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Aim An underlying atrial vulnerability or a preexisting misdiagnosed atrial fibrillation in some patients who are candidates for patent foramen ovale (PFO) closure may lead to an unnecessary percutaneous intervention. The aim of this work was to define paroxysmal atrial fibrillation rate, through a 6-month insertable loop-recorder monitoring, in patients over 55 years old with cryptogenic stroke and PFO. Methods PFO closure criteria: significant right-to-left shunt and at least one high-risk feature (permanent right-to-left shunt, atrial septal aneurysm, prominent Eustachian valve, recurrent brain ischemia, previous deep vein thrombosis, thrombophilia). Insertable cardiac monitoring criteria: previous cryptogenic stroke, more than 55 years and at least one atrial fibrillation risk factor (heart failure, hypertension, age older than 65 years, diabetes, atrial runs, left atrium dilatation, left ventricle hypertrophy, pulmonary disease, thyroid disease, obesity). Atrial fibrillation detection threshold: arrhythmia duration longer than 5 min. Results From January 2008 to March 2017, 195 patients underwent to loop-recorder monitoring. A total of 70 (36%) patients were candidates for PFO closure. The 6-month silent atrial fibrillation rate was 11.4%. In the arrhythmia-free cohort, 28 patients (45.2%) underwent percutaneous foramen ovale closure (group A) and 34 (54.8%) were medically treated (group B). Atrial fibrillation detection rate was 14.3% in group A and 0% in group B. The 36-month atrial fibrillation-free survival was 76%. Conclusion An occult preexisting atrial fibrillation may lead to unnecessary percutaneous foramen ovale closure in a significant proportion of patients. A 6-month loop-recorder monitoring may improve the patient oriented decision-making.

Background Late-onset complications of left atrial appendage occlusion (LAAO) device procedure are anecdotal and there are no such complications reported in literature using Cardia Ultraseal (Cardia, Inc., Eagan, MN, USA). Case summary We report the case of a 74-year-old Caucasian man affected by paroxysmal atrial fibrillation with significant bleeding risk (familiar thrombocytopenia, macroscopic haematuria episodes during therapy with direct oral anticoagulants, HAS-BLED risk score: 4) and ischaemic risk as well (CHADSVASC score: 3). The patient was treated with LAAO device implantation for high bleeding risk. Subsequently, after 26 days from LAAO procedure, he was admitted to the emergency department for haematic cardiac tamponade. The patient was successfully treated with subxyphoidal pericardiocentesis in the acute phase, unfortunately cardiac arrest occurred during the transfer to the referral hospital for urgent cardiac surgery. Permanent neurological damage was reported and the patient died on day 28. Discussion LAAO late-onset complications are very rare and the case presented is the first case described of late-onset pericardial effusion and tamponade secondary to the Cardia Ultraseal LAAO device implantation. We present a revision of the literature regarding the occurrence of similar adverse events and discuss the hypothetical mechanism of this major complication.

Patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions but to date only one official position paper related to left circulation thromboembolism has been published. This interdisciplinary paper, prepared with the involvement of eight European scientific societies, reviews the available evidence and proposes a rationale for decision making for other PFO-related clinical conditions. In order to guarantee a strict evidence-based process, we used a modified grading of recommendations, assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements were weighed and graded according to predefined scales. Despite being based on limited and observational or low-certainty randomised data, a number of position statements were made to frame PFO management in different clinical settings, along with suggestions for new research avenues. This interdisciplinary position paper, recognising the low or very low certainty of existing evidence, provides the first approach to several PFO-related clinical scenarios beyond left circulation thromboembolism and strongly stresses the need for fresh high-quality evidence on these topics.

Introduction: Little is still known about the prognostic impact of incident arrhythmias in hospitalized patients with COVID-19. The aim of this study was to evaluate the incidence and predictors of sustained tachyarrhythmias in hospitalized patients with COVID-19, and their potential association with disease severity and in-hospital mortality. Materials and methods: This was a retrospective multicenter observation study including consecutive patients with laboratory confirmed COVID-19 admitted to emergency department of ten Italian Hospitals from 15 February to 15 March 2020. The prevalence and the type of incident sustained arrhythmias have been collected. The correlation between the most prevalent arrhythmias and both baseline characteristics and the development of ARDS and in-hospital mortality has been evaluated. Results: 414 hospitalized patients with COVID-19 (66.9±15.0years, 61.1% male) were included in the present study. During a median follow-up of 28days (IQR: 12-45), the most frequent incident sustained arrhythmia was AF (N: 71; 17.1%), of which 50 (12.1%) were new-onset and 21 (5.1%) were recurrent, followed by VT (N: 14, 3.4%) and supraventricular arrhythmias (N: 5, 1.2%). Incident AF, both new-onset and recurrent, did not affect the risk of severe adverse events including ARDS and death during hospitalization; in contrast, incident VT significantly increased the risk of in-hospital mortality (RR: 2.55; P:.003). Conclusions: AF is the more frequent incident tachyarrhythmia; however, it not seems associated to ARDS development and death. On the other hand, incident VT is a not frequent but independent predictor of in-hospital mortality among hospitalized COVID-19 patients.

Cryptogenic cerebral ischemia in young patients is commonly ascribed to paradoxical embolism. We report the clinical case of a young patient with cryptogenic stroke and a patent foramen ovale, undergoing percutaneous closure of atrial septal defect. Contrast transoesophageal echocardiography at the end of the procedure demonstrated massive late residual right-to-left shunt, due to the coexistence of pulmonary arteriovenous fistulas that were subsequently closed. Routinary adoption of contrast transoesophageal echocardiography at the end of patent foramen ovale closure interventions may be useful to detect early and late residual shunts. Late residual shunts may be due to pulmonary fistulas, a well-known risk factor for recurrent thromboembolic events.

Patent foramen ovale (PFO) is implicated in the pathogenesis of different clinical syndromes in which it plays variable roles. In 2017 and 2018, four randomized clinical trials were published, allowing for the clarification of certain issues pertaining to cryptogenic stroke. Recently, eight European scientific societies collaborated to the writing of an interdisciplinary international position paper on PFO and cryptogenic stroke, based upon best available evidence, with the aim of defining the principles needed to guide decision making. Nonetheless, a tailored approach is not suitably addressed by standard position documents, considering that decisions about optimal management of PFO patients with left circulation thromboembolism are often challenging, mostly due to comorbidities and complex clinical scenarios.A panel of Italian cardiology experts gathered under the auspices of the Italian Society of Interventional Cardiology (SICI-GISE) for comprehensive discussion and consensus development, with the aim of providing practical recommendations, for both clinical and interventional cardiologists, regarding optimal management of PFO in patients with cerebral or systemic thromboembolism. In this position paper, various clinical scenarios in patients with and without high-risk PFO features are presented and discussed, including PFO patients with associated conditions (e.g. hypercoagulable states, deep vein thrombosis/pulmonary embolism, short runs of atrial fibrillation), and special subsets (e.g. patients with risk factors for atrial fibrillation, patients aged ≥65 years, patients who refused percutaneous PFO closure), with the Panel's recommendations being provided for each scenario.

Background Evidence-based recommendations about anticoagulation in acute type B aortic dissection (TBAD) are completely missing, but there is a diffuse conviction that it could prevent the healing process of the dissected aorta’s false lumen. However, several clinical conditions may lead to the necessity to start anticoagulant therapy among patients with acute type B aortic dissection, ranging from atrial fibrillation to more complicated clinical scenarios and the correct management in this kind of patients is still an open issue. Case presentation We are presenting a 51-years-old man with multi-infarct encephalopathy referred to us for an acute TBAD and a first diagnosis of ischemic cardiomyopathy complicated by left ventricular (LV) thrombus formation. Coronary angiography revealed a critical stenosis of left anterior descending artery (LAD) treated with drug-eluting stent deployment. The patient was addressed to triple antithrombotic therapy with acetylsalicylic acid, clopidogrel and warfarin with target INR 2.0–2.5. After 6 months, computed tomography angiography revealed the stability of the dissection flap. Cardiac magnetic resonance imaging, however, confirmed the persistence of a small thrombotic formation in LV apex, thus double antithrombotic therapy with warfarin and clopidogrel was instituted. The patient remained asymptomatic during the follow-up period but was advised to suspend his job and physical activities. Conclusion Current guidelines do not discuss anticoagulant therapy in the setting of TBAD and large randomized trials are lacking. Despite it is generally considered unsafe to administer anticoagulants in patients with TBAD, we present a case in which triple antithrombotic therapy was well tolerated and did not lead to progression of the intimal flap after 6 months.

Objectives The purpose of this study is to compare the long-term outcomes of patent foramen ovale (PFO) closure using angiography or transesophageal echocardiography as procedural guidance. Background The interventional treatment is emerging as a safe and efficient option for patients with high likelihood of PFO-related cryptogenic stroke and high risk of recurrence. The "gold-standard" guidance technique remains an issue. Methods Two cohorts of patients undergoing PFO closure for cryptogenic stroke in two catheterization laboratories of the same institution, using similar inclusion criteria but different guidance, were compared with propensity score matching. Results A total of 374 patients were enrolled, 161 in Angio-group and 213 in Echo-group. No difference was detected in the procedural complication rate. In Angio-group, radiological exposure (P = .001) and 6-month residual shunt (16.8% vs 8.0%, P = .015) were higher. After a mean follow-up of 41 ± 30 months, 28 patients (7.5%) presented any adverse event (death, recurrent cerebral ischemia, device-related complications, reintervention), with a higher rate in Angio-group (13.0% vs 3.3%, P = .001), mainly due to repeated percutaneous intervention (10.6% vs 1.4%, P = .001). The results were confirmed after propensity score matching (118 patients/group). The rate of recurrent cerebral ischemia was 1.9% and was not significantly different in the two groups. Intra-procedural guidance and atrial septum aneurysm were independent predictors of the composite primary endpoint (OR 1.2, P = .016). Conclusions The use of intra-procedural transesophageal echocardiography (TEE) guidance for PFO closure allows lower residual shunt rate, radiological exposure, and adverse events, mainly driven by a significant reduction in percutaneous reintervention.

Cardiac cell-based therapy has emerged as a novel therapeutic option for patients dealing with untreatable refractory angina (RA). However, after more than a decade of controlled studies, no definitive consensus has been reached regarding clinical efficacy. Although positive results in terms of surrogate endpoints have been suggested by early and phase II clinical studies as well as by meta-analyses, the more recent reports lacked the provision of definitive response in terms of hard clinical endpoints. Regrettably, pivotal trials designed to conclusively determine the efficacy of cell-based therapeutics in such a challenging clinical condition are therefore still missing. Considering this, a comprehensive reappraisal of cardiac cell-based therapy role in RA seems warranted and timely, since a number of crucial cell- and patient-related aspects need to be systematically analysed. As an example, the large variability in efficacy endpoint selection appears to be a limiting factor for the advancement of cardiac cell-based therapy in the field. This review will provide an overview of the key elements that may have influenced the results of cell-based trials in the context of RA, focusing in particular on the understanding at which the extent of angina-related endpoints may predict cell-based therapeutic efficacy.

The presence of a patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions; however, the subject remains controversial and no official statements have been published. This interdisciplinary paper, prepared with involvement of eight European scientific societies, aims to review the available trial evidence and to define the principles needed to guide decision making in patients with PFO. In order to guarantee a strict process, position statements were developed with the use of a modified grading of recommendations assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements of particular management options were weighed and graded according to predefined scales. Despite being based often on limited and non-randomised data, while waiting for more conclusive evidence, it was possible to conclude on a number of position statements regarding a rational general approach to PFO management and to specific considerations regarding left circulation thromboembolism. For some therapeutic aspects, it was possible to express stricter position statements based on randomised trials. This position paper provides the first largely shared, interdisciplinary approach for a rational PFO management based on the best available evidence.

Background: The risk/benefit balance of transcatheter aortic valve implantation (TAVI) in patients with low-gradient aortic stenosis (LGAS) remains to be well defined. Aim of the study was to investigate the impact of LGAS in patients undergoing TAVI. Methods: Medline, Cochrane Library, and Scopus were searched for articles reporting outcome of patients with LGAS undergoing TAVI. The primary endpoint was 12-months all-cause mortality and the secondary endpoint was 30-day all-cause mortality. Using event-rates as dependent variable, a meta-regression was performed to test for interaction between baseline clinical features (age, gender, diabetes mellitus, coronary artery disease, left ventricular ejection fraction (LVEF) and type of implanted valve) and transaortic gradient for the primary endpoint. Results: Eight studies with a total of 12,589 patients were included. Almost one-third of the patients presented with LGAS (27.3%: 24.4–29.2). Median LVEF was 48% in patients with LGAS and 56% in patients with high-gradient AS. Patients with LGAS were more likely to have diabetes mellitus, previous coronary artery disease, higher mean Logistic EuroSCORE, and lower EF. At 12 (12–16.6) months, low transaortic gradient emerged as independently associated with all-cause death, both if evaluated as a dichotomous and continuous value (respectively OR 1.17; 1.11–1.23 and OR 1.02; 1–1.04, all CI 95%). Clinical variables, including EF did not affect this result. Conclusions: In a population of TAVI patients, LGAS appears to be independently related to dismal prognosis. © 2016 Wiley Periodicals, Inc.

Introduction Cardiovascular diseases are the leading cause of mortality worldwide. Apical periodontitis (AP) has been associated with an increased risk of cardiovascular diseases. A correlation has been shown between chronic AP and endothelial dysfunction (ED), but there is no evidence to indicate ED improves after endodontic treatment in patients with periapical lesions. The aim of this study was to investigate vascular and molecular markers of early ED before and after root canal treatment in young adults with chronic AP. Methods Twenty control subjects and 21 patients with AP were assessed at baseline. The AP patients were also evaluated 2 and 12 months post-treatment. Endothelial flow reserve was assessed via an endothelial function test, and enzyme-linked immunosorbent assays were used to evaluate plasma levels of proinflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor alpha; vasoconstrictor ED marker endothelin (ET)-1; circulating endothelial adhesion markers intercellular adhesion molecule 1 (ICAM-1)/CD54 and soluble vascular cellular adhesion molecule (sVCAM)-1/CD106; soluble CD14; and the endothelial leukocyte adhesion molecule (E-selectin). Results AP was associated with increased serum levels of ET-1, ICAM-1, E-selectin, IL-1, and sCD14, suggesting early vascular ED, with no macroscopic evidence of a reduction in endothelial flow reserve. Root canal treatment ameliorated inflammation and early ED, lowering plasma levels of IL-1, sCD14, ET-1, ICAM-1/CD54, and E-selectin to those of control subjects. Conclusions Our findings suggest that AP may drive early vascular ED and that the endodontic therapy of AP ameliorates early ED.

Background Cell therapy with bone marrow (BM)-derived progenitors has emerged as a promising therapeutic for refractory angina (RA) patients. In the present study, we evaluated the safety and preliminary efficacy of transcatheter delivery of autologous BM-derived advanced therapy medicinal product CD133+ cells (ATMP-CD133) in RA patients, correlating perfusion outcome with cell function. Methods In the phase I “Endocavitary Injection of Bone Marrow Derived CD133+ Cells in Ischemic Refractory Cardiomyopathy” (RECARDIO) trial, a total of 10 patients with left ventricular (LV) dysfunction (ejection fraction ≤ 45%) and evidence of reversible ischemia, as assessed by single-photon emission computed tomography (SPECT), underwent BM aspiration and fluoroscopy-based percutaneous endomyocardial delivery of ATMP-CD133. Patients were evaluated at 6 and 12 months for safety and preliminary efficacy endpoints. ATMP-CD133 samples were used for in vitro correlations. Results Patients were treated safely with a mean number of 6.57 ± 3.45 × 106 ATMP-CD133. At 6-month follow-up, myocardial perfusion at SPECT was significantly ameliorated in terms of changes in summed stress (from 18.2 ± 8.6 to 13.8 ± 7.8, p = 0.05) and difference scores (from 12.0 ± 5.3 to 6.1 ± 4.0, p = 0.02) and number of segments with inducible ischemia (from 7.3 ± 2.2 to 4.0 ± 2.7, p = 0.003). Similarly, Canadian Cardiovascular Society and New York Heart Association classes significantly improved at follow-up vs baseline (p ≤ 0.001 and p = 0.007, respectively). Changes in summed stress score changes positively correlated with ATMP-CD133 release of proangiogenic cytokines HGF and PDGF-bb (r = 0.80, p = 0.009 and r = 0.77, p = 0.01, respectively) and negatively with the proinflammatory cytokines RANTES (r = − 0.79, p = 0.01) and IL-6 (r = − 0.76, p = 0.02). Conclusion Results of the RECARDIO trial suggested safety and efficacy in terms of clinical and perfusion outcomes in patients with RA and LV dysfunction. The observed link between myocardial perfusion improvements and ATMP-CD133 secretome may represent a proof of concept for further mechanistic investigations. Trial registration ClinicalTrials.gov, NCT02059681. Registered 11 February 2014.

The impact of the severity of coronary artery disease (CAD) and percutaneous coronary interventions (PCI) on outcomes after transcatheter aortic valve implantation (TAVI) remains a matter of debate. We therefore performed a meta-analysis to evaluate the impact of CAD, of its severity and of PCI on mortality after TAVI.All published studies evaluating the impact of CAD on 30-day and one-year mortality after TAVI at multivariable analysis were included. The primary endpoint was the impact of CAD severity (assessed with the SYNTAX score [SS]) on one-year mortality by pooling with logarithmic transformation results of multivariable adjusted effect estimates from each individual study. Secondary endpoints were the impact of the presence of CAD on 30-day and one-year mortality at multivariable analysis and the impact of residual SYNTAX score (rSS) on one-year mortality at multivariable analysis. A total of 8,334 patients with a median age of 81.3 (81-82) years and STS score of 6.2% (IQR 6.0-6.7) from 13 studies were included. Patients with an SS22 showed higher one-year mortality at multivariable analysis (OR 1.71 [1.24-2.36]). The presence of CAD did not impact on 30-day and one-year mortality at multivariable analysis (respectively, OR 1.57 [0.71-3.46] and OR 1.25 [0.74-2.11]). Regarding PCI, patients with rSS8 showed lower one-year mortality (OR 0.34 [0.012-0.93]).The risk of death after TAVI is closely related to the complexity of CAD. Patients with an SS22 present higher mortality. SS may represent a useful tool to select patients undergoing TAVI who could benefit from coronary revascularisation. In this regard, reaching an rSS8 reduced one-year mortality. Randomised controlled trials are needed to confirm these results.

Introduction Different devices have been released for closure of femoral vascular access after coronary angiography or percutaneous coronary intervention, whereas evidence about their efficacy and safety when compared with manual compression or head to head is lacking, especially across different diameters of sheaths, age and sex. Results A total of 30 studies were included in the analysis. Manual compression was evaluated as the control group in all of the included studies (5620 patients), Angioseal in 15 studies (17-29) (1812 patients), Exoseal in two studies (30-31) (1773 patients), Perclose in six (29, 32-37) (849 patients), Vasoseal in eight (36, 38-43) (699 patients), DUETT in one study (44) (392 patients), StarClose in two studies (23, 45) (334 patients), Techstar in two studies (37, 46) (252 patients) and extravascular staple in one study (47) (242 patients). At network meta-analysis, all the devices resulted as not superior to manual compression to reduce all vascular complications, and these results did not vary at metaregression for age, sex and diameter of sheaths. Manual compression significantly increased time to hemostasis when compared with Femoseal (5.72; 1.91-19.10), Vasoseal (5.11; 2.32-11.33), Perclose (3.46; 1.70-7.06), Angioseal (14.95; 7.84-28.57) and Techstar (9.78; 1.81-53.65), while was similar to StarClose, DUETT and Exoseal. Conclusion Different vascular devices for closure of femoral access did not results superior to manual compression to reduce complications, whereas offered a shorted time to hemostasis. StarClose was the device with the highest probability to perform best in terms of complication, whereas Angioseal was superior in terms of reduction of time to hemostasis.

Objectives The aim of this study is to describe the cerebral ischemia recurrence rate after percutaneous patent foramen ovale (PFO) closure in patients older than 55 years and their outcomes, compared with younger patients. Background The registries data and the recent randomized trials about PFO closure are focused on patients younger than 55 years. Little is known about older patients’ long-term outcome. Methods In total, 458 patients underwent PFO closure for cryptogenic cerebral ischemia and were stratified into an “older” (≥55 years, 151 patients) and a “younger” (

Introduction The increasing use of primary percutaneous coronary intervention (pPCI) has improved clinical outcome in ST-segment elevation myocardial infarction (STEMI) patients, but the impact of sex on early and mid-term outcomes remains to be defined. Methods Medline, Cochrane Library, Biomed Central, and Google Scholar were searched for articles describing differences in baseline, periprocedural, and midterm outcomes after pPCI, by sex. The primary end point was all-cause mortality at early and mid-term follow-up. Secondary endpoints included in-hospital bleeding and stroke. Results Sixteen studies were included. Women were older, had more frequent hypertension, diabetes mellitus, and hypercholesterolemia, as well as longer ischemia time and more shock at presentation. Men were more likely to have had a previous myocardial infarction. Female sex emerged as independently associated to early mortality (OR 1.1; 95%CI, 1.02–1.18) but not to mid-term mortality (OR, 1.01; 95%CI, 0.99–1.03). The pooled analysis showed a significantly higher risk of in hospital stroke (OR, 1.69; 95%CI, 1.11–2.56) and major bleeding (OR, 2.04; 95%CI, 1.51–2.77) in women. Conclusions As compared to men, women undergoing pPCI have more bleedings and strokes, and a worse early, but not mid-term mortality. These findings may allow a better risk stratification of pPCI patients.

Coronary stent fracture is a relatively rare but potentially serious complication of coronary artery stenting, in particular with sirolimus-eluting stents. It has been recognized as one possible cause of in-stent restenosis as well as acute stent thrombosis. The formation of coronary artery aneurysm is one of the critical complications after percutaneous coronary intervention and it has been described after a stent fracture too. We report here a case of formation of four coronary artery aneurysms associated with the fracture of a sirolimus-eluting stent.

Objectives Culprit plaque characteristics in young patients who experience an Acute Coronary Syndrome (ACS) evaluated by OCT (Optical Coherence Tomography) have to be defined. The OCT-FORMIDABLE is a multicentre retrospective registry enrolling consecutive patients with ACS who performed OCT in 9 European centres. Methods Patients were divided in two groups according to age at presentation: juvenile-ACS (age ≤ 50 years) and not juvenile-ACS (age > 50 years). Primary end-point was the prevalence of plaque rupture (PR). Secondary end point was the prevalence of thin cap fibro atheroma (TCFA), fibrocalcific and fibrotic plaque. Results 285 patients were included, 71 (24.9%) in juvenile-ACS group and 215 (75.1%) in not juvenile-ACS group. Younger patients showed a trend for a higher prevalence of TCFA (70 vs. 58%, P = 0.06) and thrombus presence (62 vs. 51%, P = 0.1), while no statistical difference concerning PR (70 vs. 64%, P = 0.29). Of interest patients younger that 35 years showed a higher prevalence of PR compared to patients aged between 35 and 45 or 45 and 50 years (100 vs. 72 vs. 55%, P = 0.03). Culprit plaque in juvenile-ACS group showed more frequently a reduced mean cap thickness (119 ± 66 vs. 155 ± 95 nm, P = 0.05) and less frequently fibrotic (32 vs. 57%, P

Ischemic diseases are the major cause of death and morbidity in Western countries. In the last decade, cell therapy has been suggested to be a promising treatment both in acute/chronic myocardial and peripheral ischemia. Different cell lineages have been tested, including endothelial progenitor cells. A subpopulation of bone marrow-derived immature ECPs, expressing the highly conserved stem cell glycoprotein antigen prominin-1 or CD133 marker, was shown to possess pro-angiogenic and antiapoptotic effects on ischemic tissues. The mechanisms implicated in CD133+ cells ability to contribute to neovascularization processes have been attributed to their ability to directly differentiate into newly forming vessels and to indirectly activate pro-angiogenic signaling by paracrine mechanisms. A large body of in vivo experimental evidences has demonstrated the potential of CD133+ cells to reverse ischemia. Moreover, several clinical trials have reported promising beneficial effects after infusion of autologous CD133+ into ischemic heart and limbs exploiting various delivery strategies. These trials have contributed to characterize the CD133+ manufacturing process as an advanced cell product (AMP). The aim of this review is to summarize available experimental and clinical data on CD133+ cells in the context of myocardial and peripheral ischemia, and to focus on the development of the CD133+ cell as an anti-ischemic AMP.

A 74-year-old female had urgent surgery with replacement of the ascending aorta for acute type A dissection. Postprocedure, the electrocardiogram showed an ST-segment elevation myocardial infarction in the antero-lateral leads. Angiography revealed a thrombotic occlusion of the left anterior descending artery, treated successfully with bivalirudin administration, thrombus aspiration and a balloon angioplasty. This case involves the rare coexistence of acute type A aortic dissection and myocardial infarction due to coronary plaque thrombosis. doi: 10.1111/jocs.12577 (J Card Surg 2015;30:583–585)

Background: Transcatheter closure of patent foramen ovale (PFO) is a widespread procedure, but no randomized study on its outcome in high-risk patients is available. Our aims were to determine the efficacy and safety of this procedure in a cohort of high-risk patients through the observation of clinical adverse events and residual shunt, to evaluate the impact of transesophageal echocardiography (TEE) guidance during the procedure, and investigate the relationship between the anatomical and clinical characteristics and the outcome. Methods and Results: Ninety-five patients underwent PFO closure for cryptogenic cerebral ischemia; each of them presented one or more of the following risk factors: recurrent cerebral ischemia (9.5%), atrial septum aneurysm (ASA, 74.5%), prominent Eustachian valve (EV, 23.2%), severe basal shunt (9.5%), thrombophilic factors (20%), deep vein thrombosis (4.2%). The procedure was performed successfully in all patients. On median follow-up of 18 months, the neurologic recurrent events rate was 1.1% and the major adverse cardiac event (MACE) rate was 1.1%. At 6-month TEE follow-up, the residual shunt rate was 12.6% (3.1% moderate to severe). A significant correlation was found between residual shunt and prominent EV alone (P = 0.036) or in association with ASA (P = 0.021). All adverse events occurred in the first 8 months, and the event-free survival rate was 86.2%. Conclusions: Our study suggests that transcatheter PFO closure is a safe procedure even in a selected population of high-risk patients, presenting satisfactory efficacy and safety. The presence of a prominent EV alone or with ASA correlates positively with the occurrence of residual shunt. (J Interven Cardiol 2011;24:477–484)

Aims: D rug eluting stents (DES) are currently considered the gold standard for reducing restenosis of coronary artery lesions. Owing to their effect on the healing process, DES use requires mandatory prolonged dual antiplatelet therapy (DAT). The endothelial progenitor cell (EPC) capture stent, attracting circulating EPCs, promotes vascular healing and allows a short post-procedural period of DAT. The aim of the present study was to evaluate the short and long term clinical outcomes of the use of the Genos R stent™ in a selected high risk population with “no option” for DES. Methods and results: From December 2005 to October 2008, 61 high risk patients with clear contraindications to a prolonged period of DAT who underwent PCI with EPC capture stent implantation in our institution were prospectively selected and analysed. Technical success rate was 100%. Procedural success rate was 95.1%. After two years, major adverse cardiovascular events (MACE) free survival was 80.6%. According to the Academic Research Consortium definitions, cardiac death occurred in 1.6% of patients, and re-infarction, target lesion revascularisation (TLR), and target vessel revascularisation (TVR) occurred in 6.6%, 9.8%, and 11.5% of patients, respectively. Definite stent thrombosis occurred in one patient (specifically at 0 days). In patients who underwent surgery, no post-procedural MACE and no stent thrombosis were recorded. Conclusions: EPC capture stent implantation in high-risk patients with no option for DES seems encouraging, with satisfactory clinical outcomes both at short and at long term follow-up.

Iatrogenic erosion of the septum primum after foramen ovale closure is an anecdotal event. We report the case of a 39-year-old woman admitted to our institution for multifocal cryptogenic cerebral ischemia and a patent foramen ovale (PFO) associated with an aneurysm of the septum primum. The patient underwent percutaneous closure of the PFO with an Amplatzer PFO Occluder device. At the 6-months follow up, the device was in the right position, but a jagged defect of the septum primum and evidence of significant left-to-right shunting was detected. The atrial septal defect was then repaired by a surgical approach. Although this event is not life-threatening, it should be considered as a therapeutic pitfall, resulting in a risk of paradoxical embolism recurrences and long-term hemodynamic impairment. © 2013 Wiley Periodicals, Inc.

Aims: The aim of the study was to validate a novel formula for aortic valve area (AVA) based on the principle of continuity equation, that substitutes Doppler-derived stroke volume (SV) by SV directly measured with real time simultaneous triplane three-dimensional echocardiography (RT3P). RT3P has proved accuracy for left ventricular volume calculation. So far, however, neither this potential has been applied to hemodynamic assessment, nor RT3P has succeeded in the evaluation of aortic valve disease. Methods and results: AVA was measured in 21 patients with aortic stenosis using Gorlin's equation, Doppler continuity equation (two-dimensional echocardiography), the novel RT3P method, and by substituting Doppler-derived SV by SV measured with two-dimensional stroke volume (2DSV). RT3P has the best linear association (R2= 0.61) and the best correlation with Gorlin of all noninvasive methods (even if not statistically significant). RT3P carries significantly lower mean differences with catheterization, as compared with 2D and 2DSV (Table 4). Standard deviations of mean differences between RT3P and catheterization and between the other echocardiographic methods are not statistically different, even if RT3P seems to be nearer to catheterization. Inter- and intraobserver variability were, respectively, 0.03 ± 0.11 cm2 and 0.02 ± 0.03 cm2, better than 2D and 2DSV. Conclusions: RT3P has revealed to be more accurate than two-dimensional method in AVA quantification, with a better intraobserver agreement. In addition, it allows simple and fast image acquisition. (Echocardiography 2010;27:644-650)

A 74-year-old female had urgent surgery with replacement of the ascending aorta for acute type A dissection. Postprocedure, the electrocardiogram showed an ST-segment elevation myocardial infarction in the antero-lateral leads. Angiography revealed a thrombotic occlusion of the left anterior descending artery, treated successfully with bivalirudin administration, thrombus aspiration and a balloon angioplasty. This case involves the rare coexistence of acute type A aortic dissection and myocardial infarction due to coronary plaque thrombosis.

The increasing use of primary percutaneous coronary intervention (pPCI) has improved clinical outcome in ST-segment elevation myocardial infarction (STEMI) patients, but the impact of sex on early and mid-term outcomes remains to be defined.Medline, Cochrane Library, Biomed Central, and Google Scholar were searched for articles describing differences in baseline, periprocedural, and midterm outcomes after pPCI, by sex. The primary end point was all-cause mortality at early and mid-term follow-up. Secondary endpoints included in-hospital bleeding and stroke.Sixteen studies were included. Women were older, had more frequent hypertension, diabetes mellitus, and hypercholesterolemia, as well as longer ischemia time and more shock at presentation. Men were more likely to have had a previous myocardial infarction. Female sex emerged as independently associated to early mortality (OR 1.1; 95%CI, 1.02-1.18) but not to mid-term mortality (OR, 1.01; 95%CI, 0.99-1.03). The pooled analysis showed a significantly higher risk of in hospital stroke (OR, 1.69; 95%CI, 1.11-2.56) and major bleeding (OR, 2.04; 95%CI, 1.51-2.77) in women.As compared to men, women undergoing pPCI have more bleedings and strokes, and a worse early, but not mid-term mortality. These findings may allow a better risk stratification of pPCI patients.

To assess sex differences in clinical presentation, in-hospital and long-term outcome in ST-elevated myocardial infarction (STEMI) patients undergoing primary PCI (PPCI).Several studies have shown higher rates of mortality in women. These differences are not always confirmed after adjusting for confounding variables.From January 2007 to December 2011, 325 consecutive patients (23.1% females and 76.9% males) were prospectively treated and retrospectively analyzed. Primary outcome was in-hospital and long-term mortality.Women were older (71.8±11.7 vs. 62.5±12.6years; p0.0001), presented more renal failure (45.3% vs. 20.8%; p0.0001) and severe haemodynamic impairment (9.3% vs. 3.6%; p=0.04). In-hospital overall mortality (14.7% vs. 4.8%; p=0.003) and cardiac death (12% vs. 2%; p=0.002) were significantly higher in women. The multivariate analysis identified age (OR 1.07; 95% CI: 1.01-1.13), resuscitated cardiac arrest (CCA) and cardiogenic shock (CS) (OR 15.31; 95% CI: 4.30-61.75), renal failure (OR 0.20; 95% CI: 0.06-0.68), but not sex (OR 1.49; 95% CI: 0.53-4.22) as independent prognostic factors of in-hospital mortality. During a median follow-up of 46.5months (IQR range 32.7-63.1months), long-term overall mortality (24.2% vs. 11.0%; p=0.007) and cardiac death (4.8% vs. 1.7%; p=0.02) were significantly higher in women. The multivariate analysis identified age (HR 1.06; 95% CI: 1.02-1.11), previous AMI (HR 3.9; 95% CI: 1.63-9.35), renal failure (HR 5.21; 95% CI: 2.12-12.85), technical success (HR 0.35; 95% CI: 0.14-0.84) but not sex (HR 0.90; 95% CI: 0.42-1.94) as independent prognostic factors of long-term mortality.Worse clinical presentation rather than sex may explain the excess of mortality in women with STEMI undergoing PPCI.

Percutaneous coronary intervention (PCI) with drug-eluting stents is an accepted alternative to surgery for the treatment of unprotected left main coronary artery (ULMCA) disease, but the long-term outcome in elderly patients is unclear. Aim of our study was to compare the clinical outcomes of octogenarians with ULMCA disease treated either with PCI with drug-eluting stents or coronary artery bypass grafting (CABG). The primary study end point was the composite of death, cerebrovascular accident, and myocardial infarction at follow-up. A total of 304 consecutive patients with ULMCA stenosis treated with PCI or CABG and aged 80 years were selected and analyzed in a large multinational registry. Two hundred eighteen were treated with PCI and 86 with CABG. During the hospitalization, a trend toward a higher mortality rate was reported in PCI-treated patients (3.5% vs 7.3%, p = 0.32). At a median follow-up of 1,088 days, the incidence of the primary end point was similar in the 2 groups (32.6% vs 30.2%, p = 0.69). Incidence of target vessel revascularization at follow-up was higher in PCI-treated patients (10% vs 4.2%, p = 0.05). At multivariate analysis, left ventricular ejection fraction was the only independent predictor of the primary end point (hazard ratio 0.95, 95% confidence interval 0.91 to 0.98, p = 0.001). After adjustment with propensity score, the revascularization strategy was not significantly correlated to the incidence of the primary end point (hazard ratio 0.98, 95% confidence interval 0.57 to 1.71, p = 0.95). In octogenarians, no difference was observed in the occurrence of the primary end point after PCI or CABG for the treatment of ULMCA disease. However, the rate of target vessel revascularization was higher in the PCI group. (C) 2014 Elsevier Inc. All rights reserved.

Several clinical and procedural factors have been identified as predictors of early and midterm events after transcatheter aortic valve implantation (TAVI), but incidence and prognostic impact of diabetes mellitus (DM), especially insulin treated, on short- and midterm outcomes remain to be defined. All consecutive patients who underwent TAVI at our institutions were enrolled and stratified according to DM status. All-cause mortality at 30 days or in hospital and at follow-up was the primary end point, whereas periprocedural complications, rates of myocardial infarction, stroke, and reintervention at follow-up were the secondary ones. All end points were adjudicated according to the Valve Academic Research Consortium definitions. In all, 511 patients were enrolled: 361 without DM, 78 with orally treated DM, and 72 with insulin-treated DM. Orally treated DM patients were more frequently women, whereas insulin-treated DM patients were younger. Thirty-day Valve Academic Research Consortium mortality was not significantly higher in patients with orally treated DM and insulin-treated DM compared with patients without diabetes (6.4%, 9.7%, and 4.7%, p = 0.09). Bleedings, vascular complications, postprocedural acute kidney injury, and periprocedural strokes were not significantly different in the 3 groups. At midterm follow-up (median 400 days), patients with insulin-treated DM had a significantly higher mortality rate (33.3% vs 18.6%, p = 0.01) and higher myocardial infarction incidence (8.3% vs 1.4%, p = 0.002) if compared with patients without diabetes. Strokes and reinterventions at follow-up were similar in the 3 groups. After multivariable adjustment, insulin-treated DM was independently correlated with death (hazard ratio 2, 95% confidence interval 1.3 to 3.3) and myocardial infarction (hazard ratio 3.73, 95% confidence interval 1.1 to 13). In conclusion, DM does not significantly affect rates of complications in patients who underwent TAVI. Insulin-treated DM, but not orally treated DM, is independently associated with death and myocardial infarction at midterm follow-up and should be included into future TAVI-dedicated scores.

Iatrogenic erosion of the septum primum after foramen ovale closure is an anecdotal event. We report the case of a 39-year-old woman admitted to our institution for multifocal cryptogenic cerebral ischemia and a patent foramen ovale (PFO) associated with an aneurysm of the septum primum. The patient underwent percutaneous closure of the PFO with an Amplatzer PFO Occluder device. At the 6-months follow up, the device was in the right position, but a jagged defect of the septum primum and evidence of significant left-to-right shunting was detected. The atrial septal defect was then repaired by a surgical approach. Although this event is not life-threatening, it should be considered as a therapeutic pitfall, resulting in a risk of paradoxical embolism recurrences and long-term hemodynamic impairment. © 2013 Wiley Periodicals, Inc.

To investigate the safety and efficacy of Genous Bio-engineered R stent (GRS) with ≤ 15-day or15-day dual antiplatelet therapy (DAT), in patients undergoing percutaneous coronary intervention (PCI), with known or expected low compliance to long-term DAT (Antiplatelet theRapy after Genous EPC-capturing coroNary stenT implantatiOn--ARGENTO study).Consecutive patients without ≤ 12-month revascularization history, known statins allergy, known hypersensitivity reaction or previous or concomitant monoclonal and/or recombinant antibodies therapy, treated with single- or multivessel PCI plus GRS, were prospectively enrolled, at four PCI centers. Major adverse cardiac events (MACEs), the composite of cardiac death, any myocardial infarction (MI) and target vessel revascularization (TVR), and stent thrombosis (ST) cumulative incidences were evaluated.Between March 2008 and March 2010, 384 patients (70.3% male, 423 lesions) were enrolled. At follow-up (22.8 ± 13.6 months), 8.6% MACEs, 3.4% cardiac death, 3.4% any MI, 4.7% TVR and 2.3% overall ST (definite/probable ST 1.3%) rates were reported, without differences between ≤ 15-day and15-day DAT groups. At Cox multivariable-adjusted regression analysis (Hosmer-Lemeshow statistic, p=0.50) female sex, diabetes, previous PCI history,45% left ventricular ejection fraction at admission and lesion length were identified as independent MACE predictors. DAT time duration (hazard ratio 1.98; 95% confidence interval 0.57-6.80, p=0.27) was not independent risk factor for MACEs.In consecutive, prospectively enrolled patients with PCI indication and known or supposed low compliance to long-term DAT, GRS implantation might be a safe and effective option regardless of DAT duration after stenting (≤ 15 days or15 days).

Same-day discharge after coronary angiography or percutaneous coronary interventions (PCI) is safe. It allows a decrease in length of hospital stay, waiting list and operating expenses with increased patient satisfaction. The aim of this study was to evaluate the feasibility and safety of this approach in our center.798 selected patients considered suitable for same-day discharge were enrolled in our study and underwent coronary angiography and/or PCI procedures over a period of 5 years. All procedures were performed by femoral approach using the 6-8F AngioSeal closure device. A follow-up telephone interview was carried out in all patients after 7-10 days from discharge with particular regard to bleeding/vascular complications.After PCI procedures, 738 patients (92.4%) were discharged as day cases. The remaining 60 patients (7.6%) were kept in hospital for longer observation. Procedural success was achieved in 100% of patients. Hemostasis with the AngioSeal closure device was successfully obtained in 98.4% of cases. At follow-up, 6 patients developed mild size hematoma on femoral access site, without any other vascular complications or major bleeding needing blood transfusion.In our experience same-day discharge after coronary angiography or PCI was found to be feasible and safe in selected patients undergoing uncomplicated procedures performed by femoral approach using a closure device.

Background aims Bone marrow (BM)-derived cells appear to be a promising therapeutic source for the treatment of acute myocardial infarction (AMI). However, the quantity and quality of the cells to be used, along with the appropriate time of administration, still need to be defined. We thus investigated the use of BM CD34 + -derived cells as cells suitable for a cell therapy protocol (CTP) in the treatment of experimental AMI. Methods The need for a large number of cells was satisfied by the use of a previously established protocol allowing the expansion of human CD34 + cells isolated from neonatal and adult hematopoietic tissues. We evaluated gene expression, endothelial differentiation potential and cytokine release by BM-derived cells during in vitro culture. Basal and expanded CD34 + cells were used as a delivery product in a murine AMI model consisting of a coronary artery ligation (CAL). Cardiac function recovery was evaluated after injecting basal or expanded cells. Results Gene expression analysis of in vitro -expanded cells revealed that endothelial markers were up-regulated during culture. Moreover, expanded cells generated a CD14 + subpopulation able to differentiate efficiently into VE-cadherin-expressing cells. In vivo , we observed a cardiac function recovery in mice sequentially treated with basal and expanded cells injected 4 h and 7 days after CAL, respectively. Conclusions Our data suggest that combining basal and expanded BM-derived CD34 + cells in a specific temporal pattern of administration might represent a promising strategy for a successful cell-based therapy.

Transcatheter closure of patent foramen ovale (PFO) is a widespread procedure, but no randomized study on its outcome in high-risk patients is available. Our aims were to determine the efficacy and safety of this procedure in a cohort of high-risk patients through the observation of clinical adverse events and residual shunt, to evaluate the impact of transesophageal echocardiography (TEE) guidance during the procedure, and investigate the relationship between the anatomical and clinical characteristics and the outcome.Ninety-five patients underwent PFO closure for cryptogenic cerebral ischemia; each of them presented one or more of the following risk factors: recurrent cerebral ischemia (9.5%), atrial septum aneurysm (ASA, 74.5%), prominent Eustachian valve (EV, 23.2%), severe basal shunt (9.5%), thrombophilic factors (20%), deep vein thrombosis (4.2%). The procedure was performed successfully in all patients. On median follow-up of 18 months, the neurologic recurrent events rate was 1.1% and the major adverse cardiac event (MACE) rate was 1.1%. At 6-month TEE follow-up, the residual shunt rate was 12.6% (3.1% moderate to severe). A significant correlation was found between residual shunt and prominent EV alone (P = 0.036) or in association with ASA (P = 0.021). All adverse events occurred in the first 8 months, and the event-free survival rate was 86.2%.Our study suggests that transcatheter PFO closure is a safe procedure even in a selected population of high-risk patients, presenting satisfactory efficacy and safety. The presence of a prominent EV alone or with ASA correlates positively with the occurrence of residual shunt.