Holographic mixed reality for planning transcatheter aortic valve replacement.

BACKGROUND: Using three-dimensional (3D) modalities for optimal pre-procedure planning in transcatheter aortic valve replacement (TAVR) is critical for procedural success. However, current methods rely on visualizing images on a two-dimensional screen, using shading and colors to create the illusion of 3D, potentially impeding the accurate comprehension of the actual anatomy structures. In contrast, a new Mixed Reality (MxR) based software enables accurate 3D visualization, imaging manipulation, and quantification of measurements. AIMS: The study aims to evaluate the feasibility, reproducibility, and accuracy of dimensions of the aortic valve complex as measured with a new holographic MxR software (ARTICOR®, Artiness srl, Milano, Italy) compared to a widely used software for pre-operative sizing and planning (3mensio Medical Imaging BV, Bilthoven, The Netherlands) . METHODS: This retrospective, observational, double-center study enrolled 100 patients with severe aortic stenosis who underwent cardiac computed tomography (CCT) before TAVR. The CCT datasets of volumetric aortic valve images were analyzed using 3Mensio and newly introduced MxR-based software. RESULTS: 98% of the CCT datasets were successfully converted into holographic models. A higher level of agreement between the two software systems was observed for linear metrics (short, long, and average diameter). In comparison, agreement was lower for area, perimeter, and annulus-to-coronary ostia distance measurements. Notably, the annulus area, annular perimeter, LVOT area, and LVOT perimeter were significantly and consistently smaller with the MxR-based software compared to the 3Mensio. Excellent interobserver reliability was demonstrated for most measurements, especially for direct linear measurements. CONCLUSIONS: Linear Measurements of the aortic valve complex using MxR-based software are reproducible compared to the standard CCT dataset analyzed with 3Mensio. MxR-based software could represent an accurate tool for the pre-procedural planning of TAVR.

SGLT2i effect on atrial fibrillation: A network meta-analysis of randomized controlled trials.

INTRODUCTION: Gliflozins are recommended as first-line treatment in patients with heart failure and/or cardiovascular comorbidities and are demonstrated to reduce atrial fibrillation (AF) occurrence. However, it is not well known which gliflozin yields the larger cardioprotection in terms of AF occurrence reduction. Hence, we aimed to compare data regarding AF recurrence associated with different gliflozins. METHODS: An accurate search of online scientific libraries (from inception to June 1, 2023) was performed. Fifty-nine studies were included in the meta-analysis involving 108 026 patients, of whom 60 097 received gliflozins and 47 929 received placebo. RESULTS: Gliflozins provided a statistically significant reduction of AF occurrence relative to standard of care therapy in the overall population (relative risks [RR]: 0.8880, 95% CI: [0.8059; 0.9784], p = .0164) and in patients with diabetes and cardiorenal diseases (RR: 0.8352, 95% CI: [0.7219; 0.9663], p = .0155). Dapagliflozin significantly decreased AF occurrence as compared to placebo (0.7259 [0.6337; 0.8316], p < .0001) in the overall population, in patients with diabetes (RR: 0.2482, 95% CI: [0.0682; 0.9033], p = .0345), with diabetes associated with cardiorenal diseases (RR: 0.7192, 95% CI: [0.5679; 0.9110], p = .0063) and in the subanalysis including studies with follow-up ≥1 year (RR: 0.7792, 95% CI: [0.6508; 0.9330], p = .0066). No significant differences in terms of AF protection were found among different gliflozins. CONCLUSIONS: Dapagliflozin use was associated with significant reduction in AF risk as compared to placebo in overall population and patients with diabetes, whereas the use of other gliflozins did not significantly reduce AF occurrence.

Prevention and Risk Assessment of Cardiac Device Infections in Clinical Practice.

The implantation of cardiac electronic devices (CIEDs), including pacemakers and defibrillators, has become increasingly prevalent in recent years and has been accompanied by a significant rise in cardiac device infections (CDIs), which pose a substantial clinical and economic burden. CDIs are associated with hospitalizations and prolonged antibiotic therapy and often necessitate device removal, leading to increased morbidity, mortality, and healthcare costs worldwide. Approximately 1-2% of CIED implants are associated with infections, making this a critical issue to address. In this contemporary review, we discuss the burden of CDIs with their risk factors, healthcare costs, prevention strategies, and clinical management.

Mechanical Circulatory Support Systems in the Management of Ventricular Arrhythmias: A Contemporary Overview.

Ventricular tachycardias (VTs) and electrical storms (ES) are life-threatening conditions mostly seen in the setting of structural heart disease (SHD). Traditional management strategies, predominantly centered around pharmacological interventions with antiarrhythmic drugs, have demonstrated limited efficacy in these cases, whereas catheter ablation is related with more favorable outcomes. However, patients with hemodynamically unstable, recurrent VT or ES may present cardiogenic shock (CS) that precludes the procedure, and catheter ablation in patients with SHD portends a multifactorial intrinsic risk of acute hemodynamic decompensation (AHD), that is associated with increased mortality. In this setting, the use of mechanical circulatory support (MCS) systems allow the maintenance of end-organ perfusion and cardiac output, improving coronary flow and myocardial mechanics, and minimizing the effect of cardiac stunning after multiple VT inductions or cardioversion. Although ablation success and VT recurrence are not influenced by hemodynamic support devices, MCS promotes diuresis and reduces the incidence of post-procedural kidney injury. In addition, MCS has a role in post-procedural mortality reduction at long-term follow-up. The current review aims to provide a deep overview of the rationale and modality of MCS in patients with refractory arrhythmias and/or undergoing VT catheter ablation, underlining the importance of patient selection and timing for MCS and summarizing reported clinical experiences in this field.

High-density mapping of Koch's triangle during sinus rhythm and typical atrioventricular nodal re-entrant tachycardia, integrated with direct recording of atrio-ventricular node structure potential.

BACKGROUND: The mechanism of typical slow-fast atrioventricular nodal re-entrant tachycardia (AVNRT) and its anatomical and electrophysiological circuit inside the right atrium (RA) and Koch's Triangle (KT) are not well known. OBJECTIVE: To identify the potentials of the compact AV node and inferior extensions and to perform accurate mapping of the RA and KT in sinus rhythm (SR) and during AVNRT, to define the tachycardia circuit. METHODS: Consecutive patients with typical AVNRT were enrolled in 12 Italian centers and underwent mapping and ablation by means of a basket catheter with small electrode spacing for ultrahigh-density mapping and a modified signal-filtering toolset to record the potentials of the AV nodal structures. RESULTS: Forty-five consecutive cases of successful ablation of typical slow-fast AVNRT were included. The mean SR cycle length (CL) was 784.1 ± 6 ms and the mean tachycardia CL was 361.2 ± 54 ms. The AV node potential had a significantly shorter duration and higher amplitude in sinus rhythm than during tachycardia (60 ± 40 ms vs. 160 ± 40 ms, p < .001 and 0.3 ± 0.2 mV vs. 0.09 ± 0.12 mV, p < .001, respectively). The nodal potential duration extension was 169.4 ± 31 ms, resulting in a time-window coverage of 47.6 ± 9%. The recording of AV nodal structure potentials enabled us to obtain 100% coverage of the tachycardia CL during slow-fast AVNRT. CONCLUSION: Detailed recording of the potentials of nodal structures is possible by means of multipolar catheters for ultrahigh-density mapping, allowing 100% of the AVNRT CL to be covered. These results also have clinical implications for the ablation of right-septal and para-septal arrhythmias.

Working in interventional cardiology laboratories: The perceived impact of radiation exposure as a health and gender hazard. A NEXT generation ANMCO initiative.

BACKGROUND: Gender-related discrepancies in personal and professional life have been reported among radio-exposed workers. We assessed this topic among cardiac catheterization workers in Italy, with a focus on gender and working position. METHODS: Radio-exposed workers affiliated with the Italian Association of Hospital Cardiologists were invited to answer an online survey, which included 41 questions formatted as multiple choice. RESULTS: Overall, 237 workers responded. The proportion of males was significantly higher than that of females in the population aged >50 years. A greater portion of females than males perceived female-gender discrimination regarding career advancement (77.2% vs 30.9%, p < 0.001) and work compensation (49.1% vs. 17.1%, p < 0.001). There was no difference in perceived gender- discrimination in terms of career advancement opportunities between physician and non-physicians. A larger portion of females than males experienced workplace discrimination (51.8% of females vs. 8.1% of males, p < 0.0001). Non-physician responders made up 38.8% of all respondents and reported a lower yearly radiation exposure than physicians. Non-physicians were more aware of the laws regulating lab access during pregnancy than physicians (93.5% vs. 48.3%, p < 0.0001). A greater percentage of female nurses than physicians communicate without hesitation the pregnancy status to their employers (45.6% vs 20%, p < 0.001). CONCLUSIONS: Gender-based career disparities were perceived among physicians and non-physician staff of cardiology interventional laboratories. Strategies should be implemented to ensure gender equality in career opportunities and to increase knowledge of radioprotection and the laws regulating access to laboratories during pregnancy.

[ANMCO Position paper: Ionizing radiation exposure and radioprotection in the cath-lab]. / Position paper ANMCO: Radioesposizione e radioprotezione nei laboratori di cardiologia interventistica.

In the last decades, because of the improvements in the percutaneous treatment of coronary heart disease, valvular heart disease, congenital heart defects, and the increasing number of cardiac resynchronization therapy and cardioverter-defibrillator implantations, the interventional cardiologists' radio-exposure has importantly risen, causing concerns for ionizing radiation-associated diseases such as cancer and neurodegenerative disorders. Consequently, the radiation exposure issue importantly affects operators' safety. However, our knowledge of this field is poor and most operators are unaware to be at risk, especially because of the absence of effective preventive measures. The aim of this ANMCO position paper is to improve the awareness of operators and identify new ways of reducing operator ionizing radiation dose and minimizing the risk.

Tako-Tsubo syndrome in patients with COVID-19: a single centre retrospective case series.

Growing evidence shows that COVID-19 is associated with an increase in Tako-Tsubo syndrome (TTS) incidence. We collected data from patients hospitalized in our multidisciplinary COVID-19 department who had a diagnosis of TTS during the second and third wave of the pandemic in Italy. We reported four cases of TTS associated with COVID-19. No patient had any classical trigger for TTS except for COVID-19. Mean age was 72 years (67-81) and all patients had a SARS-CoV-2-related interstitial pneumonia confirmed by computed tomography. Typical apical ballooning and transitory reduction in left ventricle (LV) systolic function with a complete recovery before discharge were observed in all patients. The mean LV ejection fraction (LVEF) at TTS onset was 42% (40-48%). ECG showed ST-segment elevation in two cases, while an evolution with negative T waves and QTc prolongation was observed in all patients. Three patients underwent coronary angiography. Two patients had Alzheimer's disease. The time interval from hospital admission to TTS onset was 4 (2-6) days, and the time interval from COVID-19 symptom onset to TTS diagnosis was 10 (8-12) days.  COVID-19 may be a trigger for TTS, though TTS pathophysiology in COVID-19 patients remains unclear, likely due to its multifactorial nature.

ANMCO position paper on vericiguat use in heart failure: from evidence to place in therapy.

In the growing therapeutic armamentarium for heart failure (HF) management, vericiguat represents an innovative therapeutic option. The biological target of this drug is different from that of other drugs for HF. Indeed, vericiguat does not inhibit neuro-hormonal systems overactivated in HF or sodium-glucose co-transporter 2 but stimulates the biological pathway of nitric oxide and cyclic guanosine monophosphate, which is impaired in patients with HF. Vericiguat has recently been approved by international and national regulatory authorities for the treatment of patients with HF and reduced ejection fraction who are symptomatic despite optimal medical therapy and have worsening HF. This ANMCO position paper summarises key aspects of vericiguat mechanism of action and provides a review of available clinical evidence. Furthermore, this document reports use indications based on international guideline recommendations and local regulatory authority approval at the time of writing.

Treatment with gentamicin-impregnated collagen sponges in reducing infection of implantable cardiac devices: 10-year analysis with propensity score matching.

INTRODUCTION AND OBJECTIVES: The incidence of device infection has increased over time and is associated with increased mortality in patients with cardiac implantable electronic devices (CIEDs). Gentamicin-impregnated collagen sponges (GICSs) are useful in preventing surgical site infection (SSI) in cardiac surgery. Nevertheless, to date, there is no evidence concerning their use in CIED procedures. Our study aims to determine the effectiveness of treatment with GICSs in preventing CIED infection. METHODS: A total of 2986 adult patients who received CIEDs between 2010 and 2020 were included. Before device implantation, all patients received routine periprocedural systemic antibiotic prophylaxis. The study endpoints were the CIED infection rate at one year and the effectiveness of the use of GICSs in reducing CIED infection. RESULTS: Among 1524 pacemaker, 942 ICD and 520 CRT implantations, CIED infection occurred in 36 patients (1.2%). Early reintervention (OR 9 [95% CI 3.180-25.837], p<0.001), pocket hematoma (OR 11 [95% CI 4.195-28.961], p<0.001), diabetes (OR 2.9 [95% CI 1.465-5.799], p=0.002) and prolonged procedural time (OR 1.02 [95% CI 1.008-1.034], p=0.001) were independent risk factors for CIED infection. Treatment with GICSs reduced CIED infections significantly ([95% CI -0.031 to -0.001], p<0.001). CONCLUSIONS: The use of GICSs may help in reducing infections associated with CIED implantation.

The polypill strategy in cardiovascular disease prevention: It's time for its implementation.

A polypill strategy has been demonstrated to improve treatment adherence in several cardiovascular disease (CVD) settings. However, data on the prognostic impact in the secondary prevention setting have been scarce. The Secondary Prevention of Cardiovascular Disease in the Elderly trial, the results of which have been recently published, has demonstrated a benefit in terms of major adverse CVD event reduction. This finding, in addition to previous evidence, should lead to a broader polypill implementation in CVD prevention.

[ANMCO Position paper: Vericiguat use in heart failure: from evidence to place in therapy]. / Position paper ANMCO: Impiego di vericiguat nello scompenso cardiaco: dalle evidenze al posizionamento terapeutico.

In the growing therapeutic armamentarium for heart failure management, vericiguat represents an innovative therapeutic option. The biological target of this drug is different from that of other drugs for heart failure. Indeed, vericiguat does not inhibit neurohormonal systems overactivated in heart failure or sodium-glucose cotransporter 2 but stimulates the biological pathway of nitric oxide and cyclic guanosine monophosphate, which is impaired in patients with heart failure. Vericiguat has recently been approved by international and national regulatory authorities for the treatment of patients with heart failure and reduced ejection fraction who are symptomatic despite optimal medical therapy and have worsening heart failure. This ANMCO position paper summarizes key aspects of vericiguat mechanism of action and provides a review of available clinical evidence. Furthermore, this document reports use indications based on international guideline recommendations and local regulatory authority approval at the time of writing.

Adaptive Response in Rat Retinal Cell Cultures Irradiated with γ-rays.

Retina can receive incidental γ-ray exposure from various sources. For example, although radiation therapy is a crucial tool for managing head and neck tumors, patients may develop ocular complications as collateral damage from accidental irradiation. Recently, there has been concern that retinal irradiation during space flight may compromise mission goals and long-term quality of life after space travel. Previously, in our in vitro model, we proved that immature retinal cells are more vulnerable to γ-radiation than differentiated neurons. Here, we investigate if a low-dose pre-irradiation (0.025 Gy), known to have a protective effect in various contexts, can affect DNA damage and oxidative stress in cells exposed to a high dose of γ-rays (2 Gy). Our results reveal that pre-irradiation reduces 2 Gy effects in apoptotic cell number, H2AX phosphorylation and oxidative stress. These defensive effects are also evident in glial cells (reduction in GFAP and ED1 levels) and antioxidant enzymes (catalase and CuZnSOD). Overall, our results confirm that rat retinal cultures can be an exciting tool to study γ-irradiation toxic effects on retinal tissue and speculate that low irradiation may enhance the skill of retinal cells to reduce damage induced by higher doses.

New insights into atrioventricular nodal anatomy, physiology, and immunochemistry: A comprehensive review and a proposed model of the slow-fast atrioventricular nodal reentrant tachycardia circuit in agreement with direct potential recordings in the Koch's triangle area.

Atrioventricular nodal reentrant tachycardia (AVNRT) is the most frequent regular tachycardia in humans. In this review, we describe the most recent discoveries regarding the anatomical, physiological, and molecular biological features of the atrioventricular junction that could underlie the typical slow-fast AVNRT mechanisms, as these insights could lead to the proposal of a new theory concerning the circuit of this arrhythmia. Despite several models have been proposed over the years, the precise anatomical site of the reentrant circuit and the pathway involved in the slow-fast AVNRT have not been conclusively defined. One possible way to evaluate all the hypotheses regarding the nodal tachycardia circuit in humans is to map this circuit. Thus, we tried to identify the slow potential of nodal and inferior extension structures by using automated mapping of atrial activation during both sinus rhythm and typical slow-fast AVNRT. This constitutes a first step toward the definition of nodal area activation in sinus rhythm and during slow-fast AVNRT. Further studies and technical improvements in recording the potentials of the atrioventricular node structures are necessary to confirm our initial results.

Rationale and design of the sirolimus eluting balloon utilization for treatment of vasculogenic erectile dysfunction: the SUASION Registry.

BACKGROUND: Conventional angioplasty balloon catheter, drug coated balloon (DCB), or angioplasty with drug eluting stent (DES) have been used on the percutaneous treatment of erectile dysfunction (ED). Currently available DCBs are paclitaxel eluting balloon (PEB), very recently, sirolimus eluting balloon (SEB). Although endovascular revascularization with balloon resulted in improvement of ED, there have been no prior reports on the feasibility of SEB treatment for ED. METHODS: We present an observational, retrospective-prospective multicentre registry in patients evaluating the use of SEB for the treatment of de novo stenosis in native internal pudendal arteries. We will include 100 patients affected by vasculogenic ED non responder to PDE5i with up to two lesions requiring treatment. ED patients should present a IIEF-5 Score<15, positive dynamic doppler (PSV <25 cm/s) and/or evidence at basal CT angiography. At 30 days, 180, 240, and 365 days following the index procedure, IIEF-5 score will be assessed, and medication regimen and adverse event monitoring will be assessed. At 8 months a dynamic Doppler will be performed. Patients will be followed up for 2 years. The primary endpoints are the Delta IIEF-5 Score and a Delta PSV between basal and 8 months follow-up. The secondary endpoint is the incidence of major adverse event (MAE), binary restenosis and late loss in patients who will repeat control angiography if clinically indicated. CONCLUSIONS: Considering the limitations and safety concerns of PEB, POBA and DES used so far in ED clinical investigations, we hypothesize that sirolimus nanocarriers-coated balloon can potentially be an improved next-generation treatment for ED patients.

Autologous Immune Cell-Based Regenerative Therapies to Treat Vasculogenic Erectile Dysfunction: Is the Immuno-Centric Revolution Ready for the Prime Time?

About 35% of patients affected by erectile dysfunction (ED) do not respond to oral phosphodiesterase-5 inhibitors (PDE5i) and more severe vasculogenic refractory ED affects diabetic patients. Innovative approaches, such as regenerative therapies, including stem cell therapy (SCT) and platelet-rich plasma (PRP), are currently under investigation. Recent data point out that the regenerative capacity of stem cells is strongly influenced by local immune responses, with macrophages playing a pivotal role in the injury response and as a coordinator of tissue regeneration, suggesting that control of the immune response could be an appealing approach in regenerative medicine. A new generation of autologous cell therapy based on immune cells instead of stem cells, which could change regenerative medicine for good, is discussed. Increasing safety and efficacy data are coming from clinical trials using peripheral blood mononuclear cells to treat no-option critical limb ischemia and diabetic foot. In this review, ongoing phase 1/phase 2 stem cell clinical trials are discussed. In addition, we examine the mechanism of action and rationale, as well as propose a new generation of regenerative therapies, evolving from typical stem cell or growth factor to immune cell-based medicine, based on autologous peripheral blood mononuclear cells (PBMNC) concentrates for the treatment of ED.

Repurposing Dipyridamole in Niemann Pick Type C Disease: A Proof of Concept Study.

Niemann Pick type C disease (NPC) is a rare disorder characterized by lysosomal lipid accumulation that damages peripheral organs and the central nervous system. Currently, only miglustat is authorized for NPC treatment in Europe, and thus the identification of new therapies is necessary. The hypothesis addressed in this study is that increasing adenosine levels may represent a new therapeutic approach for NPC. In fact, a reduced level of adenosine has been shown in the brain of animal models of NPC; moreover, the compound T1-11, which is able to weakly stimulate A2A receptor and to increase adenosine levels by blocking the equilibrative nucleoside transporter ENT1, significantly ameliorated the pathological phenotype and extended the survival in a mouse model of the disease. To test our hypothesis, fibroblasts from NPC1 patients were treated with dipyridamole, a clinically-approved drug with inhibitory activity towards ENT1. Dipyridamole significantly reduced cholesterol accumulation in fibroblasts and rescued mitochondrial deficits; the mechanism elicited by dipyridamole relies on activation of the adenosine A2AR subtype subsequent to the increased levels of extracellular adenosine due to the inhibition of ENT1. In conclusion, our results provide the proof of concept that targeting adenosine tone could be beneficial in NPC.

Matching Imaging and Remodulation Effects: Benefits of Cardiac Contractility Modulation Shown by Global Longitudinal Strain: A Case Report.

Cardiac Contractility Modulation (CCM) has been proposed for inpatients affected by heart failure with reduced ejection fraction (HFrEF), with relapsing HF symptoms. We present a case of a patient treated with percutaneous coronary intervention (PCI) in the setting of acute coronary syndrome without persistent ST-segment elevation, with the best medical therapy for decompensated HF. The patient refused the implantable cardioverter-defibrillator (ICD), and to reduce the increasing number of hospitalizations for HF exacerbations, we proposed the use of the cardiac contractility modulation device. After the implant, the patient demonstrated a marked improvement in exercise effort and quality of life (QOL) with a six-minute walk test (SMWT), Minnesota Living with Heart Failure Questionnaire (MLWHFQ), and echocardiographic parameters. At 9 months after discharge, no hospital admissions for HF were recorded. We showed with the speckle tracking imaging how the improvement in global longitudinal strain (GLS) correlates with the remodeling effects on myocardial cells.

Unequal opportunities in Italian cardiovascular research: focus on gender.

BACKGROUND: Despite unanimous calls for more equitable access and support to female researchers, there are persistent barriers to women's career progression and professional fulfillment. These discriminative hurdles undermine female gender in science and have detrimental effects on research activities and female professionals and patients. There is no data on women's outlook in cardiovascular research in Italy, which limits appropriate remedial actions. We aimed at providing an updated perspective on top Italian cardiovascular researchers, focusing on women versus men comparisons. METHODS: Top Italian cardiovascular researchers were retrieved from a dedicated and validated Scopus query. Researchers' sex was assigned according to the given name with a consensus process. Several metrics were compared, including global rank, total cites, total cites adjusted by academic age, H-index, and self-citation percentage. Bivariate and propensity score-adjusted analyses were used for inferential purposes. RESULTS: Our analysis shows the existence of a gender gap: the number of scientific articles published by Italian male researchers in their careers is significantly higher than their female counterparts (P=0.002). For men, the year of first publication is earlier (P=0.001); they also published more articles as a single author, or single + first author or single + first + last author. Men's papers cited at least once were more than those of women (P≤0.001), and the total number of citations was significantly higher for men (P=0.002). These results remain significant both in the analysis excluding self-citations as well as in the analysis including self-citations. The single-year analysis (2019) confirms the significance of the career analysis, adding that men have a higher rank based on composite score (P=0.041, or P=0.005 if including self-citation). Finally, men have a higher percentage of self-citation in 2019 than women (P=0.008). CONCLUSIONS: The gender disparity is still a limiting factor in Italian cardiovascular research. Despite career advancement, women continue to be underrepresented. Men retain more leadership positions in academia and maintain the edge for scientific work productions. More efforts are needed to ensure equity between men and women.