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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 Takotsubo syndrome (TTS) is an acute cardiac condition characterized by a temporary wall motion abnormality of the left ventricle that mimics an acute coronary syndrome (ACS). TTS usually occurs following emotionally or physically triggering event. We report a rare case of Takotsubo syndrome following a pacemaker implantation. Methods and results A 77-year-old woman was admitted to our hospital with a third-degree atrioventricular block. She was asymptomatic with a history of hypertension, diabetes, hyperlipidaemia and extrapyramidal syndrome. Laboratory tests reported High-Sensitive cardiac Troponin T (HS-cTnT) 32.9 ng/L (ULN Conclusions The trigger of this case of TTS was the pacemaker implantation, a relatively brief and painless procedure that, in her case could have constitute a considerable emotional and physical stress. To the best of our knowledge 13 cases of TTS after pacemaker implantation have been described to date. Of those cases, four had an asymptomatic course. Therefore, the real incidence of TTS following pacemaker implantation may be underestimated and ECG and echocardiography should always be performed after pacemaker implantation.

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.

An 82 years old woman was admitted to our Division for worsening dyspnoea. Her past medical history showed: arterial hypertension, chronic atrial fibrillation on oral anticoagulation, a non-critical single-vessel coronary artery disease, previous mitral transcatheter edge-to-edge repair through 2 Mitraclip NTR. After an initial improvement in clinical symptoms following Mitraclip implantation, the patient was admitted several times for acute decompensated heart failure. Haematological exams at admission were normal, exception of NTproBNP (1909 pg/mL). The ECG documented atrial fibrillation with normal ventricular rate. Transthoracic echocardiography demonstrated mid-range heart failure (EF 45–50%) with D-shape morphology of the left ventricle. Colour-doppler analysis shows presence of Mitraclip devices in place with mild residual insufficiency, dilation of the right side, torrential tricuspid regurgitation (tTR) with estimated pulmonary arterial pressure of 45 mmHg. Preprocedural transesophageal echocardiography confirmed these findings showing dilation of the tricuspid annulus with two large regurgitating jets. After positioning Amplatzer Superstiff guide in superior vena cava through guide catheter TSGC0202, a Triclip XT was placed in commissural region between anterior and septal leaflets. A two-grade reduction in tricuspid regurgitation (TR) grade from torrential (5+) to moderate (3+) was achieved without significant transvalvular gradient. The patient was successful discharged after 2 days, asymptomatic and in good clinical conditions. A great reduction in NTproBNP values at discharge was observed (1612 pg/mL). We report a case of successful tricuspid transcatheter repair in patient with chronic decompensated heart failure and previous Mitraclip treatment. The clinical impact of TR reduction is probably due to a positive right ventricular (RV) remodelling, with a reduction in RV size. RV dysfunction and its implications (liver, renal, and haemostatic consequences) are definitely a matter of concern for fragile patients with TR. In fact, many patients with severe TR have a reduced RV function. The reduction in volume and pressure overload of the right heart side, the progressive anatomic and functional reverse of the RV disfunction, may lead to a significant clinical benefit and to a lower hospitalizations rates also through to an important improvement of the left ventricular function as a consequence of the reduction in pressure overload.

A substantial part of the training programme for cardiologists in training includes several hours per week of face-to-face teaching. Since the pandemic's beginning, most of these activities in the universities have been conducted virtually using one of the available secure and reliable video platforms. The proven standard educational method is top-down education. The teacher guides the instruction, focuses on what the students ‘need to know’, and transmits the knowledge to the fellows, then verifies the learning. Unfortunately, this method does not stimulate critical, creative ability and does not always represent what the fellows ‘want to know’. A new additional model of education in the Board of Cardiology of the Magna Graecia University and the University of Trieste has been designed to develop education from the bottom up. The topics that have been chosen are those of the training programme in Cardiology and necessary to complete the training period. A participants list of 60 fellows in training and a panellist list of 3 teachers were then created. The first topic was ‘Myocarditis’. Next, each fellow was asked about one topic/question (Figure 1) (see additional data). All participants then had to vote for the best five from the pool of 60 questions. Therefore, a pyramid of priorities was made between the topics/questions and assigned to the three panellists, based on specific expertise, 3 days before the event (see additional data). Then a 1, 15 H zoom session was opened at 7:00 AM, and all participants were invited. In the digital session, the fellow authors of the first 15 questions read the question by his/herself, then the moderator entrusted the answer to one of the expert panellists. With this approach, the student started with a question of the selected topic, performs self-directed research or experimentation, and, finally, arrives at explicit knowledge. The general rule of this approach is that participants are the producers and advantages of this method are to teach students how to seek knowledge on their own, even outside the virtual event. In conclusion, this bottom-up educational programme presented can be a valuable teaching aid in the training trajectory of the new generation of physicians. 805 Figure 1.

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.

Aims conduction disturbances requiring pacemaker implantation (PPM) are among the most common complications in patients undergoing transcatheter aortic valve replacement (TAVR). Introduction in clinical practice of a new generation of TAVR devices is contributing to a significant reduction in procedural complications. However, limited data is available regarding PPM implantation after TAVR with the latest available devices. Accordingly, in this analysis we aimed to investigate the incidence and risk factors for new permanent pacemaker implantation after TAVR according to the type and diameter of valve implanted. Methods Patients who underwent TAVR at our Institution from September 2008 to November 2020 were included in this analysis. Out of 407, 38 (9.3%) were excluded because they already presented a PPM/ICD, received only balloon angioplasty or for procedural unsuccess. The independent association between baseline clinical and procedural variables and the occurrence of PPM implantation was investigated with cross-sectional logistic regression analysis. Results Out of 368 TAVR procedures included in the final analysis, 89 (24.2%) required in-hospital PPM implantation. No differences were observed for age and common cardiovascular risk factors between groups. Among procedural variables, patients requiring PPM had lower left ventricular ejection fraction (LVEF) and experienced a longer intensive care unit stay. Valve types used were Corevalve n = 98 (26.6%) (first-generation devices), Evolute R, n = 191 (51.9%), Evolute Pro, n = 3 (1.1%), Portico n = 2 (0.5 %), or Sapien 3, n = 73 (19.8%) (second-generation devices). Clinical and procedural correlates of PPM implantation were depicted in Figure. Of note, compared to the first generation of self-expandable devices, the second generation is associated with a lower risk of PPM implantation, albeit non-significant for the subgroup of second generation self-expandable devices. Finally, valve diameter was also an independent predictor of PPM implantation Conclusions PPM was required in 24.2% of patients who underwent TAVR with first- and second-generation balloon or self-expandable valves. For instance, in our population, second-generation TAVR devices were associated with a lower risk of PPM implantation compared to the previous generation. However, further investigations are warranted to assess the impact of new implantation techniques and valve technology on such an important outcome.

Aims The transfemoral (TF) approach appeared to be the safest and the broadest used approach in TAVI, characterized by a lower rate of periprocedural bleedings and vascular complications and is currently recommended by the guidelines as a first line approach when feasible. If in the early experience TF access was achieved using a surgical cutdown approach, through the last years, there has been increasing evidence of the safety and efficacy of a fully percutaneous approach over a surgical access, albeit available evidences are controverting and mostly including first generation prostheses and high risk patients. The aim of the study is to compare percutaneous and surgical access in a large, real-word, multicentre of TF TAVI. Methods and results Consecutive patients undergoing successful TF TAVI were prospectively enrolled in local clinical registries of five high volume centres in Italy: IRCCS Ospedale Policlinico San Martino (Genoa), IRCCS Policlinico San Donato (Milan), Città Della Salute e della Scienza, (Turin), Ospedale Niguarda Ca’ Granda (Milan), Magna Graecia University, (Catanzaro), between January 2014 to December 2019. Univariate and multivariate analysis using IPTW were performed. A total of 1946 TF TAVI patients (female 42.8%) were prospectively included. Patients underwent surgical access had a significantly higher surgical risk (STS score of 8.9 vs. 6.4, P Conclusions The performance of the percutaneous transfemoral TAVI approach was safe and feasible and resulted in fewer major vascular complications, bleedings and AKI than the surgical femoral isolation. Procedural time and hospital length were also lower in the percutaneous group. Routine application of the percutaneous approach might reduce acute complications in patients undergoing transfemoral TAVI and reduce procedural time and hospital length.

Aims The management of acute myocardial infarction (AMI) in elderly patients is often challenging for their peculiar clinical profile and the limited clinical evidence available. This represents a major unmet need in cardiovascular medicine, given the progressive ageing of population in western Countries. To investigate the clinical characteristics of elderly patients with AMI at a single tertiary university hospital. Methods and results The EMIR is an ongoing registry including elderly patients (≥75 years) consecutively referred to a single tertiary centre with diagnosis of acute myocardial Infarction with indication for coronary angiography. A total of 760 patients were enrolled to date, 39.6% were female, while mean age was 80 ± 4 years. Most patients had a NSTEMI, while 28% had a STEMI. Time from symptoms’ onset to presentation was 9.4 ± 14.6 for STEMI and 26.5 ± 30.4. Percutaneous coronary intervention (PCI) was performed in 64% of cases. Concomitant PCI of a non-target lesion (NTL) was performed within the same procedure in 8.8% of cases. A staged PCI of NTL was performed in 14% of cases. An elective surgical revascularization was performed after PCI of the IRA in 2.1% of cases. Altogether, a complete revascularization was achieved in 43% of cases before discharge. No evidence of critical coronary stenoses (CCS) was reported in 12.1% of cases, more frequently in females (18%) than in males (8.3%). Patients with no CCS were younger (P = 0.007), more frequently female (P Conclusions Elderly patients with AMI are a specific population, posing peculiar clinical needs and demanding dedicated clinical management protocols.

Aims Device implantation is growing exponentially, as well as associated infections, ranging from isolated pocket erosion to endocarditis and bacteraemia, all worsening the prognosis of patients with frailty and comorbidity. Transvenous lead extraction (TLE) can resolve the complications, although a 1-year mortality risk of up to 25% is reported; despite higher health costs, prolonged hospitalization, and poor quality of life, strategies for predicting increased infection risk and reduced infection incidence are yet missing. Currently applied clinical scores do not consider etiologic microbial agents. We aimed to assess whether PADIT and UPCM scores could be implemented when bacteria or fungi are known to be causative of infection, and how these agents affected the outcome. Methods and results A retrospective analysis of patients undergone cardiac implantable electronic device (CIED) pocket revision, and/or TLE between 2016 and 2021 was performed. For each procedure, microbiological samples of both generator pocket tissue and intracardiac portions of the leads were analysed. In addition, blood cultures were performed in three sets. Transesophageal echocardiography was performed in all cases for ruling out suspected endocarditis. Spearman ad Pearson coefficients were tested for correlation among microorganism, prior infection and/or procedure, PADIT and UPCM scores; a P-value less than 0.05 was considered significant. We analysed 14 patients (10 males, 4 females, mean age ± SD: 72 ± 13): one case (4%) affected by pocket erosion, seven cases (50%) affected by both pocket site and lead infection (with associated bacteraemia in one subject), and one case (4%) due to lead-related infective endocarditis. Of these, five (36%) underwent device replacement, while nine (64%) to extraction or pocket/lead revision. Nine (64%) patients had positive culture examinations (Figure 1). The correlation method gave a statistically significant association between Gram- infection and prior sepsis (r 0.63; P-value 0.02). We considered the number of procedures on the same pocket and/or CIED previous infections as markers of frailty and increased infectious risk. As expected, the PADIT score, but not UPCM, significantly correlated with the number of previous procedures (r 0.70; P-value 0.006). Indeed, both scores had a similar infectious risk prediction. Conclusions In our analysis, predictive PADIT score of infectious risk performed better than UPCM, while both proved their reliability in identifying high-risk patients. The absence of correlation between UPCM score and infective agents is not conclusive, but probably due to the small sample size. Interestingly, growing rate of device reinfection correlates with the risk of Gram- bacterial infection. Thus, the integration of the microbiological data in the current prediction models could significantly increase their performance.

Aims Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure (HF), reduced left ventricular ejection fraction (EF ≤ 35%) and high-grade intraventricular conduction delays. CRT improves cardiac function, symptoms and well-being, and reduces morbidity and mortality in this setting. However, there are patients unresponsive to CRT. Responders show reverse ventricular remodelling, volumes and diameters reduction, and EF improvement. Noninvasive cardiovascular imaging for visualization and quantitation of intracardiac flows and turbulences has not been assessed thoroughly in CRT. This study seeks to evaluate if the quantitative analysis of intracardiac flow dynamics in HF patients treated by CRT might provide additional information for device optimization and clinical response. Methods and results Fifteen HF patients (five females, age 69.6 ± 9.4 years, NYHA class II/III, EF 29.3 ± 4.6%) were enrolled in the study. Eleven had primitive dilated cardiomyopathy and four had post-ischaemic etiology with completed revascularization. Pacemaker-dependent cases were excluded. MyLab™ X8 platform was used for echocardiographic assessment of intracardiac flow dynamics performed on apical three chamber views. All examinations were realized in baseline (active CRT) and after 5 min of biventricular pacing switch off. The hyperDoppler software was used to assess intracardiac vortexes properties. The analyzed parameters were: vortex area, vortex length, vortex depth, and kinetic of energy dissipation (ΔKE). Categorical variables are expressed as numbers and percentages. Quantitative variables are expressed as mean and standard deviation (SD). Shapiro–Wilk test, D’Agostino Pearson test, and visual inspection of Q–Q-plots were executed to evaluate if variables were normally distributed. Quantitative variables were evaluated with paired sample T-test or Wilcoxon test when appropriate. Clinical features, biochemical parameters, electrocardiograms with and without cardiac pacing, and EF before and after CRT implantation were collected. Although no difference was observed in vortex area/depth/length, a significant increase in KE dissipation after switching OFF the CRT devices (from 1.2 ± 0.9 to 3.5 ± 2.3 J, P Conclusions Noninvasive intracardiac flow dynamics in HF patients represents a complementary tool to standard echocardiography, and provides additional parameters for assessing prognosis and outcomes in CRT recipients. The impact of maladaptation in intracardiac flow dynamic on progressive LV remodelling could be useful to evaluate the prognostic meaning of implanted CRT device and to predict the response to device implantation, based on cardiac flow analysis.

Aims A growing number of patients is undergoing transcatheter treatment of severe Aortic Stenosis. Changes in cardiac mechanics after removal of afterload in these patients are under-investigated. Myocardial Work (MW) is emerging as a useful non-invasive correlate of invasively measured myocardial performance and oxygen consumption. Aim of this study was to assess the usefulness of non-invasive MW indices in the clinical assessment of patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). Methods and results Consecutive patients with severe aortic stenosis referred for TAVI in a single tertiary centre were included. Echocardiography recordings (GE-Healthcare) with systolic and diastolic non-invasive pressures, were obtained immediately before TAVI and after TAVI to measure myocardial work index (MWI), myocardial constructive work (MCW), myocardial wasted work (MWW), and myocardial work efficiency (MWE). Consecutive patients with severe AS (n = 73) undergoing TAVI and matched controls (n = 50) were included. Mean transaortic gradient, AV area, and peak transvalvular velocity were significantly improved (all P Conclusions The use of non-invasive myocardial work might be useful to further classify patients with AS and could be useful to predict non responders.

Aims Over the past decades growing evidence have demonstrated the promising role of intracardiac fluid-dynamics in evaluating cardiac performance. To investigate quantitative changes in vortices parameters in patients with different ventricular geometry. Methods and results We enrolled 50 consecutive patients with one of the following: LV concentric hypertrophy (CH), eccentric hypertrophy (EH), concentric remodelling, and normal LV geometry (CTRL). They underwent a complete echocardiographic examination with intracardiac fluid-dynamic analysis by Color Vector Flow Mapping (Hyperdoppler). The following parameters were obtained: vortex area (VA); vortex length (VL); and vortex depth (VD). Bland Altman Plot has been used to assess intra and inter-observer variability. Mean VD was higher in CR, CH, and EH compared to CTRL (P = 0.013, P = 0.001, and P = 0.022, respectively). Moreover, CH showed higher VL (P = 0.006) and larger VA (P = 0.012) compared to CTRL. A similar trend was noticed in EH patients, despite did not reach statistical significance (P = 0.21 and P = 0.07 for VA and VL, respectively). No significative differences in vortices parameters have been observed between CH and EH. Conclusions This is the first study providing quantitative echocardiographic parameters of vortex location and morphology in different LV geometries. Quantitative fluid-dynamic assessment was feasible and reliable in the whole population.

Aims Complications of acute myocardial infarction (MI) can be life-threatening leading to sudden cardiac death. While guidelines recommend prompt revascularization and prolonged intensive care hospitalization, predictors of major adverse cardiovascular outcomes are yet poorly understood. The role of implantable cardioverter-defibrillators, even in cases of non-sustained arrhythmias is still debated. To date, it is unknown how to follow-up patients with mild cardiac dysfunction after MI. Implantable cardiac monitors (ICMs) can be helpful for stratifying patients in the early discharge period, and remote monitoring might speed up arrhythmia recognition and treatment. We investigated the role of remote monitoring of ICMs to detect arrhythmic events in post-MI patients without overt cardiac dysfunction. Methods and results We enrolled 13 patients (9 males; 69.8 years) after either ST-segment (N = 7) or non-ST-segment elevation (N = 6) MI with a left ventricular ejection fraction (LVEF) >35%, admitted to our coronary care unit for urgent revascularization between September 2019 and September 2021. Twelve patients underwent percutaneous myocardial revascularization, whereas one was treated with medical therapy only. All patients received an ICM during hospitalization according to echo and EKG parameters. We considered LVEF ≤ 40% as sole risk factor or LVEF between 40% and 50% in addition to either PQ length prolongation, or QRS widening, or pathologic heart rate variability, or non-sustained ventricular tachycardia/paroxysmal advanced second degree atrioventricular block. Patients with multiple revascularization procedures and several hospital admissions were excluded. Implanted ICM were frequently monitored both remotely and in-office when required. During follow-up, brady- and tachy-arrhythmias were recorded in four patients (30.8%). The remote monitoring of the ICM documented new-onset atrial fibrillation, high-degree atrioventricular block, severe bradycardia, and sustained ventricular tachycardia. Three patients required hospitalization and upgrade of the implanted device with pacemakers and cardioverter/defibrillator. For arrhythmic risk stratification, patients were divided into two subgroups; group A included patients with LVEF 40% associated with heart rate > 60 b.p.m., PQ length >160 ms and QRS width >86 ms (N = 4); group B included patients with EF 41%/50%, PQ length Conclusions OFF-label implementation of ICMs coupled with remote device monitoring may be effective for early detection of serious adverse cardiac rhythm alterations in patients after MI and LVEF higher than 35%. Further monitoring is ongoing for assessing the occurrence of multiple arrhythmias or their increased occurrence.

Aims The TAVI registry represents a single-centre observational retrospective study that consecutively collected symptomatic patients with severe aortic stenosis between September 2009 and February 2021 at the Magna Graecia University (Catanzaro, Italy). Our aim was to evaluate the rate of complications which can occur after Transcatheter aortic valve replacement (TAVR) and its possible predictors. Methods We included a total of 346 consecutive patients, admitted to our institution between September 2009 and February 2021. Inclusion criteria were: severe aortic stenosis in high-risk patients unsuitable for surgery after cardiac team consent, valve anatomy adjusted according to device instructions for use, life expectancy> 1 year. Clinical, echocardiographic and procedural data were collected and reported in an electronic database. Surgical risk was prospectively assessed using the European Cardiac Operational Risk Assessment System (EuroSCORE II, https://www.euros core.org/calc.html). The mean age of the population was 80.3 ± 5.4 years; 144 patients (41.6%) were male. The average EuroSCORE II was 6.3 ± 5.7. All reported P-values are two-sided and P-values Results Out of the total population analysed, the number of patients who underwent a vascular complication was 23 or 6.6%. Female sex was an independent predictor of vascular complication (P 0.015) regardless of the presence of peripheral vascular disease (OR 3.73; 95% CI 1.20–11.5), while no correlation was found with BSA. The number of patients experiencing severe bleeding and/or need for transfusion was 85 or 24.6% of the total. Mean baseline haemoglobin values were 12.1 g/dL ± 1.7 with lower mean values reported during hospitalization of 9.2 g/dL ± 1.4 (P 120 ms after the procedure was 92 (26.5%). Out of the total number of patients analysed, the number of subjects who required PM implantation was 77 patients, i.e. 22.3% of the total. Of these, 25 patients (32.4%), Evolut R 45 patients (58.6%) and Sapien 7 patients (9.0%) had received implants. The need for pacemaker implantation did not affect the average length of stay (P 0.5). Conclusions Since its advent, the transfemoral aortic valve prosthesis implant has experienced impressive and continuous growth, radically revolutionizing the treatment of symptomatic severe aortic stenosis. Furthermore, the clear improvement of the procedural safety and efficacy profiles, due on the one hand to the technological evolution of the devices, of the introduction and release systems and of the experience of the operators, has reduced the number of complications related to the implant and improved the management of the same.

Aims A small effective orifice area (EOA) by body surface area (BSA), defined as prosthesis–patient mismatch (PPM), is associated with elevated transprosthetic pressure gradients, less ventricular remodelling, and a worse prognosis. Calculating PPM by dividing the normal reference value of EOA for the model and size of the prosthetic valve (predicted PPM), instead of using the continuity equation has been recently confirmed as more accurate after trans catheter aortic valve intervention (TAVI), providing a stronger association with post-procedural haemodynamic outcomes. However, current evidence using this new definition is still limited, thus impairing generalizability. Accordingly, this analysis aims to extend such evidence providing incidence, and determinants of predicted PPM (PPMp) in an all-comers population undergoing TAVR with a high prevalence of self-expandable devices. Methods 395 patients who underwent TAVI at our Institution from September 2008 to November 2020 were included in this analysis. PPMp was then classified as moderate if ≤ 0.85 cm2/m2 and severe if ≤ 0.65 cm2/m2 as well as moderate if ≤ 0.70 cm2/m2 and severe if ≤ 0.55 cm2/m2 for patients with a body mass index > 30, as recommended by the Valve Academic Research Consortium-3 definition. The independent association between baseline clinical and procedural variables and the presence of moderate or severe PPMp was investigated with cross-sectional logistic regression analysis. Results 11 patients (2.78%) had severe and 33 (8.35%) moderate PPMp. Patients with moderate or severe PPMp (m/s PPMp) were younger, female, with a higher prevalence of hypercholesterolaemia, prior aortic valve implantation and balloon expandable device and lower prevalence of chronic obstructive disease (COPD). Post-procedural mean gradient was higher in patients with m/s PPMp. The independent clinical and procedural correlates associated with higher likelihood of m/s PPMp were valve in valve procedure (ViV) and the use of a balloon-expandable device. Conclusions Moderate or severe PPMp was observed only in a small part of patients underwent TAVI, leading, however, a higher post-procedural mean gradient compared to those without PPMp. Balloon expandable devices and ViV were the strongest determinant of moderate or severe PPM.

Aims Transcatheter implantation of a balloon-expandable aortic valve is associated with an acute stent recoil . Conversely, the acute effects of nitinol-based stent frame- self expandable valve on post-deployment dimensions have not been reported. Accordingly, the aim of this study was to assess the occurrence and degree of acute prosthetic dimension changes after Evolute R valve implantation. Methods A total of 58 consecutive patients undergoing transcatheter aortic valve intervention (TAVI) with a widely used nitinol based self-expandable device (Evolute R, Medtronic, Minneapolis, USA) were included in this study. We measured valve diameters at three different sections: a) distal (aortic) level, b) central (annulus) level, and c) proximal (ventricular) level. Valve expansion was calculated as the difference between the diameters calculated immediately after valve deployment (A) and at the end of the procedure (B). The absolute and relative acute stent recoil were defined as B-A and (B-A)/B*100, respectively. A linear regression model was performed to test the association between the degree of valve extension, with baseline, as well as procedural characteristics. Results Final stent diameters were significantly higher compared to those achieved immediately after valve implantation in proximal (20.87±3.20 mm versus 20.37±3.27 mm, P Conclusions This is the first study that documented a significant degree of post-deployment recoil of the Evolute R self-expandable valve, that was consistent across all the segments. The stent-valve expansion of the proximal segment was associated with a greater annulus dissymmetry reported by the maximum and minimum diameter ratio assessed by CT scan. However, further studies are required to assess the short and long-term time-course of self-expandable valve enlargement and the clinical relevance of this finding.

Aims Many efforts have been made in the last decade to minimize the risk of bleeding in patients undergoing transcatheter aortic valve replacement (TAVR), such as a less intensive antithrombotic therapy and technical improvement in devices implantation. Conversely, evidence on high atherothrombotic status (HATR) is still lacking in patients undergoing TAVR. Accordingly, in this analysis, we aimed to evaluate frequency and impact of atherothrombotic status in patients undergoing transcatheter aortic valve replacement. Methods Patients who underwent TAVR at our Institution from September 2008 to November 2020 were included in this analysis. Out of 407 patients, 6 (1.5%) were excluded as they underwent only balloon angioplasty or for procedural unsuccess. HATR status includes patients with prior percutaneous coronary intervention/coronary artery bypass graft, prior stroke/transient ischaemic attack (TIA), or with a diagnosis of diabetes. Continuous variables following normal distribution were compared with the student’s t-test and categorical data were analysed with the chi-square test. A Cox regression model was used to evaluate the association between HART status and all-cause mortality at one 1-year follow-up. Results Compared to patients with low atherothrombotic status (LATR) (n = 238; 59.4%), HART patients (n = 163; 40.6%) were older, more likely female and with a higher prevalence of common cardiovascular risk factors including chronic kidney disease, smoke, and hyperlipidaemia. Between LATR and HATR groups, no differences have been observed, in terms of procedural time, type of devices used (Balloon vs. self-expandable device), or hospitalization length. Compared to LART, HART patients were more likely to be discharged on statin (63.7% vs. 83%, P Conclusion In our population, no differences in procedural and in-hospital adverse events have been observed according to the atherothrombotic profile. HATR patients were more likely to be discharged with more intensive antithrombotic and hypolipidaemic strategies, despite the coexistent high prevalence of bleeding determinants. However, ATR status does not impact 1-year mortality even after adjustment for baseline characteristics.

AimsThis international multi-center study aimed to demonstrate the feasibility and reliability of non-invasive myocardial work (MW) parameters in the pediatric population, and to provide normal reference ranges for this useful echocardiographic tool in this specific subset of patients.Methods and ResultsIn this retrospective multi-center study involving three pediatric laboratories, 150 healthy children and adolescents (mean age of 10.6 ± 4.5, 91 males) were enrolled. A complete echocardiographic examination has been performed, including global longitudinal strain (GLS) assessment. The following parameters of non-invasive MW have been obtained through a dedicated software: global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE), using left ventricular (LV) strain loops and non-invasive brachial artery cuff pressure values. The lowest expected values were for GWI 1,723 mmHg% in males and 1,682 mmHg% in females, for GCW 2,089 and 2,106 mmHg%, for GWE 95.9 and 95.5% whereas the highest expected value for GWW was 78 mmHg% in men and 90 mmHg% in women. The univariable and multivariable analysis showed significant associations between either GWI or GCW with SBP (β coefficient = 0.446, p < 0.001; β coefficient = 0.456, p < 0.001, respectively) and LV GLS (β coefficient = −0.268, p = 0.001; β coefficient = −0.233, p = 0.003, respectively). Inter- and intra-observer variability showed good reproducibility of non-invasive MW parameters.ConclusionNon-invasive MW parameters were feasible and reliable in the pediatric population. This study provided normal reference ranges of these useful echocardiographic indices.

Left ventricular hypertrophy (LVH) is remarkably prevalent among end-stage kidney disease (ESKD) on chronic dialysis and has a strong prognostic value for adverse outcomes. In experimental models, the endogenous cardiotonic steroid Marinobufagenin (MBG) promotes cardiac hypertrophy and accelerates uremic cardiomyopathy. In this study, we investigated the possible relationships between MBG, LV geometry and cardiac dysfunction in a clinical setting of ESKD.Plasmatic MBG was measured in 46 prevalent ESKD patients (n = 30 HD, n = 16 PD) together with a thorough laboratory, clinical, bioimpedance and echocardiography assessment. Different patterns of LV geometry were defined by left ventricular mass index (LVMi) and ventricular morphology. Diastolic dysfunction was diagnosed by the ASE/EACVI criteria.MBG levels were significantly higher in ESKD patients than in healthy controls (p = 0.001) and more elevated in PD than in HD (p = 0.02). At multivariate analyses, E/e' (β = 0.38; p = 0.009) and LVMi (β = 0.42; p = 0.02) remained the sole independent predictors of MBG. A statistically significant trend in MBG levels (p = 0.01) was noticed across different patterns of LV geometry, with the highest values found in eccentric LVH. MBG levels were higher in the presence of diastolic dysfunction (p = 0.01) and this substance displayed a remarkable diagnostic capacity in distinguish patients with normal LV geometry, LV hypertrophy and, particularly, eccentric LVH (AUC 0.888; p 0.0001) and diastolic dysfunction (AUC 0.79; p = 0.001).Deranged plasma MBG levels in ESKD patients on chronic dialysis reflect alterations in LV structure and function. MBG may, thus, candidate as a novel biomarker for improving cardiac assessment in this high-risk population.

Introduction Sleep apnea (SA), as measured by polysomnography, is a risk factor for atrial fibrillation (AF). The DASAP-HF study previously demonstrated that the Respiratory Disturbance Index (RDI) computed by an implantable cardioverter defibrillator (ICD) algorithm accurately identifies severe SA, is associated with cardiovascular events, and independently predicts death. Purpose In the present analysis we tested the hypothesis that device-detected RDI could also predict AF burden. Methods Patients with left ventricular ejection fraction ≤35% implanted with an ICD were enrolled and followed-up for 24 months. One month after implantation, patients underwent a polysomnographic study. The weekly average RDI value was considered, as calculated by the algorithm during the entire follow-up period and over a 1 week period preceding the sleep study, and patients were stratified according to an RDI value ≥ or Results 164 enrolled patients had usable RDI values during the entire follow-up period. Severe SA (RDI≥30 episodes/h) was diagnosed in 92 (56%) patients at the time of the polysomnographic study. During a median follow-up of 25 months, AF burden ≥5 minutes/day was documented in 70 (43%), ≥6 hours/day in 48 (29%), and ≥23 hours/day in 33 (20%) patients. Device-detected RDI≥30 episodes/h at the time of the polysomnographic study, as well as the polysomnography-measured apnea hypopnea index ≥30 episodes/h, were not associated with the occurrence of the endpoints, using a Cox regression model. However, using time-dependent Cox model continuously measured weekly average RDI≥30episodes/h was independently associated with AF burden ≥5 minutes/day (HR: 2.13, 95% CI: 1.24–3.65, p=0.006), ≥6 hours/day (HR: 2.75, 95% CI: 1.37–5.49, p=0.004), and ≥23 hours/day (HR: 2.26, 95% CI: 1.05–4.86, p=0.037), after correction for history of AF, left atrial diameter, and gender. Conclusions In heart failure patients implanted with an ICD, device-diagnosed severe SA is associated with a higher risk of AF. In particular, severe SA on follow-up data review identifies patients who are from two- to three-fold more likely to experience an AF episode, according to various thresholds of daily AF burden. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Promoted by the Italian Heart Rhythm Society (AIAC).Supported by a research grant from Boston Scientific.

Background Assessment of intracardiac flows and turbulence has acquired rising significance in the past few years, due to the development and introduction of technologies for non-invasive cardiovascular imaging. Recent studies have shown that alterations in intracardiac fluid dynamics can be helpful to identify abnormalities in cardiac function. Purpose This study investigates the additional information provided by the quantitative assessment of intracardiac flow dynamics for the evaluation of patients with aortic stenosis (AS), by using an advanced echocardiography vortex-based approach. Methods Sixty-one patients with severe AS (33 females) and 38 healthy sex- and BSA-matched controls (CTRL) (15 females) were prospectively included and underwent echocardiographic assessment of intracardiac flow dynamics. Echocardiographic measurements were performed on apical three chamber views. The HyperDoppler software adapted to the echo-scanner without contrast injection was used to assess intracardiac vortex properties. The following parameters were obtained: vortex area (VA) (the ratio between the total vortex area and the left ventricular (LV) area); vortex length (VL) (the longitudinal length of the vortex relative to the total LV length; vortex depth (VD) (the distance of the vortex center from the LV base relative to the total LV long axis). Inter-rater variability was measured using intraclass correlation coefficients (ICCs) between two independent operators. Results Patients with severe AS (mean gradient: 47,5±13,9 mmHg; aortic valve area: 0.7±0.2 cm2; ejection fraction: 53±7%) had increased LV wall thickness (p0.001, respectively) were significantly higher in AS patients compared with CTRL. Among those who underwent TAVR, we observed a significant difference in the delta values of VA and VL pre-postTAVR in patients with and without significant paravalvular leak (p Conclusions The newly defined VA, VL and VD, quantitative indices of vortical flow, were significantly increased in the LV cavity of patients with severe AS compared to normal subjects. These indices, whose measurement was feasible and reliable, might provide complementary information to standard echocardiography, useful for the further diagnostic and prognostic characterization of the heterogeneous population of patients with severe AS. Funding Acknowledgement Type of funding sources: None.

Background Over the last decades growing evidence have demonstrated the promising role of intracardiac flow dynamic analysis in evaluating cardiac performance. Diastolic forces contribute to the formation of vortices, complex structures capable of kinetic energy storage and responsible of a smoother transition of blood from left ventricular (LV) inlet to outlet. Change in shape and location of these structures has been related with cardiovascular disease and prognosis. Purpose To investigate quantitative changes in vortices parameters in patients with different ventricular geometry. Methods We enrolled 72 consecutive patients (age 66±11 years, 49 male, 68%) with LV concentric hypertrophy (CH, n=15), eccentric hypertrophy (EH, n=13), concentric remodeling (CR, n=15) and normal LV geometry (CTRL, n=29). Each patient underwent a complete echocardiographic examination and a non-invasive intracardiac fluid dynamic analysis by Color Vector Flow Mapping. A 3-chamber apical view with a frame rate between 22 and 25 Hz has been acquired and subsequently analyzed offline by a semi-automatic software obtaining the following parameters: vortex area (VA) (the ratio between the total vortex area and the left ventricular (LV) area); vortex length (VL) (the longitudinal length of the vortex relative to the total LV length; vortex depth (VD) (the distance of the vortex center from the LV base relative to the total LV long axis). Bland Altman Plot has been used to assess intra and inter-observer variability. Results Mean VD was higher in CR, CH and EH compared to CTRL (p=0.013, p=0.001 and p=0.022, respectively). Moreover, CH showed higher VL (p=0.006) and larger VA (p=0.012) compared to CTRL. A similar trend was noticed in EH patients, despite did not reach statistical significance (p=0.21 and p=0.07 for VA and VL respectively). No significative differences in vortices parameters have been observed between CH and EH. Conclusion(s) This is the first study providing quantitative echocardiographic parameters of vortex location and morphology in different LV geometries. Higher values of VD were found in CR, CH and EG. Quantitative intra dynamic fluid assessment was feasible and reliable in the whole population and could provide additional information to the standard echocardiographic examination. Funding Acknowledgement Type of funding sources: None.

Background Evaluation of left atrial (LA) function is an emerging biomarker of cardiovascular disease (CVD). LA strain by 2D speckle tracking echocardiography (LA strain, LAS) is feasible and reliable, and has been recently associated with adverse long-term outcomes in CVD, including aortic stenosis (AS). Purpose To evaluate the changes in left atrial strain (LAS) after correction of severe AS with transcatheter aortic valve replacement (TAVR) and assess its prognostic impact. Methods One hundred consecutive patients with severe symptomatic AS who underwent TAVR at the Magna Graecia University of Catanzaro have been enrolled. Echocardiographic examination before and after TAVR was performed using Vivid E95 system and analysed using the EchoPAC 112.99 workstation (GE Healthcare). Patients underwent clinical follow up visits regularly. The primary study outcome was the difference in ΔLAS (postTAVR-preTAVR) between patients that met the main clinical endpoint (a composite of cardiovascular mortality and heart failure hospitalization) and those not meeting the endpoint. Statistical analyses were performed using JASP (version 0.14.1) and KMWin (version 1.52). Continuous variables were presented as mean and standard deviation and were compared through the unpaired Student's t test or the Mann-Whitney U test in case of a non-normal distribution. Differences between categorical variables were tested with the chi-square test. Multiple logistic regression analysis was performed to identify independent correlates of ΔLAS and to calculate Hazard Ratios (HR) with 95% CI. Kaplan-Meier was used to assess adverse event. Results During a median follow-up of 31 months, 35 patients (35%) met the composite clinical endpoint. The difference between LAS post-TAVR and LAS pre-TAVR (ΔLAS) was significantly larger in patients who met the combined endpoint (HR=0.76 [0.67–0.86]; p Conclusions A lower reduction in ΔLAS after TAVR was an independent predictor of the primary composite outcome of cardiovascular death and hospitalization for HF. Funding Acknowledgement Type of funding sources: None.

In this preliminary study, the nonlinear mixed-effects modeling-based methodology has been chosen to investigate and evaluate the possible implication of some clinical cofactors on the release of biomarker cardiac troponin T (cTnT) in patients with acute myocardial infarction (AMI) and ST-segment elevation (STEMI). The aim of the study consists of the identification of subclasses of STEMI patients with different characteristics and, potentially, different clinical or pharmacological needs. An ad-hoc mathematical model, describing the biomarker release process subsequent to AMI, has been devised and exploited to estimate typical parameter values, and to evaluate the impact of covariates on the cTnT release curve. Among all the available co-factors, the mixed-effect analysis has found dyslipidemia to be a statistically significant one. More specifically, it has highlighted a relevant effect on the model parameters related to cTnT clearance. By increasing the number of co-factors, and enlarging the patients dataset, this approach may be useful in the automatic categorization and to unravel potentially unknown interactions between cofactors in AMI patients.

Item does not contain fulltext OBJECTIVES: This study sought to evaluate sex differences in procedural characteristics and clinical outcomes of instantaneous wave-free ratio (iFR)- and fractional flow reserve (FFR)-guided revascularization strategies. BACKGROUND: An iFR-guided strategy has shown a lower revascularization rate than an FFR-guided strategy, without differences in clinical outcomes. METHODS: This is a post hoc analysis of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate stenosis to guide Revascularization) study, in which 601 women and 1,891 men were randomized to iFR- or FFR-guided strategy. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization. RESULTS: Among the entire population, women had a lower number of functionally significant lesions per patient (0.31 +/- 0.51 vs. 0.43 +/- 0.59; p < 0.001) and less frequently underwent revascularization than men (42.1% vs. 53.1%; p < 0.001). There was no difference in mean iFR value according to sex (0.91 +/- 0.09 vs. 0.91 +/- 0.10; p = 0.442). However, the mean FFR value was lower in men than in women (0.83 +/- 0.09 vs. 0.85 +/- 0.10; p = 0.001). In men, an FFR-guided strategy was associated with a higher rate of revascularization than an iFR-guided strategy (57.1% vs. 49.3%; p = 0.001), but this difference was not observed in women (41.4% vs. 42.6%; p = 0.757). There was no difference in MACE rates between iFR- and FFR-guided strategies in both women (5.4% vs. 5.6%, adjusted hazard ratio: 1.10; 95% confidence interval: 0.50 to 2.43; p = 0.805) and men (6.6% vs. 7.0%, adjusted hazard ratio: 0.98; 95% confidence interval: 0.66 to 1.46; p = 0.919). CONCLUSIONS: An FFR-guided strategy was associated with a higher rate of revascularization than iFR-guided strategy in men, but not in women. However, iFR- and FFR-guided strategies showed comparable clinical outcomes, regardless of sex. (Functional Lesion Assessment of Intermediate Stenosis to guide Revascularization [DEFINE-FLAIR]; NCT02053038).

In the light of growing global epidemic of type 2 diabetes mellitus (T2DM), significant efforts are made to discover next-generation biomarkers for early detection of the disease. Multiple mechanisms including inflammatory response, abnormal insulin secretion and glucose metabolism contribute to the development of T2DM. Platelet activation, on the other hand, is known to be one of the underlying mechanisms of atherosclerosis, which is a common T2DM complication that frequently results in ischemic events at later stages of the disease. Available data suggest that platelets contain large amounts of microRNAs (miRNAs) that are found in circulating body fluids, including the blood. Since miRNAs have been illustrated to play an important role in metabolic homeostasis through regulation of multiple genes, they attracted substantial scientific interest as diagnostic and prognostic biomarkers in T2DM. Various miRNAs, as well as their target genes are implicated in the complex pathophysiology of T2DM. This article will first review the different miRNAs studied in the context of T2DM and platelet reactivity, and subsequently present original results from bioinformatic analyses of published reports, identifying a common gene (PRKAR1A) linked to glucose metabolism, blood coagulation and insulin signalling and targeted by miRNAs in T2DM. Moreover, miRNA–target gene interaction networks built upon Gene Ontology information from electronic databases were developed. According to our results, miR-30a-5p, miR-30d-5p and miR-30c-5p are the most widely regulated miRNAs across all specified ontologies, hence they are the most promising biomarkers of T2DM to be investigated in future clinical studies.

Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are crucial in vascular remodeling. They exert pivotal roles in the development and progression of atherosclerosis, vascular response to injury, and restenosis after transcatheter angioplasty. As a witness of their importance in the cardiovascular system, a large body of evidence has accumulated about the role played by micro RNAs (miRNA) in modulating both VSMCs and ECs. More recently, a growing number of long noncoding RNA (lncRNAs) came beneath the spotlights in this research field. Several mechanisms have been revealed by which lncRNAs are able to exert a relevant biological impact on vascular remodeling. The aim of this review is to provide an integrated summary of ncRNAs that exert a relevant biological function in VSMCs and ECs of the vascular wall, with emphasis on the available clinical evidence of the potential usefulness of these molecules as circulating biomarkers of in-stent restenosis.

The tricuspid valve (TV) has been neglected for many years. Only recently, new studies demonstrated the prognostic role of the tricuspid valve lesions. In addition to that, new interventional approaches offer the possibility to non-invasively treat tricuspid valve disease. In this review, our aim is to summarize the role of different imaging techniques in the assessment of tricuspid valve with particular regards to congenital heart diseases. Finally, we analyze the importance of the TV and its adjacent regions from an electrophysiological point of view, both in structurally normal hearts and in congenital heart diseases. The most relevant transthoracic echocardiography (TTE) views to visualize the TV are the "modified" parasternal long axis, the apical views and subcostal projections, such as right oblique or left oblique views. However, simultaneous visualization of the three leaflets is possible only with three-dimensional TTE, or, sometimes, in parasternal short axis and subcostal short axis views in children. 3D echocardiography (3DE) is promising in this field. Indeed, its unique projections, such as en face views from the right ventricular and atrial perspectives, are able to define the spatial relationship of the tricuspid leaflets with the surrounding structures. Moreover, multimodality imaging assessment has been recently proposed for the diagnostic assessment of the TV, especially before percutaneous intervention. Cardiac Computed Tomography (CCT) provides valuable anatomic spatial information of the TV apparatus. Cardiac Magnetic Resonance (CMR) is able to provide, non-invasively, detailed morphological and functional information of the valve.

The inherited and acquired long QT is a risk marker for potential serious cardiac arrhythmias and sudden cardiac death. Smartwatches are becoming more popular and are increasingly used for monitoring human health. The present study aimed to assess the feasibility and reliability of evaluating the QT interval in lead I, lead II, and V2 lead using a commercially available Apple Watch. One hundred nineteen patients admitted to our Cardiology Division were studied. I, II, and V2 leads were obtained after recording a standard 12-lead ECG. Lead I was recorded with the smartwatch on the left wrist and the right index finger on the crown. Lead II was obtained with the smartwatch on the left lower abdomen and the right index finger on the crown. The V2 lead was recorded with the smartwatch in the fourth intercostal space left parasternal with the right index finger on the crown. There was agreement among the QT intervals of I, II, and V2 leads and the QT mean using the smartwatch and the standard ECG with Spearman’s correlations of 0.886; 0.881; 0.793; and 0.914 (p

Coronavirus disease 2019 (COVID-19) is a highly contagious disease that appeared in China in December 2019 and spread rapidly around the world. Several patients with severe COVID-19 infection can develop a coagulopathy according to the ISTH criteria for disseminated intravascular coagulopathy (DIC) with fulminant activation of coagulation, resulting in widespread microvascular thrombosis and consumption of coagulation factors. We conducted a meta-analysis in order to explore differences in coagulopathy indices in patients with severe and non-severe COVID-19. An electronic search was performed within PubMed, Google Scholar and Scopus electronic databases between December 2019 (first confirmed Covid-19 case) up to April 6th, 2020. The primary endpoint was the difference of D-dimer values between Non-Severe vs Severe disease and Survivors vs Non-Survivors. Furthermore, results on additional coagulation parameters (platelet count, prothrombin time, activated partial thromboplastin time) were also analyzed. The primary analysis showed that mean d-dimer was significantly lower in COVID-19 patients with non-severe disease than in those with severe (SMD − 2.15 [− 2.73 to − 1.56], I2 98%, P 2 98%, P 2 96%, P 2 97%, P 2 98%, P 2 98%, P

Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus first identified in Wuhan, China. The global number of confirmed cases of COVID-19 has surpassed 28,285,700 with mortality that appears higher than for seasonal influenza. About 20% of COVID-19 patients have experienced cardiac involvement and myocardial infarction in patients infected with SARS-CoV-2 had a worse prognosis. Furthermore, the widespread use of antiviral drugs can be linked to a worsening of heart function. Arrhythmias and hypertension have also been reported in patients with Covid-19. On the other hand, previous cardiac diseases are present in 30% of patients infected with SARS-CoV-2. There is uncertainty in the use of ace inhibitors and angiotensin II (Ang II) antagonists in the COVID-19 era. The mechanism of action of SARS-CoV-2 has been elucidated. It has been demonstrated that angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the new coronavirus SARS-CoV-2 and it is required for host cell entry and subsequent viral replication. The effect of the SARS-CoV-2 infection is the downregulation of ACE2 that may contribute to the severity of lung pathologies as well as the cardiac function. ACE2, a homolog of ACE, is a monocarboxypeptidase that converts Ang II into angiotensin 1-7 (Ang 1-7) that with its vasodilatory, antifibrotic, antihypertrophic effects counterbalances the negative effects of Ang II. On the other hand, angiotensin-converting enzyme inhibitors (ACEi) and AT1R blockers have been shown to upregulate the expression of ACE2. Based on the mechanism of action of SARS-CoV-2, the use of renin angiotensin system (RAS) inhibitors was questioned although all scientific societies did not recommend discontinuation when clinically recommended. The BRACE CORONA, a phase 4, randomized study tested two strategies: temporarily stopping the ACE inhibitor/angiotensin receptor blockers (ARB) for 30 days versus continuing ACE inhibitors/ARBs in patients who were taking these medications chronically and were hospitalized with a confirmed diagnosis of COVID-19 was also discussed. Therefore, the goal of this review is to summarize recent laboratory and clinical investigations concerning the use of ACEi and ARBs during the COVID-19 pandemic. The available data, based also on a randomized trial, suggest that ACEIs or ARBs, when clinically indicated, should be regularly used in the COVID-19 era.

Kawasaki disease (KD) can be associated with high morbidity and mortality due to coronary artery aneurysms formation and myocardial dysfunction. Aim of this study was to evaluate the diagnostic performance of non-invasive myocardial work in predicting subtle myocardial abnormalities in Kawasaki disease (KD) children with coronary dilatation (CADL). A total of 100 patients (age 8.7 ± 5 years) were included: 45 children with KD and CADL (KD/CADL) (Z-score > 2.5), 45 age-matched controls (CTRL) and, finally, an additional group of 10 children with KD in absence of coronary dilatation (KD group). Left ventricular (LV) systolic function and global longitudinal strain (GLS) were assessed. Global myocardial work index (MWI) was calculated as the area of the LV pressure-strain loops. From MWI, global Constructive Work (MCW), Wasted Work (MWW) and Work Efficiency (MWE) were estimated. Despite normal LV systolic function by routine echocardiography, KD/CADL patients had lower MWI (1433.2 ± 375.8 mmHg% vs 1752.2 ± 265.7 mmHg%, p . MWI, MCW and MWE were significantly reduced in KD children despite normal LVEF and normal GLS. These abnormalities seems independent from CADL. Thus, in KD with normal LVEF and normal GLS, estimation of MWI may be a more sensitive indicator of myocardial dysfunction.

Background The genetic architecture of Brugada syndrome (BrS) is emerging as an increasingly complex area of investigation. The identification of genetically homogeneous populations can provide mechanistic insights and improve genotype-phenotype correlation. Objective To characterize and define the clinical implications of a novel BrS founder mutation. Using a haplotype-based approach we investigated whether 2 SCN5A genetic variants could derive from founder events. Methods Single nucleotide polymorphisms were genotyped in 201 subjects, haplotypes reconstructed, and mutational age estimated. Clinical phenotypes and historical records were collected. Results A SCN5A variant (c.3352C>T; p.Gln1118Ter) was identified in 3 probands with BrS originating from south Italy. The same mutation was identified in a proband from central Italy and in 1 U.S. resident subject with Italian ancestry. The 5 individuals carried a common core haplotype, whose frequency was extremely low in local noncarrier probands and in population controls (0%–6.06%). The clinical presentation included multigenerational dominant transmission of Brugada electrocardiographic pattern, high incidence of sudden cardiac death (SCD), and cardiac conduction defects (CCD). We reconstructed 7-generation pedigrees with common geographic origin. Variant’s age estimates suggested that origin of the p.Gln1118Ter dates back 76 generations (95% confidence interval: 28–200). A second SCN5A variant (c.5350G>A; p.Glu1784Lys) identified in the region did not show similar founder signal. Conclusion p.Gln1118Ter is a novel BrS/CCD/SCD founder mutation. We illustrate how these findings provide insights on the inheritance patterns and phenotypes associated with SCN5A mutation.

The burden of atherosclerotic disease worldwide necessitates implementing the treatment of its risk factors. Among them, hypercholesterolemia has a central role. In addition to conventional small organic compounds and the recently introduced monoclonal antibodies, new technologies are arising such as the antisense oligonucleotides and small interfering RNAs (siRNAs) that operate upstream, blocking the mRNA translation of the proteins specifically involved in lipid metabolism. In this review, we briefly explain the mechanisms of action of these molecules and discuss the difficulties related to their in vivo use as therapeutical agents. We go over the oligonucleotides tested in clinical trials that could potentially revolutionize the care of patients by acting on proteins involved in the lipoprotein metabolism and regulation, namely: angiopoietin-like protein 3 (ANGPTL3); lipoprotein a (Lp(a)); apolipoprotein B (Apo B); apolipoprotein C III (Apo C-III); and proprotein convertase subtilisin–kexin type 9 (PCSK9). Finally, the differences between ASOs and siRNAs, their future possible clinical applications, and the role of Inclisiran, a siRNA direct against PCSK9 to reduce LDL-C, were reviewed in detail.

ObjectiveApproximately 3.4% of adults aged >75 years suffer from aortic stenosis (AS). Guideline indications for aortic valve replacement (AVR) distinguish between patients with symptomatic and asymptomatic severe AS. The present analysis aims to assess contemporary practice in the treatment of severe AS across Europe and identify characteristics associated with treatment decisions, namely denial of AVR in symptomatic patients and assignment of asymptomatic patients to AVR.MethodsParticipants of the prospective, multinational IMPULSE database of patients with severe AS were grouped according to AS symptoms, and stratified into subgroups based on assignment to/denial of AVR.ResultsOf 1608 symptomatic patients, 23.8% did not undergo AVR and underwent medical treatment. Denial was independently associated with multiple factors, including severe frailty (p=0.024); mitral (p=0.002) or tricuspid (p=0.004) regurgitation grade III/IV, and the presence of renal impairment (p=0.017). Of 392 asymptomatic patients, 86.5% had no prespecified indication for AVR. Regardless, 36.3% were assigned to valve replacement. Those with an indexed aortic valve area (AVA; p=0.045) or left ventricular ejection fraction (LVEF; pConclusionsThere may be considerable discrepancies between guideline-based recommendations and clinical practice decision-making in the treatment of AS. It appears that guidelines may not fully capture the complete clinical spectrum of patients with AS. Thus, there is a need to find ways to increase their acceptance and the rate of adoption.

Background and objectives The most advanced technologies and continuous innovations in the medical field require a necessary interaction between the clinical and the engineering world. In this context, software applications are proposed as a bridge between the two scientific fields and, therefore, as powerful tools, easy to use, and with great analytical skills. In this work, we propose CBRA as an innovative software platform, moving towards personalized medicine, which aims to simplify and speed up the triage of patients and support doctors in the diagnostic and prognostic phase. Methods The computational core of the devised software application consists of a model-based identification algorithm, which enables the reconstruction of the cardiac biomarkers release curves in patients with ST-Elevation Acute Myocardial Infarction (STEMI). Identification and parametric optimization techniques allow the application of the proposed approach to each singular patient: based on a few experimental acquisitions, CBRA can extrapolate several quantitative features of high clinical relevance, thus facilitating and rendering more objective the clinical evaluation and therapeutic choices. A dedicated database to collect and manage patients clinical and personal data, as well as a graphical user interface, provides clinicians and researchers with an intuitive and user-friendly environment. Results In the following work, we present some examples of the possible applications of CBRA, ranging from the management of the cardiac biomarkers time-series, up to the real analysis of the clinical features that CBRA can extract from the reconstructed curve, such as, e.g., maximum concentration values of biomarkers in the plasma and relative times, in the distinct phases of the acute myocardial infarction, or identification of the time to onset of symptoms. Conclusions CBRA makes it easy for clinicians to use modeling and parametric identification tools to reconstruct release curves. Furthermore, CBRA provides support to the clinical decision, thanks to its capability to extract information of high clinical relevance, not easily obtainable from the mere visual analysis of experimental samples. Having information about the previously listed clinical parameters could allow, e.g., identify in which stage of AMI the patient is, when She/He goes to the emergency room, with significant benefits in the therapy.

Aim This review represents a joint effort of the Italian Societies of Cardiology (SIC) and Diabetes (SID) to define the state of the art in a field of great clinical and scientific interest which is experiencing a moment of major cultural advancements, the cardiovascular risk management in type 2 diabetes mellitus. Data synthesis Consists of six chapters that examine various aspects of pathophysiology, diagnosis and therapy which in recent months have seen numerous scientific innovations and several clinical studies that require extensive sharing. Conclusions The continuous evolution of our knowledge in this field confirms the great cultural vitality of these two cultural spheres, which requires, under the leadership of the scientific Societies, an ever greater and effective collaboration.

Quantitative analysis of biochemical parameters is crucial for a correct diagnosis and prognosis of patients subject to acute myocardial infarction (AMI). In order to achieve a quantitative understanding of the dynamics of cardiac biomarkers, we have developed a mathematical model that can be exploited to extrapolate the release curve of cardiac troponin T (cTnT) into the plasma from few experimental acquisitions. The present work introduces a novel approach, based on the cTnT-release model, aimed at the identification of the infarct onset time. Indeed, in spite of the clinical importance of such information, in many cases, it is not easy to establish the exact time of occurrence of the ischemic event. We show that using a model-based optimization approach, the infarct onset time can be reliably estimated using the cTnT concentration acquisitions taken in the first few hours post-AMI. The assessment of the proposed approach is conducted on an experimental dataset, in which the infarct has been artificially induced and, therefore, the onset time is exactly known. In particular, the effectiveness of the devised estimation algorithm has been tested under several scenarios, with the first cTnT acquisition taken up to 12 h after AMI. Altogether, the proposed model-based approach provides a useful tool to help the clinicians in the quantitative estimation of important clinical parameters from the release curves of the cardiac biomarkers.

Cardiovascular magnetic resonance (CMR) has emerged as an accurate diagnostic technique for the evaluation of patients with cardiac disease in the majority of clinical settings, thanks to an established additional diagnostic and prognostic value. This document has been developed by a joined group of experts of the Italian Society of Cardiology (SIC) and Italian Society of Radiology (SIRM) to provide a summary about the current state of technology and clinical applications of CMR, to improve the clinical diagnostic pathways and to promote its inclusion in clinical practice. The writing committee consisted of members and experts of both societies in order to develop a more integrated approach in the field of cardiac imaging. This section 2 will cover myocarditis, pericardial disease, cardiomyopathies and valvular heart disease.

AimsTo investigate the changes in left atrial strain (LAS) after correction of severe aortic stenosis (AS) with transcatheter aortic valve replacement (TAVR) and assess its prognostic impact.Methods and resultsOne hundred consecutive patients with severe symptomatic AS who underwent TAVR at the Magna Graecia University of Catanzaro underwent echocardiographic examination including assessment of LAS before and after TAVR. Independent investigators collected outcome data and information. The primary study outcome was the difference in ΔLAS (postTAVR–preTAVR) between patients those met the main clinical endpoint (a composite of cardiovascular mortality and heart failure hospitalisation) and those not meeting the endpoint.During a median follow-up of 31 months, 35 patients (35%) met the combined clinical endpoint. The difference between LAS post-TAVR and LAS pre-TAVR (ΔLAS) was significantly larger in patients who met the combined endpoint (HR=0.76 (0.67–0.86); pConclusionsA lower reduction in ΔLAS after TAVR was an independent predictor of the primary composite outcome of cardiovascular death and hospitalisation for heart failure.

Contemporary evidence supports device-based transcatheter interventions for the management of patients with structural heart disease. These procedures, which include aortic valve implantation, mitral or tricuspid valve repair/implantation, left atrial appendage occlusion, and patent foramen ovale closure, profoundly differ with respect to clinical indications and procedural aspects. Yet, patients undergoing transcatheter cardiac interventions require antithrombotic therapy before, during, or after the procedure to prevent thromboembolic events. However, these therapies are associated with an increased risk of bleeding complications. To date, challenges and controversies exist regarding balancing the risk of thrombotic and bleeding complications in these patients such that the optimal antithrombotic regimens to adopt in each specific procedure is still unclear. In this review, we summarize current evidence on antithrombotic therapies for device-based transcatheter interventions targeting structural heart disease and emphasize the importance of a tailored approach in these patients.

Funding Acknowledgements Type of funding sources: None. Background Left ventricular non-compaction cardiomyopathy (LVNC) is associated with poor clinical outcome in childhood, with heart failure, arrhythmias, and embolic events as main clinical manifestations. LV twist has recently been demonstrated having good predictive value in diagnosing LVNC in young patients. However, how LV twist may influence long-term clinical outcome of LVNC children and adolescents is still unknown. The aim of this study was to analyse a set of echocardiographic parameters to find imaging predictors of worse clinical outcomes in a long-term follow-up of LVNC children and young patients. Methods Children and adolescents, followed from May 2012 to June 2020, were enrolled in a retrospective study. All patients underwent 2-dimensional speckle tracking echocardiography and cardiovascular magnetic resonance imaging (1.5 Tesla) at our Institution’s first evaluation. Death, heart failure hospitalization, aborted sudden cardiac death, ventricular arrhythmias (sustained and non-sustained ventricular tachycardia), and embolisms (i.e. stroke, peripheral arterial embolism and/or pulmonary thromboembolism) were registered and referred to as major adverse cardiovascular events (MACEs). Results Recruited for the study were 47 children (mean age: 11.1± 5; age range: 0–18 years). Twenty-three patients fulfilled the cardiovascular magnetic resonance imaging diagnostic criteria for LVNC (LVNC group), while the remaining 24 did not and were included in the LV hypertrabeculation group (LVHT). They were followed for 4.9 ± 1.0 years, and MACEs were registered. Thirteen children (56% of LVNC, 28% of total) had at least one MACE. Global longitudinal, circumferential and radial strains (GLS, GCS, GRS), LV twist and LVEF resulted being significantly reduced in children with MACEs at follow-up. A multivariable analysis was performed by combining four parameters: LV ejection fraction, GLS, GCS, LV twist. These independent variables were chosen according to univariable analyses and clinical relevance. The results from the analysis demonstrated that LV twist was the only independent predictor (P = 0.033, coeff. B 0.726) of worse clinical outcomes in young patients with LVNC. Conclusions LV twist is a promising tool to stratify and predict prognosis in LVNC young patients. Our findings show the importance of LV twist assessment to detect the severity of LVNC and to plan for early clinical intervention.