Cardiac Structures Research Articles

The use of Intracardiac Echocardiography in Catheter Ablation of Atrial Fibrillation.

Intracardiac echocardiography (ICE) provides real-time, fluoroless imaging of cardiac structures, allowing optimal catheter positioning and energy delivery during ablation procedures. This review summarizes the use of ICE in catheter ablation of atrial fibrillation (AF). Growing evidence suggests that the use of ICE improves procedural safety and facilitates radiofrequency and cryoballoon AF ablation. ICE-guided catheter ablation is associated with reduced procedural duration and fluoroscopy use. Recent studies have examined the role of ICE in guiding novel ablation techniques, such as pulsed field ablation. Finally, the use of ICE allows for early detection and timely management of potentially serious procedural complications. Intracardiac echocardiography offers significant advantages during AF ablation procedures and its use should be encouraged to improve procedural safety and efficacy.

Clinical and Pathoanatomical Characteristics of Hypoplastic Left Heart Syndrome a Clinical Case

Hypoplastic left heart syndrome (HLHS) is a common congenital heart defect, accounting for 4 to 16% of cases, and is one of the most prognostically unfavorable, involving single-­ventricle hemodynamics. HLHS involves hypoplasia of the left ventricle, often in combination with atresia and/or stenosis of the aortic and/or mitral valves, as well as hypoplasia of various parts of the aorta. Intrauterine reduction in blood flow to the left heart structures at early stages of fetal development subsequently leads to severe changes in cardiac structures, often not amenable to surgical correction. Objective. To study the clinical and morphological features of HLHS using a clinical case as an example. Materials and Methods. The patient was a child from the first pregnancy, which was complicated by anemia and first-­trimester preeclampsia. The defect was diagnosed prenatally at 23/24 weeks. At 39 weeks, labor was induced, and the infant was hospitalized in the intensive care unit with symptoms of cardiac and respiratory failure. On the 6th day of life, surgical treatment was performed — a Norwood operation, which is a single-­ventricle hemodynamic surgical correction of the defect. Despite intensive care measures, multiple organ failure progressed, leading to the development of disseminated intravascular coagulation (DIC) and subsequent death on the 10th day of life. Results. Autopsy, including staining of the myocardium with Masson’s trichrome and hematoxylin and eosin, showed pronounced plethora of the microcirculatory vessels with formation of erythrocyte thrombi. Pronounced perivascular edema and fraying of muscle fibers were detected. Fibroelastosis of the endocardium of the left ventricle was observed, characterized by pronounced sclerotic thickening due to significant proliferation of fibrous tissue, with the spread of connective tissue strands into the myocardium. Endocardial fibroelastosis is a component of HLHS and one of the determining factors in the outcome of cardiac surgery. Conclusion. The results of this work indicate the complexity of HLHS as a developmental defect, the severity of its clinical manifestations, and the limited prospects of currently existing surgical treatment methods. These patients may require heart transplantation in the first days of life. A potential alternative to early postnatal heart transplantation may be the development of methods for intrauterine correction of the existing developmental defect.

Pilot study to assess the early cardiac safety of carbon ion radiotherapy for intra- and para-cardiac tumours.

Modern photon radiotherapy effectively spares cardiac structures more than previous volumetric approaches. Still, it is related to non-negligible cardiac toxicity due to the low-dose bath of surrounding normal tissues. However, the dosimetric advantages of particle radiotherapy make it apromising treatment for para- and intra-cardiac tumours. In the current short report, we evaluate the cardiac safety profile of carbon ion radiotherapy (CIRT) for radioresistant intra- and para-cardiac malignancies in areal-world setting. We retrospectively analysed serum biomarkers (TnI, CRP and NT-proBNP), echocardiographic, and both 12-lead and 24-hour Holter electrocardiogram (ECG) data of consecutive patients with radioresistant intra- and para-cardiac tumours irradiated with CIRT between June 2019 and September 2022. In the CIRT planning optimization process, to minimize the delivered doses, we contoured and gave ahigh priority to the cardiac substructures. Weekly re-evaluative 4D computed tomography scans were carried out throughout the treatment. Atotal of 16patients with intra- and para-cardiac localizations of radioresistant tumours were treated up to atotal dose of 70.4 Gy relative biological effectiveness (RBE) and amean heart dose of 2.41 Gy(RBE). We did not record any significant variation of the analysed serum biomarkers after CIRT nor significant changes of echocardiographic features, biventricular strain, or 12-lead and 24-hour Holter ECG parameters during 6months of follow-up. Our pilot study suggests that carbon ion radiotherapy is apromising radiation technique capable of sparing off-target side effects at the cardiac level. Alarger cohort, long-term follow-up and further prospective studies are needed to confirm these findings.

The Z-scores of cardiac indices among healthy children: a systematic review and meta-analysis

BackgroundThe application of z-scores in normalizing the cardiac size function and structural dimension will be of immense benefit to the clinician, especially in evaluating children with cardiac anomalies. However, heterogeneity in the obtained z- score results is high, thus a subgroup analysis by region (or continent) to assist healthcare practitioners is necessary.ObjectivesThe review aimed to ascertain the overall mean z-scores for cardiac structures and function.MethodsA thorough search of several databases, EMBASE, PubMed/MEDLINE, and Google Scholar was made. Articles published between January 1999 and December 2023 were recruited, of which the last search was done in December 2023. Keywords used in the search were “z-scores”, Children; echocardiography; cardiac structures; cardiac function; and body surface area (BSA)”. We restricted our search to children. Besides, additional relevant articles were manually searched. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was used to highlight selected studies using a pre-defined search protocol. The I2 statistics were used to ascertain statistical heterogeneity.ResultsTwo hundred and forty citations were identified in our search strategy, of which a total of 34 studies were identified. Twenty-four were excluded from the thirty-four studies. A total of 11 studies met our inclusion criteria shown in the PRISMA. Apart from different z scores reading obtained from various countries and regions, some authors focused on few cardiac parameters while others were exhaustive. The mean z-scores of the cardiac structures from various countries/regions range as follows; The range of Z scores obtained by different studies and regions above are as follows; MV;-1.62-0.7 AV: -1.8 -0.5 TV: -2.71 -0.7; PV ; -1.52- (-0.99) MPA; -1-81 -0.8 LPA;-1.07-0.4; RPA;-0.92- 0.1 IVSD; -0.1.77–1.89 LVPWD; -0.12-1.5 LVPWS; -0.1-0.15 LVPWS; 0.03–0.18 LVIDD; -1.13- (-0.98) LVIDS; -0.84-10.3 respectively. The mean z-score from the pooled studies showed mitral valve diameter as -0.24 ± 0.9 and pulmonary valve annuls as -1.10 ± 0.3. The left ventricular end diastolic diameter is -0.93 ± 0.3 while the left ventricular end systolic diameter is -0.05 ± 0.5. The total pooled sample size of the eleven included studies was 9074 and the mean at 95% interval was 824.9 ± 537.344. The pooled mean is presented under the model of the Mean raw (MRAW) column. The heterogeneity discovered among the selected studies was statistically significant.ConclusionDue to heterogeneity involved in the reportage of the z-scores of cardiac structures and function, it may be necessary for every region to use their z-scores domiciled in their locale. However, having a pooled mean z-score of cardiac structures and function may be useful in the near future.

Intrapericardial Teratoma and Associated 3q29 Deletion in a Fetus: Case Report.

Depending on its location, size, and proximity to the cardiac structures, an intrapericardial teratoma may lead to severe circulatory disturbances and even fetal demise. A 34-year-old G2P1 presented at 20w5d with a solid cystic mass in the right thorax of the fetus, originating from the right atrium or lung, with signs of non-immune fetal hydrops, soon resulting in intrauterine fetal death. Detailed post-mortem autopsy revealed signs of hydrops fetalis universalis due to a spherical tumor mass originating from the aortic root. Histologic examination of the tumor showed the characteristic morphology of a teratoma. A 1.6-Mb microdeletion at 3q29 was identified by single nucleotide polymorphism array. This is the first report presenting the diagnosis of an intrapericardial teratoma in a fetus with a microdeletion of 3q29. Intrapericardial teratoma has a poor prognosis and the fetal outcome relies on the development of hydrops. A post-mortem examination is essential in order to make a definitive diagnosis, which underlines the status of the fetal pathologist and the need for interdisciplinary cooperation.

Presentation of mitral valve cleft with concurrent atrial septal defect and ventricular septal defect detected by three-dimensional transesophageal echocardiography: a case report

BackgroundCleft in the mitral valve leaflet is a primary cause of congenital mitral regurgitation, stemming from developmental anomalies in the mitral valve and frequently associated with other congenital heart defects. Concurrent presence of cleft in mitral valve leaflet with atrial septal defect and ventricular septal defect is relatively rare. Echocardiography, especially transesophageal echocardiography, is essential in diagnosing cleft mitral valve leaflet and related congenital heart defects, providing critical, detailed imagery for accurate assessment. This study presents a young female patient whose anterior mitral cleft, along with atrial septal defect and ventricular septal defect, was revealed through three-dimensional transesophageal echocardiography.Case presentationA 25-year-old Iranian female, experiencing progressive dyspnea and diminished physical capacity over 3 months, was referred to our hospital. Initial examination and transthoracic echocardiography indicated severe mitral regurgitation. Further evaluation with transesophageal echocardiography corroborated these findings and identified a cleft in the anterior mitral valve leaflet, coupled with mild left ventricular enlargement and significant left atrial enlargement. The complexity of the patient’s condition was heightened by the diagnosis of cleft mitral valve leaflet in conjunction with atrial septal defect and ventricular septal defect, showing the complex nature of congenital defects.ConclusionThis case emphasizes the critical role of transthoracic echocardiography in diagnosing cleft of mitral valve leaflet and associated cardiac anomalies, showcasing its superiority over transthoracic echocardiography for detailed visualization of cardiac structures. The identification of multiple congenital defects highlights the necessity for a comprehensive diagnostic approach to manage and treat patients with complex congenital heart diseases effectively. Future research should aim to refine diagnostic methodologies to enhance patient outcomes for cleft of mitral valve leaflets and related congenital conditions.

Aberration correction in 3D transthoracic echocardiography

Three-dimensional cardiac imaging has been available in the clinic for more than two decades. Continuous improvement in image quality has occurred in this period due to the development of probe technology and beamforming techniques. The purpose of this article is to quantitatively and qualitatively analyze the effect of a commercially available aberration correction algorithm on clinically acquired 3D transthoracic echocardiography (3D TTE) images. Clinical triplane and 3D volume cineloops of at least one cardiac cycle of pre-beamformed channel data were captured from 50 patients using a GE HealthCare Vivid E95 system with the 4Vc-D matrix array probe. This resulted in a total of 3200 vol and 3136 triplane frames. The data were post-processed with and without aberration correction. Quantitatively, assessed by an image quality parameter based on coherence, all recordings were improved by aberration correction compared to those without aberration correction. Triplane data obtained a larger improvement in image quality than volume data. Qualitatively, as demonstrated by case examples, aberration-corrected images appear sharper, have a brighter tissue signal compared to the cavity, and provide better delineation of cardiac structures. 3D rendering of valves can also be significantly improved. In general, aberration correction provides a systematic improvement in clinical cardiac triplane and 3D volume images.

Self-assembling Peptides Based Fibers: A Pioneering Innovation for Regenerative Medicine

Self-assembling peptides (SAPs) have emerged as a groundbreaking platform in regenerative medicine, offering innovative strategies for tissue engineering and repair. These biomolecules, designed to autonomously organize into nanofibers, mimic the natural extracellular matrix, providing essential structural support and biological cues for tissue regeneration. This review highlights the versatile applications of SAPs in regenerating diverse tissues, including bone, cartilage, cardiac, neural, and dermal structures, showcasing their potential to address a broad spectrum of medical challenges. The unique properties of SAPs, such as biocompatibility, biodegradability and specific cell receptor interaction capabilities, make them ideal for developing advanced therapeutic strategies. We discuss here the molecular design principles that allow for precise control over the nanofibers physical and chemical characteristics, facilitating the creation of scaffolds that promote cell attachment, proliferation, and differentiation. Additionally, the review covers the use of SAPs in drug delivery systems, emphasizing their ability to control the release of therapeutic agents, a critical aspect in enhancing tissue repair processes. Moreover, we address key considerations regarding the safety, biodegradability and potential immunogenicity of SAPs, underscoring the importance of thorough preclinical and clinical evaluations. The future directions and challenges in optimizing SAPs design and functionalization for maximizing regenerative outcomes are also explored.

The New Frontiers of Fetal Imaging: MRI Insights into Cardiovascular and Thoracic Structures.

Fetal magnetic resonance imaging (fMRI) represents a second-line imaging modality that provides multiparametric and multiplanar views that are crucial for confirming diagnoses, detecting associated pathologies, and resolving inconclusive ultrasound findings. The introduction of high-field magnets and new imaging sequences has expanded MRI's role in pregnancy management. Recent innovations in ECG-gating techniques have revolutionized the prenatal evaluation of congenital heart disease by synchronizing imaging with the fetal heartbeat, thus addressing traditional challenges in cardiac imaging. Fetal cardiac MRI (fCMR) is particularly valuable for assessing congenital heart diseases, especially when ultrasound is limited by poor imaging conditions. fCMR allows for detailed anatomical and functional evaluation of the heart and great vessels and is also useful for diagnosing additional anomalies and analyzing blood flow patterns, which can aid in understanding abnormal fetal brain growth and placental perfusion. This review emphasizes fMRI's potential in evaluating cardiac and thoracic structures, including various gating techniques like metric optimized gating, self-gating, and Doppler ultrasound gating. The review also covers the use of static and cine images for structural and functional assessments and discusses advanced techniques like 4D-flow MRI and T1 or T2 mapping for comprehensive flow quantification and tissue characterization.

Abstract Mo048: Cereblon as a potential biomarker for early detection of diabetic cardiomyopathy

Type 2 diabetes mellitus (T2DM) patients have a higher risk of heart failure and cause cardiomyopathy without other cardiac disease. There is no specific biomarker for discriminating patients with diabetic cardiomyopathy (DCM). In this study, we investigated the cereblon (CRBN) level in mice and human samples to determine its potential as a biomarker for early detection of diabetic cardiomyopathy (DCM). C57BL/db/db male mice at 6 and 8 weeks of age, as the early DCM model with obesity and T2DM were investigated. We confirmed that mitochondrial function was decreased in the 8 weeks old db/db mice without alterations of cardiac function and structures. Compared to the control mice, CRBN protein level was significantly increased and phosphorylation of AMPK, a negative regulator by CRBN, was significantly decreased in the heart tissue of 8 weeks old db/db mice. Blood CRBN level was also significantly increased in both 6 and 8 weeks old db/db mice compared with control mice. In blood of diabetic patients, CRBN level was significantly correlated with IL-6, IL-1b, TNF-a, IGFBP-7, and adiponectin, which are previously reported biomarkers of DCM. However, CRBN level was not correlated with cardiac troponin I, NT-proBNP, and ST2, which are biomarkers of myocardial injury and heart failure. Furthermore, the CRBN level showed a higher tendency in patients with diastolic dysfunction without systolic dysfunction compared to patients with normal function and systolic dysfunction, although the difference was not statistically significant. In conclusion, cardiac mitochondrial dysfunction occured and CRBN levels of heart and blood increased prior to cardiac functional and structural changes in the early DCM mouse model, and CRBN might serve as a potential biomarker for the early detection of DCM in T2DM patients.

Effect of cross-platform variations on transthoracic echocardiography measurements and clinical diagnosis.

Accurate cardiac chamber quantification is essential for clinical decisions and ideally should be consistent across different echocardiography systems. This study evaluates variations between the Philips EPIQ CVx (version 9.0.3) and Canon Aplio i900 (version 7.0) in measuring cardiac volumes, ventricular function, and valve structures. In this gender-balanced, single-centre study, 40 healthy volunteers (20 females and 20 males) aged 40 years and older (mean age 56.75 ± 11.57 years) were scanned alternately with both systems by the same sonographer using identical settings for both 2D and 4D acquisitions. We compared left ventricular (LV) and right ventricular (RV) volumes using paired t-tests, with significance set at P < 0.05. Correlation and Bland-Altman plots were used for quantities showing significant differences. Two board-certified cardiologists evaluated valve anatomy for each platform. The results showed no significant differences in LV end-systolic volume and LV ejection fraction between platforms. However, LV end-diastolic volume (LVEDV) differed significantly (biplane: P = 0.018; 4D: P = 0.028). Right ventricular (RV) measurements in 4D showed no significant differences, but there were notable disparities in 2D and 4D volumes within each platform (P < 0.01). Significant differences were also found in the LV systolic dyssynchrony index (P = 0.03), LV longitudinal strain (P = 0.04), LV twist (P = 0.004), and LV torsion (P = 0.005). Valve structure assessments varied, with more abnormalities noted on the Philips platform. Although LV and RV volumetric measurements are generally comparable, significant differences in LVEDV, LV strain metrics, and 2D vs. 4D measurements exist. These variations should be considered when using different platforms for patient follow-ups.

Right parasternal echocardiographic reference values in the healthy male Iranian Shall sheep.

Among the large animals, the heart of sheep is functionally and structurally very similar to the human heart. In research, sheep are used as an animal model to study the process of cardiac disease pathogenesis and treatment. Therefore, determining the normal values of the heart structures of sheep with echocardiography is of particular emphasis. The purpose of the present research is to define the normal echocardiography values of heart in Iranian Shall breed sheep. In 20 healthy Iranian Shall male sheep weighing 30-35kg and aged 4-6 months, standing echocardiography was done from the right parasternal approach concentrated on the 3rd to 5th intercostal spaces by 2.5-5MHz phased array transducer in the longitudinal and transverse views by B-mode, M-mode and Doppler systems. In M-mode echocardiographic, the parameters of interventricular septal, left ventricular internal diameter, left ventricular free wall, right ventricular free wall and right ventricular internal diameter in diastole and systole as well as end point septal separation, ejection fraction (EF) slope, aortic root diameter, left atrial appendage, left atrial diameter/aortic valve diameter, left ventricular ejection time, fractional shortening, end-diastolic volume, end-systolic volume, EF, stroke volume and cardiac output and in pulsed-wave spectral Doppler echocardiographic, the parameters of mitral valve maximum velocity (Vmax), mitral valve mean velocity (Vmean), mitral valve maximum pressure gradient (PGmax), mitral valve mean pressure gradient (PGmean), mitral valve velocity time integral (VTI), mitral valve E-wave (MV-E), MV-E pressure gradient, mitral valve A-wave (MV-A), MV-A pressure gradient, aortic Vmax, aortic valve Vmean, aortic valve PGmax, aortic valve PGmean, aortic valve VTI, left ventricular outflow tract (LVOT)-Vmax, LVOT-Vmean were measured. All the sheep in this study were healthy and had no signs of heart disease. In this study, the parameters of M-mode and spectral Doppler echocardiographic were assessed and recognized in Iranian Shall sheep. The results demonstrated the parameters of echocardiographic could be dependably determined in Shall sheep which, established normal reference values for these parameters and left ventricular function indices in healthy Shall sheep. These results can be beneficial in appropriate imagination, recognition and measuring cardiac structures. This study can be exerted as a reference for the assessment and diagnosis of heart diseases in sheep medicine and human cardiovascular research in sheep experimental models.

Development and first implementation of a novel multi-modality cardiac motion and dosimetry phantom for radiotherapy applications.

Cardiac applications in radiation therapy are rapidly expanding including magnetic resonance guided radiation therapy (MRgRT) for real-time gating for targeting and avoidance near the heart or treating ventricular tachycardia (VT). This work describes the development and implementation of a novel multi-modality and magnetic resonance (MR)-compatible cardiac phantom. The patient-informed 3D model was derived from manual contouring of a contrast-enhanced Coronary Computed Tomography Angiography scan, exported as a Stereolithography model, then post-processed to simulate female heart with an average volume. The model was 3D-printed using Elastic50A to provide MR contrast to water background. Two rigid acrylic modules containing cardiac structures were designed and assembled, retrofitting to an MR-safe programmable motor to supply cardiac and respiratory motion in superior-inferior directions. One module contained a cavity for an ion chamber (IC), and the other was equipped with multiple interchangeable cavities for plastic scintillation detectors (PSDs). Images were acquired on a 0.35 T MR-linac for validation of phantom geometry, motion, and simulated online treatment planning and delivery. Three motion profiles were prescribed: patient-derived cardiac (sine waveform, 4.3mm peak-to-peak, 60 beats/min), respiratory (cos4 waveform, 30mm peak-to-peak, 12 breaths/min), and a superposition of cardiac (sine waveform, 4mm peak-to-peak, 70 beats/min) and respiratory (cos4 waveform, 24mm peak-to-peak, 12 breaths/min). The amplitude of the motion profiles was evaluated from sagittal cine images at eight frames/s with a resolution of 2.4mm × 2.4mm. Gated dosimetry experiments were performed using the two module configurations for calculating dose relative to stationary. A CT-based VT treatment plan was delivered twice under cone-beam CT guidance and cumulative stationary doses to multi-point PSDs were evaluated. No artifacts were observed on any images acquired during phantom operation. Phantom excursions measured 49.3±25.8%/66.9±14.0%, 97.0±2.2%/96.4±1.7%, and 90.4±4.8%/89.3±3.5% of prescription for cardiac, respiratory, and cardio-respiratory motion profiles for the 2-chamber (PSD) and 12-substructure (IC) phantom modules respectively. In the gated experiments, the cumulative dose was<2% from expected using the IC module. Real-time dose measured for the PSDs at 10Hz acquisition rate demonstrated the ability to detect the dosimetric consequences of cardiac, respiratory, and cardio-respiratory motion when sampling of different locations during a single delivery, and the stability of our phantom dosimetric results over repeated cycles for the high dose and high gradient regions. For the VT delivery, high dose PSD was<1% from expected (5-6 cGy deviation of 5.9Gy/fraction) and high gradient/low dose regions had deviations<3.6% (6.3 cGy less than expected 1.73Gy/fraction). A novel multi-modality modular heart phantom was designed, constructed, and used for gated radiotherapy experiments on a 0.35 T MR-linac. Our phantom was capable of mimicking cardiac, cardio-respiratory, and respiratory motion while performing dosimetric evaluations of gated procedures using IC and PSD configurations. Time-resolved PSDs with small sensitive volumes appear promising for low-amplitude/high-frequency motion and multi-point data acquisition for advanced dosimetric capabilities. Illustrating VT planning and delivery further expands our phantom to address the unmet needs of cardiac applications in radiotherapy.

HeartMate 3 for Heart Failure with Preserved Ejection Fraction: In Vitro Hemodynamic Evaluation and Anatomical Fitting.

Heart failure with preserved ejection fraction (HFpEF) constitutes approximately 50% of heart failure (HF) cases, and encompasses different phenotypes. Among these, most patients with HFpEF exhibit structural heart changes, often with smaller left ventricular cavities, which pose challenges for utilizing ventricular assist devices (VADs). A left atrial to aortic (LA-Ao) VAD configuration could address these challenges, potentially enhancing patient quality of life by lowering elevated mean left atrial pressure (MLAP). This study assessed the anatomical compatibility and left atrial unloading capacity using a simulated VAD-supported HFpEF patient. A HeartMate3-supported HFpEF patient in an LA-Ao configuration was simulated using a cardiovascular simulator. Hemodynamic parameters were recorded during rest and exercise at seven pump flow rates. Computed tomography scans of 14 HFpEF (NYHA II-III) and six heart failure with reduced ejection fraction patients were analysed for anatomical comparisons. HFpEF models were independently assessed for virtual anatomical fit with the HM3 in the LA-Ao configuration. Baseline MLAP was reduced from 15 to 11mmHg with the addition of 1L/min HM3 support in the rest condition. In an exercise simulation, 6L/min of HM3 support was required to reduce the MLAP from 29 to 16mmHg. The HM3 successfully accommodated six HFpEF patients without causing interference with other cardiac structures, whereas it caused impingement ranging from 4 to 14mm in the remaining patients. This study demonstrated that the HM3 in an LA-Ao configuration may be suitable for unloading the left atrium and relieving pulmonary congestion in some HFpEF patients where size-related limitations can be addressed through pre-surgical anatomical fit analysis.

Cardiac Substructure Dose and Survival in Stereotactic Radiotherapy for Lung Cancer: Results of the Multi-Centre SSBROC Trial

Background and PurposeStereotactic ablative body radiotherapy (SABR) is increasingly used for early-stage lung cancer, however the impact of dose to the heart and cardiac substructures remains largely unknown. The study investigated doses received by cardiac substructures in SABR patients and impact on survival. Materials and MethodsSSBROC is an Australian multi-centre phase II prospective study of SABR for stage I non-small cell lung cancer. Patients were treated between 2013 and 2019 across 9 centres. In this secondary analysis of the dataset, a previously published and locally developed open-source hybrid deep learning cardiac substructure automatic segmentation tool was deployed on the planning CTs of 117 trial patients. Physical doses to 18 cardiac structures and EQD2 converted doses (α/β = 3) were calculated. Endpoints evaluated include pericardial effusion and overall survival. Associations between cardiac doses and survival were analysed with the Kaplan–Meier method and Cox proportional hazards models. ResultsCardiac structures that received the highest physical mean doses were superior vena cava (22.5 Gy) and sinoatrial node (18.3 Gy). The highest physical maximum dose was received by the heart (51.7 Gy) and right atrium (45.3 Gy). Three patients developed grade 2, and one grade 3 pericardial effusion. The cohort receiving higher than median mean heart dose (MHD) had poorer survival compared to those who received below median MHD (p = 0.00004). On multivariable Cox analysis, male gender and maximum dose to ascending aorta were significant for worse survival. ConclusionsPatients treated with lung SABR may receive high doses to cardiac substructures. Dichotomising the patients according to median mean heart dose showed a clear difference in survival. On multivariable analyses gender and dose to ascending aorta were significant for survival, however cardiac substructure dosimetry and outcomes should be further explored in larger studies.

Twin-Reversed Arterial Perfusion (TRAP) Sequence: Case Report and Literature Review

Introduction and Importance: The TRAP sequence or cardiac mass is a serious pathology that occurs in monochorionic twin pregnancies, characterised by the absence of development of cardiac structures with a series of malformations in the transfused fetus, which is never viable, and numerous complications affecting the transfused twin. Case Presentation: We report a case of TRAP sequence in a presumed pregnancy at 7 months. Discussion: The TRAP sequence is an exceptional and specific complication of monochorionic twin pregnancies, affecting on average one birth in 35,000 and 1% of monozygotic pregnancies. The differential diagnosis includes in utero fetal death of a twin without anomalies, anencephaly associated with cystic hygroma and placental tumour. Management of the TRAP sequence in complicated twin pregnancies is aimed at the survival and compensation of the transfused fetus. Conclusion: Analysis of this observation highlights the importance of prenatal diagnosis in the prevention of its consequences.

Cardiac magnetic resonance reveals concealed structural heart disease in patients with frequent premature ventricular contractions and normal echocardiography: A systematic review

Premature ventricular contractions (PVCs) are a common form of arrhythmic events, often representing an idiopathic and benign condition without further therapeutic interventions. However, in certain circumstances PVCs may represent the epiphenomenon of a concealed structural heart disease (SHD). Surface 12‑leads EKG and 24-h dynamic EKG are necessary to assess their main characteristics such as site of origin, frequency and complexity. Echocardiography represents the first-line imaging tool recommended to evaluate cardiac structures and function. Cardiac Magnetic Resonance (CMR) is recognized as a superior modality for detecting structural cardiac alterations, that might evade detection by conventional echocardiography. Moreover, in specific populations such as athletes, CMR may have a crucial role to exclude a concealed SHD and the risk of serious arrhythmic events during sport activity. Some clinical characteristics such as male sex, older age or family history of sudden cardiac death (SCD) or cardiomyopathy, and some electrocardiographic features of PVCs, in particular a right branch bundle block (RBBB) with superior/intermediate axis morphology, the reproducibility of VAs during exercise test (ET) or the evidence of complex ventricular arrhythmias, may warrant a CMR evaluation, due to the high probability of SHD. In this systematic review our objective was to provide an exhaustive overview on the role of CMR in detecting a concealed SHD in patients with high daily burden of PVCs and a normal echocardiographic evaluation, paving the way for a more extensive utilization of CMR in presence of certain high-risk clinical and/or EKG features identified during the diagnostic workup.

A comparison of fixation and immunofluorescence protocols for successful reproducibility and improved signal in human left ventricle cardiac tissue.

Immunohistochemistry (IHC) and immunofluorescence (IF) are crucial techniques for studying cardiac physiology and disease. The accuracy of these techniques is dependent on various aspects of sample preparation and processing. However, standardised protocols for sample preparation of tissues, particularly for fresh-frozen human left ventricle (LV) tissue, have yet to be established and could potentially lead to differences in staining and interpretation. Thus, this study aimed to optimise the reproducibility and quality of IF staining in fresh-frozen human LV tissue by systematically investigating crucial aspects of the sample preparation process. To achieve this, we subjected fresh-frozen human LV tissue to different fixation protocols, primary antibody incubation temperatures, antibody penetration reagents, and fluorescent probes. We found that neutral buffered formalin fixation reduced image artefacts and improved antibody specificity compared to both methanol and acetone fixation. Additionally, incubating primary antibodies at 37°C for 3 h improved fluorescence intensity compared to the commonly practised 4°C overnight incubation. Furthermore, we found that DeepLabel, an antibody penetration reagent, and smaller probes, such as fragmented antibodies and Affimers, improved the visualisation depth of cardiac structures. DeepLabel also improved antibody penetration in CUBIC cleared thick LV tissue fragments. Thus, our data underscores the importance of standardised protocols in IF staining and provides various means of improving staining quality. In addition to contributing to cardiac research by providing methodologies for IF, the findings and processes presented herein also establish a framework by which staining of other tissues may be optimised.

Maturation of human cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) on polycaprolactone and polyurethane nanofibrous mats

Investigating the potential of human cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) in in vitro heart models is essential to develop cardiac regenerative medicine. iPSC-CMs are immature with a fetal-like phenotype relative to cardiomyocytes in vivo. Literature indicates methods for enhancing the structural maturity of iPSC-CMs. Among these strategies, nanofibrous scaffolds offer more accurate mimicry of the functioning of cardiac tissue structures in the human body. However, further research is needed on the use of nanofibrous mats to understand their effects on iPSC-CMs. Our research aimed to evaluate the suitability of poly(ε-caprolactone) (PCL) and polyurethane (PU) nanofibrous mats with different elasticities as materials for the maturation of iPSC-CMs. Analysis of cell morphology and orientation and the expression levels of selected genes and proteins were performed to determine the effect of the type of nanofibrous mats on the maturation of iPSC-CMs after long-term (10-day) culture. Understanding the impact of 3D structural properties in in vitro cardiac models on induced pluripotent stem cell-derived cardiomyocyte maturation is crucial for advancing cardiac tissue engineering and regenerative medicine because it can help optimize conditions for obtaining more mature and functional human cardiomyocytes.

Cardiac substructure radiation dose study of conventional radiotherapy for stage N2-3 non-small cell lung cancer.

e20071 Background: There has been widespread reporting on predictive dose parameters for cardiac substructures in radiotherapy for non-small cell lung cancer (NSCLC). However, most advanced NSCLC patients are staged as N2-3, and there is a lack of research on the dose distribution, dose contribution and prognosis of the heart in conventional radiotherapy for N2-3 stage NSCLC. Methods: Retrospective analysis of 274 patients of stage N2-3 NSCLC treated with radiotherapy (RT) of prescription dose from 60Gy to 70Gy. Experienced radiation oncologists delineated the cardiac substructures. All patients were categorized according to different lymph node irradiation and tumor spatial locations. Spearman and linear regression were used for variation of dose-volume parameters, as well as the impact of different primary tumor locations and irradiated lymph nodes on the parameters of the entire heart and substructures. Receiver operating characteristic (ROC) curves, Kaplan-Meier, and Cox regression were performed on the influencing factors of adverse cardiac events after radiotherapy and prognosis analysis. Results: There are significant differences in the dose-volume parameters of the whole heart and its substructures. Mean heart doses (MHD),and the mean doses (Dmean) for the left atrium, right atrium, right ventricle, left ventricle and the left anterior descending coronary artery (LAD) were 15.7Gy (range 0.2-30.0Gy), 19.7Gy (range 0.3-55.0Gy), 9.7Gy (range 0.3-59.8Gy), 7.9Gy (range 0.1-48.2Gy), 6.4Gy (range 0.1-52.6Gy) and 5.2Gy (range 0.1-45.0Gy), respectively. The left atrium Dmean has the most significant impact on MHD compared to other substructures (B = 0.418, P &lt; 0.05). Dose-volume parameters of the whole heart and the left atrium were positively correlated with the irradiation of the 7th lymph node region (P &lt; 0.05). MHD and left atrium Dmean for tumors located in the lower region were significantly higher than those in the upper region (P &lt; 0.001). Patients with LAD V30 ≥ 26.9% had a significantly higher risk of mortality compared to those with LAD V30 &lt; 26.9% (P = 0.003, HR = 2.883, 95% CI = 1.436-5.788). Conclusions: With the dose distribution differences among the whole heart and its substructures. We observed the base of the heart received the highest dose, the dose to the left atrium is particularly required attention. The irradiation of different lymph nodes and different primary lesions has an impact on the dose variations of different cardiac structures. LAD V30 is an independent influencing factor of overall survival (OS) for N2-3 stage NSCLC. This study provides considerable information for the dose optimization of cardiac substructure in radiotherapy planning for N2-3 stage NSCLC.