Myocardial Wall Research Articles

Llgl1 mediates timely epicardial emergence and establishment of an apical laminin sheath around the trabeculating cardiac ventricle.

During heart development, the embryonic ventricle becomes enveloped by the epicardium, which adheres to the outer apical surface of the heart. This is concomitant with onset of ventricular trabeculation, where a subset of cardiomyocytes lose apicobasal polarity and delaminate basally from the ventricular wall. Llgl1 regulates the formation of apical cell junctions and apicobasal polarity, and we investigated its role in ventricular wall maturation. We found that llgl1 mutant zebrafish embryos exhibit aberrant apical extrusion of ventricular cardiomyocytes. While investigating apical cardiomyocyte extrusion, we identified a basal-to-apical shift in laminin deposition from the internal to the external ventricular wall. We find that epicardial cells express several laminin subunits as they adhere to the ventricle, and that the epicardium is required for laminin deposition on the ventricular surface. In llgl1 mutants, timely establishment of the epicardial layer is disrupted due to delayed emergence of epicardial cells, resulting in delayed apical deposition of laminin on the ventricular surface. Together, our analyses reveal an unexpected role for Llgl1 in correct timing of epicardial development, supporting integrity of the ventricular myocardial wall.

Embryonic alcohol exposure in zebrafish predisposes adults to cardiomyopathy and diastolic dysfunction.

Fetal alcohol spectrum disorders (FASDs) impact up to 0.8% of the global population. However, cardiovascular health outcomes in adult patients, along with predictive biomarkers for cardiac risk stratification, remain unknown. Our aim was to utilize a longitudinal cohort study in an animal model to evaluate the impact of embryonic alcohol exposure (EAE) on cardiac structure, function, and transcriptional profile across the lifespan. Using zebrafish, we characterized the aftereffects of embryonic alcohol exposure (EAE) in adults binned by congenital heart defect (CHD) severity. Chamber sizes were quantified on dissected adult hearts to identify structural changes indicative of cardiomyopathy. Using echocardiography, we quantified systolic function based on ejection fraction and longitudinal strain, and diastolic function based on ventricular filling dynamics, ventricular wall movement, and estimated atrial pressures. Finally, we performed RNA sequencing on EAE ventricles and assessed how differentially expressed genes (DEGs) correlated with cardiac function. Here, we demonstrate that embryonic alcohol exposure (EAE) causes cardiomyopathy and diastolic dysfunction through persistent alterations to ventricular wall structure and gene expression. Following abnormal ventricular morphogenesis, >30% of all EAE adults developed increased atrial-to-ventricular size ratios, abnormal ventricular filling dynamics, and reduced myocardial wall relaxation during early diastole despite preserved systolic function. RNA sequencing of the EAE ventricle revealed novel and heart failure-associated genes (slc25a33, ankrd9, dusp2, dusp4, spry4, eya4, and edn1) whose expression levels were altered across the animal's lifespan or correlated with the degree of diastolic dysfunction detected in adulthood. Our study identifies EAE as a risk factor for adult-onset cardiomyopathy and diastolic dysfunction, regardless of CHD status, and suggests novel molecular indicators of adult EAE-induced heart disease.

The associations of leukocyte telomere length and intermediary cardiovascular phenotype with adverse cardiovascular outcomes in the white population

The evidence about the associations of leukocyte telomere length (LTL) and intermediary cardiovascular phenotypes with adverse cardiovascular outcomes is inconclusive. This study assessed these relationships with cardiovascular imaging, electrocardiography, and the risks of sudden cardiac death (SCD), coronary events, and heart failure (HF) admission. We conducted a cross-sectional analysis of UK Biobank participants enrolled between 2006 and 2010. LTL was measured using quantitative polymerase chain reactions. Electronic health records were used to determine the incidence of SCD, coronary events, and HF admission. Cardiovascular measurements were made using cardiovascular magnetic resonance imaging and machine learning. The associations of LTL with SCD, coronary events, and HF admission and cardiac magnetic resonance imaging, electrocardiogram parameters of 33,043 and 19,554 participants were evaluated by multivariate regression. The median (interquartile range) follow-up period was 11.9 (11.2–12.6) years. Data was analyzed from January to May 2023. Among the 403,382 white participants without coronary artery disease or HF, 181,637 (45.0%) were male with a mean age of 57.1 years old. LTL was independently negatively associated with a risk of SCD (LTL third quartile vs first quartile: hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.72–0.92), coronary events (LTL third quartile vs first quartile: HR: 0.88, 95% CI: 0.84–0.92), and HF admission (LTL fourth quartile vs first quartile: HR: 0.84, 95% CI: 0.74–0.95). LTL was also independently positively associated with cardiac remodeling, specifically left ventricular mass index, left-ventricular-end systolic and diastolic volumes, mean left ventricular myocardial wall thickness, left ventricular stroke volume, and with electrocardiogram changes along the negative degree of T-axis. Cross-sectional study results showed that LTL was positively associated with heart size and cardiac function in middle age, but electrocardiography results did not show these associations, which could explain the negative association between LTL and risk of SCD, coronary events, and HF admission in UK Biobank participants.

MADR-Net: multi-level attention dilated residual neural network for segmentation of medical images

Medical image segmentation has made a significant contribution towards delivering affordable healthcare by facilitating the automatic identification of anatomical structures and other regions of interest. Although convolution neural networks have become prominent in the field of medical image segmentation, they suffer from certain limitations. In this study, we present a reliable framework for producing performant outcomes for the segmentation of pathological structures of 2D medical images. Our framework consists of a novel deep learning architecture, called deep multi-level attention dilated residual neural network (MADR-Net), designed to improve the performance of medical image segmentation. MADR-Net uses a U-Net encoder/decoder backbone in combination with multi-level residual blocks and atrous pyramid scene parsing pooling. To improve the segmentation results, channel-spatial attention blocks were added in the skip connection to capture both the global and local features and superseded the bottleneck layer with an ASPP block. Furthermore, we introduce a hybrid loss function that has an excellent convergence property and enhances the performance of the medical image segmentation task. We extensively validated the proposed MADR-Net on four typical yet challenging medical image segmentation tasks: (1) Left ventricle, left atrium, and myocardial wall segmentation from Echocardiogram images in the CAMUS dataset, (2) Skin cancer segmentation from dermoscopy images in ISIC 2017 dataset, (3) Electron microscopy in FIB-SEM dataset, and (4) Fluid attenuated inversion recovery abnormality from MR images in LGG segmentation dataset. The proposed algorithm yielded significant results when compared to state-of-the-art architectures such as U-Net, Residual U-Net, and Attention U-Net. The proposed MADR-Net consistently outperformed the classical U-Net by 5.43%, 3.43%, and 3.92% relative improvement in terms of dice coefficient, respectively, for electron microscopy, dermoscopy, and MRI. The experimental results demonstrate superior performance on single and multi-class datasets and that the proposed MADR-Net can be utilized as a baseline for the assessment of cross-dataset and segmentation tasks.

Laser catheter ablation of atrial zones with ganglionated plexi: impact on atrial fibrillation inducibility and the risk of esophageal damage in experimental settings

Aim. To study the potential applicability of transcatheter laser ablation for the destruction of atrial ganglionated plexi (GP) zones and the safety of this technique in relation to inadvertent esophageal damage.Methods. This was a two-stage investigation: (1) ex vivo experiments: the risk of esophageal damage during ablation on the dorsal (posterior) left atrial (LA) wall was assessed; three swine organ complexes were used, which included the heart, lungs and esophagus; (2) in vivo experiments assessing the effects of laser catheter ablation of GP zones on the inducibility of atrial fibrillation (AF) and changes in atrial effective refractory period - included 13 landrace pigs (average weight 38.8±1.2 kg).Ex vivo: laser catheter ablations were performed from the endocardial surface of the LA towards the esophagus with a power of 15 watts of varying duration; ablation was performed under thermal scanning of the LA and esophagus; then a macroscopic examination of the myocardial and esophageal walls was performed.In vivo: before and after catheter laser ablation (15 W) of the GP zones in the right atrium and atrial septum, atrial ERP was assessed with programmed stimulation, and AF induction with high-frequency (33 Hz, 2 min) stimulation was evaluated. At the end of the experiment, the animals were euthanized, and the heart and lungs were collected in a single unit.Results. Ex vivo experiments: in two cases, damage to the endocardium of the LA was detected at an exposure time of 30 s. Damage to the esophagus was observed with a longer exposure time (> 30 seconds) with a 11.3-15.4°C increase in temperature. In the in vivo experiments, 78 laser applications (6±1 in one swine) were delivered to the posterior wall of the right atrium and atrial septum. Atrial effective refractory period was not altered after ablation (183±20 ms vs 186±18 ms, P=0.99). At the baseline, AF was induced in 12 out of 13 animals (92%). After ablation, AF was induced in 7 animals (54%) (P=0.03). There was a trend toward a decrease in the duration of AF after laser ablation of GP zones (18 [5; 141] vs. 2 [0; 14] s after ablation, P=0.06). Transmural damage was observed in 46% of the hearts. No damage to extra-cardiac structures was detected.Conclusion. Ex vivo, laser ablation on the dorsal (posterior) wall of the LA with a power of 15 W and duration <30 s does not lead to visible damage to the esophagus. Laser ablation of atrial GP zones is feasible and reduces the inducibility of AF. No change in atrial effective refractory period is detected following GP zones ablation, when performed from the right atrium.

Echocardiographic assessment of cardiovascular physiology of preterm miniature piglets supported with a pumped artificial placenta system.

We evaluated fetal cardiovascular physiology and mode of cardiac failure in premature miniature piglets on a pumped artificial placenta (AP) circuit. Fetal pigs were cannulated via the umbilical vessels and transitioned to an AP circuit composed of a centrifugal pump and neonatal oxygenator and maintained in a fluid-filled biobag. Echocardiographic studies were conducted to measure ventricular function, umbilical blood flow, and fluid status. In utero scans were used as control data. AP fetuses (n=13; 102±4d gestational age [term 115d]; 616±139g [g]; survival 46.4±46.8h) were tachycardic and hypertensive with initially supraphysiologic circuit flows. Increased myocardial wall thickness was observed. Signs of fetal hydrops were present in all piglets. Global longitudinal strain (GLS) measurements increased in the left ventricle (LV) after transition to the circuit. Right ventricle (RV) and LV strain rate decreased early during AP support compared with in utero measurements but recovered toward the end of the experiment. Fetuses supported for >24h had similar RV GLS to in utero controls and significantly higher GLS compared to piglets surviving only up to 24h. Fetuses on a pump-supported AP circuit experienced an increase in afterload, and redistribution of blood flow between the AP and systemic circulations, associated with elevated end-diastolic filling pressures. This resulted in heart failure and hydrops. These preterm fetuses were unable to tolerate the hemodynamic changes associated with connection to the current AP circuit. To better mimic the physiology of the native placenta and preserve normal fetal cardiovascular physiology, further optimization of the circuit will be required.

Imaging-derived tissue visualization guides catheter ablation of premature ventricular contractions

Abstract Background The presence of myocardial scarring is associated with worse outcomes after catheter ablation of premature ventricular contractions (PVCs). Three-dimensional substrate characterization is emerging for peri-procedural ablation guidance, but its value for tissue visualization during PVC ablation is unknown. Purpose The aim of the present study was to assess the impact of imaging-derived tissue visualization on lesion planning, procedural and clinical outcomes of PVC ablation. Methods Thirteen consecutive patients (92.3% male, 62.2±12.4 years) undergoing unipolar (n=8) or bipolar (n=5) PVC catheter ablation with integrated three-dimensional imaging from multidetector computed tomography or cardiac magnetic resonance imaging were included. All patients presented with assumed myocardial scarring due to an underlying cardiomyopathy and/or after previous ablation. Results Among all patients (30.8% (peri-)myocarditis, 20.0% ischemic, 15.4% dilated cardiomyopathy, 15.4% idiopathic, 7.7% nonischemic, 7.7% congenital heart disease) undergoing ablation of 20 PVC morphologies (median 1 (IQR 1-2) per patient; 75.0% non-outflow tract; 70.0% left-sided), myocardial scarring was present in 11/13 (84.6%). Wall thinning <5 mm covering an area of 36.1±17.8 cm² contained the PVC origin in 4/13 (30.8%) patients and was safely targeted with radiofrequency lesions with up to 45 W (maximum power: median 32 W (IQR 30-35)) (Figure 1). Imaging-guided bipolar ablation was performed in 5/8 (62.5%) patients with previously therapy-refractory PVCs including foci at the left ventricular summit and the right ventricular outflow tract each in 2 and the left coronary cusp in one patient (Figure 2). PVCs were efficiently suppressed with less radiofrequency lesions (5.4±3.8 vs. 55.8±36.9; p=0.0160) with shorter duration (4.1±3.2 min vs. 23.3±13.5 min; p=0.0152) compared to prior unipolar ablation. Bipolar lesions resulted in a higher impedance (158 Ω (IQR 101-174) vs. 106 Ω (IQR 99-124); p=0.0025), while requiring a lower temperature (36 °C (IQR 35-38) vs. 39 °C (IQR 36-43); p=0.0001) and less power (26 W (IQR 20-30) vs. 30 W (IQR 25-31); p=0.0376). Complete suppression of the clinical PVC was reached in all 13 patients. During a follow-up of 396.8±299.7 days, PVC burden decreased from 20.1±14.3% to 1.7±1.6% (p=0.0172). Conclusions Imaging-derived tissue visualization enables determination of myocardial wall thinning <5 mm as a substrate for recurrent PVCs, which can be safely targeted. Three-dimensional imaging efficiently guides high power lesion application and bipolar ablation of PVCs at anatomically challenging foci.Anatomically challenging fociImaging-guided bipolar ablation

Evaluating left atrial wall thickness: a new frontier in predicting atrial scar and reentrant tachycardia

Abstract Background and Objective Reentrant atrial tachycardias (AT) are commonly observed in patients with atrial scar. These scars form a substrate in the atrium, characterized by areas of slow conduction, crucial for initiating reentrant cycles. During these cycles, zones of slow conduction often act as critical isthmuses (CI), becoming prime targets for ablation. Late potential mapping is a technique used to identify these slow conduction zones. Moreover, recent advancements in imaging software now allow for the precise measurement of myocardial wall thickness, aiding in the identification of thin myocardial areas that could potentially have the CI of AT. Methods We conducted a retrospective study of patients who underwent catheter ablation for AT. The study focused on patients who either presented with AT or in whom it was induced and who had undergone late potential mapping of the left atrium. To identify deceleration zones (DZ), we created voltage maps and isochronal late activation maps (ILAM) during sinus or paced rhythm. Electrograms exhibiting a continuous-fragmented morphology were explicitly marked. Upon induction of AT, activation mapping was employed to pinpoint the CI of the tachycardia circuit. Additionally, the thickness of the left atrial (LA) wall and LA volume were measured using ADAS3D software. Results A total of 39 patients, with 25 (65.1%) being female, were enrolled in the study. The mean age of the participants was 62.5 ± 9.5 years. The average volume of the left atrium was measured at 124.8 ± 35.5 mL, and the mean thickness of the LA wall was 1.58 ± 0.2 mm. In most patients (16, 41.0%), the septal wall was the thinnest part of the left atrium. However, significant thinning of the LA wall was observed predominantly on the anterior wall in 29 patients (74.2%) and on the LA roof in 18 patients (46.2%). The sensitivity and positive predictive value (PPV) of thinning in the LA anterior wall in detecting late potentials were 74.1% and 68.9%, respectively. For detecting critical isthmuses, these values were 76.9% (sensitivity) and 66.7% (PPV). Regarding the LA roof, the diagnostic value for thinning in detecting late potentials and critical isthmuses showed a sensitivity of 57.1% and 57.9%, respectively, and a PPV of 57.1% and 52.4%, respectively. Conclusion Evaluating LA thickness represents a novel approach that can potentially identify LA scars and late potentials before the procedure, particularly in the LA anterior wall. While the observed positive predictive values are acceptable, the negative predictive values and specificity are relatively low. Future advancements in imaging software, along with the development of standardized cardiac computed tomography protocols, can potentially enhance these outcomes. Consequently, preprocedural computed tomography could become increasingly significant in managing and treating AF and AT beyond LA anatomy evaluation.TablesLeft Atrial Wall Thickness

LMNA–RELATED DILATED CARDIOMYOPATHY PRESENTING WITH REGIONAL WALL AKINESIS AND TRANSMURAL LATE GADOLINIUM ENHANCEMENT

Abstract A 26–year–old girl was admitted at hospital in December 2022 for a syncopal episode. She referred fatigue and dyspnea in the last 2 months. EKG was markedly abnormal showing peripheral low voltages, poor R wave progression in prechordial leads, negative T waves V4–V6, DII, DIII and aVF, fragmented QRS (Fig.1). Echo showed moderately dilated left ventricle (LV) with apical akinesia and apical aneurysm (no thrombi) and hypo–akinesia and hyperechoic appearance of the middle segments of the infero–posterior and lateral wall (Fig.2a). EF was 38%. There was no family history for sudden cardiac death and cardiomyopathy. Creatine kinase and neurological examination were normal. The diagnostic work–up included: myocardial scintigraphy which showed fixed tracer uptake deficit at apical and posterolateral levels (Fig.2b); cardiac magnetic resonance (CMR): apical aneurysm with extended late gadolinium enhancement (LGE) due to fibrosis, focally transmural, on the left ventricle’s midapical and infero–lateral thinned–hypokinetic myocardial walls (Fig.3a, 3b); Coronary angiography showed no stenosis. Due to myocardial aneurysm in absence of CAD, Chagas disease was excluded. We performed LV endomyocardial biopsy which showed cardiomyopathic changes and replacement fibrosis. Due to fibrosis extension, complex ventricular extrasystoles detected on monitoring and syncope, ICD was implanted. Finally genetic testing showed c.1621C>Tp.Arg541Cys LMNA pathogenetic mutation leading to the diagnosis of LMNA–related LV cardiomyopathy, with extensive fibrosis in multiple areas of left ventricle including the apical segments at a very young age. Patients with LMNA mutation-related heart disease are characterized by conduction abnormalities, ventricular tachyarrhythmias (VA) and high risk of sudden cardiac death with mildly impaired systolic function, often without chamber dilation. About 88% LMNA– cardiomyopathy have typical myocardial fibrosis, predominantly in the mid-myocardium of the basal septum. However, our patient and previous reported cases with the same p.R541 LMNA mutation presents with a specific phenotype including regional LV akinesis, segmental transmural LGE, significant LV dilatation and systolic dysfunction and VA without conduction abnormality. Of note, EKG shows normal A–V conduction but low voltage and negative T waves in precordial and inferior leads. These features are not typical for LMNA–disease and underline the phenotypic variability of cardiomyopathies.

THE APEX TALKS…CARDIAC METASTASIS MIMICKING ST SEGMENT ELEVATION MYOCARDIAL INFARCTION

Abstract A 78–year–old man with a recent diagnosis of lung squamous cell carcinoma was referred to our cardiology department for marked ECG abnormalities (ST segment elevation in V2–V4 and T waves inversion in the antero–lateral leads, Fig.1) in the absence of ischemic symptoms and for the detection of an intramyocardial mass at the apical segments on the CT scan. He had no significant previous cardiovascular history. A transthoracic echocardiogram (TTE) was performed and showed an isoechoic mass at the LV apical segments measuring 3 x 4 cm apparently incorporating the myocardial wall without a clear cleavage plane (Fig.2a). The EF was normal. No pericardial effusion present. The contrast echocardiography with Sonovue revealed a late uptake of the contrast (Fig.2b). Cardiac magnetic resonance (CMR) showed an ovular image in the para–apical area of 40 x 23 cm consistent with a secondary lesion (Fig.3). Unfortunately, the exam was interrupted early due to a patient’s claustrophobic crisis, without having acquired the post–contrast images. Due to infiltrative appearance of the mass and the oncology history, this formation was highly suspicious for metastasis. No complicated ventricular arrhythmias were detected on ECG monitoring. No symptoms of heart failure were reported. Due to the marked EKG repolarization abnormalities the patient underwent coronary angiography which excluded significant stenosis. FDG PET/CT showed areas of increased metabolism also at liver and adrenal left gland. Finally, the patient was transferred to the oncology department for specific management. Cardiac metastases are more common than primary cardiac malignancy and are more frequently related to primary lung cancer, followed by breast cancer and hematologic malignancies. Typical presentation includes arrhythmias or conduction disturbances. The imaging findings of cardiac metastases are non–specific but mostly infiltrative, heterogeneous, and multiple masses may be present. Echocardiography is the initial imaging test for the detection of cardiac metastasis, although CMR, CT and PET/CT may be helpful. Herein we described a case of cardiac metastasis with EKG mimicking acute coronary syndrome. This finding is not uncommon among these patients. EKG findings of myocardial ischemia or injury, particularly localized and prolonged ST elevation, in the absence of ischemic symptoms have been reported in previous studies as high specificity for cardiac metastasis in patients with malignancy.

DILATED CARDIOMYOPATHY, GUIDELINES PERSONALIZATION OF CARE

Abstract The term Dilated cardiomyopathy (CMD) refers to a family of diseases characterized by complex interactions between environment and genetic predisposition. Diagnostic tools as cardiac magnetic resonance imaging (MRI) must be systematically implemented in clinical practice to define the etiological cause and undertake a specific therapeutic treatment. We present the case of a young man with CMD and severe left ventricular dysfunction (ejection fraction, EF: 14%; left ventricular end–diastolic volume (LVEDV): 251 ml/m2; left ventricular end–systolic volume (LVESV): 197 ml/m2. The patient has a family history of sudden cardiac death (SCD). He is affected by a psychiatric pathology (ADHD) and has a history of alcohol and drug addiction. Many diagnostic hypotheses have been considered for etiological research (viral myocarditis, genetic or alcoholic–induced cardiomyopathy, toxic substances such as narcotics and psychiatric drug–induced cardiomyopathy). MRI after 11 days in hospital confirmed FE 14%, LVEDV: 320 ml/m2, LVESV: 275 ml/m2; reduction of the wall thickness at the antero–septal wall to the middle tract; areas of altered signal, hyperintense in T2W sequences, at the left ventricular myocardial wall suspected of myocardial edema, associated with extended signal hyperintensity of periventricular tissue, which show marked enhancement immediately after intravenous contrast agent administration (Fig. 1). The underlying psychiatric pathology and the possibility of poor adherence to the maintenance of the wearable defibrillator did not facilitate the clinical follow–up which should have included the identification of the etiological cause and the appropriate treatment guaranteeing the temporary prevention of SCD. So, it was decided to make a personalized therapeutic choice, the patient underwent implantation of a subcutaneous defibrillator, pending a better diagnostic definition and the possible need of other therapies as cardiac transplantation/implantation of mechanical assistance device.

EOSINOPHILIC MYOPERICARDITIS: A CASE SERIES

Abstract Background Eosinophilic myocarditis is characterized by acute myocardial inflammation due to eosinophilic tissue infiltration. Methods Diagnosis was based on laboratory tests, Echo and CMR; EMB was performed in uncertain cases. Treatment was performed according to the etiology of EM. All patients underwent regular follow–up at our Center. Results This study includes 9 patients (89% Caucasian, 78% women, mean age 48.2±13.6 years), admitted in our Center from February 2021 to November 2023. 66.67% cases occurred in the setting of eosinophilic granulomatosis with polyangiitis, 11% was secondary to B–cell lymphoblastic leukemia, and 22% were labelled as idiopathic EM. All patients presented with high eosinophil count (6133±4893/mcL), elevated CRP (57±66 mg/L) and hs–troponin I (3610±5166 ng/L) levels, and 67% cases NT–proBNP (10751±4038 ng/L) was elevated. 67% patients presented with dyspnea, 56% with chest pain, and 56% with fever. On ECG, sinus tachycardia, low QRS voltages and ST segment depression with negative T–waves were common. Thickening of the myocardial walls with reduction of GLS was seen in all cases; in 44% cases, the EF was below 50%; 56% cases had mild pericardial effusion. 1 patient had intraventricular thrombi at CMR, another one had bilateral pulmonary embolism. On CMR, all patients had areas of hypokinesia, myocardial edema, and myo–pericardial late gadolinium enhancement. EMB was performed in 5 cases, confirming the presence of intramyocardial eosinophilic infiltrates. 7 patients required CICU, and 1 needed inotrope (dobutamine) use. The patient with ALL was treated with combined chemotherapy. The other EM cases were treated with immunosuppressive therapy consisting of corticosteroids and either cyclophosphamide or rituximab or mepolizumab. All patients received cardioprotective therapy with BBs and ACE–inhibitors; in patients with pericardial involvement, colchicine was administered. All patients showed rapid clinical improvement following immunosuppressive therapy initiation, with prompt reduction of circulating eosinophils and hs–troponin I values and normalization of the ejection fraction. On CMR imaging, edema disappeared at follow–up, with LGE replacement in one case. All patients were alive and in good conditions at the last follow–up. Conclusions EM is an underdiagnosed life–threatening disease. A careful assessment of the etiology, as prompt therapy, is mandatory to achieve clinical amelioration and good mid–term prognosis.

MyoFold: Joint myocardial tissue composition and wall motion quantification via a highly folded sequence.

This study aims to develop and evaluate a novel cardiovascular MR sequence, MyoFold, designed for the simultaneous quantifications of myocardial tissue composition and wall motion. MyoFold is designed as a 2D single breathing-holding sequence, integrating joint T1/T2 mapping and cine imaging. The sequence uses a 2-fold accelerated balanced SSFP (bSSFP) for data readout and incorporates electrocardiogram synchronization to align with the cardiac cycle. MyoFold initially acquires six single-shot inversion-recovery images, completed during the diastole of six successive heartbeats. T2 preparation (T2-prep) is applied to introduce T2 weightings for the last three images. Subsequently, over the following six heartbeats, segmented bSSFP is performed for the movie of the entire cardiac cycle, synchronized with an electrocardiogram. A neural network trained using numerical simulations of MyoFold is used for T1 and T2 calculations. MyoFold was validated through phantom and in vivo experiments, with comparisons made against MOLLI, SASHA, T2-prep bSSFP, and the conventional cine. In phantom studies, MyoFold exhibited a 10% overestimation in T1 measurements, whereas T2 measurements demonstrated high accuracy. In vivo experiments revealed that MyoFold T1 had comparable accuracy to SASHA and precision similar to MOLLI. MyoFold demonstrated good agreement with T2-prep bSSFP in myocardial T2 measurements. No significant differences were observed in the quantification of left-ventricle wall thickness and function between MyoFold and the conventional cine. MyoFold presents as a rapid, simple, and multitasking approach for quantitative cardiovascular MR examinations, offering simultaneous assessment of tissue composition and wall motion. The sequence's multitasking capabilities make it a promising tool for comprehensive cardiac evaluations in clinical settings.

Course and treatment of diabetes: from cardiovascular risk to catastrophe. Clinical case

As of today, type 2 diabetes mellitus and its complications impose a significant burden on healthcare systems worldwide. Myocardial infarction stands as a leading cause of death among patients with type 2 diabetes mellitus due to macroangiopathy resulting from glucose metabolism disorders and endothelial damage [5]. Unfortunately, even with timely assistance, patients with myocardial infarction may develop mechanical complications such as cardiac aneurysm, posing serious risks of myocardial wall rupture with a high likelihood of fatality. In most cases, interventricular septal rupture occurs, manifesting in 0,21% of cases of ST-segment elevation myocardial infarction (STEMI) and 0,04% of cases of non-STEMI. Surgical correction of the defect remains the only effective treatment method, albeit associated with a high risk of mortality. Consequently, intra- and post-operative complications in such patients prompt the search for alternative treatment modalities, including transcatheter closure of the defect [6]. Interventricular septal rupture more commonly occurs in older patients, women, those with hypertension, and chronic kidney disease. Typically, the defect arises against the backdrop of the first myocardial infarction in the absence of timely or absent reperfusion therapy. Interventricular septal rupture may develop within 1–14 days after STEMI. However, the incidence usually demonstrates a bimodal peak within the first 24 hours or 3–5 days after the infarction [12]. A clinical case of a patient with combined cardiometabolic pathology, namely, severe type 2 diabetes mellitus and post-infarction interventricular septal defect, is presented. The case underscores the issue of comorbidity in severe patients. Successful treatment of the patient was achieved through collaborative efforts of cardiac surgeons, intensivists, cardiologists and endocrinologists.

Study of Attenuation Correction Using a Cardiac Dynamic Phantom: Synchronized Time-Phase-Gated Attenuation Correction Method.

In cardiac nuclear medicine examinations, absorption in the body is the main factor in the degradation of the image quality. The Chang and external source methods were used to correct for absorption in the body. However, fundamental studies on attenuation correction for electrocardiogram (ECG)-synchronized CT imaging have not been performed. Therefore, we developed and improved an ECG-synchronized cardiac dynamic phantom and investigated the synchronized time-phase-gated attenuation correction (STPGAC) method using ECG-synchronized SPECT and CT images of the same time phase. Methods: As a basic study, SPECT was performed using synchronized time-phase-gated (STPG) SPECT and non-phase-gated (NPG) SPECT. The attenuation-corrected images were, first, CT images with the same time phase as the ECG waveform of the gated SPECT acquisition (with CT images with the ECG waveform of the CT acquisition as the reference); second, CT images with asynchronous ECG; third, CT images of the 75% region; and fourth, CT images of the 40% region. Results: In the analysis of cardiac function in the phantom experiment, left ventricle ejection fraction (heart rate, 11.5%-13.4%; myocardial wall, 49.8%-55.7%) in the CT images was compared with that in the STPGAC method (heart rate, 11.5%-13.3%; myocardial wall, 49.6%-55.5%), which was closer in value to that of the STPGAC method. In the phantom polar map segment analyses, none of the images showed variability (F (10,10) < 0.5, P = 0.05). All images were correlated (r = 0.824-1.00). Conclusion: In this study, we investigated the STPGAC method using a SPECT/CT system. The STPGAC method showed similar values of cardiac function analysis to the CT images, suggesting that the STPGAC method accurately reconstructed the distribution of blood flow in the myocardial region. However, the target area for attenuation correction of the heart region was smaller than that of the whole body, and changing the gated SPECT conditions and attenuation-corrected images did not affect myocardial blood flow analysis.

Myocardial motion in acute ischemia: revealing invisible deformation by echocardiography.

Echocardiography has been used clinically to assess regional myocardial wall motion for the diagnosis of acute myocardial ischemia or stress-induced ischemia, but it is often difficult to distinguish hypokinetic motion from normal motion. Myocardial wall motion is affected by loading conditions as well as intrinsic contractility, making it challenging to define a normal range of wall motion. Therefore, hypokinesis is usually diagnosed by comparing target areas with other areas of myocardium considered normal (relative hypokinesis). Myocardial strain analysis by tissue Doppler echocardiography and speckle-tracking echocardiography has enabled objective and quantitative evaluation of regional myocardial wall motion. Peak systolic strain decreases during acute ischemia, but subtle and invisible myocardial motion, such as early systolic lengthening (ESL) and postsystolic shortening (PSS), also occurs, and the analysis of these subtle motions can improve the diagnostic accuracy of ischemia. However, the diagnosis of ischemic myocardium by strain analysis is not widely performed in clinical practice at this time due to several limitations. This article reviews the features of myocardial motion during acute ischemia, the mechanisms of ESL and PSS, the diagnosis of ischemic myocardium using strain analysis, and current approaches and future challenges to overcome the limitations in the detection of relative hypokinesis. This article also explains the use of ESL and PSS to detect myocardial ischemic memory that remains after brief ischemia.

A Novel Approach to Cardiac Magnetic Resonance Scar Characterization in Patients Affected by Cardiac Amyloidosis: A Pilot Study.

Background and Objectives: Cardiac magnetic resonance (CMR) imaging has become an essential instrument in the study of cardiomyopathies; it has recently been integrated into the diagnostic workflow for cardiac amyloidosis (CA) with remarkable results. An additional emerging role is the stratification of the arrhythmogenic risk by scar analysis and the possibility of merging these data with electro-anatomical maps. This is made possible by using a software (ADAS 3D, Galgo Medical, Barcelona, Spain) able to provide 3D heart models by detecting fibrosis along the whole thickness of the myocardial walls. Little is known regarding the applications of this software in the wide spectrum of cardiomyopathies and the potential benefits have yet to be discovered. In this study, we tried to apply the ADAS 3D in the context of CA. Materials and Methods: This study was a retrospectively analysis of consecutive CMR imaging of patients affected by CA that were treated in our center (Marche University Hospital). Wherever possible, the data were processed with the ADAS 3D software and analyzed for a correlation between the morphometric parameters and follow-up events. The outcome was a composite of all-cause mortality, unplanned cardiovascular hospitalizations, sustained ventricular arrhythmias (VAs), permanent reduction in left ventricular ejection fraction, and pacemaker implantation. The secondary outcomes were the need for a pacemaker implantation and sustained VAs. Results: A total of 14 patients were deemed eligible for the software analysis: 8 patients with wild type transthyretin CA, 5 with light chain CA, and 1 with transthyretin hereditary CA. The vast majority of imaging features was not related to the composite outcome, but atrial wall thickening displayed a significant association with both the primary (p = 0.003) and the secondary outcome of pacemaker implantation (p = 0.003). The software was able to differentiate between core zones and border zones of scars, with the latter being the most extensively represented in all patients. Interestingly, in a huge percentage of CMR images, the software identified the highest degree of core zone fibrosis among the epicardial layers and, in those patients, we found a higher incidence of the primary outcome, without reaching statistical significance (p = 0.18). Channels were found in the scar zones in a substantial percentage of patients without a clear correlation with follow-up events. Conclusions: CMR imaging plays a pivotal role in cardiovascular diagnostics. Our analysis shows the feasibility and applicability of such instrument for all types of CA. We could not only differentiate between different layers of scars, but we were also able to identify the presence of fibrosis channels among the different scar zones. None of the data derived from the ADAS 3D software seemed to be related to cardiac events in the follow-up, but this might be imputable to the restricted number of patients enrolled in the study.

Extended MRI-based PET motion correction for cardiac PET/MRI

PurposeA 2D image navigator (iNAV) based 3D whole-heart sequence has been used to perform MRI and PET non-rigid respiratory motion correction for hybrid PET/MRI. However, only the PET data acquired during the acquisition of the 3D whole-heart MRI is corrected for respiratory motion. This study introduces and evaluates an MRI-based respiratory motion correction method of the complete PET data.MethodsTwelve oncology patients scheduled for an additional cardiac 18F-Fluorodeoxyglucose (18F-FDG) PET/MRI and 15 patients with coronary artery disease (CAD) scheduled for cardiac 18F-Choline (18F-FCH) PET/MRI were included. A 2D iNAV recorded the respiratory motion of the myocardium during the 3D whole-heart coronary MR angiography (CMRA) acquisition (~ 10 min). A respiratory belt was used to record the respiratory motion throughout the entire PET/MRI examination (~ 30–90 min). The simultaneously acquired iNAV and respiratory belt signal were used to divide the acquired PET data into 4 bins. The binning was then extended for the complete respiratory belt signal. Data acquired at each bin was reconstructed and combined using iNAV-based motion fields to create a respiratory motion-corrected PET image. Motion-corrected (MC) and non-motion-corrected (NMC) datasets were compared. Gating was also performed to correct cardiac motion. The SUVmax and TBRmax values were calculated for the myocardial wall or a vulnerable coronary plaque for the 18F-FDG and 18F-FCH datasets, respectively.ResultsA pair-wise comparison showed that the SUVmax and TBRmax values of the motion corrected (MC) datasets were significantly higher than those for the non-motion-corrected (NMC) datasets (8.2 ± 1.0 vs 7.5 ± 1.0, p < 0.01 and 1.9 ± 0.2 vs 1.2 ± 0.2, p < 0.01, respectively). In addition, the SUVmax and TBRmax of the motion corrected and gated (MC_G) reconstructions were also higher than that of the non-motion-corrected but gated (NMC_G) datasets, although for the TBRmax this difference was not statistically significant (9.6 ± 1.3 vs 9.1 ± 1.2, p = 0.02 and 2.6 ± 0.3 vs 2.4 ± 0.3, p = 0.16, respectively). The respiratory motion-correction did not lead to a change in the signal to noise ratio.ConclusionThe proposed respiratory motion correction method for hybrid PET/MRI improved the image quality of cardiovascular PET scans by increased SUVmax and TBRmax values while maintaining the signal-to-noise ratio.Trial registration METC162043 registered 01/03/2017.

Analysis of morphology, histology characteristics, and circadian clock gene expression of Onychostoma macrolepis at the overwintering period and the breeding period.

Fish typically adapt to their environment through evolutionary traits, and this adaptive strategy plays a critical role in promoting species diversity. Onychostoma macrolepis is a rare and endangered wild species that exhibits a life history of overwintering in caves and breeding in mountain streams. We analyzed the morphological characteristics, histological structure, and expression of circadian clock genes in O. macrolepis to elucidate its adaptive strategies to environmental changes in this study. The results showed that the relative values of O. macrolepis eye diameter, body height, and caudal peduncle height enlarged significantly during the breeding period. The outer layer of the heart was dense; the ventricular myocardial wall was thickened; the fat was accumulated in the liver cells; the red and white pulp structures of the spleen, renal tubules, and glomeruli were increased; and the goblet cells of the intestine were decreased in the breeding period. In addition, the spermatogenic cyst contained mature sperm, and the ovaries were filled with eggs at various stages of development. Throughout the overwintering period, the melano-macrophage center is located between the spleen and kidney, and the melano-macrophage center in the cytoplasm has the ability to synthesize melanin, and is arranged in clusters to form cell clusters or white pulp scattered in it. Circadian clock genes were identified in all organs, exhibiting significant differences between the before/after overwintering period and the breeding period. These findings indicate that the environment plays an important role in shaping the behavior of O. macrolepis, helping the animals to build self-defense mechanisms during cyclical habitat changes. Studying the morphological, histological structure and circadian clock gene expression of O. macrolepis during the overwintering and breeding periods is beneficial for understanding its unique hibernation behavior in caves. Additionally, it provides an excellent biological sample for investigating the environmental adaptability of atypical cavefish species.

Identification of Circulating Plasma Proteins as a Mediator of Hypertension-Driven Cardiac Remodeling: A Mediation Mendelian Randomization Study.

This study focused on circulating plasma protein profiles to identify mediators of hypertension-driven myocardial remodeling and heart failure. A Mendelian randomization design was used to investigate the causal impact of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure on 82 cardiac magnetic resonance traits and heart failure risk. Mediation analyses were also conducted to identify potential plasma proteins mediating these effects. Genetically proxied higher SBP, DBP, and pulse pressure were causally associated with increased left ventricular myocardial mass and alterations in global myocardial wall thickness at end diastole. Elevated SBP and DBP were linked to increased regional myocardial radial strain of the left ventricle (basal anterior, mid, and apical walls), while higher SBP was associated with reduced circumferential strain in specific left ventricular segments (apical, mid-anteroseptal, mid-inferoseptal, and mid-inferolateral walls). Specific plasma proteins mediated the impact of blood pressure on cardiac remodeling, with FGF5 (fibroblast growth factor 5) contributing 2.96% (P=0.024) and 4.15% (P=0.046) to the total effect of SBP and DBP on myocardial wall thickness at end diastole in the apical anterior segment and leptin explaining 15.21% (P=0.042) and 23.24% (P=0.022) of the total effect of SBP and DBP on radial strain in the mid-anteroseptal segment. Additionally, FGF5 was the only mediator, explaining 4.19% (P=0.013) and 4.54% (P=0.032) of the total effect of SBP and DBP on heart failure susceptibility. This mediation Mendelian randomization study provides evidence supporting specific circulating plasma proteins as mediators of hypertension-driven cardiac remodeling and heart failure.