Early Detection of Cardiotoxicity From Systemic and Radiation Therapy in Patients With Breast Cancer: Protocol for a Multi-Institutional Prospective Study.

BACKGROUND: The incidence of breast cancer is rising worldwide. Recent advances in systemic and local treatments have significantly improved survival rates of patients having early breast cancer. In the last decade, great attention has been paid to the prevention and early detection of cardiotoxicity induced by breast cancer treatments. Systemic therapy-related cardiac toxicities have been extensively studied. Radiotherapy, an essential component of breast cancer treatment, can also increase the risk of heart diseases. Consequently, it is important to balance the expected benefits of cancer treatment with cardiovascular risk and to identify strategies to prevent cardiotoxicity and improve long-term outcomes and quality of life for these patients. OBJECTIVE: This CardioTox Breast study aims to investigate the use of cardiac imaging, based on cardiac magnetic resonance and echocardiography, and to identify associated circulating biomarkers to assess early tissue changes in chemo-induced and radiation-induced cardiotoxicity in the time window of 12 months after the end of radiotherapy in patients with breast cancer. METHODS: The CardioTox Breast trial is a multicenter observational prospective longitudinal study. We aim to enroll 150 women with stage I-III unilateral breast cancer, treated with breast conserving surgery, who planned to receive radiotherapy with or without systemic therapy. Baseline and follow-up data include cardiac measurements based on cardiac magnetic resonance imaging, echocardiography, and circulating biomarkers of cardiac toxicity. RESULTS: This study details the protocol of the CardioTox Breast trial. Recruitment started in September 2020. The results of this study will not be published until data are mature for the final analysis of the primary study end point. CONCLUSIONS: The CardioTox Breast study is designed to investigate the effects of systemic and radiation therapy on myocardial function and structure, thus providing additional evidence on whether cardiac magnetic resonance is the optimal screening imaging for cardiotoxicity. TRIAL REGISTRATION: ClinicalTrials.gov NCT04790266; https://clinicaltrials.gov/ct2/show/NCT04790266. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31887.

Multimodality Imaging of the Anatomy of Tricuspid Valve.

Even though the tricuspid valve is no longer "forgotten", it still remains poorly understood. In this review, we focus on some controversial and still unclear aspects of tricuspid anatomy as illustrated by noninvasive imaging techniques. In particular, we discuss the anatomical architecture of the so-called tricuspid annulus with its two components (i.e., the mural and the septal annulus), emphasizing the absence of any fibrous "ring" around the right atrioventricular junction. Then we discussed the extreme variability in number and size of leaflets (from two to six), highlighting the peculiarities of the septal leaflet as part of the septal atrioventricular junction (crux cordis). Finally, we describe the similarities and differences between the tricuspid and mitral valve, suggesting a novel terminology for tricuspid leaflets.

From secondary to tertiary mitral regurgitation: the paradigm shifts, but uncertainties remain.

Secondary mitral regurgitation (MR) is the most common and undertreated form of MR, whose contribution to poor prognosis and indications to correction remains under discussion. MR has been characterized into 'proportionate' or 'disproportionate', based on left ventricle (LV) and regurgitant volumes, whereas 'tertiary' MR identifies conditions, in which regurgitation is pathologic per se and actively contributes to LV dysfunction. Echocardiographic and anatomo-pathological studies revealed that secondary MR prompts subtle leaflet maladaptive changes, actively contributing to the dynamic progression of secondary MR. We critically discuss the paradigm shift from secondary to tertiary MR and question the notion that MV leaflets play a passive role in secondary MR. We also review the role of standard transthoracic echocardiography for appraising and quantifying maladaptive MV leaflet changes and LV volumes and call for a more sophisticated and comprehensive imaging framework for classifying MR in future interventional studies.

Better Take a Second Look: The Fameless Face of Subacute Takotsubo Syndrome.

We have recently published in the journal the case of a 66-year-old female affected by typical Takotsubo syndrome (TTS) with apical ballooning, who presented important novel apical wall thickening despite normalization of left ventricular ejection fraction at a follow-up cardiac magnetic resonance (CMR) 1 month after the acute event. In the absence of significant elevated edema-sensitive T2 values at CMR, this constellation was interpreted as apical hypertrophic cardiomyopathy, initially mimicked by TTS. However, a routine late follow-up echocardiography and CMR after 6 months showed complete resolution of apical wall thickening. "Pseudohypertrophy" caused by transient significant myocardial edema seems to be a more frequent phenotype in the subacute phase of TTS than is yet known, which may cause diagnostic confusion.

Mitral annulus morphometry in degenerative mitral regurgitation phenotypes.

OBJECTIVES: Degenerative mitral regurgitation (DMR) is classified into different phenotypes based on the extent of leaflet degeneration. Our aim is to demonstrate that phenotype complexity predicts the extent of structural abnormalities of mitral annulus (MA). METHODS AND RESULTS: Seventy-five patients with DMR and severe valve regurgitation and 23 patients with normal mitral valve were studied using 3D transesophageal echocardiography. Classification of DMR was done by allocating each 3D echocardiography result under five categories: fibroelastic deficiency (FED), FED+, forme fruste, Barlow's disease Mitral annular disjunction (BD MAD)- or BD MAD+. MA was reconstructed in early systole and in end systole. We tested for a trend toward enlargement and flattening of MA in end systole and for a difference in MA dynamics from early systole to end systole with a worsening of DMR phenotype, in the whole spectrum of subjects ranging from controls to BD MAD+. A significant trend was observed toward larger anteroposterior diameter, intercommissural diameter, annulus circumference, and annulus area (P < .001). A reduction was found in annulus height to commissural width ratio (P = .003): This indicates a progressive MA flattening. Prolapse height and prolapse volume tended to be larger (P < .001). CONCLUSION: Based on the extent of leaflet degeneration, DMR is classified into different phenotypes. As the disease progresses, a related increase in MA size is found, with rounder annular shape, loss of saddle shape, and increase in height and volume of leaflet prolapse. The most pronounced alterations are found in BD MAD+.

Apical Hypertrophic Cardiomyopathy Masked by Takotsubo Syndrome.

We describe the case of a 66-year-old female presented to our emergency department (ER) with acute chest pain and diagnosed with Takotsubo syndrome that initially prevented from suspecting an apical hypertrophic cardiomyopathy at echocardiography.

Multimodality imaging anatomy of interatrial septum and mitral annulus.

The detailed anatomy of the interatrial septum (IAS) and mitral annulus (MA) as observed on cardiac magnetic resonance, computed tomography and two-dimensional/three-dimensional transthoracic and transesophageal echocardiography is reviewed. The IAS comprises of two components: the septum primum that is membrane-like forming the floor of the fossa ovalis (FO) and the septum secundum that is a muscular rim that surrounds the FO. The latter is an enfolding of atrial wall forming an interatrial groove. Named Waterston's groove, it is filled with adipose tissue on the epicardial side. Thus, the safest area for transseptal puncture (TSP) is within the limits of the FO floor, which provides direct interatrial access. While crossing an intact septum is a well-established procedure, TSP is a more complex and time-consuming procedure in the presence of patent foramen ovalis, aneurysmal FO or atrial septal defect closure devices. MA comprises two distinctive segments: an anterior-straight and a posterior-curved segment. The posterior MA is a thin, discontinuous fibrous 'string', interspersed with adipose tissue, where four components converge: the atrial and ventricular musculature, epicardial adipose tissue and the leaflet's hinge line. In parts of where this fibrous string is deficient or absent, the posterior leaflet is inserted directly on ventricular and atrial myocardium rendering the MA less robust and producing an 'asymmetric' dilation. The marked vulnerability of posterior MA to calcifications might be due to its insertion on the crest of ventricular myocardium being subject to friction injury due to the contraction and relaxation of LV.

Use of Contemporary Imaging Techniques for Electrophysiological and Device Implantation Procedures.

Recent technological advances in cardiac imaging allow the visualization of anatomic details up to millimeter size in 3-dimensional format. Thus, it is not surprising that electrophysiologists increasingly rely upon cardiac imaging for the diagnosis, treatment, and subsequent management of patients affected by various arrhythmic disorders. Cardiac imaging methods reviewed in the present work involve: 1) the prediction of arrhythmic risk for sudden cardiac death in patients with heart disease; 2) catheter ablation of atrial fibrillation or ventricular tachycardia; and 3) cardiac resynchronization therapy. Future integration of diagnostic and interventional cardiac imaging will further increase the effectiveness of cardiac electrophysiological procedures and will help in delivering patient-specific therapies with ablation and cardiac implantable electronic devices.

Capillary Hemangioma of the Left Ventricle.

We present the case of a young woman complaining of aspecific symptoms of malaise and dyspnea admitted to our Cardiology Department for investigations. Two-dimensional (2D)/3D transthoracic echocardiography showed an echogenic, sessile mass adhering to the midsegment of the posterior interventricular septum. The patient refused transesophageal echocardiography. For further investigation, a cardiac magnetic resonance imaging was performed, which raised suspicion of a benign tumor. Ultimately, the patient underwent uncomplicated cardiac surgery with total excision of the mass. Histopathology examination revealed a capillary hemangioma.

"Where is the Heart?" When Cardiac Magnetic Resonance Imaging Helps if Echocardiography is Inconclusive.

Cardiovascular magnetic resonance (CMR) is the gold standard technique to comprehensively assess cardiac structure and function. A 64-year-old male, planned for surgical coronary revascularization, underwent transthoracic and transesophageal echocardiography for a mitral regurgitation, with an eccentric jet of unclear mechanism; these examinations were inconclusive because of the lack of adequate visualization of the cardiac structures. A CMR was then performed to quantify mitral regurgitation and, additionally, it documented a giant hiatus hernia with gastric sliding into the thorax. In this case, CMR helped to better define the severity of a valvular disease and provided ancillary information from the extracardiac findings.

Sustained Improvement of Left Ventricular Strain following Transcatheter Aortic Valve Replacement.

PURPOSE: Left ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS). Transcatheter aortic valve replacement (TAVR) has become a widespread technique for patients with severe AS considered inoperable or high risk for open surgery. This procedure could have a positive impact in LV mechanics. The aim of the study was to evaluate the effect of TAVR on LV function recovery, as assessed by myocardial deformation parameters, both immediately and in the long term. METHODS: One-hundred nineteen consecutive patients (81.2 ± 6.9 years, 50.4% female) from 10 centres in Europe with severe AS who successfully underwent TAVR with either a self-expanding CoreValve (Medtronic, Minneapolis, MN, USA) or a mechanically expanded Lotus valve (Boston Scientific, Natick, MA, USA) were enrolled in a prospective observational study. A complete echocardiographic examination was performed prior to device implantation, before discharge and 1 year after the procedure, including the assessment of LV strain using standard 2D images. RESULTS: Between baseline and discharge, only a modest but statistically significant improvement in GLS (global longitudinal strain) could be seen (GLS% -14.6 ± 5.0 at baseline; -15.7 ± 5.1 at discharge, p = 0.0116), although restricted to patients in the CoreValve group; 1 year after the procedure, a greater improvement in GLS was observed (GLS% -17.1 ± 4.9, p < 0.001), both in the CoreValve and the Lotus groups. CONCLUSIONS: Immediate and sustained improvement in GLS was appreciated after the TAVR procedure. Whether this finding continues to be noted in a more prolonged follow-up and its clinical implications need to be assessed in further studies.

Immediate improvement of left ventricular mechanics following transcatheter aortic valve replacement.

BACKGROUND: Left ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS). Transcatheter aortic valve replacement (TAVR) has become a widespread technique for patients with severe AS considered inoperable or high risk for traditional open-surgery. This procedure could have a positive impact in LV mechanics. The aim of this study was to evaluate the immediate effect of TAVR on LV function recovery, as assessed by myocardial deformation parameters. METHODS: One-hundred twelve consecutive patients (81.4 ± 6.4 years, 50% female) from 10 centres in Europe with severe AS who successfully underwent TAVR with either a self-expanding CoreValve (Medtronic, Minneapolis, MN) or a mechanically expanded Lotus valve (Boston Scientific, Natick, MA) were enrolled in a prospective multi-center study. A complete echocardiographic examination was performed at baseline and immediately before discharge, including the assessment of LV strain using standard two-dimensional images. RESULTS: Echocardiographic examination with global longitudinal strain (GLS) quantification could be obtained in 92 patients, because of echocardiographic and logistic reasons. Between examinations, a modest statistically significant improvement in GLS could be seen (GLS% -15.00 ± 4.80 at baseline;-16.15 ± 4.97 at discharge, p = 0.028). In a stratified analysis, only women showed a significant improvement in GLS and a trend towards greater improvement in GLS according to severity of systolic dysfunction as measured by LV ejection fraction could be noted. CONCLUSIONS: Immediate improvement in GLS was appreciated after TAVR procedure. Whether this finding continues to be noted in a more prolonged follow-up and its clinical implications need to be assessed in further studies.

Speckle-Tracking Layer-Specific Analysis of Myocardial Deformation and Evaluation of Scar Transmurality in Chronic Ischemic Heart Disease.

BACKGROUND: Identification of the extent of scar transmurality in chronic ischemic heart disease is important because it correlates with viability. The aim of this retrospective study was to evaluate whether layer-specific two-dimensional speckle-tracking echocardiography allows distinction of scar presence and transmurality. METHODS: A total of 70 subjects, 49 with chronic ischemic cardiomyopathy and 21 healthy subjects, underwent two-dimensional speckle-tracking echocardiography and late gadolinium-enhanced cardiac magnetic resonance. Scar extent was determined as the relative amount of hyperenhancement using late gadolinium-enhanced cardiac magnetic resonance in an 18-segment model (0% hyperenhancement = normal; 1%-50% = subendocardial scar; 51%-100% = transmural scar). In the same 18-segment model, peak systolic circumferential strain and longitudinal strain were calculated separately for the endocardial and epicardial layers as well as the full-wall myocardial thickness. RESULTS: All strain parameters showed cutoff values (area under the curve > 0.69) that allowed the discrimination of normal versus scar segments but not of transmural versus subendocardial scars. This was true for all strain parameters analyzed, without differences in efficacy between longitudinal and circumferential strain and subendocardial, subepicardial, and full-wall-thickness strain values. Circumferential and longitudinal strain in normal segments showed transmural and basoapical gradients (greatest values at the subendocardial layer and apex). In segments with scar, transmural gradient was maintained, whereas basoapical gradient was lost because the reduction of strain values in the presence of the scar was greater at the apex. CONCLUSIONS: The two-dimensional speckle-tracking echocardiographic values distinguish scar presence but not transmurality; thus, they are not useful predictors of scar segment viability. It remains unclear why there is a greater strain value reduction in the presence of a scar at the apical level.

Predictors of disagreement between prospectively ECG-triggered dual-source coronary computed tomography angiography and conventional coronary angiography.

AIMS: To identify causes of misinterpretation in second generation, dual-source coronary computed tomography angiography (CCTA). METHODS: A retrospective re-interpretation was performed on 100 consecutive CCTA studies, previously performed with a 2×128 slice dual-source CT. Results were compared with coronary angiography (CA). CCTA and CA images were interpreted by 2 independent readers. At CCTA vessel diameter, image quality, plaque characteristics and localization (bifurcation vs. non) were described for all segments. Finally, aortic contrast-to-noise ratio (CNR) and the total Agatston calcium score were quantified. Agreement between CCTA and CA was assessed with the Kappa statistic after categorizing the stenosis severity at significant (≥50%) and critical (≥70%) cut-offs, and independent predictors of disagreement were determined by multivariable logistic regression, including patient characteristics such as body mass index (BMI), heart rate (HR), age and gender. RESULTS: Per-segment sensitivity and specificity at ≥50% and ≥70% stenosis was of 83-95%, and 73-97%, respectively. There was a substantial agreement between CCTA and CA (kappa-50%=0.78, SE=0.03; kappa-70%=0.72, SE=0.03). Worse motion-related quality score, smaller vessel diameter, calcification within the segment of interest and LAD location were independent predictors of disagreement at 50% stenosis. The same factors, excluded LAD location, in addition to bifurcation-location of the coronary lesion predicted misdiagnosis at 70% stenosis. HR per se and BMI did not predict disagreement. CONCLUSION: According to the literature a substantial agreement between CCTA and CA was found. However, discrepancies exist and are mainly related with motion-related degradation of image quality, specific vessel anatomy and plaque characteristics. Awareness of such potential limitations may help guiding interpretation of CCTA.

[The emerging role of three-dimensional transesophageal echocardiography in guiding the MitraClip procedure]. / L'emergente ruolo dell'ecocardiografia transesofagea tridimensionale come guida durante la procedura di MitraClip.

Percutaneous edge-to-edge mitral valve repair with the MitraClip device has been shown to be a safe and effective procedure in selected patients with moderate-to-severe mitral regurgitation. Two-dimensional transesophageal echocardiography (2D TEE) is the primary imaging modality for guidance of the procedure. Real-time three-dimensional (3D) TEE has recently been used as additional imaging modality during the MitraClip procedure. In comparison with 2D TEE, 3D TEE provides additional information in several steps of the procedure, including precise positioning of the clip delivery system into the left atrium, correct alignment of the clip arms perpendicular to the coaptation line and confirmation of the correct grasping location. This review describes the relevant role of 3D TEE imaging during the procedure, but also its limitations.

3D TEE during catheter-based interventions.

Guidance of catheter-based procedures is performed using fluoroscopy and 2-dimensional transesophageal echocardiography (TEE). Both of these imaging modalities have significant limitations. Because of its 3-dimensional (3D) nature, 3D TEE allows visualizing the entire scenario in which catheter-based procedures take place (including long segments of catheters, tips, and the devices) in a single 3D view. Despite these undeniable advantages, 3D TEE has not yet gained wide acceptance among most interventional cardiologists and echocardiographists. One reason for this reluctance is probably the absence of standardized approaches for obtaining 3D perspectives that provide the most comprehensive information for any single step of any specific procedure. Therefore, the purpose of this review is to describe what we believe to be the most useful 3D perspectives in the following catheter-based percutaneous interventions: transseptal puncture; patent foramen ovale/atrial septal defect closure; left atrial appendage occlusion; mitral valve repair; and closure of paravalvular leaks.

Artifacts in three-dimensional transesophageal echocardiography.

Three-dimensional (3D) transesophageal echocardiography (TEE) is subject to the same types of artifacts encountered on two-dimensional TEE. However, when displayed in a 3D format, some of the artifacts appear more "realistic," whereas others are unique to image acquisition and postprocessing. Three-dimensional TEE is increasingly used in the setting of percutaneous catheter-based interventions and ablation procedures, and 3D artifacts caused by the metallic components of catheters and devices are particularly frequent. Knowledge of these artifacts is of paramount relevance to avoid misinterpretation of 3D images. Although artifacts and pitfalls on two-dimensional echocardiography are well described and classified, a systematic description of artifacts in 3D transesophageal echocardiographic images and how they affect 3D imaging is still absent. The aim of this review is to describe the most relevant artifacts on 3D TEE, with particular emphasis on those occurring during percutaneous interventions for structural heart disease and ablation procedures.