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An 81-years-old with a history of hypertension, dyslipidemia, and chronic ischemic heart disease with prior stent implantation of right coronary artery in 2011. Due to its poor compliance, no recurrent symptoms, and, finally, the COVID-19 pandemic, the patient did not perform any cardiological follow-up during these years. Unfortunately, the last six months he has reported the onset of dyspnea and typical angina due to moderate efforts, undervalued by the patient. Because of the rapid worsening of dyspnea and typical angina in the last 5 days, he went to the local emergency department (ED). The role in/role out routine exams performed in the ED documented a COVID-19 infection. At the ED, his vital signs were normal, with a blood pressure of 135/75 mm Hg, heart rate of 74 regular beats/min, body temperature of 36.5 °C, oxygen saturation of 97% in ambient air, and respiratory rate of 16/min. Of note, the chest x-ray was normal, as well as no alterations were documented at the CT scan performed a few hours later. First-line blood sample tests were within range except for Hb 10 mg/dl. Therefore, a cardiological evaluation was requested. Electrocardiogram (ECG) showed inverted T-waves in V1-4 leads, and echocardiography showed normal left ventricular ejection fraction (FE 55% Simpson), left ventricular anterolateral wall hypokinesia, and severe aortic stenosis (V max 4.78 m/s, Gr max 4.78 m/s, Gr medium 59 mmHg). Since myocardial necrosis enzymes were increased (T-hs 118.7 ng/dl; CK-MB 6.3 ng/L; NT-ProBNP 761 ng/dl), leading to the suspicion of acute coronary syndrome the patient underwent coronary angiography, showing critical stenoses of the left descending artery (LAD), circumflex (LCX), I obtuse marginal (IOM), and patent stent of the right coronary artery. Therefore, the Heart team deemed the patient at high operatory risk choosing, in agreement with the patient, for a percutaneous coronary intervention (PCI) followed by TAVR. Accordingly, the patients underwent PCI of LAD with the implantation of a Xience-Serra 3.0×15 mm and PCI of LCX with the implantation of an Onyx 2.75×18 mm stent. After COVID -19 resolution, which happen 7 days later, the patient was moved to our cardiology department. Two days later in the same procedure, we performed the first PCI of I-OM with the implantation of a Xience Sierra 3.0×18 mm stent following a TAVI with the implantation of Evolute Pro valve 29 mm. The post-procedure echocardiogram showed an optimal valve position with a transvalvular mean pressure gradient of 4 mm Hg. After six days post-TAVI, for a complete atrioventricular block, the patient also underwent a pacemaker implantation. The patient was finally discharged after 10 from TAVI. Discussion This case report offers several foods for thought. First, the COVID-19 pandemic has negatively affected primary and secondary prevention, even for patients affected by cardiovascular disease. Our patient has postponed clinical checks even when the symptoms reappeared, also because of the concerns lead by the COVID-19 pandemic. Second, completeness and timing of coronary disease revascularization, which in this case was staged and performed before TAVI. Finally, the late occurrence of advanced heart block requiring PM implantation. For instance, in an era of fast-track TAVI, more studies are warranted to identify patients who are at higher risk of late PM implantation.

Aims The ideal phenotype of patients with functional mitral regurgitation (FMR) who benefit most of transcatheter edge-to-edge repair (TEER) is still unclear. Some studies have suggested that patients with disproportionate FMR may have a better outcome. The purpose of this study is to evaluate the prognostic value of proportionate versus disproportionate FMR, in patients undergoing TEER with MitraClip system. Methods and Results The multicenter observational MITRA-CTV registry includes 200 patients with moderate-severe (3+) to severe (4+) FMR undergoing MitraClip, between March 2013 and June 2021, at three European institutions such as Magna Graecia University of Catanzaro, University of Turin (Italy) and University of Vigo (Spain). Patients were defined as having proportionate or disproportionate FMR if their EROA/LVEDV (left ventricular end diastolic volume) ratio was ≤ or > from the median value (0.15), respectively. The primary endpoint was the composite of death from all causes and rehospitalizations for HF, at 1-year follow-up. The secondary endpoint was composed of the individual components of the primary endpoint and cardiovascular death. Patients with disproportionate FMR had higher EROA (0.47±0.2 cm2 vs 0.27±0.1 cm2) and smaller ventricles (LVEDV: 207 ± ml vs 239 ± 83 ml) than those with proportionate FMR. Procedural success was achieved in 95% of patients. Notably, 30-day residual MR was comparable in patients with disproportionate versus proportionate FMR. There were 4 (2%) deaths during hospitalization, and the median hospital stay after the procedure was 9 days (IQR 7- 9 days). At Kaplan-Meier analysis, an EROA/LVEDV ratio both higher and lower than the median value (0.15) was not associated with an increased incidence of the primary endpoint of death and rehospitalization for HF (HR 1.17 CI 95%[0.72;1.90],p=0.50). The only independent predictors of clinical outcomes at 1 year were: the presence of CKD (HR 4.11 95% CI[1.73;9.75], p=0.0014) and a post TMVR hospital stay >10 days (HR 2.53 95% CI[1.24;5.18],p=0.0111). Conclusion In our study, there were no significant differences in outcome in patients with proportionate versus proportionate FMR undergoing TEER with Mitraclip system.

Background Gender Identity (GI) is defined by a complex interplay between biological, psychological, environmental, and cultural factors. Health care services provide counseling, hormone treatment, and gender-affirming surgery. Testosterone is used for cross-sex hormone therapy in female-to-male transgender persons. Previous evidence suggests that testosterone administration is associated with hypertension, decreased high-density lipoprotein (HDL), increased low-density lipoprotein (LDL), and obesity, thus increasing cardiovascular risk. Hereafter, we report the case of a patient female-to-male on testosterone therapy undergoing percutaneous coronary intervention (PCI) and stent implantation for acute myocardial infarction. Case Description A 44-year-old Italian transgender (female-to-male) without common cardiovascular risk factors and family risk was admitted to the local emergency room with a sudden onset of anterior chest pain. The electrocardiogram showed anterior ST-Segment Elevation, and accordingly, the patient was transferred to our Institution for emergency coronary angiography. Past medical history revealed breast reduction, osteosynthesis of the right femur, hemorrhoidal pathology, and iron deficiency anemia. Of interest, drug history revealed a hormonal therapy with intramuscular testosterone undecanoate over the from 2005 for gender conversion (250 mg every 3 weeks) and Tamoxifen 20 mg/die from 2006. The coronary angiography performed after 90 minutes to the symptom onset revealed a total occlusion of the proximal left anterior descending artery (LAD) and minimal atherosclerosis of the remaining vessels. Recanalization of the LAD was achieved by pre-dilatations with a 2.5×15mm balloon catheter, showing diffuse atherosclerosis of the middle and distal LAD involving the origin of a diagonal branch (Medina 1,1,1). Then the lesion was treated with the implantation of three drug-eluting stents in overlap, followed by POBA (Plain Old Balloon Angioplast) of the diagonal branch with a 2.5×12 mm balloon at the ostium (Final TIMI flow III). The patient was then moved to the intensive care unit. Laboratory tests showed an altered lipid panel (overall cholesterol 210 mg/dl and LDL-cholesterol 153 mg/dl), elevated levels of cardiac enzymes (CK-MB 92.5 ng/ml, myoglobin 1606 ng/ml, TnT hs 1014 ng/L and NTproBNP 1263 pg/ml) and anaemia (Hb 9,1 mg/dl). The echocardiogram revealed akinesia of the apex with thrombotic formation (2.0×1.0 mm) and mid-distal anterior wall, with a 40% ejection fraction. Accordingly, parenteral anticoagulant was started. No further complications were observed the day after the procedure, with a progressive reduction of the miocardionecrosis enzymes and thrombotic formation. Ten days after, at the resolution of the thrombotic formation, the patient was discharged. Discussion This case report highlights the importance of primary prevention in patients undergoing long-term testosterone therapy for gender conversion, regardless of age and risk factors. For instance, prior evidence about the risk of recurrent ischemic events in these high-risk patients is poor with a high heterogeneity across the studies. Accordingly, high quality prospective and multicentric studies are needed to assess if there is a correlation between hormonal therapy for gender conversion and cardiovascular disease.

Background mitral regurgitation (MR) is the second most common valvular heart disease in Europe. In the contest of functional (or secondary) MR recently has emerged a new entity, the atrial functional MR. This form is due to left atrial dilatation, it has no significant degenerative change in mitral valve complex or significant LV systolic disfunction. Conversely the ventricular functional mitral regurgitation (V-FMR) is due to systolic disfunction and left ventricular dilatation. Aim the aim of this study was to evaluate the differences in clinical characteristics and outcomes of patients with AFMR and VFMR treated with Mitraclip. Methods a retrospective analysis collected consecutive patients with functional MR who underwent transcatheter mitral valve repair using Mitraclip system in our division. A total of 161 patients were divided into the following two categories: VFMR (127 patients), defined as EF48 mL/m2. Baseline and clinical characteristics, echocardiographic parameters and 12 months clinical outcomes (overall mortality at 12 months, MACE at 12 months, re-hospitalization for heart failure (HF), re-hospitalization from other causes at 12 months and number of re-hospitalization at 12 months) were analyzed. Results compared to AFMR, patients with VFMR were younger (73 vs 78 years) had a higher man prevalence (72,4% vs 50%), higher rate of: hypercholesterolemia (79,5% vs 67,6%), smokers (14,2% vs 5,9%), diabetes (39,4% vs 20,6%), chronic kidney disease (55,9% vs 47,1%), NT-proBNP mean value (4403,437 pg/ml vs 2063,409 pg/ml), NYHA class ≥III (84.3 vs 52.9%) and lower rate of hypertension (85% vs 97.1%). In AFMR population there was higher prevalence of atrial fibrillation (70.6% vs 45.7%) and tricuspid valve regurgitation ≥2+ (82.3% vs 68,5%). Moreover, in this group, was lower the all-cause mortality rate at 12 months (9.4 vs 22%), MACE at 12 months (4.5 vs 24.5%), re-hospitalization for HF (15.6% vs 33.1%), re-hospitalization from other causes at 12 months (18.8% vs 31.6%) and number of re-hospitalization at 12 months ≥1 (31,3% vs 59.9%). Conclusion our analysis demonstrated that clinical outcomes at 12 months were lower for the AFMR group. These data are consistent with the literature, where AFMR is considered to have a better prognosis than VFMR, and underline the importance of differentiating these two types of population.

Background Multivessel disease occurs in approximately half of patients presenting with STEMI and the best management non-culprit lesions is still unclear. The case reported a patient with inferior STEMI, in which the non-culprit lesion has been evaluated with a “full-physiology” approach by a pressure wire. Case Description A 52-year-old woman with a history of hypertension and diabetes was admitted to our center diagnosed with inferior STEMI. Coronary angiography showed a thrombotic occlusion (TIMI 0) of the right coronary artery (culprit lesion) and intermediate stenosis of proximal left anterior descending (LAD). Primary PCI (p-PCI) of the right coronary artery has been performed. After 4 days a stepwise complete physiological approach on the LAD artery has been performed. The physiological study showed a negative discrepancy between FFR - and RFR + with increased index of microvascular resistance (IMR). Discussion The fractional flow reserve (FFR) represents the best-known invasive method for the functional evaluation of intermediate coronary stenosis. Unlike the FFR, the resting flow ratio RFR is a non-hyperemic index that does not require the administration of a vasodilator such as adenosine as does the iwFR. There are many factors that can lead to a negative discrepancy between hyperemic and non-hyperemic indices. In the case presented, the functional values found were: FFR: 0.90 RFR: 0.86 and IMR = 76; CFR = 1.0. The FFR-/ RFR+ disagreement may reflect the attenuating influence of microvascular disease on adenosine-mediated vasodilation. Therefore, we decided to treat the LAD lesion according the RFR value with a DES 3.0×33 mm implantation. Conclusion Myocardial infarction can result in altered microvascular and endothelial dysfunction also in the non-culprit territory. The FFR - / RFR + disagreement may reflect the attenuating influence of microvascular disease on adenosine-mediated vasodilation.

Aims Mitral regurgitation is the second-most frequent VHD in Europe. According to the latest ESC Guidelines, transcatheter edge-to-edge repair (TEER) was included as a treatment option in patients with severe symptomatic MR at high risk for surgery (Class IIb recommendation) for primary MR and a Class IIa recommendation for secondary MR. We sought to investigate predictors of clinical outcome in patients with mitral regurgitation undergoing percutaneous valve repair. Methods and Results The MITRA-UMG study, a single-center registry, retrospectively collected consecutive patients with symptomatic moderate-to-severe or severe MR undergoing MitraClip therapy between March 2012 to October 2021 at Magna Graecia University. Clinical, echocardiographic and procedural data were collected and compared with post procedural outcomes. Procedural success was defined as successful implantation of one or more clip(s) with a post-procedure reduction of MR of 2 + or less at discharge. The primary endpoint was the composite of cardiovascular death or rehospitalization for heart failure. The median follow-up was 456 days (IQR 372–1130 days) with a complete 1-year follow- up in 188 of 200 (97%) patients. A functional aetiology was classified in 75% of patients. Procedural success was obtained in 98% of patients. The composite primary endpoint of cardiovascular death or rehospitalization for HF was met in 77 patients (36%) with cumulative incidences of 7% at 30 days and 25% at 1 year. In the Cox multivariate model, NYHA functional class and left ventricular end-diastolic volume index (LVEDVi), independently increased the risk of the primary endpoint at long-term follow-up. At Kaplan–Meier analysis, a LVEDVi > 92 ml/m2 was associated with an increased incidence of the primary endpoint (HR 3.55, 95%CI [2.03, 6.18], P Conclusions In this study, patients presenting with dilatated ventricles (LVEDVi > 92 ml/m2) and advanced heart failure symptoms (NYHA IV) carried the worst prognosis after TEER.

Background Vascular access complications are a significant source of morbidity and mortality after transcatheter aortic valve replacement (TAVR). Ultrasound-guided cannulation (UGC) of central veins or arteries is a widely used approach for patients undergoing invasive procedures. Whether UGC significantly decreases the risk of vascular access complications also for large-bore access procedures, such as TAVR, lacks evidence Objectives in this study, we aimed to evaluate the benefits of routine use of UGC in patients undergoing TAVR. Methods Data were retrospectively collected from two high-volume TAVR centers from September 2009 to March 2022. UGC was performed using a two-dimensional ultrasound short-axis views, while manual palpation, fluoroscopy, or contralateral angiography were used for the other patients. The odds ratio (OR) for vascular complications was calculated using a multivariate logistic regression model including as dependent variables all relevant baseline and procedural characteristics (forward stepwise selection process). Vascular complications were adjudicated according to the Valve Academic Research Consortium definitions 3. Results Out of 874 patients included in the study, UGC access was performed in 177 subjects. Overall mean age was 80.2±5.8 years old, 60% of patients were females, 35.5% had diabetes, 61.4% had dyslipidemia, and 27.8% had chronic kidney disease, with a mean left ventricular ejection fraction of 52.7±9.7%. Looking at the procedural variables Euroscore II was 5.8±5.4, second and third valves generation have been used in 85% of the cases, while suture-based closure devices in 84% of subjects. After adjustment for clinical and procedural variables, routinely use of UGC was associated with a lower rate of total [Odds Ratio (OR): 0.38; 95% confidence interval (CI) 0.15% to 0.95%)] and major vascular complications [Odds Ratio (OR): 0.21; 95% confidence interval (CI) 0.05% to 0.75%)], while no differences were observed for minor vascular complications. Conclusions Routinely use of UGC significantly decreases the risk of vascular complications in patients undergoing TAVR. However, a dedicated randomized clinical trial assessing the safety and efficacy of this approach is warranted to confirm our results in this high-risk population.

Background Calcified coronary artery disease and severe valvular aortic stenosis (AS) often coexist. For instance, severely calcified lesions may strongly influence the revascularization strategy in patients undergoing transcutaneous aortic valve replacement (TAVR). Shock wave intravascular lithotripsy (S-IVL) (Shockwave Medical Inc. Santa Clara, CA) is the only technology available that cracks both medial and intimal calcium while minimizing trauma to the vessel wall, thus allowing a safe plaque debulking. We report a case of percutaneous coronary intervention (PCI) and TAVR in the same procedure, where S-IVL has been used to treat a heavily calcified lesion and optimize stent under-expansion. Case Report A 79 years-old male patient with a history of diabetes mellitus type 2, hypertension, and peripheral artery disease, was admitted to our institution with symptomatic severe AS and severe calcified left anterior descending (LAD) artery lesion at CT scan. Deemed eligible for TAVR, Heart Team planned a percutaneous coronary intervention (PCI) of LAD and TAVR in the same procedure. Through the left radial artery, coronary angiography confirmed 90% stenosis of the LAD at the central segment. Accordingly, pre-dilatation of the stenosis was performed with a 2.5×12 mm non-compliant balloon (NCB) and, because of the severe calcification, S-IVL with a 3.0×12 mm balloon inflated at 4-6 Atmospheres (ATM), delivering 40 pulses. Following, a 3.5×18-mm drug-eluting stent was implanted at 18 ATM. After implantation, an inadequate expansion of the stents was observed, which persisted despite post-dilation with 3.75×8 mm NCB at high-pressure. Bail-out S-IVL was then performed with the 3.0×12 mm balloon inflated at 4-6 ATM, delivering 40 pulses in-stent, followed by a further stent post-dilated with a 3.75×8 mm NCB up to 20 ATM. The final angiogram showed a satisfactory stent expansion. Since the low contrast volume was used, we decided to go ahead with transfemoral TAVR. Therefore, through the left femoral artery access, a 34-mm self-expandable Evolut R valve was implanted. Transthoracic echocardiography showed optimal valve implantation with a trivial periprosthetic leak. No complications were observed after the procedures and the patient was discharged after 6 days with 6 months of mandated dual antiplatelet therapy (Aspirin and Clopidogrel). Discussion In this case, the bail-out use of S-IVL was essential for an optima stent implantation, allowing TAVR procedure and avoiding prolonged theoretical antithrombotic therapy underlying suboptimal stent implantation. Despite encouraging initial results, future large studies with long-term observation are required to evaluate the safety and efficacy of S-IVL in this scenario.

Hemorrhages represent one of the most frequent complications during TAVI. Their rapid recognition and a prompt treatment are necessary to avoid hemorrhagic shock, which can lead the patient to death in a short time. We report the case of a 79-year-old woman affected by severe and symptomatic aortic stenosis, who underwent TAVI in our Cath-lab. Through a right femoral echo-guided arterial access, implantation of a 26 mm self-expandable aortic bio-prosthesis and hemostasis in the site of puncture with 18F Manta vascular closure device were performed. At the end of the procedure, through radial artery, a femoral angiography was performed, showing an important leak of contrast medium upper the site of puncture, without any change in arterial pressure or heart rate. After echo-guided cannulation of left femoral artery with 8F sheath, implantation of endoprosthesis in the site of hemorrhage and hemostasis of left femoral artery with 8F AngioSeal VIP vascular closure device were performed. In cardiac intensive care unit (CICU) low dosage of vasoactive agents and blood were administered, guaranteeing a good arterial pressure. Computed tomography (CT) was performed after two days and confirmed the presence of a retroperitoneal hematoma, without active bleeding. After six days, the patient left CICU and was admitted to the cardiological ward, starting a gradual mobilization. However, after 48 hours she reported abdominal pain and became rapidly hypotensive, tachycardic and asthenic, requiring readmission in CICU. Serum exams showed low hemoglobin concentration, an abdominal CT was perfomed, showing an active bleeding from left femoral artery and a homolateral retroperitoneal hematoma. The patient was rapidly lead in the cath lab. Angiography confirmed the hemorrage and an endoprosthesis was successfully implanted in the left femoral artery. Blood and vasoactive agents were administered with a progressive improvement in hemodynamic and clinical conditions of the patients. Post-operative course was complicated by fever and empiric antiobiotic therapy was administered until blood culture revealed no bacterial growth. A third CT showed the stability of the hematomas and the absence of active bleeding, allowing hospital discharge of the patient. Vascular complications are frequent and sneaky during TAVI procedures. A prompt treatment is of paramount importance to prevent hemorrhagic shock. TAVI operators should have experience in the field of peripheral intervention for the management of vascular complications.

Objective interventional edge-to-edge repair by MitraClip ™ is widely demonstrated to be able to reduce the degree of MR in patients with high surgical risk. The left atrial (LA) dysfunction in patients with severe MR is associated with poor prognosis and its changes after MV repair is reported in several studies. While, little is known about the full evaluation of the LA function by Two-dimensional speckle echocardiography tracking (2D STE) Materials and methods from March 2015 to December 2021, clinical and echocardiographic data of 67 patients with MR who underwent Mitraclip™ implantation in our division were evaluated for LA function. Strain Reservoir (S_R), Conduit Strain (S_Cd), Contractile Strain (S_Ct), LA emptying Fraction (LAEF_4CH), LAESV (Left atrial end-systolic volume), LAEDV (Left atrial end-diastolic volume) at baseline, at 1 month, at 6 months and 1 year of follow up were assessed. The variation of continuous variables was evaluated using a student T test for paired data. The categorical variables between baseline, at 1 month, at 6 months and 1 year of follow up were evaluated using the ANOVA test. The Multiple Bonferroni test comparison was conducted as a post hoc analysis P values Results the etiology of the MR was primary in 29,2% and secondary in 70,8% of the included patients. The MR degree was 3+ in 16,9% of patients and 4+ in 81,5%. When compared to baseline at 6 months and 1 year a statistically significant improvement was observed for LAEF_4CH (p 0.006 and Conclusions the MR improvement after MitraClip™ procedure allows hemodynamic changes with LA remodeling which can be detected by 2D STE through an improvement in LA function. These data emphasize the hypothesis that these echocardiographic parameters represent an advanced method to evaluate the response to device implantation.

An 87-year-old male patient with worsening dyspnea was admitted to our institution. The patient had a history of acute myocardial infarction treated with coronary stenting of the left descending artery (LAD), diagonal (Diag), right coronary artery (RCA), and chronic kidney disease. For acute pulmonary edema, the patient was admitted to our cardiac intensive care unit and rapidly treated with non-invasive positive-pressure ventilation with continuous positive airway pressure (C-PAP), IV high dosage diuretic therapy, inotropes, and vasoactive agents. Chest X-ray revealed cardiomegaly (cardiothoracic ratio, 56%) and pulmonary congestion. Electrocardiogram revealed sinus tachycardia and diffuse ST-segment abnormalities. An echocardiogram demonstrated left ventricular apical akinesia, with a left ventricular ejection fraction (LVEF) of 25% and severe mitral regurgitation. Blood tests revealed very high levels of NT-pro-brain natriuretic peptide (NT-proBNP) (>30000 pg/ml) and myocardial necrosis markers (hs-Trop 5055 ng/l; CK-MB 72 ng/ml). After 24 hours, the patient was placed on intra-aortic balloon pump (IABP) support to further hemodynamic support through the right femoral artery, nonetheless, he showed no improvement in symptoms or urine output. Because of a state of hypoxemic and hypercapnic respiratory failure, non-invasive ventilation (NIV) was given to the patient with a gradual improvement in blood gas analysis. The optimization of diuretic therapy allowed to treat the state of acute oliguric kidney disease, avoiding dialytic treatment. After 48 hours, because of a new worsening in hemodynamic state, we decided for a percutaneous left ventricular assist device (Impella CP, Denver, Massachusetts, USA). After placing the Impella device, coronary angiography was performed, showing critical stenosis of the left main (LM), involving the origin of the left anterior descending artery and a collateralized chronic occlusion of the circumflex artery and the LAD, after the origin of a large first diagonal branch. Because of the high procedural risk, we decided to perform only percutaneous coronary intervention and stent implantation of LM. After 3 days his symptoms improved, the required dose of inotropic agents and furosemide decreased and Impella was removed. After 12 days the patient was admitted to the cardiological ward and discharged after 21 days because of a urinary infection requiring antibiotic therapy. The management of acute heart failure in very old patients is challenging, limiting in many cases the use of invasive procedures such as coronary angiography or left ventricular assist devices. In this case, although the patient presented a very high-risk profile considering age and comorbidities, the use of Impella resulted to be safe and guaranteed hemodynamic support during the procedure of revascularization and in the immediate post-operative phase.

Background Transcatheter aortic valve replacement (TAVR), is the treatment of choice for most patients with aortic stenosis. Transfemoral access remains the most widely used peripheral vascular approach for TAVR and dedicated plug-based or suture-based vascular closure devices are available to achieve femoral hemostasis. However, the comparative safety of such strategies is controversial in patients undergoing transfemoral TAVR. Objectives in this study, we aimed to evaluate the rates of vascular access complications according to the use of plug-based or suture-based vascular closure in patients undergoing TAVR. Methods Data were retrospectively collected from two high-volume TAVR centers from September 2009 to March 2022. Patients were categorized according to the use of plug-based or suture-based vascular closure devices. The plug-based platform used was MANTA (Teleflex), while the suture-based devices were the Perclose ProGlide™ or the Prostar™ Systems (Abbott Vascular). Baseline demographic, clinical, and echocardiographic variables were compared between these groups using an independent-sample Student's t-test for continuous variables, presented as mean±SD, and the chi-square test for categorical or binary variables, presented as number and percentage, as appropriate. The odds ratio (OR) for vascular complications was calculated using a multivariate logistic regression model including as dependent variables all relevant baseline and procedural characteristics. The closure device variable was included in the multivariate model using the Prostar™ XL device group as reference. Vascular complications were adjudicated according to the Valve Academic Research Consortium definitions 3. Results Out of 874 patients, hemostasis was achieved with Prostar™ XL PVS in 120 (13.7%) patients, with Perclose ProGlide™ in 525 (60.1%), and with MANTA 229 (26.2%). No differences in age and common cardiovascular risk factors were observed between the group except for the prevalence of peripheral arterial disease (30.6% vs. 17.0%, p Conclusions Both suture-based and plug-based devices have comparable outcomes with regard to the risk of vascular complications. Further randomized clinical trials are warranted to confirm this observation in high-risk sub-group patients with for example heavily calcified access or obesity.

Background The most commonly used method to assess peripheral oxygen saturation (SpO2) in clinical practice is pulse oximetry. Smartwatches are widespread and are increasingly being used for digital health information. The smartwatch Apple Watch 6 was developed with a new sensor and an app that allows taking on-demand readings of blood oxygen and background readings, day and night. Aims The primary aim of the study was the head-to-head comparison of the measurements of SpO2 and heart rate (HR) by the smartwatch and the standard pulse oximeter. The secondary aim was the comparison of the measurements of SpO2 and HR between subgroups (lung disease, cardiovascular disease, healthy subjects). Methods and results We enrolled study participants with lung or cardiovascular disease and healthy subjects. A total of 265 subjects were screened for enrollment in this study. After screening, 257 subjects were included in the present study. The measurements of SpO2 and HR were obtained with the Apple Watch 6 and the Nellcor system and taken within 1 minute of each other in order to ensure comparability between the two devices. The correlation between the two technologies was assessed using linear regression and estimated with Pearson analysis for normally distributed data and Spearman analysis for nonparametric data. A plot of the differences between techniques was created according to the method described by J.M. Bland and D.G. Altmann. We observed a strong positive correlation between the smartwatch and the standard commercial device in the evaluation of SpO2 measurements (r=0.89, p< 0.0001; Figure 1A) and HR measurements (r=0.98, p< 0.0001; Figure 1B). A very good concordance was found between SpO2 (bias, -0.2289; SD, 1.66; lower limit, -3.49; and upper limit, 3.04; Figure 2A) and HR (bias, -0.1052; SD, 2.93; lower limit, -5.84; and upper limit, 5.63; Figure 2B) measured by the smartwatch in comparison with the standard commercial device using Bland–Altman analysis. We observed similar agreements and concordance even in the different subgroups. Conclusions In conclusion, our study demonstrates the feasibility and agreement of the Apple Watch 6 compared with the standard device used to assess SpO2 in patients with cardiovascular or lung diseases and in healthy subjects.

Background The COAPT randomized trial has shown a huge benefit in the survival of patients with heart failure and functional mitral regurgitation treated with Mitraclip. However, patients in COAPT trial were highly selected and the clinical course in real-world patients with and without fulfilment of the trial inclusion criteria is unclear. Methods and Results The present study examined the clinical outcome in consecutive patients (n=146) with symptomatic moderate-to-severe or severe MR of dominant functional etiology undergoing Mitraclip therapy by the presence of the inclusion criteria of the COAPT trial (left ventricular ejection fraction >20%, left ventricular end-systolic dimension 4 cm2, no prior mitral valve leaflet surgery or any currently implanted prosthetic mitral valve or any prior transcatheter mitral valve procedure). The primary endpoint was the composite of all-cause mortality or heart failure hospitalization. Secondary endpoints were the single components of the primary endpoint (heart failure hospitalization, all-cause mortality) and cardiovascular mortality. Among 146 patients who underwent Mitraclip implantation 35.6% fulfilled the inclusion criteria of COAPT. The composite endpoint was significantly less frequent in patients fulfilling the COAPT selection criteria than in those not fulfilling the criteria [HR 0.3851 (0.2266 to 0.6642); p=0.0017] (Figure). Conclusion In this single center study the outcome of patients with functional mitral regurgitation undergoing Mitraclip therapy was significantly worse in patients not fulfilling COAPT inclusion criteria, indicating that these criteria might help identify futility.

Aims Patients affected by severe functional Mitral Regurgitation (MR) complaining symptoms despite optimal medical therapy should undergo intervention. When the surgery, the gold standard, is not indicated due to high surgical risk, the transcatheter edge-to-edge repair (TEER) should be considered, if feasible. In patients undergoing TEER, the clinical outcome is not always optimal and strongly correlates to the patient's clinical conditions, so a correct selection of the patients is essential. In this regard, some studies have evaluated the RV-PA coupling as an important predictor of outcome in patients with Heart Failure (HF). In clinical practice, RV-pulmonary artery (PA) coupling could be estimated in a non-invasive way through the relationship between TAPSE (systolic excursion of the annular plane of the tricuspid valve) /PAPs (systolic pressure of the pulmonary artery) ratio that gives information about the state of contractility and adaptability to the load of the RV. In this study, we sought to evaluate how the TAPSE /PAPs ratio at baseline may improve prognostic stratification in patients undergoing TEER with the MitraClip system. Methods and Results Data from 236 patients with symptomatic, moderate to severe functional MR, subjected to implantation of MitraClip between March 2012 and June 2021, were obtained from the University's MITRA-CTV, multicenter observational register comprising data from the Magna Graecia University of Catanzaro (Italy), the University of Turin (Italy) and the University of Vigo (Spain). The median follow-up was 686 days (IQR 393-1131 days), with a 1-year follow-up in 224 of 236 (95%) patients. We divided the population into two groups based on the median value of the ratio TAPSE / PAPs ≤ 0.35 and TAPSE / PAPs> 0.35. The primary endpoint of this study includes Re-hospitalization for HF and Death from all causes at one-year follow-up. At Cox regression analysis, Hospital stay> 10 days (HR 1.67, 95% CI [1.03-2.77], p = 0.039) and the TAPSE / PAPs ratio ≤ 0.35 (HR1.58, 95% CI [1, 01-2.48], p = 0.0488) independently increased the risk of the primary endpoint at long-term follow-up. At Kaplan Meier analysis, a TAPSE / PAPs ratio of ≤ 0.35 was related to an increased incidence of the primary endpoint of Rehospitalization for HF and Death (HR 1.54, 95% CI [ 1-2.41], p = 0.0464). Conclusion In our study, the right ventricular-arterial coupling, estimated through TAPSE/PAPs Ratio, was identified as a predictor of outcome in patients with severe functional MR undergoing TEER.

Background in-stent restenosis remains a significant clinical problem for which optimal treatment is under debate. Intravascular lithotripsy (IVL) is mostly used for safe and effective treatment of de novo coronary calcifications, while the use of this technology to support bailout procedures, including stent under-expansion, is still off-label. One of the advantages of lithotripsy is the possible use after stent deployment. Case presentation a 66-year-old male patient was admitted to our Institution due to a medically refractory angina and a coronary computed tomography (CCT) detecting three vessel disease with multiple critical stenosis. The patient had multiple comorbidities including history of hypertension, dyslipidemia, type 2 diabetes and multiple myocardial rivascularization. In 2003 he underwent coronary artery by-pass (CABG) with left internal mammal artery (LIMA) to left anterior descending (LAD) artery and free saphenous vein graft (VG) to the ramus intermedius (RI). In 2009 the patient underwent percutaneous coronary intervention (PCI) of the right coronary artery (RCA) with the implantation of a stent at the central segment, and a second stent at the crux cordis. For recurrent in-stent restenosis of the stent previously implanted at the central segment the patient was treated in 2013 with percutaneous balloon angioplasty (POBA) and in 2017 with the implantation of another drug eluting stent (Resolute Onyx, Medtronic, Santa Rosa, California) overlapping the proximal part of the scaffold. Coronary angiography revealed, a severe coronary artery disease with 80% stenosis of distal left main. The LAD was occluded at the middle segment and the ramus presented 99% stenosis at the proximal segment. The RCA had a diffuse severe in-stent restenosis involving the Resolute Onyx stent. Therefore, the operator decided to treat the restenosis with a direct stenting (Xience, Abbott Vascular Santa Clara, USA), but he was unaware of the fact that there was already an Onyx stent that was barely visible. After implantation, an inadequate expansion of the stents was observed (Figura 1A-B), which persisted despite post-dilation with non-compliant balloon (NCB) at high-pressure (Figure 1C). Given the persistence of stents under-expansion, it was decided to perform bail-out intravascular lithotripsy (IVL) therapy with a Shockwave balloon catheter (Figure 2A). The stent was then post-dilated with a NCB (Figure 2B). The final angiographic image and intravascular ultrasound (IVUS) showed an optimal stent expansion (Figure 3). Conclusion intravascular lithotripsy could be used to treat undilatable stent-in-stent restenosis. Of interest, the case presented demonstrated, for the first time, the possible use of IVL in 2-stent layers, with an optima final stent expansion.

Objectives The UEFA 2020 European Football Championship held in multiple cities across Europe from June 11 to July 11, 2021, was won by Italy, providing an opportunity to examine the relationship between emotional stress and the incidence of cardiovascular events. Methods and Results Cardiovascular hospitalizations in the Cardiac Care Units of 49 hospital networks in Italy were assessed by emergency physicians during the UEFA Euro 2020 Football Championship. We compared the events that occurred during matches involving Italy with events that occurred during the remaining days of the championship as the control period. Acute cardiovascular events were assessed in 1235 patients. Cardiovascular events during the UEFA Euro 2020 Football Championship semifinal and final, the most stressful matches ended with penalties and victory of the Italian team, were assessed. A significant increase in the incidence of Takotsubo Syndrome (TTS) by a factor of 11.41 (1.6 - 495.1, P Conclusions The data of this national registry demonstrated an association between the semifinal and final of UEFA Euro 2020 and TTS suggesting that it can be triggered by also positive emotions as the victory of the European Football Championship finals.

Background: Simultaneous ulnar and radial artery compression (SURC) has emerged as a strategy to increase radial artery flow and mitigate radial artery occlusion (RAO) while achieving adequate hemostasis after transradial access (TRA), though its technical adoption has been limited worldwide. Methods: A systematic search of studies comparing SURC versus isolated radial artery compression after TRA for coronary angiography and/or intervention was performed. Data were pooled by meta-analysis using random-effects models. Odds ratios (OR) with relative 95% confidence intervals (CI) and standardized mean difference were used as measures of effect estimates. The primary endpoint was the occurrence of overall RAO. Results: A total of 6 studies and 6793 patients were included. SURC method as compared to isolated radial artery compression was associated with a lower risk of RAO both overall (OR 0.29; 95% CI, 0.13–0.61, p < 0.001; number needed to treat to benefit [NNTB] =38) and in-hospital (OR 0.28; 95% CI: 0.10 to 0.75; p = 0.01, NNTB = 36), with a reduced risk of unsuccessful patent hemostasis (OR: 0.13; 95% CI: 0.02 to 0.85; p = 0.03, NNT = 5) and upper extremity pain (OR: 0.48; 95% CI: 0.24 to 0.95; p = 0.04, NNTB = 124). No significant difference was observed in hemostasis time and in the risk of hematoma. Conclusion: Compared to isolated radial artery compression, SURC is associated with lower risk of RAO, unsuccessful patent hemostasis, and reported upper limb pain, without any trade-off in safety outcomes. With further development of dedicated dual compression devices, the proposed technique should be freed from usage constraints.

Silent myocardial ischaemia (SMI) is defined as objective evidence of ischaemia without angina (or equivalent symptoms) in the presence of coronary artery disease, differing from silent coronary artery disease. Silent myocardial ischaemia represents the majority of episodes of myocardial ischaemia at Holter monitoring. During transient myocardial ischaemia, the symptoms appear after the contraction anomalies of the left ventricle and after the ECG changes. The cause of silent myocardial ischaemia is still not well established. The severity and duration of ischaemia have been theorized as important elements in the SMI mechanism. Another possible mechanism responsible for SMI is represented by changes in the perception of painful stimuli with an increased pain threshold. Finally, a neuronal dysfunction of the diabetic, in post-infarction or a cardiac neuronal ‘stunning’ could play a role in SMI. In the pre-stent era, the SMI was associated with a worse prognosis. In patients with diabetes mellitus, SMI seems to be more represented because autonomic dysfunction is present in this category of patients. In conclusion, SMI is more frequent than symptomatic ischaemia. However, despite the presence of countless studies on the subject, it is not clear today whether medical therapy has equalized the risk and what the real prognosis of SMI is.

Percutaneous mitral valve repair has been increasingly performed worldwide after approval. We sought to investigate predictors of clinical outcome in patients with mitral regurgitation undergoing percutaneous valve repair. The MITRA-UMG study, a single-centre registry, retrospectively collected consecutive patients with symptomatic moderate-to-severe or severe MR undergoing MitraClip therapy. The primary endpoint was the composite of cardiovascular death or rehospitalization for heart failure. Between March 2012 and July 2018, a total of 150 consecutive patients admitted to our institution were included. Procedural success was obtained in 95.3% of patients. The composite primary endpoint of cardiovascular death or rehospitalization for HF was met in 55 patients (37.9%) with cumulative incidences of 7.6%, 26.2%, at 30 days and 1-year, respectively. In the Cox multivariate model, NYHA functional class and left ventricular end-diastolic volume index (LVEDVi), independently increased the risk of the primary endpoint at long-term follow-up. At Kaplan–Meier analysis, a LVEDVi > 92 ml/m2 was associated with an increased incidence of the primary endpoint. In this study, patients presenting with dilated ventricles (LVEDVi > 92 ml/m2) and advanced heart failure symptoms (NYHA IV) at baseline carried the worst prognosis after percutaneous mitral valve repair.

Background Many patients with cancer have a hypercoagulable state and an increased risk of developing venous thromboembolism (VTE), arterial occlusion, and pulmonary emboli. Patients with cancer may also have an increased risk of bleeding with anticoagulant treatment. Recent trials have reported that direct oral anticoagulants (DOACs) are noninferior to the low-molecular-weight heparin, dalteparin, in preventing VTE, but have a higher bleeding rate. Objectives This study compared the efficacy and risks of DOACs versus dalteparin in patients with cancer-related VTEs across all randomized controlled trials (RCTs). Methods This study performed a systematic analysis of RCTs published in PubMed, SCOPUS, and Google Scholar from September 1, 2007 through March 31, 2020 that reported clinical outcomes of treatment with DOACs versus dalteparin in patients with cancer with acute VTE. Two investigators independently performed study selection and data extraction. Extracted data were recorded and exported to statistical software for all analyses (OpenMetaAnalyst). Results This study included 4 randomized trials (N = 2,907). Compared with DOACs, dalteparin was associated with higher VTE recurrence (risk ratio [RR]: 1.55; 95% confidence interval [CI]: 1.19 to 2.03; p = 0.001), whereas clinically relevant nonmajor bleeding (CRNMB) was significantly less frequent with dalteparin than that with DOACs (RR: 0.68; 95% CI: 0.54 to 0.86; p = 0.001). The risk of CRNMB was largely observed with patients with gastrointestinal malignancies. No significant differences were observed in major bleeding (RR: 0.74; 95% CI: 0.52 to 1.06; p = 0.11). Conclusions DOACs were noninferior to dalteparin in preventing VTE recurrence in patients with cancer without a significantly increased risk of major bleeding. However, DOACs were associated with higher rates of CRNMB compared with dalteparin, primarily in patients with gastrointestinal malignancies., Central Illustration

We describe a case with unfavorable calcified femoral access in which the implantation of a 34-mm self-expandable transcatheter aortic valve was possible after intravascular lithotripsy. Although the aortic valve was successfully implanted, we observed a severe vascular complication requiring the implantation of a covered stent of the femoral artery. (Level of Difficulty: Advanced.), Graphical abstract, We describe a case with unfavorable calcified femoral access in which the implantation of a 34-mm self-expandable transcatheter aortic valve was…

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 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.

Changes in cardiac mechanics after correction of severe Aortic Stenosis (AS) are under-investigated. Myocardial Work (MW) is emerging as a useful non-invasive correlate of invasively measured myocardial performance and oxygen consumption. The aim of this study was to assess the usefulness of MW in the clinical management of patients with AS undergoing transcatheter aortic valve implantation (TAVI). Consecutive patients referred for TAVI were included in this observational study. Echocardiograms were performed before and after TAVI to measure Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW), and Global Work Efficiency (GWE). Mean transvalvular gradient was significantly improved (p < 0.05), without significant changes in left ventricular ejection fraction, nor in global longitudinal strain (GLS). GWI (p < 0.001) and GCW (p < 0.001), but not GWW (p = 0.241) nor GWE (p = 0.854) were significantly reduced after TAVI. Patients with a low flow low gradient (LF-LG) AS had lower left ventricular ejection fraction (LVEF) (p < 0.001), worse global longitudinal strain (GLS) (p < 0.001), and lower baseline GWI (p < 0.001), GCW (p < 0.001) and GWE (p = 0.003). The improvement in GWI and GCW observed after TAVI in the general study population were abolished among LF-LG patients. In conclusion, non-invasive MW might be useful to further classify patients with AS and to predict non responders.

Pulmonary embolism (PE) represents the third leading acute cardiovascular syndrome in the world and it is burdened with high mortality and morbidity rates. Percutaneous or catheter-based treatments of high- and intermediate-risk patients have garnered interest because of the limitations of both systemic thrombolysis and anticoagulation strategies. However, data on these techniques are heterogeneous and limited to small non-randomized evidences.This survey was jointly performed by the GISE Young Committee with the support of the SICI-GISE Society and ICOT group with the aim of evaluating the view of the cardiology community on interventional therapies for PE. A web-based questionnaire based on 19 questions was distributed to SICI-GISE and ICOT members.The survey was distributed to 1550 physicians with 220 (14%) responses, 65% from North Italy. Multidisciplinary diagnostic and therapeutic pathways for patients with PE were not available in most centers (56%), and transcatheter treatment was available in 55% of centers, most of them at low volume (5 percutaneous treatments/year). Among the devices used, mechanical thrombectomy was the predominant one (62%) in the absence of significant differences in the availability of devices within the three Italian geographic macro-areas. Respondents recognize the theoretical benefits of percutaneous treatment of PE, including: improving a prompt hemodynamic stabilization and respiratory exchange (89%) in high-risk patients, avoiding hemodynamic deterioration (39%) and right ventricular dysfunction (51%) in intermediate-risk patients, and reducing hemorrhagic complications related to systemic thrombolysis (36%). According to participants' judgement, the main factors limiting the use of percutaneous transcatheter treatment of PE in clinical practice are the lack of specific operator training (60%), lack of solid clinical data to support it (39%), difficult patient selection (34%), high costs (30%), and risk of procedural complications (26%).Currently, transcatheter treatment of PE appears to be widely supported but poorly used in clinical practice. Solid evidences are needed regarding the safety and efficacy profile of the different available devices, the identification of patient selection criteria, alongside the enhancement of the availability of techniques and technologies.

The vascular system is largely exposed to the effect of changing flow conditions. Vascular cells can sense flow and its changes. Flow sensing is of pivotal importance for vascular remodeling. In fact, it influences the development and progression of atherosclerosis, controls its location and has a major influx on the development of local complications. Despite its importance, the research community has traditionally paid scarce attention to studying the association between different flow conditions and vascular biology. More recently, a growing body of evidence has been accumulating, revealing that ncRNAs play a key role in the modulation of several biological processes linking flow-sensing to vascular pathophysiology. This review summarizes the most relevant evidence on ncRNAs that are directly or indirectly responsive to flow conditions to the benefit of the clinician, with a focus on the underpinning mechanisms and their potential application as disease biomarkers.

Iterations in stent technologies, advances in pharmacotherapy, and awareness of the implications of implantation techniques have markedly reduced the risk of stent failure, both in the form of stent thrombosis (ST) and in-stent restenosis (ISR). However, given the number of percutaneous coronary interventions (PCI) performed worldwide every year, ST and ISR, albeit occurring at a fairly low rate, represent a public health problem even with contemporary DES platforms. The understanding of mechanisms and risk factors for these two PCI complications has been of fundamental importance for the parallel evolution of stent technologies. Risk factors associated with ST and ISR are usually divided into patient-, lesion-, device- and procedure-related. A number of studies have shown how certain risk factors are related to early (1 month) versus late/very late ST (between 1 month and 1 year and >1 year, respectively). However, more research is required to conclusively show the role of time-dependence of risk factors also in the incidence of ISR (early [1 year] or late [>1 year]). A thorough risk assessment is required due to the complex etiology of ST and ISR. The most effective strategy to treat ST and ISR is still to prevent them; hence, it is crucial to identify patient-, lesion-, device- and procedure-related predictors.

Aims Post-procedural bleedings have a significant impact on mortality in patients undergoing transcatheter aortic valve replacement (TAVR). Unfortunately, the source of these bleedings is often undetermined, causing difficulties in diagnosis and related treatment. Furthermore, the frequency and determinants of ‘non-overt’ bleeding are largely lacking in TAVR studies. Accordingly, in this analysis, we aimed to assess the frequency and determinants of haemoglobin drop without overt bleeding in patients undergoing TAVR. Methods Patients undergoing TAVR at Magna Graecia University in Catanzaro from September 2008 to November 2020 were included in this study. Post-procedural haemoglobin (Hb) drop was calculated subtracting the lowest value observed after the procedure to the one obtained at admission (Hb drop). The association between baseline clinical and procedural variables with Hb drop was investigated with a linear regression model. Results Out of 407 patients undergoing TAVR at our institution, 119 (29.2%) were excluded because experiencing overt bleeding, red blood cells transfusion, were treated with only balloon angioplasty, or for procedural unsuccess. Among the 288 patients included in the final analysis, 239 (83.0%) were older than 74 y.o., 148 (51.4%) were female, 94 (32.6%) were diabetics, and 69 (24.0%) had CKD. All the patients were deemed at intermediate/high operatory risk and treated using the transfemoral approach. After TAVR, Hb significantly decreased (12.6 ± 1.6 g/dL to 9.7 ± 1.3 g/dL, P Conclusions Post-procedural reduction of Hb without overt bleeding or RBC transfusion is frequent, involving almost half of the patients undergoing TAVR. The introduction in clinical practice of new-generation valve devices is significantly associated with a reduction of this adverse event. However, further and thorough investigation should be accomplished to reclassify this large part of patients into a well-defined category.

Aims Acute coronary syndrome (ACS) are a leading cause for mortality and morbility worldwide. Despite ACS usually affects the older population, it also occurs in younger individuals. Young ACS patients (YACS) have a significantly worse prognosis compared to their age-mates in the general population. Despite YACS are characterized by a different risk profiles compared to their older mates, many aspects still remain elusive. Aim of this study was to describe the clinical profile of young adults with Acute Coronary Syndrome. Methods and results Young patients (≤50 years) with the first diagnose of Acute Coronary Syndrome admitted to the Magna Graecia University Hospital were enrolled in the ongoing GENEPAMY registry. Over 7 years, a total of 675 eligible patients with Acute Coronary Syndrome aged 44 ± 8 years were included. Men accounted for 84.9% of all patients. Overall, 11.9% of patients had diabetes, 69.1% hypertension, 17.6% obesity, 93.6% dyslipidemia, while 75.5% were smokers. In the overall cohort, 44.1% were first diagnosed with STEMI, 45.9% with NSTEMI, while the remaining had been admitted for Unstable Angina. Cardiogenic shock was present at admission in 2.7% of cases. Multivessel disease was present in 39% of cases and was significantly less frequent in women (P Conclusions Our data highlight that YACS present a peculiar clinical profile. In particular, the high cardiovascular risk profile demands attention. Finally, despite most patients were men, young women with ACS present several relevant differences compared to men, needing a more careful clinical management.

Aims Vascular smooth muscle cells (VSMCs) play a key role in the vessel wall, being active partaker in vascular remodelling and influencing multiple pathophysiological phenomena, such as progression of atherosclerosis, in-stent restenosis and vascular reactivity. Recently antisense oligonucleotides have shown promising results as a therapeutic option. The aim of this study was to analyse the expression profile and function of T-UCRs in vascular smooth muscle cells (VSMCs)—both in vitro and in vivo—and to evaluate the effects of their inhibition by the use of specific antisense oligonucleotides. Methods After obtaining cell cultures of vascular smooth muscle cells, we modified their phenotype varying growth conditions. A microarray and qRT-PCR expression profile analysis and a cell cycle analysis with cell proliferation/apoptosis/migration assay were performed. In vivo studies were performed on rat carotids after cell damage and administration of specific antisense oligonucleotides. Results There were significant differences in the expression of T-UCRs in VSMCs with a proliferating and quiescent phenotype. In particular, 5 T-UCRs were found to be upregulated in VSMCs. These types of cells were subsequently transfected with specific antisense oligonucleotides obtaining a reduction in their proliferative activity in particular with the inhibition of the T-UCRs uc.194 and uc.443 + A. MiR-10A and miR-34b-5p were identified with complementary sequences respectively to uc.194 and uc.443 + A. The increase of these miRs following the inhibition of the T-UCRs were closely related to the inhibition of the proliferative signals of VSMCs. Similarly, the same results were obtained in vivo. Conclusions The expression levels of non-coding RNAs uc.194 and uc. 443 + A increase in proliferating smooth muscle cells in vitro and in the vascular wall following damage, suggesting an important role of these molecules in the phenomenon of intra-stent restenosis. Through the inhibition of uc.194 and uc.443 + A using an antisense strategy, we demonstrated a reduction in cell proliferation and migration processes and, consequently, in the formation of neointima. A possible relationship was also highlighted between the aforementioned non-coding RNAs and some micro-RNAs (miR-10A and miR-34b-5p), negative regulators of the proliferative phenotype of VSMCs. The inhibition of the analysed T-UCRs would allow the maintenance of the contractile phenotype thanks to the activity of the miRs analysed in this study. Our results might pave the way for the identification of new therapeutic targets in order to prevent and reduce the incidence of intra-stent restenosis.

Aims The COAPT randomized trial has shown a huge benefit in the survival of patients with s heart failure and functional mitral regurgitation treated with MitraClip. However, patients in COAPT were highly selected and the clinical course in real-world patients with and without fulfilment of the trial inclusion criteria is unclear. Methods The present study examined the clinical outcome in consecutive patients with symptomatic moderate-to-severe or severe MR of dominant functional aetiology undergoing MitraClip therapy by the presence of the inclusion criteria of the COAPT trial (left ventricular ejection fraction >20%, left ventricular end-systolic dimension 4 cm2, no prior mitral valve leaflet surgery or any currently implanted prosthetic mitral valve or any prior transcatheter mitral valve procedure). Results The composite endpoint of all-cause mortality or heart failure hospitalization and the endpoint of heart failure hospitalization were analysed. Among 118 patients who underwent MitraClip implantation 61% fulfilled the inclusion criteria of COAPT. The composite endpoint was significantly less frequent (P = 0.05) in patients fulfilling the COAPT selection criteria than in those not fulfilling the criteria, with an estimated 1-year event rate of 25% vs. 49%. Heart failure hospitalization was significantly less frequent (P = 0.04) in patients fulfilling COAPT selection criteria than in those who did not, with an estimated 1-year event rate of 19% vs. 36.8%. Conclusions In this single centre study the outcome of patients with functional mitral regurgitation undergoing MitraClip therapy was significantly worse in patients not fulfilling COAPT inclusion criteria, indicating that these criteria might help identify futility.