Inflammatory Reprogramming Mediates Changes in Three-Dimensional Strain Capacity and Cardiac Function in Beagle Dogs with Doxorubicin-Related Cardiomyopathy.

Background: The cardiotoxicity of doxorubicin (DOX) limits its use in cancer treatment. To address this limitation, we developed a novel animal model that uses beagle dogs to investigate DOX-induced cardiac disorders. Unfortunately, the lack of effective cardioprotection strategies against DOX-induced cardiotoxicity poses a significant challenge. To establish a canine model for low-mortality DOX-induced cardiac dysfunction and explore the relationship between inflammatory reprogramming and DOX-related cardiotoxicity. Methods: Twenty male beagle dogs aged two years were randomly assigned into the DOX (N = 10) and control (CON) (N = 10) groups. DOX was infused (1.5 mg/kg) every two weeks until doses cumulatively reached 12 mg/kg. Serum biomarkers and myocardial pathology were evaluated, while real-time fluorescence-based quantitative polymerase chain reaction (RTFQ-PCR), two- and three-dimensional echocardiography (2DE and RT3DE), functional enrichment, and matrix correlation were also performed. Results: In the DOX group, high-sensitive cardiac troponin T (hs cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were significantly increased. Myocardial pathology indicated early to medium myocardial degeneration via a decreased cardiomyocyte cross-sectional area (CSA). Increased levels of inflammatory gene transcripts (interleukin 6 (IL6), tumor necrosis factor (TNF), transforming growth factor ß (TGF ß ), intercellular adhesion molecule 1 (ICAM1), interleukin 1 (IL1), interleukin 1 ß (IL1 ß ), and interleukin 8 (IL8)), of collagen metabolism and deposition regulatory genes (matrix metalloproteinase (MMP) family and tissue inhibitor of matrix metalloproteinase (TIMP) family), and the natriuretic peptide family (NPS) (natriuretic peptide A, B and C (NPPA, NPPB, and NPPC)) were observed. Strain abnormalities in the right ventricular longitudinal septal strain (RVLSS), right ventricular longitudinal free-wall strain (RVLFS), left ventricular global longitudinal strain (LVGLS), and left ventricular global circumferential strain (LVGCS) were detected at week 28 (vs. week 0 or CON group, p < 0.05, respectively). A significant decline in RVLSS and RVLFS occurred at week 16, which was earlier than in the corresponding left ventricular areas. A significant right ventricular ejection fraction (RVEF) decline was noted at week 16 (vs. week 0, 33.92 ± 3.59% vs. 38.58 ± 3.58%, p < 0.05), which was 12 weeks earlier than for the left ventricular ejection fraction (LVEF), which occurred at week 28 (vs. week 0, 49.02 ± 2.07% vs. 54.26 ± 4.38%, p < 0.01). The right ventricular strain and functional damages correlated stronger with inflammatory reprogramming (most R from 0.60 to 0.90) than the left ones (most R from 0.30 to 0.65), thereby indicating a more pronounced correlation. Conclusions: Inflammatory reprogramming mediated disorders of strain capacity and cardiac function predominantly in the right side of the heart in the newly established DOX-related cardiomyopathy beagle dog model.

Comparative assessment of left atrial volume in healthy cats by two-dimensional and three-dimensional echocardiography.

BACKGROUND: The left atrium (LA) is an important prognostic parameter in cardiac pathologies of cats. Its size is currently measured in one-dimensional methods, while human medicine considers two- and three-dimensional echocardiography as standard. The objectives of this study were to compare monoplane, biplane, triplane and real-time three dimensional echocardiography for volumetric measurement of the left atrium in healthy cats and establish a reference interval for further studies on cats with heart disease. Additionally, the influence of age, sex and weight on left atrial volume (LAV) was tested. RESULTS: One dimensional monoplane Simpson method of discs (SMOD) in the right parasternal four chamber view (r4) and the left apical 2 chamber view (l2) as well as biplane SMOD had no significant difference for left atrial maximum volume (LAMax). They can be used as equivalent in future studies and one common reference range was set up (1.96 ± 0.54 ml). Those three methods produced significantly higher volumes than triplane echocardiography (RTTPE) and real time three dimensional echocardiography (RT3DE) using TomTec® software. LA volumetry with RTTPE and RT3DE-TomTec™ was more feasible than expected, but low RT3DE image quality was the main reason for excluding patients. Neither age nor weight had an influence on LA volume in healthy cats. Male LAV results were only slightly, but in 2D and RTTPE significantly higher than those of female cats with a range of + 10.46% to + 19.58%. CONCLUSIONS: Monoplane, biplane, triplane and real-time three dimensional echocardiography were feasible for LA volumetry in healthy cats and showed acceptable intra- and interobserver variability. One common LAMax reference range for monoplane r4, l2 and biplane SMOD was set up. Raw data can be used for LA volumes and does not need to be correlated with the cat's weight or age. Male cats have only slightly but significantly larger atria than females in 2D and RTTPE. Therefore, under reservation, also sex related limit values were defined.

Predictive value of left ventricular dyssynchrony for short-term outcomes in three-vessel disease patients undergoing coronary artery bypass grafting with preserved or mildly reduced left ventricular ejection fraction.

Background and objective: Coronary artery bypass grafting (CABG) is the reference standard intervention in coronary artery disease (CAD) patients with three-vessel disease (3VD). We aimed to evaluate the predictive value of left ventricular (LV) dyssynchrony for short-term adverse outcomes in patients with 3VD undergoing CABG with preserved or mildly reduced LV ejection fraction (LVEF). Materials and methods: This study involved ninety-five 3VD patients with preserved or mildly reduced LVEF undergoing scheduled on-pump CABG. The pre-operative diameters and volumes of LV and LVEF were obtained by two-dimensional echocardiography. LV dyssynchrony parameters were acquired by real-time three-dimensional echocardiography (RT-3DE) and analyzed by HeartModel quantification software. And the perfusion index of LV was obtained by contrast echocardiography. The clinical endpoints of short-term adverse outcomes comprised 30-day mortality and/or composite outcomes of postoperative complications. Univariate and multivariate logistic regression analyses were used to identify risk factors for the occurrence of post-CABG short-term adverse outcomes. Results: Short-term adverse outcomes occurred in 12 (12.6%) patients. These patients had higher LV dyssynchrony parameters obtained through RT-3DE. The standard deviation (SD) of the time to minimum systolic volume (Tmsv) corrected by heart rate over 16 segments (Tmsv16-SD%) [odds ratio (OR), 1.362; 95% confidence interval (CI) (1.090-1.702); P = 0.006], one of the LV dyssynchrony parameters, was independently associated with short-term adverse outcomes. Patients with poor synchronization tended to spend more time in the intensive care unit (ICU) and hospital after surgery. Conclusion: Pre-operative LV dyssynchrony parameter Tmsv16-SD% obtained through RT-3DE could be a useful additional predictor of postoperative short-term adverse outcomes in 3VD patients with preserved or mildly reduced LVEF undergoing CABG.

Quantitative in vivo assessment of human mitral valve coaptation area after undersized ring annuloplasty repair for ischemic mitral regurgitation.

Objectives: Long-term outcomes of mitral valve repair procedures to correct ischemic mitral regurgitation remain unpredictable, due to an incomplete understanding of the disease process and the inability to reliably quantify the coaptation zone using echocardiography. Our objective was to quantify patient-specific mitral valve coaptation behavior from clinical echocardiographic images obtained before and after repair to assess coaptation restoration and its relationship with long-term repair durability. Methods: To circumvent the limitations of clinical imaging, we applied a simulation-based shape-matching technique that allowed high-fidelity reconstructions of the complete mitral valve in the systolic configuration. We then applied this method to an extant database of human regurgitant mitral valves before and after undersized ring annuloplasty to quantify the effect of the repair on mitral valve coaptation geometry. Results: Our method was able to successfully resolve the coaptation zone into distinct contacting and redundant regions. Results indicated that in patients whose regurgitation recurred 6 months postrepair, both the contacting and redundant regions were larger immediately postrepair compared with patients with no recurrence (P < .05), even when normalized to account for generally larger recurrent valves. Conclusions: Although increasing leaflet coaptation area is an intuitively obvious way to improve long-term repair durability, this study has implied that this may not be a reliable target for mitral valve repair. This study underscores the importance of a rigorous understanding of the consequences of repair techniques on mitral valve behavior, as well as a patient-specific approach to ischemic mitral regurgitation treatment within the context of mitral valve and left ventricle function.

Cardiac Tumors: JACC CardioOncology State-of-the-Art Review.

Cardiac masses are rare, but remain an important component of cardio-oncology practice. These include benign tumors, malignant tumors (primary and secondary) and tumor-like conditions (e.g., thrombus, Lambl's excrescences, and pericardial cyst). The advent of multimodality imaging has enabled identification of the etiology of cardiac masses in many cases, especially in conjunction with information from clinical settings. This paper provides a comprehensive review of the epidemiology, clinical presentation, imaging, diagnosis, management, and outcomes of cardiac masses.

Left atrial volumetric assessment using a novel automated framework for 3D echocardiography: a multi-centre analysis.

AIMS: This study aims at validating a software tool for automated segmentation and quantification of the left atrium (LA) from 3D echocardiography. METHODS AND RESULTS: The LA segmentation tool uses a dual-chamber model of the left side of the heart to automatically detect and track the atrio-ventricular plane and the LA endocardium in transthoracic 3D echocardiography. The tool was tested in a dataset of 121 ultrasound images from patients with several cardiovascular pathologies (in a multi-centre setting), and the resulting volumes were compared with those assessed manually by experts in a blinded analysis using conventional contouring. Bland-Altman analysis showed good agreement between the automated method and the manual references, with differences (mean ± 1.96 SD) of 0.5 ± 5.7 mL for LA minimum volume and -1.6 ± 9.7 mL for LA maximum volume (comparable to the inter-observer variability of manual tracings). The automated tool required no user interaction in 93% of the recordings, while 4% required a single click and only 2% required contour adjustments, reducing considerably the amount of time and effort required for LA volumetric analysis. CONCLUSION: The automated tool was validated in a multi-centre setting, providing quantification of the LA volume over the cardiac cycle with minimal user interaction. The results of the automated analysis were in agreement with those estimated manually by experts. This study shows that such approach has clinical utility for the assessment of the LA morphology and function, automating and facilitating the time-consuming task of analysing 3D echocardiographic recordings.

Real Time 3D Echocardiographic Evaluation of Iatrogenic Atrial Septal Defects After Percutaneous Transvenous Mitral Commissurotomy.

INTRODUCTION: Percutaneous transvenous mitral commissurotomy (PTMC) is a safe and effective procedure for relief of severe mitral stenosis. PTMC is being done widely and many transseptal procedures requiring large diameter catheters, sheaths are becoming popular. The knowledge of iatrogenic atrial septal defect (iASD) is vital. This study assessed the use of real-time 3D echocardiography (RT3DE) and incidence of iASD in a cohort of patients undergoing transseptal catheterization during PTMC. METHODS: One hundred ten patients underwent PTMC. The reliability and accuracy of RT3DE for iASD detection was determined, RT3DE was compared with 2D echocardiography (2DE) for iASD occurrence, influencing variables analyzed and followed up for 1 year. RESULTS: RT3DE is more reliable and accurate for the study of iASD than 2DE. Color RT3DE detected iASD in 94 (85.5%), with 2DE iASD was detected in 74 (67.3%) (P < .0001).On follow up 85% had iASD post procedure, 56% at 6 months, 19% at 1 year follow up. The mean iASD diameter was 5.41 ± 3.12 mm and area 6.57 ± 3.81 mm(2). iASD correlated with patient height, Wilkins score, pre-PTMC LA 'v', and post-PTMC LVEDP. CONCLUSION: RT3DE imaging is superior in accuracy to traditional 2DE techniques. All the modes of RT3DE are useful in the assessment of iASD. iASD measured by RT3DE correlates with several patient, procedural and echocardiographic variables.

Age-related normal range of left ventricular strain and torsion using three-dimensional speckle-tracking echocardiography.

BACKGROUND: Three-dimensional (3D) speckle-tracking echocardiography (STE) is an emerging technology used to quantify left ventricular (LV) function. However, the accuracy and normal values of LV strain and twist using 3D STE have not been established in a large group of normal subjects. The aims of this study were to (1) to evaluate the accuracy of 3D STE analysis of LV strain against a cardiac magnetic resonance (CMR) reference and (2) to establish age-related normal values of LV strain and torsion using real-time 3D echocardiographic (RT3DE) images. METHODS: In protocol 1, RT3DE data sets and CMR images were acquired on the same day in 19 patients referred for clinically indicated CMR. Global LV longitudinal, circumferential, and radial strain was compared between the two modalities. In protocol 2, global and regional strain and twist and torsion were measured in 313 healthy subjects using 3D STE. RESULTS: In protocol 1, good correlations for each LV strain component were noted between RT3DE imaging and CMR (r = 0.61-0.86, P < .001). In protocol 2, normal global longitudinal, circumferential, radial, and 3D strain were -20.3 ± 3.2%, -28.9 ± 4.6%, 88.0 ± 21.8%, and -37.6 ± 4.8%, respectively. A significant age dependency was observed for global longitudinal and 3D strain. Aging also affected LV torsion: the lowest values were found in children and adolescents, and values subsequently increased with age, while further aging was associated with a gradual reduction in basal rotation accompanied by an increase in apical rotation. CONCLUSIONS: This study provides initial validation of 3D strain analysis from RT3DE images and reference values of normal 3D LV strain and torsion. The age-related differences in LV strain and torsion may reflect myocardial maturation and aging.

Left atrial and left ventricular diastolic function in chronic Chagas disease.

BACKGROUND: Left atrial (LA) and left ventricular (LV) diastolic function analysis can yield new strategies to recognize early cardiac involvement and prognostic indicators in Chagas disease. METHODS: Patients with Chagas disease with the indeterminate (n = 69) or with the cardiac form (32 with changes limited to electrocardiography [stage A], 25 with changes in LV systolic function but no heart failure [HF; stage B], and 26 with HF) underwent evaluation of LV diastolic function (mitral inflow, pulmonary vein flow, color M-mode echocardiography, and tissue Doppler analysis), and LA function by three-dimensional echocardiography and strain analysis and were prospectively followed for the occurrence of clinical events. Echocardiograms were also obtained from 32 controls. RESULTS: LV diastolic dysfunction was gradually more prevalent and severe across groups from patients with the indeterminate form of Chagas disease to patients with HF. Tissue Doppler was the best tool to demonstrate the worsening of LV diastolic function across the groups (E' velocity: controls, 12.6 ± 2.3 cm/sec; patients with the indeterminate form, 12.1 ± 3.1 cm/sec; stage A, 10.3 ± 2.9 cm/sec; stage B, 8.3 ± 2.8 cm/sec; patients with HF, 5.6 ± 1.9; P < .0001). Although maximum LA volume was increased only in patients with HF, minimum LA volume (controls, 8 ± 2 mL/m(2); patients with the indeterminate form, 8 ± 2 mL/m(2); stage A, 9 ± 3 mL/m(2); stage B, 11 ± 4 mL/m(2); patients with HF, 27 ± 17 mL/m(2); P < .0001) and precontraction LA volume (controls, 11 ± 3 mL/m(2); patients with the indeterminate form, 12 ± 3 mL/m(2); stage A, 13 ± 4 mL/m(2); stage B, 16 ± 5 mL/m(2); patients with HF, 32 ± 19 mL/m(2); P < .0001) were increased in all cardiac form groups. LA conductive function was depressed in all cardiac form groups, while LA contractile function was depressed only in patients with HF. Cox proportional-hazards regression analysis revealed that end-systolic LV diameter (hazard ratio, 1.6; 95% confidence interval, 0.9-2.8; P = .09), E' velocity (hazard ratio, 0.5; 95% confidence interval, 0.3-0.8; P = .001), and peak negative global LA strain (hazard ratio, 1.21; 95% confidence interval, 1.02-1.4; P = .03), were independent predictors of clinical events. CONCLUSIONS: LV diastolic dysfunction was found in all forms of chronic Chagas disease, including those without LV systolic dysfunction. LV diastolic dysfunction may contribute to changes in LA volume and conductive function found in early stages of the cardiac form. Both LV diastolic function and LA contractile function were independent predictors of clinical events.

Visualization of patent ductus arteriosus using real-time three-dimensional echocardiogram: Comparative study with 2D echocardiogram and angiography.

PURPOSE: To determine the feasibility and accuracy of real time 3D echocardiography (RT3DE) in determining the dimensions and anatomical type of the patent ductus arteriosus (PDA). METHODS: The study included 42 pediatric patients with a mean age of 3.6 years (ranging from 2 months to 14 years) who were referred for elective percutaneous PDA closure. All patients underwent full 2D echocardiogram as well as RT3DE with off line analysis using Q lab software within 6 h from their angiograms. The PDA was studied as regard the anatomical type, length of the duct as well as the ampulla and the pulmonary end of the PDA. Data obtained by RT3DE was compared against 2D echocardiogram and the gold standard angiography. RESULTS: Offline analysis of the PDA was feasible in 97.6% of the cases while determination of the anatomical type using gated color flow 3D acquisitions was achieved in 78.5% of the cases. The pulmonary end of the duct was rather elliptical using 3D echocardiogram. There was significant difference between the pulmonary end measured by 3D echocardiogram and angiography (P < 0.001). There was no significant difference between either the length or the ampulla of the PDA measured by 3D echocardiogram and that measured by angiography (P value = 0.325 and 0.611, respectively). There was a good agreement between both 2D or 3D echocardiogram and angiography in determining the anatomical type of the PDA (K = 0.744 and 0.773, respectively). However 3D echocardiogram could more accurately determine type A and type E ductus compared to 2D echocardiogram. CONCLUSION: 3D echocardiogram was more accurate than 2D echocardiogram in determining the length and the ampulla of the PDA. The morphologic assessment of the PDA using gated 3D color flow was achieved in 78.5% of the patients. Nevertheless the use of 3D echocardiogram in assessment of small vascular structures like PDA in children with rapid heart rates is still of limited clinical value.