The heart-mind relationship in women cardiovascular primary prevention: the role of depression, anxiety, distress and Type-D personality in the 10-years cardiovascular risk evaluation.

Introduction: Cardiovascular diseases are the leading cause of death among women. Prevention programmes underscore the need to address women-specific risk factors. Additionally, mental well-being is a significant aspect to consider when grappling with cardiovascular disease in women, particularly depression, anxiety, distress, and personality traits. This study aimed to create "at-risk" psychological profiles for women without prior cardiovascular disease history and to evaluate the association between anxiety, depression, distress, and Type-D personality traits with increased cardiovascular risk over 10 years. Methods: 219 women voluntarily participated in the "Monzino Women's Heart Centre" project for primary prevention and early diagnosis of cardiovascular diseases. Psychological profiles were developed utilising cluster analysis. Results: The primary finding indicating that belonging to the "at-risk" psychological cluster was associated with a surge in the 10-year cardiovascular risk prediction score, despite the number of comorbid risk factors (Psychological "at-risk" cluster: ß = .0674; p = .006; Risk factors: ß = .0199; p = .242). Conclusions: This finding suggests that psychological well-being of women should be assessed from the very beginning of cardiovascular prevention programmes.

The RISE Study: Retrospective Registry for the International Safety and Efficacy Results of Patent Foramen Ovale Closure with Figulla Flex Il PFO and UNI Occluders.

Background: Transcatheter closure of a patent foramen ovale (PFO) is performed in cryptogenic stroke and other conditions. Information is lacking for some devices. Methods: We aimed to evaluate the Figulla Flex II PFO Occluder (FFP) and Figulla Flex UNI Occluder (FFU) through a retrospective multi-center registry. Results: 527 patients were included. Mean age was 48.9 (±13.8) years. The procedure was under transthoracic, transesophageal or intracardiac echocardiography in 185 (35.1%), 193 (36.6%) and 149 (28.3%) cases, respectively, and under general anesthesia in 191 patients (36.2%). The FFP and FFU were used in 408 (77.4%) and 119 (22.6%) cases, respectively. The success rate was 99.1%. Median follow-up was 1.1 (0.5-2.5) years. A new atrial fibrillation/flutter within six months occurred in 14 (2.7%) cases, with no difference between devices. One device embolization in the pulmonary artery was identified two years post-procedure. Residual shunts occurred in 18 (6.9%) cases at 1 year, with TIA in three (16.6%) patients. Out of 437 patients with stroke/TIA, 260 (59%) were followed more than one year after closure. Median follow-up was 2.1 (1.17-3.1) years, with four recurrent strokes/TIA. Conclusions: The FFP and FFU devices are safe and effective for PFO closure, with very few atrial fibrillation/flutter and neurologic events, except in cases with a residual shunt.

Long-term impact of intravascular ultrasound-guidance for percutaneous coronary intervention on unprotected left main. The IMPACTUS-LM, an observational, multicentric study.

INTRODUCTION: The potential benefit on long term outcomes of Percutaneous Coronary Intervention (PCI) on Unprotected Left Main (ULM) driven by IntraVascular UltraSound (IVUS) remains to be defined. METHODS: IMPACTUS LM-PCI is an observational, multicenter study that enrolled consecutive patients with ULM disease undergoing coronary angioplasty in 13 European high-volume centers from January 2002 to December 2015. Major Adverse Cardiovascular Events (MACEs) a composite of cardiovascular (CV) death, target vessel revascularization (TVR) and myocardial infarction (MI) were the primary endpoints, while its single components along with all cause death the secondary ones. RESULTS: 627 patients with ULM disease were enrolled, 213 patients (34%) underwent IVUS-guided PCI while 414 (66%) angioguided PCI. Patients in the two cohorts had similar prevalence of risk factors except for active smoking and clinical presentation. During a median follow-up of 7.5 years, 47 (22%) patients in the IVUS group and 211 (51%) in the angio-guided group underwent the primary endpoint (HR 0.42; 95% CI [0.31-0.58] p < 0.001). After multivariate adjustment, IVUS was significantly associated with a reduced incidence of the primary endpoint (adj HR 0.39; 95% CI [0.23-0.64], p < 0.001), mainly driven by a reduction of TVR (ad HR 0.30, 95% CI [0.15-0.62], p = 0.001) and of all-cause death (adj HR 0.47, 95% CI [0.28-0.82], p = 0.008). IVUS use, age, diabetes, side branch stenosis, DES and creatinine at admission were independent predictors of MACE. CONCLUSIONS: In patients undergoing ULM PCI, the use of IVUS was associated with a reduced risk at long-term follow-up of MACE, all-cause death and subsequent revascularization.

Prognostic Impact of Prefrailty and Frailty in Women Undergoing TAVR: Insights From the WIN-TAVI Registry.

BACKGROUND: The risks of prefrail and frail women undergoing transcatheter aortic valve replacement (TAVR) have not been fully examined. The aim of the analysis was to assess the prognostic impact of prefrailty and frailty in women undergoing TAVR. METHODS: Women at intermediate or high surgical risk with severe aortic stenosis undergoing TAVR from the prospective multicentre WIN-TAVI (Women's International Transcatheter Aortic Valve Implantation) registry were stratified based on the number of Fried frailty criteria (weight loss, exhaustion, low physical activity, slow gait, weakness) met: nonfrail (no criteria), prefrail (1 or 2 criteria), or frail (3 or more criteria). The primary outcome at 1 year was the Valve Academic Research Consortium 2 (VARC-2) efficacy end point, a composite of mortality, stroke, myocardial infarction, hospitalisation for valve-related symptoms or heart failure, and valve-related dysfunction; secondary outcomes included the composite of VARC-2 life-threatening or major bleeding. RESULTS: Out of 1019 women, 297 (29.1%) met at least 1 frailty criterion: 264 (25.9%) had prefrailty and 33 (3.2%) frailty. The 1-year risk of the primary outcome was significantly higher in prefrail and frail (20.2%) than in nonfrail (14.9%) women (adjusted hazard ratio [aHR] 1.51, 95% confidence interval [CI] 1.07-2.12). The risk of VARC-2 life-threatening or major bleeding was higher in prefrail or frail (19.9%) than in nonfrail (10.0%) women (aHR 2.06, 95% CI 1.42-2.97). These risks were consistently increased in the prefrail and frail groups assessed separately. CONCLUSIONS: In women undergoing TAVR, the presence of prefrailty or frailty conferred an increased risk of the VARC-2 efficacy end point and of VARC-2 life-threatening or major bleeding.

Achievement of target LDL-cholesterol level in patients with acute coronary syndrome undergoing percutaneous coronary intervention: The JET-LDL registry.

BACKGROUND: In patients with acute coronary syndromes (ACS), current guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level < 1.4 mmol/L (<55 mg/dL). METHODS: The JET-LDL is a multicenter, observational, prospective registry created to investigate levels of LDL-C in consecutive patients with ACS undergoing PCI at 35 Italian hospitals, and to report their lipid lowering therapies (LLT). Follow-up was planned at 1 and 3 months. LDL-C reduction >50% from baseline or level < 55 mg/dL at 1-month was the primary endpoint. RESULTS: A total of 1095 patients were included: median age was 67 (58-75); 33.7% were already on LLT. Baseline LDL-C levels was 105 (76.5-137) mg/dL. At hospital discharge all patients were on LLT: 98.1% received statins (as mono or combination therapy), ezetimibe and PCSK9i were used in 60.1% and 8.5% of cases, respectively. Primary endpoint was achieved in 62% (95% CI 58-65) of cases. At 1-month LDL-C levels dropped to 53 (38-70) mg/dL (p < 0.001 vs baseline) and it was <55 mg/dL in 53% (95% CI 49-57) of patients; however, PCSK9i were added to 7 further cases. At 3-months 58% (95% CI 55-62) of patients achieved the target level, but PCSK9i was added to only 11 new patients. CONCLUSIONS: In this real-world registry of ACS patients undergoing PCI, recommend LDL-C levels were obtained in 62% of patients, but PCSK9i prescription was limited to 10% of cases. As LLT pattern appeared mainly improved at hospital discharge, an early and strong treatment should be considered.

Percutaneous suture-based patent foramen ovale closure: A state-of-the-art review.

Percutaneous closure of a patent foramen ovale (PFO), a common variation of interatrial septum anatomy, is a commonly performed procedure in the catheterization laboratory to reduce the risk of recurrent stroke in selected patients and to treat other PFO-related syndromes. In the last twenty years, disc-based devices have represented the armamentarium of the interventional cardiologist; recently, suture-based devices have become an attractive alternative, despite limited data regarding their long-term performance. The present review gives an overview of the current evidence regarding suture-based PFO closure, the device's characteristics, the echocardiographic evaluation of the PFO anatomy, and recommendations for patient selection. A detailed procedural guide is then provided, and potential complications and future developments in the field are discussed.

Hemostatic system in Takotsubo patients at long-term follow-up: A hidden activation?

BACKGROUND: Takotsubo cardiomyopathy (TTS) has long been considered a benign condition, despite recurrent events and long-term adverse outcomes are often reported. Endothelial damage, blood hyperviscosity, and platelet activation described in acute phase persist in long-term follow-up; however, TTS pathophysiology is still not fully understood. Here, we explored the hemostatic system at a median of 3.1 years after TTS to uncover additional long-lasting changes in these patients. METHODS: We assessed hemostatic parameters in women with TTS (n = 23) or coronary artery disease (CAD; n = 31) and in control women (n = 26) age-matched, by thromboelastographic analysis, prothrombin time (PT) and partial thromboplastin time (aPTT) coagulation assays and microparticle exposing Tissue Factor (MP-TF). Functional fibrinogen and fibrin polymerization were analyzed by Clauss method and spectrophotometry, respectively. Platelet reactivity was evaluated by light transmission aggregometry, whereas plasminogen activator inhibitor-1 (PAI-1) and brain-derived neurotrophic factor (BDNF) were measured by ELISA kit. RESULTS: Compared with control subjects, TTS patients exhibit an accelerated clot formation, higher percentage of fibrin polymerization and higher PAI-1 levels. Compared with CAD, TTS patients showed sustained residual platelet activation but decreased functional fibrinogen, fibrin polymerization and MP-TF levels, prolonged aPTT and a marked BDNF increase. CONCLUSIONS: The long-term activation of hemostatic system observed in TTS patients compared to control subjects suggests a persistent humoral abnormality that may be related to the propensity for TTS recurrence. The higher residual platelet activity observed in TTS than in CAD patients invites investigation on TTS-tailored antiplatelet therapy potentially needed to prevent TTS adverse outcomes.

Cell Surface Platelet Tissue Factor Expression: Regulation by P2Y12 and Link to Residual Platelet Reactivity.

BACKGROUND: ADP-induced platelet activation leads to cell surface expression of several proteins, including TF (tissue factor). The role of ADP receptors in platelet TF modulation is still unknown. We aimed to assess the (1) involvement of P2Y1 and P2Y12 receptors in ADP-induced TF exposure; (2) modulation of TFpos-platelets in anti-P2Y12-treated patients with coronary artery disease. Based on the obtained results, we revisited the intracellular localization of TF in platelets. METHODS: The effects of P2Y1 or P2Y12 antagonists on ADP-induced TF expression and activity were analyzed in vitro by flow cytometry and thrombin generation assay in blood from healthy subjects, P2Y12-/-, and patients with gray platelet syndrome. Ex vivo, P2Y12 inhibition of TF expression by clopidogrel/prasugrel/ticagrelor, assessed by VASP (vasodilator-stimulated phosphoprotein) platelet reactivity index, was investigated in coronary artery disease (n=238). Inhibition of open canalicular system externalization and electron microscopy (TEM) were used for TF localization. RESULTS: In blood from healthy subjects, stimulated in vitro by ADP, the percentage of TFpos-platelets (17.3±5.5%) was significantly reduced in a concentration-dependent manner by P2Y12 inhibition only (-81.7±9.5% with 100 nM AR-C69931MX). In coronary artery disease, inhibition of P2Y12 is paralleled by reduction of ADP-induced platelet TF expression (VASP platelet reactivity index: 17.9±11%, 20.9±11.3%, 40.3±13%; TFpos-platelets: 10.5±4.8%, 9.8±5.9%, 13.6±6.3%, in prasugrel/ticagrelor/clopidogrel-treated patients, respectively). Despite this, 15% of clopidogrel good responders had a level of TFpos-platelets similar to the poor-responder group. Indeed, a stronger P2Y12 inhibition (130-fold) is required to inhibit TF than VASP. Thus, a VASP platelet reactivity index <20% (as in prasugrel/ticagrelor-treated patients) identifies patients with TFpos-platelets <20% (92% sensitivity). Finally, colchicine impaired in vitro ADP-induced TF expression but not α-granule release, suggesting that TF is open canalicular system stored as confirmed by TEM and platelet analysis of patients with gray platelet syndrome. CONCLUSIONS: Data show that TF expression is regulated by P2Y12 and not P2Y1; P2Y12 antagonists downregulate the percentage of TFpos-platelets. In clopidogrel good-responder patients, assessment of TFpos-platelets highlights those with residual platelet reactivity. TF is stored in open canalicular system, and its membrane exposure upon activation is prevented by colchicine.

Patent foramen ovale closure with the Occlutech Figulla flex II device: A long-term (up to 10-years) follow-up.

BACKGROUND: Percutaneous closure represents the first line of treatment in patients with cryptogenic stroke and documented patent foramen ovale (PFO). Scarce data report the long-term outcomes of patients undergoing PFO closure with the Figulla Flex II device (Occlutech, Germany). METHODS: Consecutive patients undergoing PFO closure with a Figulla Flex II device at a single, high-volume Institution were included. Baseline clinical and procedural features were collected and patients were followed up for up to 10 years. The device's long-term safety was assessed, as well as mortality, recurrent cerebrovascular events, new-onset atrial fibrillation (AF) and residual shunt. RESULTS: Overall, 442 patients were included. The main indication for PFO closure was cryptogenic stroke/transitory ischemic attack (65.5%), followed by migraine (21.7%), silent lesions at MRI (10.8%), and decompression disease (2.0%). Atrial septal aneurysm was present in 20.8% of cases, Eustachian valve in 9.0%, Chiari network in 19.9%. The most frequently implanted device was the 23/25 mm (49.5% of cases). One procedural failure due to device embolization; in-hospital complications occurred in 15 cases (3.4%; 4 minor access site complications, 11 transient supraventricular tachycardias (SVT)/AF). After a follow-up of 9.2 years, 2 patients suffered recurrent TIA (with no residual R-L shunt detected). A moderate or severe residual shunt was observed in 3 patients after discharge. CONCLUSIONS: Figulla Flex II devices for PFO closure are associated with high procedural success and low incidence of adverse events even at long-term follow-up.

Migraine and cardiovascular disease: what cardiologists should know.

Migraine is a chronic neurovascular disease with a complex, not fully understood pathophysiology with multiple causes. People with migraine suffer from recurrent moderate to severe headache attacks varying from 4 to 72 h. The prevalence of migraine is two to three times higher in women compared with men. Importantly, it is the most disabling disease in women <50 years of age due to a high number of years lived with disability, resulting in a very high global socioeconomic burden. Robust evidence exists on the association between migraine with aura and increased incidence of cardiovascular disease (CVD), in particular ischaemic stroke. People with migraine with aura have an increased risk of atrial fibrillation, myocardial infarction, and cardiovascular death compared with those without migraine. Ongoing studies investigate the relation between migraine and angina with non-obstructive coronary arteries and migraine patients with patent foramen ovale. Medication for the treatment of migraine can be preventative medication, such as beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, antiepileptics, antidepressants, some of the long-acting calcitonin gene-related peptide receptor antagonists, or monoclonal antibodies against calcitonin gene-related peptide or its receptor, or acute medication, such as triptans and calcitonin gene-related peptide receptor antagonists. However, these medications might raise concerns when migraine patients also have CVD due to possible (coronary) side effects. Specifically, knowledge gaps remain for the contraindication to newer treatments for migraine. All cardiologists will encounter patients with CVD and migraine. This state-of-the-art review will outline the basic pathophysiology of migraine and the associations between migraine and CVD, discuss current therapies, and propose future directions for research.

Diagnostic accuracy of subendocardial vs. transmural myocardial perfusion defect for the detection of in-stent restenosis or progression of coronary artery disease after percutaneous coronary intervention.

BACKGROUND: The ADVANTAGE study demonstrated in a cohort of stented patients a diagnostic accuracy of stress myocardial CT perfusion (CTP) significantly higher than that of coronary CT angiography (CCTA) for the detection of in-stent restenosis (ISR) or CAD progression vs. quantitative coronary angiography (QCA). This is a pre-defined subanalysis of the ADVANTAGE aimed at assessing the difference in terms of diagnostic accuracy vs. QCA of a subendocardial vs. a transmural perfusion defect using static stress CTP. METHODS: We enrolled consecutive patients who previously underwent coronary stenting and were referred for QCA. All patients underwent stress CTP and rest CTP â€‹+ â€‹CCTA. The diagnostic accuracy of CCTA and CTP were evaluated in territory-based and patient-based analyses. We compared the diagnostic accuracy of "subendocardial" perfusion defect, defined as hypo-enhancement encompassing >25% but <50% of the transmural myocardial thickness within a specific coronary territory vs. "transmural" perfusion defect, defined as hypo-enhancement encompassing >50% of the transmural thickness. RESULTS: In 150 patients (132 men, mean age 65.1 â€‹± â€‹9.1 years), the diagnostic accuracy of subendocardial vs. transmural perfusion defect in a vessel-based analysis was 93.5% vs. 87.7%, respectively (p â€‹< â€‹0.0001). The sensitivity and specificity of subendocardial vs. transmural defect were 87.9% vs. 46.9% (p â€‹< â€‹0.001) and 94.9% vs. 97.9% (p â€‹= â€‹0.004), respectively. In a patient-based analysis, the diagnostic accuracy of the subendocardial vs. transmural approach was 86.6% vs. 68% (p â€‹< â€‹0.0001). CONCLUSIONS: This study shows that detection of a subendocardial perfusion defect as compared to a transmural defect is significantly more accurate to identify coronary territories with ISR or CAD progression.

The 'Trawl Fishing' Technique: A Quick Engagement of the Left Common Carotid Artery With the Simmons Catheter During Carotid Artery Stenting From the Right Radial Approach.

BACKGROUND: Transradial approach for carotid artery stenting (TRCAS) is an established technique in specific anatomies potentially associated with high periprocedural event rate from femoral catheterization. The engagement of left common carotid artery originating from the aortic arch is the most challenging scenario requiring specific catheters and techniques. METHODS: Among 542 consecutive TRCAS 66 had left, non-bovine carotid stenosis as the target vessel. We retrospectively compared the feasibility, safety, efficacy, fluoroscopy time and radiation exposure of two different techniques, the standard (ST) and the 'trawl-fishing' (TFT), to engage the LCCA with the 5F, 125 cm-long Simmons-2 catheter. RESULTS: The ST was initially used in 20 patients with a technical success of 85 % (17/20). In the following 46 patients, the TFT was successfully tested first as bailout after ST failure in 12 cases and as first option in the remaining 34 patients. Full technical success was obtained in all patients at the first attempt. No MACCEs or vascular complications occurred in all patients. Fluoroscopy time and radiation exposure were significantly lower with the TFT vs. ST (p < 0.001). CONCLUSIONS: TFT represents a definite improvement in the technique of LCCA engagement during TRCAS.

Outcomes in Patients With Early Menopause Who Underwent Transcatheter Aortic Valve Implantation.

Early menopause is associated with an increased risk of cardiovascular diseases, including aortic stenosis (AS). We sought to investigate the prevalence and impact of early menopause on clinical outcomes in patients who underwent transcatheter aortic valve implantation (TAVI) for severe symptomatic AS. Women's International TAVI is a multinational, prospective, observational registry of women who underwent TAVI for severe symptomatic AS (n = 1,019). Patients were divided into 2 groups based on age of menopause: early menopause (age ≤45 years) and regular menopause (age >45 years). The primary outcome of interest was Valve Academic Research Consortium 2 efficacy end point, a composite of mortality, stroke, myocardial infarction, hospitalization for valve-related symptoms, or heart failure or valve-related dysfunction at 1-year follow-up. Of 732 patients with available data on menopause age, 173 (23.6%) were classified as having early menopause. These patients presented for TAVI at a younger age (81.6 ± 6.9 vs 82.7 ± 5.9, p = 0.05) and had a significantly lower Society of Thoracic Surgeons score (6.6 ± 4.8 vs 8.2 ± 7.1, p = 0.03) than those with regular menopause. However, the total valve calcium volume was smaller among patients with early versus regular menopause (731.8 ± 850.9 mm3 vs 807.6 ± 633.8 mm3, p = 0.002). Other co-morbidities were similar between the 2 groups. At 1-year follow-up, there were no significant differences in clinical outcomes between patients with early versus regular menopause (hazard ratio 1.00, 95% confidence interval 0.61 to 1.63, p = 1.00). In conclusion, despite presenting for TAVI at a younger age, patients with early menopause had a similar risk of adverse events as patients with regular menopause at 1 year after TAVI.

In-hospital outcomes in nonagenarian patients undergoing primary percutaneous coronary intervention.

BACKGROUND: The aim of the present analysis was to evaluate the incidence and predictors of in-hospital adverse outcomes in nonagenarian patients undergoing primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI). METHODS: Consecutive nonagenarian patients undergoing pPCI for STEMI from 2009 to 2019 were retrospectively included in an international multicenter registry. In-hospital all-cause death was the primary outcome. RESULTS: A total of 308 patients were included (mean age 92.5±2.5 years, 65.6% female). Mean systolic blood pressure (SBP) at hospital admission was 130.7±33.5 mmHg, 46 (17%) patients presented with a Killip class III-IV, mean left ventricle ejection fraction (LVEF) was 40.0±11.5% and 147 (58%) patients were independent in everyday activities. In-hospital death occurred in 99 patients (32%). After multivariate adjustment, lower LVEF (OR per unit reduction 1.08, 95% CI: 1.03-1.11, P value <0.001), lower SBP (OR 1.02 per mmHg reduction, 95% CI: 1.01-1.03, P value 0.001) and being not independent at home (OR 2.56, 95% CI: 1.25-5.26, P value 0.01) resulted independent predictors of in-hospital mortality. A sensitivity analysis performed in final TIMI 3 flow population confirmed the prognostic role of LVEF and independency on in-hospital mortality. CONCLUSIONS: Nonagenarian patients presenting with STEMI and undergoing pPCI have high in-hospital mortality. Independency in everyday life is a strong independent predictor of survival to hospital discharge.

Pre-procedural oral anticoagulant use is associated with cardiovascular events in women after transcatheter aortic valve replacement: An analysis from the WIN-TAVI cohort.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become an accepted treatment for patients with severe aortic stenosis (AS). Predicting which patients are at risk for adverse clinical outcomes after TAVI remains difficult, especially in women. AIM: To identify predictors of adverse events in the WIN-TAVI cohort. METHODS: The WIN-TAVI study is an observational registry of 1019 women undergoing TAVI for severe symptomatic AS. Follow-up was 1 year. The primary outcome was defined according to VARC-2: a composite of mortality, stroke, myocardial infarction or hospitalization for valve-related symptoms or heart failure. The secondary outcome was a composite of cardiovascular mortality or hospitalization for valve-related symptoms or heart failure. RESULTS: We included 1019 women with severe AS (mean age of 82.5 ± 6.3 years). At 1 year, 16.4% of the patients experienced the primary endpoint and 12.6% the secondary endpoint. The use of oral anticoagulants (OAC) was the strongest independent predictor of the primary outcome (adjusted hazard ratio [aHR] 1.51, 95% confidence interval [CI] 1.079-2.106, p = 0.016). Independent predictors of the secondary endpoint were age (aHR 1.04 per year, 95% CI 1.01-1.074, p = 0.016) and use of OAC (aHR: 1.79, 95% CI 1.24-2.60, p = 0.002). OAC use was not associated with higher bleeding risk. CONCLUSION: Pre-procedural use of OAC was the strongest predictor of adverse outcomes during 1-year follow-up, likely reflecting a combination of high-risk factors and comorbidities, but was not related to increased bleeding risk.

A large, prospective, multicentre study of left main PCI using a latest-generation zotarolimus-eluting stent: the ROLEX study.

BACKGROUND: Data on left main (LM) percutaneous coronary interventions (PCI) have mostly been obtained in studies using drug-eluting stent (DES) platforms without dedicated large-vessel devices and with limited expansion capability. AIMS: Our study aimed to investigate the safety and efficacy of LM PCI with the latest-generation Resolute Onyx DES. METHODS: ROLEX (Revascularization Of LEft main with resolute onyX) is a prospective, multicentre study (ClinicalTrials.gov: NCT03316833) enrolling patients with unprotected LM coronary artery disease and a SYNTAX score <33 undergoing PCI with the Resolute Onyx zotarolimus-eluting coronary stent, that includes dedicated extra-large vessel platforms. The primary endpoint (EP) was target lesion failure (TLF): a composite of cardiac death, target vessel myocardial infarction (TVMI) and ischaemia-driven target lesion revascularisation (ID-TLR), at 1 year. All events were adjudicated by an independent clinical event committee. An independent core lab analysed all procedural angiograms. RESULTS: A total of 450 patients (mean age 71.8 years, SYNTAX score 24.5±7.2, acute coronary syndrome in 53%) were enrolled in 26 centres. Of these, 77% of subjects underwent PCI with a single-stent and 23% with a 2-stent technique (8% double kissing [DK] crush, 6% culotte, 9% T/T and small protrusion [TAP] stenting). Intravascular imaging guidance was used in 45% (42% intravascular ultrasound [IVUS], 3% optical coherence tomography [OCT]). At 1 year, the primary EP incidence was 5.1% (cardiac death 2.7%, TVMI 2.7%, ID-TLR 2.0%). The definite/probable stent thrombosis rate was 1.1%. In a prespecified adjusted subanalysis, the primary EP incidence was significantly lower in patients undergoing IVUS/OCT-guided versus angio-guided PCI (2.0 vs 7.6%; hazard ratio [HR] 0.28, 95% confidence interval [CI]: 0.13-0.58; p<0.001). CONCLUSIONS: In this large, multicentre, prospective registry, LM PCI with the Resolute Onyx DES showed good safety and efficacy at 1 year, particularly when guided by intracoronary imaging.

Diagnostic performance of exercise stress tests for detection of epicardial and microvascular coronary artery disease: the UZ Clear study.

BACKGROUND: Cardiac stress tests remain the cornerstone for evaluating patients suspected of having obstructive coronary artery disease (CAD). Coronary microvascular dysfunction (CMD) can lead to abnormal non-invasive tests. AIMS: We sought to assess the diagnostic performance of exercise stress tests with indexes of epicardial and microvascular resistance as reference. METHODS: This was a prospective, single-arm, multicentre study of patients with an intermediate pretest probability of CAD and positive exercise stress tests who were referred for invasive angiography. Patients underwent an invasive diagnostic procedure (IDP) with measurement of fractional flow reserve (FFR) and index of microvascular resistance (IMR) in at least one coronary vessel. Obstructive CAD was defined as diameter stenosis (DS) >50% by quantitative coronary angiography (QCA). The objective was to determine the false discovery rate (FDR) of cardiac exercise stress tests with both FFR and IMR as references. RESULTS: One hundred and seven patients (137 vessels) were studied. The mean age was 62.1±8.7, and 27.1% were female. The mean diameter stenosis was 37.2±27.5%, FFR was 0.84±0.10, coronary flow reserve was 2.74±2.07, and IMR 20.3±11.9. Obstructive CAD was present in 39.3%, whereas CMD was detected in 20.6%. The FDR was 60.7% and 62.6% with QCA and FFR as references (p-value=0.803). The combination of FFR and IMR as clinical reference reduced the FDR by 25% compared to QCA (45.8% vs 60.7%; p-value=0.006). CONCLUSIONS: In patients with evidence of ischaemia, an invasive functional assessment accounting for the epicardial and microvascular compartments led to an improvement in the diagnostic performance of exercise tests, driven by a significant FDR reduction.

Transradial/brachial carotid artery stenting with proximal protection: technical instructions, acute results and long-term outcomes.

BACKGROUND: The aim of this study was to evaluate the feasibility, safety and efficacy of transradial/brachial (TR/TB) carotid artery stenting (CAS) with proximal cerebral protection (PCP) as a first line of treatment of carotid artery stenosis. METHODS: Among 556 patients with significant (>50% if symptomatic or >70% if asymptomatic by Doppler US) unilateral, lipid-rich carotid artery stenosis undergoing TR/TB CAS, 137 (24.5%) deemed at high-risk for periprocedural cerebral embolization were scheduled for PCP with Mo.MA Ultra or Mo.MA mono-balloon. In patients with very complex anatomy the standard technique was modified loading the Mo.MA catheter without mandrel on two-wire system (so called 'No MAndrel 2 wire' technique, No.MA2) to increase support and deliverability. Device, technical and procedural successes both acute and at follow-up were the main outcomes. RESULTS: Mean patients' age was 74±7 years (93% male), 15% were symptomatic and 59.6% owned 'high-surgical-risk' features. Stenosis degree was 85±7% with soft composition in all (by CT-angiography). TR and TB approach were selected in 92 (67%) and 45 (33%) patients, respectively. Target carotid axes were right, left bovine and left non bovine in 55%, 38% and 7% of patients. Procedures were successfully completed in all patients (intention-to-treat basis) with the standard Mo.MA Ultra system in 129 patients and the Mo.MA mono-balloon in 8 patients. No.MA2 technique was succesfully used in 16 patients as 'bailout' and in 27 patients as 'first line'). Device and technical success was 97% (133/137 patients) due to crossover to femoral access in 3 cases, and Mo.MA too short to engage the ECA in 1 patient. The procedural success was 96.7% (131/137, two minor strokes). Procedural time and fluoroscopy time were increased with No.MA2 technique. One major vascular complication occurred, in the TB group, while chronic radial occlusion was detected by Doppler ultrasound in 7/92 patients (7.1%) at 372±163 days of follow-up. The event-free survival was 91% and the stroke rate was 0%. CONCLUSIONS: TR/TB CAS with proximal protection is a feasible, safe and effective strategy and may be considered a first line strategy in all comer patients.

Migraine in Patients Undergoing PFO Closure: Characterization of a Platelet-Associated Pathophysiological Mechanism: The LEARNER Study.

The association between migraine and patent foramen ovale (PFO) has been documented. We aimed to investigate platelet activation, prothrombotic phenotype, and oxidative stress status of migraineurs with PFO on 100 mg/day aspirin, before and 6 months after PFO closure. Data show that, before PFO closure, expression of the classical platelet activation markers is comparable in patients and aspirin-treated healthy subjects. Conversely, MHA-PFO patients display an increased prothrombotic phenotype (higher tissue factorpos platelets and microvesicles and thrombin-generation potential), sustained by an altered oxidative stress status. This phenotype, which is more controlled by P2Y12-blockade than by aspirin, reverted after PFO closure together with a complete migraine remission. (pLatelEts And MigRaine iN patEnt foRamen Ovale [LEARNER]; NCT03521193).