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Optimal dual antiplatelet therapy (DAPT) duration for patients undergoing percutaneous coronary intervention (PCI) for coronary bifurcations is an unmet issue. The BIFURCAT registry was obtained by merging two registries on coronary bifurcations. Three groups were compared in a two-by-two fashion: short-term DAPT (≤ 6 months), intermediate-term DAPT (6-12 months) and extended DAPT (>12 months). Major adverse cardiac events (MACE) (a composite of all-cause death, myocardial infarction (MI), target-lesion revascularization and stent thrombosis) were the primary endpoint. Single components of MACE were the secondary endpoints. Events were appraised according to the clinical presentation: chronic coronary syndrome (CCS) versus acute coronary syndrome (ACS). 5537 patients (3231 ACS, 2306 CCS) were included. After a median follow-up of 2.1 years (IQR 0.9-2.2), extended DAPT was associated with a lower incidence of MACE compared with intermediate-term DAPT (2.8% versus 3.4%, adjusted HR 0.23 [0.1-0.54], p

Spontaneous coronary artery dissection (SCAD) may occur in middle age population without any cardiovascular risk factor. We retrospectively evaluated anatomic features of 11 patients with SCAD using a coronary arteries computed tomography (CCT), compared to age and sex balanced patients who underwent CCT.CCT was performed in 11 patients (7 females and 4 males) as follow-up in patients with SCAD (left anterior descending - LAD or circumflex artery - Cx) and compared, using the propensity score matching analysis, with 11 healthy patients. Several anatomic features were evaluated: Left main (LM) length, angle between descending coronary artery (LAD) and its first branch, angle between LAD and LM, distance from the annulus to RCA (a-RCA distance) and LM (a-LM distance) ostia and their ratio; ratio between LM length and length a-LM and tortuosity score of the vessel with SCAD. A fluid dynamic analysis has been performed to evaluate the effects on shear stress of vessels wall.LM length was significantly shorter in patients with SCAD versus healthy subjects (P=0.01) as well as LM length/a-LM (P=0.03) and the angle between LAD and the first adjacent branch was sharper (P0.01). Tortuosity score showed a statistically significant difference between groups (P0.001). Fluid dynamic analysis demonstrates that, in SCAD group, an angle90 degree is present at the first bifurcation and it can be a cause of increased strain on vessel wall in patients with high tortuosity of coronary artery.Tortuosity and angle between the LAD and the adjacent arterial branch combined may determine increased shear stress on the vessel wall that increases the risk of SCAD.

CoronaVIrus Disease-19 (COVID-19) had a huge impact on human health and economy. However, to this date, the effects of the pandemic on the training of young cardiologists are only partially known. To assess the consequences of the pandemic on the education of the cardiologists in training, we performed a 23-item national survey that has been delivered to 1443 Italian cardiologists in training, registered in the database of the Italian Society of Cardiology (SIC). Six hundred and thirty-three cardiologists in training participated in the survey. Ninety-five percent of the respondents affirmed that the training programme has been somewhat stopped or greatly jeopardized by the pandemic. For 61% of the fellows in training (FITs), the pandemic had a negative effect on their education. Moreover, 59% of the respondents believe that they would not be able to fill the gap gained during that period over the rest of their training. A negative impact on the psycho-physical well being has been reported by 86% of the FITs. The COVID-19 pandemic had an unparalleled impact on the education, formation and mental state of the cardiologists in training. Regulatory agencies, universities and politicians should make a great effort in the organization and reorganization of the teaching programs of the cardiologists of tomorrow.

BACKGROUND/AIM: Extraordinary restrictions aimed to limit Sars-CoV-2 spreading; they imposed a total reorganization of the health-system. Oncological treatments experienced a significant slowdown. The aim of our multicentric retrospective study was to evaluate screening suspension and surgical treatment delay during COVID-19 and the impact on breast cancer presentation. PATIENTS AND METHODS: All patients who underwent breast surgery from March 11, 2020 to May 30, 2020 were evaluated and considered as the Lockdown group. These patients were compared with similar patients of the previous year, the Pre-Lockdown group. RESULTS: A total of 432 patients were evaluated; n=223 and n=209 in the Lockdown and Pre-lockdown-groups, respectively. At univariate analysis, waiting times, lymph-nodes involvement and cancer grading, showed a statistically significant difference (p

AIMS Unruptured aortic root pseudoaneurysm (UARP) is a rare complication of aortic valve endocarditis. Infectious spread to the valvular annulus or myocardium can cause septic complications that manifest as wall thickening, and spontaneous abscess drainage leads to pseudoaneurysm formation. We report the first patient series in which transcatheter aortic valve implantation (TAVI) using a single valve-resolved aortic valvulopathy associated with UARP was performed. METHODS At our center, from December 2017 to October 2019, 138 patients underwent TAVI for aortic valve stenosis and/or regurgitation, 20 of whom (12 female patients, 8 male patients) had associated incidental UARP and were considered as our study population. The average age of these patients was 76.9 ± 5.2 years. All patients were assessed using preprocedural and postprocedural multimodality imaging, including transthoracic echocardiography, transesophageal echocardiography, and cardiac computed tomography angiography (CCTA). RESULTS In all cases, the final angiographic examination showed correct valve positioning with complete coverage of the false aneurysm. Post-TAVI CCTA showed presence of total or subtotal UARP thrombosis. The mean follow-up period was 17.5 months (12-23 months). During follow-up, imaging showed normal prosthetic valve function, no significant leakage (trace or mild), and complete UARP exclusion in all patients, without any complications. CONCLUSION In conclusion, percutaneous valve positioning can simultaneously solve pseudoaneurysm complications by excluding the sac and promoting thrombosis.

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International audience; Background: The PARIS risk score (PARIS-rs) and percutaneous coronary intervention complexity (PCI-c) predict clinical and procedural residual ischemic risk following PCI. Their accuracy in patients undergoing unprotected left main (ULM) or bifurcation PCI has not been assessed.Methods: The predictive performances of the PARIS-rs (categorized as low, intermediate, and high) and PCI-c (according to guideline-endorsed criteria) were evaluated in 3,002 patients undergoing ULM/bifurcation PCI with very thin strut stents.Results: After 16 (12-22) months, increasing PARIS-rs (8.8% vs. 14.1% vs. 27.4%, p < .001) and PCI-c (15.2% vs. 11%, p = .025) were associated with higher rates of major adverse cardiac events ([MACE], a composite of death, myocardial infarction [MI], and target vessel revascularization), driven by MI/death for PARIS-rs and target lesion revascularization/stent thrombosis for PCI-c (area under the curves for MACE: PARIS-rs 0.60 vs. PCI-c 0.52, p-for-difference < .001). PCI-c accuracy for MACE was higher in low-clinical-risk patients; while PARIS-rs was more accurate in low-procedural-risk patients. ≥12-month dual antiplatelet therapy (DAPT) was associated with a lower MACE rate in high PARIS-rs patients, (adjusted-hazard ratio 0.42 [95% CI: 0.22-0.83], p = .012), with no benefit in low to intermediate PARIS-rs patients. No incremental benefit with longer DAPT was observed in complex PCI.Conclusions: In the setting of ULM/bifurcation PCI, the residual ischemic risk is better predicted by a clinical risk estimator than by PCI complexity, which rather appears to reflect stent/procedure-related events. Careful procedural risk estimation is warranted in patients at low clinical risk, where PCI complexity may substantially contribute to the overall residual ischemic risk.

Background The clinical impact of stent strut thickness in coronary bifurcation lesions in small vessels has not been assessed in a real-world population. Methods and results All 506 patients enrolled in the RAIN study, undergoing PCI in a vessel with a diameter 2.5 mm or less were retrospectively evaluated and divided into two groups according to stent strut thickness: 74 μm (n = 206) versus 81 μm (n = 300); 87.1% of the lesions involved bifurcations. TLF [defined as a composite of myocardial infarction (MI) and target lesion revascularization (TLR)] was the primary endpoint, with MACE (a composite of death, MI and TLR), its components and stent thrombosis the secondary endpoint. After 16 (14-18) months, a lower incidence of TLF (4.3 vs. 9.8%, P = 0.026) and ST (1.0 vs. 3.0%, P = 0.042) was seen in the 74 μm group, whereas MACE occurred in 60 of 506 patients, with no statistical difference between the two groups (9.7 vs. 13.3%, P = 0.070). At multivariate analysis, chronic renal failure increased the risk of TLF while thinner strut was an independent protective factor (hazard ratio 0.51, CI 0.17-0.85, P = 0.005). Conclusion In this real-world population, patients being treated for small vessels lesions with thinner strut stents had lower rates of TLF, MI and ST.

Patients affected by the human immunodeficiency virus (HIV) show an increased risk of myocardial infarction. Clinical and angiographic features of HIV positive (HIV+) patients presenting with the first episode of an acute coronary syndrome (ACS) are not well defined in previous studies.To demonstrate that HIV + patients with acute coronary syndrome had different features than non-HIV patients.We identified 48 HIV + patients without previous cardiovascular events admitted to our Emergency Department with ACS diagnosis between 2012 and 2020. Clinical and angiographic characteristics were compared with a control group of 48 non-HIV consecutive patients affected by ACS as first episode.HIV + patients were most frequently men (87.5% vs 62.5%,HIV + patients with the first episode of ACS are generally young men with higher triglycerides and most frequently presenting with anterior STEMI and LAD involvement. The strict control of risk factors and a program for the early identification of coronary artery disease are strongly recommended in this subset of patients.

Background The role of aortic valve Lambl's excrescence (LEs) in determining ischemic events has not been well clarified, but they can represent a potential embolic source during procedures with catheter/device manipulation through the aortic valve. Aim of our study was to assess the prevalence of LEs and the rate of embolism in patients with aortic valve stenosis scheduled for transcatheter aortic valve implantation (TAVI). Methods Our population was divided into two groups, named LEs and no-LEs. In each group, the rate of cerebral embolic events was assessed, as well as other TAVI-related complications. Results In our study population 28 patients (37%) had aortic strands and 48 (63%) did not have them. A cerebral protection device was used in 4 patients of LEs group (14% vs 0, p=0.03). The mean procedural time was similar in the two groups: 50±19 and 55±26 minutes (p=0.38) in LEs and no-LEs groups, respectively. The device success was achieved in 96% of LEs and 88% of no-LEs patients (p=0.37). Two patients of no-LEs group died during the procedure. Major complications were observed in both groups without any significant differences. Only one case of stroke occurred in the population without LEs (0 LEs vs 2% no-LEs, 0.78). No cases of peripheral embolism were observed. Conclusions In our population the observation of LEs is not uncommon. Despite the presumed high risk of embolism, we have not observed an increase in the rate of cerebral ischemic events or other TAVI related complications in patients with LEs.

AIMS The aim of our study was to assess the effects of an early percutaneous coronary intervention on changes of in-hospital left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) in patients with ST-segment elevation myocardial infarction. METHODS The study population consisted of 324 consecutive patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention, divided into two groups, according to the first medical contact (FMC)-to-reperfusion time, respectively, 90 min or less (n = 173) and more than 90 min (n = 151). Moreover, we performed a sub-analysis in the group of patients who showed at discharge an improvement in the LVEF of at least 10%. RESULTS In both groups at baseline, patients suffered from a moderately reduced LVEF (40.88 ± 8.38% in ≤90 min group vs. 40.70 ± 8.98% in >90 min group; P = 0.858). A WMSI of more than 1 was recorded uniformly: 1.71 ± 0.37 in patients with FMC-to-reperfusion 90 min or less and 1.72 ± 0.38 in patients more than 90 min (P = 0.810). At the time of discharge, a significant improvement in LVEF (43.82 ± 8.38%, P = 0.001) and WMSI (1.60 ± 0.41, P = 0.009) exclusively emerged in the 90 min or less group. Furthermore, we identified 105 patients who experienced an improvement in the LVEF of at least 10% compared with baseline values. In these patients FMC-to-reperfusion and total ischemic time resulted as significantly shorter, when compared with patients with LVEF improvement of less than 10%. CONCLUSION Our study confirms and reinforces the concept that reducing the duration of the time between FMC and reperfusion, as well as the total ischemic time influences a positive recovery of left ventricular global and regional function during in-hospital stay.

Background After the coronavirus disease 2019 outbreak, social isolation measures were introduced to contain infection. Although there is currently a slowing down of the infection, a reduction of hospitalizations, especially for myocardial infarction, was observed. The aim of our study is to evaluate the impact of the infectious disease on ST‐segment–elevation myocardial infarction (STEMI) care during the coronavirus disease 2019 pandemic, through the analysis of recent cases of patients who underwent percutaneous coronary intervention. Methods and Results Consecutive patients affected by STEMI from March 1 to 31, 2020, during social restrictions of Italian government, were collected and compared with patients with STEMI treated during March 2019. During March 2020, we observed a 63% reduction of patients with STEMI who were admitted to our catheterization laboratory, when compared with the same period of 2019 (13 versus 35 patients). Changes in all time components of STEMI care were notably observed, particularly for longer median time in symptom‐to‐first medical contact, spoke‐to‐hub, and the cumulative symptom‐to‐wire delay. Procedural data and in‐hospital outcomes were similar between the 2 groups, whereas the length of hospitalization was longer in patients of 2020. In this group, we also observed higher levels of cardiac biomarkers and a worse left ventricular ejection fraction at baseline and discharge. Conclusions The coronavirus disease 2019 outbreak induced a reduction of hospital access for STEMI with an increase in treatment delay, longer hospitalization, higher levels of cardiac biomarkers, and worse left ventricular function.

Background Management of elderly patients with acute myocardial infarction (AMI) is challenging due to lack of knowledge about the link between fragility, outcomes and interventional procedures. Aims The aim of this study was to establish the prognostic role of the Multidimensional Prognostic Index (MPI) in elderly with AMI. Methods A total of 241 patients ≥ 65 years old with AMI were continuously enrolled in this prospective study and divided into three groups according to the MPI score. The primary endpoint was 30-day mortality. Secondary endpoints were 6-month mortality and rate of adverse events. Results In-hospital overall mortality rate was higher in MPI-3 (p = 0.009). Patients of MPI-3 had a significantly higher mortality rate regarding the primary endpoint with 30-day survival of 78.9%, compared to 97.4% and 97.2%, in MPI-1, MPI-2 (p p Discussion Our findings are in agreement with the results of other studies that evaluated the risk of in-hospital complications and mortality in older patients. In our “real-world” population of elderly hospitalized for AMI we observed poorer outcomes in patients belonged to higher MPI groups. Conclusions In the setting of AMI, MPI may be very useful in the daily clinical practice to manage older patients and predict the risk of in-hospital and follow-up complications.

Background: There are limited data regarding the impact of final kissing balloon (FKI) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations. Methods: All patients undergoing left main or bifurcations percutaneous coronary intervention enrolled in the RAIN registry (Very Thin Stents for Patients With MAIN or BiF in Real Life: The RAIN, a Multicenter Study) evaluating ultrathin stents were included. Major adverse cardiac event (a composite of all-cause death, myocardial infarction, target lesion revascularization, and stent thrombosis) was the primary end point, while its components, along with target vessel revascularization, were the secondary end points. The main analysis was performed comparing patients with and without FKI after adjustment with inverse probability of treatment weighting. Subgroup analyses were performed according to FKI (short [ Results: Two thousand seven hundred forty-two patients were included. At 16 months (8–20) follow-up, inverse probability of treatment weighting adjusted rates of major adverse cardiac event were similar between FKI and no-FKI group (15.1% versus 15.5%; P =0.967), this result did not change with use of imaging, proximal optimization technique, or routine versus bail-out FKI. In the 2-stent subgroup, FKI was associated with lower rates of target vessel revascularization (7.8% versus 15.9%; P =0.030) and target lesion revascularization (7.3% versus 15.2%; P =0.032). Short overlap FKI was associated with a lower rate of target lesion revascularization compared with no FKI (2.6% versus 5.4%; P =0.034), while long overlap was not (6.8% versus 5.4%; P =0.567). Conclusions: In patients with bifurcations or unprotected left main treated with ultrathin stents, short overlap FKI is associated with less restenosis. In a 2-stent strategy, FKI was associated with less target vessel revascularization and restenosis. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03544294.

Incidence and predictors of adverse events after dual antiplatelet therapy (DAPT) cessation in patients treated with thin stents (

BACKGROUND Cardiac magnetic resonance is a valuable tool in the diagnosis of acute myocarditis, but dyspnea or chest pain often reduce patient's compliance, so definition of faster magnetic resonance protocols is of paramount importance. METHODS Short tau inversion recovery (STIR) and phase sensitive inversion recovery images for the assessment of late gadolinium enhancement (LGE)of 22 patients with clinical suspicion of acute myocarditis were retrospectively evaluated. Signal intensity in STIR images was measured by 2 readers by placing region of interests (ROIs) within the area of maximal signal intensity in each myocardial segment derived from the ACC/AHA segmental scheme. Segmental T2 ratio was assessed with the formula: signal intensity of myocardium/signal intensity of muscle. Receiver operating characteristic (ROC) curves were used to compare diagnostic performance of T2 Signal intensity and T2 ratio in predicting the presence of LGE in each myocardial segment. Bland-Altman analysis was used to assess inter reader agreement. RESULTS Signal intensity in STIR images showed an area under the curve (AUC) of 0.54 (95% CI: 0.44-0.63) for reader 1 and 0.53(95% CI: 0.44-0.63) for reader 2. Segmental T2 ratio showed an AUC of 0.8 (95% CI: 0.73-0.87) for reader 1 and 0.77 (95% CI: 0.71-0.84) for reader 2. Bland-Altman analysis showed good agreement for both T2 signal intensity (mean difference =-18.5 reader1 vs. reader 2 and 2SD=247.3) and T2 ratio (mean difference=0.03 vs. reader2 and 2SD=0.9). CONCLUSIONS Segmental T2 ratio showed a good diagnostic accuracy in predicting the presence of LGE in patients with clinical suspicion of acute myocarditis and might be a promising approach in reducing scan times with no reduction in diagnostic accuracy.

International audience; Objectives: To evaluate the independent clinical impact of stent structural features in a large cohort of patients undergoing unprotected left main (ULM) or coronary bifurcation percutaneous coronary intervention (PCI) with a range of very thin strut stents.Background: Clinical impact of structural features of contemporary stents remains to be defined.Methods: All consecutive patients enrolled in the veRy thin stents for patients with left mAIn or bifurcatioN in real life (RAIN) registry were included. The following stent structural features were studied: antiproliferative drugs (everolimus vs. sirolimus vs. zotarolimus), strut material (platinum-chromium vs. cobalt-chromium), polymer (bioresorbable vs. durable), number of crowns (

Doxorubicin (DOXO) is one of the most widely used antineoplastic drugs. Despite its highly beneficial effects against several malignancies, the clinical use of DOXO is often associated to cardiomyopathy that leads to congestive heart failure. Here we investigated the antioxidant and cardioprotective effects of a polyphenol-rich fraction of citrus bergamot (BPF), in DOXO-induced cardiac damage in rats. Moreover, we evaluated the effect of BPF on cardiomyocyte survival and resident endogenous cardiac stem/progenitor cell (eCSC) activation. Adult male Wistar rats were i.p. injected with saline (serving as controls, CTRL, n = 10), BPF (20 mg/kg daily for 14 consecutive days, n = 10), DOXO (6 doses of 2,5 mg/Kg from day 1 to day 14, n = 10), and DOXO + BPF (n = 10). Animals were then sacrificed 7 days later (i.e., at 21 days). DOXO administration reduced cardiac function at 21 days, an adverse effect significantly attenuated in animals receiving DOXO + BPF. No changes were detected in rats receiving just saline or BPF alone. The cardioprotective effect of BPF on DOXO acute toxicity was also associated with a significant antioxidant effect coupled with protective autophagy restoration, and attenuation of cardiomyocyte apoptosis and reactive hypertrophy. Finally, treatment of rats with BPF prevented eCSCs attrition by DOXO which was followed by a limited but significant increase of newly-formed BrdU+ cardiomyocytes. In conclusion, BPF reduces DOXO-induced cardiotoxicity by counteracting reactive oxygen species (ROS) overproduction, thereby restoring protective autophagy and attenuating cardiomyocyte apoptosis and pathologic remodeling. This beneficial effects on the early toxicity of DOXO is associated with enhanced CSCs survival and regenerative potential. Overall these data point to a potential clinical role by diet supplementation with polyphenol-rich fraction of citrus bergamot in counteracting antracycline-induced cardiomyopathy.

BACKGROUND AND AIM Cardiovascular diseases (CVDs) are the most frequent causes of death in the world. Inflammation and oxidative damage contribute significantly to the development of atherosclerosis and CVDs. European Food Safety Authority scientific opinion has acknowledged that hydroxytyrosol (3,4-dihydroxyphenylethanol) and derivatives, contained in extra virgin olive oil (EVOO), typically used in Mediterranean diet may play a crucial role in the reduction of the inflammatory pathway and in the prevention of CVDs. The aim of the study was to determine the effect in healthy volunteers of 25 g of phenols-rich EVOO (p-EVOO). METHODS The clinical study was a randomized, controlled trial to determine the acute effect in the postprandial time of 25 g of p-EVOO. We evaluated nutritional status using anthropometric parameters, body composition, serum metabolites, oxidative stress biomarkers and gene expression of eight genes related to oxidative stress and human inflammasome pathways, lasting 2 h after p-EVOO administration. Twenty-two participants resulted as eligible for the study. RESULTS A significant reduction of oxidized LDL, malondialdehyde, triglycerides and visceral adiposity index was highlighted (P

Introduction Percutaneous coronary intervention (PCI) for complex lesions, including unprotected left main (ULM) and bifurcations, is gaining a relevant role in treating coronary artery disease with good outcomes, also thanks to new generation stents. The daily risk of adverse cardiovascular events and their temporal distribution after these procedures is not known. Methods All consecutive patients presenting with a critical lesion of ULM or bifurcation treated with very thin struts stents, enrolled in the RAIN-Cardiogroup VII study, were analyzed. The daily risk of major acute cardiovascular events (MACE), target lesion revascularization (TLR) and stent thrombosis (ST) and their temporal distribution in the first year of follow-up was the primary endpoint. Differences among subgroups (ULM, patient presentation, kind of stent polymer) were the secondary endpoint. Results 2745 patients were included, mean age 68 ± 11 years, 33.3% diabetics, 54.5% had an acute coronary syndrome (ACS); 88.5% of treated lesions were bifurcations, 27.2% ULM. Average daily risk was 0.022% for MACE, 0.005% for TLR and 0.004% for ST, in the first year. Bimodal distribution of adverse events, especially TLR, with an early peak in the first 50 days and a late one after 150 days, was observed. Patients with ULM presented a significantly higher daily risk of events, and ACS patients presented higher MACE risk. No difference emerged according to the type of stent polymer. Conclusions The daily risk of adverse events in the first year after complex PCI in our study is acceptably low. PCI on ULM carries a higher risk of complications.

Few data are available about the impact on outcomes of procedural strategies for percutaneous coronary intervention with thin-struts stents on unprotected left main (ULM): 792 patients with an ULM stenosis treated with percutaneous coronary intervention with thin-strut stents were enrolled in the present multicenter registry. Target lesion revascularization (TLR) was the primary end point. MACE (a composite of all-cause death, myocardial infarction, TLR, and stent thrombosis) and its single components, along with target vessel revascularization were the secondary end points. Subgroup analyses were performed according to complex versus noncomplex bifurcation lesions. After 16 months, 5.5% of patients experienced a TLR. At multivariate analysis, provisional stenting (odds ratio [OR] 0.46: 0.85 to 0.23, p = 0.006), use of imaging (OR 0.45: 0.23 to 0.98, p = 0.003) and final kissing balloon (FKB) (OR 0.41: 0.83 to 0.21, p = 0.001) reduced risk of TLR. FKB reduced risk of overall TLR only for 2 stents-strategy (6.2% vs 32.4%, p

Transcatheter MitraClip repair is a new tool for the management of severe mitral regurgitation in patients at very high risk for conventional surgery. Aim of our study was reporting one-year clinical outcomes in candidates to MitraClip procedures, divided into three groups according to the cardiovascular medicine heart failure (CVM-HF) index. The study population consists of 46 consecutive patients, divided, in accordance with CVM-HF index, as follows: one patient in the low-risk category (group A); 27 patients in the medium-risk (group B) and 18 patients in high-risk category (group C). The primary study endpoint was a combined of all-cause mortality and re-hospitalization rate. Secondary endpoints were all-cause mortality and cardiac mortality. Patients of group B and group C were compared. Regarding the primary endpoint, patients in group C had significantly poorer outcomes than patients in group B, with a 12-month survival freedom from events of 44.4 and 74.1 %, respectively (log-rank test, p = 0.039); survival freedom from cardiac mortality was 100 and 83.3 % in group B and C, respectively (log-rank test, p = 0.027). One-year survival free from re-hospitalization was 74.1 % in group B and 39.9 % in group C (log-rank test; p = 0.036). Survival free from all-cause of mortality was 92.6 and 77.8 %, respectively (log-rank test; p = 0.129). In our initial experience the CVM-HF index showed to be valuable for understanding if the patient with advanced heart failure and functional mitral regurgitation can really benefit by MitraClip therapy.

Background Overproduction of oxidized-low density lipoproteins (oxyLDLs) has been found to contribute in endothelial cell (EC) dysfunction thereby leading to atherosclerosis development and progression. In particular, oxyLDLs lead to apoptotic cell death of EC via oxidative stress production, mostly subsequent to the overexpression of the scavenger receptor LOX-1. Here, we hypothesize that LOX-1 expression in EC represents a crucial event which attenuates protective autophagic response, thereby enhancing programmed endothelial cell death. Methods and results Bovine aortic endothelial cells (BAECs) in culture were exposed to oxyLDL (1–100μM). After 48h incubation, oxyLDL produced pronounced malondialdehyde (MDA) elevation and apoptotic cell death of BAEC as detected by FACS analysis, an effect counteracted by antioxidant N-acetyl-cysteine (NAC) as well as by the NO-donor SNAP. OxyLDL-induced apoptotic cell death was also accompanied by reduced VEGF-dependent phosphorylation of constitutive NO synthase (cNOS) in BAEC and consistent attenuation of autophagic response as detected by the expression of Beclin-1 and LC3, two reliable biomarkers of autophagy. Moreover, silencing LOX-1 receptor significantly restored LC3 expression in oxyLDL-treated BAEC, thus suggesting a key role of LOX-1 overproduction in oxyLDL-induced endothelial dysfunction. Conclusions OxyLDL leads to impaired NO generation and apoptotic cell death in BAECs. This effect occurs via the overexpression of LOX-1 and subsequent attenuation of protective autophagic response thereby contributing to the pathophysiology of oxyLDL-induced endothelial dysfunction which characterizes early stages of atherosclerotic process.

We report our experience with the CardiAQ prosthetic valve using both transapical and transseptal access. Aim of our study was proving the feasibility, safety and effectiveness of a novel transcatheter mitral valve bioprosthesis.Four patients with severe mitral regurgitation, not eligible for mitral valve surgery, were treated with the CardiAQ valve. The procedures were performed under general anaesthesia, fluoroscopic and transesophageal echocardiographic guidance. We used a transapical approach in two patients and transseptal access in the others.Procedural success was obtained in all patients without extracorporeal circulation support. Mean procedure time was 128 min (range 90-180) and mean hospitalization duration was 12 days (range 4-24). The transseptal approach resulted in significantly shorter in-hospital stay with quick recovery. One patient died on day 35 from septicaemia and another one died after 5 months from major bleeding. The survival patients are presently in New York Heart Association I-II with improved left ventricular ejection fraction and normal quality of life.CardiAQ valve placement is safe using a transapical or transseptal approach. Following valve replacement, there was a marked functional improvement in survivors. Transcatheter mitral valve replacement is a promising therapy for mitral regurgitation in a selected patient population.

The occurrence of Metabolic Syndrome (MS) represents an independent risk factor for developing cardiovascular disease states in patients suffering from type 2 diabetes mellitus. Moreover, both the size of LDL particles and liver dysfunction identified as non alcoholic fatty liver disease (NAFLD) represent important biomarkers for the development of cardiometabolic risk in patients with MS. Here we studied the effect of bergamot polyphenolic fraction (BPF) in patients with MS and NAFLD. 107 patients were enrolled at the San Raffaele IRCCS (Rome). All of them showed ultrasonografic evidences of NAFLD and at least three out of five previous identified criteria for the diagnosis of MS. Patients were divided into two groups: one receiving placebo and the second receiving BPF 650 mg twice a day for 120 consecutive days. In the group receiving BPF 650 mg twice a day, a significant reduction of fasting plasma glucose, serum LDL cholesterol and triglycerides alongside with an increase of HDL cholesterol was found. This effect was accompanied by significant reduction of both ultrasonographic and metabolic biomarkers of NAFLD. Moreover, a significant reduction of small dense LDL particles, as detected via proton NMR Spectroscopy, was found after BPF treatment. In conclusion, our data confirm the beneficial effect of bergamot-extract in patients with MS an effect highlighted by significant reduction of small dense LDL particles and by improvement of NAFLD biomarkers. This suggests a potential preventive role of bergamot derivatives in reducing cardiometabolic risk.

Cardiovascular diseases (CVD) including coronary artery disease (CAD) and ischemic heart disease (IHD) are the main cause of mortality in industrialized countries. Although it is well known that there is a difference in the risk of these diseases in women and men, current therapy does not consider the sexual dimorphism; i.e., differences in anatomical structures and metabolism of tissues. Here, we discuss how genetic, epigenetic, hormonal, cellular or molecular factors may explain the different CVD risk, especially in high-risk groups such as women with diabetes. We analyze whether sex may modify the effects of diabetes at risk of CAD. Finally, we discuss current diagnostic techniques in the evaluation of CAD and IHD in diabetic women.

PURPOSE The aim of our study was to assess the arterial cerebral blood flow variations in patients with aortic valve stenosis, immediately after the transcatheter aortic valve implantation (TAVI). METHODS The study population includes 62 consecutive patients who underwent TAVI for aortic valve stenosis (95%) and sugical bioprosthesis degeneration (5%). Carotid Doppler examination was performed recording blood flow, systolic peak velocity, time average mean velocity and mean acceleration time at baseline, after balloon aortic valvuloplasty, and within 10 min after the device release. RESULTS A significant improvement of blood flow was recorded at the end of the procedure (from 315.05 ± 141.72 to 538.67 ± 277.46 ml/min; P

Trans-catheter mitral valve implantation (TMVI) is actually the most attractive technique for treating patients with severe mitral regurgitation, who are denied surgical therapy. Recently, trans-catheter implantation of aortic biological prosthesis in mitral position has been done in compassionate cases, and very few experiences of TMVI in native non-calcified valves have been recently reported in very-high-risk patients, mainly with functional mitral regurgitation.Here, we report our case of TMVI using the second-generation CardiAQ prostheisis (CardiAQ Valve Technologies, Irvine, California, USA), reviewing the current state of the art.

The CoreValve Revalving System (CRS) (Medtronic Inc., Minneapolis, MN, USA) is currently available in four sizes: 23 mm, 26 mm, 29 mm and 31 mm. Aim of our study was to assess the acute clinical results after implantation of a 31 mm CRS.We assessed device safety, procedural success and 30-day outcomes of 76 consecutive patients who underwent transcatheter aortic valve implantation (TAVI) from January 2012 to September 2013, for severe aortic valve disease. The device sizes used were 26 mm in 21 (28%), 29 mm in 20 (26%) and 31 mm in 35 (46%) patients. Patients who received the 31 mm CRS were significantly younger, predominantly male, with higher STS scores and lower left ventricular ejection fraction. Device success was obtained in 70 cases (92%) in the overall population, without significant differences among groups. Procedural, fluoroscopy and revalving time and procedural outcomes did not differ. A significant reduction in transaortic gradient was obtained in all groups. We observed a low incidence of paraprosthetic leak in the 31 mm group. Permanent pacemaker implantation, bleeding, vascular and renal complications were similar among groups. Time of hospitalisation in CRS 31 mm patients did not differ from the other groups and 30-day outcomes were comparable.The 31 mm CRS can be safely implanted in patients with complex aortic valve disease, large annuli and dilated left ventricles.

We describe an alternative access approach for patients undergoing transcatheter aortic valve implantation (TAVI) using surgical cut down of the distal axillary artery, in cases wherein transfemoral access is not feasible.From January 2012 to July 2013, 61 patients (59% men; mean age 81 ± 8 years) underwent TAVI at our institution. The mean logistic EuroSCORE and EuroSCORE II were 36 ± 24 and 14 ± 10, respectively. We assessed device success, 30-day safety and clinical efficacy using VARC II criteria.TAVI was performed with the CoreValve Revalving System (CRS) (Medtronic Inc., Minneapolis, Minnesota, USA) in all cases, using transfemoral approach in 57 patients and distal trans-axillary route in four patients. A device was successfully implanted in 94%, without any major intraprocedural complications. One case of acute kidney disease, four cases of minor vascular complication and two cases of life-threatening bleeding occurred after the procedure for pericardial bleeding requiring pericardiocentesis. Permanent pacemaker was implanted in 26% of patients. There was no instance of in-hospital mortality, while two deaths (3%) occurred in the first 30 days. The total procedure time (skin-to-skin) was longer in the trans-axillary group secondary to surgical management of access site (P = 0.027), whereas revalving and fluoroscopy time were similar (P = 0.95 and P = 0.83, respectively).The location and anatomical relations of the distal axillary artery make it a safer, reproducible and operator friendly access option for TAVI.

There are concerns about percutaneous closure of patent foramen ovale (PFO) using nitinol-alloys devices in patients with nickel hypersensitivity. We describe our experience with Atriasept II (Cardia Eagan, Minnesota, USA) used in four patients with known nickel allergy. No intraprocedural or in-hospital adverse events occurred. The follow-up was negative for allergic manifestations, without complications, as assessed by echocardiography. Because of the risk of adverse outcomes in nickel-allergic patients, devices with higher biocompatibility, low-profile, and low nickel content should be preferred in cases of known hypersensitivity. Atriasept II, containing less metallic material, appears to be a safe option in allergic patients undergoing PFO closure.

Aims We sought to assess the hemodynamic sequel and the therapy adopted in patients treated with MitraClip system, who experienced a persistent interatrial communication (IAC) after the procedure. Methods From January 2012 to March 2013, 28 consecutive patients (mean age 74 ± 8 years) underwent transcatheter MitraClip repair, as part of an ongoing prospective study to assess the IAC. Results Acute procedural success was 100% and a 30-days survival of 97% was reported. Immediately after the procedure, a residual IAC was present in all patients with an average diameter of 0.51 ± 0.39 cm. At 30 days, IAC was detected in 81% of patients with a diameter of 0.45 ± 0.31 cm (P = 0.53). To date, three patients developed different hemodynamic impairment secondary to the residual IAC, requiring percutaneous closure of the defect. Conclusion Anatomic and hemodynamic criteria for early recognition of harmful residual IAC have to be identified, in order to select those patients who are benefited the most from atrial septal defect closure.

The image describes a case of left atrial appendage occlusion in a patient with atrial fibrillation, previous haemorrhagic stroke, and left atrial appendage thrombosis. A cerebral vascular filter was used during the device implantation. The use of cerebral embolic protection device can increase the safety of left atrial appendage occlusion, in selected high-risk patients.

Background OxLDL plays a major role in the initiation and progression of atherosclerotic lesions even though further factors are needed to promote fibrous cap rupture and thrombotic occlusion of the arterial lumen. Pathogens have been implicated in this process but it remains unclear how they can cooperate with oxLDL in amplifying the destructive inflammatory response. Objective To phenotypically analyze culprit coronary inflammatory cells, evaluate their responsiveness to endotoxins and ascertain whether oxLDL alters the sensitivity of coronary mononuclear cells to bacterial components. Methods Mononuclear cells isolated from culprit and non-culprit coronary blood samples of patients with ST-segment elevation myocardial infarction (STEMI) and controls were analyzed for cell-specific surface markers and cytokines by flow-cytometry. Results and conclusions CD14 + cells contained elevated levels of TLR4, expressed high CD80, and produced huge amounts of inflammatory cytokines in response to LPS. Using a well-established model of endotoxin tolerance, we next showed that mononuclear cells isolated from control coronary artery, but not from culprit coronary artery, were tolerant to LPS, but pre-treatment of such cells with oxLDL abrogated LPS tolerance. Flow-cytometry analysis also showed that IL-17A, IL-21 and IFN-γ were over-produced by CD4 + and CD56 + cells isolated from the culprit coronary artery. All this data indicate that monocytes circulating in the culprit coronary artery of patients with STEMI are primed to synthesize high levels of inflammatory cytokines and suggest that oxLDL can amplify the inflammatory response of such cells to endotoxins.

Despite the recommendations of the current guidelines, scientific evidence continue to challenge the effectiveness of intra-aortic balloon pump (IABP) in acute myocardial infarction (AMI) complicated by cardiogenic shock. Moreover, 2 recent meta-analyses showed contrasting results. The aim of this study is to test the effect of IABP according to the type of therapeutic treatment of AMI: percutaneous coronary intervention (PCI), thrombolytic therapy (TT), or medical therapy without reperfusion. Articles published from January 1, 1986, to December 31, 2012, were collected and analyzed by meta-analysis.We evaluated the IABP impact on inhospital mortality, on safety end points (stroke, severe bleeding) and long-term survival, using risk ratio (RR) and risk difference (RD) estimates. We found that the risk of death was (i) not significantly different between the IABP and control groups (RR 0.95, P = .52; RD -0.04, P = .28), (ii) significantly reduced in the TT subgroup (RR 0.77, P.0001; RD -0.16, P.0001), and (iii) significantly increased in the PCI subgroup (RR 1.18, P = .01; RD 0.07, P = .01). There were no significant differences in secondary end points (P, not significant). In addition, we compared the meta-analyses collected over the same search period.The results show that IABP support is significantly effective in TT reperfusion but is associated with a significant increase of the inhospital mortality with primary PCI. The comparison of the meta-analyses demonstrates the key role of analysing primary clinical treatments to avoid systematic errors.

Lectin-like oxyLDL receptor-1 (LOX-1) has recently been suggested to be involved in smooth muscle cell (SMC) proliferation and neointima formation in injured blood vessels. This study evaluates the effect of the nonvolatile fraction (NVF), the antioxidant component of bergamot essential oil (BEO), on LOX-1 expression and free radical generation in a model of rat angioplasty. Common carotid arteries injured by balloon angioplasty were removed after 14 days for histopathological, biochemical, and immunohistochemical studies. Balloon injury led to a significant restenosis with SMC proliferation and neointima formation, accompanied by increased expression of LOX-1 receptor, malondialdehyde and superoxide formation, and nitrotyrosine staining. Pretreatment of rats with BEO-NVF reduced the neointima proliferation together with free radical formation and LOX-1 expression in a dose-dependent manner. These results suggest that natural antioxidants may be relevant in the treatment of vascular disorders in which proliferation of SMCs and oxyLDL-related endothelial cell dysfunction are involved.

Hyperuricemia has long been established as the major etiologic factor in gout. Alongside with an inflammatory state triggered by urate crystal deposition in the joints, hyperuricemia displayed additional pathophysiological consequences leading to tissue inflammation mainly in the vascular wall. Thus, therapeutic strategies used to treat hyperuricemia in the past decades have often been focused on limiting acute episodes. Recently, evidence has been accumulated suggesting that chronic urate deposition requires a correct treatment not limited to acute episodes based on the modulation of the activity of key enzymes involved in metabolism and excretion of urate including xanthine oxidoreductase (XO) and URAT1. The present review article will try to summarize the most recent evidences on the efficacy of XO inhibitors and uricosuric compounds in lowering uric acid levels in both the bloodstream and peripheral tissues. In particular, we will focus on the effect of novel XO inhibitors in counteracting uric acid overproduction. On the other hand, the effect of lowering uric acid levels via XO inhibition will be correlated with attenuation oxidative stress which leads to endothelial dysfunction thereby contributing to the pathophysiology of diabetes, hypertension, arteriosclerosis, and chronic heart failure. Hence, scavenging and prevention of the XO generated oxygen radical accumulation emerge as an intriguing novel treatment option to counteract uric acid-induced tissue damages.

Chronic obstructive pulmonary disease (COPD) is often associated with cardiovascular artery disease (CAD), representing a potential and independent risk factor for cardiovascular morbidity. Therefore, the aim of this study was to identify an algorithm for predicting the risk of CAD in COPD patients.We analyzed data of patients afferent to the Cardiology ward and the Respiratory Diseases outpatient clinic of Tor Vergata University (2010-2012, 1596 records). The study population was clustered as training population (COPD patients undergoing coronary arteriography), control population (non-COPD patients undergoing coronary arteriography), test population (COPD patients whose records reported information on the coronary status). The predicting model was built via causal relationship between variables, stepwise binary logistic regression and Hosmer-Lemeshow analysis. The algorithm was validated via split-sample validation method and receiver operating characteristics (ROC) curve analysis. The diagnostic accuracy was assessed.In training population the variables gender (men/women OR: 1.7, 95%CI: 1.237-2.5, P 0.05), dyslipidemia (OR: 1.8, 95%CI: 1.2-2.5, P 0.01) and smoking habit (OR: 1.5, 95%CI: 1.2-1.9, P 0.001) were significantly associated with CAD in COPD patients, whereas in control population also age and diabetes were correlated. The stepwise binary logistic regressions permitted to build a well fitting predictive model for training population but not for control population. The predictive algorithm shown a diagnostic accuracy of 81.5% (95%CI: 77.78-84.71) and an AUC of 0.81 (95%CI: 0.78-0.85) for the validation set.The proposed algorithm is effective for predicting the risk of CAD in COPD patients via a rapid, inexpensive and non-invasive approach.