A new echocardiographic index to select patients for PFO suture-mediated percutaneous closure.

OBJECTIVES: To identify a simple echocardiographic predictor of procedural success to select patient for percutaneous suture-mediated patent fossa ovalis (PFO) closure. BACKGROUND: Percutaneous suture-mediated PFO closure has been shown as a safe and advantageous alternative to device-based PFO closure, yet its overall success is slightly lower in unselected patients. METHODS: Preprocedural transesophageal echocardiogram (TEE) of 302 patients (113 men, 45 ± 12 years) who underwent percutaneous suture-mediated PFO closure were reviewed. RESULTS: At echocardiographic follow-up (3-6 months), residual right-to-left shunt (RLS) ≥2 was found in 60 (19.9%) patients. At multivariable analysis, only two anatomical variables measured at preprocedural TEE were found as independent predictors of residual RLS ≥ 2 at follow-up: PFO maximum width (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.16-3.40, p = 0.02) and PFO minimal septa overlapping (OR 0.58, 95% CI 0.35-0.88, p = 0.02). An index based on the ratio of PFO maximum width to PFO minimum septal overlapping (W/SO) proved to be the most powerful predictor of RLS ≥ 2 at follow-up (OR 48.1, 95% CI 9.3-352.2, p < 0.01). The ROC curve for the W/SO ratio was found to have an AUC of 0.84 (95% CI 0.75-0.93) and a cut-off value of 0.61 yielding a sensitivity of 80% and specificity of 78% with a negative predictive value of 94%. A decision tree methodology's AUC was 0.75 (95% CI 0.67-0.83). CONCLUSIONS: The results of this study indicate that the ratio between the maximum amplitude of the PFO and the minimum overlap of the septa is the best predictive index of a favorable result by using one stitch only.

Atrial function analysis after percutaneous umbrella device and suture-mediated patent fossa ovalis closure.

BACKGROUND: Atrial fibrillation is an undesirable event following percutaneous patent fossa ovalis (PFO) closure with metallic occluders, suggesting that implanting a rigid closure device could alter atrial function. Suture-mediated PFO closure is a new technique, achieving closure of the PFO by means of a simple suture. Aim of this study was to evaluate left atrial function after closure of PFO by direct suture and traditional occluders. METHODS: We studied 40 age and sex homogeneous patients, 20 undergoing PFO closure by device (OCL) and 20 by suturing (NS). Twenty healthy sex-age matched subjects made up the control group (CT). Left atrial function was evaluated by using volumetric and speckle-tracking analysis assessing the following parameters: total emptying fraction (EF), Expansion Index (EI), active emptying fraction (AEF), strain values of the reservoir (r-ED), conduit (cd-ED) and contraction phase (ct-ED). RESULTS: Compared to CT and NS, OCL patients had significantly worst indices of left atrial reservoir function (EF P=0.001, EI P=0.003, r-ED P<0.001), conduit function (cd-ED P=0.018) and contraction function (AEF P=0.010; ct-ED P<0.001). No significant differences were observed in left atrial function indices between CT and NS patients. CONCLUSIONS: Suture-mediated PFO closure does not alter left atrial function. Conversely, metallic occluder is associated with worse left atrium function. This detrimental effect on atrial function could favor the development of atrial arrhythmias.

Percutaneous suture-mediated patent foramen ovale closure: two-year clinical follow-up.

BACKGROUND: Percutaneous suture-mediated patent foramen ovale (PFO) closure has been recently introduced in clinical practice showing a favorable efficacy and safety profile in most PFO cases. The aim of this study was to assess the long-term outcomes of PFO closure by direct suture in a large consecutive series of patients. METHODS: We extracted all consecutive patients who underwent percutaneous closure of the PFO by suture technique (HeartStitch, Fountain Valley, CA, USA) from June 2016 with a follow-up of at least 2 years. After PFO closure, patients were followed-up clinically at 1, 6 and up to 12 months and microbubble transthoracic echocardiography (TTE) scheduled between 3 and 6 months, and at 12-month follow-up. After 12 months, patients were clinically checked every 6 months. RESULTS: As of September 1, 2020, 187 patients had undergone PFO closure with suture for at least two years and, of these, 181 (121 women and 60 men, mean age 45±13 years, range 15-75 years) had complete clinical and instrumental follow-up (97%). There were no peri-procedural complications. Mean follow-up was 1076±251 days (range 727-1574). At 12-month TTE, a significant residual atrial shunt was found in 39 patients (21%). At follow-up no recurrent thromboembolic or cerebral event occurred, no instrumental evidence of suture dehiscence detected and, 18 months after the procedure, one patient had an episode of transient atrial fibrillation lasting less than 24 hours and resolved spontaneously. CONCLUSIONS: Long-term follow-up data indicate that PFO closure by direct suturing is safe and effective. Two years after the procedure, there were no significant complications, no permanent arrhythmic complications and evidence of suture dehiscence.

Predictors of Residual Right-to-Left Shunt After Percutaneous Suture-Mediated Patent Fossa Ovalis Closure.

OBJECTIVES: This study sought to assess patent fossa ovalis (PFO) anatomy by transesophageal echocardiography (TEE) in patients undergoing percutaneous suture-mediated PFO closure to identify predictors of post-procedural residual atrial right-to-left shunt (RLS). BACKGROUND: Percutaneous suture-mediated PFO closure has been proven to be a safe and effective technique in most PFO patients. METHODS: From June 2016 to October 2019, 247 consecutive patients underwent percutaneous suture-mediated PFO closure at our institution. Of them, 230 (46 ± 13 years of age, 146 women) had complete and technically evaluable pre-procedural TEE. The following parameters in short-axis view were assessed: presence and grade of spontaneous RLS, PFO length and width, presence of atrial septal aneurysm and its maximal bulge, and presence of an embryonic or fetal remnant (Chiari network or Eustachian valve). RESULTS: At the first follow-up transthoracic echocardiography performed between 3 and 6 months from the closure procedure, a residual RLS ≥2 grade was found in 37 (16%) patients. Grade of pre-procedural spontaneous RLS (hazard ratio: 1.99; 95% confidence interval: 1.14 to 3.48; p = 0.016) shunt and PFO width (hazard ratio: 2.52; 95% confidence interval: 1.85 to 3.43; p < 0.001) were both found to be significantly associated with significant residual RLS at multivariable analysis. The presence of atrial septal aneurysm and its maximal bulge and of congenital remnants was not associated with significant residual RLS. CONCLUSIONS: Percutaneous suture-mediated PFO closure is feasible in the majority of septal anatomies; however, PFO >5 mm in width and spontaneous large RLS are less likely to be closed with 1 stitch only.

Slender distal radial five French coronary shockwave lithotripsy.

Despite technological evolution, percutaneous coronary interventions targeting coronary calcifications remain challenging and associated with high rates of complications and adverse outcomes. Over the years, rotational atherectomy has emerged as the reference treatment of calcified coronary artery lesions despite some inherent limitations. Also, rotational atherectomy typically requires relatively large guiding catheters which may unfavorably impact on the decision for transradial access, especially when radial artery is small, and consequently offset the relevant clinical benefits associated to transradial access. Recently, a new technology has been introduced in interventional practice to implement coronary lithotripsy. The device implements multiple small emitters enclosed in a coronary balloon creating sonic pressure waves to selectively fracture calcium within the plaque and favorably modify vessel compliance. Owing to its specific design, coronary shockwave lithotripsy could be used with small bore guiding catheters which may allow for straightforward transradial percutaneous treatment of calcified coronary lesions even in patients with a small radial artery. To illustrate this concept, we report the first experience of slender transradial coronary shockwave lithotripsy with a five French sheathless guiding catheter.

Concept and practice of transradial 5 French percutaneous treatment of coronary bifurcation lesions.

OBJECTIVES: To assess the efficacy and safety of transradial 5 French percutaneous treatment of coronary bifurcations using conventional devices. BACKGROUND: Radial artery is smaller than femoral artery, and its size may potentially limit transradial intervention, especially when coronary anatomy is not known. METHODS: Patients with bifurcations lesions undergoing transradial 5 French ad hoc revascularization were treated according to provisional side branch (SB) stenting followed by the POT-SB dilation-final POT sequence. Only conventional devices were used. RESULTS: Overall, 80 patients (58 men, 65 ± 10 years) were enrolled. True bifurcations accounted for 64% of cases, with the left anterior descending artery/diagonal branch being the most frequent bifurcation site (n = 37, 46%) and left main coronary artery bifurcation being treated in 6 (8%) patients. Angiographic success was achieved in 78 (97.5%) patients through a 5 French guiding catheter whereas in two cases, a 5-6 French guiding catheter upgrade was required to optimize SB treatment after the main bifurcation vessel have been secured. Overall, procedural success was achieved in all but one patient who had periprocedural necrosis following multivessel PCI. Another patient underwent target bifurcation revascularization because of a critical restenosis in a significant SB yielding an acute coronary syndrome five months after the index procedure. CONCLUSIONS: This study demonstrates the feasibility of transradial 5 French bifurcation intervention with nondedicated devices and preliminary supports its efficacy and safety over a wide range of bifurcation anatomy and complexity.

Safety and Efficacy of Triple Therapeutic Targets with Rivaroxaban after Acute Myocardial Infarction Complicated by Left Ventricular Thrombi in a Case of Nonvalvular Atrial Fibrillation.

We present the complex case of a high-risk patient with nonvalvular atrial fibrillation, who experienced a non-ST elevation myocardial infarction complicated by left ventricular (LV) thrombi and underwent percutaneous coronary intervention with drug-eluting stent implantation. The patient was initially treated with short-term triple therapy including aspirin, clopidogrel, and rivaroxaban 15 mg/die. Following aspirin dropping one month after discharge, the patient continued on dual therapy with clopidogrel and rivaroxaban, and a clinical and imaging follow-up at 6 and 12 months confirmed the LV thrombi resolution, with no thromboembolic episodes and a good safety profile.

Identifying a better strategy for ad hoc percutaneous coronary intervention in patients with anticipated unfavorable radial access: the Little Women study.

BACKGROUND: Transradial percutaneous coronary intervention (PCI) offers important advantages over transfemoral PCI, including better outcomes. However, when there is indication to ad hoc PCI, a 6 French workflow is a common default strategy, hence potentially influencing vascular access selection in patients with anticipated small size radial artery. METHODS: A multidimensional evaluation was performed to compare two ad hoc interventional strategies in women <160cm: a full 6 French workflow (namely 6 French introducer sheath, diagnostic catheters and guiding catheter) with a modified workflow consisting in the use of 5 French diagnostic catheters preceded by the placement of a 6 French sheath introducer and followed by a 6 French guiding catheter use for PCI. RESULTS: Overall 120 women (68±11years) were enrolled in the study. Coronary angiography has been performed using 5 French or 6 French diagnostic catheters in 57 (47.5%) and 63 (52.5%) cases, respectively. Radial spasm and switch to another access occurred more frequently among women who underwent coronary angiography with 6 French rather than 5 French diagnostic catheters (43% vs. 25%, p=0.03 and 2% vs. 11%, p=0.04, respectively). Total time to guidewire lesion crossing was also significantly higher when PCI has been preceded by 6 French rather than 5 French coronary angiography (23±11min vs 16±7min, p=0.013). CONCLUSIONS: In patients with anticipated unfavorable radial access, a workflow consisting in 6 French introducer sheath placement, 5 French coronary angiography, and 6 French coronary intervention is on multiple parameters the most straightforward and effective strategy.

Angiographic and clinical performance of polymer-free biolimus-eluting stent in patients with ST-segment elevation acute myocardial infarction in a metropolitan public hospital: The BESAMI MUCHO study.

OBJECTIVES: This study aimed at assessing the performance of a new generation polymer-free biolimus-eluting stent (BES) in real-world patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Polymers components of early-generation drug-eluting stents have been implicated in the pathogenesis of delayed arterial healing, vessel remodeling, and delayed stent thrombosis. Recently, a novel polymer-free BES has shown excellent clinical performance in clinical trial setting. METHODS: Overall, 175 consecutive patients (64 ± 14 years, 141 men) treated with the BioFreedom (Biosensors Europe, Morges, Switzerland) polymer-free BES because of STEMI were included in this study. The primary endpoint was the rate of major adverse cardiac events (MACE), a composite of cardiac death, recurrent myocardial infarction, and ischemia-driven target vessel revascularization at 1 year follow-up. A subgroup of patients underwent 6-month angiographic follow-up. Dual antiplatelet therapy was prescribed for 12 months after STEMI. RESULTS: At 1 year, the cumulative rate of MACE was 4.6%. One patient (0.6%) had an arrhythmic cardiac death and five (2.9%) had ischemia-driven target vessel revascularization, although only three (1.7%) had target lesion revascularization. Two (1.1%) patients had acute stent thrombosis yielding nonfatal myocardial infarction. In 70 patients (63 ± 14 years, 61 men), quantitative coronary angiography at 6-month follow-up revealed diameter stenosis of 24.1 ± 13.7% and minimal lumen diameter of 2.29 ± 0.56 mm, yielding a late lumen loss of 0.13 ± 0.14 mm. CONCLUSIONS: In real-world setting, implantation of a new-generation polymer-free BES during STEMI is associated with favorable clinical and angiographic results, pointing toward the overall efficacy and safety of the device in complex clinical scenarios.

NMR metabolic profiling of transgenic maize with the Cry1Ab gene.

The metabolic profiles of seeds from the transgenic maize variety 33P67 and of the corresponding traditional variety were investigated using one- and two-dimensional NMR techniques. The transgenic variety carries a functional Cry1A(b) gene, which confers to the plant the ability to produce Bt insect toxin. About 40 water-soluble metabolites in the maize seed extracts were identified, providing a more complete (1)H and (13)C NMR assignment with respect to the assignment reported in the literature. In particular ethanol, lactic acid, citric acid, lysine, arginine, glycine-betaine, raffinose, trehalose, alpha-galactose, and adenine were identified for the first time in the (1)H NMR spectrum of maize seeds extracts. The (1)H spectra of transgenic and nontransgenic seed maize samples turned out to be conservative, showing the same signals and therefore the same metabolites. However, a higher concentration of ethanol, citric acid, glycine-betaine, trehalose, as well as of another compound not yet completely identified, was observed in the transgenic extracts than in nontransgenic samples. So, it was possible to discriminate between transgenic and nontransgenic metabolic profilings through the use of an appropriate statistical analysis.

Metabolic alterations in cultured mouse fibroblasts induced by an inhibitor of the tyrosine kinase receptor Fibroblast Growth Factor Receptor 1.

Proton nuclear magnetic resonance (NMR) spectroscopy was used to identify and quantify the metabolites present in cultured mouse fibroblast cells 3T6 in their native state and after treatment with PD166866, an inhibitor of the fibroblast growth factor receptor. Cell extracts were prepared according to the Bligh-Dyer protocol which prevents artifacts deriving from the chemical demolition of macromolecules. Also the growth medium was subjected to the same extraction procedure. The NMR approach made possible the identification and quantification of about 40 different metabolites at nanomoles/mg of protein level: the biological relevance of the variation of some metabolite levels is discussed. Our experimental procedure offers a prospective method for the evaluation of variations of the metabolic profile deriving from different biochemical treatments of these cells.

Tacrine derivatives-acetylcholinesterase interaction: 1H NMR relaxation study.

Two acetylcholinesterase (AChE) inhibitors structurally related to Tacrine, 6-methoxytacrine (1a) and 9-heptylamino-6-methoxytacrine (1b), and their interaction with Electrophorus Electricus AChE were investigated. The complete assignment of the 1H and 13C NMR spectra of 1a and 1b was performed by mono-dimensional and homo- and hetero-correlated two-dimensional NMR experiments. This study was undertaken to elucidate the interaction modes between AChE and 1a and 1b in solution, using NMR. The interaction between the two inhibitors and AChE was studied by the analysis of the motional parameters non-selective and selective spin-lattice relaxation times, thereby allowing the motional state of 1a and 1b, both free and bound with AChE, to be defined. The relaxation data pointed out the ligands molecular moiety most involved in the binding with AChE. The relevant ligand/enzyme interaction constants were also evaluated for both compounds and resulted to be 859 and 5412M(-1) for 1a and1b, respectively.

Enhanced TNF alpha and oxidative stress in patients with heart failure: effect of TNF alpha on platelet O2- production.

Experimental studies have suggested that TNF alpha, a pro-inflammatory cytokine, may contribute to the deterioration of cardiovascular function through various mechanisms, including the generation of reactive oxygen species. It has not yet been demonstrated whether TNF alpha has prooxidant activity in patients with heart failure, and what the mechanism eventually resulting in this effect are. We analyzed 42 patients (38 men and 4 women, aged 26 to 74 years) with heart failure, secondary to idiopathic dilated cardiomyopathy (n=21), coronary artery disease (n=15), and valve disease (n=6), and 20 controls (18 men and 2 women, aged 49 to 67 years). Ten patients were in class I, 9 in class II, 15 in class III and 8 in class IV according to NYHA Classification. Blood samples were obtained from each patient to evaluate basal and collagen-induced platelet O(2)(-) production, and plasma TNF alpha. In vivo results showed increased platelet O(2)(-) production and plasma TNF alpha levels in NYHA class III-IV compared with that in controls or in NYHA I-II (p<0,001); platelet O(2)(-) production correlated significantly (R=0,6; p<0,01) with TNF alpha plasma levels. In vitro studies showed TNF alpha dose-dependently (5-40 pg/ml) induced platelet O(2)(-) production, and that this effect was significantly inhibited by its specific inhibitor, WP9QY (1 microM); aspirin (100 microM), AACOCF(3), a specific PLA(2) inhibitor (14 microM), and DPI, an inhibitor of NADPH oxidase, significantly inhibited TNF alpha-mediated platelet O(2)(-) production. This study suggests that in patients with heart failure, enhanced platelet O(2)(-) production is mediated by TNF alpha via activation of arachidonic acid and NADPH oxidase pathways.