Modern tools in congenital heart disease imaging and procedure planning: a European survey.

AIMS: Congenital heart diseases (CHDs) often show a complex 3D anatomy that must be well understood to assess the pathophysiological consequences and to guide therapy. Three-dimensional imaging technologies have the potential to enhance the physician's comprehension of such spatially complex anatomies. Unfortunately, due to the new introduction in clinical practice, there is no evidence on the current applications. We conducted a survey to examine how 3D technologies are currently used among CHD European centres. METHODS: Data were collected using an online self-administered survey via SurveyMonkey. The questionnaire was sent via e-mail and the responses were collected between January and June 2022. RESULTS: Ninety-eight centres correctly completed the survey. Of these, 22 regularly perform 3D rotational angiography, 43 have the availability to print in-silico models, and 22 have the possibility to visualize holographic imaging/virtual reality. The costs were mostly covered by the hospital or the department of financial resources. CONCLUSION: From our survey, it emerges that these technologies are quite spread across Europe, despite not being part of a routine practice. In addition, there are still not enough data supporting the improvement of clinical management for CHD patients. For this reason, further studies are needed to develop clinical recommendations for the use of 3D imaging technologies in medical practice.

The Impact of Atrial Fibrillation on All Heart Chambers Remodeling and Function in Patients with Dilated Cardiomyopathy-A Two- and Three-Dimensional Echocardiography Study.

Atrial fibrillation is frequently seen in patients with dilated cardiomyopathy (DCM), and its presence impacts the function of the heart, with clinical and prognostic consequences. In this prospective single-center study, we aimed to assess the impact of atrial fibrillation on cardiac structure and function, using comprehensive two- and three-dimensional echocardiography. We included 41 patients with DCM and persistent or permanent atrial fibrillation (38 male, age 58.8 ± 11 years), as well as 47 patients with DCM and in sinus rhythm (35 male, age 58 ± 12.5 years). Cardiac chambers and mitral and tricuspid valves' structure and function were assessed via standard two-dimensional, speckle-tracking, and three-dimensional echocardiography (3DE). Patients with DCM and atrial fibrillation had a more impaired left ventricular global longitudinal strain, higher 3DE left atrial volumes, and reduced function compared to patients in sinus rhythm in the presence of similar left ventricle volumes. Mitral annulus configuration was altered in atrial fibrillation DCM patients. Also, right heart volumes were larger, with more severe atrial and ventricular dysfunction, despite similar estimated pulmonary artery pressures and severity of tricuspid regurgitation. Using advanced echocardiography techniques, we demonstrated that atrial fibrillation induces significant remodeling in all heart chambers.

The Value of Multimodal Imaging in Early Phenotyping of Cardiomyopathies: A Family Case Report.

Cardiomyopathies are structural and functional myocardial disorders that are not caused by other specific conditions such as coronary artery disease, arterial hypertension, valvular disease or congenital heart diseases. They are grouped into specific morphological and functional phenotypes, and sub-classified into familial and non-familial forms, with the dilated phenotype being the most frequent. However, there are many overlapping features between these phenotypes, complicating the diagnosis and management of patients. We report here the case of three related patients with different types of cardiomyopathies, emphasizing the importance of a multimodal approach to diagnosis.

Holographic Techniques as a Novel Method for Intervention Planning: A Tertiary Centres Experience.

Advanced holographic visualization techniques are becoming increasingly important in clinical practice, not only for diagnostic purposes but also in the planning of interventional or surgical procedures. The traditional approach for visualizing anatomic structures is based on standard imaging modalities such as echocardiography, cardiac magnetic resonance (CMR) and cardiac CT scan (CCT) which, however, can only provide two-dimensional (2D) images thus limiting 3D perception. Many recent studies have shown that the use of 3D imaging modalities such as augmented reality, virtual reality, mixed reality and holography improve the short and long-term outcome of percutaneous or surgical procedures. In this article, we report our experience on the use of the hologram in different clinical scenarios and in the field of university education.

Intracardiac mass presenting as acute myocardial infarction.

Cardiac tumors, although rare, present intricate diagnostic and therapeutic challenges, necessitating timely intervention for optimal patient outcomes. This case report focuses on a 65-year-old woman admitted with chest pain and loss of consciousness, ultimately diagnosed with a left ventricular cardiac myxoma. The patient's presentation mimicked acute coronary syndrome, highlighting the diagnostic complexity associated with cardiac tumors. Advanced imaging modalities, including transthoracic echocardiography, computed tomography, and invasive coronary angiography, played a pivotal role in characterizing the intracardiac mass. Histopathological (HP) examination, utilizing immunohistochemistry, confirmed the tumor as a cardiac myxoma. The patient management involved a multidisciplinary approach, leading to surgical resection of the mass and mitral valve replacement. The case underscores the importance of the HP confirmation in patients with cardiac masses, especially when multimodality cardiac imaging suggests various tumor types, simultaneously emphasizing the need for a comprehensive diagnostic approach that includes advanced imaging and histopathology to ensure an accurate diagnosis and tailored management of cardiac tumors.

The Dysfunctional Right Ventricle in Dilated Cardiomyopathies: Looking from the Right Point of View.

Dilated cardiomyopathies (DCMs) are a heterogenous group of primary myocardial diseases, representing one of the leading causes of heart failure, and the main indication for heart transplantation. While the degree of left ventricular dilation and dysfunction are two key determinants of adverse outcomes in DCM patients, right ventricular (RV) remodeling and dysfunction further negatively influence patient prognosis. Consequently, RV functional assessment and diagnosing RV involvement by using an integrative approach based on multimodality imaging is of paramount importance in the evaluation of DCM patients and provides incremental prognostic and therapeutic information. Transthoracic echocardiography remains the first-line imaging modality used for the assessment of the RV, and newer techniques such as speckle-tracking and three-dimensional echocardiography significantly improve its diagnostic and prognostic accuracy. Nonetheless, cardiac magnetic resonance (CMR) is considered the gold standard imaging modality for the evaluation of RV size and function, and all DCM patients should be evaluated by CMR at least once. Accordingly, this review provides a comprehensive overview of the anatomy and function of the RV, and the pathophysiology, diagnosis, and prognostic value of RV dysfunction in DCM patients, based on traditional and novel imaging techniques.

Echocardiography Assessment of Cardiac Function in Adults Living with HIV: A Speckle Tracking Study in the Era of Antiretroviral Therapy.

Adults living with HIV (human immunodeficiency virus) infection (ALHIV) have high rates of cardiovascular events. New approaches are needed to detect subclinical cardiac dysfunction. We used conventional and speckle tracking echocardiography to investigate whether ALHIV display latent cardiac dysfunction. We analyzed 85 young subjects with HIV infection and free from cardiovascular risk factors (31 ± 4 years) and 80 matched healthy volunteers. We measured left ventricular (LV) layered global longitudinal strain, circumferential strain, peak longitudinal strain in the reservoir and contraction phases of the left atrium (LASr respectively LASct). In the HIV group, LV ejection fraction and s' TDI (tissue doppler imaging) were slightly lower but still in the normal ranges. Layered longitudinal strain showed no significant difference, whereas circumferential global strain was significantly lower in the HIV group (−20.3 ± 3.9 vs. −22.3 ± 3.0, p < 0.001). LASr (34.3% ± 7.3% vs. 38.0% ± 6.9%, p < 0.001) was also lower in ALHIV and multivariate analysis showed that age (ß = −0.737, p = 0.01) and infection duration (ß = −0.221, p = 0.02) were independently associated with LASr. In the absence of cardiovascular risk factors, adults living with HIV display normal LV systolic function. Left atrial reservoir strain, is, however, decreased and suggests early diastolic dysfunction.

Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy-An Animal and In-Human Comparative Study.

ApoE abnormality represents a well-known risk factor for cardiovascular diseases. Beyond its role in lipid metabolism, novel studies demonstrate a complex involvement of apoE in membrane homeostasis and signaling as well as in nuclear transcription. Due to the large spread of apoE isoforms in the human population, there is a need to understand the apoE's role in pathological processes. Our study aims to dissect the involvement of apoE in heart failure. We showed that apoE-deficient rats present multiple organ damages (kidney, liver, lung and spleen) besides the known predisposition for obesity and affected lipid metabolism (two-fold increase in tissular damages in liver and one-fold increase in kidney, lung and spleen). Heart tissue also showed significant morphological changes in apoE-/- rats, mostly after a high-fat diet. Interestingly, the right ventricle of apoE-/- rats fed a high-fat diet showed more damage and affected collagen content (~60% less total collagen content and double increase in collagen1/collagen3 ratio) compared with the left ventricle (no significant differences in total collagen content or collagen1/collagen3 ratio). In patients, we were able to find a correlation between the presence of ε4 allele and cardiomyopathy (χ2 = 10.244; p = 0.001), but also with right ventricle dysfunction with decreased TAPSE (15.3 ± 2.63 mm in ε4-allele-presenting patients vs. 19.8 ± 3.58 mm if the ε4 allele is absent, p < 0.0001*) and increased in systolic pulmonary artery pressure (50.44 ± 16.47 mmHg in ε4-allele-presenting patients vs. 40.68 ± 15.94 mmHg if the ε4 allele is absent, p = 0.0019). Our results confirm that the presence of the ε4 allele is a lipid-metabolism-independent risk factor for heart failure. Moreover, we show for the first time that the presence of the ε4 allele is associated with right ventricle dysfunction, implying different regulatory mechanisms of fibroblasts and the extracellular matrix in both ventricles. This is essential to be considered and thoroughly investigated before the design of therapeutical strategies for patients with heart failure.

Myocardial Function Assessed by Multi-Layered Two-Dimensional Speckle Tracking Analysis in Asymptomatic Young Subjects with Diabetes Mellitus Type 1.

BACKGROUND: Diabetes mellitus type 1 (DM1) is associated with a high risk for cardiovascular disease, and early detection of myocardial dysfunction is crucial for the prevention of cardiac complications. OBJECTIVES: The aim of this study was to evaluate left ventricular (LV) and right ventricular (RV) function by using both conventional echocardiography as well as multi-layered speckle tracking echocardiography (STE) in young adults with DM1. METHODS: We included 50 young asymptomatic adults diagnosed with DM1 (mean interval from diagnosis 9 ± 6 years) and 80 healthy controls. STE was acquired using the GE Vivid S60 equipment. The LV longitudinal strain (LS), layer-specific strains of the endocardium, myocardium, and epicardium (global longitudinal strain [GLS]endo, GLSmyo, GLSepi) as well as RV strain were obtained using the EchoPAC BT13 workstation. RESULTS: No significant intergroup differences in LV ejection fraction were noted. GLSendo and GLSmyo were reduced in the DM1 group (-20.6 ± 2.7 vs. -22.0 ± 2.3 and -18.0 ± 2.4 vs. -19.1 ± 1.9, respectively, p < 0.05) compared to controls. Mechanical dispersion was higher in the diabetes group (34 ± 11 vs. 29 ± 7, p < 0.05). RV strain measurements showed no significant difference between the groups. CONCLUSIONS: Young adults with DM1 and without known heart disease have subclinical myocardial dysfunction with lower LV endocardium and myocardium LS and higher mechanical dispersion demonstrated by multi-layered STE.

Immunoexpression of MMP-8, MMP-9 and TIMP-2 in dilated cardiomyopathy.

Alteration of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) expression has been studied for various cardiac diseases, including dilated cardiomyopathy (DCM), with the significance of surrogate markers of extracellular matrix (ECM) remodeling. In this study, we determined the MMP-8, MMP-9 and TIMP-2 immunoexpression in the heart of patients diagnosed with DCM in relation to a histological composite score (HCS). The study included 40 cases of heart fragments that were processed by the usual paraffin inclusion technique, followed by a semi-quantitative evaluation of histopathological parameters, which summed, allowed the establishment of a HCS. Subsequently, the cases were immunohistochemically processed for MMP-8, MMP-9 and TIMP-2, followed by the semi-quantitative evaluation of their expression intensity. MMP-8 was identified only in myocardiocytes, while MMP-9 and TIMP-2 were present in both myocardiocytes and stroma, but with different intensity. The increasing intensity of MMP-8 and TIMP-2 immunoreactions was significantly associated with low HCS. In case of MMP-9, the immunostaining intensity analysis in relation to the HCS level revealed insignificant differences, but we found an association of increased and moderate intensity with low HCS. The imbalance between TIMPs and MMPs disrupts the ECM architecture and contributes to the remodeling process in DCM, aspect that can be used in the development of new clinical therapies.

Longitudinal strain analysis allows the identification of subclinical deterioration of right ventricular function in patients with cancer therapy-related left ventricular dysfunction.

BACKGROUND: This study was designed to assess right ventricular systolic function in cancer patients. METHODS AND RESULTS: 68 consecutive patients receiving potentially cardiotoxic agents were followed for 6 months in a single-center, observational, cohort-study. Left ventricle and free-wall right ventricular longitudinal strain were analyzed prior and after 6 months of treatment, using a vendor-independent software, together with left ventricle ejection fraction, tricuspid annulus plane systolic excursion and right ventricular fractional area change. Cancer therapy-related cardiac dysfunction was defined as a left ventricle ejection fraction drop of >10% to <53%. Both left ventricle ejection fraction (59±7% vs. 55±8%, p<0.0001) and left ventricle longitudinal strain (-19.7±2.5% vs. -17.1±2.6%, p<0.0001) were reduced at follow up, along with free-wall right ventricular longitudinal strain (-24.9±4.5% vs. -21.6±4.9%, p<0.0001). Cancer therapy-related cardiac dysfunction was detected in 20 patients (29%). In 15 out of these 20 patients (75%), a concomitant relative reduction in free-wall right ventricular longitudinal strain magnitude by 17±7% was detected. Moreover, there was a significant correlation between left ventricle and free-wall right ventricular longitudinal strain at follow-up examinations (r=0.323, p<0.0001). A relative drop of right ventricular longitudinal strain >17% had a sensitivity of 55% and a specificity of 70% (AUC=0.75, 0.7-0.8, 95% CI) to identify patients with cancer treatment related cardiac dysfunction. Neither tricuspid annulus plane systolic excursion (24±5 vs. 23±4 mm, p=0.07), nor right ventricular fractional area change (45±8% vs. 44±7%, p=0.6) showed any significant change between examinations. CONCLUSIONS: Longitudinal strain analysis allows the identification of subclinical right ventricular dysfunction appearing in the course of cancer treatment when conventional indices of right ventricular dysfunction function are unaffected.

A rare case of familial restrictive cardiomyopathy, with mutations in MYH7 and ABCC9 genes.

Restrictive cardiomyopathy is the least common type of cardiomyopathy, being defined by diastolic dysfunction and often unimpaired systolic function. Restrictive cardiomyopathies can be classified as familial or non-familial. Patients with familial restrictive cardiomyopathy can develop signs and symptoms of this condition anytime from childhood to adulthood. The evolution of the disease is towards signs and symptoms of pulmonary and systemic congestion and, without treatment, there is a five-year mortality rate of approximately 30% in these patients. We discuss the case of a 43-year-old patient diagnosed with familial restrictive cardiomyopathy with positive genetic tests for mutations of MYH7 gene and ABCC9 gene, who was first hospitalized in 2011 for palpitations. The echocardiography performed in evolution showed a continuous alteration of right ventricle function, without important differences of left ventricular function.  She developed heart failure symptoms six years after diagnosis and she had seven hospitalizations in the past two years, currently with an increasing need of diuretics and persistent hepatic dysfunction. Cardiac transplantation or left ventricular assist device therapy should be considered in patients with severe heart failure symptoms and no longer effective treatment. However, elevated pulmonary vascular resistance excludes the patient from cardiac transplantation.

Variability of right ventricular global and segmental longitudinal strain measurements.

OBJECTIVES: We evaluated intra-observer, test-retest, and inter-observer reproducibility of right ventricular (RV) longitudinal strain (LS) measurements derived from two-dimensional speckle tracking echocardiography. BACKGROUND: The assessment of RV deformation has demonstrated to hold valuable prognostic and diagnostic data in clinical practice. Data about the reproducibility of the measurements, however, are missing. METHODS: In 200 subjects, apical modified four-chamber view focused on the right ventricle (RV) was obtained. In 150 subjects (75%), a second set of images was acquired for test-retest analysis. Global RV LS (RVGLS-4C), free wall strain (RVFW-4C), and segmental maximum peak strain (base, mid, and apex) were calculated (EchoPac vBT13, GE Vingmed Ultrasound, Horten, Norway). Additionally, the reliability and feasibility of RV free wall strain derived from single wall tracking (RVFW-SWT) were tested. The absolute difference between repeated measurements and inter-class correlation coefficients (ICC) for consistency was calculated. RESULTS: RVGLS-4C and RVFW-4C measurement could be obtained in all subjects. RVGLS-4C demonstrated lower intra-observer, test-retest, and inter-observer absolute difference compared to RVFW-4C (1.4 ± 1.2%, 1.8 ± 1.5%, and 1.7 ± 1.9%, respectively, vs 2.4 ± 2.4, 2.2 ± 1.9, and 2.6 ± 3.0, respectively, P < 0.01). ICC ranged between 0.83 and 0.90 for RVGLS-4C measurements and between 0.76 and 0.79 for RVFW-4C measurements. RVFW-SWT was feasible in 82.5% of the subjects and showed noninferior reproducibility compared to RVFW-4C. Basal and apical segments demonstrating the highest variability. CONCLUSIONS: The measurement of RVGLS-4C appears to be reliable in clinical practice and demonstrates better reproducibility compared to RV free wall LS measurements. Segmental LS measurements presented high variability and such parameters should be interpreted with caution.

Variability of longitudinal strain measurements: levelling the playing field.

Speckle tracking echocardiography offers a unique opportunity to evaluate myocardial function, and global longitudinal strain (GLS) is currently recommended as a measurement of global left ventricular function. To facilitate clinical applicability of the method, collective efforts have been made to standardise strain measurements and to raise awareness of the potential sources of variability. The purpose of this review is to familiarise the reader with the most common sources of variability of longitudinal strain measurements and detail the possible measures to increase the accuracy and reproducibility of strain parameters.

Effects of boron-containing compounds on cardiovascular disease risk factors - A review.

Boron is considered to be a biological trace element but there is substantial and growing support for it to be classified as an essential nutrient for animals and humans, depending on its speciation. Boron-containing compounds have been reported to play an important role in biological systems. Although the exact biochemical functions of boron-containing compounds have not yet been fully elucidated, previous studies suggest an active involvement of these molecules in the mediation of inflammation and oxidative stress. Chronic inflammation and oxidative stress are known to amplify the effects of the main cardiovascular risk factors: smoking, diet, obesity, arterial hypertension, dyslipidemia, type 2 diabetes (as modifiable risk factors), and hyperhomocysteinemia and age (as independent risk factors). However, the role of boron-containing compounds in cardiovascular systems and disease prevention has yet to be established. This paper is a review of boron-containing compounds' existence in nature and their possible functions in living organisms, with a special focus on certain cardiovascular risk factors that may be diminished by intake of these compounds, leading to a reduction of cardiovascular morbidity and/or mortality.

Left and right ventricular morphology and function in athletes with elevated pulmonary systolic arterial pressure.

OBJECTIVES: The objective of the study was to evaluate the prevalence and potential impact of elevated pulmonary arterial systolic pressure (PASP) on left and right cardiac morphology and function in young elite athletes. METHODS: In total, 85 professional athletes (40 endurance, 20 strength, and 25 mixed training, mean age 17.8 ± 4.0) and 50 sedentary controls (mean age 18.6 ± 3.3) underwent transthoracic echocardiographic examination. Two-dimensional measurements of the right (RV) and left ventricle (LV) were obtained. PASP was estimated from the peak tricuspid regurgitant velocity (TRV). Speckle tracking-derived longitudinal LV and RV strain measurements (RV_LS) were calculated for function estimation. RESULTS: Maximum TRV (2.2 ± 0.3 vs 2.0 ± 0.2 m/s, P < .01) and PASP (26 ± 5 vs 22 ± 5 mm Hg, P < .01) were higher in athletes compared to controls. PAPS above 30 mm Hg (35 ± 3 mm Hg, range 31-40 mm Hg) was identified in 11 athletes (12.9%). Athletes with elevated PASP demonstrated higher LV mass (P < .01), LV stroke volume indexed (P < .01), larger RV-end-systolic area (ESAi), RV-end-diastolic area (EDAi), right atrium ES volume and ED volume, and decreased RV fractional area change (FAC) (P < .01) when compared to matched controls and higher RV-EDAi (13.0 ± 1.6 vs 11.1 ± 1.5, P < .01), RV-ESAi (8.2 ± 1.5 vs 6.1 ± 0.9, P < .01), and significantly reduced RV FAC (38.1 ± 5.8 vs 44.6 ± 2.5, P < .01) when compared to matched athletes. LV global longitudinal strain and RV_LS showed no differences between the groups. CONCLUSIONS: Pulmonary arterial systolic pressure elevation in young athletes is associated with pronounced right ventricular enlargement, even when compared to matched athletes. Conventional and speckle tracking echocardiography showed preserved right ventricular function.

In-hospital and short-term prognostic factors in acute pulmonary edema: clinical and morphological features.

INTRODUCTION: There are extensive records which have included patients with acute heart failure (AHF), but specific studies about prognosis in acute pulmonary edema (PE) are scarce and have enrolled a small number of patients. The objectives of this study were to evaluate the predictive factors of short-term evolution in patients with PE. PATIENTS, MATERIALS AND METHODS: This was a prospective, two-center survey of 70 consecutive patients admitted for acute cardiogenic PE. The follow-up was performed one month after discharge. The composite endpoint was in-hospital death, and death of any cause or readmission for heart failure (HF) at one month after discharge. Heart and lung tissue analysis was performed postmortem to identify morphological features of PE. RESULTS: In-hospital mortality was 4.2%, another 14.2% died in the first month, and an additional 10% required rehospitalization for HF. The characteristics significantly associated with end-point occurrence were: history of kidney disease, anemia, diabetes mellitus, lack of prior angiotensin-converting enzyme inhibitor÷angiotensin-receptor blocker treatment, lower systolic blood pressure (BP) at admission, lower diastolic BP at admission, creatinine at admission and at discharge, an increase in creatinine during stay, glomerular filtration rate at admission, serum sodium at admission, decrease in serum sodium during hospitalization, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) at discharge, right ventricle fractional area change, left atrium volume index. We created a multiple logistic regression model and identified five prognostic factors: age, diabetes, creatinine, diastolic BP, serum sodium. This model correctly classified 48 (96%) patients without worsening and 13 (65%) patients with worsening, providing an overall accuracy of 87.1%. Necropsy was performed on five patients and fragments of left ventricle myocardium and lung were harvested for histopathological and immunohistochemical studies. The myocardium exhibited fibrosis areas where the myocytes were completely or partially replaced by collagen fibers. Lung tissue analysis revealed some case-to-case differences, but the common finding was alveoli size larger than normal, with the lumen completely or almost completely covered by an eosinophilic liquid. CONCLUSIONS: The factors that best predicted the short-term outcome in PE were age, diabetes, diastolic BP, creatinine, serum sodium.

Progress in interventional cardiology: challenges for the future.

Cardiovascular disease is the leading cause of death in the western and developing countries. Percutaneous transluminal coronary interventions have become the most prevalent treatment option for coronary artery disease; however, due to serious complications, such as stent thrombosis and in-stent restenosis (ISR), the efficacy and safety of the procedure remain important issues to address. Strategies to overcome these aspects are under extensive investigation. In this review, we summarise relevant milestones during the time to overcome these limitations of coronary stents, such as the development of polymer-free drug-eluting stents (DES) to avoid pro-inflammatory response due to the polymer coating or the developement of stents with cell-directing drugs to, simultaneously, improve re-endothelialisation and inhibit ISR amongst other techniques most recently developed, which have not fully entered the clinical stage. Also the novel concept of fully biodegradable DES featured by the lack of a permanent foreign body promises to be a beneficial and applicable tool to restore a natural vessel with maintained vasomotion and to enable optional subsequent surgical revascularisation.