Periprocedural acute haemodynamic decompensation during substrate-based ablation of scar-related ventricular tachycardia: a rare and unpredictable event.

AIMS: Patients with structural heart disease (SHD) undergoing catheter ablation (CA) for ventricular tachycardia (VT) are at considerable risk of periprocedural complications, including acute haemodynamic decompensation (AHD). The PAINESD score was proposed to predict the risk of AHD. The goal of this study was to validate the PAINESD score using the retrospective analysis of data from a large-volume heart centre. METHODS AND RESULTS: Patients who had their first radiofrequency CA for SHD-related VT between August 2006 and December 2020 were included in the study. Procedures were mainly performed under conscious sedation. Substrate mapping/ablation was performed primarily during spontaneous rhythm or right ventricular pacing. A purposely established institutional registry for complications of invasive procedures was used to collect all periprocedural complications that were subsequently adjudicated using the source medical records. Acute haemodynamic decompensation triggered by CA procedure was defined as intraprocedural or early post-procedural (<12 h) development of acute pulmonary oedema or refractory hypotension requiring urgent intervention. The study cohort consisted of 1124 patients (age, 63 ± 13 years; males, 87%; ischaemic cardiomyopathy, 67%; electrical storm, 25%; New York Heart Association Class, 2.0 ± 1.0; left ventricular ejection fraction, 34 ± 12%; diabetes mellitus, 31%; chronic obstructive pulmonary disease, 12%). Their PAINESD score was 11.4 ± 6.6 (median, 12; interquartile range, 6-17). Acute haemodynamic decompensation complicated the CA procedure in 13/1124 = 1.2% patients and was not predicted by PAINESD score with AHD rates of 0.3, 1.8, and 1.1% in subgroups by previously published PAINESD terciles (<9, 9-14, and >14). However, the PAINESD score strongly predicted mortality during the follow-up. CONCLUSION: Primarily substrate-based CA of SHD-related VT performed under conscious sedation is associated with a substantially lower rate of AHD than previously reported. The PAINESD score did not predict these events. The application of the PAINESD score to the selection of patients for pre-emptive mechanical circulatory support should be reconsidered.

Experimental Approaches to Scar Modeling through Mechanical Skin Damage and Chemical Burn in Sprague Dawley Rats.

Creating of a scar model in laboratory animals is the most acceptable option for the preclinical search of scar treatment. However, due to high skin regeneration rate in laboratory rodents, creating an optimal animal model of scar formation is a challenge. Here we describe five methods for modeling a scar tissue in rats that we have tested. These methods allowed achieving different histopathological features and different stages of skin scar formation.

Functional substrate mapping of atrium in patients with atrial scar: A novel method to predict critical isthmus of atrial tachycardia.

Atrial tachycardia (AT) is a common rhythm disorder, especially in patients with atrial structural abnormalities. Although voltage mapping can provide a general picture of structural alterations which are mainly secondary to prior ablations, surgery or pressure/volume overload, data is scarce regarding the functional characteristics of low voltage regions in the atrium to predict critical isthmus of ATs. Recently, functional substrate mapping (FSM) emerged as a potential tool to evaluate the functionality of structurally altered regions in the atrium to predict critical sites of reentry. Current evidence suggested a clear association between deceleration zones of isochronal late activation mapping (ILAM) during sinus/paced rhythm and critical isthmus of reentry in patients with left AT. Therefore, these areas seem to be potential ablation targets even not detected during AT. Furthermore, abnormal conduction detected by ILAM may also have a role to identify the potential substrate and predict atrial fibrillation outcome after pulmonary vein isolation. Despite these promising findings, the utility of such an approach needs to be evaluated in large-scale comparative studies. In this review, we aimed to share our experience and review the current literature regarding the use of FSM during sinus/paced rhythm in the prediction of re-entrant ATs and discuss future implications and potential use in patients with atrial low-voltage areas.

Antiarrhythmic and Anti-Inflammatory Effects of Sacubitril/Valsartan on Post-Myocardial Infarction Scar.

BACKGROUND: Sacubitril/valsartan (Sac/Val) is superior to angiotensin-converting enzyme inhibitors in reducing the risk of heart failure hospitalization and cardiovascular death, but its mechanistic data on myocardial scar after myocardial infarction (MI) are lacking. The objective of this work was to assess the effects of Sac/Val on inflammation, fibrosis, electrophysiological properties, and ventricular tachycardia inducibility in post-MI scar remodeling in swine. METHODS: After MI, 22 pigs were randomized to receive ß-blocker (BB; control, n=8) or BB+Sac/Val (Sac/Val, n=9). The systemic immune response was monitored. Cardiac magnetic resonance data were acquired at 2-day and 29-day post MI to assess ventricular remodeling. Programmed electrical stimulation and high-density mapping were performed at 30-day post MI to assess ventricular tachycardia inducibility. Myocardial samples were collected for histological analysis. RESULTS: Compared with BB, BB+Sac/Val reduced acute circulating leukocytes (P=0.009) and interleukin-12 levels (P=0.024) at 2-day post MI, decreased C-C chemokine receptor type 2 expression in monocytes (P=0.047) at 15-day post MI, and reduced scar mass (P=0.046) and border zone mass (P=0.043). It also lowered the number and mass of border zone corridors (P=0.009 and P=0.026, respectively), scar collagen I content (P=0.049), and collagen I/III ratio (P=0.040). Sac/Val reduced ventricular tachycardia inducibility (P=0.034) and the number of deceleration zones (P=0.016). CONCLUSIONS: After MI, compared with BB, BB+Sac/Val was associated with reduced acute systemic inflammatory markers, reduced total scar and border zone mass on late gadolinium-enhanced magnetic resonance imaging, and lower ventricular tachycardia inducibility.

Cosmetic and functional impact of fascia lata harvest for use in surgery for stress urinary incontinence.

INTRODUCTION: There has been increased interest in using autologous tissues since the Food and Drug Administration banned transvaginal mesh for pelvic organ prolapse in 2019. Our study aims to assess patients' perspective of functional and cosmetic impact on the fascia lata harvest site in patients undergoing fascia lata harvest for the treatment of stress urinary incontinence (SUI). METHODS: This is a prospective survey study of a retrospective cohort of patients who underwent a fascia lata pubovaginal sling between 2017 and 2022. Participants completed a survey regarding the functional and cosmetic outcomes of the harvest site. RESULTS: Seventy-two patients met the inclusion criteria. Twenty-nine patients completed the survey for a completion rate of 40.3%. For functional symptoms, 24.1% (7/29) of patients reported leg discomfort, 10.3% (3/29) reported leg weakness, 10.3% (3/29) reported a bulge, 17.2% (5/29) reported scar pain, 14.8% (4/27) reported scar numbness, and 17.2% (5/29) reported paresthesia at the scar. For cosmetic outcomes, 72.4% (21/29) reported an excellent or good scar appearance. On the PGI-I, 75.9% (22/29) reported their condition as very much better (48.3%, 14/29) or much better (27.6%, 8/29). CONCLUSIONS: The majority of patients reported being satisfied with the functional and cosmetic outcomes of their harvest site as well as satisfied with the improvement in their SUI. Less than 25% of patients report harvest site symptoms, including leg weakness, scar bulging, scar pain, scar numbness, or paresthesia in the scar. This is important in the context of appropriate preoperative discussion and counseling regarding fascia lata harvest.

Intramural needle ablation or repeated standard ablation in patients referred for repeat ablation of scar-related ventricular tachycardia.

INTRODUCTION: When ventricular tachycardia (VT) recurs after standard RF ablation (sRFA) some patients benefit from repeat sRFA, whereas others warrant advanced methods such as intramural needle ablation (INA). Our objectives are to assess the utility of repeat sRFA and to clarify the benefit of INA when repeat sRFA fails in patients with VT due to structural heart disease. METHODS: In consecutive patients who were prospectively enrolled in a study for INA for recurrent sustained monomorphic VT despite sRFA, repeat sRFA was considered first. INA was performed during the same procedure if repeat sRFA failed or no targets for sRFA were identified. RESULTS: Of 85 patients enrolled, acute success with repeat sRFA was achieved in 30 patients (35%), and during the 6-month follow-up, 87% (20/23) were free of VT hospitalization, 78% were free of any VT, and 7 were lost to follow-up. INA was performed in 55 patients (65%) after sRFA failed, or no endocardial targets were found abolished or modified inducible VT in 35/55 patients (64%). During follow-up, 72% (39/54) were free of VT hospitalization, 41% were free of any VT, and 1 was lost to follow-up. Overall, 59 out of 77 (77%) patients were free of hospitalization and 52% were free of any VT. Septal-origin VTs were more likely to need INA, whereas RV and papillary muscle VTs were less likely to require INA. CONCLUSIONS: Repeat sRFA was beneficial in 23% (18/77) of patients with recurrent sustained VT who were referred for INA. The availability of INA increased favorable outcomes to 52%.

Impact of late gadolinium enhancement image acquisition resolution on neural network based automatic scar segmentation.

BACKGROUND: Automatic myocardial scar segmentation from late gadolinium enhancement (LGE) images using neural networks promises an alternative to time-consuming and observer-dependent semi-automatic approaches. However, alterations in data acquisition, reconstruction as well as post-processing may compromise network performance. The objective of the present work was to systematically assess network performance degradation due to a mismatch of point-spread function between training and testing data. METHODS: Thirty-six high-resolution (0.7×0.7×2.0 mm3) LGE k-space datasets were acquired post-mortem in porcine models of myocardial infarction. The in-plane point-spread function and hence in-plane resolution Δx was retrospectively degraded using k-space lowpass filtering, while field-of-view and matrix size were kept constant. Manual segmentation of the left ventricle (LV) and healthy remote myocardium was performed to quantify location and area (% of myocardium) of scar by thresholding (≥ SD5 above remote). Three standard U-Nets were trained on training resolutions Δxtrain = 0.7, 1.2 and 1.7 mm to predict endo- and epicardial borders of LV myocardium and scar. The scar prediction of the three networks for varying test resolutions (Δxtest = 0.7 to 1.7 mm) was compared against the reference SD5 thresholding at 0.7 mm. Finally, a fourth network trained on a combination of resolutions (Δxtrain = 0.7 to 1.7 mm) was tested. RESULTS: The prediction of relative scar areas showed the highest precision when the resolution of the test data was identical to or close to the resolution used during training. The median fractional scar errors and precisions (IQR) from networks trained and tested on the same resolution were 0.0 percentage points (p.p.) (1.24 - 1.45), and - 0.5 - 0.0 p.p. (2.00 - 3.25) for networks trained and tested on the most differing resolutions, respectively. Deploying the network trained on multiple resolutions resulted in reduced resolution dependency with median scar errors and IQRs of 0.0 p.p. (1.24 - 1.69) for all investigated test resolutions. CONCLUSION: A mismatch of the imaging point-spread function between training and test data can lead to degradation of scar segmentation when using current U-Net architectures as demonstrated on LGE porcine myocardial infarction data. Training networks on multi-resolution data can alleviate the resolution dependency.

Unrecognized myocardial scar by late-gadolinium-enhancement cardiovascular magnetic resonance: Insights from the population-based Hamburg City Health Study.

BACKGROUND: The presence of myocardial scar is associated with poor prognosis in several underlying diseases. Late-gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging reveals clinically silent "unrecognized myocardial scar" (UMS), but the etiology of UMS often remains unclear. This population-based CMR study evaluated prevalence, localization, patterns, and risk factors of UMS. METHODS: The study population consisted of 1064 consecutive Hamburg City Health Study participants without a history of coronary heart disease or myocarditis. UMS was assessed by standard-phase-sensitive-inversion-recovery LGE CMR. RESULTS: Median age was 66 [quartiles 59, 71] years and 37% (388/1064) were females. UMS was detected in 244 (23%) participants. Twenty-five participants (10%) had ischemic, and 217 participants (89%) had non-ischemic scar patterns, predominantly involving the basal inferolateral left-ventricular (LV) myocardium (75%). Two participants (1%) had coincident ischemic and non-ischemic scar. The presence of any UMS was independently associated with LV ejection fraction (odds ratios (OR) per standard deviation (SD) 0.77 (confidence interval (CI) 0.65-0.90), p = 0.002) and LV mass (OR per SD 1.54 (CI 1.31-1.82), p < 0.001). Ischemic UMS was independently associated with LV ejection fraction (OR per SD 0.58 (CI 0.39-0.86), p = 0.007), LV mass (OR per SD 1.74 (CI 1.25-2.45), p = 0.001), and diabetes (OR 4.91 (CI 1.66-13.03), p = 0.002). Non-ischemic UMS was only independently associated with LV mass (OR per SD 1.44 (CI 1.24-1.69), p < 0.001). CONCLUSION: UMS, in particular with a non-ischemic pattern, is frequent in individuals without known cardiac disease and predominantly involves the basal inferolateral LV myocardium. Presence of UMS is independently associated with a lower LVEF, a higher LV mass, and a history of diabetes.

Applications of ultrasound elastography to hand and upper limb disorders.

Ultrasound elastography is a recently developed method for accurate measurement of soft tissue stiffness in addition to the clinician's subjective evaluation. The present review briefly describes the ultrasound elastography techniques and outlines clinical applications for tendon, muscle, nerve, skin and other soft tissues of the hand and upper limb. Strain elastography provides a qualitative evaluation of the stiffness, and shear-wave elastography generates quantitative elastograms superimposed on a B-mode image. The stiffness in degenerative tendinopathy and/or tendon injury was significantly lower than in a normal tendon in several studies. Elastography is also a reliable method to evaluate functional muscle activity, compared to conventional surface electromyography. The median nerve is consistently stiffer in patients with carpal tunnel syndrome than in healthy subjects, on whatever ultrasound elastography technique. Elastography distinguishes normal skin from scars and can be used to evaluate scar severity and treatment. Elastography has huge clinical applications in musculoskeletal tissues. Continued development of systems and increased training of clinicians will expand our knowledge of elastography and its clinical applications in the future.

Fibroblasts in heart scar tissue directly regulate cardiac excitability and arrhythmogenesis.

After heart injury, dead heart muscle is replaced by scar tissue. Fibroblasts can electrically couple with myocytes, and changes in fibroblast membrane potential can lead to myocyte excitability, which suggests that fibroblast-myocyte coupling in scar tissue may be responsible for arrhythmogenesis. However, the physiologic relevance of electrical coupling of myocytes and fibroblasts and its impact on cardiac excitability in vivo have never been demonstrated. We genetically engineered a mouse that expresses the optogenetic cationic channel ChR2 (H134R) exclusively in cardiac fibroblasts. After myocardial infarction, optical stimulation of scar tissue elicited organ-wide cardiac excitation and induced arrhythmias in these animals. Complementing computational modeling with experimental approaches, we showed that gap junctional and ephaptic coupling, in a synergistic yet functionally redundant manner, excited myocytes coupled to fibroblasts.

Effectiveness of various methods of manual scar therapy.

BACKGROUND: The skin is a protective barrier of the body against external factors, and its damage leads to a loss of integrity. Normal wound healing results in a correct, flat, bright, and flexible scar. Initial skin damage and patient specific factors in wound healing contribute that many of these scars may progress into widespread or pathologic hypertrophic and keloid scars. The changes in cosmetic appearance, continuing pain, and loss of movement due to contracture or adhesion and persistent pruritis can significantly affect an individual's quality of life and psychological recovery post injury. Many different treatment methods can reduce the trauma and surgical scars. Manual scar treatment includes various techniques of therapy. The most effectiveness is a combined therapy, which has a multidirectional impact. Clinical observations show an effectiveness of manual scar therapy. MATERIAL AND METHODS: The aim of this work was to evaluate effectiveness of the scar manual therapy combined with complementary methods on the postoperative scars. Treatment protocol included two therapies during 30 min per week for 8 weeks. Therapy included manual scar manipulation, massage, cupping, dry needling, and taping. RESULTS: Treatment had a significant positive effect to influence pain, pigmentation, pliability, pruritus, surface area, and scar stiffness. Improvement of skin parameters (scar elasticity, thickness, regularity, color) was also noticed. CONCLUSION: To investigate the most effective manual therapy strategy, further studies are needed, evaluating comparisons of different individual and combined scar therapy modalities.

Heterogeneous repolarization creates ventricular tachycardia circuits in healed myocardial infarction scar.

Arrhythmias originating in scarred ventricular myocardium are a major cause of death, but the underlying mechanism allowing these rhythms to exist remains unknown. This gap in knowledge critically limits identification of at-risk patients and treatment once arrhythmias become manifest. Here we show that potassium voltage-gated channel subfamily E regulatory subunits 3 and 4 (KCNE3, KCNE4) are uniquely upregulated at arrhythmia sites within scarred myocardium. Ventricular arrhythmias occur in areas with a distinctive cardiomyocyte repolarization pattern, where myocyte tracts with short repolarization times connect to myocytes tracts with long repolarization times. We found this unique pattern of repolarization heterogeneity only in ventricular arrhythmia circuits. In contrast, conduction abnormalities were ubiquitous within scar. These repolarization heterogeneities are consistent with known functional effects of KCNE3 and KCNE4 on the slow delayed-rectifier potassium current. We observed repolarization heterogeneity using conventional cardiac electrophysiologic techniques that could potentially translate to identification of at-risk patients. The neutralization of the repolarization heterogeneities could represent a potential strategy for the elimination of ventricular arrhythmia circuits.

Differentiation of Active Corneal Infections from Healed Scars Using Deep Learning.

PURPOSE: To develop and evaluate an automated, portable algorithm to differentiate active corneal ulcers from healed scars using only external photographs. DESIGN: A convolutional neural network was trained and tested using photographs of corneal ulcers and scars. PARTICIPANTS: De-identified photographs of corneal ulcers were obtained from the Steroids for Corneal Ulcers Trial (SCUT), Mycotic Ulcer Treatment Trial (MUTT), and Byers Eye Institute at Stanford University. METHODS: Photographs of corneal ulcers (n = 1313) and scars (n = 1132) from the SCUT and MUTT were used to train a convolutional neural network (CNN). The CNN was tested on 2 different patient populations from eye clinics in India (n = 200) and the Byers Eye Institute at Stanford University (n = 101). Accuracy was evaluated against gold standard clinical classifications. Feature importances for the trained model were visualized using gradient-weighted class activation mapping. MAIN OUTCOME MEASURES: Accuracy of the CNN was assessed via F1 score. The area under the receiver operating characteristic (ROC) curve (AUC) was used to measure the precision-recall trade-off. RESULTS: The CNN correctly classified 115 of 123 active ulcers and 65 of 77 scars in patients with corneal ulcer from India (F1 score, 92.0% [95% confidence interval (CI), 88.2%-95.8%]; sensitivity, 93.5% [95% CI, 89.1%-97.9%]; specificity, 84.42% [95% CI, 79.42%-89.42%]; ROC: AUC, 0.9731). The CNN correctly classified 43 of 55 active ulcers and 42 of 46 scars in patients with corneal ulcers from Northern California (F1 score, 84.3% [95% CI, 77.2%-91.4%]; sensitivity, 78.2% [95% CI, 67.3%-89.1%]; specificity, 91.3% [95% CI, 85.8%-96.8%]; ROC: AUC, 0.9474). The CNN visualizations correlated with clinically relevant features such as corneal infiltrate, hypopyon, and conjunctival injection. CONCLUSIONS: The CNN classified corneal ulcers and scars with high accuracy and generalized to patient populations outside of its training data. The CNN focused on clinically relevant features when it made a diagnosis. The CNN demonstrated potential as an inexpensive diagnostic approach that may aid triage in communities with limited access to eye care.

Ventricular longitudinal shortening is an independent predictor of death in heart failure patients with reduced ejection fraction.

Reduced ventricular longitudinal shortening measured by atrioventricular plane displacement (AVPD) and global longitudinal strain (GLS) are prognostic markers in heart disease. This study aims to determine if AVPD and GLS with cardiovascular magnetic resonance (CMR) are independent predictors of cardiovascular (CV) and all-cause death also in heart failure with reduced ejection fraction (HFrEF). Patients (n = 287) were examined with CMR and AVPD, GLS, ventricular volumes, myocardial fibrosis/scar were measured. Follow-up was 5 years with cause of death retrieved from a national registry. Forty CV and 60 all-cause deaths occurred and CV non-survivors had a lower AVPD (6.4 ± 2.0 vs 8.0 ± 2.4 mm, p < 0.001) and worse GLS (- 6.1 ± 2.2 vs - 7.7 ± 3.1%, p = 0.001). Kaplan-Meier analyses displayed increased survival for patients in the highest AVPD- and GLS-tertiles vs. the lowest tertiles (AVPD: p = 0.001, GLS: p = 0.013). AVPD and GLS showed in univariate analysis a hazard ratio (HR) of 1.30 (per-mm-decrease) and 1.19 (per-%-decrease) for CV death. Mean AVPD and GLS were independent predictors of all-cause death (HR = 1.24 per-mm-decrease and 1.15 per-%-decrease), but only AVPD showed incremental value over age, sex, body-mass-index, EF, etiology and fibrosis/scar for CV death (HR = 1.33 per-mm-decrease, p < 0.001). Ventricular longitudinal shortening remains independently prognostic for death in HFrEF even after adjusting for well-known clinical risk factors.

Exon skip-inducing variants in FLNA in an attenuated form of frontometaphyseal dysplasia.

Pathogenic variation in the X-linked gene FLNA causes a wide range of human developmental phenotypes. Loss-of-function is usually male embryonic-lethal, and most commonly results in a neuronal migration disorder in affected females. Gain-of-function variants cause a spectrum of skeletal dysplasias that present with variable additional, often distinctive, soft-tissue anomalies in males and females. Here we present two, unrelated, male individuals with novel, intronic variants in FLNA that are predicted to be pathogenic. Their phenotypes are reminiscent of the gain-of-function spectrum without the skeletal manifestations. Most strikingly, they manifest urethral anomalies, cardiac malformations, and keloid scarring, all commonly encountered features of frontometaphyseal dysplasia. Both variants prevent inclusion of exon 40 into the FLNA transcript, predicting the in-frame deletion of 42 amino acids, however the abundance of FLNA protein was equivalent to that observed in healthy individuals. Loss of these 42 amino acids removes sites that mediate key FLNA functions, including binding of some ligands and phosphorylation. This phenotype further expands the spectrum of the FLNA filaminopathies.

Mechanical Effects of a Maylard Scar During a Vaginal Birth After a Previous Caesarean.

Caesarean section is one of the most common surgeries worldwide, even though there is no evidence supporting maternal and perinatal long-term benefits. Furthermore, the mechanical behavior of a caesarean scar during a vaginal birth after caesarean (VBAC) is not well understood since there are several questions regarding the uterine wound healing process. The aim of this study is to investigate the biomechanical Maylard fiber reorientation and stiffness influence during a VBAC through computational methods. A biomechanical model comprising a fetus and a uterus was developed, and a chemical-mechanical constitutive model that triggers uterine contractions was used, where some of the parameters were adjusted to account for the matrix and fiber stiffness increase in the caesarean scar. Several mechanical simulations were performed to analyze different scar fibers arrangements, considering different values for the respective matrix and fibers stiffness. The results revealed that a random fiber arrangement in the Maylard scar has a much higher impact on its mechanical behavior during a VBAC than the common fibers arrangement present in the uninjured uterine tissue. An increase of the matrix scar stiffness exhibits a lower impact, while an increase of the fiber's stiffness has no significant influence.