator, with each regimen including illumination with both ablative and a nonablative lasers applied in a grid mode sequence. Scar microtopography was assessed at baseline and 6 months after the last treatment session. At baseline, all patients had both box and rolling scars, while only three had icepick scars. Six months following treatment, mean scar volume improved from 5.7 ± 5.2 mm3 at baseline to 3.1 ± 3.0 mm3 and mean affected area improved from 165.6 ± 134.0 mm2 94.0 ± 80.1 mm2, translating to 47.0 ± 7.9% and 43.2 ± 8.6% reductions from baseline, respectively. Patients were highly satisfied with treatment outcomes, and no serious adverse reactions were documented during the course of treatment or follow-up. Multimodal CO2 and 1570-nm laser treatment improved the surface profilometry of patients with atrophic facial acne scars. Customization of both treatment intervals and laser settings to cosmetic regions, scar profiles and skin phototypes may further enhance treatment outcomes and expand its applicability to additional skin deformities.

A novel method for the percutaneous induction of myocardial infarction by occlusion of small coronary arteries in the rabbit.

Arrhythmic sudden cardiac death (SCD) is an important cause of mortality following myocardial infarction (MI). The rabbit has similar cardiac electrophysiology to humans and is therefore an important small animal model to study post-MI arrhythmias. The established approach of surgical coronary ligation results in thoracic adhesions that impede epicardial electrophysiological studies. Adhesions are absent following a percutaneously induced MI, which is also associated with reduced surgical morbidity and so represents a clear refinement of the approach. Percutaneous procedures have previously been described in large rabbits (3.5-5.5 kg). Here, we describe a novel method of percutaneous MI induction in smaller rabbits (2.5-3.5 kg) that are readily available commercially. New Zealand White rabbits (n = 51 males, 3.1 ± 0.3 kg) were anesthetized using isoflurane (1.5-3%) and underwent either a percutaneous MI procedure involving microcatheter tip deployment (≤1.5 Fr, 5 mm), coronary ligation surgery, or a sham procedure. Electrocardiography (ECG) recordings were used to confirm ST-segment elevation indicating coronary occlusion. Blood samples (1 and 24 h) were taken for cardiac troponin I (cTnI) levels. Ejection fraction (EF) was measured at 6-8 wk. Rabbits were then euthanized (Euthatal) and hearts were processed for magnetic resonance imaging and histology. Mortality rates were similar in both groups. Scar volume, cTnI, and EF were similar between both MI groups and significantly different from their respective sham controls. Thus, percutaneous coronary occlusion by microcatheter tip deployment is feasible in rabbits (2.5-3.5 kg) and produces an MI with similar characteristics to surgical ligation with lower procedural trauma and without epicardial adhesions.NEW & NOTEWORTHY Surgical coronary ligation is the standard technique to induce myocardial infarction (MI) in rabbits but is associated with procedural trauma and the generation of thoracic adhesions. Percutaneous coronary occlusion avoids these shortcomings and is established in pigs but has only been applicable to large rabbits because of a mismatch between the equipment used and target vessel size. Here, we describe a new scalable approach to percutaneous MI induction that is safe and effective in 2.5-3.5-kg rabbits.

Simultaneous Viability Assessment and Invasive Coronary Angiography Using a Therapeutic CT System in Chronic Myocardial Infarction Patients.

In a preclinical study using a swine myocardial infarction (MI) model, a delayed enhancement (DE)-multi-detector computed tomography (MDCT) scan was performed using a hybrid system alongside diagnostic invasive coronary angiography (ICA) without the additional use of a contrast agent, and demonstrated an excellent correlation in the infarct area compared with histopathologic specimens. In the present investigation, we evaluated the feasibility and diagnostic accuracy of a myocardial viability assessment by DE-MDCT using a hybrid system comprising ICA and MDCT alongside diagnostic ICA without the additional use of a contrast agent. We prospectively enrolled 13 patients (median age: 67 years) with a previous MI (>6 months) scheduled to undergo ICA. All patients underwent cardiac magnetic resonance (CMR) imaging before diagnostic ICA. MDCT viability scans were performed concurrently with diagnostic ICA without the use of additional contrast. The total myocardial scar volume per patient and average transmurality per myocardial segment measured by DE-MDCT were compared with those from DE-CMR. The DE volume measured by MDCT showed an excellent correlation with the volume measured by CMR (r=0.986, p<0.0001). The transmurality per segment by MDCT was well-correlated with CMR (r=0.900, p<0.0001); the diagnostic performance of MDCT in differentiating non-viable from viable myocardium using a 50% transmurality criterion was good with a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 87.5%, 99.5%, 87.5%, 99.5%, and 99.1%, respectively. The feasibility of the DE-MDCT viability assessment acquired simultaneously with conventional ICA was proven in patients with chronic MI using DE-CMR as the reference standard.

Scar characterisation to predict arrhythmia and death in ischaemic cardiomyopathy: insights from the REVIVED trial

Abstract Background Ischaemic cardiomyopathy continues to have unacceptably high mortality despite contemporary medical and device therapy (1). Ventricular arrhythmias are a leading cause of both death and morbidity in this population. Current guidelines recommend implantable cardioverter defibrillator (ICD) implantation in patients with a left ventricular ejection fraction (LVEF) below 35% but many who meet criteria never receive a therapy and there is a persistent sudden cardiac death risk in those who do not. Scar characteristics are not currently included in risk stratification algorithms, however both volume and entropy, a measure of myocardial heterogeneity, have been linked to arrhythmic risk. Purpose To assess whether left ventricular scar burden and morphology predicts fatal and non-fatal arrhythmia, independent of LVEF in severe ischaemic cardiomyopathy. Methods REVIVED-BCIS2 was a prospective, randomized controlled trial, which recruited 700 patients from 40 centres across the United Kingdom (1). Trial eligibility required the presence of ≥4 dysfunctional but viable myocardial segments; the majority of patients had viability assessed by cardiac magnetic resonance imaging (CMR). Semi-quantitative CMR scar burden was determined through consensus by two CMR experts in a blinded core laboratory. Scar morphology was further characterised by left ventricular entropy measured using novel dedicated software (TexRAD Ltd., Feedback plc, UK). The primary outcome was the composite of all-cause death and aborted sudden death (in turn, defined as appropriate ICD therapy or resuscitated cardiac arrest). Cox proportional hazard models were used to determine the effect of scar burden and entropy on clinical outcomes, adjusted for baseline LVEF, extent of coronary disease, type of implantable device and randomized treatment. Results Four hundred and ninety one patients underwent viability assessment by CMR and 478 were included in this analysis (Figure 1). Mean age was 69 ± 9; median follow up duration was 3.3 [2.3-4.9] years. By the end of trial follow up, 257/478 had a device in situ (CRT-D 99, ICD 147, CRT-P 11). The primary outcome occurred in 182 patients (38.1%). Each 10% increase in scar volume was associated with a 24% increase in the incidence of the primary outcome (adjusted HR per 10% 1.24, 95% CI: 1.11 to 1.39, p = 0.0002)(Figure 2). LVEF at baseline was not predictive (adjusted HR per 5% increase 0.94, 95% CI 0.86 – 1.02, p = 0.13). The relationship between LV entropy and outcomes will be presented at ESC. Conclusions In patients with severe ischaemic cardiomyopathy, scar volume was predictive of death and potentially fatal arrhythmias. Left ventricular ejection fraction was not a significant predictor in this cohort. Scar characteristics should form an integral part of risk stratification.Consort diagramPrimary outcome by scar burden

Ventricular arrhythmia outcomes in hypertrophic cardiomyopathy from a high level myectomy centre

Abstract Background The presence of ≥15% late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (MRI) is used as a prognostic indicator for sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). [1] According to the European Society of Cardiology clinical practice guidelines (2014), septal myectomy is only indicated for symptomatic relief from left ventricular outflow tract obstruction (LVOTO) that is refractory to medical therapy, provided LVOTO gradient ≥ 50 mmHg. [2] At present, there is scarce data correlating the burden of ventricular arrhythmia and sudden cardiac death with LGE percentage or showing benefit of myectomy in reducing the burden of the same. Purpose We aimed to compare the burden of ventricular arrhythmia burden in patients with HCM who underwent septal myectomy compared with those who did not. Methods Adult patients with HCM followed in the advanced heart failure outpatient clinic at Allegheny General Hospital were included in this study. All included patients had cardiac MRI with LGE quantification and data related to cardiac events through devices placed for various indications (such as evaluation of reported palpitations, established supraventricular tachycardia, implantable cardioverter-defibrillator for primary or secondary prevention). Patients were divided into 2 groups: those undergoing myectomy (post myectomy group) and those that did not undergo myectomy (non-myectomy group). Chi square test was used to calculate incidence of premature ventricular contractions (PVCs), non-sustained ventricular tachycardia (NSVT) and sustained ventricular tachycardia (SVT) in the non-myectomy and post myectomy group. Results 76 patients with HCM (interventricular septal thickness ≥1.5 cm and LGE positive) longitudinally followed in the Allegheny General Hospital advanced heart failure outpatient clinic from 2016 to 2022 were included. 37 patients underwent septal myectomy. Baseline characteristics of post myectomy and non-myectomy group were matched and are listed in table 1. Left ventricular mass index was expectedly higher in patients undergoing myectomy. LGE was quantified on cardiac MRI prior to myectomy (mean 16.4% in myectomy group, 14.6% in non-myectomy group). Burden of ventricular arrhythmia (PVCs, NSVT and SVT) was found to be significantly lower in the post myectomy group (n=13, 44.83%) compared to the non-myectomy group (n=36, 92.31%). None of the patients included were noted to have ventricular fibrillation or sudden cardiac death. Conclusion Septal myectomy may reduce the incidence of ventricular arrhythmia and thus impact outcomes related to sudden cardiac death. This is likely a consequence of removal of arrhythmogenic scar tissue. Larger studies are required to further evaluate the burden and correlation of ventricular arrhythmia with scar tissue volume measured on cardiac MRI.

Abstract 18924: Structural and Electrical Remodeling Differences in Ischemia-Reperfusion versus Non-Reperfusion Myocardial Infarction

Background: Structural and electrical remodeling following myocardial infarction (MI) can result in the development of arrhythmogenic substrate and ventricular tachycardia (VT). Various clinical factors such as reperfusion status, and occluded coronary distribution can impact the size of post-infarction scar. Objective: To investigate the structural and electrical remodeling characteristics in 2 different porcine models of MI. Methods: Fourteen swine underwent anterior infarction via 180min balloon occlusion followed by reperfusion (IR Group, n=7) or chronic total occlusion by embolizing the mid-LAD with a coil (CTO Group, n=7). Cardiac MRI and electroanatomic substrate mapping (Thermocool ST-SF) and high-resolution activation mapping (Pentaray 2-6-2mm) was performed in all subjects 8-9 weeks following infarction. Low bipolar voltage area (&lt;1.5mV), very low bipolar voltage area (&lt;0.5mV), and CMR LGE intensity volume reconstruction (inHeart Medical) were assessed. Programmed stimulation from the Ventricular apex was performed for VT inducibility assessment. Results: The CTO group had more extensive low bipolar voltage area (CTO: 36±6cm 2 vs. IR: 23±12cm 2 , p=0.04) and dense low bipolar voltage areas (CTO: 20±7cm 2 vs. IR: 7±6cm 2 , p=0.01). LV EDV was similar (CTO: 122±14ml vs. IR: 136±38ml, np) and there was no significant difference in LVEF (CTO: 28±4% vs. IR: 26±4%, np) and CMR LGE scar volume (CTO: 12±3ml vs. IR: 12±4ml, np). Voltage mapping demonstrated clear significant differences in substrate size and LV Endocardial CMR LGE intensity was more homogeneous in the CTO group than the IR group (Figure). Monomorphic VT was inducible in all 14 subjects. A total of 19 VTs were induced in CTO group (range 1-4, TCL 241±33ms) and 12 in IR group (range 1-2, TCL 208±17ms). Conclusions: Creation of a chronic infarct results in a significantly larger area of abnormal arrhythmogenic substrate than 180 minutes of ischemia-reperfusion.

A novel combined technology for treating hypertrophic scars: adipose tissue extract combined with fractional CO2 laser.

Introduction: Owing to the need for liposuction and its unsuitability for allogeneic transplantation, the clinical application of stromal vascular fraction gel (SVF-gel) combined with fractional CO2 laser for scar treatment is limited. Adipose tissue extract (ATE), rich in cytokines and growth factors, offers a more convenient option for clinical practice as it can be easily prepared using purely physical methods and has low immunogenicity. We aimed to evaluate the effectiveness of ATE combined with fractional CO2 laser in the treatment of hypertrophic scars. Methods: ATE was prepared using discarded liposuction fluid from patients undergoing liposuction. A rabbit ear hypertrophic scar model was established and treated with ATE, fractional CO2 laser, or a combination. PBS was used as a control. The scar appearance and histological changes were observed. The immunohistochemistry method was used to evaluate the expression of α-SMA, while perilipin was detected using immunofluorescence. Additionally, the level of adipogenic signal C/EBPα and PPARγ mRNA was studied. Results: Following treatment, the volume of hypertrophic scar decreased, resulting in a softer texture and thinner dermis. Additionally, there was a decrease in the infiltration of inflammatory cells, and the collagen arrangement became looser and more regular, and the expression of α-SMA also decreased, with the combination of ATE and fractional laser showing the most significant improvement. Moreover, the combination group was found to promote subcutaneous fat regeneration and increase the expression of adipogenic signals C/EBPα and PPARγ. Conclusion: The combination of ATE and fractional CO2 laser treatment has been shown to inhibit the development of hypertrophic scars. This effect may be attributed to the enhancement of adipogenesis and decrease in collagen deposition.

Incorporation of view sharing and KWIC filtering into GRASP-Pro improves spatial resolution of single-shot, multi-TI, late gadolinium enhancement MRI.

While single-shot late gadolinium enhancement (LGE) is useful for imaging patients with arrhythmia and/or dyspnea, it produces low spatial resolution. One approach to improve spatial resolution is to accelerate data acquisition using compressed sensing (CS). Our previous work described a single-shot, multi-inversion time (TI) LGE pulse sequence using radial k-space sampling and CS, but over-regularization resulted in significant image blurring that muted the benefits of data acceleration. The purpose of the present study was to improve the spatial resolution of the single-shot, multi-TI LGE pulse sequence by incorporating view sharing (VS) and k-space weighted contrast (KWIC) filtering into a GRASP-Pro reconstruction. In 24 patients (mean age = 61 ± 16 years; 9/15 females/males), we compared the performance of our improved multi-TI LGE and standard multi-TI LGE, where clinical standard LGE was used as a reference. Two clinical raters independently graded multi-TI images and clinical LGE images visually on a five-point Likert scale (1, nondiagnostic; 3, clinically acceptable; 5, best) for three categories: the conspicuity of myocardium or scar, artifact, and noise. The summed visual score (SVS) was defined as the sum of the three scores. Myocardial scar volume was quantified using the full-width at half-maximum method. The SVS was not significantly different between clinical breath-holding LGE (median 13.5, IQR 1.3) and multi-TI LGE (median 12.5, IQR 1.6) (P = 0.068). The myocardial scar volumes measured from clinical standard LGE and multi-TI LGE were strongly correlated (coefficient of determination, R2 = 0.99) and in good agreement (mean difference = 0.11%, lower limit of the agreement = -2.13%, upper limit of the agreement = 2.34%). The inter-rater agreement in myocardial scar volume quantification was strong (intraclass correlation coefficient = 0.79). The incorporation of VS and KWIC into GRASP-Pro improved spatial resolution. Our improved 25-fold accelerated, single-shot LGE sequence produces clinically acceptable image quality, multi-TI reconstruction, and accurate myocardial scar volume quantification.

Effectiveness of Mesenchymal Stem Cell Secretome on Wound Healing: A Systematic Review and Meta-analysis.

Secretome provides promising potential in replacing cell-based therapies in wound repair therapy. This study aimed to systematically review and conduct a meta-analysis on the effectiveness of secretome in promoting wound healing. To ensure the rigor and transparency of our study, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, as registered in PROSPERO with ID: CRD42023412671. We conducted a comprehensive search on four electronic databases to identify studies evaluating the effect of secretome on various clinical parameters of wound repair. In addition, we evaluated the risk of bias for each study using the Jadad and Newcastle-Ottawa scale. To synthesize the data, we employed a fixed-effects model and calculated the mean difference or odds ratio (OR) with a 95% confidence interval (CI). Based on six included articles, secretome is known to affect several clinical parameters in wound healing included the size and depth of ulcers during healing; the E´chelle d'évaluation clinique des cicatrices d'acne (ECCA) score, epidermal thickness, collagen fibers, abnormal elastic tissues, volume of atrophic acne scars, skin pore volume, and erythema during acne scar healing; and microcrust areas, erythema index, transepidermal water loss, volume of atrophic acne scars, erythema, and relative gene expression of procollagen type I, procollagen type III, and elastin were evaluated in wound healing after laser treatment. Meta-analysis studies showed that secretome reduced ulcer size (mean difference: 0.87, 95% CI of 0.37-1.38, p = 0.0007), decreased ulcer depth (mean difference: 0.18, 95% CI of 0.11-0.25, p < 0.00001), and provided patient satisfaction (odds ratio: 9.71, 95% CI of 3.47-21.17, p < 0.0001). However, secretome failed to reach significance in clinical improvement (OR 0.38, 95% CI 0.10, 1.53, p = 0.06). The secretome provides good effectiveness in accelerating wound healing through a mechanism that correlates with several clinical parameters of wound repair.

Substrate Imaging Before Catheter Ablation of Ventricular Tachycardia: Risk Prediction for Acute Hemodynamic Decompensation

BackgroundThe PAINESD (Pulmonary disease, Age, Ischemic cardiomyopathy, NYHA functional class, Ejection fraction, Storm, Diabetes mellitus) risk score has been validated as a predictor of periprocedural acute hemodynamic decompensation (AHD) in patients undergoing ventricular tachycardia (VT) ablation. Whether the addition of total scar volume (TSV) determined by preprocedure computed tomography imaging provides additional risk stratification has not been previously investigated. ObjectivesThe purpose of this study was to evaluate the impact of TSV on the risk of AHD and its adjunctive benefit to the PAINESD score newly modified as Pulmonary disease, Age, Ischemic cardiomyopathy, NYHA class, Ejection fraction, Storm, Scar volume, Diabetes mellitus (PAINES2D) based on the addition of scar volumes. MethodsThis was a retrospective analysis of all index VT ablations at a quaternary care center from 2017 to 2022. Associations between TSV and AHD were evaluated among patients with structural heart disease. ResultsAmong 61 patients with TSV data, 13 (21%) had periprocedural AHD. TSV and PAINESD were independently associated with AHD risk. Both TSV and PAINESD were associated with AHD (P = 0.016 vs P = 0.053, respectively). The highest TSV tertile (≥37.30 mL) showed significant association with AHD (P = 0.018; OR: 4.80) compared to the other tertiles. The PAINESD and PAINES2D scores had significant impact on AHD (P = 0.046 and P = 0.010, respectively). The PAINES2D score had a greater impact on AHD compared to PAINESD (area under the curve: 0.73; P = 0.011; 95% CI: 0.56-0.91 and area under the curve: 0.67; P = 0.058; 95% CI: 0.49-0.85, respectively). ConclusionsAddition of TSV to a modified PAINESD score, PAINES2D, enhances risk prediction of AHD. Further prospective study is needed to assess benefit in various cardiomyopathy populations undergoing VT ablation.

Vitamin D in Keloids: An alternative to steroids?

Madam, Keloids are wound healing scars with well-demarcated overgrowth of fibrotic tissue, mainly involving excessive collagen proliferation produced by fibroblasts. They extend beyond the original injury site, and are associated with pain and pruritus (1,2). Few treatments available few for Keloids include occlusive dressings, compression therapy and intralesional corticosteroid injections (1). Triamcinolone acetate, a corticosteroid injection, is considered the first line treatment as it possesses anti-inflammatory and anti-mitotic activities, which reduce scar volume and prevent a recurrence. However, approximately 50percent of keloids are considered to be steroid resistant (3, 4). Moreover, as per literature, the usage of intralesional corticosteroid injections can cause several local and systemic adverse effects such as telangiectasias, skin necrosis, skin and subcutaneous fat atrophy, and Cushing’s syndrome (5) In light of the above, researchers are keen on finding other treatment modalities for treating these lesions, and among them Vitamin D, is being investigated. Vitamin D is a steroid hormone that normally plays a role in regulating serum calcium, inhibiting cellular proliferation and promoting cell differentiation and apoptotic activities. Transforming growth factor-beta (TGF-B), an inflammatory marker, has been implicated in the pathogenesis of keloids. TGF-B is believed to be inhibited with localised Vitamin D. Furthermore, Vitamin D deficiency plays a significant role in keloidogenesis, a process mediated by dysregulation of koebnerisin, an antimicrobial polypeptide (2). A study was conducted recently, where 40 adults, aged 18 to 60 years, were administered intralesional Vitamin D, on keloids sized atleast 5 cm, with sessions carried out every week for a maximum of 3-4 sessions. This study showed a highly significant reduction in the Vancouver Scar Scale, a scarring scoring system (1). However, further trials, specially comparative studies, are needed to effectively weigh in the efficacy of Vitamin D over steroids. Advantages of Vitamin D are evident and promising so far – it’s cost-friendly, and shows mild side effects such as burning, pain, swelling and tenderness that shortly disappears on its own.

Influence of surface burnishing process with single strain path and reciprocating strain path on copper wear behavior

A single strain path (SSP) and reciprocating strain path (RSP) burnishing processes are implemented on copper surfaces using a multi-ball surface burnishing tool. Dry wear tests are performed on both machined samples to investigate the effect of different strain paths on the wear behavior. A backscattered scanning electron microscope and nanoindentation are operated to characterize the microstructure and mechanical properties between samples machined via different strain paths. Molecular dynamics models are developed to explore the mechanism that enhances wear resistance through the gradient grain structure in the surface layers machined by SSP and RSP. The wear test results show that the wear scar volumes of the SSP treated samples are about 70% of the original samples, while the RSP treated samples are about 60%, indicating that the RSP further enhances the wear resistance of copper. Compared to SSP machining, RSP machining activates the Bauschinger effect in the copper to produce the gradient structure with a larger thickness (500 μm–700 μm) and greater hardness (1.72 GPa–1.82 GPa). Consequently, RSP machining further improves the resistance to crack initiation and expansion, resistance to plastic deformation, total strain capacity, and elastic recovery in the wear process, which is why samples machined with RSP have better wear resistance.