Endothelial Glycocalyx and Cardiomyocyte Damage Is Prevented by Recombinant Syndecan-1 in Acute Myocardial Infarction.

The outer layer of endothelial cells (ECs), consisting of the endothelial glycocalyx (eGC) and the cortex (CTX), provides a protective barrier against vascular diseases. Structural and functional impairments of their mechanical properties are recognized as hallmarks of endothelial dysfunction and can lead to cardiovascular events, such as acute myocardial infarction (AMI). This study investigated the effects of AMI on endothelial nanomechanics and function and the use of exogenous recombinant syndecan-1 (rSyn-1), a major component of the eGC, as recovering agent. ECs were exposed in vitro to serum samples collected from patients with AMI. In addition, in situ ECs of ex vivo aorta preparations derived from a mouse model for AMI were employed. Effects were quantified by using atomic force microscopy-based nanoindentation measurements, fluorescence staining, and histologic examination of the mouse hearts. AMI serum samples damaged eGC/CTX and augmented monocyte adhesion to the endothelial surface. In particular, the anaphylatoxins C3a and C5a played an important role in these processes. The impairment of endothelial function could be prevented by rSyn-1 treatment. In the mouse model of myocardial infarction, pretreatment with rSyn-1 alleviated eGC/CTX deterioration and reduced cardiomyocyte damage in histologic analyses. However, echocardiographic measurements did not indicate a functional benefit. These results provide new insights into the underlying mechanisms of AMI-induced endothelial dysfunction and perspectives for future studies on the benefit of rSyn-1 in post-AMI treatment.

Underlying mechanisms and cardioprotective effects of SGLT2i and GLP-1Ra: insights from cardiovascular magnetic resonance.

Originally designed as anti-hyperglycemic drugs, Glucagon-Like Peptide-1 receptor agonists (GLP-1Ra) and Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated protective cardiovascular effects, with significant impact on cardiovascular morbidity and mortality. Despite several mechanisms have been proposed, the exact pathophysiology behind these effects is not yet fully understood. Cardiovascular imaging is key for the evaluation of diabetic patients, with an established role from the identification of early subclinical changes to long-term follow up and prognostic assessment. Among the different imaging modalities, CMR may have a key-role being the gold standard for volumes and function assessment and having the unique ability to provide tissue characterization. Novel techniques are also implementing the possibility to evaluate cardiac metabolism through CMR and thereby further increasing the potential role of the modality in this context. Aim of this paper is to provide a comprehensive review of changes in CMR parameters and novel CMR techniques applied in both pre-clinical and clinical studies evaluating the effects of SGLT2i and GLP-1Ra, and their potential role in better understanding the underlying CV mechanisms of these drugs.

Segmental and global longitudinal strain differences between Kawasaki disease and multi-system inflammatory syndrome in children.

BACKGROUND: Multi-system inflammatory syndrome in children and Kawasaki disease have overlapping clinical features but comparative echocardiographic studies are lacking. METHODS: We reviewed echocardiography findings of all multi-system inflammatory syndrome cases between 1st April and 31st July, 2020 and typical Kawasaki disease patients with coronary arteries abnormalities consecutively followed between 1st October, 2016 and June 30th, 2019. RESULTS: We included 40 multi-system inflammatory syndrome children (25 males, 62.5%) and 45 Kawasaki disease patients (31 males, 68.9%) at a mean age of 6.4 years old and 8 years old, respectively. Four out of 40 multi-system inflammatory syndrome children had coronary arteries abnormalities. Left ventricle ejection fraction was normal in both groups. Global longitudinal strain was normal although Kawasaki disease group had significantly lower values (-20.0 versus -21.7%; p = 0.02). Basal segments were the most affected in Kawasaki disease patients with significant differences in the basal anterior, anterolateral, and anteroseptal strain: -18.2 versus -23.0% (p = 0.002), -16.7 versus -22.0% (p < 0.001), -16.7 versus -19.5% (p = 0.034), respectively. The basal anterolateral and anteroseptal segments in Kawasaki disease patients were the only ones with an absolute reduction of longitudinal strain (-16.7% both) consistent with the greater left main coronary involvement in this cohort. CONCLUSIONS: Our findings are consistent with the transient cardiac involvement in multi-system inflammatory syndrome, as opposed to the subtle and chronic myocardial involvement in Kawasaki disease children with coronary arteries abnormalities. We speculate that the mechanism of cardiac impairment in the few multi-system inflammatory syndrome children with reduced global longitudinal strain is not related to coronary arteries abnormalities.

Polarizing Macrophage Functional Phenotype to Foster Cardiac Regeneration.

There is an increasing interest in understanding the connection between the immune and cardiovascular systems, which are highly integrated and communicate through finely regulated cross-talking mechanisms. Recent evidence has demonstrated that the immune system does indeed have a key role in the response to cardiac injury and in cardiac regeneration. Among the immune cells, macrophages appear to have a prominent role in this context, with different subtypes described so far that each have a specific influence on cardiac remodeling and repair. Similarly, there are significant differences in how the innate and adaptive immune systems affect the response to cardiac damage. Understanding all these mechanisms may have relevant clinical implications. Several studies have already demonstrated that stem cell-based therapies support myocardial repair. However, the exact role that cardiac macrophages and their modulation may have in this setting is still unclear. The current need to decipher the dual role of immunity in boosting both heart injury and repair is due, at least for a significant part, to unresolved questions related to the complexity of cardiac macrophage phenotypes. The aim of this review is to provide an overview on the role of the immune system, and of macrophages in particular, in the response to cardiac injury and to outline, through the modulation of the immune response, potential novel therapeutic strategies for cardiac regeneration.

Unusual case of severe aortic regurgitation in a child with bicuspid aortic valve.

Aortic regurgitation (AR) is common after aortic balloon valvuloplasty in children and it has been associated with large balloon/annulus ratio, abnormal valve morphology and aortic valve prolapse. We present a rare case of severe AR after aortic balloon valvuloplasty due to aortic strands rupture, causing prolapse of the co-joined cusp.  These findings were identified by 3D echocardiography, highlighting the importance of this imaging technique even in pediatric patients.

Altered circulating marinobufagenin levels and recurrent intradialytic hypotensive episodes in chronic hemodialysis patients: a pilot, prospective study.

Intradialytic hypotension (IDH) is a sudden and often serious complication of chronic hemodialysis (HD). In this prospective study, we aimed at evaluating the clinical predictors of IDH in a homogeneous cohort of chronic HD patients, with a particular focus on marinobufagenin (MBG), an endogenous cardiotonic steroid which alterations have previously been involved in various cardiovascular disorders. MBG levels in HD patients were significantly higher than in controls (p = 0.03), remained unchanged throughout a single HD session and were not correlated with the absolute or partial fluid loss achieved. During a 30-day follow-up, 19 patients (65.5%) experienced at least one IDH (73 total episodes). An inverse correlation was found between baseline MBG and the number of IDH (R = -0.55; p = 0.001). HD patients experiencing IDH presented remarkably lower baseline MBG as compared to others (p = 0.008) with a statistically significant trend during HD (p = 0.02). At Kaplan-Meier analyses, HD patients with lower MBG manifested a four-to-six fold increased risk of IDH during follow-up (crude Hazard Ratio ranging from 4.37 to 6.68). At Cox regression analyses, MBG measurement at different time points resulted the strongest time-dependent predictors of IDH among all the variables considered (HR ranging from 0.068 to 0.155; p: 0.002 to <0.0001). Findings obtained suggest that differently altered MBG in chronic HD patients may reflect a diverse vascular and hemodynamic tolerance to HD stress, eventually leading to recurrent IDH episodes. Further studies are needed to confirm the prognostic capacity of MBG for identifying HD patients at high risk of IDH, particularly those with apparently optimal fluid status.

Empagliflozin prevents doxorubicin-induced myocardial dysfunction.

BACKGROUND: Empagliflozin showed efficacy in controlling glycaemia, leading to reductions in HbA1c levels, weight loss and blood pressure, compared to standard treatment. Moreover, the EMPA-REG OUTCOME trial demonstrated a 14% reduction of major adverse cardiovascular events (MACE), a 38% reduction in cardiovascular (CV) death and a 35% reduction in the hospitalization rate for heart failure (HF). These beneficial effect on HF were apparently independent from glucose control. However, no mechanistic in vivo studies are available to explain these results, yet. We aimed to determine the effect of empagliflozin on left ventricular (LV) function in a mouse model of doxorubicin-induced cardiomyopathy (DOX-HF). METHODS: Male C57Bl/6 mice were randomly assigned to the following groups: controls (CTRL, n = 7), doxorubicin (DOX, n = 14), DOX plus empagliflozin (DOX + EMPA, n = 14), or DOX plus furosemide (DOX + FURO group, n = 7). DOX was injected intraperitoneally. LV function was evaluated at baseline and after 6 weeks of treatment using high-resolution echocardiography with 2D speckle tracking (Vevo 2100). Histological assessment was obtained using Haematoxylin and Eosin and Masson's Goldner staining. RESULTS: A significant decrease in both systolic and diastolic LV function was observed after 6 weeks of treatment with doxorubicin. EF dropped by 32% (p = 0.002), while the LS was reduced by 42% (p < 0.001) and the CS by 50% (p < 0.001). However, LV function was significantly better in the DOX + EMPA group, both in terms of EF (61.30 ± 11% vs. 49.24 ± 8%, p = 0.007), LS (- 17.52 ± 3% vs. - 13.93 ± 5%, p = 0.04) and CS (- 25.75 ± 6% vs. - 15.91 ± 6%, p < 0.001). Those results were not duplicated in the DOX + FURO group. Hearts from the DOX + EMPA group showed a 50% lower degree of myocardial fibrosis, compared to DOX mice (p = 0.03). No significant differences were found between the DOX + FURO and the DOX group (p = 0.103). CONCLUSION: Empagliflozin attenuates the cardiotoxic effects exerted by doxorubicin on LV function and remodelling in nondiabetic mice, independently of glycaemic control. These findings support the design of clinical studies to assess their relevance in a clinical setting.

Statins Stimulate New Myocyte Formation After Myocardial Infarction by Activating Growth and Differentiation of the Endogenous Cardiac Stem Cells.

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert pleiotropic effects on cardiac cell biology which are not yet fully understood. Here we tested whether statin treatment affects resident endogenous cardiac stem/progenitor cell (CSC) activation in vitro and in vivo after myocardial infarction (MI). Statins (Rosuvastatin, Simvastatin and Pravastatin) significantly increased CSC expansion in vitro as measured by both BrdU incorporation and cell growth curve. Additionally, statins increased CSC clonal expansion and cardiosphere formation. The effects of statins on CSC growth and differentiation depended on Akt phosphorylation. Twenty-eight days after myocardial infarction by permanent coronary ligation in rats, the number of endogenous CSCs in the infarct border zone was significantly increased by Rosuvastatin-treatment as compared to untreated controls. Additionally, commitment of the activated CSCs into the myogenic lineage (c-kitpos/Gata4pos CSCs) was increased by Rosuvastatin administration. Accordingly, Rosuvastatin fostered new cardiomyocyte formation after MI. Finally, Rosuvastatin treatment reversed the cardiomyogenic defects of CSCs in c-kit haploinsufficient mice, increasing new cardiomyocyte formation by endogenous CSCs in these mice after myocardial infarction. In summary, statins, by sustaining Akt activation, foster CSC growth and differentiation in vitro and in vivo. The activation and differentiation of the endogenous CSC pool and consequent new myocyte formation by statins improve myocardial remodeling after coronary occlusion in rodents. Similar effects might contribute to the beneficial effects of statins on human cardiovascular diseases.

MicroRNAs fingerprint of bicuspid aortic valve.

Aortic valve tissue is largely exposed to high blood flow. Cells belonging to aortic valve tissues are able to detect and respond to flow conditions changes. Bicuspid aortic valve (BAV) presents altered morphology, with only two abnormal cusps instead of three. This results in an alteration of blood flow dynamics on valve cusps and aortic wall, which may, in turn, increase the risk to develop aortic stenosis and/or regurgitation, endocarditis, aortopathy and/or aortic dissection. MicroRNAs (miRNAs) are short RNA strands regulating gene expression mainly through the inhibition of their target mRNAs. They are largely involved in cardiovascular pathophysiology and heart disease. More recently, it has been observed that the expression of specific miRNAs can be modulated in response to changes in hemodynamic conditions. Using a bioinformatic approach, this article analyses available scientific evidence about the differential expression of miRNAs in the bicuspid aortic valve, with a focus on the differential modulation compared to the calcific-degenerative tricuspid aortic valve.

Percutaneous Closure Versus Medical Treatment in Stroke Patients With Patent Foramen Ovale: A Systematic Review and Meta-analysis.

Background: New evidence emerged recently regarding the percutaneous closure of patent foramen ovale (PFO) to prevent recurrent stroke in patients with cryptogenic stroke. Purpose: To compare risks for recurrent cerebrovascular events in adults with PFO and cryptogenic stroke who underwent PFO closure versus those who received medical therapy alone. Data Sources: PubMed, Scopus, and Google Scholar from 1 December 2004 through 14 September 2017; references of eligible studies; relevant scientific session abstracts; and cardiology Web sites. Study Selection: Randomized controlled trials, published in English, that compared PFO closure using a currently available device with medical treatment alone and that reported, at minimum, the rates of stroke or transient ischemic attack (TIA) or of new-onset atrial fibrillation (AF) or atrial flutter (AFL). Data Extraction: 2 investigators independently extracted study data and assessed study quality. Data Synthesis: 4 of 5 trials comparing PFO closure with medical therapy used commercially available devices. These 4 trials, involving 2531 patients, found that PFO closure reduced the risk for the main outcome of stroke or TIA (risk difference [RD], -0.029 [95% CI, -0.050 to -0.007]) and increased the risk for new-onset AF or AFL (RD, 0.033 [CI, 0.012 to 0.054]). The beneficial effect of PFO closure was associated with larger interatrial shunts (P = 0.034). Limitation: Trials were not double-blind, and inclusion criteria were heterogeneous. Conclusion: Compared with medical treatment, PFO closure prevents recurrent stroke and TIA but increases the incidence of AF or AFL in PFO carriers with cryptogenic stroke. Primary Funding Source: Italian Ministry of Education, University and Research (MIUR). (PROSPERO: CRD42017074686).

Evaluation of cardiac function by global longitudinal strain before and after treatment with sofosbuvir-based regimens in HCV infected patients.

BACKGROUND: Possible cardiotoxicity of sofosbuvir in humans has not been demonstrated yet. Also, since HCV can exert deleterious effects on hearth function, it is of interest to know whether HCV eradication provides any benefits using global longitudinal strain (GLS), a measure of left ventricular function more reliable than ejection fraction (EF). METHODS: Patients eligible for treatment with the combination therapy for HCV were invited to perform a transthoracic cardiac ultrasound at four different time points: before starting treatment, after one month, at the end of treatment and, after six month. Left ventricular function was measured with both EF and GLS. RESULTS: From March 2015 to December 2016, 82 patients were enrolled. Fifty-six percent patients were males. Mean age was 66.12 (SD: 9.25) years. About 20% patients did not present any cardiovascular risk factors or comorbidities. A worsening trend of GLS was observed. Variations were not found to be statistically significant when EF was studied along the follow-up. However, when GLS was studied, its variations were found to be statistically significant indicating a worsening effect, albeit with different trends in patients who underwent treatment for three months compared to six months. Worsening of GLS was found to be statistically significant even after adjusting for body mass index and liver fibrosis, independently from treatment duration. CONCLUSIONS: Our results showed unexpected worsening of left ventricular function when measured through GLS after HCV treatment response induced by DAAs including sofosbuvir. Although this result is not proven to be clinically significant, the safety profile of sofosbuvir-based regimens needs to be studied further.

Long-term outcomes of coronary artery bypass grafting versus stent-PCI for unprotected left main disease: a meta-analysis.

BACKGROUND: Coronary artery bypass graft (CABG) surgery has traditionally represented the standard of care for left main coronary artery (LMCA) disease. However, percutaneous coronary intervention with stent implantation (PCI) has more recently emerged as a valuable alternative. The long-time awaited results of the largest randomized trials on the long-term impact of PCI versus CABG in LMCA disease, the newly published NOBLE and EXCEL studies, revealed contrasting results. Thus, aim of the present meta-analysis was to review the most robust evidence from randomized comparisons of CABG versus PCI for revascularization of LMCA. METHODS: Randomized studies comparing long-term clinical outcomes of CABG or Stent-PCI for the treatment of LMCA disease were searched for in PubMed, the Chochrane Library and Scopus electronic databases. A total of 5 randomized studies were selected, including 4499 patients. RESULTS: No significant difference between CABG and PCI was found in the primary analysis on the composite endpoint of death, stroke and myocardial infarction (OR = 1·06 95% CI 0·80-1·40; p = 0·70). Similarly, no differences were observed between CABG and PCI for all-cause death (OR = 1·03 95% CI 0·81-1·32; p = 0·81). Although not statistically significant, a lower rate of stroke was registered in the PCI arm (OR = 0·86; p = 0·67), while a lower rate of myocardial infarction was found in the CABG arm (OR = 1·43; p = 0·17). On the contrary, a significantly higher rate of repeat revascularization was registered in the PCI arm (OR = 1·76 95% CI 1·45-2·13; p < 0·001). CONCLUSIONS: The present meta-analysis, the most comprehensive and updated to date, including 5 randomized studies and 4499 patients, demonstrates no difference between Stent-PCI and CABG for the treatment of LMCA disease in the composite endpoint of death, stroke and myocardial infarction. Hence, a large part of patients with unprotected left main coronary artery disease can be managed equally well by means of both these revascularization strategies.

Clinical Usefulness of a Mobile Application for the Appropriate Selection of the Antiarrhythmic Device in Heart Failure.

BACKGROUND: Appropriate selection of implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) device can be challenging in patients with left ventricular (LV) dysfunction. In this setting, limited information exists about the role of medical applications in helping physicians to choose the most useful device. METHODS: We developed a medical application that provides guidelines-based algorithms for helping doctors in decision process using the Apache Cordova application programming interface. e-CRTD App was tested in 36 consecutive patients (age 66.4 ± 8.5 years, 31 males) with diagnosis of heart failure (HF) addressed to electrophysiology laboratory for evaluation of ICD (N = 18) or CRT with defibrillator device (CRT-D; N = 18) implantation. Two separate teams evaluated each patient independently: expert electrophysiologists (Group A); cardiologists in training using the App (Group B). RESULTS: The outcomes of the clinical evaluation performed by Groups A and B were similar in 100% of patients in terms of classes of recommendations to device (Class I in eight cases, Class IIa in seven cases, Class III in the remaining 21). Surprisingly, the majority of indications from the general practitioners to cardiac device were inappropriate (N = 17 ICD, and N = 4 CRT-D, Class III); nevertheless, e-CRTD App helped Group B (nonexpert cardiologists) in excluding all these cases. CONCLUSIONS: This study describes and validates a mobile application realized to help the decision-making process in HF patients candidate to ICD/CRT-D. This application supports physicians to assess the eligibility for ICD or CRT-D according to current guidelines in patients with LV dysfunction.

The duration of balloon inflation affects the luminal diameter of coronary segments after bioresorbable vascular scaffolds deployment.

BACKGROUND: Adequate expansion is critical to achieve optimal Bioresorbable Vascular Scaffolds (BVS) apposition to the vessel wall. However, compared to metallic stents, BVS present different mechanical properties. Hence, slow deployment and maintenance of balloon inflation for at least 30" is recommended for BVS implantation. However, since no evidences are available demonstrating the superiority of a longer balloon dilatation time, the implantation technique is highly variable among different centers. METHODS: A total of 24 BVS-treated lesions were included in the present analysis. After BVS deployment at 12 atmosphere (ATM) the balloon was rapidly deflated and scaffold expansion was documented with an angiogram. The same balloon was then inflated again and kept at 12 ATM for 30". Finally, a further angiogram was obtained to evaluate BVS expansion. Quantitative coronary angiography (QCA) was performed at each step. RESULTS: A significant increase of minimal luminal diameter (MLD)-to-reference scaffold diameter (RSD) ratio (MLD to RSD Ration, MR-Ratio) from 0.70 ± 0.10 after initial stent deployment to 0.79 ± 0.10 after the 30"-long balloon dilation was observed (p < 0.001). Of note, this result was consistent across all sub-segments, as well as across almost all lesion subgroups. A substantial reduction in the prevalence of residual stenosis from 29 % to 17 % was registered after the 30"-long dilation. CONCLUSIONS: Our results strongly support the maintenance of balloon inflation for at least 30" during BVS deployment to achieve optimal scaffold expansion and minimize the occurrence of residual stenosis.

Mechanisms of Cardiovascular Calcification and Experimental Models: Impact of Vitamin K Antagonists.

Cardiovascular calcification is a multifactorial and complex process involving an array of molecular mechanisms eventually leading to calcium deposition within the arterial walls. This process increases arterial stiffness, decreases elasticity, influences shear stress events and is related to an increased risk of morbidity and mortality associated with cardiovascular disease. In numerous in vivo and in vitro models, warfarin therapy has been shown to cause vascular calcification in the arterial wall. However, the exact mechanisms of calcification formation with warfarin remain largely unknown, although several molecular pathways have been identified. Circulating miRNA have been evaluated as biomarkers for a wide range of cardiovascular diseases, but their exact role in cardiovascular calcification is limited. This review aims to describe the current state-of-the-art research on the impact of warfarin treatment on the development of vascular calcification and to highlight potential molecular targets, including microRNA, within the implicated pathways.

Pediatric Hypertension: A Condition That Matters.

Systemic hypertension has been considered mainly as an adult health issue for a long time, but it is now being increasingly acknowledged as a significant problem also among pediatric patients. The frequency of pediatric hypertension has grown mostly because of increases in childhood obesity and sedentary lifestyles, but secondary forms of hypertension play a role as well. Considering that unaddressed hypertension during childhood can result in enduring cardiovascular complications, timely identification and intervention are essential. Strategies for addressing this disease encompass not only lifestyle adjustments, but also the use of medications when needed. Lifestyle modifications entail encouraging a nutritious diet, consistent physical activity, and the maintenance of a healthy weight. Moreover, educating both children and their caregivers about monitoring blood pressure at home can aid in long-term management. Thus, the aim of this review is to discuss the etiologies, classification, and principles of the treatment of hypertension in pediatric patients.

Complete Transposition of the Great Arteries in the Pediatric Field: A Multimodality Imaging Approach.

The complete transposition of the great arteries (C-TGA) is a congenital cardiac anomaly characterized by the reversal of the main arteries. Early detection and precise management are crucial for optimal outcomes. This review emphasizes the integral role of multimodal imaging, including fetal echocardiography, transthoracic echocardiography (TTE), cardiovascular magnetic resonance (CMR), and cardiac computed tomography (CCT) in the diagnosis, treatment planning, and long-term follow-up of C-TGA. Fetal echocardiography plays a pivotal role in prenatal detection, enabling early intervention strategies. Despite technological advances, the detection rate varies, highlighting the need for improved screening protocols. TTE remains the cornerstone for initial diagnosis, surgical preparation, and postoperative evaluation, providing essential information on cardiac anatomy, ventricular function, and the presence of associated defects. CMR and CCT offer additional value in C-TGA assessment. CMR, free from ionizing radiation, provides detailed anatomical and functional insights from fetal life into adulthood, becoming increasingly important in evaluating complex cardiac structures and post-surgical outcomes. CCT, with its high-resolution imaging, is indispensable in delineating coronary anatomy and vascular structures, particularly when CMR is contraindicated or inconclusive. This review advocates for a comprehensive imaging approach, integrating TTE, CMR, and CCT to enhance diagnostic accuracy, guide therapeutic interventions, and monitor postoperative conditions in C-TGA patients. Such a multimodal strategy is vital for advancing patient care and improving long-term prognoses in this complex congenital heart disease.

The mechanics of congenital heart disease: from a morphological trait to the functional echocardiographic evaluation.

Advances in pediatric cardiac surgery have resulted in a recent growing epidemic of children and young adults with congenital heart diseases (CHDs). In these patients, congenital defects themselves, surgical operations and remaining lesions may alter cardiac anatomy and impact the mechanical performance of both ventricles. Cardiac function significantly influences outcomes in CHDs, necessitating regular patient follow-up to detect clinical changes and relevant risk factors. Echocardiography remains the primary imaging method for CHDs, but clinicians must understand patients' unique anatomies as different CHDs exhibit distinct anatomical characteristics affecting cardiac mechanics. Additionally, the use of myocardial deformation imaging and 3D echocardiography has gained popularity for enhanced assessment of cardiac function and anatomy. This paper discusses the role of echocardiography in evaluating cardiac mechanics in most significant CHDs, particularly its ability to accommodate and interpret the inherent anatomical substrate in these conditions.

Repaired Tetralogy of Fallot: Have We Understood the Right Timing of PVR?

Despite many advances in surgical repair during the past few decades, the majority of tetralogy of Fallot patients continue to experience residual hemodynamic and electrophysiological abnormalities. The actual issue, which has yet to be solved, is understanding how this disease evolves in each individual patient and, as a result, who is truly at risk of sudden death, as well as the proper timing of pulmonary valve replacement (PVR). Our responsibility should be to select the most appropriate time for each patient, going above and beyond imaging criteria used up to now to make such a clinically crucial decision. Despite several studies on timing, indications, procedures, and outcomes of PVR, there is still much uncertainty about whether PVR reduces arrhythmia burden or improves survival in these patients and how to appropriately manage this population. This review summarizes the most recent research on the evolution of repaired tetralogy of Fallot (from adolescence onwards) and risk factor variables that may favor or delay PVR.